THE ROLE OF THE CHARGE-TRANSFER COMPLEX
IN THE ALTERNATING COPOLYMERIZATION OF
N-SUBSTITUTED MALEIMIDES AND VINYL ETHERS
KURT GORDON OLSON
A DISSERTATION PRESENTED TO THE GRADUATE COUNCIL OF
THE UNIVERSITY OF FLORIDA
IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE
DEGREE OF DOCTOR OF PHILOSOPHY
UNIVERSITY OF FLORIDA
Kurt Gordon Olson
I would like to express my deep appreciation and gratitude to my
research director, Dr. George B. Butler, for his encouragement and
guidance during the course of this work.
I would also like to thank Dr. Roy W. King for teaching me how
to use the FX-100 NMR spectrometer, and for many helpful discussions.
Thanks are also due to Dr. Thieo E. Hogen-Esch for numerous discus-
sions. I would like to thank Dr. Wallace Brey and Mr. Paul Kanyha
for running the 15N, 19F, and 300 MHz IH NMR spectra described herein.
The friendship and cooperation of my coworkers in the polymer
chemistry laboratories are greatly appreciated. Discussions with
Mr. David P. Vanderbilt were especially helpful during the course of
I would like to thank Miss Patty Hickerson for the skillful typ-
ing of this manuscript. Special thanks are due to my wife, Leslie,
for her constant encouragement and help.
Financial support for this work from the Department of Chemistry,
the National Science Foundation (Grant No. DMR80-20206), Tennessee
Eastman Co., Gulf Oil Co., and the University of Florida Graduate
School is gratefully acknowledged.
TABLE OF CONTENTS
ACKNOWLEDGEMENTS . . . . . . . . . . . .
LIST OF TABLES . . . . . . . . . . . . .
LIST OF FIGURES . . . . . . . . . . . .
ABSTRACT . . . . . . . . . . . . . .
I. INTRODUCTION . . . . . . . . . . . .
II. EXPERIMENTAL . . . . . . . . . . . .
General . . . .
Reagents and Solvents. .
Model Compound Synthesis
Malpimidp Svnthp'si .
... ...... .. ... ... . . . . . . . . . . .
Copolymer Synthesis and Characterization . . . . .
Copolymer Epimerization . . . . . . . .
Complexation Studies . . . . . . . . .
III. RESULTS AND DISCUSSION . . . . . . . . .
Copolymer Composition . . . . . . . .
Copolymerization Kinetics . . . . . . .
Maleimide-CEVE Complexation Studies . . . . .
Carbon-13 NMR Structural Studies on N-Substituted Male-
imide Vinyl Ether Copolymers . . . . . . .
Model Compound Synthesis and Stereochemical Assignments..
Summary and Conclusions . . . . .... .
REFERENCES .................... ...... 204
BIOGRAPHICAL SKETCH... .................. . .214
LIST OF TABLES
1 13C Chemical Shifts (6, ppm from TMS) for cis and trans
11. (DMSO-d6, internal reference DMSO-d6 = 39.5)......... 36
2 Conditions for N-Phenylmaleimide-2-Chloroethyl Vinyl
Ether Copolymerizations....................... .... ... 57
3 Yield and Analysis Data for Copolymers in Table 2......... 58
4 Polymerization Conditions for Other Maleimide Polymers.... 59
5 Yield and Analysis Data for Copolymers in Table 4......... 60
6 Reactivity Ratios for the Free Radical Initiated Copoly-
merization of N-Phenylmaleimide (M1) and 2-Chloroethyl
Vinyl Ether (M2) in Dichloromethane....................... 65
7 Kinetic Data for N-Phenylmaleimide 2-Chloroethyl Vinyl
Ether Copolymerizations................ .. ...... ....... 68
8 Initial Copolymerization Rates for the Copolymerization of
N-Phenylmaleimide and 2-Chloroethyl Vinyl Ether in Di-
9 Carbon-13 Spin-Lattice Relaxation Times (T1) and Nuclear
Overhauser Enhancement Factors (NOEF) For an NPM-CEVE -
Copolymer ............................................... 76
10 Copolymer Decomposition Temperatures (Td)................. 80
11 Absorbance Data for Maleimide, 2-Chloroethyl Vinyl Ether
Complexes at 295 nm....................................... 93
12 Slopes of A295/([M] x z) vs. [CEVE] Plots................. 95
13 Chemical Shifts (6, ppm From TMS) for the Olefinic Protons
of N-Phenylmaleimide in CDC13 Solutions of Varying
2-Chloroethyl Vinyl Ether Concentration................... 108
14 The Effect of Solvent on the Chemical Shift of NPM Ole-
finic Protons (100 MHz, 6, ppm From TMS).................. 110
15 The Mole Fraction of cis Succinimide Units in NPM-CEVE
Copolymers as a Function of the Mole Fraction of NPM
in the Initial Comonomer Feed (XM)........................ 146
16 Mole Fraction of cis Succinimide Units in NPM-CEVE Copoly-
mers Prepared at Various Temperatures..................... 155
17 The Effect of Solvent on the Mole Fraction of cis Succin-
imide Units in NPM-CEVE Copolymers........................ 157
18 Carbon-13 NMR Chemical Shifts of Some N-Substituted Male-
imides.................................................. .. 161
19 The Mole Fraction cis Succinimide Units in Various N-Sub-
stituted Maleimide-CEVE Copolymers....................... 165
20 The Mole Fraction of cis Succinimide Units in NPM-Vinyl
Ether Copolymers.......................................... 173
LIST OF FIGURES
1 Kelen-Tudos Plot for the Free-Radical Initiated Copoly-
merization of N-Phenylmaleimide and 2-Chloroethyl Vinyl
Ether in Dichloromethane............................. .. 64
2 Electronic Absorption Spectra of Various N-Substituted
Maleimides in Dichloromethane........................... 87
3 Electronic Absorption Spectra of Various N-Substituted
Maleimide 2-Chloroethyl Vinyl Ether Charge-Transfer
Complexes, [CEVE] = 1.3 in all cases..................... 90
4 Effect of Varying CEVE Concentration on the Intensity of
the NPM-CEVE Charge-Transfer Band........................ 91
5 Copolymer Composition Diagram for the NPM-CEVE System.... 99
6 Initial Copolymerization Rate vs. XM for the System NPM,
CEVE, AIBN, CH2C12, 600C................................. 100
7 K295 vs. Hammett a Constants for Various Para Substi-
tuted Maleimide-CEVE Complexes in Dichloromethane........ 107
8 Noise Decoupled 13C NMR Spectrum of an NPM-CEVE Copoly-
mer, Obtained in DMSO-d6 at 1100C....................... 115
9 Complete a) and Off-resonance b) Decoupled 13C NMR Spec-
tra of NPM-Methyl Vinyl Ether Copolymer.................. 117
10 Model Compound 13C NMR Chemical Shifts................... 121
11 Homo- and Copolymer 13C NMR Chemical Shifts.............. 123
12 "Dyad" Stereochemical Possibilities for NPM-CEVE Alter-
nating Copolymers (i.e., Relative Stereochemistry Between
Two Adjacent Chiral Centers)............................. 125
13 "Triad" Stereochemical Possibilities for Alternating
Sequences in NPM-CEVE Copolymers.......................... 126
14 Effect of the Mole Fraction of NPM in the Initial
Comonomer Feed (xM) on the Appearance of Copolymer 13C
NMR Carbonyl Peaks....................................... 132
15 Effect of Copolymer Epimerization on the Carbonyl Region
of the C NMR Spectra of NPM-CEVE Copolymers............ 134
16 Effect of Copolymer Epimerization on the 1C NMR Reso-
nances Due to Carbons a to Oxygen in NPM-CEVE Copolymers. 136
17 Expanded Carbonyl Regions of the 13C NMR Spectra of Low
(a) and High (b) Conversion NPM-CEVE Copolymers.......... 138
18 Mole Fraction cis Succinimide Units in NPM-CEVE Copoly-
mers vs. XM..................................... 142
19 Nitrogen-15 NMR Spectrum of an NPM-CEVE Copolymer (20%
15N Enriched) in Acetone-d6..................... ... .. 148
20 Expanded Carbonyl Regions of the 13C NMR Spectra of NPM-
CEVE Copolymers Prepared with Different Total Monomer
Concentrations (MT) in the Initial Feed.................. 152
21 Expanded Carbonyl Regions of the 13C NMR Spectra of NPM-
CEVE Copolymers Prepared at Various Temperatures......... 154
22 Expanded Carbonyl Regions of NPM-CEVE Copolymers Prepared
in Bulk (a), Dichloromethane (b), and Benzene (c)........ 158
23 Expanded Carbonyl Regions of the 13C NMR Spectra of Some
N-(4-Substituted)-Arylmaleimide-CEVE Copolymers.......... 164
24 Mole Fraction cis Succinimide Units in N-Arylmaleimide -
CEVE Copolymers vs. Hammett o Constant................... 166
25 KE295 vs. Mole Fraction Cis Succinimide Units in N-Sub-
stituted Maleimide-CEVE Copolymers....................... 167
26 Expanded Carbonyl Regions of the 13C NMR Spectra of Co-
polymers Prepared from Several N-Substituted Maleimides
and CEVE............................................... 169
27 Expanded Carbonyl Regions of the 13C NMR Spectra of Co-
polymers Prepared from NPM and Various Vinyl Ether Co-
monomers............................................. .. 172
28 Carbon-13 NMR Spectrum of N-Phenylcitraconimide CEVE
Copolymer .............................................. 179
29 Expanded Regions of the 13C NMR Spectrum of Maleic
Anhydride-CEVE Copolymer................................... 182
30 Synthetic Scheme for Model Compound 16................... 184
31 Possible Conformations of Endo Diels-Alder Adduct 13..... 185
32 Proton NMR Spectrum (300 MHz) of Model Compound 16....... 190
33 Expansions of the Ring Proton Resonances Appearing in the
300 MHz 1H NMR Spectrum Shown in Figure 32............... 191
34 Synthetic Scheme for Model Compound 11................... 198
Abstract of Dissertation Presented to the
Graduate Council of the University of Florida
in Partial Fulfillment of the Requirements for the
Degree of Doctor of Philosophy
THE ROLE OF THE CHARGE-TRANSFER COMPLEX
IN THE ALTERNATING COPOLYMERIZATION OF
N-SUBSTITUTED MALEIMIDES AND VINYL ETHERS
Kurt Gordon Olson
Chairman: Dr. George B. Butler
Major Department: Chemistry
The aim of this research was to determine whether or not a co-
monomer charge-transfer complex participates significantly in the
propagation steps of free-radically initiated alternating copolymeri-
zations. Various N-substituted maleimides were shown to copolymerize
alternately with several vinyl ethers. Both the sequence distribu-
tion and the stereochemistry of these copolymers were found to depend
on such copolymerization conditions as temperature, solvent, total
monomer concentration, the initial ratio of comonomers, and the rela-
tive donor and acceptor strengths of the comonomers. Carbon-13 nu-
clear magnetic resonance (NMR) spectroscopy was used extensively for
the determination of copolymer stereoregularity.
Copolymer epimerization studies and the comparison of copolymer
C NMR chemical shifts with those of a series of stereospecific model
compounds indicated that the stereochemistry at the succinimide units
in the copolymer was predominantly cis. In general, copolymerization
conditions that were expected to enhance the fraction of maleimide
monomer in completed form (e.g., low temperature, excess vinyl ether,
"inert" solvent, higher total monomer concentration, and stronger
donor-acceptor character of the comonomer pair) yielded copolymers
possessing a higher cis:trans stereochemical ratio at the succinimide
A weak interaction between the comonomers was shown to exist by
the appearance of a new absorption in the electronic spectra of co-
monomer mixtures, which did not appear in the spectrum of either
The observed preference for cis stereochemical placements in
these copolymers was opposite to what was expected if a mechanism
involving consecutive alternate monomer additions to the radical
chain end was operational. Thus, it was proposed that succinimide
unit stereochemistry is dependent on the fraction of maleimide mono-
mer in completed form, and that the comonomer complex was participat-
ing in the propagation steps.
Although the stereochemistry at the succinimide units was mostly
cis, the relative stereochemistry between the vinyl ether methine
carbons in the copolymers, and the methine carbons of adjacent succin-
imide units proved to be nearly random. The results were interpreted
by invoking a concerted addition of the complex to the radical chain
end, with radical attack occurring preferentially on the maleimide
portion of the complex, on the side syn to the vinyl ether.
The concept of "molecular association" has long been recognized
as important in virtually all fields of chemistry. This fact is
underscored by the appearance of a plethora of books and reviews de-
voted to the subject during the past two decades.1 The concept is
that of a relatively electron poor molecule, or acceptor (A), inter-
acting in some way with an electron rich molecule, or donor (D). The
interaction is such that the binding between the components is weaker
than a covalent bond.lk This definition is sufficiently broad so as
to take in the gamut of both weak and strong interactions between
both ionic and uncharged species.
The concept has been utilized in many diverse fields of chemis-
try. Lewis acid-Lewis base interactions are, in principle, inter-
actions between donors and acceptors. i Inorganic and organometallic
chemists have used the concept to describe metal-ligand interactions.
Ion solvation, ionization equilibria, and catalysis are also fields
of chemistry where donor-acceptor interactions play important roles.1
Organic chemists have applied the terms electrophilic and nucleo-
philic to acceptor and donor molecules, respectively. The literature
abounds with such terms as "molecular complexes," "o and a complexes,"
and "charge-transfer complexes," which all refer to some sort of
Modern interest in donor-acceptor complexes has blossomed since
the discovery by Benesi and Hildebrand in 1949 of a new absorption
band in the electronic spectrum of a solution of benzene and iodine
in n-heptane, which did not appear in the spectrum of either compo-
nent alone. The explanation of this phenomenon was provided by
Mulliken in a series of papers published in 1950-1952 (reprinted in
reference le). His conclusion was that the new band was due to an
iodine-benzene complex possessing a 1:1 stoichiometry. A new elec-
tronic transition such as that described above is typical of mixtures
of donor and acceptor molecules in relatively "inert" solvents (sol-
vents which do not interact to an appreciable extent with either the
donor or acceptor component). Thus, if the new band is in the visi-
ble region, solutions of colorless donors and acceptors may appear
The relatively weak interaction between donors and acceptors,
such as the iodine-benzene system described above, is generally viewed
as an equilibrium
A + D K C
where the equilibrium constant K describes the strength of the inter-
action. The theoretical groundwork for such weak interactions has
been adequately described in the works of Mulliken and Person,le and
Kosower. c While the details of this theory will not be discussed,
several points are pertinent and will be briefly covered.
The interaction between the components of the complex was de-
scribed in the valence bond formulation.3 The ground state wave func-
tion (YN) and the excited state wave function (YE) are approximated by
N = a [O(D,A) + b YI(D+,A-) (1)
E = a T((D+,A-) b yO(D,A) (2)
where 1((D+,A-) represents the contribution to the bonding of the
components from the resonance form where there has been complete
transfer of one electron from donor to acceptor, and 0(D,A) repre-
sents the contribution from all other bonding interactions. For weak
molecular interactions, the relationship between the coefficients a
and b is, a >> b, so h0 is the major contributor in the ground state
and T1 takes precedence in the excited state. The electronic transi-
tion between these two levels is thought to be the origin of the
charge-transfer transition. One of the justifications for this theory
is the applicability of empirical relationships between the energy of
the charge-transfer transition (hv), the ionization potential of the
donor (ID), and the electron affinity of the acceptor (EA).4
hv = ID EA + C (3)
The constant C represents coulombic forces between the donor and
acceptor. The values ID and EA reflect the relative strength of
donors and acceptors, respectively, strong donors having low ID and
strong acceptors having high EA.
Another important consequence of Equations (1) and (2) is that
complexes are predicted to have favored orientations, since b2 (a
measure of the amount of charge-transfer) is proportional to the over-
lap integral between the highest occupied molecular orbital of the
donor (HOMO), and the lowest unoccupied molecular orbital (LUMO) of
the acceptor.5 In other words, since the "charge-transfer" is from
the HOMO of the donor to the LUMO of the acceptor, the maximum amount
of charge-transfer stabilization of the complex is to be expected
when the overlap between these orbitals is greatest.
It should also be mentioned that the observation of a new elec-
tronic band in a solution of donor and acceptor molecules does not
necessarily imply the existence of a complex. Such bands are ob-
served even when the equilibrium constant (K) for complex formation
is zero. The absorption is due to donor-acceptor pairs that are
merely close or in contact, and can be fairly intense. This phenom-
enon is known as "contact charge-transfer" and has been recently re-
viewed in an excellent article by Tamres and Strong.6 Thus, the mere
observation of a charge-transfer band in a reaction system should not
be taken as evidence for the participation of charge-transfer com-
plexes as reaction intermediates.
Kosower cd has reviewed the organic reactions in which charge-
transfer complexes may be reaction intermediates. The types of reac-
tions discussed include solvolysis, thermal electron transfer (e.g.,
the formation of radical anion-cation pairs), and reactions which
follow light absorption by a charge-transfer complex. Recent examples
of organic reactions in which charge-transfer complexes have been
postulated as intermediates include the electrophilic addition of
bromine and mercuric salts to olefins,7 and the cleavage of alkyltin
compounds by mercuric salts.8
Especially pertinent to this work are reactions that Kosowerlcd
categorizes as class G reactions, or reactions that depend on the ge-
ometry of the charge-transfer complex. He describes these reactions
as reactions which lead to a product structure other than that which
might have been expected on the basis of random collision of the reac-
tants or a knowledge of similar reactions in related molecules. He
includes as examples the stereospecific hydrolysis of substrates by
enzymes and Diels-Alder reactions. A recent example of the applica-
tion of the charge-transfer concept to asymmetric induction in intra-
molecular Diels-Alder reactions is given by Trost, O'Krongly and
Belletire. Stereoselectivity has also been observed in photochemical
2+2 cycloadditions, where only the charge-transfer band was irradi-
Charge-Transfer Complexes in Polymerization Processes
Several recent reviews have dealt with the influence of charge-
transfer complexes on polymerization processes.11,12 This disserta-
tion deals with the influence of the charge-transfer complex on the
propagation steps in alternating, radical-initiated copolymerizations.
Alternating copolymerizations are characteristic in that a
nearly 1:1 ratio of comonomers is found in copolymers produced from
a wide variety of comonomer mole fractions in the initial monomer
solution (referred to as the monomer feed). In a random copolymeri-
zation, the monomer ratio in the copolymer corresponds closely to
that in the feed. The degree of alternation depends strongly on the
polarity differences between the comonomers. If one monomer is a
donor, while the other is an acceptor, the copolymer resulting from
the polymerization of these monomers will possess a certain amount of
alternation, which depends on the strength of the interaction between
the comonomers. This effect was noticed very early in the develop-
ment of copolymerization theory, and the Q,e scheme was introduced in
order to provide a quantitative, empirical comparison of the polarity
of various monomers.13 The e value (polar parameter) is positive for
electron-deficient olefins and negative for electron-rich olefins.
The Q value is determined by resonance effects.
The influence of the charge-transfer complex in alternating co-
polymerizations has been the subject of debate for many years. Sev-
eral mechanisms have been proposed to explain the alternation ob-
served. First, the postulate was put forth by Walling et al.14 that
polarity differences between the radical chain end and the incoming
monomer would lower the energy of activation of a cross-propagation
reaction, as opposed to a homopropagation reaction, thus producing
alternating copolymers when the comonomers have widely different
polarities. This mechanism will henceforth be referred to as the
"free monomer" mechanism.
The second possible explanation for alternation in these systems
was first proposed by Bartlett and Nozaki in 1946.15 These workers
postulated that donor and acceptor monomers formed a charge-transfer
complex which, due to an inherently higher reactivity of the complex
relative to the free monomers, preferentially added to the chain end.
In other words, the alternating nature of the copolymer results from
a "homopolymerization" of the charge-transfer complex. Support for
this theory may be found in the works of Butler and coworkers 19
maleicc anhydride-divinyl ether and maleic anhydride-furan copoly-
mers), Iwatsuki, Yamashita and Kokubo20,21,22 maleicc anhydride-
vinyl ether and maleic anhydride-anethole copolymers), Gaylord and
coworkers23,24 maleicc anhydride-conjugated diene copolymers) and
Caze and Loucheux25 maleicc anhydride-vinyl acetate copolymers). This
mechanism has been termed the "complex" mechanism.
A third possibility is that both of the mechanisms described
above are important in alternating copolymerizations. Tsuchida and
Tomono,26 and Tsuchida et al.27 introduced this concept to explain re-
sults obtained for the styrene-maleic anhydride system. Seiner and
Litt,28 Litt,29 and Litt and Seiner331 derived a series of kinetic
equations that included the complex as a propagating species and ob-
tained better fits to experimental copolymer composition data than
could be obtained by using the classical "terminal" copolymerization
model developed by Mayo and Lewis,3 and Alfrey and Goldfinger.33 The
terminal model predicts copolymer compositions based on a kinetic
scheme which does not include a complex, and assumes random introduc-
tion of comonomers into the chain (i.e., only four possible propaga-
tion steps are included for two comonomers). Karad and Schneider34
have extended the Seiner-Litt equations to systems (e.g., styrene-
fumaronitrile) where the assumption of a small charge-transfer equi-
librium constant does not hold. Still more recently, Cais, Farmer,
Hill and O'Donnell35 have presented an alternative to the Seiner-Litt
complex participation model in which either copolymer composition data
or triad fractions can be used to test the various copolymerization
models. This treatment is unique in that it treats sequence number
fractions in terms of transition probabilities as well as reactivity
Perhaps one of the strongest pieces of evidence for complex
participation in alternating copolymerizations is that the overall
rate of polymerization (R ) exhibits a maximum at a monomer feed
ratio of nearly 1:1, where the concentration of the complex is great-
est. Shirota et al.,36 and Yoshimura et al.37'38 have pointed out
that the rate maximum for alternating copolymerizations seldom occurs
at exactly 1:1 feed ratio. They also point out that the rate of
polymerization at constant feed ratio and initiator concentration is
generally greater than first order in total monomer concentration.
If only the cross-propagation of free monomers operates, the rate
should be proportional to the total monomer concentration. Thus,
they also support the theory that both completedd" and "free" monomers
participate in the propagation reactions. They have also derived a
scheme based on the change of R with total monomer concentration
(at constant feed ratio), whereby a quantitative separation of the
rate due to complex addition, and that due to free monomer addition,
can be achieved. These workers applied their method to the systems
N-vinylcarbazole (VCZ)-diethyl fumarate (DEF), and VCZ-fumaronitrile
(FN). They concluded that the overall rate of copolymerization was,
at most, 17% due to the addition of the complex in the VCZ-DEF sys-
tem. Ten percent of the overall rate was due to complex addition for
the VCZ-FN system. Georgiev and Zubov39 have also developed a scheme
that allows the determination of the ratio of rate constants for
addition of completedd" and "free" monomers. Their method utilizes
the shift in the overall rate maximum as a function of the total mono-
mer concentration. They found that a significant amount of complex
participation occurs in the copolymerization of maleic anhydride and
The last copolymerization theories to be considered are the
penultimate and antepenultimate models first suggested by Mertz,
Alfrey and Goldfinger,40 and later by Barb41 and Ham.42 These work-
ers felt that deviations in copolymer composition from that predicted
by the terminal model could be explained by invoking the effect of
the penultimate or antepenultimate units in the copolymer chain. In
other words, the reactivity of the chain end radical may differ de-
pending on which monomer unit is in the penultimate or antipenulti-
In spite of the large amount of data that has been amassed on
systems that produce alternating copolymers (especially the styrene-
maleic anhydride system), there is still disagreement as to what the
exact mechanism is. Hyde and Ledwith11 have pointed out that the
actual concentration of complex in systems that show a tendency to
alternately copolymerize is invariably very low (equilibrium con-
stants for complex formation (K) are generally in the range 0.01 -
0.5). Thus, if the complex has any role in the propagation steps,
it necessarily must have an extremely high reactivity relative to the
free monomers. This is a point that is still open to some debate.
Dodgson and Ebdon43 have reanalyzed styrene-maleic anhydride copoly-
mer composition as a function of initial feed ratio. They conclude
that the penultimate model gives as good a fit to the experimental
data as the complex model. Regel and Canessa4 have examined the
complexation and copolymerization behavior of difluoromaleic anhydride
with a variety of donors, and have come to the conclusion that donor-
acceptor complexes have no significant involvement in the copolymeri-
It should be kept in mind that in nearly all of the studies dis-
cussed in this section, only two basic sources of experimental data
have been used to make a large number of conclusions. These sources
of data are copolymer composition (and sequence analysis) and kinetic
data. As Hyde and Ledwith11 point out, these kinetic analyses in-
variably assume relative values of certain rate constants in order to
obtain good fits with experimental data. Copolymer composition is
generally calculated from either elemental analysis data or integra-
tion of copolymer NMR spectra. Copolymerization rates are typically
calculated from a single copolymer weight obtained after a certain
polymerization time. The polymers are routinely isolated by precipi-
tation into a nonsolvent, so an implicit assumption is that the co-
polymers are completely insoluble in this nonsolvent. All of these
experimental techniques are subject to errors which are seldom dis-
cussed. While the derivations, schemes and analyses discussed above
are not questioned, it seems necessary to have accurate and copious
data in order to distinguish between such mechanistic subtleties as
complex formation prior to addition to the chain end, and complex
formation with the chain end itself.
Thus, it was thought that some new source of data was needed in
order to help resolve the question of whether or not charge-transfer
complexes play a significant role in alternating copolymerizations.
Since, according to Mulliken theory, a donor-acceptor complex is
expected to have a preferred geometry videe supra), it may be that
if the complex adds to the chain end in a concerted manner (as op-
posed to stepwise addition of the complex components), a certain de-
gree of stereoregularity may be introduced into the copolymer chain.
As mentioned earlier, in organic reactions where charge-transfer com-
plexation between components has been observed, stereoselectivity is
often observed in the product distribution. If the "free" monomers
preferentially add to the chain end, the resulting copolymer stereo-
chemistry may be expected to be nearly random since the chain end is
expected to be either planar or possess a rapidly inverting pyramidal
Thus, a detailed study of copolymer structure and stereochemis-
try as a function of copolymerization conditions was carried out.
Conditions were selected so as to shift the complex equilibrium one
way or the other. The system N-phenylmaleimide (NPM) 2-chloro-
ethyl vinyl ether (CEVE) was selected for study. Nitrogen and chlo-
rine elemental analysis allowed relatively accurate determination of
the composition of copolymers produced from these monomers. N-Phenyl-
maleimide is an acceptor monomer with an e value of +3.24.46 CEVE
is a donor monomer with an e value of -1.58.46 Thus, they were ex-
pected to form alternating copolymers. Indeed, NPM has been shown to
form alternating copolymers with styrene.47 Maleic anhydride copoly-
merizes alternately with CEVE.26'48
Several interesting reports have appeared that deal with asym-
metric induction into alternating copolymers. Kurokawa et al.49
copolymerized NPM with optically active menthyl vinyl ether and found
that the copolymer retained some optical activity even after cleavage
of the optically active side chain. Beredjick and Schuerch50 obtained
similar results with the system (-)-a-methylbenzyl methacrylate -
maleic anhydride, although Chiellini et a1.51 have questioned whether
they obtained complete hydrolysis of the side groups. Optically ac-
tive N-bornylmaleimide was copolymerized with styrene, methyl meth-
acrylate and vinylidene chloride by Yamaguchi and Minoura.52 They
found that more optical activity was observed in the copolymers which
had a higher degree of alternation. It may be that a charge-transfer
complex between the monomers plays an important role in these asym-
metric inductions. Kurokawa and Minoura,53 however, have explained
such induction of asymmetry as being the result of the influence of
the chiral chain end on the incoming monomer. Asakura, Yoshihara
and Maeshima54 have recently published an interesting report in which
they describe the copolymerization of maleic anhydride with isobutyl
vinyl ether, styrene, methacrylic acid, methyl acrylate, and methyl
methacrylate in optically active solvents such as 1-menthol. They
found that optically active copolymers were produced only for the
systems that copolymerized alternately maleicc anhydride-styrene and
maleic anhydride-isobutyl vinyl ether). They postulate that the chi-
ral solvent may interact with the charge-transfer complex, forming
a trimolecular complex that may be important in the asymmetric induc-
tion observed. In spite of some disagreement about the results ob-
tained in these studies, it seems at least plausible that an associa-
tion of the monomers prior to addition to the chain end may influence
the resulting stereochemistry.
Hirai et al.,55 and Okuzawa et al.56 have shown that in polymers
prepared in the presence of a Lewis acid, stereoregularity often
accompanies rate enhancement. This observation may also mean that
the formation of molecular complexes has an effect on polymer stereo-
chemistry. To the best of our knowledge, a detailed study of the
stereochemistry of alternating copolymers prepared by using conven-
tional free radical initiation, has thus far not appeared.
Carbon-13 NMR was used for the study of NPM-CEVE copolymer ster-
eochemistry. Synthesis of a series of stereospecific model compounds
aided in the interpretation of the copolymer 1C results.
All temperatures are uncorrected and are reported in degrees
centigrade. Melting points were determined in open capillary tubes
using a Thomas-Hoover Melting Point Apparatus. Pressures are ex-
pressed as millimeters of mercury.
Infrared (IR) spectra were obtained by using a Perkin Elmer
Model 281 Infrared Spectrophotometer. Spectra were calibrated using
the 1601 cm- line of a polystyrene film. Spectra of oils and liq-
uids were performed neat as a smear on a sodium chloride plate, and
those of solids were obtained by using KBr pellets. Vibrational
transition frequencies are expressed in wavenumbers (cm- ), with
bands being assigned the following classifications: weak (w), medi-
um (m), strong (s), very strong (vs) and broad (b).
Proton nuclear magnetic resonance (NMR) spectra (60 MHz) were
obtained on either a Varian A-60A or a Jeol JNM-PMX-60 spectrometer.
Carbon-13 (25.00 MHz) and 100 MHz proton NMR spectra were recorded
on a Jeol JNM-FX-100 instrument. Chemical shifts are expressed in
parts per million (ppm) downfield from tetramethylsilane (TMS) unless
stated otherwise. Multiplicities of proton and off-resonance de-
coupled 1C resonances are designated as singlet (s), doublet (d),
triplet (t), quartet (q) or multiple (m). Coupling constants (J)
are expressed in Hertz (Hz).
Mass spectra [low resolution (LRMS) and high resolution (HRMS)]
were recorded on an Associated Electronics Industries (AEI) Model
Ultraviolet (UV) spectra were run on a Beckman ACTA V Spectro-
photometer using 1 cm or 2 mm quartz cells.
Catalytic hydrogenations were carried out in a low pressure,
shaker type Parr Series 3910 Catalytic Hydrogenation Apparatus.
Polymer number average molecular weights (M ) were determined
using a Wescan 233 Molecular Weight Apparatus (vapor pressure osmo-
Chemical analyses were performed by Atlantic Microlab, Inc.,
Compound headings appear with the common name listed first,
followed by the systematic name (according to Chemical Abstracts) in
parentheses. Registry numbers are given in brackets for known com-
pounds. The Chemical Abstracts numbering scheme is used throughout
to designate protons or carbons (e.g., coupling constants in NMR
Reagents and Solvents
Unless otherwise noted, reagents were obtained from Aldrich
Chemical Co. Dichloromethane (CH2C12) was distilled from P4010 im-
mediately before use. Purification of other solvents was carried out
using standard procedures57 and is described in the text. Deuterated
solvents [chloroform-d (CDC13), d6-acetone, dimethylsulfoxide-d6
(DMSO-d6), and dichloromethane-d2 (CD2C12)] for NMR spectra were
obtained from either Merck and Co. Inc., Stohler Isotope Chemicals
or Aldrich Chemical Co., and were used without further purification.
N-Phenylmaleimide was obtained from Aldrich Chemical Co., and was
recrystallized from cyclohexane before use.
Model Compound Synthesis
N-Phenylsuccinimide (l-Phenyl-2,5-pyrrolidine-dione), [83-25-0], (1)
Method A. The procedure of Umrigar58 was used for the synthesis
of this compound. Exactly 10.0 g succinic anhydride (0.1 mole)
(Aldrich) and 18.6 g distilled aniline (0.2 mole) were dissolved in
approximately 100 ml dimethylformamide (DMF) in a 250 ml round-bot-
tomed flask. The flask was fitted with a reflux condenser, and the
solution was refluxed for six hours. The bulk of the solvent was
then removed via rotary evaporation. The deep red residue was dis-
solved in hot ethanol (95%), and about 1 g decolorizing carbon was
added to the solution. After boiling for about ten minutes, the solu-
tion was filtered hot. The filtrate was allowed to cool slowly, and
N-phenylsuccinimide (1) crystallized as nearly colorless needles.
The needles were suction filtered and washed with cold ethanol. The
product was recrystallized again from ethanol to give 9.0 g 1 (51.4%),
mp 154-1550C literaturee9 mp 1560C).
H NMR (60 MHz,CDC13) 6 2.79(s, 4H), 7.38(m, 5H).
3C NMR (CDC13) 6 28.21(t), 126.32(d), 128.42(d), 128.95(d), 131.83(s),
IR (KBr) 3439(w), 3030(w), 2921(w), 1779(w), 1705(vs), 1593(w),
1500(m), 1391(s), 1290(m), 1190(vs), 1148(m), 1077(w), 1030(w),
1002(w), 927(m), 819(m), 766(m), 696(s), 670(m), 625(w) cm-1
Method B. N-Phenylmaleimide (NPM) could be reduced to N-phenyl-
succinimide (1) by using the procedure of Medvedeva and Belotsvetov.60
To a 125 ml Erlenmeyer flask containing a solution of 25 ml glacial
acetic acid and 50 ml deionized water was added 1.0 g NPM (5.8 mmole)
and 3.0 g iron powder (53.7 mmole). The resulting slurry was stirred
magnetically and heated on a hot plate to 900C. After stirring for
about twenty minutes, the yellow solution turned light green. After
forty-five minutes, the solution had a red-brown color. At the end
of one hour of stirring, the flask was allowed to cool, and the red-
brown precipitate was filtered. The filtrate was neutralized with
solid NaHCO3 and then extracted with CHC13 (2 x 25 ml). The organic
layer was dried over anhydrous MgS04, and then filtered. The solvent
was removed on a rotary evaporator, and the residue recrystallized
from 95% ethanol to yield 0.4 g 1 (39%) as colorless needles. The
spectral properties (IR, NMR) and melting point were identical to
those of 1 synthesized via Method A.
Dimethyl maleic anhydride (Aldrich) (5.0 g, 39.6 mmole) was dis-
solved in 75 ml CHC13. This solution was stirred magnetically while
5.0 g (53.7 mmole) freshly distilled aniline was added dropwise. This
solution was stirred on a hot plate at 40-45C for ninety-one hours.
No precipitation of the expected maleamic acid was noted. The CHC13
was removed on a rotary evaporator to leave an orange crystalline
mass. This residue was dissolved in a small amount of acetone and
precipitated dropwise into rapidly stirred acidic water (100 ml +
5 drops 18 M H2S04). The precipitate was suction filtered, washed
with water, and dried in a vacuum oven (50C) overnight. After dry-
ing, the residue was recrystallized from cyclohexane to yield 4.6 g
(57.6%) of pale green needles, mp 90-91C.
1H NMR (60 MHz, CDC13) 6 2.05(s, 6H), 7.38(s, broad, 5H).
1C NMR (CDC13) 6 8.82, 125.69, 127.33, 128.94, 132.03, 137.39,
IR (KBr) 3450(w), 3048(w), 2987(w), 2953(w), 2920(w), 1750(w),
1699(vs), 1594(m), 1490(s), 1438(m), 1392(vs), 1123(m), 1090(s),
1070(m), 926(m), 769(s), 727(m), 700(s), 633(m).
LRMS (70eV, m/z, relative intensity) 202 (13.7), 201 (M 100.0),
157 (7.9), 142 (28.0), 119 (19.0), 91 (16.9), 77 (11.0), 64
(12.5), 54 (62.0), 53 (25.0).
cis-3,4-Dimethyl-N-phenylsuccinimide (DMNPS) (3.4-Dimethyl-1-phenyl-
To a 250 ml capacity hydrogenation bottle was added 1.0 g (5.0
mmole) 3,4-dimethyl-N-phenylmaleimide, approximately 150 ml 95%
ethanol, and 0.01 g PtO2 (Englehard Industries). The bottle was
placed on the Parr shaker, and the system was pressurized to 55 PSI
with hydrogen gas. The solution was shaken for about five minutes,
and the apparatus was then evacuated (aspirator). The system was
pressurized with H2 and evacuated twice more, then pressurized to
55 PSI. The solution was shaken for 18.5 hours at room temperature.
The catalyst was removed by filtration, and the solvent removed via
rotary evaporation. The residue was recrystallized from CC14 to
yield 0.97 g (95%) very fine, colorless needles, mp 128-1290C
literaturee1 mp 1270C). The cis:trans isomer ratio (calculated
from 13C NMR peak intensities) was > 14, or expressed as a percent-
age, the product was > 94% cis.
1H NMR (100 MHz, CDC13) 6 1.27(d, 6H, broad), 3.04(m, 2H), 7.35(m,5H).
1C NMR (CDC13) 6 11.55, 38.40, 126.38, 128.28, 128.57, 128.96,
IR (KBr) 3455(w), 3046(w,b), 2980(w), 1750(shoulder), 1700(vs),
1591(m), 1490(s), 1452(w), 1427(m), 1395(vs), 1375(shoulder),
1203(m), 1125(m), 1090(s), 1070(m), 935(b), 769(s), 750(m),
727(m), 697(s), 632(w), 615(w) cm-1
trans-3,4-Dimethyl-N-phenylsuccinimide (DMNPS) (trans-3,4-Dimethyl-
l-phenyl-2,5-pyrrolidinedione), [35393-95-4], (4)
The trans isomer of 3,4-dimethyl-N-phenylsuccinimide could be
conveniently prepared by epimerization of the cis compound. Thus,
approximately 0.2 g of the cis isomer was dissolved in 0.4 ml DMSO-d6,
and the resulting solution was filtered into a clean NMR tube. A 13C
NMR spectrum was run (see below for chemical shifts of cis isomer in
DMSO-d6). A drop of 2,2,6,6-tetramethylpiperidine (TMP) (Aldrich)
was then added to the tube, and the tube was placed in a 600C water
bath. After being heated overnight, another 1C spectrum was run.
The peaks due to the small amount of the trans isomer originally pre-
sent (- 5-6%) had grown at the expense of the peaks attributed to the
cis compound. Indeed, the trans isomer was in excess. Continued
epimerization at 600C (monitored periodically with 13C NMR) for about
one week gave a maximum trans:cis ratio of about 6 (86% trans), as
judged from 13C NMR peak intensities. That no epimerization took
place in the absence of TMP was verified by heating another sample of
the cis isomer at 600C in DMSO-d6 for several days and observing the
C3 NMR spectrum. No change was observed. An analytical sample of
4 was isolated by evaporation of most of the DMSO-d6, followed by
extraction of the residue with boiling cyclohexane. The hot cyclo-
hexane was decanted from the residue and on cooling, 4 crystallized
as colorless needles, mp 145-1470C literaturee1 mp 1460C).
Compound 3 13C NMR (DMSO-d6, internal reference DMSO-d6 = 39.562)
6 11.28, 37.99, 127.18, 128.30, 128.88, 132.69, 179.72.
Compound 4 13C NMR (DMSO-d6, internal reference DMSO-d6 = 39.562
6 13.94, 42.42, 126.98, 128.06, 128.71, 132.78, 178.45.
1H NMR (100 MHz, DMSO-d6, internal reference DMSO-d6 = 2.4962) 6
1.33(d, broad, 6H), 2.67(m, 2H), 7.37(m, 5H).
IR (KBr) 3450(w), 3062(w,b), 2980(w), 2937(w), 2875(w), 1780(w),
1710(vs), 1598(w), 1493(m), 1456(w), 1398(s), 1375(m), 1314(w),
1193(s), 1169(m), 1156(w), 1103(w), 1077(w), 948(m), 912(w),
852(w), 775(m), 738(m), 693(s), 620(w), 611(w) cm- .
cis-Hexahydrophthalanilic acid (2-[(Phenylamino)-carbonyl]cyclohexane-
carboxylic acid) (5)
Cis-1,2-cyclohexanedicarboxylic anhydride (Aldrich) (5.0 g, 32.4
mmole) was dissolved in 200 ml CHC13 in a 500 ml Erlenmeyer flask.
Freshly distilled aniline (3.0 g, 32.2 mmole) was slowly added (drop-
wise over ten minutes) while rapidly stirring the solution. The
solution was stirred for three hours. During this time a white pow-
dery precipitate formed. The precipitate was suction filtered and
dried in a 50C vacuum oven to yield 7.0 g 5 (87.4%), mp 176-177C
literaturee3 mp 172-173C).
H NMR (60 MHz, DMSO-d6) 6 1.52(s, broad, 4H), 1.83(m, 4H), 2.57(m,
1H), 2.99(m, 1H), 6.85-7.73(m, 5H), 9.63(s, 1H), 11.78(s, broad,
13C NMR (DMSO-d6, internal reference DMSO-d6 = 39.562) 6 22.49, 24.10,
25.32, 27.85, 42.13, 42.67, 119.19, 122.74, 128.54, 139.66,
IR (KBr) 3388(s), 3060(s,b), 2935(s), 2860(m), 1718(vs), 1647(vs),
1597(vs), 1532(vs), 1498(m), 1433(vs), 1400(m), 1327(m), 1238(m),
1210(s), 1188(vs), 1130(m), 962(w), 938(w), 890(w), 860(w),
774(m), 746(m), 731(m), 691(s), 610(w) cm-1
dione) (cis-HHPI), [26491-47-4], (6)
Compound 5 (6.7 g, 27.1 mmole) was dissolved in 300 ml acetic
anhydride and stirred magnetically at 80C for twenty-four hours.
The solution was cooled and slowly added to vigorously stirred water
(dropwise over 1.5 hours). The cream colored precipitate that formed
was suction filtered and dried in a 500C vacuum oven overnight. The
precipitate was mixed with 100 ml CHC13, filtered, and washed several
times with CHC13. The chloroform insoluble part proved to be un-
reacted starting material (2.6 g). The chloroform was removed from
the filtrate on a rotary evaporator, leaving 3.8 g residue. This
residue was recrystallized from CC14 to give 3.2 g fine white needles
(84.2% based on recovered starting material), mp 130-133C (litera-
ture63 mp 132-133C).
H NMR (CDC13, 100 MHz) 6 1.48(m, 4H), 1.85(s, broad, 4H), 2.98(m,
2H), 7.35(m, 5H).
C NMR (CDC13) 6 21.81, 23.93, 40.06, 126.25, 128.28, 129.03, 132.15,
IR (KBr) 3468(w), 2942(m), 2911(m), 2858(m), 1775(w), 1709(vs),
1592(w), 1491(m), 1460(w), 1433(w), 1378(s), 1356(m), 1342(w),
1327(w), 1295(w), 1227(w), 1193(m), 1181(s), 1172(s), 1159(m),
1130(s), 1087(m), 921(w), 902(w), 887(m), 830(m), 776(m), 743(m),
698(m), 617(w) cm-'
trans-Hexahydrophthalanilic acid (2-[(Phenylamino)carbonyl]-cyclohex-
anecarboxylic acid) (7)
To a 125 ml Erlenmeyer flask was added 2.0 g (13.0 mmole) trans-
cyclohexanedicarboxylic anhydride (Aldrich) and 75 ml CHC13. The
resulting solution was stirred magnetically while 1.3 g (14.0 mmole)
distilled aniline was added dropwise. The solution was stirred at
500C for one hour. During this time, a white powdery precipitate
formed. The precipitate was suction filtered and dried in a vacuum
oven to yield 2.9 g of product (90.2%), mp 206-2120C literaturee3
1H NMR (100 MHz, DMSO-d6) 6 1.30(s, broad, 4H), 1.75(s, broad),
1.98(s, broad), 2.54(s, broad, 2H), 6.93-7.78(m, 5H), 9.92(s,
1H), 12.06(s, broad, 1H).
1C NMR (DMSO-d6, internal reference DMSO-d6 = 39.562) 6 24.93, 25.12,
28.58, 28.88, 29.53, 44.35, 44.47, 46.54, 119.12, 122.79, 128.47,
139.53, 173.48, 175.94, 176.04.
IR (KBr) 3325(m), 3060(b), 2950(m), 2927(m), 2862(w), 1699(vs),
1655(s), 1601(m), 1533(s), 1500(w), 1443(m), 1416(m), 1328(m),
1313(m), 1262(m), 1205(m), 1186(w), 1115(w), 920(m), 900(w),
770(w), 745(m), 692(m), 672(w) cm-1
To a 125 ml Erlenmeyer flask was added 2 g 8 and 100 ml acetic
anhydride. The resulting solution was stirred at 80C for twenty-
two hours and then allowed to cool to room temperature. The solution
was added dropwise to a vigorously stirred aqueous NaC1 solution (500
ml). Some white precipitate formed. The mixture was cooled in an
ice bath for several hours, and the white crystalline solid that
formed was suction filtered, washed with water, and dried overnight
in a 50C vacuum oven. Recrystallization from CC14 yielded 1.2 g
colorless, very fine crystals, mp 194-1960C literaturee3 mp 195-
H NMR (CDC13, 100 MHz) 6 1.32-1.67(m, 4H), 1.7-2.3(m, 4H), 2.3-2.5
(m, 2H), 7.2-7.5(m, 5H).
C NMR (CDC13) 6 25.15, 25.54, 47.52, 126.25, 128.03, 128.98, 132.15,
IR (KBr) 3462(w), 3060(w), 2922(m), 2860(w), 1773(w), 1711(vs),
1595(w), 1490(m), 1446(w), 1375(s), 1292(w), 1270(w), 1229(w),
1212(w), 1174(s), 1105(s), 1072(w), 1046(w), 922(w), 877(m),
753(m), 692(m), 670(w), 620(w) cm-1
To a 125 ml Erlenmeyer flask was added 20 g (200 mmole) 4-
methoxy-3-buten-2-one (Aldrich), 30 g (202 mmole) triethyl ortho-
formate (Aldrich), 0.1 g p-toluenesulfonic acid monohydrate (Aldrich)
and 50 ml absolute ethanol. The solution turned deep black soon after
the addition of the p-toluenesulfonic acid. The reaction was somewhat
exothermic. The flask was stoppered and allowed to stand at room
temperature for sixteen hours. At the end of this time, the mixture
was fractionally distilled through a Vigreaux column. Distillation
at atmospheric pressure yielded a fraction boiling at 52-570C (~ 20
ml) presumed to be ethyl format literaturee4 bp 54.50C). Excess
ethanol was also removed at atmospheric pressure. The distillation
flask was allowed to cool and the pressure reduced to 10mmHg. Con-
tinued distillation gave 16.6 g (37.7%) colorless liquid with a boil-
ing range 85-95C (10 mm). The product proved to be a mixture of
isomers (various monomethoxy-triethoxybutanes).
H NMR (100 MHz, acetone-d6) 6 1.02-1.32(m, 4 overlapping triplets,
J = 7.0 Hz, 9H), 1.25(s, 3H), 1.88(d, J = 4.7 Hz, 2H), 3.09,
3.10, 3.21 and 3.23 (4 singlets, combined area 3H), 3.26-3.65
(m, overlapping quartets, J = 7.0 Hz, 6H), 4.50-4.60(m, over-
lapping triplets, J = 4.7 Hz, 1H).
C NMR (acetone-d6) 6 15.64, 15.74, 22.51, 22.56, 23.03, 23.07,
41.18, 41.64, 42.13, 47.86, 47.91, 51.73, 55.75, 60.58, 60.67,
60.94, 61.16, 100.54, 100.59, 101.40.
IR (thin film) 2980(vs), 2938(s), 2883(s), 1614(w), 1512(m), 1483(w),
1445(m), 1393(m), 1377(m), 1306(m), 1276(w), 1247(m), 1172(m),
1160(m), 1120(s,b), 1092(m), 1058(s,b), 999(w,b), 948(m),
The N-phenylmaleimide (NPM) used in this preparation was obtained
from Aldrich Chemical Co., and was recrystallized from cyclohexane
before use. N-Phenylmaleimide (5.0 g, 29.0 mmole) and 1-methoxy-1,3,
3-triethoxybutane (6.7 g, 30.4 mmole) were mixed in a 100 ml, one-
necked round-bottom flask. Hydroquinone (0.3 g) and Na2HPO3 (0.3 g)
were also added. The flask was evacuated to 25 mmHg with a vacuum
pump and immersed in a 70C oil bath. The yellow crystalline mass
soon dissolved, and the resulting solution was stirred magnetically
at 70-80C and 25 mmHg, until its weight decreased by about 2.5 g
(2 equivalents of ethanol). This took about one week (6.8 days). The
temperature was controlled so that it did not exceed 85C at any time.
The flask was cooled to room temperature, and the yellow solid mass
was triturated with absolute ethanol. The cream colored precipitate
that formed was filtered, and the ethanol was removed from the fil-
trate via rotary evaporation. The residue was triturated again to
yield more cream colored powder, which was filtered. This process
was repeated again, and the combined precipitates were recrystallized
from ethanol:water (3:1) to yield 5.2 g (56.9%) colorless plates, mp
H NMR (100 MHz, CDC13) 6 1.09(t, J = 6.96, 3H), 1.31(t, J = 6.96,
3H), 2.35(broad AB quartet, 2H), 3.20(dd, J3a,4 = 3.9, J3a,7a
8.9, 1H), 3.24-3.98(complex m, 5H), 4.21(apparent q, J4,5 = 2.8,
J4,5a J4,3a = 3.9, 1H), 4.95(dd, J7,5 = 1.5, J7,7a = 3.9,
J7,5 = 0, 1H), 7.20-7.55(m, 5H).
C NMR (CDC13) 6 14.45(q), 15.30(q), 30.85(t), 39.21(d), 44.47(d),
62.53(t), 65.02(t), 72.50(d), 86.68(d), 126.60(d), 128.33(d),
129.01(d), 132.35(d), 152.72(s), 176.16(s), 176.94(s).
IR (KBr) 3480(w), 3059(w), 2973(m), 2938(m), 2890(m), 1779(w),
1717(vs), 1668(m), 1594(w), 1492(m), 1450(m), 1386(s), 1342(w),
1324(w), 1300(m), 1279(m), 1260(m), 1233(m), 1210(s), 1194(s),
1183(s), 1170(s), 1163(s), 1150(m), 1076(m), 1045(m), 1020(m),
924(w), 895(w), 864(w), 838(w), 789(m), 777(m), 744(s), 687(m),
626(w), 610(w) cm-1
LRMS (70 eV, m/z, relative intensity) 315(M 10.0), 271 (18.8), 242
(15.2), 168 (12.3), 139 (21.5), 119 (100.0).
HRMS (C18H21N04 requires 315.14706) found 315.14699.
Analysis. Calculated for C 8H21N04: C, 68.55; H, 6.71; N, 4.44.
Found: C, 68.54; H, 6.74; N, 4.44.
Raney nickel catalyst was prepared65 by slowly adding 70 ml 16%
aqueous NaOH to 10 g Raney nickel alloy (PCR) in a 250 ml beaker. The
beaker was cooled in an ice bath if the generation of hydrogen became
too violent. After the addition of the NaOH solution was complete,
the beaker was heated gently on a hot plate until the evolution of
hydrogen stopped (~ 2 hours). The solution was diluted with water and
the black, active catalyst was isolated by suction filtration, and
washed with water until the filtrate was neutral to litmus. Care was
taken so as not to let the catalyst become dry, since Raney nickel
ignites spontaneously when dry.
Compound 10 (1.75 g, 5.5 mmole) was dissolved in 200 ml 95%
ethanol in a 250 ml hydrogenation bottle, and the moist, freshly made
catalyst was added. The solution was heated to 700C with a heating
tape wrapped around the bottle, and the bottle was placed in the Parr
hydrogenation apparatus. The apparatus was pressurized with hydrogen,
evacuated (aspirator) several times, and finally pressurized to 51
PSI. The solution was shaken at this hydrogen pressure and 70-80C
for 1.5 hours. At the end of this time, the solution was cooled to
room temperature and the pressure released. The solution was filtered
into a round-bottom flask, and the solvent was removed by rotary evap-
oration to leave 1.6 g oily residue. NMR analysis showed that the
residue was about 25% starting material. The residue was treated
with absolute ethanol, and the cream colored precipitate that formed
was isolated by filtration (0.25 g). Rotary evaporation of the fil-
trate left 1.2 g (91.4% based on recovered starting material) pale
green oil. This oil was purified further by percolation through a
short (~ 15 cm) silica gel column using isooctane:CH2C12:methanol
1H NMR (100 MHz, CDC13) 6 1.10(t, J = 7.0, 3H), 1.20(t, J = 7.0, 3H),
1.75-2.35(m, J5,4 = 2.2, J5,6 = 6.5, 4H), 2.79-3.07(m, J3a,4 =
3.5, J7a,7 = 6.3, Ja, 76 = 10.6, J3 ,7a = 9.5, 2H), 3.20-3.81
(m, 5H), 4.01-4.16(m, J4,3a = 3.5, 1H), 7.20-7.50(m, 5H).
13C NMR (CDC13) 6 15.30(q), 15.55(q), 25.98(t), 32.58(t), 37.48(d),
43.72(d), 63.75(t), 64.43(t), 72.89(d), 74.03(d), 126.57(d),
128.40(d), 129.03(d), 132.30(s), 176.67(s), 178.43(s).
IR (smear on NaC1 plate) 3480(w), 3070(w), 2979(m), 2925(m), 2880(m),
1778(w), 1715(vs), 1598(w), 1500(s), 1457(w), 1445(w), 1376(s),
1290(w), 1262(w), 1230(w), 1190(s), 1160(m), 1105(s), 1079(m),
922(w), 840(w), 797(w), 758(m), 736(m), 690(m), 620(m) cm-1
LRMS (70 eV, m/z, relative intensity) 317 (3.5, M+), 273 (57.6, meta-
stable), 227 (100.0).
HRMS (C18H23NO4 requires 317.1627) found: 317.1625.
Analysis. Calculated for C18H23N04: C, 68.12; H, 7.30; N, 4.41.
Found: C, 67.98; H, 7.32; N, 4.36.
1-Methoxy-3-(trimethylsiloxy)butadiene, [59414-23-2], (12)
This compound was made according to the procedure of Danishefsky
and Kitahara.66 Freshly fused ZnC12 (1.0 g) and 58.0 g triethylamine
(distilled from KOH) were added to a dry 500 ml Erlenmeyer flask. The
flask was stoppered, and the contents magnetically stirred for one
hour to form a white, milky suspension. At the end of the hour, 25.0
g (0.25 mole) of 4-methoxy-3-buten-2-one (Aldrich) dissolved in 75 ml
benzene was added to the suspension. Then 54.2 g (0.50 mole) chloro-
trimethylsilane (Pierce Chemical Co.) was added with a 30 ml syringe.
An exothermic reaction took place on addition of the chlorotrimethyl-
silane, and an orange precipitate formed immediately. This suspension
was stirred at 40-500C overnight and then poured into 500 ml of anhy-
drous ether. The precipitate was suction filtered and washed several
times with anhydrous ether. The filtrate was concentrated on a ro-
tary evaporator and then distilled. The colorless fraction distilling
at 48-500C (4.5mmHg) was collected to yield 24.3 g (56.5%) 1-methoxy-
3-(trimethylsiloxy)butadiene literaturee6 bp 54-55C, 5mm Hg).
H NMR (100 MHz, CDC13) 6 0.22(s, 9H), 3.54(s, 3H), 4.06(d, J = 3.4,
2H), 5.32(d, J = 12.3, 1H), 6.81(d, J = 12.3, 1H).
1C NMR (CDC13, internal reference CDC13 = 77.062) 6 -0.34(q), 55.87
(q), 90.62(t), 102.85(d), 150.06(d), 153.71(s).
IR (thin film) 3120(w), 3080(w), 3006(w), 2963(m), 2903(w), 2837(w),
1652(s), 1596(m), 1453(w), 1323(vs), 1257(s), 1213(vs), 1167(s),
1133(m), 1022(vs), 994(m), 960(w), 939(m), 921(m), 850(vs),
753(m), 682(w), 638(m), 617(m) cm-1.
The procedure used was analogous to that used by Danishefsky
et al.67 To a 125 ml Erlenmeyer flask was added 10.0 g solid N-
phenylmaleimide (57.8 mmole), then 11.1 g l-methoxy-3-(trimethylsil-
oxy)butadiene. The flask was swirled, and evolution of heat was
noted. A homogeneous, light yellow solution resulted. After about
five minutes, the solution began to cool. A yellowish white crystal-
line mass formed on cooling. This crude product was broken up and
washed with a small amount of cold absolute ether. The product was
filtered, yielding 16.3 g pure white crystals. The ether washings
were evaporated, yielding more crystalline product. This residue was
washed, this time with a smaller amount of ether, and filtered to
yield 1.5 g more product. The total yield was 17.8 g (89.4%) of
white crystals, mp 114-116C. Repeated recrystallization from cyclo-
hexane failed to yield product that gave a satisfactory elemental
analysis. This was probably due to partial hydrolysis of the silyl
H NMR (100 MHz, CDC13) 6 0.25(s, 9H), 2.28-2.55(dd, "B" part of AB
quartet, J73,7 = 16.9, J7,7a = 10.1, J76,5 0, 1H), 2.66-2.93
(ddd, "A" part of AB quartet, J7a,76 = 16.9, J7a,7a = 6.4,
7a,5 = 2.4, 1H), 2.98-3.16(dd, "B" part of AB quartet, J3a,7a
9.5, 3a,4 = 4.0, 1H), 3.20(s, 3H), 3.20-3.47(6 lines of ex-
pected 8 line pattern, "A" part of AB quartet, J7a,75 = 10.1,
J7a,3a = 9.5, J7a,7a = 6.4, 1H), 4.35(dd, J4,5 = 6.4, J4,3a =
4.0), 5.18(dd, J5,7 = 2.4, J ,4 = 6.4, J5,7 0, 1H), 7.20-
1C NMR (CDC13) 6 0.121(q), 27.07(t), 37.43(d), 45.69(d), 55.54(q),
73.06(d), 100.94(d), 126.64(d), 128.35(d), 128.98(d), 132.35(s),
156.20(s), 176.06(s), 178.77(s).
IR (KBr) 3477(w), 3075(w), 2985(w), 2958(w), 2922(w), 2900(w),
2820(w), 1775(w), 1712(vs), 1643(m), 1597(w), 1496(m), 1455(w),
1388(s), 1360(m), 1342(m), 1308(m), 1271(m), 1257(m), 1228(m),
1197(s), 1182(s), 1097(m), 1081(m), 1021(w), 975(m), 928(m),
896(m), 854(s), 822(m), 748(m), 693(.m), 622(m) cm-1
LRMS (70 eV, m/z, relative intensity) 345 (3.1), 345 (M+, 12.1), 330
(39.4), 314 (41.6), 296 (12.2), 172 (30.4), 157 (100.0).
Analysis. Calculated for C18H23N04Si: C, 62.58; H, 6.71; N, 4.05.
Found: C, 63.63; H, 6.54; N, 3.90.
Silyl enol ether 13 was hydrolyzed to ketone 14 via two different
methods. The first uses the procedure of Danishefsky et al.67 Thus,
10.0 g (29.0 mmole) of silyl enol ether 13 was treated with 100 ml of
a solution comprised of 0.1N HC1 and tetrahydrofuran (THF) (1:4 by
volume). After stirring for 0.5 hour, the pale yellow solution was
poured into 300 ml 5% NaHCO3. The resulting deep yellow aqueous solu-
tion was extracted with CHC13 (4 x 75 ml). The combined organic
layers were dried over anhydrous MgSO4 overnight. The MgSO4 was
separated by filtration, and the solvent removed by rotary evapora-
tion. The resulting pale green oil was placed in a dessicator that
was subsequently evacuated. After drying at reduced pressure for
twenty-four hours, the oil solidified, yielding 7.2 g (90.9%) very
pale green solid.
The method of Semmelhack et al.68 was preferable for the desilyl-
ation of 13 because the reaction is easy and the product very clean.
Enough unactivated 3 A molecular sieves (Linde) were added to a 125
ml Erlenmeyer flask to cover the bottom. Then 1.0 g 13 dissolved in
100 ml of a solution of methanol:CHC13 (1:1) was added to the flask.
The flask was stoppered and allowed to stand at room temperature over-
night. The molecular sieves were removed by filtration and the sol-
vent evaporated on a rotary evaporator, to leave 0.80 g pale green
oil (101%). The product was dissolved in 5 ml of absolute ethanol:
chloroform (1:1). Slow evaporation of this solution yielded color-
less crystals which were isolated by filtration and washed with cold
absolute ethanol. After drying in a vacuum oven (50C) overnight,
the product weighed 0.70 g. Another workup of the ethanol washings
yielded an additional 0.05 g colorless crystals for a total isolated
yield of 0.75 g (95%), mp 107-1080C. Both of the above methods pro-
duced products with identical spectral properties.
H NMR (100 MHz, CDC13) 6 2.17(dd, "B" part of AB quartet, J58,4
2.2, J5,5a = 18.3, 1H), 2.50-3.50(m, J73,7a = 7.5, 7,7a ~
9.5, J,4 3.2, 3a,7a 9.4, J3a,4 3.5, 5H), 4.18 (appar-
ent q, 1H), 7.19-7.53(m, 5H).
1C NMR (CDC13) 6 36.10(d), 36.83(t), 40.46(t), 44.38(d), 57.25(q),
75.21(d), 126.54(d), 128.65(d), 129.09(d), 132.02(s), 175.31(s),
IR (KBr) 3480(w), 3078(w), 3054(w), 2998(w), 2965(w), 2952(w),
2935(w), 2904(w), 2838(w), 1778(w), 1710(vs), 1598(w), 1494(m),
1458(w), 1409(m), 1389(s), 1347(m), 1328(w), 1308(w), 1263(w),
1240(w), 1230(w), 1203(s), 1181(m), 1098(m), 1082(m), 1041(w),
1021(w), 968(w), 913(w), 897(w), 889(w), 814(m), 779(w), 758(m),
732(m), 693(m), 624(m) cm-1
LRMS (70 eV, m/z, relative intensity) 273(M 72.4), 243 (28.1), 188
Analysis. Calculated for C15H15N04: C, 65.92; H, 5.53; N, 5.12.
Found: C, 65.98; H, 5.54; N, 5.09.
Ketone 14 was reduced to alcohol 15 by catalytic hydrogenation.
Thus, 2.5 g (9.15 mmole) ketone 14 was dissolved in 200 ml 95% etha-
nol in a 500 ml capacity hydrogenation bottle. A catalytic amount
(~ 0.01 g) of PtO2 (Englehard Industries) was added to the solution,
and the bottle was placed in the Parr shaker. The hydrogenation
apparatus was flushed with hydrogen several times and finally pres-
surized to 46 PSI with hydrogen. The shaker was started, and the
solution was shaken at room temperature for four hours. At the end
of this time, the apparatus was depressurized, and the catalyst was
removed by filtration. The solvent was removed by rotary evaporation
to yield a pale green oil that crystallized on standing in a dessi-
cator for several days. This procedure yielded 2.5 g (99%) colorless
crystals of alcohol 15, mp 125-1270C.
H NMR (100 MHz, CDC13) 6 1.6-2.4(m, J5,4 = 3.8, J5s,6 : 6.1, J5,5 =
15.1, J7u,6 : 7.2, J7a,7a = 6.0, 4H), 2.76-3.10(m, 2H), 3.2(s,
broad, 1H), 3.33(s, 3H), 3.6-4.2(m, 2H), 7.10-7.54(m, 5H).
1C NMR (CDC13) 6 28.80(t), 32.21(t), 36.48(d), 43.86(d), 57.73(q),
64.97(d), 76.18(d), 126.60(d), 128.52(d), 129.11(d), 132.18(s),
IR (KBr) 3507(s), 3043(w), 2979(w), 2960(w), 2915(w), 2892(w),
2856(w), 2808(w), 1772(w), 1704(vs), 1596(w), 1493(m), 1457(w),
1392(s), 1352(w), 1292(m), 1279(m), 1263(m), 1230(w), 1200(m),
1178(s), 1151(m), 1099(m), 1084(m), 1064(m), 973(w), 938(w),
918(w), 901(w), 846(w), 805(m), 761(m), 736(m), 691(w), 618(w),
LRMS (70 eV, m/z, relative intensity) 275(M+, 57.0), 245 (24.9), 227
(11.4), 188 (23.3), 119 (24.5), 103 (91.5), 84 (100.0).
Analysis. Calculated for C15H17N04: C, 65.44; H, 6.22; N, 5.09.
Found: C, 65.42; H, 6.22; N, 5.09.
This compound was prepared by methylation of alcohol 15 using
trimethyloxonium tetrafluoroborate.69 Alcohol 15 (1.5 g, 5.45 mmole)
was dissolved in 250 ml freshly distilled (from P205) CH2C12 in a
500 ml Erlenmeyer flask with a ground glass stopper. Excess (~ 3 g)
trimethyloxonium tetrafluoroborate (Alfa) was added under a blanket
of dry nitrogen, i.e., the bottle was opened and the transfer made
under an inverted funnel connected to a nitrogen line. The trimethyl-
oxonium tetrafluoroborate was largely insoluble in CH2CI2. The flask
was tightly stoppered, and the suspension was stirred magnetically
for sixty hours at room temperature. At the end of this time, 100 ml
H20 was added. Then, solid NaHCO3 was added to the stirred solution
in small increments until further additions no longer resulted in the
evolution of CO2 bubbles. The organic layer was separated, and the
aqueous layer was extracted further with CHC13 (2 x 20 ml). The com-
bined organic layers were dried over anhydrous MgSO4 for several
hours. The MgSO4 was separated by filtration and the solvent removed
by rotary evaporation to yield a yellow orange oil. This oil was
purified by percolation through a short (15 cm) silica gel column
using hexane:CH2C12:MeOH (50:20:1). A pale yellow oil remained after
solvent evaporation. This oil solidified on standing in a dessicator
(~ 1 week). Recrystallization of this solid residue from absolute
ethanol gave 1.4 g (89%) colorless crystals, mp 120-1220C.
H NMR (300 MHz, CDC13) 6 1.841-2.072(dddd, J5,4 = 2.8, J5,6 = 5.6,
J5a,4 = 4.7, J5a,6 = 8.6, J5,58 15.3, 2H), 1.914-2.029 (appar-
ent q, center peakssplit, J7,7 = 11.9, J7,7a = 10.7, J7 ,6
11.2, 1H), 2.303-2.383(ddd, J7a,77 = 11.9, J7a,7a = 7.1, J7a,6
4.3, 1H), 2.878-2.923(dd, J3a,4 = 3.8, J3a,7a = 9.6, 1H), 2.949-
3.040(ddd, J7a,3a = 9.6, J7a,7 = 10.7, J7a,7 = 7.1, 1H),
7a,3a 7a,73 7a,7a
3.306(s, 3H), 3.333(s, 3H), 3.430-3.529(dddd, J6,7: = 11.2,
J6,5a = 8.6, J6,5 = 5.6, J6,7, = 4.3, 1H), 3.959-3.996(ddd,
J4,5 = 4.7, J4,3a = 3.8, J4,5 = 2.8, 1H), 7.244-7.484(m, 5H).
3C NMR (CDC13) 5 25.46(t), 31.19(t), 37.16(d), 43.42(d), 55.95(q),
56.71(q), 74.25(d), 75.59(d), 126.60(d), 128.35(d), 128.69(d),
132.32(s), 176.33(s), 178.33(s).
IR (KBr) 3470(w), 3066(w), 2991(w), 2940(m), 2895(m), 2812(m), 1775(w),
1709(vs), 1594(w), 1497(s), 1470(w), 1452(m), 1420(w), 1388(vs),
1362(m), 1320(w), 1292(m), 1252(m), 1192(s), 1180(s), 1160(s),
1100(s), 1078(vs), 1032(w), 987(w), 973(w), 940(w), 903(w),
846(w), 805(w), 792(w), 769(m), 753(w), 738(m), 695(m), 623(w),
LRMS (70 eV, m/z, relative intensity) 289 (M+, 13.2), 259 (26.8),
227 (30.3), 175 (28.5), 173 (50.4), 119 (20.8), 111 (14.3),
110 (15.7), 109 (15.5), 101 (17.0), 93 (23.2), 85 (27.9), 84
HRMS. Required for C16H19N04: 289.13141 Found: 289.13189.
Analysis. Calculated for C16H19N04: C, 66.42; H, 6.62; N, 4.84.
Found: C, 66.32; H, 6.64; N, 4.82.
Epimerization of cis-4,6 Diethoxyhexahydro-2-phenyl-1H-isoindole-
Compound 11 (- 200 mg) was dissolved in 0.4 ml DMSO-d6, and the
solution was transferred to an NMR tube. A 13C NMR spectrum was ob-
tained on this sample. Several drops of 2,2,6,6-tetramethylpiperidine
(Aldrich) were then added to the tube, and the tube was placed in a
600C water bath. The epimerization was monitored by periodically
obtaining 1C spectra over a period of several weeks (fifty-four
days). Nine peaks with distinctly different chemical shifts from
the original compound were observed to increase in intensity with
time. The final cis/trans ratio was about three (75% cis). The 13C
chemical shifts and their assignments are given in Table 1. Carbons
not included in Table 1 did not exhibit a readily observable chemi-
cal shift change on epimerization.
1C Chemical Shifts (6, ppm from TMS) for cis
(DMSO-d6, internal reference DMSO-d6 =
and trans 11.
Carbon 6 cis 6 trans 6 cis-6 trans
1 178.65 177.72 0.93
3 176.55 176.23 0.32
7a 36.84 38.40 1.56
4* 73.93 74.74 0.81
5 25.98 27.24 1.26
7 32.24 34.63 2.39
3a 43.20 45.62 2.42
1' 132.71 132.44 0.27
* Assignments could be reversed.
Attempted reduction of ketone 14 to alcohol 15 by using sodium
borohydride (NaBH4) as a reducing agent led to bicyclic lactone 17
instead. Thus, 0.2 g (5.3 mmole) NaBH4 (Eastman) was added to a
stirred solution of 1.0 g (3.7 mmole) ketone 14 in 75 ml of 95% etha-
nol. The solution was stirred for 0.5 hour at room temperature. At
the end of this time, 12 M HC1 was slowly added (dropwise) until the
solution was acidic to litmus. Upon rotary evaporation of the bulk
of the solvent, a crystalline material formed. This material was
broken up and washed several times with water. The residue was
treated with chloroform, but was largely insoluble. Recrystalliza-
tion of the residue from ethanol:water (3:1) yielded colorless crys-
tals that had a sharp melting point (201-202C). On the basis of
the spectral information given below, the compound was assigned the
bicyclic lactone structure 17.
H NMR (100 MHz, DMSO-d6) 6 1.66-2.28(m, 4H), 2.91(ddd, 1H), 3.11(dd,
1H), 3.29(s, 3H), 3.80-3.95(m, 1H), 4.74(m, 1H), 6.95-7.63(m,
5H), 10.08(s, 1H).
13C NR (DMSO-d6) 6 27.78(t), 33.26(t), 38.28(d), 43.23(d), 55.54(q),
73.01(d), 75.91(d), 119.19(d), 123.31(d), 128.59(d), 138.93(s),
IR (KBr) 3302(m), 3282(m), 3138(w), 3067(w), 2978(w), 2967(w), 2942(w),
2877(w), 2840(w), 1736(vs), 1689(vs), 1601(s), 1540(s), 1493(m),
1443(s), 1381(m), 1362(m), 1334(m), 1320(m), 1302(m), 1279(w),
1247(m), 1212(m), 1190(m), 1150(m), 1108(s), 1088(m), 1052(m),
1018(m), 963(m), 930(w), 917(w), 788(w), 762(s), 701(m), 655(w),
LRMS (70 eV, m/z, relative intensity) 275 (M+, 50.2), 245 (7.6), 188
(9.2), 174 (4.9), 119 (13.0), 103 (36.8), 93 (100.0).
Analysis. Calculated for C15H17NO4: C, 65.44; H, 6.22; N, 5.09.
Found: C, 65.53; H, 6.38; N, 5.05.
Maleimide Synthesis: General
Many of the maleimides used in this study [N-(4-fluorophenyl),
N-(4-chlorophenyl), N-(4-bromophenyl), N-(4-nitrophenyl), N-(4-carbo-
ethoxyphenyl), N-(4-methylphenyl), N-(4-acetoxyphenyl), N-(4-methoxy-
phenyl)] had been previously synthesized in these laboratories.70
They were purified by recrystallization from cyclohexane and charac-
terized by various spectral techniques. Only the spectral data for
these maleimides are given here. The N-acetoxymaleimide used was
synthesized in these laboratories by David P. Vanderbilt,1 and was
used without further purification. N-phenylmaleimide was obtained
from Aldrich Chemical Company, and was recrystallized from cyclohex-
ane before use.
In general, the synthetic procedure first developed by Searle72
and detailed by Barrales-Rienda et al.73 was used. The procedure
involves the reaction of the appropriately substituted aniline with
maleic anhydride to form an intermediate maleanilic acid. The male-
anilic acid is then dehydrated to the maleimide using acetic anhy-
butenoic acid) (18)
The contents of a 1.0 g ampule of 97.5% 15N-enriched aniline
(Merck and Co., Inc.) were mixed with 4.0 g freshly distilled regu-
lar aniline (5.0 g total, 53.7 mmole). The mixture was dissolved in
10 ml of chloroform, and the resulting solution was added dropwise
to a rapidly stirred solution of 6.0 g maleic anhydride (61.8 mmole)
in chloroform. A cream colored precipitate formed immediately on
addition of the aniline solution. The mixture was stirred for one
hour and allowed to stand at room temperature overnight. The mixture
was suction filtered and washed with chloroform several times.. After
drying in a 50C vacuum oven for several hours, the yield of cream
colored powder was 10.3 g (100.3%), mp 203-204C literaturee4 mp
206C). The approximate percentage of 15N in this compound could be
determined by integration of the N-H resonance of the 1H NMR spec-
trum. The 15N-H resonance appears as a doublet, whereas the 14N-H
resonance is a singlet appearing at the midpoint of the 15N-H doub-
let (approximately 20% 15N).
H NMR (DMSO-d6) 6 6.41 (AB quartet, J = 12.1, 2H), 6.87-7.70(m, 5H),
10.44[d, J(15NH) = 90.3, s, 1H (d+s)], CO2H not observed.
1C NMR (DMSO-d6, internal reference DMSO-d6 = 39.562) 6 119.72(d),
124.10(d), 128.93(d), 130.59(d), 131.86[d, 2 ( 15N-CO-C) = 9.7],
138.58(s, 1 15N-C(quat. aromatic)] = 13.4), 163.39[s, 1J(15N-CO)
= 15.9], 166.95(s).
IR (KBr) 3254(m), 3193(m), 3060(m,b), 2863(w), 2240(m), 2075(w),
1876(m), 1697(s), 1620(s), 1635(vs,b), 1489(s), 1449(s), 1429(m),
1330(m), 1267(m), 1223(w), 1189(w), 998(m), 970(m), 900(m),
849(s), 800(m), 754(s), 686(m), 652(m), 605(s) cm-1
Finely divided 15N-enriched N-phenyl maleanilic acid (10.3 g,
53.9 mmole) was combined with 3.1 g freshly fused sodium acetate in
a 250 ml, three-necked, flame dried, N2 flushed round-bottom flask
equipped with a mechanical stirrer and a reflux condenser. Acetic
anhydride (32.0 g) was added, and the mixture was stirred while the
flask was heated to 80C in an oil bath. The bright yellow solution
was stirred at 800C for one hour. The flask was then allowed to cool
to room temperature while stirring was continued for two additional
hours. The reaction mixture was then added dropwise to rapidly
stirred ice water in which a small amount of salt (NaC1) had been
dissolved. The crude yellow precipitate that formed was suction
filtered, washed with water, and dried in a 50C vacuum oven over-
night. Vacuum sublimation (aspirator pressure) of the crude crystals
gave 6.4 g (68.8%) bright yellow needles, mp 87-89C literaturee5
mp 89-900C). An approximate percent enrichment was calculated by
obtaining a high resolution mass spectrum of the enriched maleimide
and comparing the observed intensity of the M+1 peak with the theo-
retical intensity [calculated from the known76 natural abundances of
13C (1.08%), 2H (0.016%), and 170 (0.04%)]. Thus, for C10H702, (1.08
x 10) + (0.016 x 7) + (0.04 x 2) = 11% of the intensity of the M+1
peak is not due to ions containing 15N. The following equation was
used for the calculation:
15 (M+1)Total 0.11 (M)
S (M) + 0.11 (M)
where the quantities in parentheses are the observed absolute inten-
sities of the corresponding ions. The calculated approximate % 15N
1H NMR (100 MHz, CDC13) 5 6.75(s, 2H), 7.22-7.52(m, 5H).
13C NMR (CDCI3) 6 126.08(d), 127.89(d), 129.11(d), 133.93(s, 1J 15N-C
(quat. aromatic)] = 14.2), 134.08[d, 2( 15N-CO-13CH) = 7.7],
169.51[s, 1J(15N-13CO) = 14.6].
IR (KBr) 3090(w), 1775(w), 1704(vs), 1592(m), 1504(m), 1383(s),
1141(m), 1071(w), 1029(w), 941(w), 904(w), 829(s), 753(m),
692(s), 622(m) cm-1
LRMS (70 eV, m/z, relative intensity) 174 (M+1, 35.2), 173 (M,
100.0), 145 (8.3), 129 (26.3), 117 (15.1).
HRMS. Required for C10H702N: 173.0477. Found: 173.0484. Molecu-
lar ion absolute intensity (M) = 908, (M+1) = 289.
15N NMR (10.11 MHz, 1H decoupled, CDC13) 217.8(s, upfield from ex-
N-Cyclohexylmaleanilic acid [4-(Cyclohexylamino)-4-oxo-(Z)-2-butenoic
acid] [21477-59-8] (20)
Slow, dropwise addition of 31.0 g cyclohexylamine (313 mmole)
to a stirred solution of 31.0 g maleic anhydride (316 mmole) in 300
ml chloroform resulted in an exothermic reaction. The amine was
added slowly enough to avoid boiling of the chloroform. The solution
was allowed to stand at room temperature overnight. A white crystal-
line mass filled the flask the next morning. This mass was broken
up, filtered, and washed with cold chloroform and hexane. Evapora-
tion of the washings produced more hexane insoluble product which was
similarly filtered and washed. Removal of the residual solvent from
the combined precipitates in a 500C vacuum oven yielded 63.1 g (102%)
pure white product, mp 153-1540C literaturee7 mp 182C).
H NMR (60 MHz, DMSO-d6) 6 0.9-2.1(broad m, 10H), 3.4-4.0(m, 1H),
6.35 (AB q, J = 12.1, 2H), 9.10(broad d, 1H), CO2H not observed.
IR (KBr) 3240(m), 3075(m), 2940(s), 2861(m), 1920(w, b), 1702(vs),
1635(s), 1578(s), 1521(vs, b), 1480(vs, b), 1406(s), 1350(m),
1320(m), 1296(m), 1256(m), 1245(m), 1150(m), 1083(s), 983(m),
925(w), 910(w), 888(w), 877(w), 855(s), 790(w), 755(w), 635(m),
N-Cyclohexylmaleimide (l-Cyclohexyl-1H-pyrrole-2,5-dione), [1631-25-0],
This compound was synthesized by thermal dehydration of the
corresponding maleamic acid.78 Thus, 15.0 g N-cyclohexylmaleamic
acid (76 mmole) and 50 ml xylene (mixed isomers) were added to a 250
ml, three-necked, round-bottom flask equipped with a nitrogen inlet,
mechanical stirrer, and reflux condenser. The suspension was stirred
as the flask and contents were heated to reflux in an oil bath. The
reflux was maintained for five hours. The flask was allowed to cool,
and most of the xylene was evaporated in vacuo. The residue was
treated with acetone, and the acetone insoluble portion (unreacted
starting material) was separated by filtration (~ 7.5 g). The acetone
was evaporated from the filtrate, and the residue was sublimed to
yield 1.5 g (22%, based on recovered starting material) colorless
needles, mp 86-87C literaturee9 mp 890C).
H NMR (100 MHz, CDCI3) 6 1.2-2.1(m, 10H), 3.75-4.03(tt, J = 3.9,
11.8, 1H), 6.66(s, 2H).
C NMR (CDC13) 6 25.10, 25.98, 29.95, 50.74, 133.91, 170.85.
IR (KBr) 3445(w), 3089(m), 2931(s), 2860(m), 1773(w), 1700(vs),
1598(w), 1579(w), 1465(w), 1457(w), 1396(w), 1403(s), 1382(m),
1371(m), 1348(m), 1265(w), 1178(m), 1140(m), 1113(m), 1018(w),
986(m), 892(w), 826(s), 748(w), 692(s), 638(m) cm-1
LRMS (70 eV, m/z, relative intensity) 179 (M 35.5), 136 (40.2),
123 (8.5), 99 (100.0).
N-Phenylcitraconamic acid [2(or 3)-Methyl-4-oxo-4-(phenylamino)-(Z)-
2-butenoic acid], [39734-91-3], (22)
Slowly adding 15.0 g aniline (161 mmole) to a stirred solution
of 17.5 g citraconic anhydride (Aldrich, 156 mmole) in CHC13 resulted
in an exothermic reaction and the immediate formation of a cream
colored precipitate. After stirring for one hour, the suspension was
filtered, washed with CHC13 and suspended in boiling CHC13 for an
additional thirty minutes. The suspension was cooled and filtered.
The precipitate was placed in a 500C vacuum oven overnight. The iso-
lated yield was 32.0 g (100%) of an off white powder, mp 175-176C
literaturee4 mp 171C). The product proved to be a mixture of the
two possible isomers (methyl substitution at the 2 or 3 position);
however, no attempt was made to separate them.
H NMR (60 MHz, DMSO-d6) 6 2.02(d, J = 1.2, 3H), 6.19(q, 3 peaks re-
solved, J = 1.2, 1H), 6.85-7.85(m, 5H), 10.13(broad s, 1H),
COOH not observed.
13C NMR (DMSO-d6, internal reference DMSO-d6 = 39.562) 6 20.83, 21.66,
119.62, 119.82, 123.67, 123.82, 128.88, 128.98, 139.12, 139.36,
142.97, 150.38, 163.10, 165.97, 168.11, 170.36.
IR (KBr) 3284(m), 3210(m), 3120(m), 2340(w), 2200(w), 1701(s),
1630(s), 1571(s), 1530(vs), 1497(vs), 1490(vs), 1442(s), 1395(m),
1378(m), 1330(s), 1253(w), 1138(w), 1041(w), 1028(w), 972(m),
896(m), 860(w), 788(w), 755(m), 688(m), 637(w) cm-1
Analysis. Calculated for C11H11N03: C, 64.38; H, 5.40; N, 6.82.
Found: C, 64.17; H, 5.49; N. 6.77.
Heating 10.0 g N-phenylcitraconamic acid (48.7 mmole) and 1.8 g
fused sodium acetate in 15 ml acetic anhydride at 900C for thirty
minutes produced a deep yellow solution. The solution was allowed
to cool to room temperature, and stirring was continued for two hours.
Precipitation of the reaction mixture into a rapidly stirred ice:
salt:water mix, followed by recrystallization of the precipitate from
cyclohexane, gave 3.5 g (38.4%) pale yellow needles, mp 92-940C (lit-
erature80 mp 94-960C).
H NMR (60 MHz, acetone-d6) 6 2.08(d, J = 1.8, 3H), 6.53(q, J = 1.8,
1H), 7.2-7.5(m, 5H).
C NMR (acetone-d6) 6 10.92, 126.91, 127.98, 128.08, 129.45, 133.10,
146.50, 170.09, 171.17.
IR (KBr) 3460(w), 3082(w), 2984(w), 2924(w), 1704(vs), 1640(m),
1596(w), 1502(m), 1400(s), 1290(w), 1205(w), 1188(m), 1140(w),
1114(m), 1073(w), 1038(w), 1012(w), 1000(w), 992(w), 888(m),
873(m), 762(m), 753(m), 708(m), 690(m), 651(w), 618(w) cm-1
LRMS (70 eV, m/z, relative intensity) 187(M 100.0), 143 (23.2), 130
(10.9), 119 (15.3), 117 (14.3), 91 (23.8).
Analysis. Calculated for C11H9N02: C, 70.06; H, 4.85; N, 7.48.
Found: C, 70.21; H, 5.40; N, 7.44.
N-(4-Trifluoromethylphenyl)maleamic acid (4-0xo-4-[(4-trifluoromethyl-
phenyl)amino]-(Z)-2-butenoic acid) (24)
A solution of 4.9 g p-aminobenzyltrifluoride (30.4 mmole, PCR)
dissolved in 10 ml CHC13 was added dropwise to a stirred solution of
3.6 g maleic anhydride in 125 ml CHC13. The solution started to be-
come turbid about five minutes after the addition was complete. The
solution-suspension was stirred for seventeen hours at room tempera-
ture and for seven hours at ~ 500C. After cooling, the bright yellow
precipitate was filtered and washed with chloroform. The powder was
added to 100 ml CHC13, and the mixture was boiled for about an hour.
The suspension was cooled, filtered and washed with CHC13. This pro-
cedure was repeated two more times. The pale, lemon yellow powder
was placed in a 500C vacuum oven overnight. This procedure yielded
7.5 g (95.2%) pale yellow product, mp 183-1840C literaturee1 mp 183-
H NMR (100 MHz, DMSO-d6) 6 6.64(AB q, J = 12.0, 2H), 7.20-8.27(m,
4H), 10.50 and 10.66 (2 unequal s, 1H).
IR (KBr) 3275(w), 3205(w), 3117(m), 3069(m), 3020(w), 2260(w, b),
1890(w, b), 1715(s), 1630(m), 1590(s), 1548(vs), 1487(m),
1427(m), 1408(m), 1322(vs), 1222(m), 1169(m), 1130(s), 1070(m),
1018(w), 975(w), 900(w), 858(m), 842(m), 755(w, b), 669(w),
pyrrole-2,5-dione], [54647-09-5], (25)
To a 100 ml, three-necked round-bottom flask equipped with a
mechanical stirrer and nitrogen inlet was added 3.0 g N-(4-trifluoro-
methylphenyl)maleamic acid (11.6 mmole), 0.75 g freshly fused sodium
acetate, and 10 ml acetic anhydride. The mixture was slowly heated
with an oil bath. At 60C, the slurry dissolved to form a bright
yellow solution. At 65C, the solution turned red. The flask was
immediately cooled to room temperature and allowed to stand for six
hours. The reaction mix was then precipitated into 300 ml rapidly
stirred ice water. The precipitate was then filtered, dried in vacuo
and recrystallized twice from cyclohexane. Activated charcoal was
added during the first recrystallization. This preparation yielded
2.4 g (86.0%) colorless needles, mp 153-155C literaturee1 mp 150-
H NMR (100 MHz, CDC13) 6 6.87(s, 2H), 7.63(AB q, broad lines, 4H).
3C NMR (acetone-d6, letters denote actual multiplicities, J's are
13C-19F coupling constants in Hertz) 6 125.03(q, J = 271.0),
126.90(q, J = 3.7), 127.52(s), 129.40(q, J = 33.0), 135.74(s),
136.49(s), 170.02(s). Off resonance decoupling caused all peaks
to split into doublets, relative to the completely decoupled
spectrum, except for those at 125.03, 129.40, 136.49 and 170.02,
which remained singlets. Selective irradiation of the ethyl-
eneic protons resulted in a much greater intensity for the 13C
peak at 135.74, relative to the other carbon resonances.
C NMR (CDC13)6123.82(q, J = 272.2), 125.79(s), 126.26(q, J = 3.7),
129.64(q, J = 33.0), 134.42(s), 134.59(s), 168.92(s).
1F NMR (CDCI3, internal CFC13) 6 -63.2(m).
IR (KBr) 3480(w), 3112(w), 3079(w), 2963(w), 1780(vs), 1705(s),
1612(w), 1521(w), 1412(m), 1372(w), 1330(s), 1260(w), 1160(s),
1127(s), 1108(s), 1069(s), 1058(m), 1020(w), 952(w), 839(m),
821(m), 815(m), 737(w), 710(w), 690(m) cm-1
LRMS (70 eV, m/z, relative intensity) 242(M+1, 12.3), 241(M+, 100.0),
197 (25.6), 185 (10.3), 172 (18.2), 171 (15.4), 54 (73.4).
N-(4-Cyanophenyl)maleamic acid (4-[(4-Cyanophenyl)amino]-4-oxo-(Z)-
2-butenoic acid), [31460-28-3], (26)
Finely ground maleic anhydride (5.0 g, 51.0 mmole) was dissolved
in 75 ml CHC13, and a solution of 5.0 g 4-aminobenzonitrile (Aldrich)
in 100 ml CHC13 was added dropwise. The immediate formation of a
cream colored precipitate was noted. The suspension was stirred at
room temperature overnight, filtered, washed with CHC13, and placed
in a 700C vacuum oven for four hours. The powder thus obtained was
purified by stirring in boiling CHCl3 for one hour, followed by fil-
tering and removal of the residual solvent in a vacuum oven. This
procedure yielded 8.55 g (93.4%) cream colored, finely divided pow-
der, mp 193-1940C.
H NMR (100 MHz, DMSO-d6, internal reference DMSO-d6 = 2.4962) 6
6.40(AB q, J = 12.0, 2H), 7.76(broad s, 4H), 10.65(s, 1H), COOH
13C NMR (DMSO-d6, internal reference DMSO-d6 = 39.562) 6 105.47,
118.65, 119.48, 129.76, 131.93, 132.93, 142.65, 163.78, 166.29.
IR (KBr) 3297(m), 3210(m), 3112(w), 3054(w), 2235(m), 1712(s),
1618(s), 1595(vs), 1540(vs), 1490(s), 1411(w), 1407(m), 1326(s),
1262(m), 1230(w), 1210(w), 1177(w), 972(m), 899(w), 858(m),
838(m), 758(w), 617(m) cm-1
A suspension of 7.0 g (4-cyanophenyl)maleamic acid (32.4 mmole)
and 1.7 g freshly fused sodium acetate in 25 ml acetic anhydride was
slowly heated in an oil bath. The maleanilic acid dissolved when the
temperature reached 650C. Stirring (mechanical) of the solution was
continued while the temperature gradually increased to 900C. This
temperature was maintained for thirty minutes, and then the reaction
mix was allowed to cool to room temperature. On cooling, the mixture
crystallized to a cream colored mass. Water (~ 75 ml) was added to
this mass of crystals, which were then separated by filtration and
washed with copious amounts of water. After drying in a 60C vacuum
oven overnight, the powdery product was recrystallized from heptane
to yield 5.2 g (81.2%) pale yellow needles, mp 131-134C.
IH NMR (100 MHz, CDC13) 6 6.92(s, 2H), 7.66(AA'BB', 4H).
13C NR (CDC13) 6 110.98(s), 118.16(s), 125.69(d), 132.93(d),
134.54(d), 135.54(s), 168.59(s). Selective decoupling of the
ethyleneic protons resulted in a dramatically greater intensity
for the peak at 134.54, relative to the other protonated carbons.
IR (KBr) 3470(w), 3170(w), 3100(m), 3095(m), 2219(m), 1770(w),
1727(vs), 1605(m), 1587(w), 1515(m), 1415(m), 1392(s), 1376(s),
1320(w), 1280(w), 1216(w), 1146(m), 1079(m), 1031(m), 951(w), 841
(s), 829(m), 818(w), 762(w), 720(m), 687(m), 656(w), 622(w) cm-1
(s), 829(m), 813(w), 762(w), 720(m), 687(m), 656(w), 622(w) cm-
LRMS (70 eV, m/z, relative intensity) 199(M+1, 12.8), 198(M 100.0),
154 (34.0), 142 (12.1), 128 (15.0), 54 (38.4).
Recrystallization from cyclohexane yielded long, pale green
needles, mp 155-156C literaturee3 mp 155C).
H NMR (100 MHz, CDC13) 6 6.83(s, 2H), 7.05-7.40(m, 4H).
13C NMR (CDC13, letters denote actual multiplicities, J's are 13C-19F
coupling constants in Hertz) 6 116.13(d, J = 22.6), 127.22(d,
J = 3.1), 127.91(d, J = 8.54), 134.22(s), 161.81(d, J = 247.8),
169.36(s). Selective irradiation of the ethyleneic protons re-
sulted in enhancement of the intensity of the resonance at
134.22, relative to the other protonated carbons.
19F NMR (CDC13, internal CFC13) 6 -113.7(m).
IR (KBr) 3460(w), 3165(w), 3101(m), 3071(w), 1900(w), 1710(vs),
1599(w), 1586(w), 1517(s), 1410(s), 1392(s), 1374(m), 1312(m),
1300(w), 1290(w), 1261(w), 1234(s), 1150(s), 1089(w), 1072(m),
1046(w), 1022(w), 950(w), 935(w), 836(s), 819(m), 765(w), 710(m),
LRMS (70 eV, m/z, relative intensity) 192(M+1, 11.4), 191(M 100.0),
147 (13.3), 121 (20.0), 109 (10.7), 82 (10.3), 54 (40.8).
Recrystallization from cyclohexane gave light yellow needles,
mp 113-115"C literaturee5 mp 114C).
H NMR (100 MHz, CDC13) 6 6.78(s, 2H), 7.34(AA'BB', 4H).
C NMR (CDC13) 6 127.08(d), 129.18(d), 129.88(s), 133.39(s),
134.17(d), 169.05(s). Irradiation of the ethyleneic protons
resulted in enhancement of the intensity of the peak at 134.17,
relative to the other carbon resonances.
IR (KBr) 3465(w), 3163(w), 3118(w), 3083(m), 1776(w), 1714(vs),
1585(w), 1497(s), 1453(w), 1402(s), 1388(s), 1372(m), 1310(m),
1278(w), 1211(w), 1149(m), 1097(m), 1071(m), 1031(m), 1019(m),
949(m), 836(s), 765(w), 743(m), 707(m), 685(m), 646(w) cm-1
LRMS (70 eV, m/z, relative intensity) 209 (31.9), 208 (11.6), 207
(M+, 100.0), 163 (15.2), 153 (10.1), 137 (19.4), 90 (11.9),
Recrystallization of this compound from cyclohexane yielded
bright yellow needles, mp 123-124C literaturee2 mp 118-120C).
1H NMR (100 MHz, CDCI3) 6 6.81(s, 2H), 7.40(AA'BB', 4H).
1C NMR (CDC13) 6 121.43(s), 127.33(d), 130.32(s), 132.18(d),
134.20(d), 168.97(s). Selective irradiation of the ethyleneic
protons resulted in enhancement of the 13C resonance at 134.20,
relative to the other carbon resonances.
IR (KBr) 3461(w), 3160(w), 3111(w), 3089(m), 1717(vs), 1589(w),
1570(w), 1490(s), 1441(w), 1398(s), 1385(s), 1367(m), 1306(w),
1275(w), 1208(w), 1147(s), 1065(m), 1029(w), 1011(m), 945(m),
828(s), 811(m), 761(w), 729(w), 705(m), 681(m), 638(w) cm-1
LRMS (70 eV, m/z, relative intensity) 254 (11.0), 253 (98.6), 252
(11.7), 251 (M+, 100.0), 209 (10.3), 207 (10.2), 197 (11.2),
183 (12.6), 181 (11.8), 116 (19.9), 90 (19.3), 86 (15.3), 82
(14.3), 63 (17.6), 54 (59.2).
Recrystallization of this compound from ethanol:cyclohexane (1:3)
gave colorless crystals, mp 167.5-169.50C literaturee5 mp 163-165C).
H NMR (100 MHz, CDC13) 6 6.94(s, 2H), 8.01(AA'BB', 4H).
1C NMR (CDC13) 6 124.48(d), 125.45(d), 134.61(d), 137.10(s),
IR (KBr) 3468(w), 3118(w), 3095(w), 1724(vs), 1682(m), 1612(m),
1594(m), 1518(s), 1500(s), 1447(w), 1398(m), 1388(m), 1373(m),
1347(s), 1300(m), 1268(w), 1217(w), 1144(m), 1107(w), 1062(m),
1030(w), 949(w), 851(m), 823(m), 761(w), 747(w), 719(w), 694(m),
l-yl)benzoic acid, ethyl ester], [14794-06-0], (31)
This compound was kindly provided by David P. Vanderbilt. Re-
crystallization from cyclohexane yielded pale yellow needles, mp 112-
113C literaturee3 mp 113C).
H NMR (100 MHz, CDC13) 6 1.39(t, J = 7.1, 3H), 4.39(q, J = 7.1, 2H),
6.86(s, 2H), 7.81(AA'BB', 4H).
13C NR (CDC13) 6 14.30(q), 61.16(t), 125.18(d), 129.47(s), 130.35(d),
134.37(d), 135.37(s), 165.71(s), 168.95(s).
Selective irradiation of the ethyleneic protons resulted in en-
hanced intensity for the 13C peak at 134.37, relative to the
other carbon resonances.
IR (KBr) 3120(w), 3091(w), 3001(w), 1718(vs), 1710(vs), 1607(m),
1509(m), 1476(w), 1417(m), 1398(m), 1386(m), 1369(m), 1310(m),
1286(s), 1217(w), 1177(m), 1146(m), 1130(m), 1110(m), 1070(w),
1025(m), 1013(w), 950(w), 857(m), 832(m), 827(m), 767(m), 701(m),
687(m), 641(w), 625(w) cm-
Recrystallization from cyclohexane yielded yellow needles, mp
151.5-152C literaturee4 mp 148.5-150C).
1H NMR (100 MHz, CDCI3) 6 2.37(s, 3H), 6.79(s, 2H), 7.18-7.25(m, 4H).
13C NMR (CDCI3) 6 21.10(q), 126.01(d), 128.57(s), 129.74(d), 134.13(d),
Selective irradiation of the ethyleneic protons resulted in en-
hancement of the 1C signal at 134.13, relative to the other
IR (KBr) 3461(w), 3170(w), 3095(m), 2928(w), 1710(vs), 1588(w),
1528(m), 1410(s), 1390(s), 1324(m), 1318(w), 1290(w), 1212(w),
1182(w), 1154(s), 1079(w), 1038(w), 952(w), 833(s), 822(m),
810(m), 710(m), 686(s), 674(m) cm-1
LRMS (70 eV, m/z, relative intensity) 188 (12.9), 187 (M+, 100.0),
143 (12.5), 130 (17.7), 117 (18.7), 54 (15.1).
dione], [6637-46-3], (33)
Recrystallization from cyclohexane yielded pale yellow needles,
mp 160-161C literaturee5 mp 156C).
1H NMR (100 MHz, CDC13) 6 2.28(s, 3H), 6.80(s, 2H), 7.27(AA'BB', 4H).
13C NMR (CDC13) 6 21.03(q), 122.23(d), 126.91(d), 128.76(s), 134.17(d),
149.79(s), 169.00(s), 169.29(s).
Selective irradiation of the ethyleneic protons resulted in en-
hanced intensity for the 1C peak at 134.17, relative to the
other carbon resonances.
IR (KBr) 3095(w), 1754(s), 1709(vs), 1589(w), 1508(s), 1473(w),
1412(m), 1400(m), 1387(w), 1368(m), 1216(s), 1197(s), 1163(m),
1153(m), 1099(w), 1016(w), 957(w), 915(w), 853(w), 840(m),
732(w), 702(w), 690(m), 651(w) cm-1
LRMS (70 eV, m/z, relative intensity) 231 (M 2.4), 190 (11.5),
189(100.0), 119 (10.0), 54 (12.6).
dione], [1081-17-0], (34)
Recrystallization from cyclohexane yielded very bright yellow
needles, mp 148-151C literaturee5 mp 1460C).
1H NMR (100 MHz, COCI3) 6 3.80(s, 3H), 6.79(s, 2H), 7.09(AA'BB', 4H).
13C NMR (CDC13) 6 55.44(q), 114.44(d), 123.84(s), 127.57(d), 134.08(d),
Selective irradiation of the ethylenic protons resulted in en-
hancement of the intensity of the 13C peak at 134.08, relative
to the other carbons.
IR (KBr) 3460(w), 3109(w), 3080(w), 3011(w), 2970(w), 2939(w),
2919(w), 2838(w), 1770(w), 1706(vs), 1607(w), 1586(w), 1507(s),
1477(w), 1449(w), 1439(m), 1415(m), 1398(s), 1305(m), 1248(s),
1180(m), 1169(m), 1156(s), 1148(s), 1106(m), 1053(w), 1027(m),
950(w), 938(w), 836(m), 826(m), 816(m), 810(m), 797(w), 720(m),
685(m), 602(w) cm-1
LRMS (70 eV, m/z, relative intensity) 204 (12.3), 203 (M 100.0),
188 (35.4), 160 (19.8), 134 (9.3), 133 (9.3), 106 (8.6), 54
Copolymer Synthesis and Characterization
All copolymers were synthesized in roughly the same manner. Azo-
bisisobutyronitrile (AIBN, Aldrich) was used as the initiator in all
cases, except where noted otherwise. The initiator was purified by
recrystallization from methanol.
Purification of 2-chloroethyl vinyl ether (Aldrich), ethyl vinyl
ether (Aldrich), and n-butyl vinyl ether (Aldrich) was carried out by
stirring over calcium hydride for at least twenty-four hours, fol-
lowed by distillation. Methyl vinyl ether (Matheson) was condensed
from a gas cylinder into a 250 ml round-bottomed flask cooled with
an ice:water:salt mixture. The round-bottomed flask was then con-
nected to a dry polymerization tube and allowed to warm to room temp-
erature while the polymerization tube was cooled in a dry ice:iso-
Maleimides were recrystallized from cyclohexane before use.
Maleic anhydride was sublimed before use. Dichloromethane was
distilled from phosphorous pentoxide. Benzene was stirred over 18 M
H2SO4 for twenty-four hours, decanted, and distilled.
Typically, solutions of the desired concentrations were made by
weighing appropriate amounts of the initiator, maleimide and vinyl
ether into a volumetric flask and diluting to the mark with solvent.
The desired volume of this solution was then introduced into a clean
polymerization tube with a pipette. The tube was connected to a high
vacuum line and degassed by at least five freeze-pump-thaw cycles,
then sealed off at < 10-5 mm Hg. Tubes thus prepared were placed in
a bath (water, oil, or isopropanol:dry ice) of the appropriate temp-
erature for the desired amount of time. At the end of this time, the
tube was removed from the bath, cooled to -78C in a dry ice:isopro-
panol bath, and opened. The solution was then added slowly (drop-
wise) to a large excess of rapidly stirred precipitation solvent
(methanol was used unless otherwise noted). In some cases it was
necessary to redissolve the copolymer in acetone and precipitate it
again in order to obtain a pure white product.
It was noted that monomer solutions containing initiator de-
colorized on standing in bright light. Precipitation of these solu-
tions, as described above, yielded pure white copolymers. Thus,
polymerizations described from now on as being carried out at "room
temperature" took place in the presence of oxygen without careful
In the copolymerization carried out at -780C, a Hanovia Utility
Quartz Ultraviolet Lamp was used as a light source. The degassed
monomer solution was placed in a dry ice:isopropanol bath,
and the light was shone through a recrystallizing dish containing
about three inches of water, which was placed on top of the dewar
containing the cold bath and tube. The water served as insulation,
so that rapid heating of the bath by the hot lamp was avoided. Inde-
pendent experiments showed that no copolymerization took place in the
absence of initiator under these conditions. A UV scan showed that
AIBN has an absorption maximum near 345 nm which is well above the
pyrex glass cutoff of about 280 nm.5
All 4-substituted phenyl maleimides copolymerized with 2-chloro-
ethyl vinyl ether, except for N-(4-nitrophenyl) maleimide, which
yielded no copolymer after being heated in the presence of initiator
and CEVE for forty-two hours in a 60.0C bath. The unreacted male-
imide could be recovered unchanged (as judged by IR spectroscopy).
A Sargent Thermonitor (Model S-W) constant temperature bath was
used to control the temperature of the water bath used to 60.00.10C.
The homopolymer of N-phenylmaleimide was prepared in exactly the
same way as the copolymers (i.e., AIBN, CH2Cl2, 60.0C).
The copolymerization conditions, yields and analysis data for
all copolymerizations, except for those performed in kinetic studies,
are given in Tables 2 5.
2-Chloroethyl Vinyl Ether Homopolymer
The 2-chloroethyl vinyl ether (CEVE) homopolymer was synthesized
by storing distilled CEVE over unactivated molecular sieves (Linde).
The viscosity of the CEVE increased with the length of time that it
was stored over the sieves. Indeed, after several months the vinyl
ether had become a brown, solid mass. This mass was dissolved in
Conditions for N-Phenvlmaleimide-2-Chloroethvl Vinyl Ether Cooolvmerizations
-78 to -68
1.56 x 10-3
Footnotes for this table appear at the end of Table 5.
0.699 i.in rn.77~1
0.9 1 _1 (0.2% 200 2
Yield and Analysis Data for Copolymers in Table 2
Sample h i k Avg. m
No. Grams 1 % N M % C1 mM Av.
0.585 9.32 0.611 0.598
0.633 9.10 0.620 0.626
0.679 8.04 0.659 0.669
Footnotes for this table appear at the end of Table 5.
Polymerization Conditions for Other Maleimide Polymersr
Sample Monomerm M a b 3c Vol.d Copolym.
No. Pair T M [AIBN] x 10 (ml) Time(Hr.)
25 NPM MVE ? 0.
[NPM]=0.250 1.14 25.0 16.0
26 NPM EVE 0.512 0.488 1.12 (0.22%) 50.0 22.5
27 NPM BVE 0.521 0.520 9 20.0 19.5
28 NPC-CEVE 0.535 0.467 2.4 (0.45%) 50.0 163.5
29 NCHX-CEVE 0.500 0.500 1.11 (0.22%) 25.0 49.8
30 PCN-CEVEn 0.500 0.500 1.10 (0.22%) 25.0 43.5
31 PCF3-CEVE 0.500 0.500 1.11 (0.22%) 25.0 50.8
32 PCO2ET-CEVE 0.501 0.499 1.06 (0.21%) 5.0 43.5
33 PF CEVE 0.500 0.498 1.14 (0.23%) 10.0 60.0
34 PC1 -CEVE 0.501 0.499 1.09 (0.22%) 25.0 42.5
35 PBr-CEVE 0.500 0.500 1.12 (0.22%) 25.0 42.0
36 POAc-CEVE 0.500 0.500 1.11 (0.22%) 15.0 42.0
37 PCH3-CEVE 0.508 0.492 1.22 (0.24%) 25.0 42.5
38 POMe-CEVE 0.502 0.498 1.14 (0.23%) 25.0 42.5
39 NOAc-CEVE 0.500 0.500 1.09 (0.22%) 100.0 61.0
40 MAH-CEVEn 0.500 0.500 1.13 (0.23%) 50.0 66.5
41 MAH-CEVEn 0.500 0.500 1.11 (0.22%) 50.0 66.5
42 PNO2-CEVE 0.500 0.500 1.11 (0.22%) 25.0 42.0
table appear at the end of Table 5.
Footnotes for this
Yield and Analysis
Data for Copolymers in Table 4
Sample Grams % %N Avg. m % C1 Avg. m Avg. mM
No. Grams % 1 N mMJ ~ mM
,. LU U.3/ -
4.30 0.530 8.15
5.15 0.557 9.39
4.93 0.568 9.43
5.79 0.551 11.75
Footnotes for Tables 2, 3, 4 and 5:
a Total monomer concentration = [M1] + [M2].
bMole fraction maleimide (or other acceptor) in the initial feed.
c Concentration of AIBN in moles/1 (mole % AIBN based on MT).
dVolume of the solution that was polymerized.
e No solvent.
Total moles of monomer.
9 Initiator was 2,4-dichlorobenzoyl peroxide (Lucidol), 1.1 x 10-3M.
hYield (%) based on theoretical maximum weight of polymer determined
from total weight of monomers initially present.
Yield (%) based on the knowledge that vinyl ethers do not homopoly-
merize under the present conditions, i.e., when [vinyl ether] >
[maleimide], the theoretical maximum conversion is 2[maleimide];
when [maleimide] > [vinyl ether], the maximum conversion is [male-
imide] + [CEVE].
SMole fraction maleimide in the copolymer calculated from nitrogen
kMole fraction maleimide in the copolymer calculated from chlorine
analysis, i.e., 1-mCEVE.
Average mM from nitrogen and chlorine analyses.
m Abbreviations used:
CEVE, 2-chloroethyl vinyl ether
BVE, n-butyl vinyl ether
EVE, ethyl vinyl ether
MVE, methyl vinyl ether
MAH, maleic anhydride
SCopolymerization proceeded heterogeneously, i.e., the copolymer was
insoluble in dichloromethane.
0 This copolymer was soluble in methanol, so petroleum ether was used
as the precipitating solvent.
P Benzene solvent.
q N-Phenylmaleimide was 20% 15N-enriched.
r Copolymerization temperature was 60.0 0.1C in all cases.
methylene chloride and precipitated into stirred methanol cooled in a
dry ice:isopropanol bath. The white precipitate was rapidly filtered
before it warmed to room temperature. On warming, the precipitate
changed to a viscous, pale yellow, transparent mass. The NMR data for
this material were consistent with that reported86 for the CEVE homo-
polymer prepared in methylene chloride using boron trifluoride ether-
H NMR (60 MHz, CDC13) 6 1.82 (broad s, 2H), 3.50 (broad s, 5H).
1C NMR (CDC13, internal reference CDC13 = 77.062)639.3 (t, broad),
40.5 (t, broad), 43.64 (t), 68.57 (t), 73.49 (d).
IR (thin film) 2930(vs), 2882(s), 2860(s), 1725(w), 1462(m), 1429(s),
1370(s), 1298(s), 1252(m), 1195(m), 1110(vs), 1150(s), 969(m),
890(w), 864(w), 825(w), 780(w), 740(m), 661(vs) cm-1
Copolymer Reactivity Ratios
The reactivity ratios for the NPM-CEVE copolymerization were
calculated using the copolymer composition data in Table 3. Two
separate methods were used to evaluate these ratios. The methods
used were those developed by Joshi and Joshi,87 and Kelen and Tudos.88
Although it is generally accepted89 that only composition data from
low conversion (< 10%) polymers should be used for these calcula-
tions, it can be seen from Table 3 that the copolymer composition
does not change significantly with conversion when the monomer feed
is rich in vinyl ether. Thus, both low and high conversion data (for
those copolymers prepared from vinyl ether-rich feeds) were used for
these calculations. The Kelen-Tudos plot is shown in Figure 1. The
numbers indicate data calculated from the corresponding samples in
Table 3. It can be seen that the plot is fairly linear, although
there are some points that deviate significantly from the line. Most
of the data that did not fall on the line were calculated from the
composition data for polymers prepared using different polymerization
conditions. Recalculation of the reactivity ratios using the ten
"best" data points did not change the results significantly. All
sixteen data points were used in the Joshi-Joshi calculation. The
results are summarized in Table 6.
The initial rate of copolymerization for the system NPM, CEVE,
CH2CI2, AIBN, 60.00C was measured as a function of the mole fraction
of maleimide in the initial comonomer feed (XM) at constant total
monomer concentration ([Mi] + [M2] = MT). A gravimetric technique was
Reactivity Ratios for the Free Radical Initiated Copolymerization
of N-Phenylmaleimide (Ml) and 2-Chloroethyl Vinyl Ether (M2)
Calculation Method rl r2
Joshi-Joshi 0.286 0.012 -0.0000024
Kelen-Tudosa 0.284 -0.0079
Kelen-Tudosb 0.275 +0.00041
a Calculated using all data points.
bCalculated using ten "best" data points.
used to follow the conversion of monomers to polymer, i.e., the mass
of copolymer formed was monitored as a function of time.
Solutions of the desired concentrations were made by weighing
the appropriate amounts of monomers and initiators into clean 100 ml
volumetric flasks and diluting to the mark with freshly distilled
(from P4010) dichloromethane. Exactly 10 ml portions of these solu-
tions were transferred via pipette into clean, dry polymerization
tubes. The tubes were connected to a high vacuum line, degassed via
five freeze-pump-thaw cycles, and sealed at < 10-5 mm Hg. The tubes
were then immersed in a 60.0 0.10C water bath. After the desired
amount of time had elapsed, a tube was removed from the bath and
immediately plunged into a dry ice:isopropanol bath. The time inter-
val between immersions in the 60.0C and -780C baths was taken as the
polymerization time, and was measured with a stopwatch. The polymer-
ization times were such that the conversion to polymer was low
(k 10% of the initial weight of monomers present), so that the ratio
of monomer concentrations was approximately constant. The cold tube
was opened as quickly as possible, and the contents were quickly added
to 100 ml of methanol in one portion. The tube was carefully rinsed
with several small portions of dichloromethane. The rinsings were
added to the methanol. The pure white precipitated polymer was then
filtered into clean, previously weighed fine porosity, fritted glass
filters. The filters were cleaned in a chromic acid bath followed by
rinsing with deionized water. Concentrated nitric acid was then
passed through the filters, which were then rinsed with copious
amounts of deionized water. The filters were then dried in a 140C
oven overnight, cooled, and weighed accurately. Tongs were used to
handle the filters after they were dried. After the polymers were
filtered, the filter and polymer were dried in vacuo at 60C overnight.
After cooling to room temperature, the filters containing polymers
were reweighed, and the weight of the polymer was calculated by
Sometimes it was necessary to digest the polymer suspension in
order to increase the particle size and facilitate filtration. This
was done by gentle heating (- 35-45C) of the suspension for about one
hour, then allowing it to stand undisturbed at room temperature for
one to three days.
The NPM used for kinetic studies was vacuum distilled (bp 109-
111C @ 0.25 mm Hg), followed by recrystallization from cyclohexane.
A high efficiency spinning band column was used to distill CEVE (bp
109C) from calcium hydride.
The initial conditions, copolymerization times, and polymer
weights obtained are given in Table 7. These weights were converted
to the concentration of polymer at the corresponding time by using
the average molecular weight of the copolymer repeat unit calculated
from the copolymer composition data in Table 3. The following equa-
tion was used for the calculation:
MW = 2[mM (173.17) + mCEVE (106.55)]
where mM and mCEVE are the mole fractions of NPM and CEVE incorporated
into the copolymer, respectively.
The slope of a [polymer] vs. time plot gives the rate of copoly-
merization (R in mole/l-min). The results are shown in Table 8,
along with the standard deviation of the slope (Sm) and the x-inter-
cept (x) of the concentration vs. time plots. The slope and the x-
intercept were calculated by a linear least squares procedure. The
x-intercept was invariably non-zero and positive, indicating that
there was an induction period during which no polymerization took
place. The dependence of the rate (R ) on the initial mole fraction
maleimide is shown graphically in Figure 6.
13C NMR. Carbon-13 NMR analysis of the copolymers proved to be
vastly superior to proton (1H) NMR because of greater spectral sim-
plicity resulting from the lack of coupling and the greater spectral
width (typically 200 ppm for 13C and 0 ppm for 1H). Indeed, 1H NMR
spectra of the maleimide-vinyl ether copolymers prepared in this
study generally appear as a series of overlapping broad humps.
Kinetic Data for N-Phenylmaleimide -
2-Chloroethyl Vinyl Ether Copolymerizations
Mole Pl. 2
Initial Conditions Time (Min.) Wt. Pol. (mg) lP. x 102
Mb = 0.500 20.1 30.84 1.10
c = 0.100 22.3 36.06 1.28
MWd = 280.52 25.0 40.38 1.44
27.5 47.10 1.68
30.1 49.78 1.77
35.9 62.08 2.21
MT = 0.501 20.2 42.43 1.49
XM = 0.200 25.0 52.80 1.86
MW = 283.98 30.0 66.55 2.34
35.1 76.95 2.71
rb = 0.500 15.1 32.97 1.16
XM = 0.300 20.0 46.24 1.63
MW = 283.98 25.0 62.90 2.21
30.0 73.44 2.59
MTb = 0.500 15.0 33.36 1.16
XM = 0.400 20.9 48.25 1.68
MW = 286.38 25.0 59.78 2.08
30.0 77.95 2.72
Initial Conditions Time (Min.) Wt. Pol. (mg) MolePol. x 102
MT = 0.501 20.0 48.27 1.69
XM = 0.499 25.0 64.25 2.24
Wd = 286.25 30.0 81.75 2.86
35.0 88.07 3.07
MT = 0.500 26.1 23.66 0.808
XM = 0.600 30.1 37.94 1.30
MW = 292.78 31.8 41.39 1.41
38.1 50.06 1.71
MTb = 0.501 26.6 36.04 1.22
XM = 0.699 30.5 40.99 1.38
MW = 296.51 35.0 48.62 1.64
41.2 60.77 2.05
MTb = 0.500 69.4 20.15 2.33
XM = 1.00 84.2 23.61 2.73
MW = 173.17 106.1 29.30 3.38
120.4 32.53 3.76
150.1 41.75 4.82
156.0 39.58 4.57
aAll sample volumes were 10.00 ml, and the solvent was dichloro-
methane in all cases.
bTotal monomer concentration in moles/l.
CMole fraction of maleimide.
dAverage molecular weight of repeat units calculated from composition
data in Table 3, i.e., MW = 2[(mM)(173.17) + (mCEVE)(106.55)].
Initial Copolymerization Rates for the Copolymerization of
N-Phenylmaleimide and 2-Chloroethyl Vinyl Ether in Dichloromethane
XM R imle )a S b (min.)c
p 1-min m m
x 104 x 104
0.10 6.92 0.115 3.98
0.20 8.33 0.102 2.36
0.30 9.80 0.213 3.16
0.40 10.3 0.272 4.12
0.50 9.52 0.421 1.61
0.60 7.22 0.334 13.41
0.70 5.75 0.103 5.98
1.00 2.81 0.112 13.54
aRp d[P]/dt = -i d([M1]+[M2])/dt; for XM = 1.00, Rp = -d[M1]/dt;
P represents polymer.
bStandard deviation in the slope of the mole polymer/l vs. time plot.
CX-intercept of the mole polymer/l vs. time plot.
Careful sample preparation proved to be essential in obtaining
good quality "high resolution" spectra. All spectra were obtained
in solution, and the solvents used were either DMSO-d6 or tetrachlolo-
ethane (TCE). Because of the low natural abundance of 13C nuclei
(1.1%90) and the complexity of the copolymer structure (numerous
magnetic environments for similar types of carbon), a very high con-
centration of copolymer was needed in order to obtain a good signal
to noise ratio in a reasonable amount of time. Thus, samples were
generally prepared by adding solid copolymer to a small amount of
solvent (0.3-0.4 ml) until the resulting solution was viscous enough
to barely flow at room temperature. Usually 200-400 mg of copolymer
was enough to achieve the desired concentration. The solution was
filtered into a clean 5 mm NMR tube through a plug of glass wool,
using heat (heat gun) and positive nitrogen pressure. When TCE was
used as the solvent, 10-15 drops of benzene-d6 or toluene-d8 was added
for internal deuterium lock. Hexamethyldisiloxane (Merck & Co., 1-2
drops) was used as a reference (2.03 ppm from TMS91) when TCE was
used as the solvent. The middle peak of the solvent heptet (39.50
ppm from TMS62) was used as the reference peak when DMSO-d6 was the
In order to minimize the dipolar line broadening caused by aniso-
tropic motion92 in the viscous polymer solution, all spectra were run
at high temperature. Acceptable line widths could be obtained at
100-110C for copolymers dissolved in DMSO-d6, and at 70-800C for
those dissolved in TCE.
Since the 13C NMR spectra of the NPM-CEVE copolymers had a large
dynamic range (difference between the intensity of the most intense
and the least intense peaks), and the Jeol-FX100 has limited space in
the computer memory for data storage, the computer word length would
overflow before an adequate signal to noise ratio was attained. For
a discussion of this effect, see Reference 90, p. 18, Reference 91,
p. 100 or Reference 93. This problem was overcome by using the fre-
quency domain (or block) averaging technique.93 This technique
amounts to the accumulation of a relatively small number of scans,
followed by Fourier transformation of the free induction decay, and
storage of the result in a separate block of computer memory. This
process is repeated, and the result of the Fourier transformation is
added to the previous result. The whole process is continued until
the desired signal to noise ratio is attained.
Since polymer carbon-13 nuclei generally have short spin-lattice
relaxation times (TI) relative to small molecules,90,91'94 a short
pulse delay (PD) and large pulse width (PW) were used to obtain 13C
spectra of the NPM-CEVE copolymers. Typical instrument parameters
for obtaining polymer spectra follow:
Number of accumulations: 20,000-35,000
Observation frequency: 47.0 KHz (TCE solvent)
47.3 KHz (DMSO-d6 solvent)
Pulse width: 12-18 ps (60-90)
Pulse delay: 180-360 ms
Acquisition time: 0.819 s
Spectral width: 5000 Hz
Exponential line broadening: 0.97 Hz
Each spectrum required eight to ten hours of accumulation. Accept-
able signal to noise ratio was not attained when the 13C NMR spectrum
of NPM homopolymer was run, until 250,000 scans had accumulated.
Copolymer TI and NOE determination. The spin-lattice relaxation
times (Ti) were determined for the carbons in the NPM-CEVE copolymer
prepared in bulk (sample 15 in Table 2). The method used for this
determination was the saturation recovery method developed by McDonald
and Leigh.95 This method proved to be superior to the inversion re-
covery (IRFT)96 or the fast inversion recovery (FIRFT)97 techniques
because of its relative insensitivity to mis-set 900 pulse angles,
the lack of a long wait time after each pulse sequence, and the very
short T1 values determined for some of the carbons in the copolymer.
Determining the 90 pulse width is a tedious, trial and error process
in which the pulse width is varied until the observed signal is nulled
(1800 pulse, the pulse width for a 900 pulse is ~ i that correspond-
ing to a 180C pulse). For the copolymer, it took ten to fifteen
minutes of accumulation to observe any signal at all, so such a trial
and error process was clearly unacceptable. The number of scans
necessary to obtain a polymer spectrum with good signal to noise ratio
(at least 2,000 under very favorable conditions) necessitated the use
of a short pulse sequence. Because of the short T1 values of some
polymer carbons, inversion of the broad carbon resonances (IRFT and
FIRFT methods) required extremely short pulse intervals, (T); and for
many values of T, some peaks did not appear above (or below) the
The saturation recovery experiment consisted of a 900 pulse
followed by a homospoil pulse (to dephase the spins). After the
system was allowed to relax for a time period -, another 900 pulse
was applied in order to sample the magnitude of the magnetization
vector. After the signal was acquired, another homospoil pulse was
applied, and the sequence was repeated until the desired signal to
noise ratio was achieved. A series of spectra were obtained using
different pulse intervals (-'s). The signal intensity was an expo-
nential function of T, with time constant T1. The relaxation times
were calculated by plotting In[SI S(T)] vs. T,95 where S and S(T)
were the signal areas corresponding to pulse intervals of infinity
and T, respectively.
By using a 10 mm tube and a high copolymer concentration, a
fairly good signal to noise ratio was obtained after 2,000 scans had
been accumulated. Thus, up to 10 spectra could be obtained (each
resulting from a different T) in a reasonable amount of time (12-
24 hours). The spectra were automatically accumulated and stored on
magnetic tape by the spectrometer. After completion of the run, each
spectrum was read off the tape, and the peaks were integrated elec-
tronically. Since the peaks were generally broad, and the signal to
noise ratio was low (especially when short T's were used), the inte-
gration was subject to large errors. Several experiments were run
using various combinations of pulse intervals and T This was neces-
sary because of the large range of T1 values encountered for different
carbon types in the copolymer (22-3,000 ms), i.e., the T's needed to
measure the short Tl's were not suitable for the measurement of long
T1's and vice versa. A linear least squares procedure was used to
calculate the slopes of the In(S S ) vs. T plots. Sometimes these
plots appeared nonlinear; however, due to the large errors involved
in the area determination, this observation was not considered signif-
icant. In these cases, the points corresponding to short T values
(and the least accurate area determinations) were invariably the
points that deviated significantly from the line, and were simply
neglected in the T1 calculation.
When using the semilogarithmic procedure described above, it is
essential that the Tm value chosen is at least five times as long as
the longest T1 to be measured.98 The results of the T1 determinations
are given in Table 9. The T1 values are shown as the range of values
determined from at least three separate experiments. The longest T
used in these experiments was 12,000 ms, which is not five times the
T1 values determined for the nonprotonated carbons. The use of a T_
value that is less than the time value results in an underestimation
of T1.98 Thus, the T1 values for the carbonyl and quaternary aromatic
carbons are probably greater than the values shown. The large varia-
tion in T1 values obtained for the same carbon in different experi-
ments underscores the inaccuracies inherent in the determination of
polymer relaxation times. The observed values are only useful for
Determination of Copolymer Nuclear Overhauser Enhancements (NOE).
Copolymer carbon-13 NOE's were determined by using the gated decoup-
ling technique.99 A spectrum was obtained using complete decoupling,
i.e., with the proton decoupler on all the time. The pulse delay used
Carbon-13 Spin-Lattice Relaxation Times (T1) and
Nuclear Overhauser Enhancement Factors (NOEF)
For an NPM-CEVE Copolymera
Carbonb 5 (ppm)c T1 Range (ms) Avg. T1 (ms) NOEd NOEFe
1 177.1 1400-2200 2000 1.82 0.82
2 174.4-175.6 1400-1900 1400 1.81 0.81
3 131.9 2100-3000 2500 1.82 0.82
4,5f 127.7-128.3 200-560 334 2.92 1.92
6 126.3 160-330 250 2.86 1.86
7 75.7-76.7 28-68 56 2.03 1.03
8 69.2-70.1 64-186 142 2.28 1.28
9 48.3-49.9 62-99 76 2.30 1.30
10 42.9 98-264 164 3.03 2.03
11 37.0-39.5 Under solvent (DMSO-d6) resonance
12 32.4-34.7 22-35 29 2.59 1.59
a Prepared in bulk (sample 15, Tables 2,3).
Numbered as in Figure 8 (low to high field).
c Internal reference DMSO-d6 = 39.5 ppm.62
dTheoretical maximum value 2.988.6
e Theoretical maximum value 1.987.9
e Theoretical maximum value 1.987.90
fThese peaks overlap.
These peaks overlap.
to obtain this spectrum was fifteen seconds (> 5 times the longest
T1). The areas for all of the carbon resonances were measured.
Another spectrum was run under exactly the same conditions, except
the decoupler was gated on during data acquisition and off during
the pulse delay. Thus, a proton decoupled spectrum was obtained,
but without the NOE. The ratio of the areas obtained by using com-
plete decoupling, and those obtained using gated decoupling, gives
the NOE ratio. The quantity NOE-1 gives the amount of signal enhance-
ment and is known as the nuclear Overhauser enhancement factor
(NOEF).90 Repeating the gated decoupled spectrum after adding some
chromium tris-acetylacetonate [Cr(acac)3]99 paramagnetic relaxation
reagent had no effect on the integrated areas relative to those ob-
tained without Cr(acac)3. The results are presented in Table 9.
Infrared Spectroscopy. Generally, the IR spectra of NPM-CEVE
copolymers did not differ significantly with varying copolymerization
conditions. Thus, only one set of spectral data is reported below.
The abbreviations used below for the various monomer pairs used to
synthesize the copolymers are the same as those used in Tables 2-5.
All spectra were obtained using the KBr pellet technique.
NPM-CEVE, 3470(w, b), 3060(w), 2958(w), 2920(w), 2880(w), 1777(w),
1709(vs), 1595(w), 1498(m), 1457(w), 1432(w), 1382(s), 1300(w),
1185(s), 1110(m), 752(m), 690(m), 662(w), 620(w) cm-1
NPM-MVE, 3460(w, b), 3060(w), 2930(w), 2812(w), 1776(w), 1707(vs),
1595(w), 1497(m), 1456(w), 1382(s), 1180(s), 1098(m), 750(m),
688(m), 618(w) cm1.
NPM-EVE, 3465(w, b), 3062(w), 2973(w), 2915(w), 2880(w), 1779(w),
1710(vs), 1596(w), 1498(m), 1455(w), 1383(s), 1290(w), 1183(s),
1090(m), 751(m), 688(m), 619(w) cm-1
NCHX-CEVE, 3455(w, b), 2938(m), 2860(w), 1773(w), 1699(vs), 1452(w),
1400(m), 1377(m), 1348(m), 1260(w), 1200(m), 1190(m), 1148(m),
1110(w, b), 1055(w, b), 986(w), 894(w), 669(w), 631(w) cm-'
NOAc-CEVE, 3450(w, b), 2940(w), 1820(m), 1787(m), 1734(vs), 1540(w),
1430(w), 1372(m), 1220(m), 1164(m), 1110(m), 1057(m), 827(w),
740(w, b), 668(w) cm-1
NPC-CEVE, 3470(w, b), 3062(w), 2910(w, b), 1775(w), 1710(vs), 1594(w),
1497(m), 1454(w), 1428(w), 1390(s), 1373(s), 1297(w), 1200(m),
1140(m), 1108(m), 750(m), 688(m), 662(w), 618(w) cm-1
PF-CEVE, 3475(w, b), 3080(w), 2960(w), 2925(w), 2870(w), 1779(w),
1708(vs), 1601(w), 1508(s), 1388(m), 1290(w), 1230(m), 1183(m),
1157(m), 1100(m), 1050(w), 1013(w), 932(w), 831(m), 750(w, b),
908(w), 660(w) cm-1
PC1-CEVE, 3480(w, b), 3100(w), 2965(w), 2920(w), 2870(w), 1780(w),
1710(vs), 1493(s), 1384(s), 1300(w), 1278(w), 1180(m), 1092(m),
1018(m), 940(w), 823(m), 731(w), 707(w), 665(w), 638(w) cm-1
PBr-CEVE, 3470(w, b), 3018(w), 2960(w), 2923(w), 2880(w), 1778(w),
1710(vs), 1490(s), 1385(s), 1303(w), 1278(w), 1181(m), 1110(m),
1073(m), 1013(m), 822(m), 704(w), 665(w), 632(w) cm-1
PCO2ET-CEVE, 3440(w, b), 2980(w), 2935(w), 2910(w), 1778(w), 1710(vs),
1608(m), 1509(m), 1414(w), 1380(m), 1280(s), 1180(m), 1110(m),
1021(m), 851(w), 767(w), 693(w), 667(w) cm-1
PCN-CEVE, 3480(w, b), 3102(w), 3060(w), 2965(w), 2927(w), 2878(w),
2218(m), 1780(w), 1711(vs), 1605(m), 1507(m), 1380(s), 1288(w),
1180(m), 1110(m), 1050(w), 954(w), 838(m), 800(w), 750(w),
POAc-CEVE, 3480(w, b), 2930(w, b), 1769(m), 1711(vs), 1600(w),
1509(m), 1390(m), 1374(m), 1200(s), 1170(m), 1110(m), 1047(w),
1020(m), 941(w), 910(w), 848(w), 640(w, b) cm-.
PCH3-CEVE, 3470(w, b), 3040(w), 2960(w), 2927(w), 2870(w), 1779(w),
1708(vs), 1515(m), 1390(s), 1300(w), 1188(m), 1110(m), 1050(w),
812(w), 910(w), 660(w) cm-1.
POMe-CEVE, 3480(w, b), 3005(w), 2960(w), 2940(w), 2920(w), 2842(w),
1778(w), 1710(vs), 1611(m), 1592(w), 1515(s), 1465(w), 1445(w),
1390(m), 1303(m), 1257(s), 1188(m), 1172(m), 1110(m), 1030(m),
830(m), 806(w), 662(w) cm-.
PCF3-CEVE, 3480(w, b), 3070(w), 2925(w), 2860(w), 1780(w), 1714(vs),
1612(m), 1517(w), 1418(m), 1382(m), 1327(s), 1172(m), 1125(m),
1110(m), 1067(m), 1019(m), 950(w), 838(m), 757(w), 697(w),
662(w), 627(w) cm-1
MAH-EVE, 2980(m), 2935(w), 2900(w), 1860(m), 1780(vs), 1732(m),
1440(w), 1405(w), 1377(w), 1350(w), 1223(m), 1093(m), 1070(m),
928(m), 730(w), 620(w) cm-1
MAH-CEVE, 2960(w), 2925(w), 2870(w), 1855(m), 1779(vs), 1732(m),
1432(w), 1350(w), 1298(w), 1220(m), 1104(m), 1048(m), 923(m),
930(w), 660(w) cm-1.
NPM Homopolymer, 3480(w), 3060(w), 2900(w, b), 1775(w), 1705(vs),
1597(w), 1496(m), 1457(w), 1387(s), 1185(m, b), 749(m), 732(m),
688(m), 657(w), 621(m), 611(w) cm-1
A peak appears at 1110-1100 cm-1 in all copolymer spectra that
is absent in the NPM homopolymer spectrum. This peak was therefore
assigned to the C-0 stretch of the ether unit in the copolymers. The
appearance of this peak was thus indicative of copolymer formation.
Differential Scanning Calorimetry (DSC). The thermal properties
of many of the copolymers that were synthesized were investigated by
use of the DSC method. The copolymers generally did not have a well-
defined crystalline melting point or glass transition temperature (T ).
Although several thermal transitions were evident in most DSC runs,
they generally were not reproducible and they were always poorly de-
fined. The temperature of decomposition, however, proved to be fairly
reproducible. The thermal stability runs were performed in air with
a Perkin Elmer DSC-1B instrument. Several runs were performed in a
helium atmosphere with no apparent effect on the decomposition temp-
erature (Td). The Td's of the copolymers tested are given in Table
10. The abbreviations used are the same as those used in Tables 2-5.
Copolymer Decomposition Temperatures (Td)
Copolymer Td (C) Copolymer Td (oC)
NPM-CEVE 272 PBr-CEVE 286
NPM-EVE 322 [ PCO2ET-CEVE 279
NPC-CEVE 285 PCH3-CEVE 265
NCHX-CEVE 280 POAc-CEVE 277
PCF3-CEVE 275 POMe-CEVE 280
PCN-CEVE 276 NOAc-CEVE 220
PF-CEVE 274 MAH-CEVE 237
PC1-CEVE 277 MAH-EVE 245
Copolymer molecular weight determinations. Although a great
deal of time was not spent on copolymer molecular weight determina-
tion, several copolymers were characterized by gel permeation chro-
matography (GPC) or vapor pressure osmometry (VPO). A low conversion
NPM-CEVE copolymer (XM = 0.2, MT = 0.5, AIBN, 600C) was analyzed on
a Waters Model 6000A GPC which was equipped with a Model 440 Absorb-
ance Detector. A Waters 104 Styragel column was used for the analy-
sis. A solution of copolymer concentration 2.3 g/l in CH2Cl2 was in-
jected. Dichloromethane was also used as the elution solvent. A
single, broad peak, typical of polymers produced by a free-radical
mechanism, was the result. The peak maximum corresponded to a
molecular weight of about 6300, based on polystyrene calibration
curves. This molecular weight corresponds to a degree of polymeri-
zation (D ) of 22-23 (based on 1:1 repeat unit).
Vapor pressure osmometry analysis of a high conversion NPM-
CEVE copolymer (sample 16, Table 2) in acetone, using a benzil cali-
bration standard, gave a number average molecular weight (Mn) of
13,250, which corresponds to a D of 47-48.
Solubility. The NPM-CEVE copolymers synthesized in this study
proved to be soluble in many organic solvents such as CHC13, CH2C12,
tetrahydrofuran, DMSO, nitromethane, ethyl acetate, acetone, aceto-
nitrile, and dimethyl formamide (DMF). The copolymers were insoluble
in benzene, alcohols, toluene, CC14 and water.
The NPM homopolymer, on the other hand, was generally insoluble
in the solvents listed above, dissolving only in DMSO, DMF and tetra-
Maleimide-vinyl ether copolymers were epimerized by using several
different bases and various reaction conditions. These conditions are
Copolymer epimerization with 2,2,6,6-tetramethylpiperidine (TMP)
in dimethylsulfoxide. The copolymer to be epimerized was dissolved in
DMSO-d6 (_ 0.25 g copolymer/0.3 ml DMSO-d6), and several drops of TMP
were added to the solution. Within 10-15 minutes, the solution turned
from colorless to a deep cobalt blue color. The solution was filtered
through a plug of glass wool into a clean, 5 mm NMR tube, which was
capped and placed in a 60.0C water bath. The progress of the epimeri-
zation could thus be monitored by periodically obtaining a 13C NMR
spectrum of the sample.
Copolymer epimerization with lithium diisopropylamide (LDA) in
tetrahydrofuran (THF). A three-necked, 200 ml round-bottomed flask
equipped with a magnetic stirring bar, addition funnel, and nitrogen
inlet was dried for several hours in a 1400C oven and then allowed to
cool in a dry nitrogen stream. One gram copolymer was dissolved in 20
ml THF (freshly distilled from lithium aluminum hydride), and the re-
sulting solution was placed in the addition funnel. About 1.0 g
solid LDA (Alfa) was added to 75 ml distilled THF which had been added
to the reaction flask. The transfer of the LDA was performed under a
blanket of dry nitrogen (inverted funnel). The reaction flask was
cooled to -750C with a dry ice:isopropanol bath. The LDA solution
was stirred magnetically under positive nitrogen pressure as the co-
polymer solution was slowly added over ten minutes. The solution
turned from colorless to deep red, and finally black opaque as the
copolymer solution was added. This solution was stirred at -750C
for one hour. At the end of this time, the solution was a deep green
color. Approximately 30 ml of saturated aqueous ammonium chloride
was quickly added while the solution temperature was still -750C.
The ammonium chloride solution froze on contact with the cold THF.
The dry ice was allowed to evaporate, so the solution slowly warmed
to room temperature with continued stirring. The organic layer of
the resulting two-phase system was now a deep cobalt blue color. The
organic layer was separated and added dropwise to rapidly stirred
methanol. The resulting light blue precipitate was filtered and
dried at reduced pressure (50C) overnight. The yield was 0.9 g
light blue powder. About one-half of this powder was treated with
20 ml hot (800C) acetic anhydride for three hours. The deep green
copolymer solution that resulted was allowed to cool, and 75 ml of
water was added. The resulting precipitate was filtered and dried
in vacuo. The resulting light green powder was dissolved in acetone
and precipitated into methanol. Three additional precipitations from
acetone into methanol failed to rid the product of all of its green
IR analysis of the original blue copolymer showed a broad peak
at 3150 cm-1, which may be due to an amide N-H stretch resulting from
partial hydrolysis of the succinimide units of the copolymer. This
band disappeared on treatment of the copolymer with hot acetic anhy-
dride. Otherwise, the IR spectrum of the epimerized copolymer was
unchanged from that of the copolymer before epimerization.
Copolymer epimerization with potassium t-butoxide in DMSO. Po-
tassium t-butoxide was synthesized by using high vacuum techniques.
About 5 ml of t-butyl alcohol was distilled from calcium oxide and
sealed into a breakseal. About 20 ml freshly distilled (from KOH)
DMSO was used to dissolve 3.5 g copolymer (sample 16, Table 3), and
the resulting solution was sealed into a clean breakseal. A solution
of 1 g ammonium chloride in 10 ml distilled DMSO was sealed into a
third breakseal. The three breakseals were attached to a 200 ml
round-bottomed flask that could be attached to a vacuum line by means
of a 14/20 ground glass joint. The flask was also equipped with a
side arm that had several constrictions through which potassium metal
could be distilled. A small test tube with a ground glass joint con-
taining a pea-sized piece of potassium metal under hexane was con-
nected to the side arm of the inverted apparatus. The whole appara-
tus was again inverted, quickly connected to the vacuum line, and
evacuated. The potassium was gently heated with a yellow flame,
causing it to melt and flow down the side arm. The reaction flask
was cooled in ice water. Continued heating of the potassium metal
caused it to distill onto the inside wall of the cool flask, forming
a blueish silver mirror. The side arm was sealed off, and the t-
butyl alcohol was introduced by breaking the corresponding breakseal.
The metal was quickly consumed. Hydrogen gas was evolved, and a
clear, colorless solution resulted. The breakseal containing the
copolymer solution was then broken, allowing the solution to flow
into the potassium t-butoxide solution. Within two minutes, the com-
bined solutions had gone from nearly colorless, to deep green, to a
deep cobalt blue color. The blue solution was stirred at room temp-
erature for forty-three hours, and the breakseal containing the ammo-
nium chloride solution was broken. No color change was noted when
the ammonium chloride solution was added. The bulk of the solvent
was removed on the vacuum line with heat (heat gun). The apparatus
was removed from the vacuum line, chloroform was added to the bright
blue residue, and the chloroform solution was extracted with water.
The organic layer was dried over anhydrous MgSO4 overnight. The MgSO4
was separated from the solution by filtration. The blue chloroform
solution was slowly added to rapidly stirred hexane (dropwise) to
yield a blue precipitate. This precipitate was filtered and dried
in a 500C vacuum oven overnight to yield 3.0 g light blue powder.
This polymer was somewhat soluble in methanol, as evidenced by the
fact that attempted precipitation of copolymer solutions into metha-
nol yielded a fine dispersion that could not be separated by filtra-
The IR spectrum of the epimerized copolymer was nearly identical
to that of the copolymer before epimerization, except for a small de-
crease in the relative intensity of the peak at 1110 cm-
Ultraviolet (UV) spectroscopy was used to study the complexation
behavior of maleimides and CEVE. Dichloromethane (CH2Cl2) was used
as the solvent in all cases. Invariably, the solvent was distilled
from P4010immediately prior to its use. CEVE was distilled from cal-
cium hydride immediately before use. The maleimides used were re-
crystallized from cyclohexane.
Solutions of CEVE in CH2C12 have absorption with Amax 275, 262,
and 254 nm. Dichloromethane solutions of N-arylmaleimides have ab-
sorptions with Amax in the range 300-320 nm and \max 255-275 nm,
depending on the maleimide. In contrast to solutions of N-arylmale-
imides, N-cyclohexylmaleimide solutions did not have an absorption at
255 nm. The absorption spectra of several maleimides are shown in
Figure 2. Addition of equal amounts of CEVE to a maleimide solution
in the sample beam of the UV spectrometer and a solvent blank in the
reference beam results in a slight intensification of the absorbance
in the 255-300 nm region. This increase in absorbance was attributed
to the formation of a charge-transfer complex and was therefore in-
vestigated further. This quantification proved to be a formidable
task due to the overlap of the charge-transfer band with the absorp-
tions of both monomers.
The experiments involved monitoring the absorbance of maleimide-
CEVE solutions of constant maleimide concentration and varying CEVE
concentration. The [CEVE] was always much greater than the [male-
imide]. In a typical procedure, the spectrum of the pure maleimide
in CH2C12 was measured against a reference of pure CH2C12 by using a
pair of 2 mm quartz cuvettes. Next, the spectrum of the solution of
the maleimide and vinyl ether was measured against a reference con-
taining the vinyl ether at the same concentration. The first spec-
trum was substracted from the second to afford the spectrum of the
charge-transfer complex. Absorbances were read directly from the dig-
ital display at 5 nm intervals, using care to optimize the slit width
before each reading so as to minimize noise. Absorbances read in this
manner were considered accurate to + 0.002 absorbance units.
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