Stereochemical and mechanistic studies on the anionic oligomerization of 2- and 4-vinylpyridines

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Title:
Stereochemical and mechanistic studies on the anionic oligomerization of 2- and 4-vinylpyridines
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xi, 94 leaves : ill. ; 28 cm.
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Meverden, Craig C., 1956-
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Vinylpyridine   ( lcsh )
Polymers   ( lcsh )
Polymerization   ( lcsh )
Anions   ( lcsh )
Stereochemistry   ( lcsh )
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bibliography   ( marcgt )
theses   ( marcgt )
non-fiction   ( marcgt )

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Thesis:
Thesis (Ph. D.)--University of Florida, 1983.
Bibliography:
Includes bibliographical references (leaves 90-93).
Statement of Responsibility:
by Craig C. Meverden.
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Typescript.
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Vita.

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STEREOCHEMICAL AND MECHANISTIC STUDIES ON THE
ANIONIC OLIGOMERIZATION OF 2- AND 4-VINYLPYRIDINES






BY

CRAIG C. MEVERDEN


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


1983































To Paula
















ACKNOWLEDGEMENTS


The author wishes to thank the members of his supervisory commit-

tee, Dr. George Butler, Dr. Merle Battiste, Dr. Wallace Brey, and Dr.

Anson Moye, for their time and support. Special thanks are extended

to Dr. Thieo Hogen-Esch for his direction, guidance, encouragement,

and most of all, patience.

The author also wishes to thank all of those who have provided

moral support in the pursuit of this degree. In particular, he

wishes to thank his wife and parents for their love and understand-

ing and his friends for their encouragement.

Thanks are also due to Ms. Patty Hickerson for her skill and

help in typing and preparing the manuscript.

















TABLE OF CONTENTS


ACKNOWLEDGEMENTS .

LIST OF TABLES .

LIST OF FIGURES. .

ABSTRACT .

CHAPTER


I. INTRODUCTION. .

II. EXPERIMENTAL. .

Purification of Reactants .

Preparation of Ethylpyridyl Al

Oligomerizations. .

Equilibrium Studies .

Degradation Reaction Studies.


kali Metal Salts.


Preparative Liquid Chromatography .

Capillary Column Gas Chromatography .

Nuclear Magnetic Resonance. . .

III. ADDITION OF ELECTROPHILES TO LIVING 2-VINYLPYRIDYL
DIMER . . .

IV. ANIONIC OLIGOMERIZATION OF 4-VINYLPYRIDINE. .

Results . . .

Discussion. . . .

V. THERMODYNAMICS OF INTRAMOLECULAR COORDINATION .


PAGE

' iii

* vi

* .viii




S. x12
. 1

. 12

. 12

. 13

. 19

. 22

. 27

. 29

. 29

. 29


. 30

. 40

. 41

. 57

. 63









VI. DEGRADATION REACTIONS OF OLIGOMER ANIONS . 74

REFERENCES ............................ 90

BIOGRAPHICAL SKETCH ....................... 94















LIST OF TABLES

Table Page

1 E:Z Ratio in Lithio-2-Ethylpyridine as a Function
of Counterion . . 3

2 Dissociation Constants for Living Polymers in THF 5

3 Methylation Stereochemistry of Anion [3] as a Function
of Cation and Solvent or Coordinating Agent 6

4 Stereochemistry of Methylation of Dimer Anions [11],
[12], and [3] . . 10
5 Stereochemistry of Electrophilic Addition to 2-Vinyl-
pyridyl Dimer Lithio Salt [3] . 32

6 Chemical Shifts and Approximate Splittings for 2,4-Di-
substituted Pentanes . . 44

7 13C NMR Chemical Shift Assignments for (m) and (r) [21] 45

8 13C Chemical Shifts for the Methyl Carbons in [22],
[7], 2,4,6-Triphenylheptane (2,4,6-TPH), and 2,4,6-
Tris(4-bromophenyl)heptane (2,4,6-TBPH) . 48

9 CH2 Chemical Shifts and Approximate Splittings for Iso-
tactic Trimers [7], [22], and 2,4,6-Triphenylheptane
(2,4,6-TPH) . . 49

10 13C Methyl Chemical Shifts for Tetramers [23], [8], and
2,4,6,8-Tetraphenyloctane (2,4,6,8-TPO) 53

11 Stereochemistry of the Anionic Oligomerization of 4-
Vinylpyridine Determined by Capillary GC. .. 60

12 Order of Elution of Stereoisomers of Styrene and 2-
Vinylpyridine Oligomers . . 62

13 Time Required for Establishment of Proton Transfer
Equilibria 4 and 5. . . 65










Table Page

14 Equilibrium Constant as a Function of Counterion,
Temperature and Concentration . 67

15 Thermodynamic Parameters for Equation 4 Determined
from a Plot of InK2 vs. 1/T ............... 69

16 Product Fractions in Equation 9 . 76

17 Product Fractions in Equation 10. . .. 78















LIST OF FIGURES

Figure Page

1 Overlap of Li p Orbital with the HOMO of the 2-Picolyl
Anion. . . . 2

2 Possible Modes of Monomer Presentation in the Anionic
Oligomerization of 2-Vinylpyridine . 4

3 Diastereomeric Ion Pairs [9] and [10] and the Role of
Intramolecular Coordination. . 8

4 Cation Side vs. Opposite Side Attack of Methyl Iodide
on a Carbanion . . 9

5 Apparatus for the Preparation of Alkali Metal 2-Ethyl-
pyridyl Salts. . . .. 14

6 Apparatus for the Recrystallization of Alkali Metal
Ethylpyridyl Salts . . 16

7 Apparatus for the Preparation of Sodio- and Potassio-
2-Ethylpyridyl Salts . . 18

8 Apparatus for Oligomerization of Vinylpyridine Monomers. 20

9 Apparatus for Carbanion Equilibrium Studies. ... 26

10 Pathways Leading to "Meso" and "Racemic" [4] 34

11 Transition States for Formation of"Meso" [4] 36

12 100 MHz 1H NMR Spectra of the (m) and (r) Stereoisomers
of Dimer [21]. . . 42

13 100 MHz 1H NMR Spectra of Trimer [22]. . 46

14 25.2 MHz 13C NMR Spectra of Trimer [22]. ... 47

15 Capillary GC Traces for Trimer [22]. . ... 51

16 25.2 MHz 13C NMR Spectra of Tetramer [23]. ... 52


viii










Figure Page

17 300 MHz 1H Spectrum of a Single Stereoisomer of
Tetramer [23] . . 55

18 Capillary GC Traces for Tetramer [23] . 56

19 Epimerization of Isotactic Tetramer [23]. ... 58

20 Appearance of Dimer Anion vs. Time in Proton Transfer
Equilibria 4 and 5. . . .. 66

21 Plot of ln K2 vs. 1/T for Dimer Anion [3] in Equation
4 with Various Counterions. . ... 70
















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


STEREOCHEMICAL AND MECHANISTIC STUDIES ON THE
ANIONIC OLIGOMERIZATION OF 2- AND 4-VINYLPYRIDINES

By

Craig C. Meverden

August, 1983

Chairman: Dr. Thieo E. Hogen-Esch
Major Department: Chemistry


In order to elucidate the mechanism of the anionic oligomeriza-

tion of 2-vinylpyridine, reactions of the 1,3-di(2-pyridyl)butane

anion lithium salt with 2-vinylpyridine as well as with other mono-

mers and electrophiles were investigated. With 2-vinylpyridine and

certain other monomers, the reaction proceeds in a non-stereoselec-

tive fashion, whereas 4-vinylpyridine and alkyl halides add with a

high degree of meso stereoselectivity. These results have been shown

to be consistent with coordination of the Li+ counterion by the penul-

timate 2-pyridine nitrogen lone pair. Such a coordination would favor

the ion pair configuration which leads to preferred meso placement of

monomer or electrophile. The corresponding anionic oligomerization

of 4-vinylpyridine indicates that the lack of intramolecular coordina-

tion of Li+ leads to random stereochemical placement of monomer and

methyl iodide.










Studies on the proton transfer equilibrium between alkali metal

salts of 2-ethylpyridine and model dimers indicate large differences

in the equilibrium constant Kapp with the different alkali metal

counterions. These are consistent with differences in intramolecular

complexation, Li+ being the most strongly completed, followed by Na+

and K In addition, cryptation of the Li counterion leads to a

marked decrease in Kapp. The temperature dependence of these equi-

libria indicates that the intramolecular coordination is favored par-

tially due to entropic factors. Dimers with penultimate groups which

are incapable of completing the M such as phenyl or 3-methyl-2-

pyridyl, yield Kapp values which approach unity in the equilibria.

Nevertheless, these dimer anions are stabilized to a small extent,

presumably due to some additional effect of the penultimate group.

Degradation reactions which occurred upon treatment of the 2-

vinylpyridyl oligomers with 2-ethylpyridyl anions were also investi-

gated. Such reactions were shown to be consistent with a mechanism

in which an alkene was formed upon expulsion of an a-pyridyl carb-

anion. These observations confirm reports by other authors of a

similar mechanism operating in the cleavage of poly-2-vinylpyridine

chains in the presence of carbanions.
















CHAPTER I

INTRODUCTION


In the past thirty years or so, there has been a great deal of

interest in the stereoregular polymerization of vinyl monomers. This

interest has been partly due to the new and important physical proper-

ties that stereoregular polymers may have, and partly due to the in-

teresting fundamental phenomena controlling the mechanism of stereo-

regulation. Factors such as monomer structure, the nature of the ini-

tiator, solvent, and temperature all may play a role in determining

the stereochemical composition of a polymer.

The anionic polymerization of 2- and 4-vinylpyridine provides a

system for which a study of the stereoregulating mechanism would be of

interest. For example, highly isotactic poly-2-vinylpyridine has been

prepared by Grignard1-4 and dialkylmagnesium3,5 initiators, but under

similar conditions 4-vinylpyridine gives only "atactic" polymers.1'2'6

A study of the corresponding anionic oligomerization processes would

provide a deeper understanding of the factors controlling stereoregu-

lation. Furthermore, the carbanionic intermediates in vinylpyridine

polymerization are very stable, and model compounds of these have been

well studied. Therefore, the role of the carbanion centers in the

oligomerization and polymerization may be more closely examined.









The simplest models for the active centers in the anionic poly-

merization of 2-vinylpyridine are the alkali metal salts of 2-ethyl-

pyridine. The lithium salt has been shown7 by NMR measurements and

CNDO/2 calculations to be sp2 hybridized at Ca with a great deal of

electron density delocalized into the pyridine ring. These studies

also suggest that the lithium ion exists above the plane of the pyri-

dine ring overlapping with the p orbitals of Ca and the nitrogen

(Figure 1). Matsuzaki et al.8 have found similar results for the

position of the lithium ion for the cumyl anion. Because of the sp2











N


Figure 1. Overlap of Li p Orbital with the
HOMO of the 2-Picolyl Anion.

hybridization and extensive delocalization into the ring, lithio-2-

ethylpyridine may exist as both the E and Z isomers. Table 1 lists

theresults as determined by 1H NMR7'9 for the E:Z ratios as a func-

tion of metal ion. Coalescence of these isomers is not observed at

temperatures up to 100C, indicating that the equilibrium between E

and Z anions is very slow on the NMR time scale. In the dimeric and









Table 1

E:Z Ratio in Lithio-2-Ethylpyridine as


a Function of Counteriona


Counterion Solvent %E:%Z


Li THF 95: 5

Na THF 86:14

K THF 80:20

Li THF/TGb 66:34

Li THF/[2.2.1] 36:64

Na THF/TGb 66:34

Kc NH3 45:55

a At 25C

b TG = tetraglyme

c At -40C; Private communication from J.A. Zoltewicz



trimeric model anions, the E:Z ratio is found to be 1:1 with both Li

and K counterions.10 This ratio is presumably the result of the mode

of monomer presentation, which must be random with respect to the

position of the nitrogen atom (Figure 2). Interestingly, monomer

placement is selective with respect to 8-carbon stereochemistry as

shown by addition of E-a-deuterio-2-vinylpyridine. 9,11

Conductance measurements12-14 on living poly-2-vinylpyridine (Na

counterion) indicate that it has a dissociation constant about two

orders of magnitude lower than living polystyrene (Na+ counterion) in

THF (Table 2), Moreover, living polystyrene capped with a single unit

of 2-vinylpyridine is somewhat more dissociated than















0


H


H 0
H +
H H





4/


CH 3


Possible Modes of Monomer Presentation in the
Anionic Oligomerization of 2-Vinylpyridine.


Figure 2.











Table 2

Dissociation Constants for Living Polymers in THF

T (oC) Kd

P2VP-,Na+ 23 8.3 x 10-10 mol/1

PSty-,Na+ 25 1.5 x 10-7 mol/l

(PSty)-2VP",Na+ 25 6.2 x 10-9 mol/l

P4VP-,Na+ 23 5 x 10-9 mol/l

CH CH
POL. CH C "C'CH
Na+'
0k


poly-2-vinylpyridine. Intramolecular coordination of the metal ion by

the penultimate pyridine group has been invoked to explain the lower

dissociation constant. The penultimate pyridine group "ties up" the

metal ion, thus decreasing ion pair dissociation. With living poly-

styrene or polystyrene capped with a unit of 2-vinylpyridine, intra-

molecular coordination is not possible, and the ion pairs may be more

readily dissociated. Intramolecular coordination of the metal ion has

also been proposed in the active centers of poly(methyl methacryl-

ate).15,16
Previous studies on the anionic oligomerization of 2-vinylpyri-

dine 1117-20 (Equation 1) have indicated that the high methylation

stereoselectivity of the lithium salt of dimer [3] is consistent with










CHCH2 n-BLi > CH3CH-,Li >
S -780C
R R

[1] [2] ()

CH3-CHCH -CH ,Li H3 CH3-+CHCH2 -CHCH3

R R R R

[3] [5] [6] [8]
R = 2-pyridyl; [3], [6] n = 1; [4], [7] n = 2; [5], [8] n = 3

intramolecular coordination of the metal ion by the penultimate pyri-
dine group. When the oligomerization is initiated by other alkali
metal salts of 2-ethylpyridine, the stereoselectivity of methylation

decreases with increasing cation radius (Table 3). The addition of

Table 3

Methylation Stereochemistrya of Anion [3] b as a
Function of Cation and Solvent or Coordinating Agent

Cation Solvent/Coordinating Agent % Meso Reference

Li THF >99 21
Na THF -99 21
K THF 85 21
Rb THF 76 21
Li THF/[2.1.1] 65 22
Na THF/[2.2.2] 58 22
Na THF/18-crown-6 58 22

a At -780C
b ~10-2 M









cation solvating agents such as crown ether or cryptand also results

in a loss of methylation stereoselectivity. Moreover, methylation of

the corresponding 4-vinylpyridyl dimer anion results in an approxi-

mately 50:50 mixture of meso and racemic products.17 Clearly, upon

disruption of the intramolecular coordination, methylation occurs in

a relatively non-stereoselective fashion.

The high meso stereoselectivity has been attributed to the pre-

dominance of ion pair diastereomer [9] over [10] (Figure 3). Examina-

tion of models of these diastereomeric ion pairs indicates that [9a]

will be favored over [10a] because of butane-gauche interactions be-

tween the CH3 group and the CH2C- bond as well as non-bonded interac-

tions between the CH3 group and the ion pair. Rotation of the CH2-CH- -

R bond by 1800 followed by inversion of the carbanion pair leads to

structure [lOb] which would seem less likely since the metal ion is

further removed from the penultimate group. Additional steric inter-

actions are seen in [10a] with the methyl group interacting with the

ultimate pyridyl group and the solvation shell of the counterion.

Thus, the overall free energy of [9] may be several kilocalories lower

than [10] and would result in a large predominance of [9]. Alkyla-

tion of [9] from the cation side leads to the observed meso product.

Cation side attack is assumed since attack from the opposite side

would result in a product separated ion pair (Figure 4). Such an ion

pair is expected to be quite unfavorable.

Further support for the intramolecular coordination is provided

by the lack of methylation stereoselectivity of dimer anion [11]

(Table 4).23 Methyl substitution at the 3'-position of the










M 2-p.
'\P.


H 2-Py M*


[9] 0


[9a]


[9a]


Figure 3.


[LOa]


[10]


[lOb]


[lOa]


Diastereomeric Ion Pairs [9] and [10] and the Role
of Intramolecular Coordination.


2-Pt
-=H


CH-I











+ IM

CH -- '

( R 0 R







SR M


CH3
R CH3
I6 I



Figure 4. Cation Side vs. Opposite Side Attack of Methyl
Iodide on a Carbanion.




CH3CH-CH2CH-, Li +

R
00




[11] R = CH3, R' = H
[12] R = H, R' = CH3









Table 4

Stereochemistryof Methylation of Dimer Anions [11], [12] and [3]a

% (R,S or S,R) % (R,R or S,S)
Dimer Anion meso-like racemic-like

[11] 24 76
[12] 99 1

[3] >99 <1
aDetermined by capillary GC.


penultimate pyridine ring decreases the stereoselectivity of methyla-
tion with respect to unsubstituted dimer, while substitution at the
electronically equivalent 5'-position does not significantly lower
methylation stereoselectivity. This indicates that steric interac-
tions between the 3'-methyl group and the methyl and methylene groups
of the chain disrupt the intramolecular coordination in [11].


In contrast to the high meso-stereoselectivity of methylation,
2-vinylpyridine adds to [3] in a rather non-selective fashion (60%
meso, 40% racemic).20 The reason for this large difference in









stereoselectivity (>99/1 vs. 1.5/1) is not very well understood.

Effects such as steric bulk or electronic factors may play a role

in the stereochemistry of 2-vinylpyridine addition. This unsolved

problem is crucial to understanding the mechanism of anionic poly-

merization of 2-vinylpyridine.

Research Objectives

The purpose of this study may be summarized as follows:

A. To further our understanding of the stereoselective methyl-

ation of 2-vinylpyridine oligomer anions. Specifically, to determine

to what extent the intramolecularly completed form of the carbanionic

intermediates exists. This is accomplished by examination of the

equilibrium between alkali metal salts of 2-ethylpyridine and oligo-

meric model compounds.

B. To determine why the methylation of 2-vinylpyridine oligomer

anions is stereoselective while the addition of 2-vinylpyridine is

not. A systematic study of the reaction of these carbanions with var-

ious electrophiles and monomers is used to point up some of the fac-

tors important in controlling the stereochemistry of these reactions.

C. To elucidate the stereochemistry of the anionic oligomeriza-

tion of 4-vinylpyridine.

D. To understand degradation reactions which occur when poly-2-

vinylpyridine is treated with carbanions. Oligomers of 2-vinylpyri-

dine are used as model compounds to determine the products formed in

these degradation reactions.
















CHAPTER II

EXPERIMENTAL


Since the presence of trace amounts of electrophilic impurities

will affect anionic active centers, all reagents were carefully puri-

fied and transferred in vacuo, and all reactions were carried out in

Pyrex glass vessels under high vacuum (10-5 mm to 10-6 mm Hg). All

stopcocks and ground glass connections were lubricated with Dow

Dorning high vacuum silicone grease. Transfer of reagents was per-

formed by distillation in vacuo or through glass breakseals which may

be broken by striking with magnetic rods sealed in glass.
Purification of Reactants

In all reactions, tetrahydrofuran (THF) was used as the solvent.

THF was refluxed over Na/K alloy for several hours, then distilled

onto fresh Na/K alloy. A small amount of benzophenone (1 gram per

liter of THF) was added as an indicator. The deep purple color of the

benzophenone dianion indicated the absence of traces of water, oxygen,

or other impurities.

All reactants were liquids at room temperature and were purified

by stirring over CaH2 for at least 8 hours and degassed in vacuo fol-

lowed by distillation onto fresh CaH2 and stirring for at least an-

other 8 hours. The liquid was then distilled in vacuo into an ampule

equipped with a breakseal and sealed off. If the material as









purchased was particularly impure, a fractional distillation was per-

formed before drying over CaH2 and distillation in vacuo. Methyl io-

dide and ethyl iodide were stirred over CaH2 and distilled in vacuo

onto fresh CaH2 in a vessel equipped with a vacuum stopcock and ground

glass joint for repeated use on the vacuum line. Liquids with high

boiling points were stirred over CaH2 and degassed in vacuo followed

by filtration through sintered glass filters into ampules and sealed

off.

Lithium tetraphenyl boron prepared by the method of Szwarc

et al.24 was recrystallized from 1,2-dichloroethane and dried over-

night in vacuo. The dried solid was dissolved in THF and the solu-

tion transferred in vacuo to an ampule equipped with a breakseal and

sealed off.

Preparation of Ethylpyridyl Alkali Metal Salts

Lithio-2-ethylpyridine

A solution of n-butyllithium (Aldrich) in hexane was introduced

into a 250 ml round bottom flask with a clean, dry syringe. The ap-

paratus (Figure 5) was then sealed off and evacuated, removing the

hexane into a liquid nitrogen trap. THF was distilled into the flask

at -78C, followed by introduction of one equivalent of 2-ethylpyri-

dine with respect to n-butyllithium through a breakseal upon which the

solution immediately turned bright red. The solution was then warmed

up and kept at room temperature for at least 30 minutes, while butane

was removed periodically by opening the apparatus to the vacuum. The

apparatus was sealed from the vacuum line and the solution poured into

a side arm flask and sealed from the main flask.
















































Apparatus for the Preparation of Alkali Metal
2-Ethylpyridyl Salts.


Figure 5.









The lithio-2-ethylpyridine (2EPLi) was purified by recrystalliza-

tion in the apparatus shown in Figure 6. The crude 2EPLi solution was

introduced into the main flask (A), and the THF was removed by distil-

lation on the vacuum line until only a small amount (-10 cc) of sol-

vent remained. Approximately 40 cc of n-hexane (dried 24 hours over

Na/K alloy) was then distilled onto the viscous 2EPLi residue until

all the salt dissolved. The apparatus was sealed off and kept in a

freezer at -200C until crystallization occurred. Solvent was then de-

canted from the 2EPLi crystals into a side arm flask (B), and the

crystals were washed with hexane which was distilled back from the

side arm flask. After several washings, the side arm (B) was sealed

off and the crystals dissolved in THF freshly distilled into the ap-

paratus. The THF/2EPLi solution was poured into a second side arm

(C) (equipped with a breakseal) and sealed. Purity of the 2EPLi was

checked by isolating a small portion of the solution and terminating

this portion with CH3I and the absence of impurities verified by gas

chromatography. The concentration of 2EPLi in THF was determined by

terminating a portion of the solution with CH3I and titrating the LiI

by the method of Vollhard.25 Alternatively, the solution was termi-

nated with H20 and titrated for the total base concentration with

standard HC1 solution to pH z 7 using bromthymol blue as indicator.

The total base concentration reflected the presence of one equivalent

of 2-ethylpyridine and one equivalent of hydroxide ion. Thus, the

concentration of 2EPLi in solution was equal to half the total base

concentration.
















2EP-,M +
or 4EP-,M+


B C









Figure 6. Apparatus for the Recrystallization of Alkali Metal
Ethylpyridyl Salts.









Sodio- and Potassio-2-ethylpyridine

A sodium (or potassium) mirror was prepared in an evacuated 300

ml round bottom flask (Figure 7) by vacuum coating the walls of the

flask with the metal vapor produced by heating a reservoir (A) con-

taining the metal with a gentle flame. After forming the mirror, the

reservoir was sealed off, and THF (150 ml) was distilled into the

flask through the vacuum line. o-Methylstyrene was then added from

a breakseal at room temperature. A red color developed almost im-
mediately upon addition. After reaction of the metal with a-methyl-

styrene was complete (-1 hour), the dark red t-methylstyrene oligomer

dianion solution was poured into a side arm flask (B) and sealed from

the main flask. The flask containing the dianion solution was cooled

to -780C to polymerize any excess c-methylstyrene. After 1 hour, a

slight excess of 2-ethylpyridine was added at -780C.

The purification and titration procedures for sodio-2-ethylpyri-

dine (Na2EP) and potassio-2-ethylpyridine (K2EP) were identical to

those for Li2EP.

Lithio-4-ethylpyridine

Attempts to prepare lithio-4-ethylpyridine (4EPLi) by addition

of 4-ethylpyridine to n-butyllithium in THF at -780C failed to give

the desired carbanion. After termination with CH3 2-butyl-4-ethyl-

5-methylpyridine was produced almost quantitatively.
CH3 CH2 CH3CH2 CH3CH2

n-BuLi CH 3 CH
0 -THF7 B THF 3
N -78Nc -780C + LiI
H Li+ nBu






18
















-o

0A






*-
\ I




















CL
I *
3 o\0

( ct)
-4-

'Ui















s-











o1-










To avoid this reaction, 2,4-diphenyl-4-methyl-2-nonyllithium

(DMNL) was used to deprotonate 4-ethylpyridine. In an apparatus simi-

lar to that used for the preparation of lithio-2-ethylpyridine (Figure

5), 2 equivalents of a-methylstyrene were added to 1 equivalent of n-

butyllithium in THF at 00C. The solution was reacted for 15 minutes,

then cooled to -780C for 15 minutes to polymerize any excess a-methyl-

styrene. One equivalent of 4-ethylpyridine was then added directly at

-780C and allowed to react at room temperature for 30 minutes, the

color of the solution changing from deep red to light orange. The

solution was transferred to a side arm flask equipped with a break-

seal and sealed off. The crude lithio-4-ethylpyridine was purified by

recrystallization in a manner identical to that for lithio-2-ethyl-

pyridine.
Oligomerizations

2-Vinylpyridyl Oligomers

Purified lithio-2-ethylpyridine in THF was introduced through a

breakseal into an evacuated 250 ml round bottom flask (Figure 8), and

125-150 ml of THF was distilled into the flask at -780C. The experi-

ments were generally run with a carbanion concentration of about 5 x

10-2 M. 2-Vinylpyridine (1.5-2.0 equivalents) was distilled slowly

over a 1-2 hour period from a 25 ml round bottom flask attached to the

main flask, which was kept at -780C. After monomer addition was com-

plete, the anions were terminated with various reagents. In the case

of termination with methanol, methyl halides, or ethyl iodide, the

purified terminating agent was distilled through the vacuum line onto

the oligomer anion solution. For termination with other reagents



















Gi
C

-o
*1~


C~J~
'U-
-C

Gi
-a










which are relatively easily distilled in vacuo (i.e., trimethylsilyl

chloride, 4-vinylpyridine, acetone-d6, isopropyl bromide), the termi-

nating agent was distilled onto the carbanion from the same side arm

flask as the 2-vinylpyridine monomer. For reaction of the oligomer

anions with electrophiles which will not vacuum distill easily (i.e.,

benzyl chloride, benzhydryl chloride, 1,1-diphenylethylene, benzalde-

hyde), the electrophile was added directly to the carbanion solution

through a breakseal attached to the reaction flask. Electrophilic

reagents which, upon addition, form new anionic species were subse-

quently protonated with methanol distilled through the vacuum line.

All reactions were carried out at -780C. However, the more hindered

electrophiles, such as isopropyl bromide and benzhydryl chloride,

react very slowly at -780C, and the solutions were allowed to warm

up to about -400C in order to ensure complete reaction.

After reaction, the volatile fraction was removed by evacuation

on the vacuum line. The apparatus was then removed from the line, and

the residue was dissolved in 125 ml of 10% HC1. The HC1 solution was

washed several times with methylene chloride, then neutralized with

Na2CO3. The aqueous solution was extracted with 300 ml of methylene

chloride and the organic layer dried over anhydrous Na2SO4 overnight.

Finally, the dried methylene chloride solution was evaporated in a

rotary evaporator. The yield of oligomers was 30-80%, depending on

the monomer/initiator ratio and the rate of monomer addition. High

[M]/[I] ratios and fast rates of monomer addition led to an increased

formation of polymer, which was the major by-product. Preparative

liquid chromatography was used to separate the crude product mixture

into the various oligomer fractions.










4-Vinylpyridine Oligomers

The preparation of 4-vinylpyridine oligomers was essentially

identical to the preparation of 2-vinylpyridine oligomers, using re-

crystallized 4-ethylpyridyllithium as initiator and 4-vinylpyridine

as monomer. Termination was made with either methanol or methyl io-

dide. Isolation of the various oligomers was carried out by prepara-

tive liquid chromatography.

Epimerization Studies

Partial epimerization of isotactic 4-vinylpyridine tetramer ob-

tained by liquid chromatography was studied to assign the stereoiso-

mer peaks in gas chromatography. Samples (-50 mg) were dried in vacuo

in vessels equipped with ground glass joints. Potassium tert-butoxide

(0.09 g in 1.0 ml tBuOH), prepared by reaction of K metal with tBuOH,

was added to the sample under argon atmosphere with a clean, dry

syringe. The vessels were then capped with rubber septum stoppers.

Aliquots of the solution (-100 pl) were taken at specified intervals,

neutralized with H20, and analyzed by capillary column gas chromato-

graphy.
Equilibrium Studies

Preparation of 1,3-Di(2-pyridyl)butane

This product was obtained by vacuum distillation of the crude

mixture of protonated 2-vinylpyridyl oligomers; b.p. 125-127C (0.1

mm Hg). 1H NMR 1.26 ppm, doublet, J = 6.7 Hz, (3H); 2.05 ppm, multi-

plet, (2H); 2.83 ppm, multiple, (3H); 7.30 ppm, multiple, (6H); 8.40

ppm, multiple, (2H).









Preparation of 2,4-Di(2-pyridyl)pentane

This product was also obtained by vacuum distillation of the crude

mixture of methylated 2-vinylpyridine oligomers; b.p. 106-108C (0.25

mm Hg). 1H NMR 1.31 ppm, doublet, J = 6.5 Hz, (6H); 2.10 ppm, multi-

plet, (2H); 2.80 ppm, multiple, (2H); 7.30 ppm, multiple, (6H); 8.40

ppm, multiple, (2H).

Preparation of 2-Ethyl-3-methylpyridine

2,3-Lutidine (9.3 g, ICN K&K Laboratories) in 150 ml THF was

treated with one equivalent of n-butyllithium in vacuo at -780C. The

carbanion precipitated at -780C, so the solution was warmed to about

-50C and terminated with methyl iodide. Excess methyl iodide and

the solvent were removed by evaporation on a rotary evaporator, and

the residue was dissolved in 100 ml of methylene chloride. The solu-

tion was washed twice with 100 ml of water and dried over Na2SO4 over-

night. After removal of the solvent, the crude product, analyzed by
H NMR and gas chromatography, was shown to be about 90% 2-ethyl-3-

methylpyridine. The product was purified by fractional distillation;

b.p. 178-180C. 1H NMR 1.43 ppm, triplet, J = 7.5 Hz, (3H); 2.17

ppm, singlet, (3H); 2.74 ppm, quartet, J = 7.5 Hz, (2H); 7.12 ppm,

multiple, (2H); 8.30 ppm, multiple, (1H).

Preparation of 1-(2-Pyridyl)-3-(3-methyl-2-pyridyl) butane

In an evacuated oligomerization apparatus (Figure 8), one equiv-

alent of 2-ethyl-3-methylpyridine was added to 1.1 equivalents of n-

butyllithium in THF at -78C. The characteristic orange color of the

2-ethyl-3-methylpyridyl anion formed immediately. The solution was

warmed up to room temperature and allowed to react for 30 minutes,









then was cooled to -780C followed by in vacuo distillation of one

equivalent of 2-vinylpyridine. After monomer addition was complete,

the anion solution was protonated with deaerated methanol distilled

through the vacuum line. The crude product was extracted in the same

fashion as the 2-pyridyl oligomer crude product, and the 1-(2-pyri-

dyl)-3-(3-methyl-2-pyridyl) butane was isolated by preparative liquid

chromatography. 1H NMR 1.26 ppm, doublet, J = 7.0 Hz, (3H); 2.12

ppm, singlet, (3H); 2.15 ppm, multiple, (2H); 2.80 ppm, multiple,

(3H); 7.20 ppm, multiple, (5H); 8.47 ppm, multiple, (2H).

Preparation of 1-(2-Pyridyl)-3-phenylbutane

2-Picoline (4.0 g, Aldrich) in 150 ml THF was treated with one

equivalent of n-butyllithium in vacuo at -780C. The resultant 2-

picolyllithium was then reacted with 9.7 g of a-bromo-isopropylben-

zene (Aldrich) at room temperature for 3 hours. The color changed

from deep red to light yellow, indicating the 2-picolyllithium had

reacted completely. The volatile fraction was then removed by evacu-

ation into a liquid nitrogen trap on the vacuum line, and the remain-

ing residue was dissolved in 125 ml of 10% HCI. The HCl solution was

washed several times with methylene chloride, then neutralized with

Na2CO3. The aqueous solution was extracted with 400 ml of methylene

chloride and the organic layer dried over anhydrous Na2SO4 overnight.

After removal of the methylene chloride on a rotary evaporator, the

product was isolated (3.8 g, 41% yield) by vacuum distillation; b.p.

107-110C (0.15 mm Hg). 1H NMR 1.15 ppm, doublet, J = 6.5 Hz, (3H);

1.90 ppm, multiple, (2H); 2.58 ppm, multiple, (3H); 7.05 ppm, mul-

tiplet, (8H); 8.33 ppm, multiple, (1H).









Preparation of 3-Methyl-1,3-di(2-pyridyl) butane

This product was prepared in a manner similar to that used for

2-vinylpyridyl oligomers, using lithio-2-methylpyridine as initiator

and 2-(2-pyridyl) propene as the monomer. The reaction was terminated

by distilling methyl iodide into the carbanion solution through the

vacuum line. After work-up, the dimer was isolated from the crude

product by preparative liquid chromatography. 1H NMR 1.46 ppm,

singlet, (6H); 2.35 ppm, multiple, (4H); 7.37 ppm, multiple, (6H);

8.58 ppm, multiple, (2H).

General Procedure for Carbanion Equilibrium Reactions

In an evacuated 100 ml round bottom flask (Figure 9), 200 mg of

the desired dimer [1,3-di(2-pyridyl)-butane, 1-(2-pyridyl)-3-(3-

methyl-2-pyridyl)-butane, 2,4-di(2-pyridyl)-pentane, 3-methyl-1,3-di-

(2-pyridyl)-butane, or 1-(2-pyridyl)-3-phenylbutane]were added to one

CH3CH'M+ + CH3CHCH2CH2 K K CH3CH2 + CH3CHCH2CH-M+ (2)

2Py R 2Py 2Py R 2Py

R = 2-pyridyl, phenyl, 3-methyl-2-pyridyl

2Py = 2-pyridyl

CH3 CH3
CH3CH ,M1 + CH3-CCH2CH2 K CH 3CH2 + CH3-C-CH2CH ,M

2Py 2Py Py 2Py 2Py 2Py

equivalent of an alkali metal 2-ethylpyridine salt in 15-20 ml of THF

at room temperature. The solution was transferred to a side arm

flask, divided, and each sample was brought to the desired tempera-

ture and allowed to react. After a certain time interval, each sample













































Figure 9. Apparatus for Carbanion Equilibrium Studies.








was connected to the vacuum line and terminated with ethyl iodide dis-

tilled in vacuo. The terminated mixtures were dissolved in methylene

chloride and washed several times with water. The organic phase was

then analyzed by capillary column gas chromatography.
When completing agents (18-crown-6, [2.1.1] or [2.2.1] cryptands)

were used, the ethylpyridyl salt was allowed to react with the com-

plexing agent for 1-2 minutes at room temperature before addition of

the dimer to allow for complete cation complexation.

Determination of Equilibrium Constants

The apparent equilibrium constants in Equation 4 (p. 72) are
given by
[CH3CH2(2Py)][CH3CHRCH2CH(2Py) ,M ]
app [CH3CH(2Py)-,M+][CH3CHRCH2CH2(2Py)]

upon termination with ethyl iodide. The ratios [CH3CH2(2Py)]/[CH3-

CH(2Py)-,M+] and [CH3CHRCH2CH(2Py)",M+]/[CH3CHRCH2CH2(2Py)] may be

determined directly from the integrated areas of the GC traces of the

ethylated products. The apparent equilibrium constants are reported
as the product of these two ratios as measured on the gas chromatograph.
Degradation Reaction Studies

Preparation of 1,3,5-Tri-(2-pyridyl)-hexane and 1,3,5,7-Tetra-(2-
pyridyl)-octane

These products were isolated by preparative liquid chromatography

of the crude mixture of 2-vinylpyridyl oligomers.
General Procedure for Degradation Reaction Studies
The procedure was essentially the same as in the study of carb-
anion equilibrium reactions. The mixture of the alkali salt of 2-
ethylpyridine and the appropriate dimer, trimer, or tetramer was








terminated with either methyl iodide or methanol distilled in vacuo.

After work-up, the crude product mixture was analyzed by capillary

gas chromatography to determine product distributions. To identify

the structures of the products, the crude mixture was separated by

preparative liquid chromatography and each fraction analyzed by HNMR.

Since the products in the gas chromatograph were detected by

flame ionization, the integrated areas of each product peak had to

be corrected to take into account the different molecular formulas.

The response of the detector was dependent on the number of carbons

in the molecule as well as the oxidation state of each carbon. Using

"effective carbon numbers,"26 the following values were assigned to

each product:

CH3 CH2CH3 CH3 CHCH3 CH3CHCH2CH2



(5.75) (6.75) (7.75) (13.50)

CH3CH,C2 CHC3 CHCHCHC(CH 2CH2C(CH3 2



(14.50) (15.50) (14.50)
Effective Carbon Numbers26

C aliphaticc, aromatic) 1.0

N (tertiary amines) -0.25

Thus, a dimer with an "effective carbon number" of 15.50 would give an

integrated GC peak area twice as large as 2-isopropylpyridine, which

has a value of 7.75. Taking these values into account, a reasonable

determination of product distributions can be made from a GC trace.








This method was verified by using known mixtures of 2-ethylpyridine

and dimer [6]. The measured and calculated GC peak areas were in good

agreement ( 3%).
Preparative Liquid Chromatography

All preparative separations were performed with an Altex Model

332 programmable gradient system, fitted with a constant wavelength

UV detector (254 nm). For the separation of one -gram or less of a

sample, a Lobar B column (E. Merck) with 40-63 p LiChroprep Si60

silica gel was used. Generally, the eluents were programmed from

non-polar (hexanes) to polar (4:1 methylene chloride:methanol) over

a period of from 150 to 400 minutes,21 depending on the sample.
Capillary Column Gas Chromatography

Gas chromatographic analyses were performed with a temperature

programmable Hewlett-Packard Model 5880A instrument equipped with a

flame ionization detector. The columns used were 25 or 50 meter SE-

54 silicone gum (Hewlett-Packard) with a temperature limit of 350C.

Helium or hydrogen was used as the carrier gas.
Nuclear Magnetic Resonance

Proton NMR spectra (60 MHz) were obtained on either a Varian

A-60A or a Varian EM-360L spectrometer. Carbon-13 (25 MHz) and 100

MHz proton NMR spectra were obtained on a Jeol JNM-FX-100 instrument.

A Nicolet NT-300 NMR spectrometer (financed by the Instrument Program

of the NSF Chemistry Division) was used to obtain the 300 MHz proton

NMR spectra. Chemical shifts are expressed in parts per million (ppm)

downfield from tetramethylsilane (TMS) unless otherwise stated. Cou-

pling constants (J) are expressed in Hertz (Hz).














CHAPTER III

ADDITION OF ELECTROPHILES TO LIVING 2-VINYLPYRIDYL DIMER
In order to further elucidate the mechanism of the anionic oligo-
merization of 2-vinylpyridine, reactions of the 1,3-di(2-pyridyl) bu-
tane anion lithium salt [3] with various electrophiles have been
studied. The general reaction scheme is shown in Equation 1. In this
case, the living oligomers are terminated by addition of an electro-
philic species other than methyl iodide.
After isolation by preparative liquid chromatography, the dimers

[13] were analyzed by 1H NMR. It was previously determined19,21 in
the case of the symmetrical methylated dimer [6] that the meso stereo-
isomer gives a methyl doublet which is shifted downfield from the
racemic doublet. The dimers terminated with various electrophiles all
give two methyl doublets, the most intense of which is the furthest
downfield. Therefore, by comparison with the methylated dimer, it is
likely that the predominant stereoisomer in all cases is the meso-like
product.
CH3CHCH2 CH R R = -CH2CH3, -CH(CH3)2,
-Si(CH3)3, -CH2Ph,
S-CHPh2, -CHPhOH,
-C(CD3)2OH, -CH2CPh2H,

[13] -CH2CH2(2Py),
-CH2CH2(4Py)










The capillary gas chromatography results indicate that the pre-

dominant stereoisomer of [13] in all cases is retained the longest on

the column. With the methylated dimer [6], it was observed20'21 that

the stereoisomer with the longest retention time was the meso isomer.

Thus, since the predominant stereoisomer in each case follows the same

NMR and GC trends, it may be inferred that the stereochemical assign-

ments for [13] are consistent with those for [6].20,21 That is, the

stereoisomer having the longest GC retention time and the most down-

field methyl doublet in the 1H NMR has the same relative configuration

as meso-[6].

Quantitative measurements of stereochemistry were made with capil-

lary GC by using the integrated areas of the dimer peaks in the crude

oligomer mixture before isolation of the dimer. Dimer samples iso-

lated by preparative liquid chromatography were not used for quantita-

tive determinations since the stereoisomeric ratios of the isolated

dimer may be changed somewhat by LC peak shaving. However, in general

no large differences in the proportion of stereoisomers were found be-

tween the crude oligomer mixture and isolated dimer fractions.

Table 5 lists the stereochemical results determined by 1H NMR

and capillary GC for the reaction of various electrophiles with the

lithio salt of [3]. It can be seen that alkyl halides generally add

in a highly stereoselective fashion. Steric bulk appears to play a

small role in the stereochemistry of alkylation, with methyl halides

reacting more stereoselectively than primary and secondary halides.

Moreover, methylation stereoselectivity appears to be independent of

the nature of the halide ion and the time allowed before termination of

the living oligomers.










Table 5

Stereochemistry of Electrophilic Addition
to 2-Vinylpyridyl Dimer Lithio Salt [3]a

Configuration Configuration
Electrophile (A) (B) Electrophile (A) (B)

CH31 >99 <1 4-Vinylpyridine 97.0 3.0

CH3 1b 99.1 0.9 2CHC1 96.1 3.9

CH3 1 96.6 3.4 (CH3)2CHBr 95.4 4.6

CH3 d 98.2 1.8 1,1-Diphenyl-
CH3 <1 ethylene 92.7 7.3
CH3le >99 <1
1,1-Diphenyl-
CH3Br 99.0 1.0 ethylene f 63 37

CH3C1 99.0 1.0 (CD3)2CO 84.8 15.2

0 CH2Cl 98.0 2.0 eCHO 71.3 28.7

CH3CH21 97.8 2.2 2-Vinylpyridine 64 36

(CH3)3SiCl 97.3 2.7

a In THF, -780C.
b 0.3 Equivalents LiB4 added after monomer addition.
c 1.0 Equivalent 2-ethylpyridine added after monomer addition.
d 1.0 Equivalent 1,3-di(2-pyridyl)butane added after monomer addition.
e Terminated 3 hours after completion of monomer addition at -780C.
At 250C.


(A)
meso-like


(B)
racemic-like










Addition of vinyl compounds to [3] provides some interesting re-

sults. High stereoselectivity is observed with 4-vinylpyridine and

1,1-diphenylethylene addition, while 2-vinylpyridine addition is rather

non-stereoselective. At room temperature, 1,1-diphenylethylene also

adds non-stereoselectively. It is clear from these results that fac-

tors other than steric bulk play a role in the stereoselectivity of

addition of vinyl compounds to [3]. Carbonyl compounds (benzaldehyde

and acetone-d6) similarly add to [3] in a rather non-stereoselective

fashion.

It is interesting to note that in all cases the predominant

stereoisomer appears to have the same relative configuration as meso-

[6]. This indicates that the ion pair configuration leading to meso

placement of the electrophile or monomer is favored. Thus, cation

side attack of an electrophile on ion pair [9] (Figure 3) leads to a

meso dyad, whereas cation side attack on [10] leads to a racemic place-

ment. Intramolecular coordination of the metal ion by the nitrogen

lone pair of the penultimate pyridine ring has been evoked to explain

the predominance of ion pair diastereomer [9] over [10].11,17-20 Non-

bonded interactions between the methyl group and the ultimate pyridine

ring as well as butane-gauche interactions in [Loa] render this struc-

ture less favorable than [9a] (Figure 3).11,19

Figure 10 shows a scheme which appears to be consistent with the

observed differences in stereoselectivity seen in Table 5. Dimer anion

[3] presumably favors ion pair diastereomer [9] which is in equilib-

rium with a small amount of [10] (Figure 3). In addition, 1H and 13C

NMR studies have shown that anion [3] exists as a 1:1 mixture of the E

















I.

m


[9]-Z


[9]-E


"Meso" [4]


"Meso" [4]


III.


"Racemic" [4]


Figure 10. Pathways Leading to "Meso" and "Racemic" [4].









and Z isomers,10 which equilibrate very slowly on the NMR time

scale.7'9 Thus, addition of 2-vinylpyridine to [9]-E and [9]-Z

yields meso anion [4]. The transition states in these two pathways

differ in that the metal ion remains intramolecularly coordinated in

the addition to [9]-E (pathway II), while the penultimate pyridine

nitrogen is not in proper position to coordinate the metal ion in

pathway I. The two transition states are shown in Figure 11. Since

intramolecular coordination is a strongly favored process, the con-

tribution from pathway I would be expected to decrease. Therefore,

since [10]-Z is in equilibrium with [9]-Z, pathway III may compete

favorably with pathway I, thus increasing the overall racemic content

in the product. Alternatively, reaction of 2-vinylpyridine with the

uncomplexed dimer anion [3], which may be present in small amounts in

this system, may overtake pathway I. Uncomplexed [3] would be ex-

pected to give a random placement of monomer, and contribution from

this species may account for the lowered stereoselectivity of 2-vinyl-

pyridine addition.

For electrophiles such as alkyl halides, 4-vinylpyridine, and

1,1-diphenylethylene, intramolecular coordination with the penulti-

mate pyridine nitrogen in the transition state does not appear to be

advantageous. As a result, these electrophiles are expected to react

equally well with [9]-Z and [9]-E. The high meso addition stereo-

selectivity with these electrophiles is clearly consistent with the

predominance of ion pair structure [9] over [10].

In the transition state for alkylation of [3], intramolecular

cation coordination will probably not be important since there is no

























[9]-z


[9]-E


Transition States for Formation of "Meso" [4].


Figure 11.










new carbanion formed which may benefit from the stabilization caused

by such coordination. With 4-vinylpyridine addition, cation coor-

dination will also be unimportant since the structure of the trimeric

anion formed after monomer addition would probably not allow intra-


Li+


H ON H%


H3 H


molecular coordination to occur. The newly formed 4-pyridyl carbanion

would be highly delocalized, with a large charge density on nitro-

gen.27 The position of the Li counterion will be influenced by this

delocalization and may be located too far from the penultimate pyri-

dine ring to be coordinated. This is consistent with the non-stereo-

selective methylation of the 1-(4-pyridyl)-3-(2-pyridyl)butane lithio

salt.11 Here the lack of coordination of Li+ by the penultimate 2-

pyridine ring leads to a 50/50 mixture of stereoisomers. Thus, the

lack of intramolecular cation coordination in the transition state for

the addition of 4-vinylpyridine to [3] leads to stereoselective place-

ment in a fashion similar to alkyl halides.

1,1-Diphenylethylene addition also supports the above scheme

since it adds to [3] with high meso-selectivity at -780C. This is the

case since the diphenylmethyl anion has been shown to exist predomi-

nantly as a solvent separated ion pair at low temperatures.28 Coordi-

nation of the Li+ by penultimate pyridine in this case would have










Li

HH N


CH3


[14]

essentially no stabilizing effect on anion [14], and one would expect

that intramolecular coordination would be unimportant in the transi-

tion state as well. At 25*C, however, anion [14] would be expected to

exist predominantly as a contact ion pair,28 and intramolecular coor-

dination in the transition state is expected to be a factor. There-

fore, addition of 1,1-diphenylethylene to [3] at 25C results in a

relatively non-stereoselective placement similar to 2-vinylpyridine

addition.

Addition of carbonyl compounds to [3] leads to intermediate ster-

eoselectivity of placement. The Li+ may be coordinated by the penul-

timate group in the transition state, but perhaps not to the same de-

gree as with 2-vinylpyridine and 1,2-diphenylethylene (at 25C). This

is most likely due to the tightness of the 0-Li bond which may de-

crease the extent of intramolecular coordination.

To verify that complexation by the penultimate pyridine is in-

deed responsible for the high meso methylation stereoselectivity, one

equivalent of 2-ethylpyridine was added to the living oligomer mixture

before termination with methyl iodide. The 2-ethylpyridine may com-

pete with the penultimate pyridine group for complexation of the Li

ion, thus disrupting intramolecular coordination. This is indeed what










is observed since the methylation stereochemistry drops significantly

in the presence of one equivalent of 2-ethylpyridine (Table 5). The

stereoselection is still rather high (-28/1) and is probably due to a

large amount of residual intramolecularly coordinated dimer anion. It

was thought that 1,3-di(2-pyridyl)butane [15] might act as a bidentate

ligand and be even more effective than 2-ethylpyridine in competing

with the penultimate pyridine for the Li However, addition of one

equivalent of [15] to the living oligomer system before methylation

decreases stereoselection to a lesser extent than with the addition of

2-ethylpyridine (Table 5). Apparently [15] is a poorer ligand than

2-ethylpyridine, perhaps with only one of its pyridine groups coordi-

nating to the Li In any case, these results provide further evi-

dence that the presence of the intramolecular coordination is respon-

sible for the high methylation stereoselectivity of dimer anion [3].














CHAPTER IV
ANIONIC OLIGOMERIZATION OF 4-VINYLPYRIDINE

In light of the results presented in the previous chapter on the
mechanism of the anionic oligomerization of 2-vinylpyridine, the ster-
eochemistry of the corresponding oligomerization of 4-vinylpyridine
(Equation 3) would be of interest. Preliminary results17 have indi-
cated that methylation of the dimer anion [18] is non-selective (-50/
50 meso/racemic), but information on monomer addition stereochemistry
or methylation of the higher oligomers has not been previously re-
ported. CH3 CH3
CH3 F 1 3 CH CH28R
nBuLi + 2 ==== nBuCH2 CCH2, Li -H780C-
Ph I I THF
Ph Ph
[16]

CH3CHR', Li+ R H--CH2CHR-nCH2CHR-, Li R + (3)
[17] [18] [20]
CH3I/ CHOH


H-(CH2CHR-nCH2CHRCH3 H-fCH2CHR)+n i
[213 [23] [24] [26]

R = 4-pyridyl; [18], [21], [24] n = 1; [19], [22], [25] n = 2;

[20], [23], [26] n = 3.









Results

Since intramolecular coordination of the Li+ ion by the penulti-

mate pyridine nitrogen would not be plausible in the 4-vinylpyridyl

oligomerization, the stereoselectivity of methylation and 4-vinylpyri-

dine addition would be expected to decrease with respect to that in

the 2-vinylpyridyl oligomerization.19 To probe this, the reactions in

Equation 3 were carried out. The living 4-vinylpyridyl oligomers were

terminated with methanol to determine the stereochemistry of vinyl ad-

dition, whereas the methylated products were used to determine both

the monomer addition and methylation stereochemistry. Stereochemical

assignments were made by isolation of the individual oligomers by

preparative liquid chromatography and analysis of their IH and 13C NMR

spectra. Analyses of the proportions of the various stereoisomers

were made by integration of the capillary GC peak areas in the crude

oligomer product mixtures.

Figure 12 shows the 100 MHz 1H NMR spectra of the meso (m) and

racemic (r) isomers of [21] which were isolated by preparative liquid

chromatography. Spectrum 12a was identified as that of the meso iso-

mer due to the AA'B2 methylene pattern (1.84 ppm), indicating the

magnetic non-equivalence of HA and HA'. The spectrum of the racemic

isomer gives an A2B2 pattern characteristic of equivalent methylene


racemic (r)


meso (m)




























2.5 2.0 1.5


2.0 1.5


Figure 12.


100 MHz 1H NMR
of Dimer [21].


Spectra of the (m) and (r) Stereoisomers


1.0 ppm


1.0 ppm









protons. The methyl groups in these isomers are also found to be sen-

sitive to stereochemistry. The resonances of the meso isomer (1.25

ppm) are shifted somewhat downfield from the racemic isomer (1.17

ppm). These NMR spectra are very similar to those previously reported

for the (m) and (r) stereoisomers of 2,4-diphenylpentane [27]29,30 and
2,4-di(2-pyridyl)-pentane [61]19,31 (Table 6).

CH3CHCH2CHCH3 CH3CHCH2CHCH3




[27] [6]



In the 13C NMR spectra of the meso and racemic isomers of [21],

several resonances are found to be sensitive to stereochemistry (Table

7). The methyl carbon is particularly sensitive to stereochemistry,

with the (m) resonance shifted upfield from that of the (r) isomer.

This trend is also seen in [6],20'21 [27],32-35 and 2,4-bis(4-bromo-

phenyl)pentane.36 The (m) and (r) stereoisomers of [21] are also de-

tectable by capillary gas chromatography, with the (r) isomer eluting
first. From the GC of the dimer in the crude oligomer mixture (before

isolation by LC), the stereochemistry of methyl addition was found to
be rather non-selective (60% meso/40% racemic).
In assigning the stereochemistry of the trimer [22], three ster-

eoisomers are possible: isotactic (mm), heterotactic (mr), and syn-

diotactic (rr). Four methyl resonances are expected in the NMR of

this trimer, one for each of the symmetrical isomers (mm) and (rr) and

















-V.
S.-
o
40

C\J in.
*r-


3:
-l~ c,.


I I I


CJ

c)
9-









N C




C



4-
r-







x
o =
- I
S I

0


LO LO LO LO LO LO
CY) C14 (T) cv j C~j


C-)
r-









I -I I,

0 0 0
I 2 2I


S- r- *-




E E E
u u u


r-9 1%









Table 7

13C NMR Chemical Shift Assignments for (m) and (r) [21]

shift (ppm)
Carbon (m) (r)

CH3 21.42 22.57

CH2 45.30 44.94

CH 36.97 37.31

C4 155.81 155.55

C3, C5 122.33 122.60

C2, C6 150.01 150.04


two for the unsymmetrical isomer (mr). In the 1H spectrum, the four

methyl doublets complicate the assignment of stereoisomers (Figure

13). However, in the 13C spectrum all four methyl absorptions are

easily distinguished (Figure 14). By comparison with the dimer, the

two upfield peaks should be due to stereoisomers with an (m) dyad

adjoining the CH3 group (mm and rm) and the two downfield peaks due

to the isomers with an (r) dyad adjoining the CH3 group (rr and mr).

The stereochemical assignments, in accord with the 13C NMR results for

2,4,6-triphenyl-heptane,32"34 2,4,6-tri(2-pyridyl)heptane,20'21 and

2,4,6-tris(4-bromophenyl)heptane,36 are then as follows: (mm) 20.3

ppm, (rm) 20.6 ppm, (rr) 22.5 ppm, and (mr) 22.9 ppm (Table 8).
Figure 13b shows the 100 MHz 1H NMR spectrum of the isotactic

stereoisomer of trimer [22] isolated by collecting only the last por-

tion of the trimer fraction in the preparative LC separation of 4-

vinylpyridyl oligomers. The methylene region of this spectrum shows













C.




3.0 2.'5

b.


2.5 2.0 1.5


2.5 2.0


Figure 13.


100 MHz 1H NMR Spectra of Trimer [22]; a) mixture of
all three stereoisomers, b) isotactic [22], c) 300
MHz 1H spectrum of isotactic [22].


1.0 ppm


1.0 ppm











b.


ppm


uLjLJ_
I I I
40 30 20 ppm


Figure 14.


25.2 MHz 13C NMR Spectra of Trimer [22]; a) mixture of
all three stereoisomers, b) predominantly isotactic [22].









Table 8
13C Chemical Shifts for the Methyl Carbons in [22], [7],
2,4,6-Triphenylheptane (2,4,6-TPH)
and 2,4,6-Tris(4-bromophenyl)heptane (2,4,6-TBPH)

(mm) (rm) (mr) (rr) References

[22] 20.3 20.6 22.9 22.5 this work

[7] 20.5 20.8 22.4 21.9 20,21
2,4,6-TPH 21.2 21.3 23.8 23.4 32,33
2,4,6-TBPH 21.1 21.7 23.7 23.3 36


(mr)


CH 3 1 1 1 1 CH 3


(rm)


a simple triplet pattern which indicates that the geminal CH2 protons
as well as the CH2-CH coupling constants are nearly equivalent. The
situation is very similar in the spectrum of isotactic 2,4,6-tri-
phenylheptane.37,38 In contrast to this, HA and HA' are non-equiva-

HC HB HC
C HA B HA C

CH3 CH3


[22]

lent in the spectrum of isotactic 2,4,6-tri(2-pyridyl)-heptane [7].19
Moreover, the CH2-CH coupling constants, JAC and JAB' are unequal in








[7], resulting in a complex CH2 spectrum. The position of the pyri-

dine nitrogen atoms in [7] and [22] appears to have different effects

H H
C HA B HA

CH3 CH3





[Z]
on the NMR spectra of the backbone protons. Thus, the various stereo-
isomers of [22] would be expected to give spectra similar to those for

2,4,6-triphenylheptane. On this basis, the spectrum in Figure 13b is

shown to be consistent with the isotactic stereoisomer of [22] as as-

signed by 13C NMR.

Table 9
CH2 Chemical Shifts and Approximate Splittings for
Isotactic Trimers [7], [22] and 2,4,6-Triphenylheptane (2,4,6-TPH)

(ppm) Approximate Splittings (Hz)
Trimer A A' AC AB

[7]a 19 1.90 2.17 7.9 5.7

[22]b 1.88 1.84 7.2 7.4

2,4,6-TPHc 38 1.69 1.65 8.2d 5.9d

a In CCI4, 250C.
b In CDC13, 250C.

c In o-dichlorobenzene, 700C.
d The splitting are approximately equal in CC14 at 250C.37










The 300 MHz 1H NMR spectrum of the CH protons of isotactic [22]

is shown in Figure 13c. These protons give a hextet and pentet in a

ratio of 2:1, corresponding to HC and HB, respectively. The observed

pattern is consistent with the symmetrical nature of the isotactic

trimer. In the methyl region of the 13C NMR spectrum of predomi-

nantly isotactic [22] (Figure 14b), the isotactic (mm) resonance is

observed to be the furthest upfield, with small peaks for the (mr),

(rm) and (rr) isomers which are present in small quantities.

The GC results (Figure 15) indicate that the three trimer stereo-

isomers in the product exist in a 1:2:1 ratio, with the isotactic iso-

mer corresponding to the last eluted peak. Furthermore, GC analysis

of the protonated 4-vinylpyridyl oligomers (Equation 3, [24] [26])

indicates the presence of two trimer stereoisomers in a ratio of 1.15/

1.0 (54% meso/46% racemic). Hence, a totally random stereochemistry

of addition of both the monomer and methyl iodide is indicated. The

assignment of trimer peaks in the GC should then be (in order of elu-

tion): (rr), (mr, rm) and (mm). This random stereochemistry is not

unexpected since methylation of 4-vinylpyridyl dimer anion [18] is

found to be non-stereoselective (60/40).

Since the stereochemistry of methylation and monomer addition in

trimer is essentially random, one would expect to see equal amounts of

each possible stereoisomer in the NMR spectrum of tetramer [23]. Fig-

ure 16 shows the 13C NMR spectrum of [23] isolated by preparative LC.

Six methyl absorptions are observed indicating that not all of the

eight possible methyl absorptions (mmm, mmr, mrm, rmm, mrr, rmr, rrm

and rrr) are resolved. Following the trend for dimer and trimer, the









mr + rm


II I I


Retention Time (mins.)


Figure 15.


Capillary GC Traces for Trimer [22]; a) predominantly
isotactic [22] (from NMR spectrum in Figure 13), b)
trimer stereoisomers in oligomerization product.



























ppm


a.










I K 'I. !


30


ppm


Figure 16.


25.2 MHz 13C NMR Spectra of Tetramer [23]; a) mixture of
all stereoisomers, b) isotactic [23].











group of 4 upfield absorptions (20-21 ppm) correspond to the CH3

groups adjoining an (m) dyad, and the two downfield peaks (22.5-23.0

ppm) correspond to those adjoining an (r) dyad. The peaks may be

assigned further by analogy with the trimer assignments (Figure 14).

That is, methyl groups adjoining (mm), (rm), (rr), and (rm) triads

absorb from high field to low field, respectively. The upfield set

of peaks are further resolved into tetrads and are tentatively as-

signed as (mmm), (rmm), (rrm), and (mrm) from high to low field on

the basis of a comparison with the corresponding 2-pyridyl tetra-
mer.20,21 Table 10 lists the 13C NMR methyl chemical shifts and their

stereochemical assignments for tetramer, [23], and the corresponding

2-pyridyl and phenyl analogues.
Table 10

C Methyl Chemical Shifts for Tetramers
[23], [8], and 2,4,6,8-Tetraphenyloctane (2,4,6,8-TPO)
Chemical Shifts
Stereoisomer [231 [8] 21,31 2,4,6,8-TPO33
mmm 20.3 20.2 20.9

rmm 20.5 20.4 21.1

rrm 20.8 20.8 21.1
mrm 20.9 20.9 21.5

(rrr, mrr) 22.6 21.6 23.2 (23.1)

(mmr, rmr) 23.0 22.3 (22.2) 23.8


To verify these assignments, a single tetramer stereoisomer was

isolated by preparative LC. Figure 16b shows the 13C NMR spectrum of









this tetramer stereoisomer. The methyl resonance corresponds to the
most upfield peak in the methyl spectrum of tetramer [23] (Figure
16a). Thus, it is reasonable that the spectrum is that of the iso-
tactic tetramer. The 300 MHz 1H NMR spectrum of this stereoisomer
is shown in Figure 17. The methine protons give two multiplets of


HD H B H A B H D

CH3 IC A IC CH3

H C H A HC
0 C0

[23]

equal intensity at 2.38 and 2.48 ppm, for HD and HC, respectively.
This simple spectrum is clearly due to the symmetrical nature of this
stereoisomer. The methylene spectrum shows two multiplets in a 2:1
ratio at 1.82 and 1.95 ppm, which are assigned to Hc(Hc') and HA(HA'),
respectively. The geminal methylene protons are magnetically equiva-
lent, as with the isotactic trimer, but the Hc(Hc') protons give a
more complicated spectrum than the HA(HA') protons due to the exist-
ence of two different CH2-CH coupling constants (JBC and JCD). Capil-
lary GC data are consistent with the assignment of this stereoisomer
as isotactic, since it corresponds to the last peak eluted in the
crude tetramer fraction (Figure 18).
To assign the other peaks in the GC trace to the various tetramer
stereoisomers, the isotactic species was epimerized with potassium















































2.5 2.0 1.5 1.0 ppm

Figure 17. 300 MHz 1H Spectrum of a Single Stereoisomer of Tetramer
[23].










rrm + mmr


mr mmm
mrm .


I I
41 42


I I I I
43 44 45 46
Retention Time (mins.)


Figure 18. Capillary GC Traces for Tetramer [23]; a) isotactic [23],
b) tetramer stereoisomers in oligomerization product.










tert-butoxide in tert-butanol. The GC traces of the isotactic tetra-

mer epimerized for various amounts of time are shown in Figure 19.

The external asymmetric centers of [23] are expected to epimerizemuch

faster than the internal asymmetric centers, as observed in the epi-

merization of isotactic 2-vinylpyridine tetramer20'21 (Scheme 1).

Therefore, the first stereoisomers formed would be (mmr) and (rmr)

with the (mrr), (mrm), and (rrr) isomers formed much more slowly. The

epimerization results show the formation of only two stereoisomers

from the isotactic tetramer which must correspond to (mmr) and (rmr),

the former being the first to appear. Apparently, epimerization of

the internal asymmetric centers is extremely slow under these condi-

tions (t-BuOK, t-BuOH, 25C), since little epimerization appears to

take place at these positions after 2 weeks. However, the (mmm),

(mmr), and (rmr) assignments follow the same pattern as in the 2-

vinylpyridyl tetramer, 20,21 and it seems likely that the other stereo-

isomers follow as well. Thus, the order of elution for tetramer [23]

should be (rrr), (rmr), (rrm and mrr), (mmr and rmm), (mrm), (mmm)

(Figure 18).
Discussion

Table 11 summarizes the observed stereochemistry of the oligomer-

ization of 4-vinylpyridine according to Equation 3 and determined by

capillary GC. From these results, it can be seen that both methyla-

tion and monomer addition are stereochemically random. Since intra-

molecular coordination of Li+ in the manner invoked for 2-vinylpyri-

dine oligomerization is not possible, ion pair diastereomer [28] will

not be preferred with respect to [29], and approximately equal amounts

of the two diastereomers should be present. Thus, cation side attack















t =0









t = 30 min.








t = 8 hr.


t = 210 hr.


Figure 19. Epimerization of Isotactic Tetramer [23].


Isotactic


_ii
E


E











Scheme 1

(mrm) + (rrr)






R R





R
R R R






(mm // ()r)
R




R R R R R





R



R R
(mrr)



(mrm) + (rrr)


(rmr)










Table 11

Stereochemistry of the Anionic Oligomerization
of 4-Vinylpyridinea Determined by Capillary GC


CH3 CH3

R R


CH3 CH3

R R R


CH3 -I

R R R


c.-
CH3-

R




CH3

R


I I I ,


--CH3

R






R


(m)

(r)


(mr + rm)

(rr)


S(mmm)
(mrm)

S(mmr, rmm, rrm, mrr)

(mr)

(rrr)

(mm)

(rm + rr)

(mr)


59.6%

40.4%

26.9%

51.5%

21.6%

54.0%

46.0%

13.6%

13.8%

51.4%

12.3%

8.6%

26.9%

46.9%

26.2%


CH3I
CH3CHRCH2CHR', Li+ >CH 60% (m), 40% (r)
S4VP 54% (m), 46% (r)

CH3(CHRCH2)2CHR', Li+ CH3 > 51% (m), 49% (r)
4VP > 51% (m), 49% (r)
CH3 I
CH3(CHRCH2)3CHR-, Li' -C > 51% (m), 49% (r)

a Li+ counterion, -78*C, in THF.

















CH(3 -- H CH3 Li+

[28] [29]

of monomer or methyl iodide will result in random stereochemistry of

placement. In accord with this, the corresponding anionic polymeri-

zation of 4-vinylpyridine leads to atactic polymer.2,39

Isolation and NMR analysis of the various stereoisomers of oligo-

4-vinylpyridines would serve as a great aid in assigning the observed

stereoisomeric shifts in the polymer NMR spectra. However, using

routine preparative LC techniques, only dimer stereoisomers were com-

pletely separable. Isotactic trimer and tetramer were also isolated,

although subsequent attempts to isolate these stereoisomers proved

less than satisfactory. Isolation of syndiotactic and heterotactic

trimer was difficult, and the assignment of isotactic trimer was made

largely by comparison to the NMR spectrum of isotactic 2,4,6-tri-

phenylheptane. Due to the larger number of stereoisomers, tetramer

separation proved to be an even more difficult task.

Recycle gel permeation chromatography appears promising as a

technique for isolating individual stereoisomers of 4-vinylpyridine

oligomers. Successful separations have been performed on styrene

oligomers up to pentamer.40-42 These separations have been inter-

preted as being dependent on the differences in the predominant con-

formations adopted by these stereoisomers.40










It is interesting to note that the order of elution observed in

the separation of styrene oligomers into diastereomers33'35'37'40'41'43

follows the same trend as for 2-vinylpyridyl oligomers20,21 using

either LC or GC. The general order of elution is listed in Table 12.
Table 12

Order of Elution of Stereoisomers
of Styrene and 2-Vinylpyridine Oligomers


Dimer Trimer Tetramer

first eluting (rrr)
(rr)
(r) (rmr)
(rrm)
(Mnn)


(m) (mrm)
(mm)last elutin
last eluting (mmn)


The same elution order is followed in the GC and LC of 4-vinylpyri-

dine dimer, while the isotactic trimer and tetramer are the last

stereoisomers to elute in the trimer and tetramer fractions, respec-

tively. Thus, the remaining stereoisomers may be assigned with the

same degree of confidence by comparison of the chromatographic data

to the 2-pyridyl and phenyl analogues.
In addition to the chromatographic similarities, the 1H and 13C

NMR shifts of the various stereoisomers of 4-vinylpyridine oligomers

appear to follow the same pattern as the styrene oligomers (Tables 6-

9). Thus, the NMR spectral data coupled with the chromatographic re-

sults allow a satisfactory assignment of the various 4-vinylpyridine

oligomer stereoisomers.














CHAPTER V
THERMODYNAMICS OF INTRAMOLECULAR COORDINATION

In order to probe the thermodynamics of the intramolecular coor-
dination in the anionic oligomerization of 2-vinylpyridine, the proton
transfer reactions between model compounds [15], [30], [31], [6] and
alkali metal salts of 2-ethylpyridyl carbanion [2] were studied
(Equations 4 and 5). These proton transfer reactions result in the
formation of model anions [3], [32], [33], [34] and 2-ethylpyridine.


CH3CHR M+ +

[2]


K1
CH3CHR'CH2CH2R R 1
3Z THF
[L15], [30], [31]

CH3CH2R + CH3CHR'CH2CHR-, M+

[3], [32], [33]


[15], [3] R = R' = 2-pyridyl
[30], [32] R = 2-pyridyl
R' = 3-methyl-2-pyridyl
[31], [33] R = 2-pyridyl
R' = phenyl
M = Li+, Na+, K+


SK2

/ CH2
CH3-CH CHR

R' M
[3'], [32'], [33']










K
CH3CHR-, Li+ + CH3CHRCH2CHRCH3 app
S3 2 3 (5)
[2] [6] CH3
CH3CH2R + CH3CHRCH2CR M+

R = 2-pyridyl [34]


The attainment of the equilibrium was verified by measuring the

change in product distribution with time. This was accomplished by
rapidly alkylating each sample with ethyl iodide and determining the
product distribution with capillary gas chromatography. Alkylations

were carried out by in vacuo addition of CH3CH2I from a sealed ampule

onto the stirred carbanion solution. Alkylations were complete in
1-2 seconds as determined by the rapid disappearance of the red color

of the carbanion. Since the alkylations are very fast compared to
the rates of proton transfer, analysis of the products should reflect
the position of the proton transfer equilibrium. The apparent equil-
ibrium constant (K app) is given by


K [CH3CH2R][CH3CHR'CH2CHRC2H5]
app [CH3CHRC2H5][CH3CHR'CH2CH2R]


and may be expressed as Kapp = K1 (1+K2), where K1 is the equilibrium

constant in the absence of intramolecular cation coordination, and K2
refers to the equilibrium between dimeric anions [3], [32], [33), [34]
and their coordinated conformers [3'], [32'], [33'] and [34']. If it

is assumed that the stabilities of the carbanions are not greatly











affected by substituents beta to carbanion, it follows that K1 1 so

that Kapp 1+K.
app 2'
Figure 20 shows the changes in the product distribution with

time at 250C with [15] as the substrate and lithio-, sodio- and po-

tassio salts of 2-ethylpyridine (Equation 4). Again, it is clear that

the approach to the proton transfer equilibrium is much slower (1-4

hours) than the alkylation (1-2 seconds). Table 13 shows that the

proton transfer in Equilibrium 5 is much slower than in Equilibrium

4, apparently due to the lower kinetic acidity of the tertiary proton.


Table 13

Time Required for Establishment of
Proton Transfer Equilibria 4 and 5


Substrate Counterion Time

[15] Li+ 1 hour

[15] Na+ 4 hours

[15] K 1 hours

[6) Li 250 hours


Table 14 lists the values of K2 for anion [3] as a function of

temperature and concentration with Li, Na, and K counterions in THF.

These results indicate large values of K2 for the lithio salts of [3],

somewhat smaller values for the lithio salt of [34], and considerably









66



















S10







.- .W




w_ U

4 CO





I- -
3;-,
jE








0- 0





4- -

<0
\" 0-





EC 0







CL
E.






U, I-
\ **-


0 0\00 I 0










_. *t-









Table 14
Equilibrium Constant as a Function of
Counterion, Temperature and Concentration
Anion/ [2] Anion/ [1]
M+ T(C) (x 102M) K2 M + T(oC) (x 102M) K2

[3], Li 40 -1 14.3 [3], Na 25 ~1 2.3
[3], Li 25 12 15.2 [3], Na, CEb 25 ~1 2.5

[3], Li 25 5 15.0 [3], Na 0 ~1 3.0
[3], Li 25 0.6 15.8 [3], Na[2.2.1] 0 ~1 1.8
[3], Li 25 0.1 15.5 [3], Na -12 -1 3.3
[3], Li[2.1.1] 25 ~1 1.2 [3], Na -25 -1 3.7
[3], Li 0 -1 20.0 [3], Na -35 -1 4.1
[3], Li -12 -1 21.6 [3], K 25 -1 1.8
[3], Li -25 -1 25.3 [3], K 0 -1 1.9
[3], Li[2.1.1] -25 -1 1.5 [3], K -12 -1 2.0
[3], Li -35 -1 28.7 [3], K -25 -1 2.1
[32], Li 25 -1 1.0al [33], K 25 -1 0.3
[33], Li 25 -1 0.8 [34], Li 25 -1 4.8

a approximate value ( 0.3)
b CE = 18-crown-6


smaller values for the sodio- and potassio salts. This is consistent
with the decrease in the stereoselectivity of alkylation with increas-
ing cation size previously demonstrated for these systems.19,23 The
sharp decrease in K2 upon addition of cryptand [2.1.1] to the lithio
salt is also noteworthy and is consistent with the disruption of










intramolecular coordination. For the sodio salt, cryptation leads to

a modest reduction in K2, but interestingly addition of 18-crown-6

does not appreciably affect the equilibrium.
A decrease in K2 is noted for the lithium salt of [34] with

respect to [3], reflecting the free energy difference between tertiary
and secondary c-pyridyl carbanions. From pKa values reported for pro-

tons a to phenyl,44 carbonyl45 or sulfone46 groups, the tertiary carb-

anions are generally found to be 1-3 kcal/mol less stable than the

corresponding secondary carbanions. Comparison of the Kapp values

for the formation of the lithium salts of [3] and [34] indicate that
the tertiary carbanion in this case is about 0.6 kcal/mol less stable

than the secondary carbanion. However, the difference in activation
free energy for the formation of the lithium salts of [3] and [34] is
estimated to be about 3 kcal/mol. Thus, steric factors appear to play
a role in decreasing the kinetic acidity of the tertiary site. This
is in agreement with earlier results on the epimerization of 2-vinyl-

pyridyl oligomers.20'21 The much slower rate of tertiary proton ab-

straction clearly indicates that, at least for short reaction times,

very little tertiary proton abstraction occurs in the deprotonation of
[15] (Equation 4).
Of particular interest is the observation that Kapp (= 1+K2) ex-

ceeds unity in systems where intramolecular cation coordination is
expected to be absent. Thus for the lithio salts of [32] and [33],
the values of Kapp at 250C are about 2 and 1.8, respectively, and the

corresponding value for the [2.1.1] completed lithio salt of [3] is
2.2. In the case of anion [33], intramolecular coordination of the










metal ion is clearly impossible, and this should also be the case for

[3] where cryptation would prevent intramolecular coordination. For

[32], such coordination has also been shown to be implausible on the

basis of observed alkylation stereochemistry and by inspection of CPK

molecular models.23 Apparently, in these cases the ion pairs are

stabilized by effects of a different origin, the nature of which is

not yet completely clear.

Figure 21 shows a plot of ln K2 vs. 1/T for dimer anion [3] in

Equation 4, with Li Na+ and K+ counterions. The values of AH and

AS for these systems were determined from these plots and are listed

in Table 15. For all counterions, AH is negative, becoming less nega-

tive with increasing cation size. Interestingly, AS has a small nega-

tive value for Na+ and K and a small positive value for Li This

is consistent with the displacement of coordinated solvent molecule

from the cation upon coordination by the penultimate pyridine group.

The entropy lost upon forming the conformationally restricted intra-

molecular complex would be compensated for by the entropy gained upon

displacement of one or more solvent molecules from the metal ion

solvation shell.
Table 15

Thermodynamic Parameters for Equation 4
Determined from a Plot of InK2 vs. 1/T

Counterion AH (kcal/mol) AS (e.u.)

Li -1.39 0.10 0.81 0.40

Na -1.29 0.15 -2.60 1.00

K -0.47 0.20 -0.40 1.20















0



on
0


I 1
S0



S-
4-




*0
0o
r--




C






-
Sc-
0








0 ,--









\ \ 1-
\W \05 2

\ \ t 0









In an analogous study, Tsvetanov et al.47 used IR spectroscopy

to measure equilibrium constants for the coordination of the alkali

metal in the active center of "living" oligo-isopropenyl methyl ke-

tone by carbonyl groups on the oligomer chain (Equation 6). The

values of K2 for the corresponding lithio salts in THF were found to

be about 5 at -30C, compared with about 27 in the case of anion [3].

This is not unexpected in view of the greater coordinative ability of

the 2-pyridyl group. Tsvetanov et al. also studied the effect of the

number of monomer units in the chain on the apparent equilibrium con-
stant and found an increase in K2 as the degree of polymerization

increased up to D.P. of 3 for Li Attempts to study the effect of

the chain length on K in our case led to the formation of side
app .
products complicating such studies. Side product formation will be
dealt with in the next chapter.
CH CH CH
3 C3 3 /CH3 0
R--CH2-C -- H2-CH Li --- R-CH2-C C -CH (6)
I I I i + LH 3
C=0 C=0 CH2 CH3
I I C- CH
OH3 2 H3 CH
-- -- CH \-CH


The ionic species in Equilibria 4 and 5 may exist in several

forms, i.e., contact ion pairs, solvent-separated ion pairs, free

ions, or ion-pair aggregates. If the ratios between two or more of
these ionic species are different on each side of the equilibrium,
this would profoundly affect the apparent equilibrium constant, mak-
ing the correct determination of K1 and K2 impossible. Consider, for










example the equilibrium (7),

K.
CH CHR-, M + CH CHURCH CH R CH3CH2R + CH3CHRCH2CHR", M


Kd1 1CKd2 (7)

+ K. +
CH3CHR- + M + CH3CHRCH2CH2R --- CH CH R + CH3CHRCH2CHR- + M

R = 2-pyridyl


where a certain fraction of the ion pairs is dissociated into free

ions. The overall equilibrium constant, K app, may be shown to be47
app

(1-a1) J1
Kpp= Kp T = K ()


where a1 and a2 are the degrees of dissociation of the ion pairs

CH3CHR", M+ and CH3CHRCH2CHR-, M+, respectively. Upon dilution, the

equilibrium (7) will be expected to shift toward the salt with the

largest dissociation constant. Similar expressions can also be de-

rived for other concentration-dependent processes such as ion-pair

aggregation.48

The lack of effect of concentration upon K2 in Table 14 is clear-

ly consistent with the view that ionization and other concentration-

dependent processes such as aggregation are unimportant in the equil-
ibrium. In support of this, conductometric and NMR measurements show

that ionization of these 2-pyridyl substituted carbanions in THF is

negligible (Kd = 10-8 M).7'12-14'49'50










The fact that K1 is greater than unity in the systems in which

intramolecular coordination is not expected to be present indicates

that some additional type of stabilization is present. This is per-

haps due to a decrease in the dielectric constant of the medium in

the vicinity of the ion pair caused by the presence of the penulti-

mate group. For example, when the penultimate group is phenyl, no

intramolecular cation coordination by a heteroatom is possible. How-

ever, Kapp in this case is about 1.8 with Li indicating that the
app
phenyl group does play a role in stabilizing the ion pair. In addi-

tion, the lithium salt of [32] and the cryptated lithium salt of [3]

yield Kapp values which are also somewhat higher than unity. Since

intramolecular coordination by penultimate pyridine nitrogen is ex-

pected to be disrupted in these systems, there appears to be a simi-

lar additional stabilization of the ion pairs. Thus, the values of

K2 reported in Table 14 should be interpreted as due to both intra-

molecular cation coordination by nitrogen and this small additional

stabilizing effect.














CHAPTER VI

DEGRADATION REACTIONS OF OLIGOMER ANIONS

In studying the equilibria involving model trimers and tetramers

(Equation 8), the presence of secondary reactions of the carbanions in

CH3CHR M+ + CH3-CHRCH2+nCH2R --'

[2] [35], [36]
(8)

CH3CH2R + CH3{CHRCH2+nCHR", M+

[1] [4], [5]

[35], [4] n = 2; [36], [5] n = 3; R = 2-pyridyl

some cases complicated the determination of the equilibrium constants.
This prompted an investigation of the pathways involved in the second-
ary reactions. Furthermore, a detailed analysis of the reaction prod-

ucts was expected to contribute to an understanding of the side reac-
tions that accompany the corresponding polymerization reaction.
There are several types of secondary reactions conceivable in

these systems. For example, it has been known for many years51'52
that carbanions add to pyridine rings, and such reactions have been
observed with poly-2-vinylpyridine.53-57 Nucleophilic attack on the
pyridine ring is also claimed during the initiation of the anionic

polymerization of 2-vinylpyridine.58,59 Another possible secondary
reaction in Equation 8 is inter- or intramolecular abstraction of a









methine proton on the backbone of the oligomer, leading to tertiary
carbanions [37].
M+ R = 2-pyridyl


H CH2CHRCH2-)-CR*CH2CHR-H


m > 1


n = 0, 1, 2


[37]


When the lithium or potassium salts of [2] were reacted with
dimer [15] (Equation 9), side product formation occurred at a slow


CH3CHR", M


[1] + [6] +


+ CH3CHRCH2CH2R
[15]


THF
CH3I


R = 2-pyridyl


[1] + [6] +


[15] + [39]


[38] + [40] + [15]


CH3CHCH2 CH2

60

[15]


CH3CHCH2CHCH3


06
C6]


CH
13
CH3C CH2 CHCH3


O@f
11-


rate and did not interfere with the determination of the equilibrium
constants. The fraction of side products remained negligible for


CH 3




[39]


CH3CH2




[1]


CH3CHCH3



[40]










several hours at room temperature, whereas the proton transfer equi-

librium (Equation 4) was attained in about one hour. Table 16 lists

the products formed under various conditions as determined by LC sep-

aration followed by NMR and GC analysis. The side product obtained

upon methylation was 2-methyl-2,4-di(2-pyridyl)pentane [38]. 2-Methyl-

pyridine [39] and 2,4-di(2-pyridyl)pentane [6] were the side products

formed upon protonation with methanol.

Table 16

Product Fractions in Equation 9

Product Fractions
Electro- Monomeric Dimeric
M+ phile T(C) Time (hrs) [39] [1] [40] [15] [6] [38]

Li CH30OH 25 168 0.06 0.50 0.20 0.24 -

Li CH3I 25 168 0.30 0.35 0.16 0.20

Li CH3I 0 150 0.33 0.06 0.07 0.47 0.06

Li CH3I -25 94 0.26 0.06 0.05 0.61 0.03

Li CH3I -25 150 0.30 0.05 0.08 0.56 0.02

K CH31 25 92 0.27 0.19 0.04 0.37 0.13

K CH3I 0 92 0.29 0.21 0.10 0.31 0.09

K CH3I -25 94 0.28 0.24 0.08 0.36 0.04

K CH3I -78 94 0.15 0.36 0.19 0.25 0.05


Alkali metal salts of 2-ethylpyridine [.2] were

tetramer [36] followed by alkylation or protonation


also reacted with

(Equation 10).


The reaction products were separated by LC and identified by NMR and










CH3CHR", M
[2]




CH3CH2I1


CH 3CHRCH2--CH 2R
[1I, [15], [35], [36]
+ CH3CCHRCH24-CHRC2H5
[41] [44]


[36], [44] n = 3
[7Z], [35], [43], [46] n = 2
[6], [15], [42], [45] n = 1
[1], [41] n = 0


+ CH3CHRCH2--CH2R
[36]
THF


H 30H


[1], [15], [35], [36]
+ CH3"CHRCH2-)-n-CHRCH3
[6], [7]
+ IH-CHRCH2-) nCH2R
[45], [46]


R = 2-pyridyl


GC analysis. It appears that most of the tetramer was cleaved to dimer
and trimer within 2 hours at room temperature (Table 17). In accord
with this, other workers have observed a decrease in molecular mass of
poly-2-vinylpyridine when treated with polystyryl anions54-56 or cumyl
potassium.55
Scheme 2 shows a mechanism which is consistent with the types of
side products formed in Equations 9 and 10. Initially, formation of a
carbanion on the backbone of the oligomer occurs by inter- or intra-
molecular abstraction of a methine proton. The chain may then cleave
by an elimination reaction yielding an alpha substituted vinylpyridine


(10)



















o 0 0
oo o


C'-j


41-
Q) 0ar"
-0 X|
C w-










SI-
I-l


CMJ
I 0
0


.-I CM- CMj
o 0 0
o 0 0








o 0 0
n *-4








a C)C



"4 0 0
o 0 0


-1 P -
(c.4 csj C%j
CM wM CM)
(J (_) () C. 0


co m f m t



LO L Un) t) L..
S. X: L. S.. XC
-O I
CM.J 10 I0







1-4 ~j m -4r -4
LA LA LA L


CM. CMJ CMI CM








%^ M %n 3- %m


s-
0


-


.4.)
C 0
a) a)4~'
-o *~ ,.cI
*~ 4~ L..J
C -I-


CD% CM C0
o 0 0


* *


M 0 0
Q o 4 -


C o 6 S


0 1 C
0 C).

o -

o 0
4-4 4-4

o 0
o 0


10 LO
o 0


I I


1I 0 -4
o *- 0
o 0 0


-o

to
C)
(0


4-
C
0







4.
0*








SC
4-)





t)
I- U
.0 C
EU 0

I-





:3
VI
4-i


000 0
o o 0
oD C) D


1-







q o

C
EE

4) i-l
C-
4-1











0
10 0





S, -

r,- 0.
LaJ




.- E







0
I-.

.4




Cf


o a)
4J) +4-
cu
a)
) S-
.)
E -
4*J


L
s-
0 w1
4*) I-
4-)
4 3
(U (-t;
S- -1 a)
N
.3 .r U i
a
o W 4-3
4-) C
Q to >1
(U) 0
1- *'-1-
0
o -
to







ow
r0 0








0
U 41-) >
0 a)
.C: C i-
4- a
.4- -o












s 5 o
cm 03
C O 0


o u
0- 0
(0 CO




















CC to r
(0 >

EUI

CE
C EC -



.r- 30
4-B (D 01















tno CA* 41
C -.-




0





S- Ec
EU (D

C n o
o J ) 0
4-' 0 -
I- a)






(A -0 CV
E 4 0









=_ i- Wl
M ) 0a r_








CL 4
CC -
.r- *0 0
< 0 C
*I- U)1 i-
C C *'-
a) 3 -0 -0
-0 0 a)
.4- O.*- U)
E4- a)
U)1 0 *' E
LI C 4I-
*0 a) -0 C
i.. 0 C *-
Q- E =3 4-)
EU .0









Scheme 2


CH CHCH CH M C




[15]



M +
[3]
CH3CCHF- HCH2-CHCH3 -----




CH30OH or
CH3 I

[7] or (
CH
1 3
CH3CCHi-CHCHf-CHCH3
I I I3


[48]


B1


[2]
CH3C=CH2 -->




+
CH2 M+



2-
[49]


-M
CH3CCH2-CHCH3




CH30OH or
CH3 I

[6] or [38]


[50]


and a new carbanion. This elimination may proceed in either a con-
certed (E2) or stepwise (Elcb) fashion. The concentration of these
vinylpyridines would be expected to remain very low due to their sub-
sequent reaction with carbanions. An overall decrease in the average
molecular weight of the oligomers will be realized if the vinylpyridine









combines with an anion which is smaller than the cleaved anion frag-

ment. This is a very likely occurrence, since the 2-ethylpyridyl

anions [2] are present in large quantity in the solution. Consistent

with the proposed mechanism, small amounts(-~1%) of trimeric and

tetrameric products are also formed, presumably by addition of dimer

anion [3] to the vinylpyridine produced upon cleavage (Equation 9).
In addition, this mechanism predicts that oligomers [6] and [7] will

be formed upon protonation (Scheme 2), and this is consistent with
the observed results.
Elimination may also occur from the secondary carbanions [3] -

[5], yielding a carbanion and 2-vinylpyridine (Scheme 3). Small
amounts of oligomers [45] and [46] are observed in the product mix-

tures (Table 17), indicating the participation of this pathway.
It is interesting to note that essentially no 3-methyl-1,3-di-

(2-pyridyl)butane [47] is formed upon methylation in Equation 9.

This result is somewhat puzzling since the formation of this product
would be predicted by Scheme 2. The absence of [47] may be due to

the fact that the intermediate anion [48] would form very slowly as
described in Chapter 5. The subsequent elimination reaction may now

occur rapidly, thus keeping the concentration of anion [48] very low

at all times.
CH
13
CH3-C CH2CH2




[47]










Scheme 3


CH3*CHCH2*-CH, M+




[3] [5] n = 1, 2, 3

[49] +
CH2=CH > CH2CH2CH, M

N N


CH3+CHCH -CH-, M+

cc^N


[2] [4]

n = 0, 1, 2


CH30H


CH2CH2CH2




[45]


An important factor in the cleavage of the oligomer chains by an
elimination mechanism is the ability of an a-pyridyl carbanion to act

as a leaving group. Negatively charged carbon species are generally
considered extremely poor leaving groups in alkene-forming elimina-

tions,60 but such reactions have been reported.61 Carbanions as leav-
ing groups are quite common, however, in carbonyl-forming eliminations
such as reverse aldol, Claisen, and Michael reactions.61 Examples
involving a-pyridyl carbanions as leaving groups in an elimination
reaction include the anionic depolymerization of poly-2-vinylpyridine62









and poly-2-isopropenyl pyridine63 which occurs at high temperatures
(Equation 11). In the depolymerization, monomer is eliminated from
the living chain end resulting in the formation of a new carbanion
site.
R R R R
I I + + (11)
PCH2C-CH2-C M -- PCH2C M + CH2=C (11)




R = CH3, H

Another mechanism which could explain the observed chain cleavage
involves the nucleophilic attack of an a-pyridyl carbanion on a methyl
or methylene carbon of the oligomer followed by displacement of ano-
ther L-pyridyl carbanion (Scheme 4). This scheme is less likely for
Scheme 4



3 + O
CH3CHCH2CHCH, CH2, M,
1 +



b) CH3CH, MM CH3CHCH2CH2 -



CH3CHCH3 M+, CHCH2CH2
0 00+ 21
1U N









the following reasons. First, no 2-isopropylpyridine [40] was pro-
duced upon protonation (Equation 9 or 10) as would be expected by
this mechanism (Scheme 4b). Second, a mixture of lithio-2-ethylpyri-
dine [2] and 2-ethylpyridine in THF also failed to produce 2-isopro-
pylpyridine after 6 days at room temperature. Third, no 2-phenyl-4-
(2-pyridyl)pentane [51] was observed in the reaction of dimer [31]
with the lithium or potassium salts of [2] (Equation 12). Dimer [51]

CH3CH M++ CH3CHCH2CH2 CH2", M++ CH3CHCH2CHCH3

O + 1 -" 1- (12)


[2] [31] [1] [51]

would be expected to form if nucleophilic substitution occurs at the
methylene group but would not likely occur from an elimination process
followed by addition of a carbanion (Equation 13). The intermediate
carbanion [52] would not be expected to form, since the a-pyridyl pro-
tons are at least 5 pKa units more acidic than the benzylic proton.

CH3CCH2 CH --N CH C=CH + CH", M+



[52] (13)
[2]

M + CH30H
CH3C CH2CHCH3 ) [51]









Further evidence against a nucleophilic substitution mechanism
in the cleavage of oligomers is given by examination of the products
obtained by protonation of the equilibrium reaction shown in Equation
14. In addition to [1] and [47], substantial amounts of [6], [15],
+ 250C
(CH3)2 CH2-CH2 + CH CH, Li+ q, THF

N N 51 hrs.
1 01 C)1

[47] [2] (14)
(CH3)2CCH2-CH', Li+ + CH3CH2






and [40] are formed. All of these products could be produced by ei-
ther a substitution or an elimination mechanism (Schemes 5 and 6),
but a substitution reaction would also produce 2-methylpyridine [39]

CH3CHCH2CHCH3 CH3 HCH2CH2 CH3CHCH3




[6] [15] [40]

and 2-methyl-2,4-di-(2-pyridyl)pentane [38]. The observed lack of
these two products is consistent with an elimination mechanism.
It is interesting to note that no side products were obtained
which resulted from attack of an a-pyridyl carbanion on the pyridyl
rings of the oligomers. This is consistent with the fact that side








Scheme 5
(CH3)2CCH2CH", M'


(CH3)2C-, M'

0


CH 3OH

CH3CHCH3


[o0
[40]


CH" M +CH3C=CH2

0


+


M+
S CH3C-CH2 CH2

ag
^~ J C I


[2]

CH3CHCH2CH, M+



CH30H

CH3CHCH2CH2



[15]


M
CH3C CH2CHCH3
I I
Ci ( *


CHOH
CH--- H CH3CHCH2CHCH3
N- I 3
06 @N r^


+ CH2=CH








Scheme 6


CH3CH-, M
N
0


+ (CH3)2CCH2CH2

I I


(CH3)2C CH2CHCH3

1 30
[ 38]


CH2-, M




tCH30H

CH3

[ N
OJ


- (CH3)2C'M' + CH3CHCH2CH2
I, I

0615


CH30H


CH3CHCH3


[2]
V


CH3CHCH2CHCH3



[6]


+
CH2 M4


CH3OH
4^^










products were never formed in mixtures of 2-ethylpyridine and lithio-

2-ethylpyridine. Nucleophilic attack on the pyridine rings of poly-

2-ethylpyridine has been previously postulated53-57 with such species

as Grignard reagents, butyllithium, and polystyryl anions. These

species are generally more nucleophilic than a-pyridyl carbanions,

which may account for the lack of ring attack in the latter case.
S polymer,57
In some cases, an increase in the M of the polymer, gel forma-
w
tion,56 or cross-linking64 has been observed upon treatment of poly-

2-vinylpyridine with carbanions. Scheme 7 illustrates how this type

of phenomenon may also be consistent with the proposed mechanism.

Cleavage of the polymer chain (pathway a) leads to the formation of a

polymer with a terminal double bond which may be considered a "macro-

mer". The reaction of a "macromer" with a carbanion on another poly-

mer chain leads to branching (pathway b). When a terminal double

bond on a branched polymer reacts with a carbanion on a polymer back-

bone, cross-linking may occur (pathway c). Stannett et al.56 have

proposed a mechanism for gel formation in which a living poly-2-vinyl-

pyridine chain attacks a pyridine ring on another poly-2-vinylpyridine

chain. This does not seem very likely since there appears to be no

nucleophilic attack on the pyridine rings of dimer, trimer, and tet-

ramer of 2-vinylpyridine by a-pyridyl carbanions.

In conclusion, by using oligomeric model compounds, it has been

shown that carbanions may cleave poly-2-vinylpyridine chains probably

by means of an elimination mechanism that involves abstraction of an

a-pyridyl proton on the polymer backbone. In some cases, branching or

cross-linking may occur by this mechanism. With a-pyridyl carbanions,











a--) ---CH2CHCH2CHCH2


+
R M


,-'-CH2CHCH2CCH2
I I


+ CH2=CCH2 ---


06


CH -2CH2CH M +


b^ CH2CCH2 '-- + CH2=CCH2-


ON N
6~~ o)


^-^^-^CH2CCH2^ -^ -
I
LH 2 LCH
N
4. Qj


+ ,-- CH CCH 2

O


cross-link
formation


Scheme 7


CH,
CHI


c) H2 C=CH 2

6 0







89



no nucleophilic addition appears to occur on the pyridine rings of

the polymer, but with a more nucleophilic species such as polystyryl-

lithium this seems to be a likely possibility. Except for lack of

attack on the pyridine rings, our results are in good agreement with

the mechanism proposed by Fontanille and Sigwalt55 for cleavage of

poly-2-vinylpyridine chains by carbanions.