Group Title: investigation of factors influencing the stereochemistry of the Wittig reaction
Title: The investigation of factors influencing the stereochemistry of the Wittig reaction
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Title: The investigation of factors influencing the stereochemistry of the Wittig reaction
Alternate Title: Factors influencing the stereochemistry of the Wittig reaction
Physical Description: vi, 79 l. : illus. ; 28 cm.
Language: English
Creator: Kresse, Jerome Thomas, 1931-
Publisher: s.n.
Place of Publication: Gainesville
Publication Date: 1965
Copyright Date: 1965
Subject: Stereochemistry   ( lcsh )
Wittig reaction   ( lcsh )
Chemistry thesis Ph. D
Dissertations, Academic -- Chemistry -- UF
Genre: bibliography   ( marcgt )
non-fiction   ( marcgt )
Thesis: Thesis - University of Florida.
Bibliography: Bibliography: l. 76-79.
General Note: Manuscript copy.
General Note: Vita.
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Bibliographic ID: UF00099401
Volume ID: VID00001
Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: All rights reserved by the source institution and holding location.
Resource Identifier: alephbibnum - 000423884
oclc - 11022730
notis - ACH2289


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December, 1965


The author wishes to express his appreciation to his research director,

Dr. George B. Butler, for his guidance and encouragement during the execution

of this work.

The author also expresses his gratitude to his fellow graduate students and

associates for their helpful suggestions and criticisms.

Particular thanks are due Mrs. Frances Kost and Mrs. Thyra Johnston

for their conscientious typing of this dissertation.

The author also thanks his wife for her patience, encouragement and under-

standing. Without her cooperation this work would not have been possible.

The financial support of the Petroleum Research Fund is also gratefully




ACKNOWLEDGMENTS .......................... ii

LIST OF TABLES ............................. v

LIST OF FIGURES ................... ........ vi


I INTRODUCTION ....................... 1

Historical Background .................. 1

Stereochemistry ...................... 9

Statement of the Problem ................ 19

Method of Attack ..................... 20

I DISCUSSION AND RESULTS . . . . . . .... 22

Solvents . . . . . . . . ... ..... .22

Temperature Effects ................... 27

Reaction Times . . . . . . . .... ... .. 33

Concentration Effects . . . . . . . .... .34

Substituent Effects ......................... 37

Anion Effects ....................... 49

1, 4-Addition and Isomerization . . . . ... .51



III EXPERIMENTAL ...................... 54

Equipment and Data ...... ........... 54

Source and Purification of Materials . . . . . 54

Solvents . . . . . . . . . . . . . 55

Aldehydes . . . .. .. . . . . . . .. . 57

Miscellaneous Chemicals . . . . . . .... .57

Preparation and Purification of Phosphonium Salts . 59

Apparatus . .. . . . . . . . .. . . 161

Reactants . . . . . . . . . . . . 61

The Reaction .................... ... 65

Analysis . . . . . . . . . . . . 67

Calibration of the Internal Standard . . . .... .67

Qualitative Analysis ............. ... 69

Precision of Chromatographic Analysis . . . ... 72

IV SUMMARY ........ .. ............ . 75

LIST OF REFERENCES .......... .......... .... 76

BICGRAPHICAL SKETCH ................. ** ....... 79



1 Solvent and Halide Ion Effects 11

2 Combination Effects on Stereochemistry 13

3 Solvent Effects 23

4 Temperature Effects 28

5 Reaction Times 33

6 Concentration Effects 35

7 Substituent and Anion Effects 38

8 Ring Opening Reactions of 4-Octene Oxide and Stilbene Oxide 47

9 Anion Effects 50

10 Reactions of Methyltriphenylphosphoranes with Crotonaldehyde 52

11 Physical Constants of Phosphonium Salts 62

12 Infrared Absorption Phosphonium Salts 73



1 Energy Profile for the Reaction of a Stable Ylide 8

2 Postulated Reaction Paths of the Wittig Reaction 17

3 Possible Betaine Configurations 41

4 Reaction Manifold 63

5 Calibration Curve for trans-1, 3-pentadiene 70

6 Chromatogram of Reaction Products 71



Historical Backtrtound

Since Wittig and Geisslerl first reported the olcfin synthesis which has be-

come known as the Wittig synthesis literally hundreds of papers have been published

concerning. the synthetic and mechanistic aspects of the reaction.

This synthesis in its general form involves the reaction of a phosphorane

derived from a phosphonium salt with an aldehyde or ketone. The phosphonium

salts are usually prepared from triphenylphosphine and an alkyl or arylalkyl halide.

The phosphoralce is produced from the phosphonium salt by removal of an a-hydro-

gen by a suit-ble base. Addition of a carbonyl containing compound to a solution of

the phosphorane forms an intermediate betaine which then collapses to produce the

oiefin and uriphenylhphshine oxide.

0 P: + R R2CHX->[ P-CHR1R2]+ X-

+ -
I + B: -> BH + 3P-C-R1R

II + R3R4CO-> R R C-CR R
4 1 1P+ 3 4


I;->RtR,C= C3R + 03 P->O

Although the reaction appears straightforward synthetically, mechanistically

the reaction is exceedingly complex. The structure of the phosphorane is apparent-

ly a resonance hybrid of canonical forms IV and V. Form IV is also referred to as

an ylene and form V as an ylide. Form IV requires the assumption of d w7 bonding,

03P=CRIRa2 P CR1R2


between carbon and phosphorus. That such-bonding exists for phosphorus and.

o0therelements of-the third period-has been demonstrated by base catalyzed

a deuterium exchange studies. Form V is that of a carbanion, the extremely strong

conjugate base of the phosphonium salt.

If we assume that structures IV and V approximate the limiting forms of a

phosphorane we can see that the degree to which this structure resembles either IV

or V will be dependent on the nature of the substitutents on phosphorus and carbon.

Jaffe3 has calculated that one of the criteria for d v bonding is the existence of a

positive charge on phosphorus in its singly bonded structure. It follows that groups

on phosphorus which would be electron donating, e.g. alkyl groups would lessen the

importance of the contribution of form IV to the hybrid. Likewise the incorporation

of electron withdrawing groups on carbon, e.g. carbethoxy would tend to make form

IV more important. Regarding the reactivity of the phosphorane we find that groups

increasing the contribution of form IV to the hybrid produce a less reactive species.

This can be seen in comparing the properties of triphenylfluorenylidenephosphorane4

and tributylethylidenephosphorane. The former contains groups capable of delocal-

izing the charge on the carbon and intensifying the positive charge on the phosphorus.

It is extremely unreactive. It can only be hydrolyzed by refluxing with strong

base. The latter compound contains groups which tend to diminish the positive

charge on phosphorus and increase the carbanion character of the structure. It is

hydrolyzed rapidly on exposure to the atmosphere. Both compounds will react with

carbonyl compounds but the conditions for carrying out the reaction are much more

vigorous for the fluorenylidenephosphorane.

Between these two extremes lie almost a continuum of compounds with vary-

ing reactivities. It is this range of reactivity which has made the study of the

Wittig reaction both interesting and challenging. Work done on one system cannot

be directly correlated with a more or less reactive system. This is especially

true of the stereochemistry of the reaction.

The mechanism of the reaction as postulated by Wittig involves an attack by

form V of the phosphorane on the electrophilic carbon of the carbonyl to give a


0 0-
P+ O P+ O-
C- + C C C

R1 R2 3 4 R1 R2R3 4


The betaine then may collapse via a four membered cyclic transition state to

olefin and triphenylphosphine oxide. In attempting to elucidate the mechanism

Wittig6 studied the reaction between methylenetriphenylphosphorane and benzalde-

'P O- O3P- >
I I +
C C --> \ C''
1 2 R R R1 3 R4

hyde. During the reaction Wittig was able to trap the betaine by the addition of

hydrogen iodide giving 2-phenyl-2-hydroxyethyltriphenylphosphonium iodide which

aP= CH2 + QCHO -> 9CH- CH2



on heating gave styrene and 93P->O. He also refluxed benzophenone with the

betaine hydroiodide, but was unable to obtain 1, 1-diphenylethylene, the product one

might expect if betaine formation were reversible. Wittig therefore concluded that

betaine formation is irreversible.

However, Filszar, Hudson and Salvadori found that the lithium bromide--

ether complex of the betaine isolated by Wittig yielded no olefin products on heating

but rather benzaldehyde. These workers concluded that betaine formation is rever-

sible and that decomposition of betaine to olefin and phosphine oxide is rate deter-


(CH=CH + 0P->O
7- B: 2 3
I+ C O+ BH I


Speziale and Bissing have demonstrated the reversibility of betaine forma-

tion by reacting triphenyl and tributylphosphine with cis and trans-ethyl phenyl-

glycidate in the presence of meta-chlorobenzaldehyde.


R3P + 1CH-CHCO C H5---> R P+-CHCO2C2H
225 3 22 5
Ix x

X -> R3 P->0 + qCCH = CHCOCH5

X -> R3P = CHCO C H5 + 1CHO

XII + m-C1C H CHO-> R3P->O + m-CIC H4CH=CHCO C 2H

They found using a 1:1:1 molar ratio of triphcnylphosphine: trans-ethyl

phenylglycidate: meta-chlorobenzaldehyde that they obtained 48.7 per cent cis

ethyl cinnamate; 17.4 per cent trans ethyl cinnamate; 3.0 per cent cis meta-chloro-

cinnamate and 30. 9 per cent trans meta-chlorocinnamate.

These workers further showed through a kinetic study of the reaction between

a series of substituted benzaldehydes with carbomethoxymethylenetriphenylphos-

phorane (a stable ylido) that the rate of reaction is second order, first order in

ylide and first order in aldehyde. They found that the reaction rate is increased

by increases in solvent polarity, substitution of butyl for phenyl on the phosphorus

of the ylide and by electron withdrawing substitutents on the aldehyde.

The mechanism they postulated based on kinetics and the epoxide ring open-

ing reactions mentioned previously is slow, reversible betaine formation followed

by rapid decomposition of the betaine to olefin and phosphine oxide.

House and Rasmusson had previously suggested a mechanism for the reaction

of acetaldehyde with carbomethoxymethylenetriphenylphosphorane to give methyl

tiglate and methyl angelate in which there is a rapid reversible formation of betaines

with slow preferential decompositions of the stereoisomeric betaines to products.

Concerning reactive ylides, Wittig, Weizmann and Schlosser6 had observed

that though betaine formation with reactive ylides is rapid, taking place within a

few minutes, the decomposition of betaine requires standing at room temperature or

heating for several hours. They concluded that betaine decomposition is the slow

step in this type of reaction.

Bergelson and Shemyakin0 interpreted the stereochemistry observed in the

reaction of stable ylides (giving mostly trans olefin) as opposed to unstable or

reactive ylides (giving mostly cis olefin) by using two different reaction paths.

For reactions involving stable ylides they believed that because of the decreased

electron density about the carbon attached to the phosphorus of the ylide, attack

would take place by the carbonyl oxygen on the phosphorus rather than by the car-

banion of the ylide on the carbonyl carbon.

R' H R' H



P P -0 C -- trans olefin

I I C H R'
C C"/




This would be followed by rotation either about the phosphorus-oxygen or carbon-

oxygen bonds to give the more stable (trans) betaine which would then decompose to

olefin and phosphine-oxide. This mechanism involves irreversible betaine formation

in direct conflict with the results of Speziale and Bissing.

Reactions of reactive ylides would take place by the accepted path involving

attack of the carbanion on the carbonyl carbon.

Trippett11 recently discussed the work of Speziale and Bissing and his own

results in contrasting the kinetics and mechanism involving stable and reactive phos-

phoranes. Since stable phosphoranes produce intermediate betaines which cannot

be isolated Trippett proposes a potential energy diagram in which the "valley"

representing the betaine is quite shallow. He believes that the transition states T1

leading to the betaines from reactants and T2 leading from the betaines to products

resemble the structures of the betaines more than they resemble either the pro-

ducts or reactants.

Using these assumptions and a relative rate equation based on them he con-

cludes that the most important factor in determining the ratio of isomers in the

reaction of stable ylides is the relative rate of betaine formation with smaller

Reaction coordinate

Figure 1. Energy Profile for the Reaction of a Stable Ylide

contributions from the relative rate of betaine dissociation and decomposition all

acting in the same direction.

For the case of very reactive phosphoranes, e.g., CH2=P-<3 he maintained

that betaine formation is still reversible but now the difference lies in the isomeric

betaines. The one giving cis olefin dissociates faster than it decomposes to

products and thie one giving trans olefin decomposes to products faster than it



Although wve have already touched on the steroechemistry of the Wittig re-

action in, our discussion of the mechanism considerably more work has been done

o: this phac.e of the synthesis. If one starts with an aldehyde or an unsymmetrical

ketone and an unsymmetrical phosphorane the olefin resulting can exist in either of

two geometrical forms. The olefins receiving most attention
+ RI /R3
q3P-CR R2 + R3R4C=O0--P3P--O + C = C
Rg R4

have been those in which either R1 or R2 is H and R3 or R is H. Wittig and

Schollkoop in some early work observed that the reaction between benzaldehyde

and benzylidenetriphenylphosphorane give cis and trans stilbene in a 30:70 ratio

respectively, whereas the reaction of benzaldehyde with allylidenetriphenylphos-

phorane give cis and trans 1-phenylbutadiene in a 45:55 ratio respectively.
Ketcham and coworkers conducted a reaction between p-nitrophenylmethyl-

enetriphenylphosphorane and anisaldehyde and p-methoxyphenylmethylenetriphenyl-

phosphorane and p-nitrobenzaldehyde. The product mixture in the former reaction

consisteL of .ii trans olefin, while in the latter reaction the product contained 48

per cent cis and 52 per cent trans olefin. They reasoned that the less reactive

p-nitro ylide reacts reversible with the unreactive anisaldehyde while the reactive

p-metLhoxy yiide reacts irreversibly with the very reactive p-nitrobenzaldehyde

giving an almost stJtistically controlled product mixture.

Speziale and Rattsl3 also found that they obtained all trans olefin from p-nitro-

benzaldehyde and the stable ylide carbethoxychloromethylenetriphenylphosphorane.

Wailes14 however reported that the reaction of dodecylidenetriphenylphos-

phorane (a reactive ylide) and propynal give after treatment with ethylmagnesium

bromide and carbon dioxide the enynoic acid containing 80 per cent cis isomer.

Truscheit5 and coworkers using butylidenephosphorane and 12-acetoxy-

dodec-2-enal obtained 70 per cent of the cis diolefin. Using ethylidenephosphorane

they obtained 67 per cent cis diolefin.

Kucherov et al. using the stable carbethoxymethylenetriphenylphosphorane

and 2,4, 6-octatriene-1, 8-diol obtained a 57 per cent yield of all trans olefin. They

also obtained all trans olefin using the same aldehyde and 3-carbethoxyallylidene-


There are in the literature many more references concerning the stereo-

chemistry of the Wittig reaction but like most of those above they have not been

either intensively or extensively studied. However, there appeared in the last three

years several stereochemical studies of the reactions which deserve attention.
10, 17, 18, 19
Shemyakin and Bergelson10,1 in a series of papers have published an

abundance of useful, though sometimes controversial information concerning the

chemistry of moderately unstable ylides. The system used in their early experi-

ments was the reaction of propionaldehyde with benzylidenetriphenylphosphorane to

give phosphine oxide and P-ethylstyrene.

Using a series of solvents they obtained the results shown in Table 1. Their

explanation of the isomer ratios involves a solvent-ylide complex which may be con-

sidered either a coordination compound or a solvate. Whatever its exact nature they

say that this complex produces a "mutual inaccessibility of the phosphorus and oxygen












Ethyl Ether








* Base = CH CH20

Added Salt








% cis % trans

26 74

20 80

27 73

41 59

65 35

73 27

71 29

74 26

31 69

33 67

47 53

51 49

43 57

32 68

24 76

36 64


in the prereaction complex" and that "under such conditions the betaine" (leading to

the cis olefin) "forms more readily than its diastereoisomer. "10 The order of the

effects noted in the solvent they relate in the case of the oxygen containing com-

pounds to relative nucleophilicity while in the amine series they feel steric factors

are of particular importance. Dimethylformamide, they believe, though weakly

basic, possibly interacts with the phosphorus of the ylide through its strongly

polarized oxygen rather than its nitrogen.

These workers also found that the addition of lithium halides to the reaction

in benzene and DMF gives increased yields of the cis isomer as shown in Table 2.

The rationalization of these effects again involves a halide complex with the

positively charged phosphorus of the ylide. This diminishes its electrophilicity

thus favoring the formation of the betaine leading to the cis isomer "due to electro-

static repulsion between the halide and oxygen electronic shells. The selective

formation of cis olefins shows that this effect is considerable. "10

In their later papers Shemyakin and Bergelson have clarified their reasoning

on the interactions leading to the stereochemistry of the Wittig reaction in the

presence of Lewis bases. They propose coordination of the Lewis base with the

phosphorus which is facilitated by a transition of the phosphorus from a tetrahedral

to a trigonal bipyramidal configuration in which the three phenyl substituents be-

come coplanar. They predict that as a result of repulsion between the electronic

clouds of the phosphorus and oxygen the betaine leading to the trans olefin is "de-

stabilized by steric repulsion of the skewed R and R' substituents" thus leading to

predominant cis olefin. They point out, however, that though this might be the case

with some systems it does not prevail in all. Considering the case in which betaines










EtCH=P 3


























Ethyl Ether

Ethyl Ether












Ethyl Ether















Ylide:RCHO % Yield Cis:Trans
















are formed faster than they decompose, they reason that now the steric course of

the reaction "depends on the relative energies of the stereoisomeric betaines not

only in the most stable conformation, but also in the eclipsed reacting conforma-

tion closely allied to the four-membered transition state. If the reacting betaine

conformations are sufficiently well differentiated energetically, the over-all

equilibrium will be shifted in the direction of the betaine that most readily decom-

poses into olefin and phosphinoxide. This can lead to stereoselectivity, even when

the diastereoisomeric betaines in the most stable conformation differ little in energy."

In the case of the reaction of benzylidenetriphenylphosphorane with propionaldehyde

in benzene which gives 80 per cent trans-P-ethylstyrene they slate that the selec-

tivity illustrated here is hard to explain on the basis of the small differences in

non-bonded interactions observed in the two betaines. They believe that a more

important factor in this case is the stabilization of the incipient double bond by the

phenyl group which would only be possible in the betaine leading to the trans olefin.

They9 also consider the possibility of steric control by changing the concen-

tration of reactants, thereby reducing the reversible dissociation of the betaines.

While equimolar amounts of ethylidenetriphenylphosphorane and benzaldehyde in

benzene in the presence of lithium iodide give 34 per cent cis-P-ethylstyrene the

doubling of either the aldehyde or ylide concentration practically doubles the amount

of cis isomer found.
In another group of experiments these investigators demonstrated that sub-

stantial amounts of trans olefin could be obtained from moderately unstable ylides

contrary to the usual experience. For example, using propionaldehyde and 3-ethyl-

allylidenetriphenylphosphorane they obtained the results shown in Table 2.

House and Rasmusson investigated the reaction between acetaldehyde and 1-

carbomethoxyethylidenetriphenylphophohrane and between ethylidenetriphenylphos-

phorane and ethyl pyruvate to give mixtures of methyl angelate and methyl tiglate.

They found that the reaction between the stable phosphorane gave 96. 5 per cent

trans ester whereas the unstable phosphorane gave 68 per cent trans ester. They

rationalized these results by postulating an equilibrium in the formation of betaines

and more rapid decomposition of the betaine leading to the trans ester because of

increased stabilization in the transition state. This increased stabilization could

arise because only in the trans betaines would the carbomethoxy group be able to

become planar with the incipient double bond. In the cis betaine coplanarity of the

carbomethoxy group would be prevented by interference with the adjacent methyl

group. The increased amount of trans isomer obtained with the ethylidenephos-

phorane they said was caused by the increased reactivity of this species which

opposed the formation of the equilibrium between betaine and reactants allowing

the stereochemical outcome to be determined by the relative ease of betaine forma-


House, Jones and Frank20 recently reported the results of a series of re-

actions involving both stable and unstable ylides in different solvents in the pre-

sence of added inorganic salts and with two aldehydes of differing reactivity. They

found that stereochemically the reaction of carbomethoxymethylenetriphenylphos-

phorane and acetaldehyde is practically unaffected by changes in the polarity of the

solvent in going from methylene chloride to 1, 2-dimethoxyethane to chloroform to

dimethylformamide. They did find that solutions of lithium salts regardless of the

anion give increased yields of the cis isomer. However, they also found that a

protonic solvent such as ethanol is even more effective than added salts in in-

creasing the proportion of cis olefin. They furthermore found that chloroacetal-

dehyde gives increased amounts of the cis isomer compared to acetaldehyde.

To explain these results they propose coordination of the carbonyl oxygen by

a Lewis acki (either RGH or Li -) which could then effect the stereochemical out-

come in the following way (Figure 2).

The interconversion of the intermediate solvated betaines by either a rever-

sal of the formation reaction or through some intermediate ylide resulting from a

loss of a proton fron- either C or D may be slower than the interconvcrsion of A

and B. If the rates of decomposition of the betaine remain unaltered then the

reaction would be less stereoselective. House pointed out that even if the rate of

interconversion of the betaines is not retarded by solvation the concentration of the

solvated betaines should be different than the concentration of unsolvated betaines

because the stabilities of the solvated betaincs would be more nearly equal than the

unsoivated betaine in which the trans would be more stable. He based these con-

clusions on a consideration of the interactions of the non-bonded groups in the pre-

ferred conformations.

House also reported in this paper a repetition of work done by Shemyakin and

Bergelson in which he finds that the latter's results for the reaction of benzylidene-

triphenylphosphorane and propionaldehyde in the presence of added LiBr and LiI are

much too high. On repeating these experiments Shemyakin and Bergelson found

their results to be closer to those of House but that significant differences, partic-

ularly in the case of the dimcthylformamide solvent system still exist.

3 \


2/ 3


32 3


C +1

CR3 2 / 3

O-- - H
2O-----O H Pea


11 \/ 2 3
H3C H P03

RO-H---O 0 /

3 P93

H3 C\ /c 2c3
SC ---- C
C/ \C


Fig-ure 2. Postulated Reaction Paths of the Wittig Reaction

In 1964 Drefahl, Lorenz and Schnitt21 conducted a study of the effects of

various solvents, bases, reaction temperatures, anions, reaction times and re-

actant concentrations on the stereochemistry of the Wittig reaction. These effects

were studied on one or all of the following reactions:

SCH P q + 0CHO cis + trans stilbene



XVI + cis + trans-l-phenyl-2-(a-naphthyl)-


CH P -0

0 + XVII -- cis + trans-1, 2-bis-(a-naphthyl)ethylene


These workers found that changes in the reaction temperature, anion, reaction

time and reactant concentrations have no effect on the stereochemistry of the re-

sulting olefin. However, they observed that the bases sodium carbide and sodium

amide in benzene and tetra hydrofuran respectively produced a marked decrease in

the amount of cis isomer whereas butyl lithium in benzene produced a slight increase

in the cis isomer, all compared to sodium ethoxide in the respective solvents. Their

study of solvents showed that ethanol, methanol and aniline give approximately the

same cis:trans ratio (58:42), compared to these solvents chloroform gives an in-

creased amount of cis isomer and ethyl ether, tetra hydrofuran, dioxane, benzene,


pyridine, methylene chloride, carbon tctrachloride, acctonitrile, nitrobenzene and

dimethylformamide give a decreased amount of cis isomer. They offer no expla-

nation of these results.

In summary it appears that few conclusions or generalizations can be drawn

concerning either the mechanism or the stereochemistry of the Wittig reaction at

the present time. The studies thus far conducted have produced controversy rather

than clarity--testimony to the complexity of the reaction. Furthermore, large

gaps still exist in our knowledge of certain aspects of the synthesis. This is

particularly true of the reactions of unstable or reactive ylides which is the subject

of the research to be described.

Statement of the Problem

22 23
As a result of research2' in Dr. G. B. Butler's group on the synthetic

aspects of the Wittig synthesis a number of interesting observations were made

which had previously received little or no attention in the literature. In surveying

the literature it became apparent that the stereochemistry of the reaction had also

been largely untouched. It seemed appropriate then to study these several aspects

of the Wittig reaction at the same time since they are logically related.

The objective of this research was to study the effect of certain factors on

the stereochemistry of the Wittig reaction. The system chosen was one leading to

the isomeric 1,3-pentadienes. The factors to be studied were:

1) solvents

2) temperature

3) reaction time

4) relative concentration of reactants

5) nature of the anion

6) nature of substituents.

In addition, the possibility of a 1,4-addition of ylide to a conjugated

carbonyl system was to be studied.

Method of Attack

The choice of the 1, 3-pentadiene system was based on the following considera-

tions. First, the olefin is well characterized. Second, it is highly volatile which

was an essential property in our experimental procedure. Third, since it is the

first member of the homologous 1, 3-dienes exhibiting geometrical isomerism it

should be of general interest. Fourth, no work had previously been reported on

this system.

As it turned out the choice was fortunate since the reactivity of the allylidene-

triphenylphosphorane lies between the more widely studied stable ylides and the

unstable or reactive ylides. This should permit the ready correlation of existing

data across the spectrum of ylide reactivities encountered in the Wittig reaction.

The approach was to synthesize 1, 3-pentadiene by the Wittig reaction in three

different ways as shown. Each of the three ylides shown could be prepared from



three different phosphonium salts. These nine salts were obtained or prepared

+ -
03-P-CH2CH=CH2 I + BuLi BuH + Lil + 0 -P-CH-CH=CH3

+ -
0P-CII2CH=CHII Br + BuLi--BuH + LiBr + -P-CH-CH=CH3

+ -

03P-CH2CH=CH2 C1 + BuLi -- BuH + LiC1 + 0 -P-CH-CH=CH3

and used in investigating the nature of the anion effect.

The reaction starting with allyltriphenylphosphonium bromide, acetaldehyde

and butyl lithium in equimolar amounts was chosen as a standard and used to in-

vestigate the other factors enumerated. The standard solvent was tetrahydrofuran,

the standard reaction temperature was 00 C. and the standard reaction time was

120 seconds. These conditions were chosen for convenience and through experience

gained in preliminary work with the system.

Because of the number of reactions to be run a semi-micro technique was

employed using 1.0 millimole quantities of reactants and analyzing the products

by previously standardized vapor phase chromatography. The reactions were con-

ducted in an all glass manifold under nitrogen and no mechanical transference of

the products was required until the time of analysis.

A few auxiliary experiments were carried out so that appropriate comparisons

could be made with a somewhat different system.




Reactions in which the effect of the solvent was determined were carried out

in the standard procedure except a test solvent rather than THF was added to the


The results of these experiments are listed in Table 3. It is obvious that

the effect of solvent on the stereochemistry with but two exceptions is negligible.

On the other hand, the effect of solvent on the yield is considerable. In going from

decalin to N, N-diethylaniline one observes a 400 per cent increase in the yield.

One notes that though there is a crude correlation existing between yield and the

dielectric constant of the solvent several exceptions occur.

Both n-butyl and t-butyl alcohols give only traces of 1, 3-pentadiene under

these reaction conditions. This is not altogether unexpected since the allylidenetri-

phenylphosphorane is a very strong base, much stronger than the conjugate bases

of these two alcohols. It appears that the addition of these alcohols initiates an

acid-base reaction in which most of the ylide is converted to phosphonium salt.
4- -
3 2 22 3 2 3 2 2 2 3 22 2







N, N-Dimethylaniline

N, N-Diethylaniline


t-Butyl Alcohol

t-Butyl Alcohol

n-Butyl Alcohol

N, N-Dimethylformamide

% Yield











Cis: Trans Dielectric Constant

42:58 2.2

41:59 2.38

43:57 3.1

42:58 4.4

41:59 5.20

42:58 7.6

50:50 11.4

50:50 11.4

--- 17.8

53:47 37.6

*20 Min. reaction time


Three observations were made concerning the reaction in the butyl alcohols.

First, the fact that some 1,3-pentadiene is obtained at all seems to indicate that

an equilibrium does exist but that it is displaced far to the right. Second, further

evidence for the equilibrium is obtained in the reaction of t-butyl alcohol in which

the reaction time is lengthened from two minutes to twenty minutes. Though this

is a small change it is in the expected direction. Third, the fact that the yield of

product is greater in t-butyl alcohol than in n-butyl alcohol is in keeping with the

proposed equilibrium since the t-butoxide ion is a stronger base than the n-butoxide

ion and should cause the equilibrium to be shifted to the left.

Concerning the stereochemistry of the above two reactions it would seem

unwise to place much significance on the cis-trans ratios observed since the yields

are so low and the relative error so high.

The case of N,N-dimethylformamide (DMF) is peculiar in two respects. It

produces a 25 per cent increase in the amount of cis 1,3-pentadiene in the product

mixture whereas the yield is reduced to practically one-third of that observed in

tetrahydrofuran (THF) the next most polar solvent. This anomalous behavior is

rather difficult to explain. Shemyakin and Bergelsonl0 felt that the enhancement

of the yield of the cis isomer which they observed for reactions carried out in DMF

vs THF is caused by an interaction between the phosphorus of the ylide and the

strongly polarized oxygen of the DMF. This proposal seems unlikely for two reasons.

First, DMF, because of resonance stabilization represented by forms XX and XXII

exists as a planar molecule.24 As a planar molecule with high 7relectron density

(forms XX and XXI) on the oxygen its mode of solvation of an electrophilic center

would be through a line perpendicular to the plane of the molecule. The solvation of

HI3C 0 HI3C 0 II3C 0
S\ \+ / 3\ +/
/ / /


HC /0 0/

the ylide phosphorus would appear difficult from steric considerations if the DMF

molecule assumes the same configuration as that described by Bergelson and

Shemyakin for other Lewis bases.



Second, it has been shown that DMF is a particularly effective solvent25 for

cations such as alkali metal cations. It therefore seems likely that the species

solvated would be the lithium cation rather than the phosphorus of the ylide.

If this is the case and if the ylide exists as an ion-pair as Schlosser26 has

suggested, the amount of "free" ylide would increase in DMF in contrast to less

specific cation solvents. This would result in a more rapid but less selective

attack of ylide on aldehyde. This seems to be a more plausible explanation than

that of the Russian workers.

The low yields with DMF have been observed previously by House20 and
Shemyakin. Both of these workers found yields in DMF to be lower than those in

benzene. However, neither of them has offered an explanation of this behavior.

The possibility of side reactions seems improbable since we observed no peaks in

our chromatograms different from those seen using THF. Also other workers

have obtained under somewhat different conditions and using different starting

materials, yields in excess of 90 per cent. The only speculation that can be

offered at present is that the DMF may form a relatively stable complex with the

intermediate betaines thereby decreasing the rate of betaine decomposition to


The case of the amines is also difficult to explain. There appears to be a

steric effect operating in the solvation process which favors the somewhat less

hindered DMA over DEA but no other conclusions can be drawn at this time. One

added observation was made during the course of the solvent study. When the ylide

is first generated in decalin it is an orange-red suspension. The addition of

toluene and DEA has a negligible effect on deepening the color or increasing the

solubility of the ylide. However all of the other solvents except the alcohols

caused increased or complete solution of the ylide and an intensification of the

color to a very deep red. The alcohols each reacted a bit differently. The

n-butanol formed a yellow-orange solution that contained a small amount of white

solid while the t-butyl alcohol produced a brownish-red solution containing a larger

amount of solid. The increased solubility in the more polar solvents is to be

expected but more study is necessary before conclusions can be drawn regarding

the bathochromic shifts observed.

Temperature Effects

These reactions were carried out in the standard procedure except that the

ice bath surrounding the reaction tube was replaced by the following baths. For

the room temperature bath water which had come to equilibrium at room tempera-

ture was used. For the bath at -200C a mixture of magnesium nitrate hexahydrate and

crushed ice was used. For the -780C bath Dry Ice and acetone was used.

From the data in Table 4 one may see that over the temperature range

covered no significant change in the cis-trans ratio takes place. However, the yield

is increased by 30 per cent as one proceeds from room temperature to -780C. This

is probably the result of diminishing the rate of side reactions relative to the rate

of olefin formation. The nature of the side reaction or reactions was not extensively

explored in the present work but Butler and Hauser22 have postulated a competing

aldol condensation as being responsible for the low yields generally obtained with

aliphatic aldehydes.

A side reaction that was noted in these experiments was the production of



Temperature % Yield Cis: Trans

27 C. 41 42:58

0 C. 45 42:58

-200C. 49 43:57

-780C. 53 43:57


cis and trans 2-hexene. As one goes from higher to lower temperatures one notes

that the relative amount of the 2-hexenes produced decreases from 3. 6 to 0. The

number 3. 6 represents approximately 2 mole per cent of isomeric 2-hexenes.

Therefore this is not the only side reaction taking place.

The production of the 2-hexene may be rationalized in at least two ways.

Seyferth27 and co-workers have found evidence for pentacovalent phosphorus

intermediates in the formation of ylides and proposed the mechanism shown below.

The fact that both deuterobenzene and the hydrogen substituted benzene are produced

P-CH3 Br- 4 D< Li > Li Br + D

XXV CH =3 + D 0+ H

69% 31%

is indicative of either a structure such as XXV or an exchange mechanism. Seyferth

favors the formation of a pentacovalent intermediate. Whether an analogous

mechanism is responsible for the 2-hexenes is open to question since Seyferth noted

that the reaction of methyl lithium with a benzyltriphenylphosphonium salt gave no

benzene. He concluded that in certain cases only hydrogen abstraction took place.

The only supporting evidence we have for such a reaction sequence besides the

product is the detection of small amounts of propene in our product mixture.

However this propene could arise from the reaction of unreacted ylide with the

water quench. That such reactions take place has been demonstrated by Fenton and

P '-CH CH=CH2 Br + Bu Li >- + Li Br





c3P-CHCHCH2CH + CH3CHO 93P-->O + 2-Hexene
3 2 2 3 2 3
03P-CHCH=CH2 + H20 --- 3P(OH)CH2CH=CH2

q3P(OH)CH2CH=CH2 3P--O> + CH3CH CH

and Ingold. 28 These workers in examining a series of phosphonium hydroxides found the

order in which groups are displaced is (CH2 >p>alkyls.. Since we also found benzene

in our product mixtures it is difficult to decide for or against this path.

The other route to the 2-hexenes involves the addition of butyl lithium to

acetaldehyde and the subsequent elimination reaction as outlined.

3 2 2 2 3 3 2 2 2H O

2H 1o H 2
SP HCHCI-2C CH C--> P->O + CH CH=CH + 2-Hexene
3 '-- CH 2 2 3 '3 2 2
h 3

Speziale and Ratts have postulated a similar path for the reaction of dichloro-

methylenetriphenylphosphorane in t-butyl alcohol which yielded considerable

amounts of isobutylene. An objection to this path would be that no 1-hexene was

observed along with 2-hexene. However considering the small amount of the more

stable 2-hexene formed this would be understandable.

One might conclude that if the second reaction path is in effect, the produc-

tion of the 2-hexenes would always be accompanied by the formation of propene

and vice versa. If this is true we can rule out this path since several cases were

noted where propene was liberated but no 2-hexene could be detected. Returning

to the first reaction path one might reason similarly except that here there is an

optional reaction path. Instead of the allyl group abstracting the proton from the

butyl group, a phenyl could be used in which case benzene would be a by-product

rather than propene. Benzene is ob served to be a product but the nature of the

ylide is difficult to rationalize unless we take certain geometrical characteristics

of the species into consideration. The allyltriphenylphosphonium cation probably

has tetrahedral syrametry. If we proceed through a pentacovalent structure this

species must arise from the attack of the butyl lithium on one of the sides labeled

A, B, C or D.




If the attack takes place on sides A, B or D we obtain the trigonal bipyramid XXIX.

If the attack occurs on side C we obtain structure XXX. If we take into account the

relative basicities of the three species we find that they decrease in this order

n-butyl > 0 > allyl. The acidities would conceivably be in the reverse order how-

ever the phenyl carbon attached to phosphorus has no hydrogen to donate leaving

just allyl and butyl groups to compete in this decomposition to ylide. Considering

structure XXIX it seems probable that the more acidic allyl group would donate its

proton to the butyl group giving butane. In structure =XX the strongly basic butyl

group is no longer in position to accept a proton from the allyl group and so their

would be a competition between the two acidic groups allyl and butyl to donate a

proton to a phenyl. Since the acidity of the allyl group is greater than that of the

butyl more allylidenebutyldiphenylphosphorane would be formed than butylidene-

allyldiphenylphosphorane. This is also true of structure XXIX but the probability

would undoubtedly be reduced because of the favorable positions of the acidic allyl

and basic butyl groups. Also one notes that structure XXIX is statistically favored

by 3:1 over XXX. Whether all the ylide is produced through intermediates XXIX

and XXX is an open question as is the existence of such intermediates.

Perhaps the best evidence for this reaction path is based on the stereochem-

istry of the 2-hexenes formed. In fourteen experiments under varying conditions

ten gave an excess of the cis-2-hexene, two gave an excess of trans-2-hexene and

two were about 1:1 ratios. The predominance of cis isomer seems to be diagnostic

of a reactive ylide which the butylidenephosphorane is. If the other mechanism

were correct one might expect either a statistical distribution or a preponderance

of the more stable trans isomer.

Reaction Times

In Table 5 are the results for reactions carried out under standard conditions

but with variable reaction times. One observes that no change in the stereochem-

istry of the products takes place over the range of times covered. The yield shows

about a 10 per cent increase in going from the 30 second to the two minute reaction

time but apparently levels out beyond this.

Of greatest significance in this series of reactions is the extremely fast rate

at which the reaction proceeds. It was hoped that rough kinetics could be obtained

for the reaction during this series but this proved to be impossible under the

experimental conditions used. In the absence of kinetic data a great deal can not

be said concerning the mechanism or the transition states of this reaction except by


A kinetic study is of utmost importance in obtaining an understanding of the

mechanisms and stereochemistry of the reaction. It would appear to be the next

logical step in this research area.




30 sec. 40 42:58

120 sec. 45 42:58

1200 sec. 46 42:58

Concentration Effects

During this series of experiments all the standard conditions were in effect

except that varying amounts of phosphonium salt, acetaldehyde and butyl lithium

were used. The results of these experiments is given in Table 6.

From the Table it is evident that varying the reactant concentrations produces

no significant change in the stereochemistry of the resulting olefin. The very slight

increase in the cis olefin produced by the doubling of both aldehyde and phosphonium

salt concentrations may or may not be significant since it lies just beyond the range

of the average deviation.

Of more interest is the fluctuation in yield that one observes. Doubling the

concentration of butyl lithium produces a sharp drop in olefin yield for three possible

reasons. First, the excess butyl lithium may add across the carbon-oxygen double

bond. Second, being a strong base it may initiate aldol type condensation reactions.

Third, it may polymerize the 1,3-pentadiene produced. These reactions represent

well known modes of reaction of organolithium compounds, and could occur singly

or together. During the runs in which the butyl lithium concentration was doubled

large quantities of viscous polymeric materials were observed to form in the

reaction tube which would be indicative of the last two reactions. However, no

attempt was made to isolate or identify such by-products.

Reactions in which the acetaldehyde concentration was doubled or the butyl

lithium and phosphonium salt concentrations were doubled though they appear com-

parable proved to be otherwise from a yield standpoint. Whereas the excess

aldehyde resulted in an increased yield of olefin compared to the reaction using

equimolar amounts of reactant, the excess amount of ylide caused a slight decrease



Concentration (mmoles/6 ml. solvent)
03-P+-CH CH=CH Br n-Bu Li CH3CHO % Yield Cis:Trans

1 1 1 45 42:58

2 1 1 50 43:57

1 2 1 16 43:57

1 1 2 59 43:57

2 2 1 41 43:57

2 1 2 75 45:55

in the yield of olefin. The latter result may be rationalized by noting the strongly

basic properties of the ylide and its ability to induce base catalyzed condensations

of the aldehyde. The increase in yield produced by doubling the aldehyde concentra-

tion was expected. If the rate expression for this class of ylides is similar to the

expression obtained by Speziale and Bissing for stable ylides then the rate would

be proportional to the ylide concentration multiplied by the aldehyde concentration.

We might expect twice the amount of product for this reaction provided there were

no side reactions and that the reaction was still in its early stages where this kinetic

expression would be linear. However, as was observed in our experiments on the

reaction time, this reaction is very fast. It begins to level off in approximately 30

seconds. Under these circumstances we would not expect to observe a doubling of

yield with a doubling of the aldehyde concentration but an increase of variable magnitude.

Doubling the concentration of phosphonium salt would appear to have little

effect on the yield since it should not alter the concentration of either reactant.

However, the data shows that this conclusion is not completely correct.

An examination of the chromatograms from the reaction of equimolar amounts

of ylide and aldehyde under varying conditions invariably reveals the presence of

small amounts of n-butane. The exact amount of n-butane cannot be ascertained

because of the overlap of the n-butane peak with the propene peak which is almost

always present and the lack of calibration for n-butane with the internal standard.

However, to make a very rough estimate the n-butane would probably be around 5

mole per cent plus or minus 3 per cent. This represents the n-butyl lithium left

after the reaction has been completed. The n-butane is formed by the hydrolysis

of this unreacted n-butyl lithium with the aqueous quench. Although the chromat-

ogram from the reaction using double salt concentration does not reveal a decrease

in the amount of n-butane it shows an increase in the amount of propene produced.

This is comparable to an increase in the amount of ylide which would account for

the increased yield. The point of this rationale is that the reaction between the

phosphonium salt and n-butyl lithium does not go to completion under the reaction

conditions used in this work. This leaves a fair amount of n-butyl lithium (perhaps

more than 10 mole per cent) free in solution to react with the aldehyde thus

decreasing the yield. The additional phosphonium salt converts part of this

unreacted n-butly lithium to ylide in which state it can then react with aldehyde to

give an increased amount of product. The observation that no 2-hexene is formed

in this particular reaction is probably caused by increasing the odds for normal

hydrogen abstraction from the allyl group rather than the butyl group by increasing

the number of phosphonium ions present.

The highest yield was observed to occur when both the phosphonium salt and

acetaldehyde concentrations alone led to increased yields of 1,3-pentadiene. The

magnitude of the increase suggests a synergistic effect which may be explained by

reasoning similar to that used for the increase accompanying the doubling of the

salt concentration. Since the increased amount of salt would form more ylide and

we now have a large excess of aldehyde with which it may react, one would expect

a substantial increase in yield.

Substituent Effects

In this series of reactions standard conditions were used except that the nature



No. R-P-33 X R'-CHO Yield Cis: Trans

R X R'

1 CII 2CHCH2- I CH3- 42 48:52

2 CH 2CHCI2- Br CH 45 42:58

3 CH =CHCH2- Cl CI 3- 21 42:58

4 CH3CH2- I CH2=CH- 17 61:39

5 CH3CH2- Br CH2-CH- 40 59:41

6 CH3CH2- Cl CH2=CH- 47 74:26

7 CH2C-I2CH2- Br CH3- -- 71:29*

8 CH3CH2- Br CH3CH2- -- 72:28*

* Product is 2-pentene

of the phosphonium salts and aldehydes was varied. From Table 7. one observes a

very striking change in the stereochemical outcome of the reaction as one changes

either the aldehyde or the salt. When one exchanges the "R" group attached to the

aldehyde and ylide in reaction 1 through 6 the cis to trans isomer ratio is reversed.

In reactions 7 and 8 we can see the effect of replacing a vinyl group in the

allyl ylide or acrolein with an ethyl group. The result is a 75 per cent increase

in the cis isomer for allyl ylide and a 20 per cent increase for acrolein. To be

sure these systems are not strictly comparable since the product of allyl ylide

and acetaldehyde and ethyl ylide and acrolein give 1,3-pentadiene while ethyl ylide

and propionaldehyde and propyl ylide and acetaldehyde give 2-pentene as the product.

However the two systems are similar enough so that the concusions regarding the

stereochemistry involved should be fairly valid.

Since all of the ylides used in this work are "reactive" ylides we may assume

that the initial step in the reaction, betaine formation is very fast. It follows then

that this process will be unselective giving equal amounts of "cis" and "trans"

betaines. Since the ratio of products in no case shows this exact 1:1 cis to trans

ratio it would seem probable that the equilibrium postulated for unreactive and

less reactive ylides must also be operating here.

Assuming the attainment of an equilibrium between ylide and aldehyde and the

isomeric betaines one must conclude that the factor determining the stereochemistry

is the relative magnitude of the rate constants for dissociation and decomposition

of betaine as expressed by Speziale and others. The key word here is magnitude

since similar arguments have been made in rationalizing products containing greater

than 95 per cent trans isomer down to 50:50 ratios. If one makes several assump-

tions one can arrive at a fairly satisfactory rationalization of the entire range of

Wittig reactions.

First it is assumed that in the initial attack of ylide upon aldehyde, unreactive

ylides are more selective giving a predominance of "trans" betaine compared to

reactive ylides. In comparing conformation of the ensuing betaines (Figure 3)

one observes that the largest effect on the orientation of ylide and aldehyde is

played by the electrostatic attraction between the developing opposite charges.

For unreactive ylides, conformations leading to XXXLII and XXXVII would be the

least likely of those shown. Of the remaining possibilities conformation leading

to "trans" betaines would be favored over those leading to "cis" betaines. The

case for reactive ylides would be quite different since betaine formation is very

rapid and hence less selective perhaps to the point of being statistical.

Second, in the absence of any stabilization, other than weakly inductive effects,

the decomposition of "cis" betaine will be favored over the "trans." Further, the

placement of the stabilizing group on the carbon attached to the phosphorus will

have a greater effect than if attached to the carbonyl carbon. These stabilizing

groups described will either exhibit a (+R) and a (-I) effect e.g. Cl or -0 or a

(-R) and (-I) effect e.g. CEN or COOR. However, if one is dealing with an

unreactive ylide the addition of an electron withdrawing group to the aldehyde will

generally increase the amount of "cis" betaine since it will increase the reaction

rate and lower the selectivity of betaine formation.

The postulate that a "cis" betaine will decompose to olefin (cis) faster than

the "trans" betaine when not stabilized is not without precedent. There are cases

of steric acceleration in the literature although none are strictly analogous to the

+ + p+ 0-^

H R 0 H R

H R' H R H R H



Sp Z P 043 P3

R H 0 R H




Fig. 3 Possible Bctainc Configurations

present system. Brown and Bcrncis30 showed that the solvolysis of halide XXXIX

is twenty-one times as fast as t-butyl chloride XLI and that XL is five hundred

times as fast. Since one could not possibly ascribe such differences to inductive

or hyperconjugative effects Brown reasoned that the phenomenon could best be

C-C-C-c1 c-C-c c-C-ci
C C C-C-C1 C

explained by the release of steric strain. The chlorides on ionization give carbonium

ions in which the dihedral angle between the alkyl substituents is increased from

1090 to 1200

If we consider the two possible betaine configurations involved in the forma-

tion of 2-pentene we can see that as the methyl group eclipses the ethyl group in



O" PO O P^
0- 3 0- 13

cis XLII trans XLIII

the "cis" configuration the repulsive interaction produced will increase the bond

angles a and P. At the same time angles y and 6 will decrease slightly and the

distance between negatively charged oxygen and positively charged phosphorus

will decrease. In the case of the "trans" betaine this extra push toward phosphorus-

oxygen bond formation is not structurally possible. Since there exists an

equilibrium between the two betaines via reactants, the observed isomer ratio can

thus be rationalized.

Turning to the reaction of allyl ylide and acetaldehyde in which the products

consisted of a 42:58 ratio of cis to trans 1, 3-pentadiene we would predict that

the allyl ylide though very reactive is less reactive than an alkyl ylide. Therefore,

the initial attack on aldehyde would be somewhat slower and a bit more selective,

giving more "trans" than "cis" betaine. In this case since we have a stabilizing

group present, located on the carbon attached to phosphorus, it should have a

substantial effect in altering the stereochemical outcome of the reaction. XLIV

represents a possible transition state leading from betaine to olefin. This structure

shows the cyclized betaine in the process of breaking a phosphorus-carbon bond.



0 3
O---PQ 3


That this bond should break rather than the carbon-oxygen would be predicted on

the difference in bond energies which is about 7 kcal/mole, the release of

steric strain and the probability that this is an axial bond making it somewhat

weaker than a normal tri- or tetra-covalent carbon-phosphorus bond. As charge

is developed on carbon (2) the ability of the vinyl group to delocalize it will be

dependent on its ability to lie in a plane passing through carbons (1) and (2) and

perpendicular to the departing phosphorus. XLV and XLVI show that stabiliza-

tion of the developing negative charge and the double bond can be best accomplished

for steric reasons when the vinyl and methyl groups are trans to one another.



+ +

cis XLV trans XLVI

The 50 per cent increase in cis isomer obtained on exchange of the vinyl

and methyl groups between aldehyde and ylide as shown in reactions 4, 5 and 6

can be explained in a similar manner. We now have a more reactive ylide than

the allyl ylide which should give us less selectivity in betaine formation with an

increased amount of "cis" betaine. A transition state similar to that pictured for

the allyl ylide-acetaldehyde case would show that since the vinyl is not attached

to a center of primary charge-formation the stabilization of the intermediate

through a coplanar vinyl group is of less importance than the steric acceleration

promoting decomposition of the "cis" betaine.

Using the foregoing assumptions one can justify other examples of predom-

inant cis olefin as reported in the literature in a similar manner.

There is oie point which we have neglected in the foregoing argument--the

dissociation of botaine. XLVII represents a possible transition state for betaine

dissociation. We assume the conformation shown since this structure should lead


state fo betaine dt ti p
i e C +C C



"*aus" betain T. S. XLVII reactants

to the least electrostatic attraction between the oxygen and phosphorus and thus

be the least likely state for betaine decomposition to olefin. In this proposed

transition state we have the partial breaking of the C1 C2 bond with a shifting

oi the boidi4-. pair of electrons to C the ylide carbon. This situation necessari-

ly means that C1 ill be somewhat electron-deficient and C2 somewhat electron-

rich. Stabili-ation of such a transition state and an accompanying increased rate

of dissociation would result if electron withdrawing groups were attached to C2

and electron-donating groups were attached to C .

Using this reasoning we would conclude that in the series studied in this

work, the rate of dissociation would decrease in the following order:

allyl ylide + acetaldehyde > ethyl ylide + acrolein > ethyl ylide + propionaldehyde =

propyl ylid +- acetaldehyde. The relationship of these rates to the stercochem-

ical outcome of the reaction arises from the ensuing equilibrium between reactants

and betaine. However conclusions cannot be drawn without taking into account

the rate of betaine decomposition. Furthermore, the relative rates of dissoci-

ation of the isomeric bctains must be considered. Bissing and Spczialc31 have

recently published work in which they have determined the relative rates of

dissociation vs decomposition for three systems. Starting with isomeric 4-octene

oxides they treat these with triphenylphosphine generating the betaine in situ. If

an excess of the more reactive m-chlorobenzadehyde is present any butylidene-

triphenylphosphorane formed through equilibration would react with it in preference

to butyraldehyde giving 1-(m-chlorophenyl)-l-pentene. The ratio of l-(m-chloro-

phenyl)-l-pentene to 4-octene would then be an indication of the ratio of betaine

dissociation to betaine decomposition. They find for the 4-octene oxides this


P3 O



03 7

ratio to be quite small indicating that the rate of betaine dissociation for unstabi-

lized betaines is low. They also found that this ratio increases for stilbene oxide

and ethyl phenylglycidates which we would also expect. Their work on the 4-octene

oxides and stilbene oxides is particularly interesting since it also reveals infor-

nation concerning the relative rate of dissociation of "cis" and "trans" betaines.

Table 8 shows the results of their work with the pure isomeric epoxides. They

assumed that a cis epoxide would lead to trans betaine and trans epoxide would

lead to cis betaine.



Epoxide % 4-Octene % l-(m-chlorophenyl) -1- pentene

cis trans cis trans

cis 4-octene oxide 31 55 6 9

trans 4-octene oxide 73 12 7 9

cis stilbene oxide 21 23 12 44

trans stilbene oxide 22 22 16 39

If all of their assumptions are correct only three products should result from

each isomeric epoxide. In the case of cis-4-octene oxide one should obtain trans-

4-octene and cis and t-rans l-(_-chlorophenyl)-l-pentene. However we see that

a fairly large amount of cis-4-octene is also produced and the second isomer

arises in the other two reactions as well. The authors state that the "forbidden"

isomer may arise from either direct attack of the triphenylphosphine on oxygen of

the epoxide or from a proton exchange.

+ +
H C3 3 H H C3H7
73 37
SP C=-C3H7
3- 3 7

HC 3 7 H C3 7


The point to be observed here is that the ratio of betaine dissociation to

betaine decomposition is the same for "cis" and "trans" betaine derived from

4-octene-oxide and from stilbene oxide. Though this conclusion may be correct

for the stilbenes it is not correct for the octenes. The fact that the "cis"-4-octene

betaine gives 73 per cent cis 4-octene while the "trans"-4-octene betaine gives

only 53 per cent trans -4-octane is indicative that the rates of betaine decompo-

sition are quite different. The authors state that the reliability of the dissocia-

tion to decomposition ratio is probably not too high so it seems probable that the

rate of betaine decomposition is higher for the "cis" than the "trans" betaine

whereas for dissociation the reverse is true.

We can rationalize the latter phenomenon by considering models of a

possible transition state leading to dissociation for the isomeric betaines. Since

no stabilizing groups are attached to the carbon atoms making up the bond about

to be broken the difference in the energy of the transition state should be a

reflection of steric considerations alone. In the "trans" structure there will

result a skew interaction between the adjacent n-propyl groups which is absent

in the "cis" structure. If we invoke steric acceleration we would predict the

"trans" isomer to dissociate to reactants faster than the "cis." However, when

one or both of the n-propyl groups are replaced by stabilizing groups such as

vinyl, carbomethoxy, etc., the reverse would be true since the ability of that

group to stabilize the charged center would be dependent on its ability to become

co-planar. It could accomplish this much more easily in the "cis" structure than

in the "trans".

Anion Effects

In looking at the data in Table 7 we note two reactions which gave higher

proportions of the cis-1,3-pentadiene than the others. The reaction using

allyltriphenylphosphonium iodide gives a 48:58 ratio. The reaction of ethyl-

triphenylphosphonium chloride gives a 74.26 cis :trans ratio while the other ethyl-

phosphonium salts give a 60 :40 ratio. Whether we are observing a halide effect

or an experimental error cannot be said with certainty. The latter is a possibility

only because the explanation of the former postulation is so difficult.

Shemyakin and Bergelsonl9 reported a result similar to ours for reactions

4 and 6. They reacted propylidenetriphenylphosphorane with benzaldehyde in

ethyl ether to give P-ethyl styrene in the presence of added lithium halides.

Their results are shown in Table 9. Their results exhibit the same trends

in yield and stereochemistry as ours.




Solvent Salt Ylide:RCHO Yield Cis:Trans

EtOEt LiC1 1:1 70% 80:20

EtOEt LiI 1:1 46% 22:78

lH LiC1 1:1 62% 79:21

IH Lil 1:1 33% 35:65

In another series of experiments32 these investigators reacted the ylide

derived from benzyltriphenylphosphonium chloride and iodide with propionaldehyde

in benzene. With the chloride they obtained a 20 : 80 cis to trans ratio while with

the iodide they obtained a 41: 59 ratio. They gave no yield data. This reflects

a similar increase in the amount of cis isomer we experienced in comparing

reactions (3) and (1). The benzyl and allyl ylide are roughly comparable and we

have demonstrated the absence of a solvent effect for this system so that the

analogy is not without some merit.

Even if we can justify our results by comparing it with the work of others

there still remains the need of a better explanation or a satisfactory mechanism.


Regarding the question of a "halide effect" we have two opposite schools of thought.

Shemyakin and Bergelson feel the effect is caused by the halide ion acting on the

phosphorus of the ylide while House believes that it is caused by a lithium cation

acting on the oxygen of the carbonyl function.

Whatever the mechanism of this effect it seems clear from our results

and those of the Russians that it is of a synergistic nature. The presence of a

specific halide (cation) only has an effect on the stereochemistry when a specific

ylide is used. When used with a different ylide no effect on the stereochemistry

is produced.

There appears to be no explanation for these results at the present time.

Too few data are available on the solubilities and other factors which certainly

have a bearing on this phenomenon. Until we have such data it seems best to

avoid unsubstantiated postulates.

1,4-Addition and Isomerization

The reactions in Table 10 were carried out under standard conditions

except the specified mcthylphosphonium salts and crotonaldehyde were used. The

commercially available crotonaldehyde is apparently almost all trans isomer.

V.p.c. analysis showed but one peak on two different columns but there is still the

possibility that neither column could resolve the mixture of isomers.

From the Table 10 one observes a constant cis-trans isomer ratio of 5 : 95.

This indicates that if the starting aldehyde was a 5 : 95 mixture of cis and trans

isomers no isomerization took place under the reaction conditions used, that is,




Sal: % Yield cis-trans
Me P I 19 5:95

MeP Br 17 5:95

Me P Cl 25 5:95

standard conditions.

The increased yield with the chloride may be indicative of a "halide effect"

as discussed in the previous section.

The other purpose for running this series of experiments was to see if a

possible i,4-addi-ion of the ylide to aldehyde would take place. There are several

references 3334,3 in the literature to such reactions but none have been reported

for s.uh a simple system as crotonaldehyde. If 1,4-addition occurred it would

do so by the path shown.



O :--0

02-C2 -+


'3P O


No evidence for such a reaction occurring was concluded by the observation

that no isoprene is formed.

To further show that no isomerization took place under our reaction con-

ditions a small amount of pure trans 1, 3 -pentadiene was added to the reaction

between methylenetriphenylphosphorane and acetaldchyde. No cis 1,3-pentadiene

was observed among the products.



Equipment and Data

All temperatures are reported in degrees centigrade and are uncorrected.

Pressures are reported in millimeters of mercury as determined by either a

Zimmerli or McLeod gauge.

Infrared spectra were either obtained with a Perkin-Elmer Infracord or a

Beckman IR 10 under the conditions noted.

Refraction indexes were obtained using a Bausch and Lomb Abbe 34 Refrac-

tometer equipped with an achromatic compensating prism.

Vapor phase chromatography (v.p. c.) was carried out on a F and M Model

700 chromatograph using a hydrogen flame-ionization detector and the columns

and conditions stipulated.

Elemental analyses were performed by Galbraith Laboratories, Knoxville,


Source and Purification of Materials

The absence of water and purity of the solvents and aldehydes were checked

by infrared and v.p.c. analysis on two columns having the following specifications:

8 ft. 10% Carbowax 20M on 60-SO mesh Diatoport S

8 ft. 10% Silicone Fluid (Nitrile) on 60-80 mesh Diatoport S


The temperatures and flow rates for the v.p. c. analysis were selected to

give optimum resolution.

Distillations at atmospheric pressure were carried out under nitrogen.


Tetrahydrofuran was J. T. Baker reagent grade material. It was pre-dried

over "Dri-Na" for several days, then refluxed with and distilled from lithium
20.1 20
aluminum hydride. B.p. 66.3-66.4C., n20 1.4078; lit. (36)b.p. 65.4C., n2

1.407. The infrared spectrum showed a trace of water which may have been intro-

duced into the exceedingly hygroscopic solvent during sampling. V.p.c. on both

columns showed a single peak.

Decalin was Fisher Laboratory Grade--a mixture of cis and trans isomers.

It was washed successively with three portions of concentrated sulfuric acid, three

portions of 5 per cent aqueous sodium hydroxide and four portions of distilled water.

It was dried overnight with anhydrous calcium chloride or "Dri-Na" and distilled

under vacuum, a 10 per cent forerun being discarded. Infrared examination showed

water to be absent and v.p. c. showed just two peaks.

Triethylamine was "white label" grade obtained from Distillation Products

Industires, Division of Eastman Kodak Company. It was refluxed with and distilled
21 2
from anhydrous barium oxide. B.p. 88.7-88. 80 C., nD 1.4005; lit. (37) b.p.
89.30 C., nD 1.4003. Infrared showed a trace of water and v.p. c. showed just

one peak.

Toluene was J. T. Baker reagent grade material. It was distilled, discarding
the first one-third of the distillate. B.p. 110. 00 C., nD 1.4968; lit. (38) b. p.

110.60 C., n 1.4969. Infrared showed no water to be present and v.p. c.

showed but one peak.

N, N-diethylaniline was "white label" grade "mono-free" material obtained

from Distillation Products Industries Division of Eastman Kodak Company. It was

refluxed with and distilled from anhydrous barium oxide under reduced pressure.

o 20.8 22.3
B.p. 52.6-52.7 C./0.8 mm n 1.5417; lit. (39) b.p. 217. 5 C./760 mm n22

1. 5411. Infrared showed no water or primary and secondary amine to be present.

V.p.c. showed a single peak.

N, N-dimethylaniline was "white label" grade "mono-free" material obtained

from Distillation Products Industries of Eastman Kodak Company. It was refluxed

with and distilled from anhydrous barium oxide under reduced pressure. B.p.
21.0 20
63. 50C./2. mm n1 1.5581; lit. (40) b. p. 194. 20 C./760 mm, nD 1.5587.

Infrared showed the absence of water or primary and secondary amines. V.p. c.

showed a single peak on the Carbowax column and a small shoulder of less than 1

per cent total area on the Silicon column.

N, N-dimethylformamide was reagent grade material obtained from Fisher

Scientific Company. It was refluxed with and distilled from anhydrous barium

oxide, b. p. 149. 5 C., n0 1. 4301; lit. (41) b.p. 1530C., n 41.4294. Infra-

red showed a trace of water present. V.p. c. showed a single peak.

n-Butyl alcohol was reagent grade material obtained from J. T. Baker Chemi-

cal Company. It was refluxed with and distilled from sodium and di-n-butyl

phthalate. B.p. 118.5-118.7C., n204 1.3995; lit. (42) b.p. 118 C., n2 1.3991.

V.p. c. showed a single peak.


tert-Butyl alcohol was J. T. Baker reagent grade material. It was refluxed
with and distilled from sodium metal. B.p. 83.7-83.80 C., nD 1.3867; lit. (42)
b.p. 82.60C., n0 1.3878. V.p.c. showed a single peak.


Acetaldehyde was "white label" grade material obtained from Distillation

Products Industries Division of Eastman Kodak Company. It was distilled through

a 12-inch vacuum-jacketed Vigreux column. The condenser temperature was kept

at approximately 100 C. by external cooling. B.p. 22-230 C. ; lit. (43) b.p. 20. 20 C.

V.p. c. showed a single peak.

Acrolein was "white label" grade material obtained from Distillation Pro-

ducts Industries Division of Eastman Kodak Company. It was dried with anhydrous

magnesium and sodium sulfates then distilled. B.p. 52. 5-52.70 C. ; lit. (44) b.p.

52. 50 C. Infrared showed a trace of water. V.p. c. on the Carbowax column showed

two small extra peaks of total area approximately 1 per cent. Only one small peak

besides that of acrolein was noted on the silicone column.

Crotonaldehyde was "white label" grade material obtained from Distillation

Products Industries, Division of Eastman Kodak Company. It was dried with
anhydrous magnesium sulfate and distilled. B.p. 102.9-103.20 C., nD 1.4370;

lit. (45) b.p. 102.20C., n205 1.4362. Infrared showed a trace of water to be

present. V.p.c. showed a single peak.

Miscellaneous Chemicals

Samples of cis and trans-1, 3-pentadiene, cis and trans-2-hexene and cis

and trans-2-pentene were obtained from Chemical Samples Company. V.p. c.

analysis of these compounds was carried out on a 25 ft. e, e-oxydipropionitrile


Cis-1,3-pentadiene shows characteristic infrared absorption54 at 771 cm-1

21 20
V.p.c. gives a single peak. n 1.4367; lit. (52) nD 1.4363.

Trans-1, 3-pentadiene exhibits characteristic infrared absorption54 at 814

cm V.p.c. shows a small peak in addition to the main peak. This small peak

precedes the larger and constitutes approximately 5-10 per cent of the larger peak.

21 20
nD 1.4298; lit. (52) nD 1.4301.

Cis-2-hexene exhibits characteristic infrared absorption3 at 691 cm
V.p.c. shows a very small peak preceding the main peak. nD 1.3974; lit. (52)
nD -1. 3977.
53 -1
Trans-2-hexene exhibits characteristic infrared absorption5 at 964 cm-

V.p. c. shows a small peak preceding the main peak. The area of the small peak
21 20
is approximately 3-5 per cent of the main peak. n2 1. 3941; lit. (52) nD 1.3935.
53 -1
Cis-2-pentene exhibits characteristic infrared absorption at 696 cm
21 7
V.p.c. shows a very small peak preceding the main peak. n 7 1.3832; lit. (52)

n 1.3830.

Trans-2-pentene exhibits characteristic infrared absorption5 at 964 cm-1
21.7 20
V.p.c. shows a single peak. n17 1.3791; lit. (52) nD 1.3793.

Ethyl acetate, 2-propanol, benzene and carbon tetrachloride which were used

as solvents in the recrystallization of the phosphonium salts were Fisher reagent

grade chemicals.

The methyl isobutyl ketone and chloroform used in recrystallizations were

reagent grade chemicals obtained from J. T. Baker Chemical Company. The 95 per

cent ethanol used in recrystallizations was obtained from Union Carbide Chemical


All of the above were used without further purification.

Ethyl iodide was obtained from Columbia Organic Chemical Company and

was used without further purification.

Triphenylphosphine and methyl iodide were obtained from Peninsular

ChemResearch, Incorporated and was used without further purification.

Allyl chloride, ethyl bromide and n-propyl bromide were obtained from

Distillation Products Industries Division of Eastman Kodak Company. The allyl

chloride and ethyl bromide were redistilled before use; the n-propyl bromide was

used as received.

The Nalcite SAR 20-50 mesh anion (chloride) exchange resin was obtained

from National Aluminate Corporation.

The butyl lithium in hexane was supplied by Foote Mineral Company. The

butyl lithium was assayed using the procedure of Kamienski and Esmay.

Preparation and Purification of Phosphonium Salts

Methyltriphenylphosphonium bromide, allyltriphenylphosphonium chloride

and allyltriphenylphosphonium bromide were on hand having been used in previous

research by Dr. Butler's group.

Methyltriphenylphosphonium iodide was prepared from methyl iodide and tri-

phenylphosphine in benzene according to the procedure of Wittig and Schollkopf5

in 54 per cent yield.

Ethyltriphenylphosphonium bromide was prepared from ethyl bromide and

triphenylphosphine in benzene by the procedure of Wittig et al. in .0 per cent yield.

Ethyltriphenylphosphonium iodide was prepared from ethyl iodide and tri-


phenylphosphine in benzene by the procedure of Wittig et al. in 75 per cent yield.

Methyltriphenylphosphonium chloride was prepared in two ways. First,

18.7 g. (0.1 mole) of silver nitrate were dissolved in 50 ml. of distilled water

followed by treatment with an excess of 6 M HC1. The precipitated silver chloride

was filtered and washed with distilled water, then added to a suspension of 40.4 g.

(0.1 mole) of methyltriphenylphosphonium iodide in 200 ml. of water. The suspen-

sion was refluxed with stirring for four hours. The suspension was allowed to cool,

then filtered with suction. The aqueous filtrate containing the methyltriphenyl-

phosphonium chloride was evaporated to dryness on a rotary evaporator. The

solid remaining was dissolved in a small amount of chloroform, transferred to an

evaporating dish and the solvent evaporated. The amorphous white salt was pro-

duced in 101 per cent yield (if anhydrous).

Second, to a 4 ft. by 1 in. O. D. Pyrex column charged with 0. 5 lbs. of

Nalcite SAR anion exchange resin in the chloride form was added 5.14 g. of methyl-

triphenylphosphonium bromide in one litre of distilled water. The effluent was

evaporated to dryness on a rotary evaporator giving a small amount of white,

amorphous methyltriphenylphosphonium chloride.

Ethyltriphenylphosphonium chloride was prepared using the first procedure

described above for methyltriphenylphosphonium chloride.

Allyltriphenylphosphonium iodide was prepared by the procedure of Wittig

et al. using triphenylphosphine and allyl iodide in benzene. The yield was 96 per

cent. The allyl iodide was prepared by the procedure of Letsinger and Traynham46

from allyl chloride and sodium iodide in acetone.

n-Propyltriphenylphosphonium bromide was prepared by the procedure of

Wittig et al. using triphenylphosphine and n-propyl bromide in benzene.

All data concerning the physical constants, analyses, crystallization sol-

vents etc., for the above salts are summarized in Table 11.


The reactions were run in the all glass apparatus shown in Figure 4. The

stopcock (A) connects the manifold to a tank of Linde "high purity" nitrogen. The

nitrogen is passed through a drying tower containing indicating Drierite. Stop-

cock (B) connects the manifold to the reaction tube (G). Stopcock (C) connects the

manifold to the receiver (H). Stopcock (D) connects the manifold to the vacuum

pump through either a Dry Ice and acetone or liquid nitrogen cooling trap. Out-

let (E) leads to a Zimmerli gauge and stopcock (F) connects the system to the

atmosphere through a silicone oil bubbler and mercury trap in series.

The reaction tubes, receivers, syringes, etc., were all dried for several

hours at 1300 C. before use.


The phosphonium salts which had already been dried once were weighed to

the nearest milligram into a tared weighing bottle on an analytical balance. The

salts were then dried in a vacuum oven overnight at 1000 C., removed to a desic-

cator and stored there until used. The weight loss incurred on this second drying

was usually less than 0. 5 milligrams but in the case of the chlorides almost a

stochiometric amount of water was removed from the monohydrate. Appropriate

corrections were made in the procedure for these salts.


R-P+'-03 X- Recrystallization *m.p. 0OC. Lit. m.p. (Ref.) Analyses (found) Analyses (calcd.)
R X- Solvent(s) C H P C H P
1 st. 2 nd.
CH =CH-CH2 I F G 227-230 -- 58.36 4.58 7.27 58.63 4.69 7.20
CH2=CH-CH2 Br- C A 219-220 209-214 (47) 65.79 5.34 8.07 65.80 5.26 8.08
65.74 5.30
CH2=CH-CH2 Cl B D 227-228 225-227 (21) 72.50 6.62 4.03 74.46 5.95 9.15
74.60 6.10
CH CH2 I- A A 168-169 164-165 (48) 55.88 4.62 7.14 57.43 4.82 7.41
57.50 4.93 7.40
CH3CH2 Br C A 207-208 203-205 (49) 62.65 5.44 8.40 64.70 5.43 8.34
64.86 5.60
CH CH2 Cl E D 240-241 234-236 (50) 73.17 6.17 9.46 73.50 6.17 9.48
CH3 A A 186-187 188-189 (1) 56.62 4.25 7.84 56.46 4.49 7.67

CH3 Br A A 231-232 229-232 (1) 63.95 5.17 8.75 63.89 5.08 8.67
CH3 Cl E D 221-222 212-213 (48) 72.59 5.98 9.98 72.69 5.80 9.91
CH CH CH Br A 236-237 229-230 (51) 65.65 5.60 7.99 65.12 6.24 8.00
65.38 5.97
* All salts were dried at 1000 C. for from 12-24 hours in a vacuum oven. A = isopropyl alcohol; B = tert. butyl alcohol;
C = 1:1 isopropyl alcohol:methyl isobutyl ketone; D = 1:3 isopropyl alcohol:ethyl acetate; E = 3:3:1:1 ethyl acetate:methyl
isobutyl ketone:chloroform:n-butanol; F = 2:3 isopropyl alcohol:abs. ethyl alcohol; G = 95% ethyl alcohol.

to pump

Figure 4. Reaction nifold

Figure 4. Reaction Manifold

J = "Drierite" tower

K = Silicone oil bubbler

I, = Mercury trap

M = Zimmerli gauge

N = Magnetic stirrer

The aldehyde solutions in decalin were made up by weight on an analytical

balance. For acetaldehyde because of its volatility, five milliliter samples were

made up enough for two runs. For acrolein and crotonaldehyde both five and

ten milliliter samples were used. Acetaldehyde solutions were used the same

day and kept in the refrigerator between runs as were the other aldehydes. In

the case of acrolein, its solutions were protected from light until the sample was

withdrawn from introduction into the reaction tube. Since the solutions of aldehydes

were made up in volumetric flasks this work was carried out in the dark room at

approximately 200 C. The aldehyde solutions were withdrawn from the volumetric

flasks using a five milliliter syringe which had previously been flushed with nitro-

gen several times. The syringe was overfilled, inverted and the plunger brought

to the 2.0 ml. mark. Since the same syringe was always used along with the

foregoing procedure only small errors in the amount of aldehyde introduced should

have occurred.

The butyl lithium solution was kept in a 100 cc. amber bottle under nitrogen

sealed with a syringe cap. The bottle was kept inclined with the cap up so that

salts resulting from decomposition or hydrolysis of the reagent would collect at

the bottom of the bottle. Care was taken to obtain clear solutions of the reagent in

the one milliliter syringe perviously flushed with nitrogen. Again the same syringe

was always used for the butyl lithium solutions.

The tetrahydrofuran was kept in a 50 milliliter 2-necked flask under nitrogen.

When a sample was to be withdrawn a stream of nitrogen was first led into the flask

at a moderate rate before the second stopper was removed and the THF withdrawn

with a syringe.

Other solvents were used immediately after distillation and such rigid pre-

cautions were not found necessary.

The Reaction

The following description is what may be called a standard procedure because

it was this procedure or a variation of it that was used throughout this work. This

standard procedure involves the reaction between allylidenetriphenylphosphorane

(derived from allyltriphenylphosphonium bromide) with acetaldehyde in equimolar

amounts using tetrahydrofuran as the solvent. The reaction time is 120 seconds,

the reaction temperature is 00 C. The other reactions in this work are but varia-

tions of one of these parameters--a different temperature, etc. However, in any

experiment only one parameter is varied. The remainder are kept constant.

One millimole of phosphonium salt is transferred by a funnel from the weigh-

ing bottle to the reaction tube containing a small stirring bar. The side arm is

closed with a serum cap and 2. 0 ml. of decalin is introduced by pipet. The

reaction tube is then attached to the manifold and with stopcocks (A) and (F)

closed and (B), (C) and (D) open the system is evacuated. During this evacuation

the stirrer is activated to aid in degassing the suspension. After approximately

five minutes stopcock (D) is closed and stopcock (A) opened carefully to readmit

nitrogen to the system. This process is repeated two more times. After the

nitrogen has been admitted the third time stopcock (F) is opened and the flow rate

of nitrogen decreased.


0. 595 ml. (1 millimole) of butyl lithium is now added to the reaction tube with

a syringe through the serum cap. The suspension rapidly changes color from

yellow to orange to brick red. After two minutes stopcocks (A) and (F) are closed

and the system is evacuated. During this 30-minute evacuation period n-butane

and the hexane that was used as a solvent for the butyl lithium is removed. The

boiling point of decalin is sufficiently high so that little of it is removed in this

evacuation process. The allylidenetriphenylphosphorane and unreacted butyl

lithium are non-volatile. At the end of this evacuation, stopcock (A) is opened

and nitrogen readmitted to the system. Stopcock (F) is then opened to restore the

system to atmospheric pressure.

2. 0 ml. of tetrahydrofuran are then introduced into the reaction tube by means

of a syringe and the blood red solution is allowed to stir for ten minutes. At the

end of the ten minute period a slush ice bath is placed around the reaction tube and

the reaction mixture is allowed to equilibrate for two minutes. Stopcock (B) is then

closed and 2. 0 ml. of acetaldehyde ( 1 millimole) in decalin is introduced by syringe

into the reaction tube over a one minute period. The addition of the aldehyde solu-

tion generally results in the formation of a white solid and a lightening of the red

color. After two minutes 1. 0 ml. of distilled water is added by syringe. This

produces complete decolorization almost immediately with the formation of a two

phase liquid-liquid system. After two minutes the reaction tube is frozen out with

liquid nitrogen for three minutes. The system is evacuated after opening stopcock

(B) and closing stopcocks (A) and (F). The evacuation to less than 1 mm takes

approximately four minutes after which stopcock (D) is closed and the liquid nitro-

gen bath is transferred from the reaction tube (G) to the receiver (H).


As the reaction tube warms the volatile materials distill or sublime into the

receiver. The distillation is continued for 40 minutes. About half-way through the

distillation period the stirrer is activated to promote the transfer of the volatile

materials. At the completion of the distillation nitrogen is readmitted through

stopcock (A), stopcock (F) is opened and the liquid nitrogen bath removed from the

receiver. When the contents of the receiver have melted the receiver is discon-

nected from the manifold, sealed with a serum cap and removed to the dark room

(200 C.) where 30 p1l. of cyclohexene the internal standard is added. The mixture

is then either analyzed immediately by v.p. c. or the receiver is kept in a Dry

Ice and acetone bath until the analysis is performed.


The analyses were all run on the F and M Model 700 using a 25 ft. x 1/4 in.

O. D. column containing 10 per cent by weight of e, e-oxydipropionitrile on 60-80

mesh Chromosorb P. The column temperature was 250 + 10 C. and the flow rate

approximately 75 ml. per minute. The size of the sample injected was 0.3 pIl.

Calibration of the Internal Standard

A series of synthetic mixtures containing known amounts of trans-1,3-

pentadiene and cyclohexene, the internal standard, were prepared in tetrahydro-

furan in concentrations such that the sensitivity setting of the chromatograph would

be the same or very close to those used during the actual runs. The samples were

made up by volume at 200 C. For example, the "known" containing 50 mole per

cent 1, 3-pentadiene was prepared in the following way. Into a small vial flushed

with N2 and sealed with a serum cap was placed 0.7 ml. of tetrahydrofuran.


Next 10.04 j1. of cyclohexene was added followed by 5. 0 4-l. of trans-1, 3-penta-

diene. The mixture was shaken well and then at least two 0. 3 p1. portions were

chromatographed under the same conditions as those used for the actual runs.

In between runs the vials were kept in a Dry Ice-acetone bath. The calculations

used to arrive at the volume of internal standard and pentadiene are as follows:

Gram Molecular weight cyclohexene = 82. 1 g.

Density at 200 C. cyclohexene = 0. 811 g. /ml.

Gram Molecular weight 1, 3-pentadiene = 68.1 g.

Density at 200 C. of 1, 3-pentadiene = 0. 676 g. /ml.

1. 000 l. trans-1, 3-pentadiene = ? gram-moles

= 1 p1. x 10-3 ml. l. x 0.676 g.

ml. x 1 mole 68.1 g.

1. 000 l. = 9.93 x 10-6 moles trans-1, 3-pentadiene

9.93 x 10-6 moles cyclohexene = 7 1.

Pl. = 9.93 x 10-6 moles x 82.1g. mole- x 1 ml. (0.811 g.)- x

1 l. 10-3 ml.-1

9.93 x 10-6 moles = 1.004 P1. cyclohexene

Therefore if we want a 50 mole per cent solution of 1, 3-pentadiene we would

use 0. 500 1'l. 1, 3-pentadiene for each 1. 004 p1. cyclohexene. Since we used 5.00

vl. of 1, 3-pentadiene we would use 10.04 4l. of cyclohexene.

Using the calculations above a curve was plotted of the concentrations of

trans-1, 3-pentadiene vs. the ratio of the area under the pentadiene peak over the

area under the cyclohexene peak or
%area under pentadiene peak
% 1, 3-pentadiene area under cyclohexene peak

This was done for five concentrations of 1, 3-pentadiene, the resulting curve is

shown in Figure 5. From this curve and the areas of the 1, 3-pentadiene and

cyclohexene peaks it is possible to determine the concentration or yield of 1, 3-

pentadiene in the volatile mixture and the cis to trans isomer ratio.

To make sure that the distillation of the 1, 3-pentadiene was quantitative the

chromatogram of the residue was taken. In all cases the remaining 1, 3-pentadiene

constituted less than 1 mole per cent of the theoretical yield.

Since trans-1, 3-pentadiene was used for the calibration a possible error

might arise if the detector response differed for the cis isomer. Therefore a 20

mole per cent solution of the cis-1, 3-pentadiene was made up and analyzed using

the calibration curve based on trans-1, 3-pentadiene. The calculated amount of

cis isomer was 19. 8 per cent which is an error of 1 per cent. Therefore it was

assumed that the detector response was the same for both isomers and the one

curve was used to calculate the yields of both cis and trans-1, 3-pentadiene.

For the quantitative analysis of the 2-pentene system the isomer ratios were

calculated both by area and peak height. The two methods agreed within 2 per cent.

Qualitative Analysis

The reproduction of the chromatogram of the product mixture resulting from

the reaction of allylidenetriphenylphosphorane and acetaldehyde under standard

conditions is shown in Figure 6. The peaks are numbered from (1) through (11).

Peaks (8) (9) (10) and (11) were obtained at approximately 450 C. while peaks (1)

through (7) were obtained at 250 C.

7 60-

a 40


0 -



0 0.20 0.40 0.60 0.80 1.00

trans-1, 3-pentadiene peak area
cyclohexene peak area

Figure 5. Calibration Curve for trans-1, 3-pentadiene

Temperature ( C. )



10 15 20 25 60

Time (min.)

Figure 6. Chromatogram of Reaction Products

85 115


Peaks (10) and (11) were cis and trans decalin. They showed increased peak

height on the addition of a few drops of pure decalin (mixed isomers) to the product

mixture. Peaks (8) and (9) are tetrahydrofuran and benzene respectively which

were identified by the above procedure. Peak (7) is cyclohexene the internal

standard. Peak (6) is cis-1, 3-pentadiene and peak (5) is trans-1, 3-pentadiene

identified by the addition of authentic samples of the pure isomers to the product

mixture as above. Peaks (3) and (4) are trans and cis-2-hexene respectively also

identified by the addition of authentic samples of the pure isomers to the mixture.

Peak (8) is n-butane identified by the enhanced peak height observed on addition of

a THF solution of n-butane prepared by the hydrolysis of n-butyl magnesium bro-

mide. Peak (1) is propene identified by the addition of bromine to the product mix-

ture and then noting the propylene bromide peak enhancement following the addition

of known propylene bromide.

Precision of Chromatographic Analysis

A measure of the precision of the determination of the cis:trans isomer ratio

may be obtained by taking the average of the average deviations for the duplicate

runs. This is t 0.7 with the largest average deviation being 1 1.7.

The precision of the yield determination as given by taking the average of

the average deviations for the duplicate runs is t 2. 0 with the largest average

deviation being t 5. 0.

A summary of the infrared absorption bands for the phosphonium salts used

in this research is shown in Table 12. As a means of identifying individual phos-

phonium salts, infrared is impracticable. However the alkyl group of the lower




1979 w, 1903 w, 1820 w, 1780 w, 1671 w, 1620 w, 1595 m-s, 1490 m-s, 1443 s,
1420 m-s, 1400 m, 1339 m, 1318 m, 1306 sh, 1118 s, 998 m-s, 900 s cm-1
1978 w, 1902 w, 1821 w, 1779 w, 1671 w, 1620 w, 1594 m-s, 1489 m-s, 1442 s,
1419 m-s, 1394 m, 1338 m, 1316 m, 1304 w-m, 1116 s, 998 m-s, 899 s cm-1
1976 w, 1902 w, 1821 w, 1779 w, 1671 w, 1620 w, 1593 m-s, 1488 m-s, 1441 s,
1418 m-s, 1394 m, 1337 m, 1318 m, 1302 w-m, 1116 s, 998 m-s, 896 s cm-1

Ethyltriphenylphosphonium 1974 w, 1901 w, 1820 w, 1778 w, 1590 m, 1480 m-s, 1437 s, 1420 m-s, 1388 m,
chloride 1332 m, 1312 m, 1108 s, 994 m-s cm-1
Ethyltriphenylphosphonium 1974 w, 1908 w, 1821 w, 1777 w, 1665 w, 1591 m, 1485 m-s, 1439 s, 1420 m-s,
bromide 1390 m, 1333 m, 1313 m, 1110 s, 995 m-s cm1
Ethyltriphenylphosphonium 1978 w, 1907 w, 1824 w, 1780 w, 1672 w, 1594 m-s, 1490 m-s, 1442 s, 1425 m-s,
iodide 1389 m, 1317 m, 1113 s, 998 s, cm-1
Allyltriphenylphosphonium 1979 w, 1903 w, 1821 w, 1778 w, 1639 m, 1613 m-s, 1592 m, 1487 m-s, 1439 s,
chloride 1422 m-s, 1390 m, 1334 w-m, 1313 m-s, 1109 s, 997 m-s, 960 m cm-1
Allyltriphenylphosphonium 1981 w, 1906 w, 1820 w, 1778 w, 1616 w, 1593 m, 1487 m, 1442 s, 1423 m-s,
bromide 1394 m, 1335 w-m, 1315 w-m, 1113 s, 998 m-s, 990 sh cm-I
Allyltriphenylphosphonium 1979 w, 1899 w, 1820 w, 1776 w, 1635 w, 1611 w, 1590 m, 1483 m, 1438 s,
iodide 1420 m-s, 1391 m, 1333 w-m, 1312 w-m, 1108 s, 994 m-s, 986 sh cm-1
n-Propyltriphenylphosphonium 1978 w, 1912 w, 1822 w, 1781 w, 1673 w, 1590 m-s, 1484 m-s, 1463 m, 1438 s,
bromide 1334 m, 1313 m, 1110 s, 1076 m-s, 994 m-s cm-1


alkyltriphenylphosphonium salts may be identified by careful analysis of the


The methyltriphenylphosphonium salts all appear to have a characteristic

strong absorption at 895-900 cm-1 which is missing in the ethyl, allyl and propyl


The allyltriphenylphosphonium salts have the double bond stretching frequency
at approximately 1635-1640 cm through which they may be identified.

The ethyl and propyltriphenylphosphonium salts have no special absorption

bands by which they may be identified.

The infrared spectra were taken on the Beckman 1R 10 as 0. 25 M solutions

in chloroform in a 0.175 mm cell. The reported range is from 2000 to 800 cm-1
in chloroform in a 0.175 mm cell. The reported range is from 2000 to 800 cm



The purpose of this research was to investigate factors influencing the

stereochemistry of the Wittig reaction. Based on this work the following con-

clusions may be drawn: (1) There is no observable solvent effect on the stereo-

chemistry of the reaction under the experimental conditions used, although these

observations are contrary to the results reported by other investigations;

(2) Reaction temperature has no effect on the stereochemistry of the reaction

although it has a considerable effect on the yield of product; (3) Even though the

reaction is extremely fast at low temperature, reaction time does not affect the

stereochemistry of the reaction; (4) The relative concentration of reactants,

contrary to the reports of other investigators, has no effect on the stereochemistry

of the reaction, although by proper choice of concentrations, high yields of

products can be obtained; (5) The nature of the substituents, particularly those

on the ylide, has a profound effect on the stereochemical outcome of the reaction;

(6) There appears to be either a cation or an anion effect influencing both the

ylide and the stereochemistry of the system studied, however, the nature of this

effect is too complex to explain with the existing data; and (7) No 1,4-addition of

the methylene ylide occurred with crotonaldehyde. A proposal to explain the

observations concerned with substituent effects is offered.


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4. A. W. Johnson and R. B. LaCount, Chem. & Ind. (London), 1959, 52.

5. G. Wittig and U. Schollkopf, Ber., 87, 1318 (1954).

6. G. Wittig, H. Weizmann and M. Schlosser, Ber., 94, 676 (1961).

7. S. Fliszar, R. F. Hudson and G. Salvadori, Helv. Chim. Acta., 46 1580

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10. L. D. Bergelson and M. M. Shemyakin, Tetrahedron, 1, 149 (1963).

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12. R. Ketcham, D. Jambotkar and L. Martinelli, J. Org. Chem., 27, 4666

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Butler, J. Org. Chem., 28, 372 (1963).

23. G. B. Butler and C. F. Hauser, Unpublished results.

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25. H. E. Zaugg, J. Am. Chem. Soc., 83 837 (1961).

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27. D. Seyferth, J. K. Heoren and W. B. Hughes, Jr., J. Am. Chem. Soc., 34
1764 (1963).

28. G. W. Fenton and C. K. Ingold, J. Chem. Soc., 1929, 2342a.

29. A. J. Speziale and K. W. Ratts, J. Am. Chem. Soc., 84, 854 (1962).

30. H. C. Brown and H. L. Berneis, J. Am. Chem. Soc., 75, 10 (1953).

31. D. E. Bissing and A. J. Speziale, J. Am. Chem. Soc., 87, 2783 (1965).

32. L. D. Bergelson and M. M. Shemyakin, Private communication to H. O.
House et al., J. Org. Chem., 29, 3327 (1964) Footnote (8).

33. H. H. Inhoffen, K. Bruckner, G. F. Domagk and H. Erdmann, Ber., 88,
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34. J. P. Freeman, Chem. & Ind., 1959, 1254.

35. F. Bohlmann, Ber., 89 2191 (1956).

36. The Merck Index of Chemicals and Drugs, 7th Ed., Rahway, New Jersey,
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37. Ibid., p. 1063.

38. Ibid., p. 1052.

39. Ibid., p. 352.

0. :-' p. 37

5. p.

6. R. L. Le-Isi:.;er and J G.Traynham, J. Am. Chem. Soc., 70, 2S13 (1948).

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(3) 957.

52. S. W. Fer-is, Handbook of Hydrocarbons, Academic Press, Inc., New York,
Y., 1955, p. 21-23.

53. L. J. Bellamy, The Infrared Soectra of Complex Molecules, John Wiley &
Sons, Inc., New York, N. Y., 1955, p. 45-48.

54. R. S. Rasmiussen and R. R. Bar.atain, J. Chem. Phys., 15, 131 (1947).

55. C. W. Kamienski and D. L. Esmay, J. Org. Chem., 25, 115 (1960).


Jerome Thomas Kresse was born December 29, 1931, at Buffalo, New York.

He obtained his elementary and secondary education in Buffalo graduating from

Buffalo Technical High School in 1949. He attended the University of Buffalo from

1949 until 1953. After spending two years in the United States Army he worked

for 18 months as a technician with the Silicone's Division of Union Carbide Corpora-

tion in Tonawanda, New York. In April 1957 he entered Michigan State University

and received the degree of Bachelor of Science in Chemistry in June 1958. He

entered the Graduate School of the University of Florida in September 1958.

The author is a member of Alpha Chi Sigma, Professional Chemistry

Fraternity and the American Chemical Society. He is married to the former

Joan Margaret Schmid and is the father of two children, Jennifer Ann and

Michael Jerome.

This dissertation was prepared under the direction of the chairman
of the candidate's supervisory committee and has been approved by all members
of that committee. It was submitted to the Dean of the College of Arts and
Sciences and to the Graduate Council, and was approved as partial fulfillment
of the requirements for the degree of Doctor of Philosophy.

December 18, 1965

/--^ ---

Dean, College of Arts and Sciences

Dean, Graduate School

Supervisory Committee:


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