REACTIONS OP N-(SUBSTITUTED)PHTHALIMIDES

WITH n-ALKYLAMINES

APPROVED:

Major Professor

Mirî n Professor

Director of the Department of Chemistry

Dean o'f the Graduate School

REACTION OF N-(SUBSTITUTED)PHTHALIMIDES

WITH n-ALKYLAMINES

THESIS

Presented to the Graduate Council of the

North Texas State University in Partial

Fulfillment of the Requirements

For the Degree of

MASTER OF SCIENCE

by

D. Pat Johnson, B. A.

Denton, Texas

August, 1970

PREFACE

The author would like to thank the Samuel Roberts

Noble Foundation, Incorporated of Ardmore, Oklahoma for

providing financial support of this study.

Pat Johnson

July, 1970

iii

TABLE OF CONTENTS

LIST OF TABLES

LIST OF ILLUSTRATIONS . .

Chapter

INTRODUCTION . .

EXPERIMENTAL . .

Organic Syntheses

I.

II.

N-(Substituted)phthaiimides N,N'-(Disubstituted)phthalamides Ethyl 3-phthalimidopropionate Ethyl 3-{o-[N-(substituted)carbamoyl]-

benzamido} propionates . . . .

Quantitative Analysis

Study of Melting Points of Mixtures Spectral Analysis by Ultraviolet Spectral Analysis by Infrared

III. RESULTS AND DISCUSSION

BIBLIOGRAPHY

Page v

vi

1

5

5

5 6

7

7

11

11 13 14

21

33

IV

LIST OF TABLES

Table ' Page

I. N-Benzyl-N'-(substituted)phthalamides 8

II. N-n-Decyl-N'-(substituted)phthalamides . . . . 9

III. N-n-Butyl-N'-(substituted)phthalamides . . . . 10

IV. Ethyl 3-{o-[N-(substituted)carbamoyl]-benzamido}propionates 12

v

LIST OP ILLUSTRATIONS

Figure Page

1. Reaction of 3-phthalimidopropionyl chloride

with n-alkylamines 2

2. Infrared spectra of N-benzylphthalimide . . . . 16

3. Infrared spectra of N-benzyl-N'-n-pentyl-phthalamide 17

4. Infrared absorption at the 1400, 1670, and 1720 cm"1 peaks for samples containing varying ratios of N-benzylphthalimide and N-benzyl-N'-n-pentylphthalamide . 18

5. Infrared spectra of the resulting reaction mixture of N-benzylphthalimide and N-benzyl-N'-n-pentylphthalamide 19

6. Preparation of N,N'-(disubstituted)phthalamid.es . 22

7. Preparation of ethyl 3-fo-[N-(substituted)carbam-oyl] benzamido/ propionates 22

8. Yields of the reactions of N-benzylphthalimide with different n-alkylamines to produce N-benzyl-N'-(substituted)phthalamides . . . 25

9. Yields of the reactions of N-n-butylphthalimide with different n-alkylamTnes to produce N-n-butyl-N'- (substituted)phthalamic!es . . 25

10. Yields of the reactions of N-n-decylphthal-imide with different n-aTkylamines to produce N-n-decyl-N' -Jsubstituted)-phthalamides 27

11. Per cent cleavage of ethyl 3-phthalimido-propionate in reaction with different n-alkylamines 27

12. Proposed mechanism for the base catalyzed cleavage of an N-(substituted)phthalimide . 29

vi

CHAPTER I

INTRODUCTION

An investigation of the reaction of an N-(substituted)-

phthalimide with various alkylamines indicated that certain

N-alkylphthalimides reacted with alkylamines to form the

N,N'-(disubstituted)phthalamides in good yields (2). For

example, N-methylphthalimide interacted with methylamine to

produce the N,N'-dimethylphthalamide. This reaction was

demonstrated to be reversible, as was the corresponding reac-

tion producing N,N'-diethylphthalamide (3).

In a contemporary study involving a series of reactions

between alkylamines and 3-phthalimidopropionyl chloride, it

was observed that lower molecular weight n-alkylamines

cleaved the imide bond and then condensed with the resulting

acyl group to form diamides, wheras long chain n-alkylamines

did not appear to effectively cleave the imide bond (1), as

indicated in the accompanying equations of Figure 1.

This latter study suggested that n-alkylajnines contain-

ing more than five or six carbons did not behave as nucleo-

philes to attack a carbonyl as strongly as n-alkylamines

containing fewer than six carbons. It was suggested that this

effect might be explained by a steric hindrance in the case

of the long n-alkylamines. However, examination of a model

1

i3-> 0 II

0 0

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0

R= ethyl, n-butyl, and n-pentyl

R'= n-heptyl and n-nonyl

Pig. l--Reactions of 3-phthalimidopropionyl chloride with n-alkylamines.

of an N-(substituted)phthalimide, constructed with Leybold *

atom models, indicated sufficient free area around the car-

bony 1 groups of the phthalimide to permit attack by a large

alkylamine. The initial purpose of this study was to deter-

mine, then, if steric problems would account for the difference

in the products obtained in the reaction of the N-(substitu- ~-

ted)phthalimide with low and high molecular weight amines.

In an effort to determine if the length of the alkyl

group of amines would affect their reactivity with other

N-(substituted)phthalimides, several different alkylamines

were interacted with a variety of N-(substituted)phthalimides.

A comparison of the yields of the reaction products was made

after a reaction time of one hour. Subsequently, the maximum

Leybold Atom Models, according to Stuart and Briegleb, LaPine Scientific Company.

yields of products were determined after the various reac-

tions had been permitted to reach equilibrium. By varying

the length of the alkylamine, and by using different N-

substituents on the phthalimide nucleus, the effect of chemi-

cal structure on the yield of product after cleavage of the

phthalimide system was determined.

CHAPTER BIBLIOGRAPHY

1. Clifton, Gil, Sarah R. Bryant, and Charles G. Skinner,

Arch. Biochem. Biophys., 87, 523-^ (1970).

2. Spring, P. S., and J. C. Woods, J. Chem. Soc., 626

(1945).

3. Spring, F. S., and J. C. Woods, Nature, 67, 75̂ - (19^6).

CHAPTER II

EXPERIMENTAL

Organic Syntheses

Melting points of all compounds were determined on a

Thomas Hoover Capillary Melting Point Apparatus. Infrared

spectra were obtained on Vfo solutions in chloroform, with

a Perkin-Elmer Model 237 Grating Infrared Spectrophotometer.

Ultraviolet spectra were obtained on 0.05 mg/ml solutions

of the compounds in 95$ ethandl, with a Beckman DB Spectro-

photometer. Elemental analyses were obtained for carbon,

hydrogen, and nitrogen content with an F and M Scientific

* Model 185 Gas Chromatographic Analyzer.

N-(Substituted)phthalimides. A mixture of 0.20 mole

phthalic anhydride (29.6 g) and 0.20 mole of the appropriate

amine was heated under reflux in an oil bath at 150°C with

stirring for two hours. The resulting N-(substituted)phthal-

imide produced was recrystallized from 95$ ethanol to yield

white crystals. Additional recrystallizations were carried

out to obtain a constant melting point, and the final product

Elemental analyses were obtained in the analytical laboratory of the North Texas State University Chemistry Department through the technical assistance of Mrs. Delaney Blocker.

was dried in vacuo over CaCl^. Three different N-(substi-

tuted)phthalimides were synthesized for this study:

Melting Melting Reaction Product Point Found Point Reported

N-Benzylphthalimide 116°C 115-6°G (4)

N-n-Decylphthalimide 59-60°G 56°C (8)

N-n-Butylphthalimide 3^—5°C 34°C (9)

N,N'-(Disubstituted)phthalamides. Selected n-alkyl-

amines, containing from one to fourteen carbons, were reacted

with the previously synthesized N-(substituted)phthalimides.

Each of the reactions was carried out by dissolving 0.05 mole

of the appropriate N-(substituted)phthalimide in 50 ml diox-

ane and adding this solution dropwise to 0.05 mole of the

various n-alkylamines dissolved in 50 ml of a 1:1 mixture of

dioxane and water. The addition was carried out over a one-

hour period, with the reaction vessel being cooled in an ice

bath. Stirring was continued for an additional hour at room

temperature, after which the solvent was removed on a rotary

evaporator in vacuo at room temperature. An aliquot of the

reaction mixture was saved for later analysis to determine

the reaction yield under the specific reaction conditions.

The major quantity of product was recrystallized from

95$ ethanol, and the crystalline N,N'-(disubstituted)phthal-

a,mides were dried in vacuo over CaC^. Specific reaction de-

tails are summarized with analytical data of the products in

Tables I-III.

Ethyl 3-Phthallmidopropionate. This compound was syn-

thesized in a three-step reaction. 3-Phthalimidopropionic

acid was prepared by grinding together 74.0 g phthalic

anhydride and 44.6 g ^-alanine, and heating the resulting

mixture at 160°C over an oil bath for two hours. The re-

action mixture was then cooled, and the resulting solid

was recrystallized in 95$ ethanol to yield 85.6 g of pro-

duct with mp~ 151-2°C [reported mp= 151-2°C (4)]. 3-Phthal-

imidopropionyl chloride was prepared by heating under re-

flux 75.0 g phthalimidopropionic acid and 150 ml SOCI2 for

1.5 hours. After cooling, the solid material was recrystal-

lized from bgnzene and dried in vacuo to yield 17.7 g of

product with mp= 108-9°C [reported mp= 107-8°C (5)]. Finally,

the ethyl 3-phthalimidopropionate was synthesized by dissol-

ving 11.8 g of phthalimidopropionyl chloride in 50 ml dioxane

and adding an excess of ethanol in the presence of 8 ml

pyridine. The reaction was allowed to proceed for one hour

at 50°C, and there was recovered 5.3 g of product with mp=

72-3°C [reported mp=- 73°C (6)] .

Ethyl 3-fo-[N-(substituted)carbamoyl]benzamido}propionates.

This series of compounds was produced by reacting a solution

of ethyl 3-phthalimidopropionate in 25 ml dioxane with an

equimolar amount (0.02 mole) of the appropriate n-alkylamine

dissolved in 25 ml of dioxane-water. The reaction was allowed^

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to proceed with stirring for one hour in an ice bath and for

an additional hour at room temperature. The solvent was re-

moved by evaporation under a vacuum, and the resulting solid

material was dried over CaC^ in vacuo and, finally, re-

crystallized from 95% ethanol. Specific data on each of the

products are listed in Table IV.

Quantitative Analysis of Reaction Yields

In order to compare directly the relative effects of

different n-alkylamines on the cleavage and subsequent addi-

tion reaction with N-(substituted)phthalimides, it was nec-

essary to determine the per cent yield of the N,N'-(disub-

stituted)phthalamide in the crude reaction mixture. To

accomplish this end several different methods of quantita-

tive analysis of the crude material were examined. To deter-

mine the utility of each method, standard mixtures of the

N-(substituted)phthalimide and its corresponding N,N'-(di-

substituted)phthalamide were prepared in the ratios 3:1>

1:1, and 1:3. An intimate mixture was assured by dissolving

the weighed samples in 95$ ethanol. After removal of the

solvent, the residue was dried iri vacuo over CaC^.

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of each mixture was determined and compared with the melting

points of the pure N-(substituted)phthalimide and the pure

N,N'-(disubstituted)phthalamide. The resulting melting charac-

teristics were plotted versus the per cent of N,N'-(disub-

12

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stituted)phthalamide contained in the sample. An attempt was

made to correlate this melting point graph with melting point

data obtained from dried crude reaction products of the above

described experiments; however, this method of analysis proved

to be unsatisfactory. The various samples melted over too

large a temperature range to enable the establishment of a

suitable graph.

Spectral Analysis by Ultraviolet. Ultraviolet spectra

were obtained for the known mixtures and the two pure com-

pounds using 0.05 mg per ml solutions in 95% ethanol. N-

Benzylphthalimide showed absorption maxima at 29^ mix and at

about 220 mix. The pure N-benzyl-N'-(substituted)phthalamides

showed a single absorption maximum at 220 mp. with no appre-

ciable absorption at 29k mix. The known mixtures of the two

compounds showed both peaks, with the intensity of the 294-

mn peak increasing directly with the per cent of N-benzyl-

phthalimide in the mixture. By making a plot of the absorp-

tion at this wavelength versus the per cent of N-benzyl-

phthalimide in the sample, a graph was drawn from which the

per cent of product yield could be extrapolated, given the

ultraviolet spectra of a crude reaction product. This method

of determining reaction yields was satisfactory; however, a

similar method using infrared spectrometry was preferred be-

cause of greater precision of measurements of the absorption

peaks.

14

Spectral Analysis by Infrared. Infrared spectra of

the above known mixtures and pure compounds were obtained

on one-per cent solutions in chloroform. The spectra of

all the N-(substituted)phthalimides showed a strong absorp-

tion maximum at 1720 cm"1 which has been associated with the

stretching of the carbonyl of the imide group (1). An ab-

sorption peak was also observed at 1400 cm"1, owing to a

particular stretching mode of the five membered ring portion

of the phthalimide (6). The N,N'-(disubstituted)phthalamides,

on the other hand, showed a shift of, the carbonyl stretching

frequency down to 1670 cm"1 (7), and the absorption peak at

1400 cm 1 was not present in these compounds. The later data

are consistent with the phthalimide ring portion of the origi-

nal compound having been cleaved. Spectra of pure compounds

are reproduced in Figures 2 and 3.

The per cent absorption at 1400 cm"1, I670 cm"1, and

1720 cm"1 was subsequently plotted versus the per cent of

N,N'-(disubstituted)phthalamide present in the three known

mixtures as well as the two pure compounds. A curve was

drawn through the five absorption values, as indicated in

Figure 4. An aliquot of each crude reaction mixture was

reduced to dryness at the end of the reaction time, and the

resulting solid was analyzed directly to give a spectrum like

that in Figure 5. The absorption maximum of the sample at

1400 cm 1 was then compared with the standard absorption

15

curve at ikOO cm-"*" (Fig. 4), and the per cent product yield

was extrapolated from the graph. In a comparable manner,

the per cent yield was determined using absorption maxima

at 1670 and 1720 cm-"*". The three different per cent yield

measurements were then averaged to produce the reported data.

16

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CHAPTER BIBLIOGRAPHY

1. Abramovitch, R. A., J. Chem. Soc., 1415 (1957).

2. Fusier, Pierre, Ann. Chim. (Paris), Ser. 12, 5> 883-4

(1950).

3. Gabriel, S., Chem, Ber., 41, 243 (1908).

4. Gabriel, S., and Richard Otto, Chem. Ber., 20, 2227

(1887).

5. Hale, W. J., and E. C. Britton, J. Amer. Chem. Soc.,

41, 845 (1919).

6. Kitrizky, A. R., Quart. Rev. (London), 356 (1959).

7. Nakanishi, Koji, "infrared Absorption Spectroscopy-

Practical," Holden-Day, Inc., San Francisco, 1962,

p. 46.

8. Talvite, Y., Ann. Acad. Sci. Fennicae, No. 16, 26A,

1-94 (1927); Chem. Abstr., 21, 2658 (1927).

9. "Vanags, Gustav, Acta Univ. Latviensis, Ser. 4, No. 8,

^05 (1939); Chem. Abstr., 34, 1982 (1940).

20

CHAPTER III

RESULTS AND DISCUSSION

In a contemporary synthetic study involving the reac-

tion of selected alkylamines with 3-phthalimidopropionyl

chloride, it was observed that certain amines reacted with

the halide function, while selected lower homologs also

cleaved the phthalimido group to produce a diamide derivative

(2). As illustrated in Figure 1, Chapter I, interaction of

the amine with the acyl halide occurred in every ca.se; how-

ever, the cleavage of the phthalimido ring system was pro-

nounced only when the alkylamine used was ethyl-, n-butyl-,

or n-pentylamine. The only product recovered in the reactions

with long chain amines and 3-phthalimidopropionyl chloride

was the corresponding N-phthalimidopropionamide derivative.

In an effort to investigate the effect of chain length

of the n-alkylamine upon the rate and degree of cleavage of

N-(substituted)phthalimides, four series of reactions were

carried out with different N-(substituted)phthalimides.

Preparation of these N-(substituted)phthalimides, and sub-

sequent reactions of the phthalimides with alkylamines are

illustrated in Figures 6 and 7. The latter reaction was carried

out by adding a solution of the N-(substituted)phthalimide,

over a one-hour period, to a solution of the alkylamine in an

21

22

0 0 II fi Cx CN

0 + R-NHo >- fi T N-R lo , , c/ ^ C

X

II II 0 J. 0

0 II

aC-NH-R C-NH-R' II 0

Pig. 6—Preparation of N,N'-(disubstituted)phthal-amides.

0 0 " 0 " 0 C Jj G

|'f^f 4- H2N-CH2CH2C-OH j p T ^N-CH2CH2C-OH •* ̂ C c

|l I! 0 . 0 II

0 11 0 n • V

reflux fi^r" ii + soci2 ^n-ch2ch2c-ci

III

0

c ? Ill + CH^CH?OH —

5 0 >- [\ X NN-CH9CH9C-OC0Hr-3 i b a s e

23

ice bath. The reaction was continued one more hour at room

temperature, after which time the product yield was deter-

mined. Then to establish whether the reaction was at equi-

librium, each reaction was run for a longer time. Aliquots

of the reaction solution were taken at different time inter-

vals during the course of the reaction. These aliquots were

dessicated, infrared spectra were obtained on one-per cent

solutions in chloroform, and the per cent product yield was

extrapolated from the appropriate curve as described in

Chapter II. The per cent product yield was plotted versus

reaction time for each reaction, and when the slope of these

curves reached zero, the per cent yield at equilibrium was

determined. Bar graphs of reaction yields at two hours reac-

tion time are shown for each series of reactions in Figures

8-11, along with the maximum attainable yields of the same

reactions run for extended times.

N-Benzylphthalimide was reacted with each n-alkylamine

containing up to ten carbons, and the reaction yields were

determined after one hour and after several hours, when the

reaction was presumed to be at equilibrium. After one hour

of reaction time at room temperature, all of the amines were

found to have cleaved the phthalimide to some extent, as

evidenced by the recovery of the corresponding N-benzyl-

N'-(substituted)phthalamides. The yields varied from 37 to

47 per cent except in the case of the methyl-, n-nonyl-, and

n-decylamines, which produced appreciably higher yields

24

(Fig. 8). Each of the reactions was repeated using a twelve

to eighteen hour reaction time in an effort to establish

maximum yield. These maximal yields, also shown in Figure 8,

increased directly from about 65 to 85 per cent as the number

of carbons in the amine increased from two to seven. Methyl-

amine, n-nonylamine, and n-decylamine reaction products were

each in the range of about 79 per cent. These results, un-

like those reported in the earlier experiments with 3-phthal-

imidopropionyl chloride (2), indicate that long chain amines

do possess the ability to cleave the phthalimido group and

form the corresponding benzamide derivative. Further, it is

interesting to note that the longer chain amines gave higher

yields of product than the lower homologs (Fig. 8).

In an effort to determine if the N-substituent on the

phthalimide structure has significant influence on the reac-

tion products, several selected amines were subsequently re-

acted with N-n-butylphthalimide. This particular compound

was chosen because it has approximately the same steric size

as the 3-phthalimidopropionyl chloride. The product yields

after one hour of reaction at room temperature increased from

30 per cent for the propyl derivative to 80 per cent for the

tetradecyl derivative, as shown in Figure 9» This graph also

represents yields at longer reaction times in which the reac-

tion is presumed to be yielding the maximum amount of product.

As was previously observed in the case of the n-alkylamine

25

100

60

r

26

reactions with N-benzylphthalimide, the longer chain amines

cleaved the phthalimide group to give a higher yield of prod-

uct than did the shorter chain amines. Figure 9 indicates

that the reactions with the longer chain amines reached

equilibrium more quickly than did those reactions with the

shorter chain a.mines. Methylamine cleaved the phthalimide,

but the crystalline product was proven by elemental analysis

not to be the N-n-butyl-N'-methylphthalamide.

In order to eliminate the possibility of the aromatic

system in the N-benzyl derivative being a deciding factor,

n-decylphthalimide, having a long chain substituent of com-

parable steric effect, was chosen as a model system to inter-

act with selected n-alkylamines in a comparable fashion.

The resulting phthalimide derivatives are approximately iso-

steric with several of the N-(substituted) 3-phthalimidopro-

pionamides obtained in the previously reported study using

3-phthalimidopropionyl chloride. Under the reaction con-

ditions utilized in this study, interaction of ethyl-, n-pro-

pyl-, and n-pentylamines produced less than 30 per cent

yields of the N-n-decyl-N1-(substituted)phthalamides. In con-

trast, the n-octyl-, n-decyl-, and n-tetradecylamines reacted

to produce 65 to 95 per cent yields of the anticipated prod-

ucts when the reaction time was increased to about ten hours

(Fig. 10). A longer reaction time was required to reach

maximum yields in the N-n-decylphthalimide series than in

comparable reactions using N-n-butylphthalimide.

27

100

8o

3 60 * .

20

0

1

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Number of Carbons in Alkylamine

Fig. 10--Yields of the reactions of N-n-decylphthal-imide with different n-alkylamines to produce N-n-decyl-N' -(substituted)phthalamides.

100

80

13 6 0 iH CD

* 4o

20

0

p

L 2 3 4 5 6 7 8 9 10

Number of Carbons in Alkylamine

Pig. 11—Per cent cleavage of ethyl 3-phthalimido-propionate in reaction with different n-alkylamines.

28

Finally, 3-phthalimidopropionate was chosen as a model

reactant for the amine cleavage studies because of its sim-

ilar electronic arrangement to that of the corresponding

N-(substituted) 3-phthalimidopropionamides. The interaction

of ethylamine with ethyl 3-phthalimidopropionate yielded the

corresponding ethyl 3-(o-[N-(substituted)carbamoyl]benzamido}-

propionate in about a 75 per cent yield. The products of

similar reactions with n-pentyl- and n-nonylamines were

shown by elemental analysis not to be the expected ethyl

3-{o-[N-(sub s tituted)c arbamoyl]ben zamido} prop ionate s. Anal-'

yses suggested that these expected products were present as

a mixture with the corresponding N,N'-(disubstituted)phthal-

amide derivatives.

In a recent study of the reaction of n-butylamine with

ethyl formate, the mechanism was proposed to involve a base

catalyzed acyl cleavage involving a tetrahedral intermediate

(2). By direct analogy, the present reaction of an N-(sub-

stituted)phthalimide with an n-alkylamine might follow a

similar mechanism, as indicated in the accompanying reactions

of Figure 12. Assuming equilibrium is established in all the

reactions, the factor determining the product distribution in

this mechanism would involve the relative ease of cleavage

of the two C-N bonds represented in III. If the C-NR bond is

less stable, product IV results; however, if the C-NR' bond is

more easily cleaved, the starting material I would be the re-

sulting reaction component. If this mechanism is correct, the

29

0 0 II II

N-R 4- R'-NHo . \\ T N-R a IX -r X, a U 2 _ if i"NH2R' o 0_+ c

II

0 II

II 4- base i ̂ ^N-R.

f^NHR' 0_

III

0

^ i - N H - R III + BH s- if B"

•C-NH-R' ii 0

IV

Fig. l2--Proposed mechanism for the base catalyzed cleavage of an N-(substituted)phthalimide.

product distribution would depend on the relative electron-

attracting ability (or acidity) of the -NR-CO- and -NHR1

groups. An amide group is appreciably more acidic than an

amino function, amides having pK fs about 10-11 pK units Cb

lower than amines (3). Accordingly, it would be anticipated

that the diamide would be the favored product, and the ex-

perimental results confirm this hypothesis. The consistently

higher yields in the N-benzylphthalimide reaction sequence

may be explained by the slightly greater acidity of the

30

-NR-C0- group when R is benzyl. Benzylamine has a pKa about

•K*

1.3 pK units below that of n-butyl and n-decylamine ; thus,

the acidity of the -NR-CO- group is greater when R is benzyl

than when R is n-butyl or n-decyl in the respective N-(sub-

stituted )phthalimides.

A study of the reversibility of the reaction to form

the N,N'-(disubstituted)phthalamides revealed that the reac-

tion reverses only in the presence of a base. The mechanism

illustrated in Figure 12 includes this factor. However,

reaction of the N,N'~(disubstituted)phthalamide in base to

yield the N-(substituted)phthalimide points out the need to

indicate reversibility of the second and third reaction steps

in the mechanism.

Since the alkylamine reactants served also as the ba,se

catalysts in all the reactions run in this study, and since

all of the amines used had about the same pKa (3,̂ - 5)> the

reason for the longer chain amine reactions reaching maximal

yields faster than the others is not clear. It appears,

especially in the series of N-n-decylphthalimide reactions '

with alkylamines, that the longer chain substituted diamides

precipitate out of the reaction more quickly, thereby shifting •X* Taken from Robert C. Weast, "Handbook of Chemistry and

Physics," 49th ed, The Chemical Rubber Co., Cleveland, Ohio, 1968, pp. D-87-8.

31

the equilibrium toward higher product yields.

Results obtained in this study suggest that steric hin-

drance of the attacking alkylamine is not a primary factor

in determining yields of products. Amines of six or more

carbons in chain length reacted to produce yields greater

than lower homologs. Nor does the basicity of the attacking

alkylamine appear to be a significant factor affecting the

yield in these reactions since all alkylamines used had

comparable pK values (3A>5)- ln contrast, the N-sub-

stituent group already present in the phthalimide nucleus is

a factor as evidenced by the differential activities in the

N-n-decylphthalimide series, as well as by the previously re-

ported differences in cleavage rates of N-phthalimido-jS-

alanyla,mides (2).

The results obtained suggest that the basicity of the

amine of the phthalimide-N-substituent is an important factor

determining the rate of amine cleavage of the various N-(sub-

stituted )phthalimide derivatives. Accordingly, it would be of

interest to prepare a series of N-(substituted)phthalimides

containing substituent groups with significantly different

electronic character. For example, a series of the N-phenyl-

phthalimides (phthalanils) containing nitro, chloro, and

methyl ring substituents would have appreciably different pK cl

values, and a study of the effect of amine cleavage of these

phthalimide structures should prove to be interesting, in

light of the results already obtained.

CHAPTER BIBLIOGRAPHY

1. Bunnett, J. F., and George T. Davis, J. Amer. Chem. Soc.,

82, 666 (I960).

2. Clifton, Gil, Sarah R. Bryant, and Charles G. Skinner,

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3. Damsgaard-Sorensen, P., and A. Unmack, Z. Ph.ys. Chem.,

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32

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