Fpl/Aws. Liiufuuu/ Adviser I

THE IONIZATION CONSTANTS AND ESTERIFICATION RATES OF SUBSTITUTED PHENYLPROPIOLIC ACIDS

DISSERTATION Presented In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University

STEWART HENRY MERRILL, B.S. The Ohio State University

1953

Approved by:

/fPl/AwS. LiiUfUUU/ Adviser i

ACKNOWLEDGEMENT To Dr. Melvin S. Neman -the author wishes to express his gratitude for the suggestion and guidance of this work and for inspiration which -will serve throughout his career in chemistry.

\ s : : r ? 8 0 li

TABLE OP CONTENTS

Page I. INTRODUCTION 1

A. P u r p o s e ...... 1 B. Plan ...... 1 C. Background ...... 1 D. Present W o r k ...... 8 II. EXPERIMENTAL 11 A. Preparation of A d d s ...... 11 (1) Introduction ...... 11 (2) Phenylpropiolic A c i d ...... 11 (3) p-Chlorophenylpropiolic A c i d ...... 14 (A) nr*Chlorophenylpropiolic A c i d ...... 15 (5) o-Chlorophenylpropiolic Acid 17 (6) p-Nitro^.ienylpropiolic A d d ...... 18 (7) »-Nitrophenylpropiolic A c i d ...... 21 (8) o-Nitrophenylpropiolic Acid ...... 23 (9) p-Methoxyphenylpropiolic A c i d ...... 25 (10) m-Methoxyphenylpropioli c Acid ...... 26 (11) o-Methoxyphenylpropioli c A d d ...... 28 B. Purity of the Adds ...... 30 C. Preparation of Esters ...... 31 D. Ionisation Constants ••.••.....••• 32 E. Kinetic R u n s ...... 33 (1) Apparatus ...... 33 (2) Catalyst Solution ...... 34 (3) The Experimental R u n ...... 34 F. Spectra ...... 35 III. CALCULATIONS AND RESULTS 36 A. Ionization Constants ...... 36 B. Rates of Esterlflcation ...... 39 (1) Rate Constants...... 39 (2) Activation Energies and Entropies of Activation ...... 42 IV. DISCUSSION 45 A. Ionization Constants 45 B. Esterlflcation Rates ...... 48 C. Energies and Entropies of Activation • • • * • 54 D. Spectra ...... 55 ill

TABLE OP CONTENTS (CCNT.)

V. S U M M A R Y ...... 60

APPENDIX ...... 61 AUTOBIOGRAPHY...... 93 iv

TABLES

Pag* Table I Berger*a Parameter of Sterlc Effect ...... 3 Table II Size of Sterlc Effect According to Kindler ...... • • 4 Table III Polar and Sterlc Substituent Constants for Ortho Substituents 7 Table IV Melting Points and Neutral Equivalents of Substituted Phsnylpropiollc Acids 31 Table V Physical Constants of Ethyl Esters of Substituted Phenylpropiollc Adds 32 Table VI Ionization Constants of Substituted Phenylpropiollc Acids in 35)5 Dloxane (wt.) at 2 5 * ...... 33 Table VII Esterlflcation Rate Constants of Substituted Phenyl- propiolic Acids In Methanol Catalyzed by Hydrogen Ions (ca. 0.01N) 42 Table VIII Energi®® and Entropies of Activation for the Add- Catalyzed Esterlflcation of Substituted Phenyl— propiolic Adds 25-35* ...... 44 Table IX Comparison of Ionization Constants of Ortho— and Para- Substituted Adds in the Phenylpropiollc and Cinnamic Series ••••••• ••...*• ...... 4 6 Table X Ultraviolet Absorption Maxima of Ethyl Esters of Phenylpropiollc Adds . • ...... 57 FIGURES Pag* Figure I Hamnett Relationship between Log k and Log K/Kq for Substituted Phenylpropiolie A d d s ...... * • 50 Figure 2 Hamnett Relationship for the Esterlflcation of Substituted Benzoic Acids ...... 51 Figure 3 Hamnett Relationship for the Alkaline Saponification of Substituted Ethyl Cinnamates ...... 51 Figure A Scale Diagram of o-Nitrophenylpropiolic Add • • • • • 53 Figure 5 Ultraviolet Spectra of Ethyl Esters of Phenyl propiollc A d d s 56 - 1-

THE IONIZATION CONSTANTS AND ESTERIFICATION RATES OF SUBSTITUTED PHENYLPROPIOLIC ACIDS

I. INTRODUCTION A. Purpose The purpose of the present work was to find a benzene side chain which would be free from steric effects^" of ordinary substituents in the ortho position. A method would then be available for correlating the influence of ortho substituents with meta and para substituents on the side-chain reactivity. B. Plan Phenylpropiolic acid appeared to be a satisfactory structure for this purpose. The plan was to determine the ionization constants and the esterification rate constants of ring-substituted derivatives of this acid. steric effects could be presumed absent if a logarithmic nlot of the rate data against the ionization constants In accordance with the Hammett equation showed that the data of the ortho—substi tuted acids as vrell as the meta- and para-substituted acids obey a straight-line relationship. C. Background Thotigh steric effects in organic reactions have been recognized and studied extensively for about sixty years, few attempts have been made to separate ouantitatively the steric contribution and the polar

1. The term ITsteric effect” as used throughout this work includes all effects such as bulk interference, field effects, etc. that are due to the proximity in space of two .groups on a molecule. - 2- or purely electrical contribution which combine to influence reactivity. This is true partly because only in the last fevr years has any great progress been made in the understanding of either of these effects and partly because the number of structural types for which a suitable scheme can be devised for observing one or both of the influences separately is limited. The effect of nuclear substituents on the reactivity of benzene derivatives has been widely studied. Meta and para substituents are generally recognized to exert solely electrical effects on the reacting side chain. Ortho substituents combine a steric effect, sometimes called ortho effect, with the electrical effect. Consequently, quanti tative knowledge of either the steric effect or the electrical effect of an ortho group is difficult to obtain. In the monoraolecular hydrolysis of benzyl chloride derivatives and the alkaline saponification of substituted ethyl benzoates Berger^" assumed the polar effect of an ortho substituent to be equal to the polar effect of the same substituent in the para position and attributed the difference in reaction rates to a steric effect. He calculated a steric effect factor u» from the expression K - K o P where Kq and Kp are the rate constants of the ortho- and para-sub stituted reactants respectively. The « values for halogen deriva-

1. G. Berger, Rec. trav. chim., 46. 541 (1927)* tives are listed in Table I. The conclusion was that the steric

Table I Berger1s Parameter of Steric Effect

Substituent to CO Benzoyl Chloride Ethyl Benzoate Hydrolysis Saponification o—Cl 1.75 1.33 o-3r 1.75 1.98 o-I 1.66 2.92 effect of the halogens was constant for the hydrolysis of benzyl chloride while the steric effect increased with the size of the substituent in ethyl benzoate saponification. However, the con clusions deoend upon the validity of the premise that the difference in rate of the ortho- and nara-substituted reactants is due only to a steric effect, and the truth of this assumption is not known. Only when steric effects have been shown to be absent can the elec trical influence of an ortho substituent be measured for correlation with the influence of the substituent in the nara position. Kindler^ compared the alkaline saponification of substituted ethyl benzoate with the saponification of substituted ethyl cinnamates. He considered the saponification of cinnamates to be unhindered by ortho substituents and calculated a value for the steric effect in the saponification of each ortho—substituted benzoate. He defined the size of the steric effect to be the ratio k^/kj^ where is the rate constant of saponification of a substituted aromatic ester and

1 Kindier, Ann.. A6A. 278 (1928) and is the rate constant the ester would give if no steric effect were oresent. The known rate gave k^, and k^ was calculated from an emnerical relationshin as being proportional to the square of the saponification rate constant of the correspondingly substituted cinnamate. The results, Table II, nive the size of the steric effect for ortho—substituted ethyl benzoate as the ratio v v

Table II Size of Steric Effect According to Kindier

Substituent kh km kh^km o-F 0.272 0 .2 6 8 1 o-Gl 0.194 0.094 2 o-Br 0.461 0.093 5 o-I 0.311 0.041 7.5 o-N02 3.085 0.280 11

Kindlerfs assumntion that the saponification of ortho—sub stituted cinnamates is not subject to an ortho effect is the foundation of this treatment. This assumption was undoubtedly use ful for oualitative comparison of ortho substituents, but for a quantitative correlation it should be soundly established. Later it will be shown that ortho effects are not absent in cinnamate saoonification. Hith the advent of the Hamnett eauation^ a method became available for distinguishing the existence of steric effects not

1. L. P. Hammett, tJ. Am. Chan. Soc.. 59, 96 (1937). See also L. P. Hammett, "Physical Organic Chemistry", McGraw- Hill Book Co., Inc., New York, N. Y., 1940, n. discemable by ordinary chemical observations. The eouilibrium and rate constants of nearly all the side—chain reactions of meta— and nara-substituted benzene derivatives obey the linear relationship

log k » yo log k* + A in which k and k* are two rate or equilibrium constants, or one of each, and and A are constants. The form of the equation which is generally used is log k/kQ - yo

dCiLds.

S log K/Kq

is the ionization constant of benzoic acid, and K is the ionization constant of the substituted benzoic acid. The choice of the standard reaction was entirely arbitrary. Any other side chain reaction for which sufficient data are available would be satisfactory. Inasmuch as the Hammett equation applies to meta and oara sub stituents it is a relationship only of electrical effects. The value - 6 - of a and k, a are affected by steric factors. (log k/k0)B - (log lc/ko)A - E ^

The terms are those defined for the Hammett equation. The subscripts B and A refer to base— and acid-catalyzed hydrolysis of the same

1. H. Taft, Jr., J. Am. Chem. Soc., 74, 2120 (1952); _7£, 4231 (1953). ester. The f> values are those obtained from the corresponding reaction series of meta— and para—substituted benzoates. The sub stituent constant E ^ depends only on polar factors even when applied to ortho-substituted reactants. Another substituent constant Es which is a measure of the steric effects of an ortho—substituent can then be obtained from the equation

log k/kQ ■ ^ E r + Es

Listed in Table TIX are TaftTs E v and E s values for ortho substituted benzoates for comparison with HammettTs Q* values for

Table III Polar and oteric Substituent Constants for Ortho Substituents

tituent 0—Position p—Position E

D. Present Work In this wjrk phenylpropiolic acid and its monosubstituted chloro, nitro, and methoxy derivatives in the three ring positions were synthesized. The ionization constants and the rates of acid-catalyzed este ification in methanol were measured. These data were tested in the Hammett eouation log k/kQ - yOlog K/K0 by plotting log k/kQ against log K/RQ. In this case kQ is the esterlflcation rate of phenylpropiolic acid and k is the rate of a substituted ohenylpropiolic acid; KQ and J? are the corresponding ionisation constants. The meta and para derivatives were expected to conform to the equation as indicated by the points corresponding to them luring in a straight line. If the points on the plot corresponding to the ortho derivatives lie on the same line then steric effects can be considered absent from these reactions of ortho-substituted phenyl— propiolic acids. In this attempt to find a benzene side chain not subject to ortho ef 'ects the choice of phenylpropiolic acid was based on the particular geometrical features of the ethynylene group (-C*C-). This group is

* 1 linear and coplanar with the ring, and its special requirements are small compared to an ethylene group. A reactive function on the end of the ethynylene group away from the ring should be out of range of any ordinary ortho effect.

1. J. Robertson and I. Woodward, Proc. Roy. Soc., A164. 436 (1938). — 9 -

The acid-catalyzed esterlflcation of the phenylpropiolic acids in methanol was chosen for the kinetic studies because of its adaptability to easy experimental procedure. This reaction proceeds at a convenient rate and is easily followed by titration. The alkaline hydrolysis of the ethyl esters was considered for the kinetic studies, but these esters saponify too rapidly for accurate measurement. It should be mentioned that the Hammett values based on the ionisation of benzoic acids were not suitable for this work, because the ionization of ortho—substituted benzoic acids is known to be subject to steric effects.1 Since the choice of a reaction for the determination of substituent constants (log K/Kq) is arbitrary ionization of phenylproDiolic acids is quite acceptable and may be free of ortho effects. The determination of rate constants at two temperatures, 25° and 35*, allowed the calculation of energies and entropies of activation for the esterification of substituted phenylpropiolic acids. The advantage of thi s work over previous attempts to separate steric and electrical effects in ortho-substituted benzene derivatives is in the proposal to eliminate the steric effect entirely and to have a direct method of showing whether or not it is eliminated. If successful, the electrical influence of an ortho substituent wotfLd be determined directly for comparison with the substituent in the other ring nositions. Related substituent constants of the Hammett type

1. J. F. J. Dippy, et. al.. J_. Chem. toe., 1121 (1937). - 10 - would -then be available for substituents on all three ring positions* - 11 -

II. EXPERIMENTAL

A. Preparation of Acids (1) Introduction. The primary object of the synthetic work was the preparation of pure reagents. Consequently high yields were sacrificed to some extent for the sake of purity. The general synthetic route toward the substituted phenylpropiolic acids began with the correspondingly substituted benzaldehyde. The sequence of steps is given below. If the dehydrobromin&ting agent did not saponify the ester this was done in a separate step. CH2(C02H), 1. C2H50H x c 6h *-c h o ------x c 6h ^-c h «ch -c o 2h ------2. Br2

XC6H^-CHBr-CHBr-C02C2H5 -- -— ---- XC6H*-C«C-C02C2H5

------XC6H^-C-C-C02H

(2) Phenylpropiolic acid. A solution of 115 g. (0.654 mole) of ethyl cinnamate in 250 ml. of methylene chloride was cooled to

15° in a three-neck flask. From a dropping funnel 105 g. (O.6 5 6 mole) of bromine dissolved in 75 ml. of methylene chloride was added slowly with stirring. About eight hours were required for the bromine up take, and the mixture was allowed to stand overnight at room temperature. Evaporation of the methylene chloride left 220 g. of a partially crystalline mixture of diastereoisomers of ethyl cinnamate dibromide. - 1 2 -

The total dibromo ester (0.654 mole) was dissolved in 300 ml. of dry benzene in a two-liter three-neck flask equipped with a stirrer and a condenser topped with a drying tube. Into the flask was quickly poured 32.0 g. (1.33 mole) of sodium hydride and the s u b pension was heated to boiling. The heating mantle was removed and 3 ml. of absolute ethanol was added while stirring. The rate of evolution of hydrogen was slow at first but increased as the reaction proceeded. By adjusting the heating or cooling of the flask the rate of reaction was kept as rapid as the capacity of the condenser would allow. After two hours 2 ml. additional ethanol was added to main tain the reaction, and after another half hour 2 ml. more ethanol was added. After a total of three hours the reaction was complete; so 20 ml. additional alcohol was added to decompose any remaining sodium hydride and the mixture was stirred vigorously for a few minutes and cooled with an ice bath. About 200 ml. of ether was added followed by sufficient 5$ hydrochloric acid to acidify. Water was added to dissolve the sodium bromide and the two layers were then separated. The organic acid was removed from the organic layer with potassium carbonate solution, and the ester solution was dried, evaporated, and fractionated through eighteen—inch, packed column at 1 mm. pressure. The first fraction was 65 g. of crude ethyl phenylpropiolate, b.p. 96-108°, n ^ 1.5541. The organic acid was liberated from the carbonate solution by acidification and was then recrystallized from about 400 ml. of water (carbon) to give 6.5 g- of phenylpropiolic acid. Added to the - 13 - ethyl phenylpropiolic this represented a total yield of 64#. In a typical saponification 8.0 g. (0.046 mole) of ethyl phenylpropiolate was added to a solution of 2.2 g. (0.055 mole) of sodium hydroxide and 3 ml. of ethanol in 25 ml. of water. After warming and shaking until homogeneous the mixture was allowed to stud overnight. The solution, diluted with two parts of water, was extracted once with ether and acidified, the organic acid was taken up in ether, and the solution was dried and evaporated to dryness. Pure phenylpropiolic 1,2 acid, m.p. 136.9-137-5*, was obtained free from bromine-containing contaminants by recrystallizing this residue from carbon tetrachloride (3 times) until the acid gave a negative Beilstein test for halogen. The yield was 4.8 g. (80#). The second fraction from the distillation of the dehydrobromination product was 39 g. of an ester, b.p. 108-120* at 1 mm., n^20 1.5385. Upon alkaline saponification it yielded an acid which, after recrystallization from ethanol-water, melted at 163.0-163.4° (dec.) and gave a neutral equivalent of 195. With acidic 2,4-dinitrophenylhydrazine reagent it formed a precipitate after a half hour. When heated dry the acid decarboxylated yielding a product which upon treatment with 2,4-dinitrophenylhydrazine gave a crystalline derivative, m.p. 235-240*, Wiich corresponds to the derivative of acetophenone. The original ester was thus ethyl 0-ethoxycinnamate. The acid (M.W. 192) upon decarboxylation yielded a-ethoxy styrene which, in IT 1. All melting points were determined on Anshutz total inmersion thermometers calibrated by the National Bureau of Standards. 2. Glaser, Ann.. 154. 140 (1870), reported m.p. 136-137°. - 1 4 - the presence of acidic 2,4—dinitrophenylhydrazine reagent, decomposed 1 to acetophenone.

(3) p-Chlorophenvlpropiolic acid. Dr. M. S. Newman had pre viously prepared ethyl p-chlorophenylpropiolate by the method de scribed for the preparation of ethyl phenylpropiolate, though no ethyl p-ethoxy p-chlorocinnamate was separated by fractionation. How ever, treatment of the ester preparation with 2,4-dinitrophenylhydrazine reagent yielded considerable precipitate while pure ethyl p-chlorophenylpropiolate does not give a precipitate. Qualitative analysis by the sodium fusion method showed the presence of bromine-containing impurities which were not removed by fractionation through a six-inch column. To 500 ml. of hot ethanol containing 20 g. of 85/6 potassium hydroxide was added 61 g. of the ethyl p-chlorophenylpropiolate pre paration. On cooling the potassium salt crystallized. It was filtered, washed, and dissolved in one liter of water and carefully neutralized with 10^ hydrochloric acid and 5 ml. excess added to precipitate only a small portion of the crystalline acid. An oil separated during this acidification while the solution was still basic. The mixture of oil and crystals was extracted frcm the acidic solution with an ether- benzene mixture. This was extracted with 5% potassium carbonate and

1. V. L. Leighton, Amer. Cham. ., 20. 136 (1898), obtained ethyl p—ethoxy cinnamate by the action of sodium ethoxide on ethyl cinnamate dibromide. He reported the free acid as melting at I64-I6 5* (dec.). Acid hydrolysis of the ester yielded benzoyl acetic acid. - 15 - the neutral solution was dried, evaporated and the residue was distill ed at 1 nan., b.p. 115-125*, giving 16 g., representing 26$ of the starting ester. This substance gave an immediate precipitate when added to 2,4-dinitrophenylhydrazine reagent. When added to alcoholic potassium hydroxide it precipitated a potassium salt which, when filtered and acidified, reverted to the original oil. The infrared spectogram showed a doublet in the carbonyl region indicative of a keto ester. Thus it was probably ethyl p-chlorobenzoylacetate. Combined with the potassium carbonate wash from the above separation the partially acidified aqueous solution was completely acidified and filtered. The solid was dissolved in an ether-benzene mixture, dried, and evaporated until crystallisation occurred. The filtrates brougfcthe total yield of p-chlorophenylpropiolic acid to 19 g., a yield of 40$ from the starting ester. It softened on slow 1 heating at 185* and melted at 192-193* (dec.).

Anal: Calcd. for CgH502Cl : Cl, 19.64; Neut. equiv. 180.6.

Found: Cl, 19.48^ j Neut. equiv, 180.4* (4) m-Chlorophenylpropiollc acid. m-Chlorobenzaldehyde was 2 prepared in a yield of 70$ from m-nitrobenz,aldehyde.

In a three-neck flask equipped with reflux condenser and stirrer were combined 55 ml. of pyridine, 2 ml. of piperidine, 60 g. (0.58 mole) of malonic acid, and 65 g. (0.46 mole) of m-chlorobenzaldehyde.

1. All composition analyses by Galbraith Laboratories, Knoxville, Tennessee. 2. W. H. Carothers, Editor, "Organic Syntheses", John Wiley and Sons, Inc., New York, 1933, vol. 13, p. 28. - 16 -

The mixture was heated with stirring until the evolution of carbon dioxide began. The source of heat was removed and the reaction con tinued spontaneously for a half hour. Heating at near reflux tempera ture was then continued for 3 1/2 hours. The solution was poured into one liter of cold water and acidified with hydrochloric acid. After cooling, the acid was filtered, washed, and dried yielding 79 g. of crude m-chlorocinnamic acid. This acid was esterified directly by the azeotropic method affording 65 g. (66# frcm m-chlorobenzaldehyde) 1 of ethyl m-chlorocinnamate, b.p. 126-130* at 2-3 mm.

To 65 g. (0.404 mole) of ethyl m-chlorocinnamate in 100 ml. of methylene chloride was slowly added 65 g. (0.406 mole) of bromine in 40 ml. of methylene chloride. After standing overnight the excess branine was washed out with a small portion of sodium bisulfite solution. The organic layer was extracted once with water, dried over calcium chloride, and evaporated to dryness. The residue was recrystallized from ethanol to yield 133 g* (89^) of dibroroo ester, m.p. 74-75*. This dibromo ester was probably a mixture of diastereoisomers. Dehydrobromination of 30 g. (0.080 mole) of the dibromc ester was accomplished by refluxing it for five hours in 150 ml. of ethanol containing 21 g. (0.32 mole) of 85^ potassium hydroxide. The hot solution was then decanted from the potassium bromide and the bromide was extracted with another 50 ml. portion of boiling alcohol. On cooling the potassium salt of m—chlorophenylpropiolic acid crystallized

1. K. Kindier, Ber.. 69B. 2805 (1936) reported b.p. 158° at 10 ram. - 17 - frcm the combined solution. This salt was recrystallized from ethanol, dissolved in water and acidified. The acid was taken up in an ether- benzene mixture, dried, concentrated, and crystallized by adding high-boiling petroleum ether to the hot solution to yield 6.3 g. of 1 white needles, m.p. 144.3—31*5.1°. Recrystallization of the acid

recovered from the filtrates gave an additional 3.2 g. for a total yield of 655^* (5) o-Chlorophenylpropiolic acid. Ethyl o-chlorophenylpropiolate was prepared by Dr. M. S. Newman by the method previously described for ethyl phenylpropiolate, though no ethyl 3-ethoxy o—chlorocinnamate was noted. Qualitative analysis by the sodium fusion method showed the presence of bromine-containing impurities which could not be removed by vacuum fractionation through a six—inch column. Crude ethyl o—chlorophenylpropiolate, 132 g., was saponified with 29 g. of sodium hydroxide in 100 ml. of water containing a little ethanol as described for the saponification of ethyl phenyl propiolate. The alkaline solution was extracted once with ether then acidified with the amount of hydrochloric acid calculated to precipitate about 5^ of the organic acid. This removed the contamina ting o-chlorocinnamic acid (m.p. 208°) which precipitated at a higher pH than did o-chlorophenylpropiolic acid. A definite break in pre cipitation during addition of the mineral acid showed when the

1. M. K. Otto, J_. Am. Chem. 3oc., 1393 (1934), reported m.p. 140-141°. - 18 - impurity had been precipitated. After filtration the acidification was completed, and the crude o—chlorophenylpropiolic acid was filtered and dried. It was recrystallized as the potassium salt by dissolving in hot alcoholic potassium hydroxide. The salt was dissolved in water and acidified. The acid was taken up in an ether-benzene mixture, dried, and concentrated to crystallize 40 g. of o-chloro- 1 phenylpropiolic acid, m.p. 132.7-133.3°. The alcohol filtrate yielded an additional 27 g. giving a total yield of 593^ from the starting ester. Probably ethyl o-chlorophenylpropiolate could have been saponified in alcoholic potassium hydroxide as was ethyl p—chlorophenylpropiolate, and the o-chlorocinnamic acid would have been removed in the crystal lization of the potassium salt. (6) p-Nitrophenylpropiolic acid. Cinnamic acid was nitrated 2 following the directions of Muller, and the ortho and para isomers were separated and processed separately to the corresponding nitrophenylpropiolic acids. In a two liter three-neck flask equipped with a glass stirrer and a thermometer lJOOO ml. of filming nitric acid was cooled to 0*. Over a period of two hours 300 g. (2.02 mole) of cinnamic acid was added in small portions with stirring, maintaining the temperature

1. E. Bergmann and A. Bondi, Bar., 66. 273 (1933), and M. M. Otto, op. cit.. reported m.p. 131-132*. 2. C. L. Muller, Ann. 212. 124 (1382). - 19 - at 0—5** When the addition was complete the slurry was poured into 7 liters of ice water. The precipitate was filtered, washed thoroughly with cold water, and dried, yielding 349 g. (1.81 mole, 89^) of crude, mixed nitrocinnamic acids. The azeotropic method was employed to esterify the mixed nitro— cinnamic acids by adding 175 g. (0.907 mole) to a mixture of dry hydrogen chloride, 450 ml. of ethanol, and 600 ml. of benzene. After the esterification was complete the solution was washed free of mineral and unesterified acids and evaporated to near dryness. The mixture of esters was recrystallized twice from 200 ml. of ethanol giving 104 g. of pure ethyl p-nitrocinnamate, m. p. 138.0-138.4*. An additional 8 g. of para ester was obtained in the separation of the ortho ester from the filtrates bringing the yield to 56'/. Bromination of ethyl p-nitrocinnamate was conducted in a similar manner to that already described. The bromine take-up was very slow. Over a period of 24 hours 87 g. (0.394 mole) of p-nitro ester in 500 ml. of methylene chloride was treated with 63 g. (0.394 mole) of bromine at room temperature. After the bromine had been added the solution was allowed to stand for an additional 24 hours. The methylene chloride was entirely evaporated, and a bromine residue was removed from the dibromide crystals by washing with a little alcohol. The yield was 147 g. (98^) of crude ethyl p-nitrocinnamate dibromide. A sample was recry3tallized from ethanol giving m.p.

113.8-114.A*.1 To 132 g. (0.346 mole) of the dibromo ester dissolved in 200 ml. T: C. L. Muller. Ann.. 212. 124 (1882). -20- of dry benzene in a two—liter three-neck flask equipped with stirrer, dropping funnel, and reflux condenser topped with a drying tube was added dropwise sodium ethoxide solution prepared by dissolving 19 g. (0.79 mole) of sodium in 300 ml. of absolute alcohol. The solution wis heated to near reflux during the addition, and the rate of addition was adjusted so that no excess of base was allowed to be present for more than a few seconds. If the color began to darken the addition was interrupted. This addition required an hour, and the solution was heated for an additional hour. After cooling, 150 ml. of ether was added, and the solution was acidified. Water was added to bring the volume up to 1 1 /2 liters, and the layers were separated. After washing the aqueous layer with two portions of ether the com bined organic layer was divided into neutral and acidic fractions in the usual manner, recovering 8 .4 g. of crude p-nitrophenylpropiolic acid. The neutral portion was evaporated to remove nearly all of the solvent. The residue was recrystallized from ethanol giving crude p-nitrophenylpropiolate. This ester was distilled, b.p. 150—

155 ° at 0 .2 mm., and recrystallized twice more from ethanol to yield 41 g. of pure ethyl p-nitrophenylpropiolate, m.p. 123.0-123-8*, which gave a negative Bellstein test. With the 8.4 g. of acid pre viously recovered the yield was 66^. The alcoholic filtrates con tained brominated residues which could be treated again with sodium ethoxide if desired.

1. V. B. Drewsen, Ann.. 212. 154 (1882), reported m.p. 126*. -21-

Saponification of ethyl p-nitrophenylpropiolate was accomplished by dissolving 1 0 .0 g. (0 ,0 4 5 6 mole) in 20 ml, of dioxane, adding 16 ml. of 10?£ sodium hydroxide (a slight excess) and warming until homo geneous, The solution was evaporated to dryness with an air stream, and the sodium salt was recrystallized from about 40 ml. of 10% sodium hydroxide, washed with alkali, dissolved in water, and acidified. The precipitate was taken up in ether—benzene, dried, and evaporated to crystallization of 7 .6 g. (8750 oT p-nitrophenylpropiolic acid, m.p. 204-2 0 5* (dec.) 1 on slow heating. The sodium hydride method of dehydrobromination was unsuccessful in the preparation of the nitro acids because an excess of base was always present. In alcohol the base promoted reduction of the nitro group. (7) m-Nitrophenylpropiolic acid, m— Nitro cinnamic acid was 2 esterified by the azeotropic method and the ethyl ester, m.p. 7 4*, was crystallized from alcohol. Ethyl m-nitrocinnamate was brominated in the usual manner in methylene chloride over a period of 24 hours to give a yield of 995 ^ 3 ethyl m-nitrocinnamate dibromide, m.p. 8 6*.

1. F. G. Baddar and L. S. El-Assal, _J. Chan, doc.. 1267 (1948), reported m.p. 201-202* (dec.); V. B. Drewsen, Ann., 212, 154 (1882), reported m.p. 1 9 8* (dec.). 2. R. Schiff, Ber.. 11. 1783 (1878) reported m.p. 78-79°. 3. F. Wollrlng, Ber.. 47. 109 (1914) reported m.p. 86-87*.

4 -22-

This dibromo ester could not be dehydrobrominated successfully in one step to form the triple bond because m— nitro—alio—a-bromo- c inn ami c acid"** was formed as the principal intermediate and resisted further elimination until it had been isomerized to the trans con— 2 figuration. Consequently a three—step process was necessary: elimination and saponification to cis-a-bromo acid; isomerization to trans a—bromo acid; and finally elimination to form the acetylenic acid. To 19 g. (0.47 mole) of sodium hydroxide dissolved in a mixture of 170 ml. of water and 25 ml. of dioxane was added 2 8 .7 g- ( .0 7 5 mole) of ethyl m-nitrocinnamate dibromide. The mixture was stirred for two hours while heating at 50*. If the discoloration became excessive the heating was reduced. The resultant solution was diluted with an equal volume of water, acidified, and extracted with two portions of chloroform. The chloroform solution was dried and evaporated to about 75 ml. Bromine was added and an excess maintained over a period of three days. At intervals the m—nitro—a-bromocinnamic acid (trans) was filtered out as it crystallized, having been formed by isomerization of the cis acid by the bromine. A total of 10.5 g« (m.p. 217*) was recovered by this method. It was dissolved in about 30 ml. of 15^ aqueous sodium hydroxide from which sodium m—nitrophenylpropiolate crystallized on standing. The salt was thrice recrystallized from

1. Alio and cis designate the carboxyl group and the benzene ring in cis positions in all cases. 2. S. Reich and S. Koehler, Ber.. 46. 3727 (1913), have studied the isomeric m-nitro—a—bromocinnamic acids quite thoroughly. -23- lo£ sodium hydroxide. The salt was then dissolved in water and acidified. The acid was extracted with an ether-benzene mixture, dried, evaporated, and crystallized from benzene-ligroin. The yield I of m-nitrophenylpropiolic acid, m.p. 143.7-144-4*, was 5 .5 g. (38?6) after recovery and recrystallization of the material in the filtrates. The aqueous system for the elimination reactions was found pre ferable to alcohol because the destruction of the nitro group was avoided. The us e of a mercury—vapor lamp to isomerize the m-nitro— allo-a-bromocinnamic acid would probably offer considerable advantage over the bromine method.

(8) o-Nitrophsnylpropiolic acid. The residue which was left from the separation of ethyl p—nitrocinnamate from the mixed nitro— cinnamic esters contained both the p-nitro and the o—nitro ester. The alcoholic solution was condensed to remove all of the p-nitro ester which would crystallize, and the filtrate was evaporated to dryness. The ester residue was hydrolyzed in acetic acid containing a little hydrochloric acid. After dilution with water the free acid was collected, washed, and dried, to yield 105 g- of nitrocinnamic acid. This acid was then dissolved in an excess of sodium carbonate solution, washed once with benzene, and dilute hydrochloric acid was added until the organic acid just began to precipitate. Enough standard acid (140 ml. of 2.4 N hydrochloric acid) was then added slowly with stirring to precipitate about two-thirds of the nitrocinnamic acid. This was filtered, washed thoroughly, and recrystal—

1. S. Reich and S. Koehler, op. cit., reported m.p. 143**

i -24- lized from ethanol to give 45 g. of o—nitro cinnamic acid; m.p. 240—

243* (dec.). The acid remaining in the carbonate solution and the residue in the alcoholic filtrate were combined, esterified again, the p-nitro ester removed by crystallization, the ester residue in the filtrate hydrolyzed in acetic acid, the acid partially acidified from a sodium carbonate solution, and recrystallized from ethanol to give additional o-nitrocinnamic acid. After esterification 55 g. of ethyl o-nitrocinnamate was crystallized from ethanol in large rhombic 2 crystals, m.p. 4 1.2-4 1*8*.

Six days at room temperature were required to brominate 55 g.

(0 .2 4 8 mole) of ethyl o—nitrocinnamate in 120 ml. of methylene chloric e with 40 g. (0.250 mole) of bromine. The methylene chloride was evaporated to dryness (a preferred procedure would have been to first wash out the excess bromine with bisulfite), and the residual oil was dissolved in hot alcohol from which it crystallized on cooling 3 to 10* to yield 77 g. (8236) of dibromide, m.p. 69.0-69.5*. To 37.7 g. (.0992 mole) of the dibromo ester dissolved in 120 ml. of dry benzene in a flask equipped with stirrer and dropping funnel was added drop—wise a sodium ethoxide solution prepared by dissolving

6.85 g. (0 . 2 9 8 mole) of sodium in 120 ml. of absolute alcohol. The solution was maintained at room temperature. After about two—thirds of the base had been added the solution began to discolor; whereupon 2 ml. of water was added quickly. The remainder of the sodium

1, 2,3 C. L. Muller, Aq d ., 212, 127 (1882). -25- ethoxide was added, and the stirring was discontinued Tor 15 minutes. The first two equivalents of base had converted the dibromo ester to ethyl o-nitrophenylpropiolate, and when discoloration began water was added to hydrolyze the ester with the remaining alkali. No further discoloration took place. The solution was then acidified, 1DO ml. of ether and 300 ml. of water were added, and the phases were separated. The organic acid was extracted with potassium carbonate solution in the usual manner, taken up in an etherbenzene mixture, dried, and evaporated to crystallize. The sodium salt of the acid could not be recrystallized from alkali because of severe decomposition on heating. However, good purification was obtained by recrystallizatdon from hot (9 0*) water (carbon) which gave 14 g. (74^) of o-nitrophenylpropiolic acid, m.p. 1 6 0.5 -1 6 1.0° (dec.).

(9) p-Methoxvohenylpropiollc acid. Mr. K. Woo prepared p—methoxy—a—brcanocinnamic acid (transj m.p. 188-189*) from ethyl 2 3 p—methoxycinnamate dibromide by the method described by Reimer. *

This monobromo acid separated as the potassium salt from alcoholic solution. To 16.7 g. (0.254 mole) of 8596 potassium hydroxide in 225 ml. of ethanol was added 30.8 g. (0 .1 2 0 mole) of the p-methoxy-a-brotoo-

1. C. L. Muller, op. cit., p. 140, reported m.p. 157* (dec.). 2. M. Reimer, J^. Am. Chem. Soc., 43* 2460 (1926). 3. K. V. Hariharan and J. J. Sudborough, J_. Indian Inst. Sci. (A) 8, 189 (1925)* Chem. Zentr., 1926 I, 71), have discussed the isomeric p-methoxy—

Recovery and recrystallization of the material In the filtrates brought the yield up to 17.5 g« (83$) of p-methoxyphenylpropiolic acid. (10) m-Methoxyphenylpropiolic acid. m-Hydroxybenzaldehyde 2 was prepared in a yield of 35 $ from ra-nitrobenzaldehyde and 3 methylated with dimethylaulfate to give m-methoxybenz aldehyde ^n

a yield of 78$. m-Methoxycinnamic acid was prepared in 78$ yield by condensing m-methoxybenzaidehyde with malonic acid in the same manner as described for the preparation of m^chlorocinnamic acid. After recrystallization from ethanol-water the acid melted at 117.4-118.6*.^

1. E. Bergmann and A. Bondi, Ber. 6 6. 178 (1933), reported m.p. 141-143* (dec.), K. V. Hariharan and J. J. Sudborougta, op. cit.. reported m.p. 135—1 4 0* (dec.). 2. W. E. Bachmann, Editor, "Organic Syntheses", John Wiley and Sons, Inc., New York, 1945, vol. 25, p. 55. 3. S. N. Chakravarti, R. D. Haworth, and V. H. Perkin, Jr., J.. Chem. Soc., 2269 (1927). 4. J. I. Jones and T. C. James, £. Chem. Soc. 1600 (1935), have also studied the elimination reactions of m—methoxycinnamic acid dibromide. -27-

Jones and James found that sunlight was necessary to brcxminate m-methoxycinnamic acid in the side chain. A mercury lamp was found to be more practical in this work. It was unnecessary to prepare the ester because the acid brominated easily. A mercury discharge tube was insnersed in a boiling solution of 2 0 .2 g. (0 .1 1 3 mole) of m- methcocycinnamic acid in 30 ml. of carbon tetrachloride. A 10% carbon tetra chloride solution of bromine (18.2 g., 0.113 mole) was added slowly until no more would react. The product separated from the boiling solution during bromination. After cooling, the crystals were filtered to give 35 g. (9 1%) of m-methoxycinnamic acid dibromide; m.p. 167-1 7 0•. To 22 g. (.065 mole) of dibromo acid was added slowly a cool solution of 8 .8 g. (0 .1 3 3 mole) of 85% potassium hydroxide in 80 ml. of ethanol. The suspension was allowed to stand two days with occasional shaking. If an attempt was made to evaporate the alcohol from the alkaline solution considerable decarboxylation accurred; so the mixture was first acidified with conc. hydrochloric acid then evaporated to near dryness. The residue was added to 100 ml. of

water and the organic acid was washed out with two 75 ml* portions of chloroform. The chloroform solution was irradiated for 24 hours by immersing a mercury discharge tube in it. The irradiation con verted m—met ho x y alio—a—bromo cinnamic acid to the trans configuration# The chloroform was evaporated to dryness, the residue was taken up

1. J. I. Jones and T. C. James, J. Chem. Soc. 1600 (1935), have also studied the elimination reactions of m—methoxycinnamic acid dibromide.* -28- in aqueous potassium hydroxide and diluted to 100 ml. Saturated barium chloride solution was added to precipitate the barium salt of the trans monobrooo acid. The salt was filtered, washed, and acidified to recover the free acid. The filtrate from the filtration of the barium salt could be acidified and the recovered acid irradiated again. The trans monobromo acid (m.p. 122-124*) was boiled vdth 9.5 g. of 8996 potassium hydroxide (about 105& excess) in 150 ml. of ethanol for four hours. The alcohol was evaporated off, and the residue was taken up in 80 ml. of water, treated with 1 ml. of saturated barium chloride, and filtered. The filtrate was acidified to the first cloudiness, and the colored material was washed out with chloroform. The aqueous solution was then completely acidified. The acid was taken up in chloroform, dried, evaporated, and the m-methoxyphenylpropiolic acid, m.p. 107.8-108.8*,1 was crystallized by adding petroleum ether, which gave 6.7 g. (58?o). (11) o—Methoxyphenylpropioli c acid . o—Kethoxybenzaldehyde was condensed with malonic acid by the method previously described to 2 yield o—methoxycinnamic acid, m.p. 185-186*. This was esterified by the azeotropic method to give ethyl o—methoxycinnamate in 949& yield from the aldehyde. The bromination of 112 g. (0.544 mole) of ethyl o—methoxy— cinnamate was performed at —10* in 250 ml. of methylene chloride

1. J. I. Jones and T. C. James, op. cit.. reported m.p. 109*.

2. K. H. Slotta and H. Heller, Ber.. 6 3. 3037 (1930). -29- with 87 g. (0.54 mole) of bromine. The bromine reacted rapidly with the evolution of a small amount of hydrogen bromide. After completely evaporating the methylene chloride the dibromide was dissolved in 300 ml. of dry benzene and the elimination procedure with 2 6 .0 g. (1.08 moles) of sodium hydride was carried out as de scribed for the preparation of ethyl phenylpropiolate. The resulting ester mixture was fractionally distilled through an eighteen-inch packed column at about 0 .5 mm. pressure collecting the fraction boiling at 128-130*, nj^ 1.562, 57 g. An infrared spectrogram showed a small but definite triple bond absorption at 4 - 6 A* - It was found that advantage could be taken of the rapid saponification of the acetylenic ester to effect a separation. Considering an average molecular weight of 240 the 57 g. of ester in 1QO ml. of ethanol was

partially saponified with 5 -6 g. of 85% potassium hydroxide (equiva lent to 36% of the ester) in 60 ml. of ethanol. The cold alkali was slowly added to the ester with stirring. The alcohol was evaporated with a stream of carbon dioxide, the residue was taken up in water, washed with ether, and acidified with 10% hydrochloric acid ju3t to

the point where precipitation began, then 5 ml. more was added to precipitate the o—methoxycinnamic acid present. After filtration the acidification was completed; the organic acid was collected and re crystallized three times from benzene-ligroin, giving 8.7 g. of

o-methoxyphenylpropiolic acid, a yield of 9% from ethyl o-methoxycinnamate. By heating very slowly the acid melted with decomposition -30- at 1 2 8.0-1 2 8.4° . 1

Various attempts to eliminate hydrogen bromide from ethyl o—methoxycinnamate dibromide using aqueous and alcoholic potassium hydroxide yielded only unreasolvable mixtures of acids containing considerable bromine. Ultraviolet irradiation did not aid in con verting to a bromo acid which could be converted to an acetylenic 2 acid. Reimer and Howard brominated o-methoxycinnamic acid in carbon disulfide and were able to obtain o—methoxyphenylpropiolic acid in a manner similar to that used in the preparation of the p-methoxy compound. However, o-methoxycinnamic acid is only slightly soluble in carbon disulfide and the bromine take-up in the suspension is negligible. B. Purity of the Acids. Each of the substituted phenylpropiolic acids was recrystallized to insure that the highest melting point had been reached. All but the chloro acids gave a negative Beilstein test for halogen. The neutral equivalent of each acid (Table IV) was determined by titration with standard sodium hydroxide using phenolphthalein as indicator.

1, 2. K. Reimer and M. Howard, J.. Am. Chem. Soc. 30. 196 (1928) reported m.p. 124—125* (dec.), and E. Bergmann and A. Bondi, op. cit.. claimed m.p. 128*. -31-

Table IV Melting Points and Neutral Equivalents of Substituted Phenylpropiollc Adds

Substituent m.p., *C M. W. Neut. Eq H 136.9-137.5 1 4 6 .1 146.3 o— Cl 132.7-133.8 1 0 0 .6 180.1 m—Cl 144.3-145.1 180.6 180.5 p-Cl 192 -193 (dec.) 180.6 180.4 o-N02 1 6 0.5 -1 6 1 .0 1 9 1 .2 190.9 m-N02 143.7-144-4* 191.2 1 9 1 .8 p-no2 204 -205 (dec.) 1 9 1 .2 1 9 1 .2 o-0CH3 128.0-128.4 (dec.) 176.2 1 7 6 .6 m-0CH3 107.8-108.8 176.2 176.7 P-OCH3 144.0-144.4*(dec. ) 176.2 177.1

C. Preparation of Esters* The ethyl ester of each of the phenylpropiollc acids was pre pared for use in infrared and ultraviolet absorption studies. Ethyl p-nitrophenylpropiolate was available as an intermediate in the synthesis of the acid, and was purified by recrystallization from alcohol. With the exception of the p-methoxy compound all the other esters were prepared by dissolving 3 6- of the acid in a mixture of

30 ml. of ethanol, 50 ml. of benzene, and some dry hydrogen chloride, and slowly distilling off about half of the solvent through a column over a period of four hours. When heated with mineral acid in this manner the triple bond of p-methoxyphenylpropiolic acid (or its ester) hydrated to the ketone. Consequently this ester was prepared by dissolving 1 g. of the acid in 20 ml. of ethanol containing dry hydrogen chloride, and the solution was kept at room temperature for three days. The hydrochloric acid was neutralized and the alcohol -32- was removed with an air stream. The esters were worked up in the usual manner and distilled. A middle fraction in the distillation was taken as the product. None gave a precipitate with 2,4-dinitro- phenylhy dr azine. The nitro esters are solids and were recrystallized from ethanol after distillation.

Table V Physical Constants of Ethyl Esters of Substituted Phenylpro- piolic Acids Substituent Constant Analysis Calcd. Found

H 75.86 4 5 1-5490 C 75.88 H 5.79 5.75 o-Cl n 1.5604 Cl 17.00 1 7 .2 0 m— Cl ft 1.5586 Cl 1 7 .0 0 17.07 p-Cl « 1-5669 -> Cl 17.00 17.39 o-N0a m.p. 57.3-58.1* m—N0a tt 58.0-58.6* C 6 0 .2 6 60.36 H 4.14 3.94 p-no2 n 123.0-123.8° o-0CH3 nD 1-5592 C 7 0 .6 1 69.99 H 5.93 5.72 ra-0CH3 n 1.5547 C 7 0 .6 1 70.53 H 5.93 6.09 p-OCH3 IT 1.5675 C 7 0 .6 1 70.87 H 5.93 6 .1 1

D. Ionization Constants The ionization constant of each acid was determined by measuring the pH of a solution of the acid while titrating it with

1. A. Baeyer, Ber. . 13. 2259 (1880), reported m.p. 6 0 -6 1*. 2. V. B. Drews«n, Ann., 212, 154 (1882), reported m.p. 126°. -33- standard base. To Insure solubility cf the acid an aqueous solvent

containing 35& purified dioxane by weight was used, and the standard base was in the same solvent. The pH was measured with a line- operated Beckman model H—2 glass electrode pH meter which was standardized in an aqueous buffer at pH 4* A 0.00090 mole sample of the acid was dissolved in 60.0 ml. of aqueous dioxane in a 250 ml. beaker. The temperature was main

tained at 25-0* - 0.2* with a water bath, and the solution was continually stirred during titration with 0.1 N sodium hydroxide. The pH was read at short intervals throughout the titration up to the end point. A smooth curve of pH against volume of base was drawn from these data and pK calculated from the plot as explained in the next section. E. Kinetic Runs (l) Apparatus. The reaction vessels for the rate determinations were 25 ml. volumetric flasks with tight-fitting ground glass stoppers. During the reaction they were immersed to within one inch of the stooper in a thermostatic water bath. The temperature was controlled

at 25* and at 3 5 * to an accuracy of - 0.0 2* by an electronic relay actuated by a mercury^ to—mercury thermo regulator. All pipets were calibrated at the temperature conditions under which they were used.

1. L. F. Fieser, "Experiments in Organic Chemistry", Part II, — D. C. Heath and Co., New York, 1941, P* 369. -34-

(2) Catalyst solution. C. P. Methanol (99*5^) was dried by careful fractionation through a three-foot column.^ Hydrogen chloride was bubbled from a sintered-glass plate through a six-inch column of concentrated sulfuric acid into the dry methanol. The acid concentration was adjusted with more methanol to approximately 0.01 N, and the exact concentration was determined by titration of a sample taken at the temperature of the kinetic run. Fresh catalyst solution was prepared before each run. (3) The experimental run. Approximately 0.004 mole of the organic acid was accurately weighed into each reaction flask. Due to the low solubility of p-nitrophenylpropiolic acid only 0 .0 0 2 mole of it was used in runs at 25*. After the catalyst solution and the reaction flask reached temperature eaualibrium in the bath

separately, 1 0 .0 ml. of catalyst was added to the organic acid in each flask. After thorough mixing a one ml. sample was withdrawn and titrated for the initial concentration, using standard 0.05 N sodium hydroxide and phenolphthalein as indicator. At intervals, up to seven additional samples were withdrawn to follow the reaction. To keep the organic acid in solution during titration neutralized acetone was added to the sample. To establish that only esterification was occurring the product of experimental runs for phenylpropiollc acid and the

1. H. A. Smith, J_. Am. Chem. Soc.. 61. 254 (1939)« -35- o-chloro, o-nitro, o—methoxy, p-methoxy, and p—nitro derivatives were divided into neutral and acidic fractions. The acids were proved to be the starting material by their melting points, and the ester portions on saponification yielded the pure acetylenic acids. Since the p-methoxy compound showed the greatest tendency to hydrate the triple bond a sample from a kinetic experiment was treated with

2,4-dinitrophenylhydra*ine. No precipitate was observed after 12 hours though both the f5-keto ester and its enol ether were known to give a positive test within fifteen minutes. Another sample of the same reaction mixture was made alkaline and treated with benzene dizaonium chloride. It gave no deeper color than did a blank con taining no organic acid, indicating the absence of a phenolic group, F. Spectra. A Beckman DU spectrophotometer was used for ultraviolet absorption measurements. Solutions of the ethyl esters of the

substituted phenylpropiolic acids of about 5 x 10 ^ M in 95% alcohol were used. Extinction coefficients, E, were calculated by dividing the observed densities by the molar concentration. The absorption

curves are reproduced on p. 6 . The infrared spectra of the solid nitro esters were obtained from 10% solution in chloroform. For the others pure liquid esters were used. -36-

III, CALCULATIONS AND RESULTS

A. Ionization Constanta. The use of pH measurements during titration of acids to determine ionization constants is well explained by Glasstone.^

The common equilibrium expression is the basis

K . CH*] [A~] x [HA] 0 HA

The activity coefficients are neglected because the final use of the ionization const ant data will be in the expression log K/KQ> where

is the ionization constant of phenylpropiolic acid, and K is the ionization constant of a substituted phenylpropiolic acid. Thus it is the ratio of the constants of two similar acids which ionize to approximately the same extent. It is therefore reasonable to expect

that the ratio of activity coefficients, ^H* $k / ^**0 ^ , h a / 2Th a 0

will be very close to unity. Consequently we need only be concerned with the concentration terms. The anion concentration [A”] at any

time in the titration is equal to the concentration of salt plus the

concentration of ionized acid. The ionized acid is [H+]; so

[A“ ] - [Salt] + [H+] The unionized acid [HA] is equal to the total unneutralized acid, [acid], minus that acid which is ionized; [HA] - [acid] - [H+ ]

1. 3. 51a3stone, The Electrochemistry of Solutions. D. van Nostrand Co., New York, 1930, p. 188-189. -37-

The equilibrium expression then becomes

K - CH+] ([aalt] ♦ [H*]) . [acid] - [H*]

If the acid is very weak (pK > 4) the hydrogen ion terms are small compared to [salt] and [acid] near the midpoint of the titration and can be neglected as additive and deductive terms. However, the acetylenic acids used in this work are relatively strong and that simplification can not be made. Several terms are defined which are readily obtained from the titration data: N — normality of base. Vf — Volume of base already added at any point in the titration.

V2 » Volume of starting solution of acid (in this case 60 ml.)

V3 “ Volume of base yet to be added to equivalent point, i.e., total volume of base necessary to neutralize the acid minus V, . The amount of salt present is equal to the amount of base added which in concentration terms is

NV, [salt] — V2

The unneutralized acid is equivalent to the base needed to complete the neutralization; [acid] *______V2 -38-

The reciprocal of the antilogarithm of pH is considered to be the hydrogen ion concentration, and the equilibrium constant is now + ( ^ 1 EH ] \V» ♦ V, antilog pH I N V i ______V-i + V 2~ antilog pH

By the definitions of pK and pH this can also be written as

i pK - pH - log I T i * antiiog pH NV, 1 Vt + V2 antilog pH

This is the expression used to calculate the ionization constants from pH and titration readings directly. From the experimental data pH was plotted against volume of base. A smooth curve was drawn and three points between 35^ and 70?& equivalence were chosen at which to calculate pK. At least two titrations were made on each acid and the pK values were averaged with an estimated accuracy of — 0.02 pK units. Table VT Ionization Constants of Substituted Phenylpropiolic Acids in 35^5 Dioxane (wt.) at 25° Substituent pK K x 10^ H 3.24 (pKo) 5.8 o-Cl 3.08 8.3 m-Cl 3.00 10 p-Cl 3.07 8.5 o—N0 2 2.83 15 m—N0 2 2.73 19 p—N0 2 2.57 27 o-0CH3 3.37 4.3 m-0CH3 3.21 6.2 p-OCH3 3.44 3.6 -39-

In the determination of ionization constants in a mixed solvent an error may be introduced by using a pH meter which has been cali brated in an aqueous solution. Correction factors have been evaluated^" to convert the meter reading to hydrogen ion concentration in various dioxane—water mixtures. For the 35% dioxane solution used in the present work that correction factor is negligible. Even if a constant calibration error of as much as 0.05 pH units were introduced it would cause an equal error in the calculated pK value. Such an error would then vanish in the comparison of pK and pKQ.

B. Rates of Esterification. (1) Rate constants. The rate constants for esterification of the acids in acidic methanol have been calculated from a rate equation 2 3 developed by Goldschmidt and used by others. The esterification reaction is assumed to be between acid and alcohol complex

RCOOH + R ’O H a ► RCOOR' + H30+

1. L. G. van Uitert and C. G. Haas, J_. Am. Chem. Soc., 75 . 451 (1953). 2. H. Goldschmidt and 0. Udby, Z. physik. Chem.. 60 . 728 (1907); H. Goldschmidt and A. Thuesen, ibid., 81. 30 (1912); H. Goldschmidt and R. S. Molbye, ibid.. 145. 139 (19297; H. Goldschmidt, H. Haan- land, and R. S. Molbye, ibid.. 143. 278 (1929). 3. A. T. Williamson and C. N. Hinshelwood, Trans. Faraday Soc., 30. 1145 (1934); H. A. Smith, J,. Am. Chem. Soc.. 61. 254 (1939); 62. 1136 (1940); K. L. Loening, A. 3. Garrett, and M. 3. Newman, ibid., 74. 3929 (1952). and the rate is expressed as

d[RCOOR*] m kCRCOOH] [R'OH2+3 dt

In dry alcohol the concentration of alcohol complex may be con sidered equal to the total[H+]. As water is formed in the reaction it competes with the alcohol for the hydrogen ion, and the reaction rate decreases. An equilibrium established in the competition for the hydrogen ion necessitates the definition of a new constant, r.

[R’OHj] [H203 [R'OHj] [H20] r - — ------[H30+] [total H*3 - [R'OhJ] Solving for [R0H2] and substituting in the rate equation gives

dERCOQR1] _ k[RCOOH3 r [total H*3 , or dt r + [H20]

dx m kr (catalyst) (a-x) dt (r + x) where a is the initial concentration of organic acid, x is the con centration of ester after time t, and the catalyst is a strong mineral acid. Integration gives for k the expression

k - (r * a) In a/(a - x) -x (catalyst) rt

Goldschmidt tested the equation at 25°> and the later workers con firmed it at several temperatures. They claimed constant values of k up to 80£ reaction. Smith^ gives an excellent summary of the development of the Goldschmidt equation. The value of r in the rate equation at any one temperature is independent of the acid used, as would be expected from its definition. The values used to calculate the rate constants were interpolated from Smith1s data as 0.22 at 25* and 0.28 at 35°• The specific applicability of this rate equation to substituted phenylpropiolic acids was not tested because only one catalyst con centration, approximately 0.01 N, was used. To correct the catalyst concentration for volume expansion on mixing the initial volume V of the reaction mixture was calculated from the equation

NtV “ NcVc + A where is the normality of the reaction mixture as determined by the initial titration, Nc and Vc are the normality and volume respectively of the catalyst solution, and A is the millimoles of organic acid. The initial volume of the reaction mixture was found

to be 1 0 .3 ml. for phenylpropiolic acid and 1 0 .4 ml. for all the others. A volume of standard base equivalent to the catalyst was subtracted from the volume of base used to titrate each sample. This gave the concentration of organic acid present (a — x). Smith found that a reaction takes place between hydrogen chloride and methanol to give methyl chloride. Therefore blank runs

1. H. A. Smith, J. Am. Chem. Soc.. 61. 254 (1939). -42- were carried out- on the c&t&lyst solution to determine if the hydrogen chloride concentration decreased with time. No change in catalyst strength was found at either 25° or 3 5 * over the nuocimum period needed for the esterification runs. Table IV gives the rate constants for esterification of the substituted phenylpropiolic acids at 25° and 35*. These are the average values taken during 20-55^ reaction. Experimental error was greater earlier in the reaction, and the rate constants fell off at later stages. Though it was more convenient to record the rate data with the minute as the unit of time, the rate constants are reported in seconds in agreement with standard practice.

Table VII Esterification Rate Constants of Substituted Phenylpropiolic Acids in Methanol Catalyzed by Hydrogen Ions (ca. 0.01 N)

Substituent k x 103 at 2 5 ° k x 103 at 3 5 * 1./mole-sec. 1./mole-sec.

H 0.53 - .0 1 1.17 - .02 o-Cl 0.48 1.12 m—Cl 0.40 0.90 p-Cl 0.42 0.92 o-N02 0.41 0.93 m-N02 0.29 0.63 p—N02 0.25 0.57 o-0CH3 0.73 1.63 m—OCH3 0.50 1.15 P-OCH3 0.56 1.28

(2) Activation energies and entropies of activation. Since the rate constants were calculated at two temperatures the activation energies for the esterification reactions can be calculated from the -43-

Arrhenius equation

-E/RT k - PZe 7 , or

E log k - log PZ - 2.303 RT

When the values of k at two temperatures Tt and T2 are inserted the activation energy E is found from the expression

E - 2*303 RT-|T2 log k,/k2 Ti — T2

Once E is known log PZ can be calculated

log PZ — -----—----- + log k 2.303 RT

The change in entropy of activation is calculated as the differ ence between the activation entropies of a substituted phenylpropiolic acid ^ S* and the reference acid, phenylpropiolic acid ^ S*.

^S* - AS* • 2.303 R (log PZ - log P0Z0 ) . -44-

Table VIII Enerei.es and Entropies of Activation for the Acid-Catalyzed Esterification of Substituted Phenylpropiolic Acids, 25-35*

Substituent E cal/mole log PZ ^ S* _ ^ s|

H 14500 - 400 7.3 - 0.3 0 + o-Cl 15300 7.9 2.7 - 2 .6 m-Cl 14700 7.3 0 .1 p-Cl 14300 7.1 -0.9 o—N02 15000 7.6 1.5 m-N02 14400 7.1 -1.3 p-N02 14800 7.3 -0.3 0-OCH3 14700 7.6 1.3 m—OCH3 15200 7.8 2.4 P-OCH3 15100 7.8 2 .2 -45-

IV. DISCUSSION A. Ionization Constants.

A plot of log K/Kq of the ionization of the met a— and para- substituted phenylpropiolic acids in 3595 dioxane against Hammett (J~ values gives a straight line indicating the expected agreement of the ionization with the Hammett equation. The slope, , is +0.81. A similar plot for the ionization of substituted cinnamic acids in 1 water at 2 5 * gives p « +0.4 7* while by definition jO — 1 .0 0 for the ionization of benzoic acids in water at 25*. The low value of means that the ionization of cinnamic acid is less sensitive to variations of ring substituents than is benzoic acid. Consequently the ionization of phenylpropiolic acid would also be expected to be less sensitive than that of benzoic acid to substituent changes. No conclusion can be drawn from these data with regard to the relative sensitivity of cinnamic and phenylpropiolic acids to substituent changes because the ionization constants of the phenylpropiolic acids were determined in aqueous dioxane and the constants of cinnamic acid were measured in water. However, for the ionization

of para-substituted benzoic acids is increased from 1 .0 0 in pure 2 water to 1.29 in 3595 dioxane. Consequently the ionization of phenyl propiolic acids in pure water would probably give a of less than +0.81 though it is doubtful if it would be as low as +0.47 which is

1. L. P. Hammett, "Physical Organic Chemistry”, McGraw-Hill Book Co., Inc., New York, N. Y., 1940, p. 190. 2. Taken from data to be published by H. L. Goering, T. Rubin, and II. S. Newman in J^. Am. Chem. Soc.. 76. (1954)* for the ionization of cinnamic acids in water. Steric factors may be affecting the ionization of ortho-substituted phenylpropiolic acids. The ionization constants listed in Table IX show that p-nitrophenylpropiolic acid is stronger than o-nitrophenylpropiolic acid while p—methoxyphenylpropiolic acid is weaker than the o—methoxy acid. The same relationships exist in the cinnamic acid series.

Table IX Comparison of Ionization Constants of Ortho— and Para-Substituted Acids in the Phenylpropiolic and Cinnamic Series Substituent Substituted Phenylprop- Substituted Cin- iolic Acids, 39% Dioxane, namic Acids, water, 25° 25o1 K x lO5 K x 105

H 58 3 .6 5 o-OCHj 43 3 .4 5 p-OCH3 36 2.73 o-N02 150 7 .0 7 p-NOz 270 8 .9 9 o—Cl 83 5.83 p-Cl 85 3 .8 6

The weakness of the o—nitro acid can be explained as a com bination of two effects, inhibition of resonance and a field effect. In resonating with a benzene ring a nitro group becomes coplanar with the ring and creates positive centers at the ortho and para positions. If for steric reasons the nitro group is prevented from becoming coplanar resonance is decreased and the positive charge at

1. J. F. J. Dippy and J. E. Page, J_. Chem. Soc., 357 (1938).

4 -47- the ortho and para positions is reduced. The nearest oxygen on the nitro group of coplanar o-nitrophenylpropiolic acid is 2 .4 ft from the

side chain (Figure 4)* This is less than the sum of the Van der Vaals radii of the oxygen and carbon atoms• Therefore some replusive

force probably exists between these atoms to prevent the nitro group from becoming coplanar, though this force is not large since it is not evident in the ultraviolet spectrum. The nitro group, which cannot become coplanar with the ring, has lost some of its acid- strengthening ability because the positive charge at the ortho position has decreased. The field effect is caused by the nitrogen- oxygen dipole in the o—nitro group which presents a negative charge adjacent to the side chain. The negative charge resists the with drawal of electrons frctn the carboxyl group by electrostatic repul sion. This latter factor, peculiar to the nitro group in the ortho position, probably is the principal cause of the lower acid strength.

This field effect of an ortho substituent may explain the greater strength of the o-methoxypropiolic and o—methoxycinnamic

1. L. Pauling, "The Nature of the Chemical Bond”, Cornell Univ. Press, Ithaca, N. Y., 1943, p. 189. “48- acids compared to the corresponding p-methoxy acids. Because of resonance with the ring the methoxy group, acting as an electron donor, in the ortho or para position tends to decrease the strength of the acid by creating a negative canter at the point of attachment of the side chain. As a result the methoxy group has a positive charge. When in the ortho position this electron-attracting positive charge next to the side chain tends to counteract the acid-weakening effect of the resonance between the ring and the methoxy group. The o-methoxy acids are thereby stronger than the p-methoxy acids. A chlorine atom on an aromatic ring can act as either a donor or acceptor of electrons, but in the case of o—chlorophenylpropiolic acid these seem to be in such a balance that there is no field effect from the ortho substituent which influences the acid strength. Neither the o-chloro atoirt nor the oxygen atom of the o—methoxy group is within the van der Waals radius of the carbons in the ethynylene group; so no bulk interference can affect the resonance of the substituents. B. Esterification Rates. A plot of the logarithms of the esterification rate constants at 25° of the meta- and para-substituted phenylpropiolic acids against Hammett d" values gives a straight line showing agreement with the Hammett relationship. A plot of the rate data taken at 35° gives a similar line, and in both cases /O — —0.36. The negative /O value indicates that the weaker acids esterify at a greater rate than the stronger acids. Since a weak acid has a relatively high electron density at the carboxyl group it reacts rapidly toward acid -49- catalysis. Acid catalyzed esterification of benzoic acids gives * -0.42. The greater absolute value of /O means that the rate of esterification of benzoic acid is more sensitive to changes in ring substituents than is phenylpropiolic acid. The inductive and resonance effects produced by the ring substituents are partially dampened by the ethynylene group. Figure 1 shows the plot of the logarithms of the esterification rate constants at 25* and at 3 5 * (log k gives the same plot as log k/kQ) against the logarithms of the ionization constants (log K/Kq) for all the substituted phenylpropiolic acids. The straight lines have been drawn by the method of least squares to include all but the points corresponding to the ortho—substituted acids. It is apparent that the points corresponding to the meta and para derivatives fall in general along the lines, but the points corresponding to the ortho derivatives do not come close enough to be considered in agree ment with the Hammett relationship. Consequently some steric effect is presumed present. For comparison the esterification rate constants of substituted benzoic acids^- (Figure 2) and the alkaline saponification rate con- 2 stants of substituted ethyl cinnamates (Figure 3 ) have been plotted according to the Hammett equation. The substituent constants, log K/Kqj are based on the ionization of the benzoic acids and the

1. (a) R. J. Hartman and A. K. Borders, J_. Am. Chem. Soc., 59. 2107 (1937); (b) R. J. Hartman and A. G. Gassman, ibid.T62, 1559 (1940). 2. K. Kindler, Ann. , 464. 278 (1928). -50-

O o -O C H - 2.8

-29 -OCHs O o-C l

-3.0 p-CI -C l

-3.1 /O* -0.44 •o -O C H

-3.2 m — NO

—i P-OCH3 o-CI

m-CI P-

X 25* /o -0.44 \

0.8 - 0.2 0.2 0.4 0.6

FIGURE I Hammett R elationship between Log k and Log *Vko *or Substituted Phenylpropionic Acids -3.6 Log k . Lo« k — -3.2 - .4 0 - 08 -0 0.2 - 1.2 amt Rltosi fr h Etrfcto o Sbtttd ezi Acids Benzoic Substituted of Esterification the for Relationship Hammett amt Rltosi fr h Akln Spnfcto o Substituted of Saponification Alkaline the for Relationship Hammett - 0.1 OCH H C O - o • p - Cl - p ty Cinmates innam C Ethyl 0.1 IUE 3 FIGURE IUE 2 FIGURE -51- o Vko k V Log 0.2

- I o-C ♦ * ° / o-NOe Cl -C o Q3 2

.2 m - NO - m 4 Q p-NO* o-NO - 5 2 - cinnaraic acids respectively. in each case the points which repre sent the meta and para derivatives form a reasonably straight line while the points corresponding to the ortho derivatives are scattered.

Steric effects are evident here also. Kindler's assumption (p. 4 ) that the saponification of ortho—substituted ethyl cinnamates is not subject to steric effects is shown to be false. Inspection of Figures 1 and 2 indicates that the meta and para derivatives would more nearly form straight lines if the p-methoxy derivatives were neglected. The decreased rate of esterification of p-alkoxybenzoic acids as compared to the rate predicted by the 2 Hammett equation has been noted before without explanation.

Speculation as to the nature of the steric effect in the esterification of ortho—substituted phenylpropiolic acids is not particularly rewarding. Examination of Figure 1 shows that the steric effect increases the rate of reaction above that predicted by the Hammett equation. This indicates the absence of any hindrance due to bulk interference since that would tend to lower the rate. Consequently some electrostatic or field effect is probably responsible for the anomalous behaviour of the orthoder ivatives* Of the substituents used here the o—nitro group ccmea closest to the side chain. Figure 4 is a scale diagram? of o—nitro—

1. J. F. J. Dippy and J. E. Page, ^J. Chem. Soc., 357 (1938)* 2 . Ref. lb on page 49, and R. J. Hartman, H. K.Hoogsteen, and J. A. T'oede, _J. Am. Chem. j o c . , 6 0 . 1714 (1944). 3. L. Pauling, op. cit., pp. 160 ff. -53- phenylpropiolic acid as a planar molecule showing the distance of closest approach of a carboxyl oxygen atom and a nitro oxygen atom to be 3 -6 X between centers, while the distance from the nitro oxygen o atom to the nearest carbon atom in the ethynylene group is 2.4 A.

Thus the ortho group is probably too far from the carboxyl group to affect it noticeably but near enough to the ethynylene group to exert an appreciable influence on it. o-Hydroxyphenylacetylene has a lower boiling point than its methyl ether, and vapor pressure and kryoscopic data indicate the

o - N it ropheny Ipropiolic Acid FIGURE 4 -54- absence of intermolecular association usually present in hydroxy compounds, including o-cyanophenol. Shifts in the infrared absorp tion which usually accompany intermolecular hydrogen bonding are absent. From this evidence it was concluded^ that an internal chelation of some sort exists in o-hydroxyphenylacetylene. That work indicates the alkyne group of the phenylacetylene type structure is capable of interaction with ortho substituents. An internal interaction may be involved in ortho—substituted phenylpropiolic acids. The rates of esterification of all the ortho-substituted phenyl propiolic acids are higher than predicted from the Hammett equation. No interpretation similar to that given for the strength of these acids is satisfactory for explaining the rates. In acid—catalyzed esterification with methanol an increase in rate reflects an increase in the electrons available at the carboxyl group. For such an in crease to be brought about by the adjacent positive group as well as by a negative group is indeed unlikely. Though a sound explanation of the steric effect in ortho—sub stituted phenylpropiolic acids is not apparent, the existence of the effect is established. C. Energies and Entropies of Activation. Since the highest rate of esterification among the substituted phenylpropiolic acids studied here is only three times greater than

1. V. Prey and H. Berbalk, Monatsh., 82, 990 (1951). -55- the rate of the slowest acid the differences in activation energy and PZ factors vd.ll not be large. Therefore considerable experimental accuracy in the determination of the rate constants is necessary to distinguish these differences. The accuracy obtained in this work was not sufficient for more than loose generalizations on the cause of the rate differences. Both E and PZ appear to be responsible for changes in rate (Table VIII and as a rule an increase In E brings an increase in PZ, vhich is in accord with the behavior of these factors in the acid-catalyzed esterification of substituted benzoic 1 acids. There are not enough data to show if the tendency to increase E and PZ for ortho substituents on phenylpropiolic acid is a general one. An Increase In PZ is the same as an increase in entropy of activation. D. Spectra. The ultraviolet absorption of the ethyl esters of the sub stituted phenylpropiolic acids (Fig. 5 and Table X) was investigated for further evidence of steric hindrance. The spectra of a vast number of benzene derivatives have been studied recently and attempts at correlations made. 2 However, only seme generalizations can be

1. (a) H.J. Hartman and A. G. Gassmann, _J. Am. Chan. 3oc., 62, 1559 (1940); (b) C. N. Hinshelwood and A. R. Legard, _J. Chem. Soc., 587; 588 (1935). 2. (a) L. Doub and J. M. Vandenbelt, J. Am. Chem. Soc., 69. 2714 (1947); (b)ibid., 21* 2414 (19497; T c) C. M. Moser and A. I. Kohlenberg, .J. Chem. Soc.. 804 (1951). ~56-

5 sP®ctr« of Eth

°f ^nylpropioil 22*- UPiOlic A c i d g

So L

/<} /

0 ' OCH o rr" OCH, p - o c h :

Ol -57- made with respect to types and position of substituents on the ring. Most benzene compounds show two bands at wavelengths above 220 mu which are really bands from benzene itself but displaced by the sub stituents to various wavelengths. In many cases, particularly with p-disubstituted derivatives, the longer wavelength band disappears. This was ascribed to superimposition by the stronger band of normally shorter wavelength.^- This shorter wavelength (principal) band is

Table X Ultraviolet Absorption Maxima of Ethyl Esters of Phenylpropiolic Acids

Substituent Secondary -3 mu W X 10 ^ mu ^tnax x H 258 15.2 o—Cl 259 1 2 . 6 m—Cl 256 14-4 p—Cl 266 18.7 o-N02 232 20.2 307 4.0 m-N02 250 22.3 p-no2 286 19.6 o -0CH3 268 9.3 3 1 0 6.7 m—OCH3 262 12.7 3 0 1 4-3 P-OCH3 286 19.0

1. C. M. Moser and A. I. Kohlenberg, J. Chem. Soc.. 804 (1951) -58- more sensitive to substituents than the longer wavelength (secondary) band. The intensity of the principal band is increased by a second substituent in the para position and is usually decreased by ortho and meta substituents. The close similarity of intensity and location of the bands of ortho and meta derivatives is striking. Nitro sub stituents cause many anomalies which lack explanation. The spectra of the phenylpropiolate esters only partially conform to these previous observations. For the para-substituted compounds the single band exhibits the expected increase in intensity and wavelength over the unsubstituted ethyl phenylpropiolate. The o- and m—methoxy derivatives show both absorption bands, but the chloro derivatives have only the principal band. In both cases the spectrum of the ortho derivative is similar to that of the meta derivative. Steric hindrance of some type probably contributes to the weak absorption of the o—methoxy and o—chloro derivatives.^

The nitro compounds are again anomalous. Both the m—nitro and the o-nitro compounds have principal bands of greater intensity than the p-nitro ester. That these principal bands are shifted to 2 shorter wavelengths has precedence in the nitrocinnamic acids.

Only the o—nitro derivative has the secondary band. The spectra of o-nitro- and o—methoxyphenylpropiolic acids were nearly the same as the spectra of their respective esters. Dilution of the absorbing

1. H. B. Klevens and J. R. Platt, J_. Am. Chem. Soc. t 71. 1714 (1949). 2. J. E. Purvis, J_. Chem. Soc., 107. 966 (1915). -59- solution of ethyl p-methoxyphenylpropiolate to one-third strength did not change its spectrum, A comprehensive study of the absorption of benzene derivatives with unsaturated alkyl side chains is needed before a worthwhile interpretation of these spectra can be made. In the infrared region each ester showed a strong band at 4.5-4*6 characteristic of an alkyne. No significant shifts in this band were noted.

4 -60-

V. SUMMARY

The preparation of phenylpropiolic acid and its mono substituted chloro, nitro, and methoxy derivatives in the three ring positions is described. The ionization constants in 35% dioxane (wt.) and the rates of acid-catalyzed esterification of these acids at 25* and 35* in methanol have been determined. A field effect is proposed in partial explanation of the mag nitude the ionization constants of the ortho-substituted acids as compared to the para isomers. A plot of the logarithms of the esterification rate constants against the logarithms of the ionization constants for all the sub stituted phenylpropiolic acids according to the Hammett equation is presented. The points corresponding to the meta and para derivatives lie on a straight line but the points corresponding to the ortho derivatives do not lie on the line. Consequently a steric effect is presumed present in the ortho derivatives. Variations in esterification rates are related to changes in both the energy and entropy of activation, but no correlation of these factors with steric effects can be made. Ultraviolet and infrared absorption of the ethyl esters of the substituted phenylpropiolic acids is described. -61-

APPENDIX -62-

Ionization Constants of Phenylpropiolic Acid in 35?£ Dioxane at 25*

Titration 1; 0.0992 N sodium hydroxide. pH V, (ml.) V3 (ml.) PK 3.13 3.50 5.59 3.24 3.39 5.00 4.09 3.25 3.79 7.00 2.09 3.24

2; 0 .0992 N sodium hydroxide.

pH v, v3 pK 3.15 3.60 5.44 3.24 3.41 5.10 3.94 3.25 3.70 6.60 2.44 3.23

3; o .1006 N sodium hydroxide.

pH v T v3 pK 3.12 3.50 5.49 3.22 3.37 5.00 3.99 3.23 3.68 6.50 2.49 3.27 -63-

Ionization Constants of o-Chlorophenylpropiolic Acid

in 35?£ Dioxane at 25*

Titration 1; 0.0971 N sodium hydroxide.

pH V, (ml.) Vj (ml.) pK

3 .0 5 3 .7 5 5-48 3 .1 0 3 .3 2 5 .5 0 3.73 3 .0 9 3 .6 4 7 .1 0 2.13 3 .0 ?

2; 0 .0 9 9 2 N sodium hydroxide.

pH v, v3 pK

3 .0 0 3 .7 0 5.32 3.03 3 .2 9 5 .3 0 3 .7 2 3.06 3 .5 8 6 .8 0 2 .2 2 3.05

3; 0 .0 9 9 2N sodium hydroxide.

pH v, v3 pK

3.03 3 .6 0 5.38 3.09 3 .2 8 5.10 3 .8 8 3.09 3 .5 8 6 .6 0 2 .3 8 3.09

i -64-

Ionization Constants of m^Chlorophenylpropiolic Acid in 35% Dioxane at 25"

Titration 1; 0.1006 N sodium hydroxide. pH V, (ml.) V3 (ml.) pK 2.86 3.00 5.94 2.98 3.10 4.50 4.44 2.99 3.38 6.00 2.94 3.01

Titration 2; 0.1006 N sodium hydroxide. pH V, V3 pK 2.87 3.00 5.99 3.00 3.12 4.50 4.49 3.02 3.39 6.00 2.99 3.03 -65-

Ionization Constants of p-Chlorophenylpropiolic Acid in 39% Dioxane at 25*

Titration 1; 0.0971 N sodium hydroxide.

pH V, (ml.) V3 (ml.) PK

3-03 3 .6 0 5.35 3 .0 8 3 .3 0 5.25 3.70 3.08 3.67 7.00 1.95 3 .0 7

2; 0.0992 N sodium hydroxide.

PH v, v3 pK

3.00 3 .6 0 5.53 3.06 3.29 5.30 3-83 3.08 3 .5 8 6.70 2.43 3.10

3; 0.0992N sodium hydroxide.

pH v. v3 pK

2.97 3.60 5.46 3.02 3.24 5.10 3.96 3.06 3.52 6.60 2.46 3.04 -66-

Ionization Constants of o-Nitrophenylpropiolic Acid in Dioxane at 25*

Titration 1; 0.0992 N sodium hydroxide. PH V, (ml.) V3 (ml.) pK 2.83 3.60 5.50 2.83 3.09 5.30 3.80 2.84 3.38 6.80 2.30 2.83

2; 0.0992 N sodium hydroxide. PH Vi v3 pK 2.87 3.80 5.16 2.83 3.14 5.50 3.46 2.84 3.37 6.70 2 .2 6 2.82 -67-

Ionization Constanta of m-Nitrophenylpropiolic Acid in 35^ Dioxane at 25*

Titration 1; 0.0992 N sodium hydroxide.

pH V, (ml.) V3 (ml.) pK 2.75 3.50 5.43 2.72 2.93 5.00 3.98 2.74 3.26 6.50 2.48 2.75

Titration 2; 0.0992 N sodium hydroxide.

pH V, V3 pK 2.79 3.80 5.22 2.73 3.00 5.20 3.82 2.73 3.29 6.70 2.32 2.74 -68-

Ionization Constants of p-Nitrophenylpropiolic A d d in 35# Dioxane at 25*

Titration 1; 0.0971 N sodium hydroxide.

PH V, (ml.) V3 (ml.) pK 2.69 3.75 5.55 2.61 2.90 5.50 3.80 2.57 3.23 7.20 2.10 2.58

2; 0.0992 N sodium hydroxide.

pH v, v3 pK 2.65 3.50 5.55 2.57 2.89 5.20 3.82 2.58 3.16 6.60 2.42 2.60

Titration 3; 0.0992 N sodium hydroxide. pH V, V3 pK 2.6A 3.60 5.37 2.53 2.85 5.10 3.87 2.54 3.15 6.60 2.37 2.58 -69-

Ionization Constants of o—Methoxyphenylpropiolic Acid in 35% Dioxane at 25*

Titration 1; 0.1006 N sodium hydroxide.

pH V, (ml.) V3 (ml.) pK 3.28 3.50 5.33 3.39 3.53 5.00 3.83 3.37 3.84 6.50 2.33 3.37

2j 0.1006 N sodium hydroxide.

pH v, v3 pK 3.26 3.50 5.36 3.37 3.53 5.00 3.86 3.37 3.84 6.50 2.36 3.37 -70-

Ionization Constants or m—Methoxyphenylpropiolic Acid in 35/£ Dloxane at 25*

Titration 1; 0.1006 N sodium hydroxide.

PH V, (ml.) V3 (ml.) pK 3.03 3 .0 0 5.91 3 .2 0 3.30 4.50 4.41 3.23 3.57 6 .0 0 2.91 3 .2 2

2; 0 .1 0 0 6N sodium hydroxide.

pH v . v 3 pK 3.03 3 .0 0 5.92 3 .2 0 3.29 4.50 4.42 3 .2 2 3.57 6 .0 0 2.92 3 .2 2 -71-

Ionization Constants of p-Methoxyphenylpropiolic Acid in 359E Dioxane at 25*

Titration 1; 0.1006 N sodium hydroxide.

pH V, (ml.) V3 (ml.) pK

3 .2 2 3 .0 0 5.89 3.43 3.50 4.50 4.39 3.45 3.78 6 .0 0 2.89 3.44

25 0 .1 0 0 6N sodium hydroxide.

pH v , v 3 pK 3.23 3.00 5.90 3.44 3.50 4.50 4.40 3.45 3.78 6 .0 0 2.90 3.44 -72-

Rate of Eaterification of Phenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 25*

Run 1; 0.00971 N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of st'd base equiv. to catalyst in sample. Time in ml. of k % min. 0.04950 N 1. /mole-min. completion NaOH

0 7.85 — 0 900 6 .2 1 0.0333 21 1285 5.76 0.0321 27 1550 5.47 0.0317 31 2110 4-96 0.0315 38 2540 4.59 0 .0 3 1 8 42 3045 4.27 0 .0 3 1 0 47 3340 4.04 0 .0 3 1 6 50

Run 2; 0.00971 N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of st'd base equiv. to catalyst in sample. Time in ml. of k % min. 0.04950 N 1./mole-min. completion NaOH

0 7 .8 6 — 0 900 6 .2 2 0.0328 21 1280 5.78 0.0317 27 1545 5.53 0 .0 3 1 2 30 2110 4.95 0.0315 38 2540 4 .6 0 0.0318 42 3040 4.25 0.0313 47 3340 4.08 0.0318 49

av. 0.0318 -73-

Rate of Eaterification of o-Chlorophenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 25*

Run ; 0.00958 N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of st'd base equiv. to catalyst in sample.

Time in ml. of k % min. 0 .0 4 9 5 0 N 1. /mole-min. completion NaOH

0 7.85 — > 0 955 6 .2 6 0 .0 2 9 8 21 1335 5.84 0.0291 26 1565 5.58 0.0300 30 2160 5.09 0 .0 2 8 8 36 2590 4.77 0.0286 40 3085 4.35 0 .0 2 9 6 46 3385 4.22 0.0288 47

Run >; 0.00958 N catalyst (cor.), 0.983 ml. samples, 0 .1 9 ml. of st'd base equiv. to catalyst in sample. Time in 0.04950 N k % min. NaOH completion

0 7.82 — 0 950 6.29 0 .0 2 9 0 20 1330 5 .8 6 0 .0 2 8 6 26 1555 5.60 0 .0 2 9 0 29 2155 5-07 0.0289 36 2585 4.74 0.0290 40 3080 4.44 0.0282 44 3385 4 .2 6 0.0282 47

av. 0.0290 -74-

Rate of Esterification of m-Chlorophenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 25°

Run 1; 0.00958 N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of st’d base equiv. to catalyst in sample. Time in ml. of k % min. 0.04950 N 1./mole-min. completion NaOH

0 7.81 — 0 1090 6.33 0.0239 19 1540 5.85 0 .0 2 4 6 26 2200 5.26 0 .0 2 5 0 33 2630 5 .0 1 0.0242 37 3120 4.70 0.0243 41 3430 4.53 0 .0 2 4 2 43

Run 2; 0 .0 0 9 8 1N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of stfd. base equiv. to catalyst in sample. Time 0.04950 N k £ NaOH completion

0 7.76 - 0 1180 6.23 0.0232 20 1660 5-63 0.0254 27 2210 5.26 0.0239 33 2770 4.84 0 .0 2 4 6 39 3040 4.70 0.0240 41 3885 4 .2 2 0.0240 47 5000 3.76 0.0231 53

av. 0.0242 -75-

Rate of Esterification of p— Chlorophenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 25*

Run lj 0.00981 N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of st’d. base equiv. to catalyst in sample.

Time in ml. of k % min. 0.04950 N 1./mole-min. completion NaOH

0 7.85 0 1230 6.08 0 .0 2 6 0 23 1680 5.59 0.0267 29 2220 5.23 0 .0 2 5 6 34 2780 4-79 0 .0 2 4 8 40 3065 4.63 0.0252 42 3735 4 .2 6 0.0247 47 4475 3.92 0.0244 51

>; 0.00981 N catalyst (cor.), 0 .9 8 3 ml. samples, 0 .1 9 ml. of st’d. base equiv. to catalyst in sample. Time 0.04950 N k % NaOH completion

0 7.82 — 0 1230 6.08 0 .0 2 5 6 23 1680 5 .6 2 0.0259 29 2220 5.26 0.0244 33 2780 4.80 0.0254 40 3060 4.65 0.0249 42 3735 4.25 0 .0 2 4 8 47 4470 3.98 0.0237 50

av. 0.0252 -76-

Rate of Esterification of o-Nitrophenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 25*

Run 1; 0.00971 N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of st'd. base equiv. to catalyst in sample. Time in ml. of k % min. 0.04950 N 1./mole—min. completion NaOH

0 7.81 - 0 1240 6.10 0.0253 22 1570 5.79 0.0251 27 1980 5.45 0.0246 31 260 5 4.96 0.0246 37 2930 4 .8 6 0.0234 39 3990 4.15 0.0248 48 4660 3.86 0.0242 52

Run 2; 0.00971 N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of st'd. base equiv. to catalyst in sample. Time 0.04950 N k % NaOH completion

0 7.80 - 0 1230 6.09 0.0259 22 1555 5 .7 8 0.0257 27 1965 5.46 0.0248 31 2590 5.04 0.0240 36 3060 4.81 0.0232 39 397 5 4.2 5 0.023 5 47 4645 4.00 0.0229 50

av. 0.0245

4 -77-

Rate of Esterification of m-Nitrophenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 25*

Run 1} 0.00981 N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of stTd. base equiv. to catalyst in sample.

Time in ml. of k * min. 0.04950 N 1./mole-min. Completion NaOH

0 7.87 0 1685 6.15 0.0187 22 2280 5 .8 2 0.0172 27 3075 5.35 0.0172 33 4010 4.87 0.0172 39 4485 4.75 0.0163 41 5890 4.17 0.0167 48

Run 2; 0.00981 N catalyst (cor.), 0.983 ml. samnles, 0.19 ml. of st'd. base equiv. to catalyst in sanrnle. Time O.OA950 N £ NaOH 1./mole-min. comoletion

0 7.75 - 0 1675 6.18 0.0169 22 2275 5.74 0.0173 27 3070 5.33 0.0166 32 4005 4.78 0.0175 39 4480 4.64 0.0173 41 5205 4.32 0 .0 1 7 0 45 5885 4.17 0 .0 1 6 1 47

av. 0.0171 -78-

Rate of Esterification of p-Nitrophenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 25*

Run L; 0.00998 N catalyst (cor.), 0.983 ml. samples, 0.20 ml. of stTd. base equiv. to catalyst in sample. Time in ml. of k min. 0.04950 N 1./mole-min. completion NaOH

0 4.10 - 0 2035 3.16 0.0152 24 2985 2.89 0.0153 33 4050 2.46 0.0163 42 4715 2.29 0.0163 46 5540 2.15 0.0156 50 5985 2.07 0.0155 52

Run 2; 0.00998 N catalyst (cor.), 0.983 ml. samples, 0.20 ml. of stTd. base equiv. to catalyst in sample. Time 0.04950 N k £ NaOH completion

0 4.14 - 0 2040 3.13 0.0162 25 3120 2.81 0.0152 33 4050 2.49 0.0161 42 4710 2.29 0.0165 47 5550 2.12 0.0161 52 5985 2.05 0.0159 53

av. 0.0158 -79-

Rate of Eaterification of o-Methoxyphenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 25*

Run 1; O.OO958 N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of st'd. base equiv. to catalyst in sample. Time in ml. of k % min. 0.04950 N 1. /mole-min completion NaOH

0 7.82 — 0 600 6.33 0.0450 20 965 5 .6 8 0 .0 4 4 8 28 1080 5.54 0.0435 30 1445 5.04 0.0436 36 2020 4.39 0.0440 45 2255 4.19 0.0436 48 2540 3.93 0.0429 51 2970 3 .6 8 0.0426 54

Run 2; 0.00958 N catalyst (cor.), 0.983 ml. samples, 0 .1 9 ml. of st'd. base equiv. to catalyst in sample. Time 0.04950 N k % NaOH completi on

0 7.80 — 0 600 6.33 0.0435 20 955 5.64 0 .0 4 6 2 28 1095 5.52 0.0433 30 1435 5.03 0.0446 36 2010 4.48 0 .0 4 2 2 44 2245 4 .2 6 0 .0 4 2 1 47 2530 3.97 0 .0 4 3 0 50

av. 0.0438 -80-

Rate of Esterificatlcn of m-Methoxyphenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 25*

Run 1; 0,00981 N catalyst (cor,), 0,983 ml, samples, 0.19 ml. of st'd, base equiv, to catalyst in sample. Time in ml. of k % min. 1 . /mole-min . completion ° - « 3 P N 0 7.82 — 0 1025 6.06 0.0312 23 1410 5.65 0.0302 28 1660 5.40 0.0299 32 2155 4.92 0.0306 38 2490 4.80 0.0282 40 3070 4.28 0.0299 46 3580 3.98 0.0296 51 4080 3.73 0.0290 54

Run 2; 0.00981 N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of st'd. base equiv. to catalyst in sample. Time 0.04950 N k % NaOH completion

0 7.83 — 0 1020 6.08 0.0314 23 1405 5.61 0.0310 29 1655 5.38 0 . 0 3 H 32 2150 4.98 0.0299 37 2485 4.75 0.0290 40 3065 4.29 0.0298 46 3600 3.94 0.0300 51 4080 3.75 0.0290 53

av. 0.0300 -81-

Hate of Esterification of p-Methoxyphenylpropiolic Acid with Methanol catalyzed by Hydrogen Chloride at 25*

Run 1; 0.00958 N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of st'd. base equiv. to catalyst in sample. Time in ml. of k # min, 0.04950 N 1./mole-min. completion NaOH

0 7.77 - 0 780 6 .2 6 0.0352 20 1115 5.32 0.0341 26 1490 5.40 0.0335 31 2065 4.84 0.0338 39 2495 4.52 0.0329 43 3005 4.H 0.0336 48 3300 3.94 0.0331 51

Run 2; 0.00958 N catalyst (cor.), 0.983 ml. samples, 0.19 ml. of st'd. base equiv. to catalyst in sample. Time 0.04950 N k £ NaOH completion

0 7.78 - 0 790 6.29 0.0336 20 1110 5.85 0.0337 25 1485 5.38 0.0345 32 2060 4 .8 4 0.0334 39 2490 4.51 0.0331 43 3000 4.13 0.0332 48 3295 3.91 0.0337 51

av. 0.0336 -82-

Rate of Esterification of Phenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 35*

Run ; 0.00933 N catalyst (cor.), 0.987 ml. samples, 0.18 ml. of st'd. base equiv. to catalyst in sample. Time in ml. of k % min. 0.04985 N 1./mole-min. completion NaOH O 7.70 - 0 560 5-72 0.0700 26 1260 4.28 0.0687 46 1835 3.42 0.0707 57

Run 2; 0.00933 N catalyst (cor.), 0.987 ml. samples, 0.18 ml. of st'd. base equiv. to catalyst in s unple. Time 0.04985 N k C4 NaOH completion

0 7.74 _ 0 560 5.72 0.0690 27 1260 4.26 0.0703 46 1835 3.42 0.0713 57 -83-

Rate of Esterification of Phenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 35° (cont.)

Run 3* 0.00975 N catalyst (cor.), 0.987 nil. samples. 0.19 ml. of st'd. base equiv. to catalyst in sample. Time in ml. of k % min. 0.04950 N 1. /mole-min completion NaOH 0 7.95 — 0 450 6.10 0.0728 24 775 5.19 0.0736 35 1115 4.53 0.0717 44 1410 4.08 0.0694 50 1700 3.66 0.0690 55 1985 3.36 0.0680 59

Run A; 0.00980 N catalyst (cor.), 0.987 ml. samples, 0.19 ml. of st'd. base equiv. to catalyst in sample. ime 0.04950 N k NaOH completion

O 7.84 — 0 435 6.05 0.0720 23 545 5.77 0.0704 27 733 5.34 0.0682 33 950 4* 84 0.0688 39 1140 4.50 0.0682 44 1330 4.33 0.0634 46 1858 3.56 0.0650 56

av. 0.070 -84-

Rate of Esterification of o-Chlorophenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 35*

Run 1; 0.00942 N catalyst (cor.), 0.987 n*!- samples, 0.18 ml. of st'd. base equiv. to catalyst in sample. Time in ml. of k # min. 0.04985 N 1./mole—min. completion NaOH 0 7.83 - 0 565 5.78 0.0695 28 1270 4.40 0.0667 45 1835 3.66 0.0650 54

Run 2; 0.00977 N catalyst (cor.), 0.987 ml. samples, 0.20 ml. of st'd. base equiv. to catalyst in sample.

Time 0.04985 N k % NaOH completion

0 7.74 - o 465 5.91 0.0718 24 896 4.95 0.0665 37 1320 4.18 0.0671 47 1875 3.47 0.0654 57

Run 3; 0.00967 N catalyst (cor.), 0.987 ml. samples, 0.19 ml. of 3tfd. base equiv. to catalyst in sample. Time 0.04950 N k $> NaOH completion

O 7.88 0 475 6.06 0.0685 24 800 5.20 0.0664 36 1155 4.54 0.0675 43 1445 4.11 0.0662 49 1945 3.52 0.0644 57

av. 0.067

i -85-

Rate of Esterification of m-Chlorophenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 35*

Run 1; 0.00985 N catalyst (cor.), 0.987 ml. samples, 0.20 ml. of st'd. base equiv. to catalyst in sample. Time in ml. of k # min. 0.04950 N 1./mole-min. completion NaOH

0 7.89 - 0 510 6.22 0.0554 22 690 5.79 0.0562 27 920 5-35 0.0544 33 1065 5.06 0.0551 37 1325 4.64 0.0556 42 1625 4.32 0.0528 46 2040 3.84 0.0523 53

Run 2; 0.00985 N catalyst (cor.), 0.987 ml. samples, 0.20 ml. of st'd. base equiv. to catalyst in sample. Time 0.04950 N k % NaOH completion

0 7.87 - 0 510 6.24 0.0547 21 690 5.82 0.0546 27 920 5.31 0.0560 33 1065 5.13 0.0530 36 1325 4.66 0.0545 42 1625 4.34 0.0520 46 2040 3.84 0.0522 53

av. 0.054 -86-

Rate of Esterification of p-Chlorophenylpropiolic Acid vrith Methanol Catalyzed by Hydrogen Chloride at 35*

Run 1; 0.00966 N catalyst (cor.), 0.987 ml. samples, 0.19 ml. of st’d. base equiv. to catalyst in sample.

Time in ml. of k % min. 0.04985 N 1. /mole—min. completion NaOH

0 7.94 — 0 470 6.32 0.0582 21 903 5.38 0.0573 33 1325 4-76 0.0538 41 1885 4.10 0.0520 50 2505 3.45 0.0521 58

Run 2; 0.00970 N catalyst (cor.), 0 . 9 8 7 ml. samoles, 0 . 1 9 ml. of s t ’d. base equiv. to catalyst in sample.

Time 0.04950 N k % NaOH completion 0 7.82 — 0 480 6.20 0.0589 21 982 5.20 0.0555 34 1220 4.74 0.0565 41 1425 4.49 0.0552 44 1665 4.20 0.0 543 47 2335 3.48 0.0528 57

av. 0.055 -87-

Rate of Esterification of o—Nitrophenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 35*

Hun ; 0.00971 N catalyst (cor.), 0.987 nil. samples, 0.19 ml. of st*d. base equiv. to catalyst in sample.

Time in ml. of k % min. 0.04950 N 1./mole-min. completion NaOH 0 7.79 ~ 0 585 5.94 0.0572 24 930 5.23 0.0571 34 1350 4.55 0.0558 43 1665 4.14 0.0553 48 2035 3.73 0.0545 54

Run 2$ 0.00967 N catalyst (cor.), 0.987 ml. samples, 0.19 ml. of st*d. base equiv. to catalyst in sample.

Time 0.04950 N k % NaOH completion

0 7.88 — 0 580 6.08 0.0552 23 923 5.31 0.0560 33 1345 4.58 0.0564 43

av. 0.056 -88-

Rate of Esterification of m-Nitrophenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 35°

Run 1; 0.00975 N catalyst (cor.), 0.987 ml. samples, 0.20 ml. of st'd. base equiv. to catalyst in sample. Time in ml. of k % min. 0.04985 N 1./mole-min• completion NaOH

0 7.54 — 0 990 5.58 0.0381 27 1 H 5 5.05 0.0372 34 1910 4.55 0.0365 41

Run 2; 0.00966 N catalyst (cor.), 0.987 ml. samples, 0.19 ml. of st'd. base equiv. to catalyst in sample. Time 0.04950 N k * NaOH completion 0 7.83 — 0 810 6.00 0.0406 24 1335 5.24 0.0400 34 1625 4.88 0.0400 38 2045 4.54 0.0376 43 2625 3.97 0.0383 51 3020 3.74 0.0369 54

Run 3;3 0.00970 N catalyst (■cor.), 0.987 ml. samoles, 0.19 ml. of st'd. base equiv. to catalyst in sample. Time 0.04950 N k * NaOH completion

0 7.88 — 0 650 6.36 0.0395 1040 5.65 0 .0 4 1 0 29 1370 5.27 0.0390 33 1850 4.87 0.0357 39 2350 4.35 0.0362 46 2840 3.98 0.0357 51

av. 0.038

4 -69-

Rate of Esterification of p-Nitrophenylpropiolic Acid with Methanol Catalysed by Hydrogen Chloride at 35*

Run 1; 0.00970 N catalyst (cor.), 0.937 ml. samples, 0.19 ml. of st*d. base equiv. to catalyst in sample. Time in ml. of k % min. 0.04950 N 1./mole—min. completion NaOH

0 7.90 0 965 6.02 0.0350 24 1695 5.12 0.0345 36 2720 4.24 0.0332 47 3305 3.85 0.0328 52

Run 1; 0.00967 N catalyst (cor.), 0.987 ml. samples, 0.19 ml. oJ stTd. base equiv. to catalyst in sample. Time 0.04950 N k % NaOH completion 0 7.90 0 950 6.04 0.0356 24 1690 5.08 0.0357 37 2710 4.27 0.0332 47 3295 3.81 0.0336 53

av. 0.034 -90-

Rate of Esterification of o-Methoxyphenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 35*

Run 1; 0.00970 N catalyst (cor.), 0.987 ml. samples, 0.19 ml. of st'd. base equiv. to catalyst in sample. Time in ml. of k % min. 0.04950 N 1. /mole-min. completion NaOH

0 7.85 — 0 302 6.09 0.1049 23 493 5.41 0.0995 32 680 4.85 0.0976 39 900 4.25 0.0983 47 1065 3.93 0.0968 51 1200 3.70 0.0948 54

I; 0.00979 N catalyst (

0 7.84 — 0 295 6.14 0.1022 22 485 5.42 0.0988 32 675 4.82 0.0987 40 891 4.27 0.0980 47 106 3.93 0.0956 51 1200 3.74 0.0933 54

av, 0.098 -91-

Rate of Esterification of m-Methoxyphenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 35°

Run Ij 0.00994 N catalyst (cor.), 0.987 ml. samples, 0.20 ml. of stTd. base equiv. to catalyst in sample. Time in ml. of k min. 0.04950 N 1./mole—min. completion NaOH 0 7.83 — 0 510 5.85 0.0706 26 660 5.42 0.0704 31 790 5.10 0.0715 36 900 4.86 0.0701 39 1040 4.64 0.0689 42 1200 4.43 0.0661 45 1440 4.02 0.0670 50

Run 2; 0.00994 N catalyst (cor.), 0.987 ml. samples, 0.20 ml. of st’d. base equiv. to catalyst in sample. Time 0.04950 N k % NaOH completion

0 7.79 — 0 510 5.81 0.0706 26 660 5.38 0.0709 32 795 5.10 0.0697 35 900 4.86 0.0699 39 1040 4.58 0.0698 42 1200 4.36 0.0675 45 1440 3.97 0.0672 50

av. 0.069 -92-

Rate of Esterification of p—Methoxyphenylpropiolic Acid with Methanol Catalyzed by Hydrogen Chloride at 35*

Run ; 0.009&2 N catalyst (cor.), 0.987 ml. samples, 0.20 ml. of st'd. base equiv. to catalyst in sample. Time in ml. of k % min. 0.04985 N 1. /mole—min. completion NaOH

0 8.75 — 0 490 6.45 0.0810 27 913 5.30 0.0790 40 1338 4.51 0.0758 50 1903 3.72 0.0736 59

Run >; 0.00967 N catalyst (cor.), 0.987 ml. samples, 0.20 ml. oi st'd. base equiv. to catalyst in sample. Time 0.04985 N k NaOH completion 0 7.74 — 0 482 5.68 0.0813 27 909 4.62 0.0794 41 1332 3.89 0.0767 51 1892 3.14 0.0760 61

Run 3; 0.00990 N catalyst (cor.), 0.987 ml. samples, 0.20 ml. oj st'd. base1 equiv. to catalyst in sample. Time 0.04950 N k NaOH completion 0 7.82 — 0 405 6.03 0.0776 23 63 5 5.32 0.0788 33 780 4.97 0.0768 38 960 4.62 0.0737 42 1140 4.27 0.0745 48 1540 3.67 0.0731 55

av. 0.077 -93-

AUT03I0GHAPHY I, Stewart Henry Merrill, was b o m in Andover, Ohio, September 8, 1926, and received my secondary education in the public school of that town. After eighteen months’ service in the United States Navy I entered Case Institute of Technology from which I received the degree Bachelor of Science in 1950. In 1950 I entered the Graduate School of the Ohio State University. While there I was a teaching assistant for two years, one year each on the general chemistry and organic chemistry staffs. For the academic year 1952—1953 I received a National Science Foundation fellowship which was renewed for the reaminder of ray residence while com pleting the requirements for the Degree of Doctor of Philosophy.