m Hl‘ 145 048 __THS A SWDY OF THE ALKYLATEGN OF RYQRATROPONETRRLE WETH AMYL HALiDES Thesis for fho Degree of M. 5. MECHfGAN STATE COLLEGE Ridwrcf Lee Jacobs W55 This is to certify that the thesis entitled A Study of the Alkylation of Hydratroponitrile with Amyl Halides presented by Richard Lee Jacobs has been accepted towards fulfillment of the requirements for ___M- s- W degree in Xmas/QM Major professor Date May 199 1955 0-169 LIDRARY Michigan Scam University .1 STUDY OF THE.ALKYLATION OF HYDRATROPONITRILE WITHIAMYL HALIDES By Richard Lee Jacobs .1 THESIS smbmitted to the School of Graduate Studies of Michigan State College of Agriculture and Applied Science in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Department of Chemistry 1955 ACKNOWLEDGMENT The author wishes to express his sincere appreciation to Dr. Gordon L, Goerner, for the encouragement, aid, and guidance which he so generously gave during the course of the investigation and preparation of this thesis. W W W W {41' i ii Ky 3" .4 05:0“; 4wa Llej .h‘ i Li J VITA Name: Richard Lee Jacobs Born: August h, 1931 in Perrysburg, Ohio Academic Careers Perrysburg High School, 1915-1916 Bowling Green State University, Bowling Green, Ohio, 1910-1953 Michigan State College, East Lansing, Michigan, 11953-1955 Degrees Held: B. l. -- Bowling Green State University, 1953 iii ‘1 STUDY OF THE.1LKILITION OF HYDRATROPONITRILE ‘WITHIAMIL HALIDES By Richard Lee Jacobs AN'ABSTRACT Submitted to the School of Graduate Studies of Michigan State College of.1griculture and Applied Science in partial fulfillment of the requirements for the degree of iHASTER OF SCIENCE Department of Chemistry Year 1955 Approved‘dégtnvvézddy (71:) £g%;€VL¢4uL/L//' ‘g_ T" ABSTRACT This study was undertaken to extend prior work concerning the alkylation of hydratroponitrile with alkyl halides. This alkylation reaction proceeds according to the following equation. CH3-C-CN +12: NaNHz cna-c-CN H R Further intonation has been obtained showing (1) that the halogen of, the lllqyl halide has little effect upon the yield of allqlated product and (2) that the structure of the alkyl group is the Iajor factor in determining the yield. Branched chain anyl halides were found to be somewhat more satis- factory alkylating agents than normal.anyl halides. Tertiary'amyl chloride reacted little or not at all. These conclusions support those obtained earlier'by-Wbrkman (l). Unsaturated hydrocarbons were isolated from the reaction.nixture of tert.- amyl chloride and hydratroponitrile showing very definitely that one reason for the low yields of alkyiated products obtained when tertiary alkyl halides are used as the alkylating agents, is the de- hydrohalogenation of the tertiary alkyl group in the presence of an alkaline condensing agent. iv Since the nitriles prepared (see Table I) have not previously been reported, their physical properties were determined and each characterized‘by an appropriate derivative. This latter involved a study of the reaction.of hindered nitriles. Four of these nitriles, namely, I, II, III and VI, were hydrolyzed to the acid and converted to the corre5ponding anilide. Two others, V and IV could not be hydrolyzed, but could be reduced to the corres- ponding amines and then characterized.as their picrates. This increasing difficulty in hydrolysis wf a ' nitrile in.proceeding from less highly branched to more highly hindered, was found to be in agreement with the sixenunber concept of'Newman (2).. TABLE I PHYSICAL PROPERTIES OF NITRILES No. Compound 3,2,, , N25 d25 0 me D . h I 2-Phenyl-2-nethy1heptane- 108 1 1.h9b1 0.9281 nitrile II 2-Phenyl-2,S—dinethy1hexane- 101; 1 1.h939 0.9261), nitrile III 2-Pheny1-2,h-dinethylhexane- 99 ca.1 1.h969 0.93hl nitrile Iv 2-Phenyl-2,3-dinethylhexane- 115 2 1.5015 0.9h21 nitrile v 2-Pheny1-2-nethyl-3-ethyl- 103 1 1501.2 0.91489 pentanenitrile VI 2-Phenyl-2-cyc10pentylpropane-112 1 ‘ 1.5232 1.0010 nitrile VII 2-Pheny1-2,3,3-trinethy1- pentanenitrile REFERENCES (1) w. R. Workman, M. s. Thesis, Michigan State College (1950) , (2) M. s. Newman, J. in. Chem. Soc., 33, h783 (1950). vi TABLE OF CONTENTS Page INTRODUCTION..................................................... 1 HISTORICAL.......................... ........... .... ..... ......... 3 EXPERIMENTAL............. ....... ................................. 10 I ReagentS............................................... 10 II Preparation of IntermediateS........................... 12 1. 2-Chloropentane................................. 12 B. 3-Chlor0pentane............... ..... ... ........ .. 1h C. l-Chloro-Z-methylbutane......................... 16 D. ChlorocyclOPentane.............................. 18 E. Sodamide.................. ........ . ........ ..... 19 III Preparation of Hydratroponitrile....................... 21 IV Alkylation of Hydratroponitrile........................ 21:, V Preparation of Derivatives.... ....... .................. 27 DISCUSSION OF RESULTS...... ..................... .... ...... ....... 32 SUMMARY........................... ....... ........................ hl SUGGESTIONS FOR FURTHER RESEARCH...................... ...... ..... h3 smmTED mmcmooooooeoeoooooeoooeooeeeoooo ooooooooooooooooo e uh vii LIST OF TiBLES TABLE I ilkylation of Nitriles by Alkyl Halides... ....... ... ..... . II Alkylation of Nitriles by Organic Halides Containing Other Functional GroupS................................. ....... . III Yields of 2- and 3-Chloropentan6.......................... IV Yields of Hydratroponitrile............................... V Yields of Alkylated HydratrOponitriles.................... VI Physical Properties of Alkylated HydratrOponitrile........ VII Derivatives Prepared...................................... viii Page 5 6 15 23 26 28 31 LIST OF FIGURES Figure Page I O Struc-bures Of New Nitriles O O O O O 0 O O O O O O O O O 0 O O O O O O O O O O O O O O O O O O O 38 II. Structures of Nitriles Prepared by werkman................... 39 INTRODUCTION INTRODUCTION This problem is a continuation of a recent study (1) of the alkyla- tion of hydratroponitrile with butyl halides, in which the effect of different halogens and the effect of the structure of the alkyl group upon the yield was investigated. This alkylation reaction proceeds according to equation I. ' . Nana, I CH,-CH-,CN +RI_______; 0113-9-“ R workman (1) found that the halogen had little effect on the yield of alkylated product, but that the structure of the alkyl group did effect the yields, and that the yields decreased in the order 1803 secondary ) normal )) tertiary Since the previous study was limited in amps and since the results were not completely in agreement with the results of Tilford _e_t_ _a_l_. (2,3) it appeared desirable to extend the study to the alkylation of hydratrOpo- nitrile with the amyl halides, and in particular certain amyl chlorides. The influence of the halogen upon the yield was studied using normal amyl bromide, chloride, and iodide. By employing normal, 180, and tertiary amyl chlorides, cyc10pentyl chloride, 2- and 3-chloropentane and 2-methyl-1-chlorobutane, the effect of the structure of the alkyl group was determined. Attempts were made to isolate unsaturated hydrocarbons from certain of the reaction mixtures. Since the nitriles prepared have not previously been reported, their physical properties were determined and each characterized by an appropriate derivative. The latter involved a study of the re- actions of hindered nitriles. HI SP ORICAL HISTORICAL Nitriles of the type RCHch, which contain a reactive methylene group can be easily alkylated, to give mono or dialkylated products. The activating influence of the cyano group on an adjacent methylene group is analogous to that shown’by carbalkoxy and carbonyl groups. Just as esters condense with carbonyl compounds, nitriles react with carbonyl compounds in the presence of a basic condensing agent to yield Claisen type condensation products, as shown by equation II. NaDC ' R-CHO + R'-CH3—COOR" ———§-H—5-9 Rog = g-COOR" Rt 11 N H 11 . R-CHO + R'-CH3-CN EN 2 3.0 . C-CN This reaction has been run using ketones as the carbonyl component ()4). Esters have been condensed with nitriles in the presence of a basic condensing agent, the resulting products being Q -keto-nitriles as shown in equation III. NaNH 9f.“ In Rcooczhg + amazon—J.) R—C-CH-CN This reaction is similar in many reSpects to the well known acetoacetic ester condensation. The Dieclmann cyclization which occurs with esters of dibasic acids containing five or six carbon atoms, is an acetoacetic ester type con- densation. Dinitriles undergo a similar cyclization in the presence of sodamide . The one outstanding difference between esters of the type RCHZCOOEt and the corresponding nitriles, RCHZCN, is the fact that these esters cannot be alkylated directly whereas a nitrile can be alkylated easily. The reactive methylene group of the nitrile thus resembles that in malonic or acetoacetic ester. The sodium salt of the nitrile is formed first and this is then alkylated by alkyl halides or by simple alkyl sulfates (equation IV) . RCHch + Mimia _—9 310me Net" IV [ROI-EN]- Na+ + R'X ....5 RCHR'CN + halt The condensing agents which have be en employed include sodamide , metallic sodium (5,6,), sodium alkoxides (ethoxide and iSOpropoxide) (6,7,8), potassium amide (9), potassium hydroxide (10,11), sodium hydride (12), and lithium diethylamide (13). Sodamide is the most cosmonly used of the condensing agents and was first employed by Bodroux and Taboury in 1910 (lb) . The first report of the use of an alkyl halide as the alkylating reagent for nitriles was that by Meyer in 1889 (6). Since that time alkyl halides have been widely used. A summary of many of the sistple alkyl halides, and halides. containing other functional groups, which have been used as alkylating agents is to be found in the Masters thesis of W. R. Workman (1) . This summary includes material through 19h9. l tabulation of nitriles, alkyl halides, and alkyl halides containing other functional groups which have been reported since the study by Workman (1) is presented in Tables I and II. TABLE I ALKYLATION OF NITRILES BY ALKYL HALIUES Halide Nitrile Product Yield Reference Methyl iodide 2-Pheny1butanoic nitrile 2-Methyl-2-phenylbutanoic nitrile 7O 13 Methyl iodide 2,3-Dimethoxyphenylacetonitrile «i-(2,3-dimethoxyphenyl)~pr0pio— 75 18 nitrile Methyl iodide Diphenylacetonitrile 2,2-Diphenylpropionitriloa 80—90 12 Methyl iodide pAMethoxyphenylaoetonitrile p-inisyldimethylacetonitrile 19 Ethyl bromide 2,3-Dimethoxyphenylacetonitrile d-(2,3—dimethoxyphenyl)— butyronitrile 71 18 Ethyl bromide 2—Dheny1pr0pionitrile 2éMethy1-2-phenylbutanoic nitrileb 13 n-Propyl bromide Cyclohexyl cyanide l-(n-Propyl)—cyclohexyl cyanide 76 3 n-Butyl bromide Hydratroponitrile 2éMethyl-2-phenylhexanenitrile 71 2O neButyl bromide Cyclohexyl cyanide 1-(n-Buty1)—cyclohexyl cyanide 95 3 iso-Butyl bromide Cyclohexyl cyanide l-(iso-Buty1)-Cyclohexy1 cyanide 7S 3 n-imyl bromide Cyclohexyl cyanide l-(n-Amyl)-cyclohexyl cyanide 86 3 iso-Amyl bromide Cyclohexyl cyanide l-(iso—Amyl)-cyclohexy1 cyanide 62 3 2-Bromo pentane Cyclohexyl cyanide l-(l-Methylbutyl)-cyclohexyl cyanide 57 3' 1-Bromo-2-methy1butane Cyclohexyl cyanide 1-(2-Methy1butyl)~cyclohexyl cyanide 78 3 3-Brom0pentane Cyclohexyl cyanide l-(l-EthylprOpyl)-cyclohexy1 cyanide SS 3 n-Hexyl bromide Cyclohexyl cyanide 1-(n-nexyl)-cyclohexy1 cyanide 80 3 l-Bromo-Z—ethylbutane Cyclohexyl cyanide 1-(2-Ethy1butyl)-cyclohexyl cyanide 62 3 Il-Bromo—Z-methylpentane Cyclohexyl cyanide 1-(2-Methylpentyl)—cyclohexyl cyanide 6O 3 Cyclohexyl bromide Ai-Cyclohexenyl cyanide l-(Cyclohexyl)- Agycyclohexyl cyanide 7O 3 n-Heptyl bromide Cyclohexyl cyanide l-(n-Heptyl)-cyclohexy1 cyanide 83 3 n-Octyl bromide Cyclohexyl cyanide l-(n-Octyl)-cyclohexy1 cyanide 9h 3 {3-Cyclohexylethyl bromide Cyclohexyl cyanide. 1-((3-Cyclohexy1ethy1)-cyclohexyl 7S 3 ' cyanide Dibromomethane Phenylacetonitrile l-Phenylcyclopropyl cyanide 2 1,3-Dibrom0propane Phenylacetonitrile. l-Phenylcycldbutyl cyanide 2 1,3-Dibrom0propane Cyclohexanenitrile l-CyclohexylcyclObutyl cyanide 2 l,h—Dibromobhtane Cyclohexanenitrils l—CyclohexylcyCIOpentyl cyanide 2 l,h—Dibromobutane Phenylacetonitrile l—Phenylcyc10penty1 cyanide 8S 2 l,h-Dibromobutane .mgm49 29 ether to remove any unreacted nitrile, and then heated on a steam bath to remove the last traces of ether. Next the solution was made acid to congeared paper with concentrated hydrochloric acid. All attempts to isolate a solid acid at this point were unsuccessful. The acid solution was extracted with benzene, the benzene evaporated and the resulting liquid refluxed briefly with 5 ml. of thionyl chloride. The excess thionyl chloride was distilled and the last traces purged with benzene. The resulting solution was cooled and poured into a cold mixture of 6 ml. of aniline and 25 m1. of benzene. The aniline solution was extracted with 10% hydrochloric acid, 10% sodium hydroxide and water. Evaporation of the benzene left a brown solid, which was recrystallized from aqueous ethyl alcohol (Norite). The resulting colorless solution deposited fine white needles upon cooling. iMore product was obtained by diluting the alcoholic solution with water and cooling. Table VII summarizes the anilides prepared. Nitriles IV and V were not attacked under the conditions described above. Even when they were refluxed at 210° for 21; hours with butylene glycol and potassium hydroxide, only a slight trace of presumed anilide could be isolated although the flask was badly etched. These nitriles 'were smoothly reduced to the corresponding amines with lithium aluminum hydride according to the procedure of Amundsen and Nelson (3h). Derivatives of these amines were then prepared. The procedure follows. In a 500 ml. three-necked flask equipped with a stirrer, reflux condenser, and dropping funnel was placed a.mixture of h g. (0.106 mole) of lithium aluminum hydride and 100 ml. of anhydrous ether. Ten grams of the nitrile was dissolved in 30 ml. of anhydrous ether and added drapwise to the slurry in the flask. The addition caused gentle reflux- ing to occur. The solution was refluxed for an additional hour. The excess hydride was decomposed by adding drOpwise in order, 8 ml. of water, 3 m1. of 20% sodium hydroxide, and 18 ml. of water. The ether solution was decanted and the solid material in the flask rinsed with ether. The solid was discarded. After removal of the ether, the residual oil was distilled under reduced pressure. The following amines were obtained. B N25 N %a No. Name Grams 55,. . mm. D ’ VIII l-Amino-Z-phenyl-2,3- 9.8 136-139 7 1.5189 6.50 dimethylhexane IX l-Amino-thenyl-Z-methyl- 8.9 169-171 36 1.5170 6.73 3-ethyl pentane ' 9 Calculated for 014H21N : N, 6.82 Some difficulty was encountered in preparing derivatives of the two amines. Acetamides, benzamides, and.benzenesulfonamides were derivatives which failed to form. The phenylthiourea (35) of amine IX was a satisfactory derivative. The phenylthiourea of VIII melted over a wide range and behaved as though it contained diphenylurea. Picrates (35) of both amines were obtained from an alcoholic solution of picric acid and were recrystallized from aqueous ethyl alcohol. These deriva- tives are shown in Table VII. 31 .Hm.e .eeeee “ms.m .m «e.eHco .Hcca .Hosooad meooswm Sop.“ mmdeooc 30.36% c U .Hoaoodm mfioodos Scam magma-mam zoflnow n .oee7am ed eeeHos meteors Haseoeeetm.m ego us.~ one mo cheeses a e efiom oHoemmer we.s aa.s m.e0H-m.®0H Ozeomeeo -Haeeeeerae-~-Heeeeeum e6 oeeHeca ocmpzmmamnpolmndthmEIw idem.w mm.m .omH-eeH mezeem-eo -Heeoae-~-eeHeeuH He eenecHeeHaeeee memo-comabfiolm aw.~H oe.NH owaH-eaH eoezeemeeo -Haeeee-~-Haeeee.~-eeeeeuH e6 eeeneHm magmnahfioaflv No.mH om.NH haeH-eeH eo-zeemeeo -m.N-Haeeee-m-eceec.H eo eeeneHa eHee ee.e 4a.: eHHH-OHH ozeemeeo eeeeexeeHaeeeeee-e.N-Hseeee-m ee eeHHeee UHod no.4 2a.: eHHH..oHH ozeemeeo eHceexoeHaseoEHe7m.N-Haeeee-m no eeHHeee eHee so.m. 4a.: m.OOH-m.ee OZteeeeo eeeceedeeHaeeceumuHaceea.N me eeeHHc- Been eeeeHeeHeo m icowoppwz . o a .92 mgfioh egomsoo O HH> mama-B mama-Em mm>Hed>Hmmn DISCUSSION OF RESULTS .32. DISCUSSION or RESULTS It was necessary to prepare 2-chloropentane and 3-chloropentane in the manner described for two reasons, (1) they are not readily avail- able and (2) they tend to rearrange, the amount of rearrangement depend- ing on the method used in their preparation. The unequivocal methods used to obtain the two alcohols and the use of thionyl chloride in the presence of pyridine to convert the alcohols to the corresponding chloride insures pure samples of 2- and 3-chloropentane since there is evidence that this reaction gives the least amount of rearrangement. That these two compounds were free of rearranged product is shown by the fact that the derivatives prepared from the amines obtained by reduction of the appropriate nitrile were quite different. The behavior of the two amines towards various reagents also indicated that they were different. The chlorocyclopentane and l-chloro-Z-methyl-butane and the corres- ponding alcohols also had to be prepared as they are not readily avail- able. Further information has been gained concerning the relative reactivity of the halogen in the alkyl halide for the reaction under consideration, namely, the alkylation of nitriles. From Table V it can be observed that n-amyl bromide and n-amyl chloride are of about equal reactivity, with n-amyl chloride giving only 1% better yield than an. 33 n-amyl bromide. n-Amyl iodide gives a somewhat lower yield. One possible reason for the lower yield is that the n-amyl iodide could not be obtained completely free of iodine, as shown by the red color in the iodide used. Also, several grams of hydratrOponitrile were recovered. In the case of the n-amyl chloride and n-amyl bromide alkylations, no unchanged, hydratr0ponitrile was recovered. If one compares the percentages of conversion, it is seen that very little difference in yields of alkylated product exists. These results sub- stantiate the statement by'WOrkman that the yield of alkylated product is not greatly affected by the halogen in the alkyl halide. From Table v it can be observed also that the structure of the alkyl group affects the yield of alkylated product considerably. The best yields were obtained when chlorocyc10pentane and l-chloro-Z- methylbutane were the alkylating agents. The lowest yield, neglecting tert.-amyl chloride, was obtained when the n-amyl halides were used. The yields from iso-amyl chloride, 2- and 3-chlor0pentane, and 2-bromo- pentane were quite comparable and intermediate between the two extremes, mentioned above. These results agree with those Obtained by Workman and show (1) that normal, secondary, and iso alkyl halides give generally good yields and (2) that alkyl halides of the secondary and iso type give better yields than the normal alkyl halides. It should be noted that these results are not in agreement with those obtained by Tilford and co-workers (2,3) who report that cyclohexyl cyanide was alkylated in best yields by normal alkyl bromides and in poorer yields by secondary and branched chain bromides. These authors also state that tert.-butyl bromide gave no yield whatever of alkylated product. 38 It should be mentioned that in this work, very little or no un- changed hydratroponitrile was recovered from the individual alkylation reactions, except for those runs involving n-amyl iodide and tert.- _ amyl chloride and one run involving 2-chloropentane. Only in the case of the tert.- amyl chloride condensations was there any indication of dehydrohalogenation with the formation of alkenes. N0 unsaturated hydrocarbons were obtained from the other reactions which were investi- gated, namely, those involving 2- and 3-chloropentane. The failure to obtain more than a trace of 2-pheny1-2,3,3-trimethyl- pentanenitrile (VII) from the reaction of tert.-euny1 chloride with hydratrOponitrile was expected since workman and others have reported little or no alkylation when employing tertiary alkyl halides. workman suggested that his failure to obtain more than a trace of 2-phenyl-2,3, 3-trimethylbutanenitrile from the reaction of tert.-buty1 chloride with hydratroponitrile was due to one, or a combination of, the following factors: (1)'When tort-butyl chloride was the alkylating agent, a temperature of 800 was not reached before the addition of sodamide. The initiation temperature for the reaction, using the other alkyl halides, was above 900. Hence the reaction may not have been carried under the Optimum conditions. . (2) Steric hindrance may prevent the bulky anion from approach- ing the tertiary alkyl halide from the back and displacing the chloride ion. 35 (3) Alkaline condensing agents are known to cause dehydro- halogenation of tertiary alkyl groups with the formation of alkenes. Sodamide is, of course, an alkaline condens- ing agent and.might be expected to give this elimination type of reaction rather than alkylation. In the present study it appears that possibility (1) above, namely, the failure to have the optimum temperature for reaction, can not account for the low yields of alkylation product when tert.- amyl chloride was used. Deepite the fact that higher reaction temperatures (95-1050) were employed throughout and that correSpondingly higher yields of alkylated products were obtained in the other cases, the yields were again very low when tert.- amyl chloride was the alkylating agent. Since the same reaction temperature was used for the tort: amyl chloride as for the other amyl chlorides, it appears that the temperature factor is of only minor importance or, perhaps, of no importance in accounting for the low yield of tertiary alkylated product. workman was unsuccessful in his attempts to isolate isobutylene from the alkylations of hydratroponitrile with tert.-butyl chloride. Hence he could not demonstrate whether or not dehydrohalogenation occurred (factor 3 above). In the present study, when tert.-amyl chloride was used as the alkylating reagent, precautions were taken to trap any volatile components given off during the alkylation reaction. Several grams of low boiling, volatile material were obtained which gave characteristic tests for unsaturation, namely decolorizing a 5% 36 solution of bromine in carbon tetrachloride without the evolution of hydrogen bromide, and decolorizing a 2% solution of potassium per- manganate. Distillation of this material gave several fractions which had boiling points and refractive indices corresponding to both 2-methyl- l-butene and deethyl-Zdbutene.. The isolation of these alkenes demonstrates that dehydrohalogenation is a definite factor in the failure to obtain an alkylated product with tertiary alkyl halides. In one effort to avoid the dehydrohalogenation effect of the amide ion on tert.-amyl chloride, sodium hydride was substituted for sodamide since sodium hydride does not react with alkyl halides (LO). In place of 12 g. (0.33 mole) of sodamide, 7.2 g. (0.3 mole) of sodium hydride was used. [A lower reaction temperature and longer reflux period were also employed. In this case more low'boiling material was obtained than before. The tests for unsaturation were positive and the physical constants paralleled those of 2dmethyl-l-butene- and 24methyl-2+butene.. Hence it was demonstrated that the anion from hydratroponitrile was effective in the dehydrohalogenation of tert.-amy1 chloride. Further attempts to prepare 2-phenyl-2,3,3-trimethylpentanenitrile were abandoned. It has been observed that an increase in the number of alkyl groups on the at -carbon of the nitrile increases the difficulty of hydration or hydrolysis of these compounds. For example hydratroponitrile with an 4 -hydrogen and an d -methyl group is easily hydrated to the amide. When the 0‘ -hydrogen is replaced by an alkyl group, the resulting nitrile can no longer be hydrated to the amide (1). Workman observed that the introduction of a methyl group on the /3 -carbon in addition to the 37~ methyl group on the °'~ -carbon produced a compound, 2-phenyl-2 ,3-di- methylpentanenitrile XIII, (See Figure II), which could not be hydro- lyzed. In the present investigation it was found that none of the nitriles prepared (Table VI and Figure I) could be hydrolyzed; to the amide. Four of them (I, II, III, and VI) were ultimately hydrolyzed to the acid and converted to anilides; two (IV and V) failed to hydrolyze. The massing of methyl or' ethyl groups near the cyano group tends to lessen the ease of hydrolysis of the latter. For example, when a methyl group is in the of -position (nitrile II), conversion was easily affected. When the methyl group was in the V -position (nitrile III), the hydrolysis was more difficult to achieve. When the methyl or ethyl group occupied a fl -position (nitriles Iv and v), hydrolysis failed completely. This increasing difficulty in hydrolysis of the nitrile in proceeding from hydratroponitrile to the more hi ghly branched nitriles can be explained in a semi-quantitative manner by applying the _ru_J_.e_ E; 1135 or six-number concept advanced by Newman (36). In consider- ing the nitriles prepared by Workman, (see Chart II) onelfinds that . hydratrOponitrile (X) with an effective (slag-m of 2 was easily 1v- droly'zed to the amide by 66% sulfuric acid in fifteen minutes. 2-Phenyl- -2-methy1hennenitrile (XI) and 2-phenyl-2 ,h-dimethylpentanenitrile _ (XII) , in which the effective six-m is 5' could be hydrolyzed and convertedto the anilides but not to the amide .. When the effective gig-m rose to 8, as in 2-pheny1-2,3-dimethylpentanenitrile (XIII), Workman found it impossible to effect hydrolysis to the amide or acid. 38 FIGURE I STRUCTURE OF um: NITRILESa Six-number Structure No. -CH3-C-CN Hi1- H‘ *-c-CHz-c-CN H - C I CH3 II CH3 CH3 H“ H“ a? 2-0-ON H* CH3 - c“- c - CH H I III CH3 05H3 H H’ H‘ CH3-c*-c-CH-c-CN I H“ l H H‘cs, C... 11* 11* H . CH - C - ON I «pf-041* CH3 HIIC/ a H C‘s, \ I HzC -C\fl C -———- C - CN / ‘H* VI 11 VII No. XII XIII XIV F IGURE II STRUCTURE OF NITRILES PREPARED BY WORKMAN Structure and Name Hydratroponitrile HH*H* H* CHa-Cg-C-CHz-C-CN I I I H 11* CH, 2-Phenyl-2 methylhexanenitrile H" H‘IE H* * a I u ' fi CH3 CH3 2-Phenyl-2,h-dimethylpentanenitrile H" 11* * I H30 - C - CH - C - CN I H“ l I a * H-C;H CH3 H . 2-Phenyl-2,3-dimethylpentanenitrile H‘ H*-C-H* “‘ I ‘I' H -C —-——-' C--CN 2’ I -C | I H! nicer? CH3 H" 2-Phenyl-2,3,3-trimethylbutanenitrile 39 Six-number ll ho Although no attempt was made to hydrolyze 2-phenyl-2,3,3-trimethyl- butanenitrile (XIV), one would.predict that this nitrile would be even more difficult to hydrolyze, since the effective six-number is 11. When this concept is applied to the nitriles prepared in the present study, it is possible to predict those nitriles which should be hydrolyzed. 'When the effective sixfnumbgr is 5 or 6 (note that only a limited number of hydrogen atoms in the six position can be effective at one time in nitrile VI because of the ring structure), it should be possible to effect hydrolysis. Experimentally it was found that nitriles I, II, III and VI with effective sixrnumbers of S, S, S and 6 reapectively could be hydrolyzed and converted to the anilide. It would be predicted that nitriles with an effective six-number of 8 would not undergo hydrolysis. Such was found to be the case for nitriles IV and V. It should be impossible to hydrolyze nitrile VII which has an effective sixenumber of ll. From this it is apparent. that the critical value for the six-number in the case of these hindered nitriles lies between six and eight. SUMMARY 1. hi SUMMARY The alkylation of hydratrOponitrile with normal amyl chloride, bromide, and iodide in the presence of sodamide using the high temperature procedure of Ziegler and Ohlinger shows that the halo- gen of the alkyl halide has little effect on the yield of 2-pheny1- 2-methylheptanenitrile. The alkylations using 24brom0pentane and 2-chlor0pentane also support the above contention. In the alkylation of hydratroponitrile with normal, iso, and tertiary amyl chloride, cyc10pentyl chloride, 2- and 3-chlor0pentane, and 2-methyl-1-chlordbutane the structure of the alkyl group definitely effects the yield, the yields being in the order iso secondary normal tertiary. The results support those of‘workman. Unsaturated hydrocarbons were isolated from the reaction mixture of tert.-amyl chloride and hydratrOponitrile showing that one reason for the low yields of alkylated product obtained when tertiary alkyl halides are used as alkylation agents is due to dehydrohalogenation of the tertiary alkyl group in the presence of an alkaline condensing agent. . Seven nitriles not previously reported in the literature have been prepared, and their physical properties determined. Four of these, 2-phenyl-2-me thylheptanenitrile , 2-phenyl-2 ,S—dime thylhexanenitrile , 2~phenyl-2-cyclopentylpropanenitrile, and 2-phenyl-2,h-dimethyl- 1:2 hexanenitrile, have been hydrolyzed to the acids and converted to the anilides. Two of the nitriles, 2-phenyl-2,3-dimethylhexane- nitrile, and 2-phenyl-24methyl-B-ethylpentanenitrile have been reduced to the correSponding amines with lithium aluminum hydride, and their picrates prepared. The phenylisothiocyanate derivative of l-amino-Z-phenyl-Z-methyl-3-ethyl pentane was also prepared. The difficulty of hydrolysis of these nitriles has been discussed and rationalization in terms of the sixenumber concept of Newman applied. h3 SUGGESTIONS FOR FURTHER RESEARCH 1. Investigate in more detail the effect of the position of alkyl groups on case of hydrolysis of nitriles. Apply the six-number concept to the rate of hydrolysis of these hindered nitriles. 2. Reinvestigate the present work using the low temperature method employed by Tilford and co-workers. 3. Study the same series of amyl halides using a different nitrile, to shed further light on the role of the structure of the nitrile as it affects the yield of alkylated product.. SMTED REFERENCES l. 2. 13. 114. 15. 16. 17. 18. 19. 1414 REF ERENC ES W. R. Workman, M. S. Thesis, Michigan State College, (1950). - C. H. Tilford, M. G. VanCampen,‘ and R. S. Shelton, ‘J. Am. Chem. Soc., 92: 2902(19147). C. H. Tilford, I... A. 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J. Hickinbottom, Reactions of Organic Compounds, Longmans, Green and Co.', New York, 19148, p. 177. H. Amundsen and L. s. Nelson, J. Am. Chem. Soc., 3;, 212 (1951). L. Shriner and R. C. Fuson, Identification of Organic Compounds, Third Edition, John Wiley and Sons, Inc., New York, 19148, S. Newman, J. Am. Chem. Soc., 12, 11783 (1950). Adkins, Reactions of Hydrogen, The University of Wisconsin Press, Madisonflfisconsin, 1937, pp. 12-13. C. Whitmore and J. H. Olewine, J. Am. Chem. Soc., 69, 2569 (1938). R. Noller and R. Adams, J. Am. Chem. Soc., 53,1081; (1926). . J. Cristol, J. W. Ragsdale and J. S. Meek, J. Am. Chem. Soc., 1;, 1863 (19h9). CHEMISTRY leRAHY SEP 2 0'58 JUL 2 '57 OCT 3 .5, JUN 1 0 '53 1111-3 ‘50 FEB 15’ MAY? ‘6 T547 CEA‘IMSTRY I: TDD A u u T 7 A | 1 L' 1 854737 Jacobs at.“ — | l' I l l l I II I III! 11111111