Feb 5 , 1956
ACTIVITYOF N-BENZENESULFONYL-N-CARBOXYMETHYL-3-BENZYLMESIDINE
663
and the decomposition was accelerated by light or heat. The product was recrystallized by dissolving in ethanol a t 4-Benzenesulfonamido-2,6-dibenzenesulfonylphenol (XV) . room temperature, adding water to the cloud point and cooling. XVhite needles were obtained, m.p. 121-122.5' dec. -A solution of 0.15 g. of sodium benzenesulfinate in 2 ml. of Because of the instability of the product it was not anawater was added to a warm solution of 0.20 g. of 2-benzenesulfonyl-1,4-quinone-4-benzenesulfonimide in 10 ml. of gla- lyzed. 2-Acetamido-4-benzenesulfonamidophenol (IIj) .-A cial acetic acid. The solution was diluted with 10 ml. of water and cooled. The white product was removed by fil- solution of 6.0 g. of sodium hydrosulfite in 30 ml. of water was added to a solution of 1.00 g. of 2-azido-4-benzenesultration. The yield was 0.26 g. (96.3%). After recrystalfonamidophenol in 30 ml. of 5y0 aqueous sodium hydroxide. lization from acetic acid the product melted at 200". The resulting yellow solution was heated to boiling for 10 Anal. Calcd. for C2rH~,NGSa:C, 54.43; H , 3.62; N, minutes, diluted with water and made slightly acidic with 2.65. Found: C, 54.62; H , 3.68; S , 2.64. dilute hydrochloric acid. A white solid separated and was The 4-Benzenesulfonamido-2-benzenesulfonyl-1 -naphthol removed by filtration. The yield was 0.76 g. (83.5%,), (IIIe).-To a solution of 1.00 g. of 1,4-naphthoquinone- m.p. 165-168". Attempts to purify this amine resulted in monobenzenesulfonimide in 30 ml. of boiling glacial acetic colored solutions from which colored solids were obtained. acid was added 1.00 g. of sodium benzenesulfinate. The The crude material was therefore acetylated directly. color of the solution was quickly discharged. On cooling To a solution of 1.00 g. of crude 2-amino-4-benzcnesul1.32 g. (90%) of white, crystalliiie product separated. Re- fonamidophenol in 100 ml. of 5% aqueous hydrochloric acid crystallization from acetic acid gave white needles, m.p. was added slowly a 5% aqueous solution of sodium hydrox204.5'. ide until the mixture became slightly turbid. The turbidity Anal. Calcd. for CZZHI~NOSSZ: C, 60.12; H , 3.90; iY, was removed by the addition of a few milliliters of hydrochloric acid. A few chips of ice were added, followed by 10 3.19. Found: C,59.80; H,4.01; N,3.04. 2-Azido-4-benzenesulfonamidophenol (IIh).-A solution ml. of acetic anhydride. The mixture was shaken vigorof 1.00 g. of sodium azide in 4 ml. of water was added to a ously and a solution of 10 g. of sodium acetate in 100 ml. of warm solution of 1.50 g. of p-quinonemonobenzenesulfon- water was introduced. On cooling white crystals sepaimide in 30 ml. of acetic acid. After 5 minutes the solution rated. The yield was 1.03 g. (78.1%). Recrystallization acetone-chloroform gave small, white crystals, m.p. was colorless and it was poured into 80 ml. of water con- from 242-242.5' dec. tained in a flask wrapped with aluminum foil to prevent Anal. Calcd. for C I ~ H ~ ~ N ~C,O54.89; ~ S : H, 4.61; S , light from striking the product. When the mixture was 9.15. Found: C,54.73; H,4.22; N,8.86. cooled white needles separated weighing 1.67 g. (94.9%). The product decomposed on standing at room temperature URBANA, ILLINOIS
Anal. Calcd. for C I ~ H I ~ N O ~ C, S Z55.80; : H , 3.38; N, 3.62. Found: C, 56.11; H,3.46; N,3.88.
[CONTRIBUTION FROM
THE
NOYESCHEMICAL LABORATORY, UNIVERSITYOF ILLINOISJ
Restricted Rotation in Aryl Amines. XVIII. Effect of Remote Substituents on the Stability of Optically Active N-Benzenesulfonyl-N-carboxymethyl-3-benzylmesidine BY ROGERADAMSAND K.R.BROWER RECEIVEDACGUST1, 1955 In a series of optically active compounds having m-substituted benzyl groups in the 3-position of N-benzenesulfonyl-rcarboxymethylmesidine it was found that variation of the substituent caused no significant variation in the rate of racemization.
Previous papers in this series have reported that variation of the 4-substituent in optically active N - benzenesulfonyl- N - carboxymethyl - 1- amino - 2 methylnaphthalenes (I) produces variations in the rate of racemization, amounting in the most extreme case to a factor of The halflives of the nitro compound (X = NOz), the amino compound (X = NH2) and the unsubstituted compound were 0.42, 9.7 and 4.9 hr., respectively. CBHSSO~-K-CH~CO~H I
from the reaction center to contribute any but field effects. For this purpose compounds having msubstituted benzyl groups attached to the 3-position of N-benzenesulfonyl-N-carboxymethylmesidine (11) have been prepared and studied. From the table below it is seen that variation of the substituent causes remarkably little variation in the half-lives of the compounds of the present series. CsHsSOzNCH2COgH I
CH~J-CH~ QCHa
I
) X
The effect has been explained on the basis of variations in the resonance stabilization of the coplanar but transition state by the para there is no assurance that other factors such as inductive and field effects are not involved. The purpose of the present investigation has been to determine the susceptibility of the racemization reaction to substituents too well isolatul (1) R. Adams and R. 11. hlattson, TIIISJ O U R N A L , 76, 4923 (1054) ( 2 ) R. Adams and K V Y Sutidstrotu, tbrrl., 76, 5474 (19.54).
\CH2/ CH, I1
0'
X
Half-life, Iir.
H Br CH3
11.5 f 0 . 2 11.3 12.8 f .4 .3
cs
12.1 i . 2 12.3 .2
CHIO
The synthesis of the benzyl, m-methylbenzyl, mbromobenzyl and m-nitrobenzyl derivatives was effected by benzylation of mesitylene with the appropriate benzyl chloride, followed by nitration, reduction and introduction of the benzenesulfonyl and carboxymethyl groups on the amino nitrogen in that order. The nitration of the m-nitrobenzylmesitylene provided the dini tro compound with one nitro group in the tnesityleiie ring and the other on the benzyl group. Selective catalytic reduction
ROGERADAMSAND K. R. BKOWER
664
Vol. 78
TABLE I BENZYLMESITYLENES ,n-Subst. of benzyl group
B P.,
1.0 m m
M.P., OC.
OC.
120-130 . . ... ,.. 130- 136 Oil Rr 145-153 Oil CK 162-172 87.0-88" NO* 165-175 82.5-83. Sa Recrystallized from nicthaiiol. H
CHI
Yield,
%
66 65 73 67
...... CIiI-I2"
-_ I3
Formula
.
CdLIBr c1 7 H I 7 ii C16€IliS02
Carbon, 5'0 Calcd. Founil
Hydrogen, 76 Calcd. Found
.,.
...
91 .n3
90.75 66.37 86.78 7,s. 00
66.40 80.78 75.27
8.97 6.93 7.27 0.71
8.74 5,85 7.48 6.57
T A B L E 11 UBNZ~LNITROMESITYL~~.NES
nz-Subst. in benzyl group
B . p . . 1.0
11.I>. ,
IIIIII..
oc.
OC.
Calcd.
Furmula
car bo u , I;;,
IIydfo&cll, ',& Calcd. I'ound
Found
H xo-17n 75.20 74.72 Oil C,6HI,X:O* CH, 160-170 89-0Oa CiiHigN02 i 5 , SO 75.92 Br' 175-192 67-68" C I ~ H I O ~ K ~57.51 ~ 58,43 CN ..... 119-120" C,;H1aPi,O* 72,85 72.81 SO2 ..... 63.99 64.22 115-116" CieHiaN20r a Recrystallized from methanol. Calcd.: S , 4.19; Br, 28.81. I'outid: S , 4.02; Br, 23.40.
6.71 7.13 4.84 5.74 5.37
6.73 7.02 4.68 5.68 3.37
transformed the nitro on the benzyl group to an The authors are indebted to X r . Joseph Nemeth amino. This amino compourid was diazotized and and co-workers for the microanalyses. the amino group replaced by hydroxyl which was Experimental methylated to the m-methoxybenzyl derivative. Preparation of m-Substituted Benzylmesity1enes.-The The nitro group in the mesitylene nucleus was then procedure of Louise5 for the synthesis of benzylmesitylene reduced with hydrazine and Raney nickel. from benzyl chloride and mesitylene was applied to the apThe nitro group of 3-(m-~yanobenzyl)-nitro-propriate m-substituted benzyl chlorides .6 The results are mesitylene could not be reduced without concomi- summarized in Table I . Preparation of 2-( m-Substituted Benzyl)-nitromesitylenes. tant reductiofi of the cyano group, and it was nec-A solution of 0.2 M of m-substituted benzylmesitylene in essary to convert the latter to carboxamido previ- 60 ml. of acetic anhydride was chilled to -15" by addition ous to the reduction step. Benzenesulfonylation of Dry Ice and maintained at that temperature while a of the amino group aiid reconversion of the carbox- solution of 8.5 ml. of fuming nitric acid (sp. gr. 1.5), IO ml. of acetic anhydride was added with amido group to cyano were caused simultaneously of acetic acid and 10 ml. in the course of a few minutes. In the case of 3by tlie action of the benzenesulfonyl chloride in py- stirring rrz-cyanobenzylnitromesitylene and 3-nt-nitrobenzylnitroridine, a method which has also been described re- mesitylene the product crystallized from the reaction mixture after standing 10-15 minutes and was removed by suction cently by Stephens, Rianco and Pilgrim.3 Roberts and M~relarid'~ have studied the inter- filtration. The other compounds of the series were isolated by pouring the reaction mixture into water, treating nal ion-dipole interactions of 4-substituted bicyclo- with an excess of aqueous ammonia arid extraction with [2.2.:!]octane-l-carboxylic acid derivatives and ether. The ether layer was shaken with 5% aqueous sodium found rather large substituent effects; for example, hydroxide to remove a-nitrated by-products, washed, dried the ratio of the rates of ester hydrolysis for the 4- and distilled in vacuum. Approximately 50y0 yield was in every case. OH and 4-H compounds was twenty-to-one. In obtained Preparation of 3-(m-Substituted Benzyl)-mesidines,these tplecules the substituents have separations The nitro compounds wcre reduced by the method of Balcom and Furst? using hydrazine :is the reducing agent with of 7-5 A. In the racemizations of the mesidincs described i n Raney nickel catalyst. Other reducing agents such as hydrogen over platinum or stannous chloride were found t o this communication dimethylformamide was used react sluggishly, presumably owing to steric hindrance hy tlic 3 s solvent a t a temperature of 11s". The coin- two o-metliyl groups. Tile amines were riot i?olated in a pound may exist largely as the carboxylate ion. pure state before use in tlie following step. Preparation of N-Benzenesulfonyl-4-( $72-Substituted BenThe scale model of the molecule shows that the spxzyl)-mesidines.-The crude amine was mixed with 1.5 tial separation between the reaction center and the molar equivalents each of benzenesulfonyl chlorideonnd 5% substituent inax vary between the limits of direct aqueous sodium bicarbonate and wtrtned to IO0 on tlie contact and 10 A. The compounds of Roberts and hot-plate. After 20-30 minutes vcd by filtration alld rcaffecting each other are a t essentially a fixed dis- crystallized from ethanol. tance. In the mesidines, on the other hand, it is Preparation of N-Benzenesulfonyl-N-carboxymethyl-3-(nzpossible that such substituent effects u7ill be small Substituted Benzyl)-mesidines.-To a solution of the Nsince free rotation of the benzyl group will diminish benzenesulfonylbenzylmesirlit1e and 1.1 molar equiv'11ents of potassium ethoxide ili 7 parts of absolute ethanol was tlie probability that the charge and dipole will he added 1.1 molar equivalcnts of ethyl 1~romoacet:lte. Preproperly orientcd for the operation of :L large field cipitation of potassium bromide began itntnediately arid was effect and, in u i y event, the inductive effect iiiust (j) 13. Imttise, i l i r r a . Ozijn,, [GI 6 , 177 (1893). he ncgligiblc. ( 0 ) 'I'IIc >.':t1jcm ~ ~ I n-chl
