July, 1942
ACTIONOF ALKALION CYCLOHEXENECARBONALS
1497
devoid of optical activity in chloroform solution; i t melted a t 131-13Z0 (cor.), which is much higher than the melting point of its components, from which fact i t is evident that the crystalline substance is a true racemate.
talline methyl hemiacetal. This hemiacetal is converted by acid hydrolysis to L-xylose, which was isolated as the crystalline sugar and further characterized by preparation of L-xylose phenylSummary osazone; the latter compound combines with D-Sorbitol, in solution with 4 N hydrochloric D-XylOSe phenylosazone to yield the long known acid and one molecular equivalent of benzalde- racemic xylose phenylosazone. Also, L-xylose hyde, condenses to yield principally a cryptocrys- phenylosazone triacetate forms a true racemate talline dibenzyli#ene-D-sorbitol melting a t 219- with D-xylose phenylosazone triacetate. 221'. The latter substance, upon oxidation with The work constitutes a definitive proof that lead tetraacetate in glacial acetic acid, produces the structure of dibenzylidene-D-sorbitol is that formaldehyde and aldehydo-2,3,4,5-dibenzylidene-of 1,2,3,4-dibenzylidene-~-sorbitol. ~-xylose,which is conveniently isolated as a crys- BETHESDA, MD. RECEIVED APRIL10, 1942 -
[CONTRIBUTION FROM
THE
CHEMICAL LABORATORY, UNIVERSITY OF MISSOURI]
The Action of Alkali on Cyclohexenecarbonalsl BY H. E. FRENCH AND D. M. GALLAGHER Although the cyclohexenecarbonals possess alpha hydrogens, one might reasonably expect reactions like those of the aromatic series toward alkaline reagents, because of the steric effect of the large radical attached to the alpha carbon. I n order to test this supposition, we have investigated the reactions with several 3-cyclohexenecarbonals, particularly the 3,4,6-trimethyl derivative. Concentrated aqueous solutions of sodium or potassium hydroxide acted on this aldehyde forming a tripolymer. Similar tripolymers of cyclohexanecarbonal and of 3-cyclohexenecarbonal had previously been prepared by the action of mineral acids.2 Saturated aqueous solutions of barium hydroxide gave very small yields of the polymer, most of the aldehyde being recovered. A cold 10% solution of potassium hydroxide in methyl alcohol was also without action on the aldehyde. At 70°, using a methyl alcohol-water solution, reaction took place with the formation of the corresponding acid and the alcohol. The acid had previously been prepared from ethyl crotonate and 2,3-dimethylbutadienea The structure of the alcohol was shown by its synthesis from the aldehyde using aluminum isopropoxide, and by carbon and hydrogen analyses of the naphthyl urethan. (1) This work is part of the thesis material to be submitted by Mr. Gallagher to the graduate faculty of the University of Missouri. (2) Wallach, Ann., 847, 336 (1906); Zelinsky and Gutt, Ber., 40, 3051 (1907); Chayanov, J . Gen. Chcm. (U.S. S . R.), 8, 460 (1938). (3) Farmer and Pitkethly, J . Chem. Sac., 11 (1938).
Under similar conditions, 3,4-dimethyl-6-phenyl-3-cyclohexenecarbonal, 6-methyl-3-cyclohexenecarbonal, and 3-cyclohexenecarbonal were found to give the Cannizzaro reaction. In all cases the acids formed were known compounds* but the alcohols had not previously been reported. The/se were identified by their syntheses from the aldehydes using aluminum isopropoxide, and analyses of their phenyl or naphthyl urethans. Yields of the pure acids were of the order of 80%. Varying amounts of polymerization products were obtained if the temperature of reaction was much in excess of 70'. Freshly distilled 6-methyl-3-cyclohexenecarbonal gave but a trace of reaction in the usual reaction time, while aldehyde used after long standing, or through which air had been bubbled, readily entered into the reaction. This is in accord with the observation that peroxide is a catalyst for the Cannizzaro reaction.5 Each of the aldehydes was dissolved in aqueous methyl alcohol and heated to approximately 70' with potassium hydroxide and formalin solution. Diols, in yields of from 50 to 60% of the pure redistilled or recrystallized compounds, were obtained in all cases. The formation of these compounds presumably follows the course indicated by the equation (4) Fujisi, Horiuchi, and Takahashi, Ber., 69,2102 (1936); Chayanov and Grishiu, Colloid J . (U. S. S. R.),8, 461 (1937); Perkin, J. Chem. Sac., 86, 416 (1904). (5) Kharasch and Foy, THIS JOURNAL, S7, 1510 (1936).
€1. 11:. FRENCH .WD D. >I. GALLAGHER
I l!)i
VOI. G4
ether and methyl alcohol were removed on the water-bath. Vacuum distillation of the residue gave the carbinols as colorless liquids which readily formed urethans with a naphthyl isocyanate. In each case the identity of the carbinol was demonstrated by its synthesis from the aldehyde with aluminum isopropoxide and a comparison of the urethans. The acids were obtained from the alkaline solutions remaining after the ether extraction, in yields which were generally of the order of 78%. Melting points 3,4,B-trimethyl-3-cyclo- of the acids were found to correspond to those giveii in the camphor arid in diox- literature for those compouiids
'I'he ~iiolecularweight of hexene-1 , I -dicarbonol in 3,4-Dimethyl-6-phenyl-3-cyclohexenecarbonol.-Naphane was found to be 1S4 and 183.5, respectively, thy1 urethan; white crystals from petroleum ether; 111. 1). aiid i n the Grignard machine was found to possess 110-111 O, two active hydrogens. Each of the diols coni-Anal. Calcd. for C?eH,,O,hT: C, 81.03; H, 7.01. Found: hiried with two molecules of phenyl isocyanate to c, 80.84; €1, 7 . 3 2 . 6-Methyl-3-cyclohexenecarbonol.-Phenyl urethan; yield crystalline urethans. 'I'he ring unsaturaIs; i n p. 83 '. Anal. Calcd. for C16H1802N: was reLion of the 3-cyclohexene-l,l-dicarbonol K , 5.71, Found: h',5.80. duced. and oil oxidation the known cyclohexane3-Cyclohexenecarbonol.-Naphthyl urethan; white I , I -dioic acid was crystals from petroleum ether; m. p. 106'.
Experimental The cyclohexenccarboridls were prepared by the DielsAlder condensation, and their properties corresponded t u those given in the literature for the pure compounds. 3,4,6-Trimethyl-3-cyclohexenecarbonal with Alkali.'Twelve and one-half granis of the aldehyde was allowed to htand for twenty-four hours ai room temperature with a iolution of PO g. of potassium hydroxide in 12.5 cc. of water. An insoluble oil wa:, then heparated from the aqueous layer and washed with water. I n the course of a month this oily material partly solidified. The pasty mass was filtered with suction antl was washed with ethyl alcohol. The white solid thus obtained was found to be soluble in benzene arid in acetonc, antl insoluble in ethyl alcohol and in ether; white, powdery niaterial from acetone; 111. p. 132-1:34 .: molecular weiglit i t 1 l)cnxcne, 4x2; inolecular weight of t hc original aldchvqic, 1.72: yield of polymer, 2 g . A solution coiitaiiiiiip ?io g . of thc aldehyde in 20 cc. of ethcr was shaken for forty-eight hours aL room tempcralure with 2 0 cc. of a sa iurated solution of bariiini hydroxitic in water. Practically a l l of the aldehyde wa5 recovered from the ether solution ah the hisulfite compound. together with a trace of a n oily malerial, presumably a polymer of the aldehyde. A solution of 10 g. of the aldehyde in 20 c c . of riiethyl ~tlcoholwas shaken for three a t room teiiiperature with 10 (*c. of a l l J % solution of potassium hydroxide in methyl alcohol. Eight and a half granic of the aldehyde was recovered. The Cannizzaro Reaction. -The following procedure is typical for the Caiinizzai-o reactions using the various aldehydes. A solution of M g. of potassium hydroxide in 5 . 5 cc. of water was added iapidly to 8.5 g. of the aldehyde i n 1 1 cc. of methyl alcohol, with mechanical stirring a t 65-75' for two hour> At temperatures iiiuch in excess of Addition of I 3 , considerable pol.vmerizatioxi ucciirred. a n equal volume of water caused the separation of a second layer, which was extracted with ethrr. Afler drying, rhe - - 0
____
ifil
Wightman, J . C'Item
,>,>,
2341 ( I ! ) > t j ) ,
.4nd t:oiincl:
Calcd. for ClsHlsOnN: C, 76.86:
H, 6.76.
C , 76.92; H, 6.94.
3,4,6-Trimethyl-3-cyclohexenecarbonol.-Kaphthyl uret h a n ; white crystals from petroleum ether; in. p. 112*. ,-lntrl. Calcd. for CriH,iOeN: C, 78.01; H, 7.74. Found: C , 78.35: H, 8.05. The Cross Cannizzaro Reaction.-The following represcnts a typical maction for these aldehydes. A mixture of 8 g. of the aldehyde, 10 cc. of methyl alcohol, and 5 cc. of formalin in a 3-neck flac;k equipped with dropping funnel, motor stirrer, and reflux condenser was heated to 70",and maintained a t that temperature while a solution of 8.4 g. of potassium hydroxide in 6 cc. of water was added. The mixture was heated a t 70" for forty minutes, then refluxed for one hour. The rraction mixture was cooled, diluted with a n equal volume of water, and extracted with ether. From this ether solution the diol was obtained. The unwbstituted and thc nionomcthyl substituted compounds n-ere obtained as oils which solidified after vacuum distillation and standing for several hours in a n ice chest. The others were oljtained a b crystalline compounds, and were rccrystallizrd from petroleum ether. The diols were ohtained in yields of .50-60% of the pure compounds. I n each case the diol coiiibiiied with two molecules of phenyl i~ocvanate,yielding crystalline urethans which were recrystallized from dilute alcohol. 3,4,6-Trimethyl-3-cyclohexene-l,l-d~carbonol.-White crystal\; m. p. 8fi.5": molecular weight in camphor, 184; in dioxane, lg3.5; calcd. for CIIHXOO~, 184; active hydrogens, 1.91; urethan, m . p. t21.5-123°. Arttrl. Calcd. for CP~HSOOIPL~~: C, 71.09; H, 7.10. Found: C, 71.Dl; H, 7.34. 3,4-Dimethyl-6-phenyl-3-cyclohexene-l ,I-dicarbono1.White crystal>; m. p 131.5'; phenyl urethan, m. p. 166' Anal. Calcd. for C Z O H ~ ? O J NC,~ : 74.36; H, 6.81. I'o~md: C , 74.22: H. ij.85, 6-M ethyl-3-cyclohexene- 1,I-dicarbono1.-White c r y ,Lals; 111. p. 45'; phenyl drethan, 111. p. 1.50'. A n c i l . Calcd. for C ~ ~ H I O O I N C,~70.05; : H, 6.59; S , 7.10. Foiind: C, 70288: H, fi,::?:S , 7.o6.
July, 1942
SULFANIL.1MIDO D E R I V . i T I V E S OF N I T R O G E N BASES
1499
water was added with stirring, a t a temperature of 0". The mixture was stirred for eight hours at that temperature and allowed to warm slowly to room temperature. The excess permanganate was discharged with 1 cc. of ethyl alcohol. After atering, the solution was concen1.81. trated on a water-bath to 10 cc. using vacuum. ' HydroHydrogenation of 3,4,6-Trimethyl-3-cyclohexene-l,lchloric acid was added and the solution placed in the ice dicarbono1.-The compound was reduced a t 2500 lb. preschest. A yield of 0.8 g. of the known cyclohexane-1,lsure a t 150", using Raney nickel, to the known cyclohexdioic acid was obtained. ane-1,l-dicarbonol, in. p. 95-9ti
3-Cyclohexene-l,l-dicarbonol.-White crystals ; m. p. 92.5'; phenyl urethan, m. p. 118.5". Anal. Calcd. for C Z Z H ~ ~ O C, ~ N 69.45; ~: H, 6.36. Found: C. 69.29; H, 6.57. Active hydrogens in the diol,
'.'
Oxidation of Cyclohexane-1,l-dicarbono1.-Oxidation
Summary
with potassium permanganate in neutral and in alkaline solutions, using water and water-acetone solvents, gave only uncrystallizable oils. h'itric acid oxidation gave a sniall yield of a solid acid which was not identified. I .7 g. of the diol was dissolved in 10 cc. of pyridine. A solution of 5.5 g. of potassium permanganate in 110 cc. of
1. The action of alkaline solutions on certain cyclohexenecarbonals has been studied. 2 . These aldehydes were found to undergo the Cannizzaro reaction, and to react with formaldehyde to yield cyclohexene-1, I -dicarbonols.
(7) Franke and Sigmund, Monalsh., 46, 61 (1925).
[CONTRIBUTION FROM
THE
COLUMBIA, MISSOURI
DEPARTMENT O F CHEMISTRY, THE UNIVERSITY
RECEIVED MARCH30, 1942
O F TEXAS]
Sulfanilamido Derivatives of Nitrogen Bases from California Petroleum' BY LESLIEM. SCHENCK~ AND HENRYR. HENZE
Bobranski3 and Winterbottom4 have reported Type I pneumococcus, Staph. aureus or Strep. syntheses in the sulfanilamidoquinoline series; &iduns. The slight activity toward hemolytic however, no alkylation in the quinoline nucleus streptococci indicates that the activity of sulfanhigher than methyl was included. Since detailed ilamide is lowered by substitution of the quinoline pharmacological tests of their compounds have heterocycle a t the N 1 position. Certainly the not been published, it was considered of interest to compounds here reported do not have the desirprepare sulfanilamido derivatives of a series of able properties obtained with other heterocycles alkylated quinoline homologs encountered in ni- such as pyridine, thiazole and pyrimidine. Two of the new compounds reported herein have trogen Gases extracted from California petroleum. Since quinolines substituted in positions 2, 3 and 8 received preliminary testing for antimalarial acoccur in appreciable quantity among the complex tivity (through the courtesy of Parke, Davis and petroleum base fractions, this series was selected Company). I t is of interest to note the activity for investigation. The compounds prepared in against avian malaria of 5-sulfanilamido-2,3,8-trithis work are sulfanilamido and acetylated sul- methylquinoline in the blood, whereas larger doses fanilamido derivatives of 5-amino-2,3,8-trimethyl-of this material are inactive in the tissue. quinoline, and of the hitherto unreported 5Stage Dose, tested mg. Result amino-8-ethyl-2,3-dimethylquinoline and 5-amino5-Sulfanilamido-2,3,8-trimet€rylBlood 50 Active 2,3-dirnethyl-S-n-propylquinoline. quinoline Tissue 100 Inactive Through the courtesy and cooperation of Parke, 5- (N4-Acetylsulfani1amido)-2,3Davis and Company, the 2,3,8-trimethyl and 2 3 dimethyl-8-n-propylquinoline Blood 60 Inactive dimethyl-8-n-propylquinoline sulfanilainido deExperimental rivatives have received preliminary testing for possible pharmacological activity. No activity 2,3,8-Trimethyl-5-nitroquinoliie.-Fourteen grams of isolated from petroleum nitrowas found in mice infected with experimental 2,3,8-trimethylq~inoline,~ (1) Constructed from a portion of a thesis presented to the Graduate Faculty of the University of Texas by Leslie M. Schenck in partial fulfillment of the requirements for the degree of Doctor of Philosophy, June, 1942. (2) Parke, Davis Fellow, 18-11-1942; present uddrrsb. Geueral Aniline and Film Corporation, Grasselli. N. 1. (3) Bobranski, Arch. Phavm., 277, 75 (1939). ( 4 ) "interhottom, THISJ O I J R N A I . , 62, 100 (1940).
gen bases, was converted to 2,3,8-trimethyl-5-nitroquinoline in accordance with Burger and Modlin.B There was obtained 13 g. of purified product, crystallizing from petroleum ether as pale yellow needles melting a t 124' (cor.). ( 5 ) Poth, Schultze, King, Thompson, Slagle, Floyd a n d Bailey i b i d . , 62, 1239 (1930). (6) Burger and Modlin, ibid.. 62, 1079 (1!140),
