1112
JOHN
WALTERHYDEOLDHAM AND MARYANN OLDHAM
[CONTRIBUTION FROM THE UNITED COLLEGES OF S T .
Vol. 61
LEONARD AND ST.SALVATOR]
A Synthesis of 2,4,6-Trimethylglucose BY JOHN WALTERHYDEOLDHAMAND MARYANN OLDHAM Researches on 2,4,6-trimethylglucose formed after removal of the benzylidene residue and part of a wider investigation carried out in this methylation of the sirup so obtained, was conLaboratory some years ago. The major researches verted into a crystalline substance with the comled to ambiguous results, but we have been asked position of a mono-p-toluenesulfonyl-trimethylby Professor Freudenberg to publish this syn- methylglucoside, its method of preparation leavthesis, to which reference has already been made ing no doubt as to the positions occupied by the in the footnote of a previous communication.' various groups. It was shown to be identical with The most obvious method of approach to deriva- the crystals obtained by treating the 2,4,6-tritives of 2,4,6-trimethylglucose is through a com- methyl-P-methylglucoside (referred to in our prepound in which position 3 is occupied by a stable vious paper) with p-toluenesulfonyl chloride. group of atoms. The non-labile nature of the This trimethyl-glucose had been obtained from p-toluenesulfonyl group had long been recognized sucrose and, although good reasons had been and 3-p-toluenesulfonyl-diacetone-glucose was ac- advanced by Haworth2 to show that the methyl cordingly chosen as a suitable starting material. groups occupied positions 2,4,6, its constitution Attempts to methylate the sirupy 3-p-toluenesul- had not been established definitely. fonyl-p-methylglucoside, obtained from 3-p-toluExperimental enesulfonyl-diacetone-glucose as described in 3 p Toluenesulfonyl - triacetyl p - methylglucoside. the practical part of this paper, led, however, to -3-p-Toluenesulfonyl-diacetone-glucose was hydrolyzed unfortunate results, direct methylation being by boiling in 8.55% concentration with acetonitrile confollowed by unexpected decomposition and an taining 20% by volume of 0.1 N hydrochloric acid for indirect method being rendered difficult by steric two hours, when the rotation became constant a t 4-49.9". hindrance. An alternative route was, however, The solution was neutralized with barium carbonate, available. The 3-p-toluenesulfonyl-diacetone- evaporated to dryness a t 80' (if drying is continued too long, decomposition occurs) and the product acetylated glucose was converted to a mixture of the corre- with excess of acetic anhydride and pyridine. Two and sponding a- and P-methylglucosides by boiling one-half grams of starting material yielded 3 g. of product with methyl alcohol containing hydrogen chlo- which partly crystallized, giving 1.2 g. of crystals melting ride and this mixture, unlike the pure p-methyl- a t 170-171" and having [CY]D in chloroform +8.7' for glucoside, reacted readily with the methylating c, 5.075,a and 1.8 g. of sirup having [ d D in chloroform +42.6" for c, 5.482. On treatment with 25% of hydroreagents. The a-form of 3-p-toluenesulfonyl-2,4, bromic acid in glacial acetic acid, ether and benzene in 6-trimethylmethylglucosidewas separated in the the usual manner, the rotation of the crystals rose to crystalline state and is here described for the +170.0° and of the sirup to +141.5', indicating that the first time. Unfortunately, the p-form could not sirup contained a fair amount of compound in the ?-form. The product was converted to the p-methylglucoside be isolated from the mixture and, as it was this by reaction with methyl alcohol and silver carbonate. form that was required for identification pur- From 19.1 g. of total acetylated material, 8.9 g. of the pure poses, another method of preparation had to be @-methylglucoside,am. p. 134-136", and 1.7 g. of less pure, m. p. 125-128', were obtained. employed. The products were deacetylated with sodium methylate 2-Monomethyl-~-methylglucosidewas treated in a mixture of benzene and methyl alcohol a t the temperawith benzaldehyde and converted to the corre- ture of the room. The system was neutralized with a few sponding benzylidene compound. Its constitu- drops of glacial acetic acid and evaporated to dryness a t tion was determined by methylation of a small 40'. The sirup, so obtained, was treated with silver oxide sample from which a good yield of the well-known and methyl iodide. During the methylation, however, 2,3-dimethyl-benzylidene-~-methylglucoside was decomposition seemed to occur. 3 - p - Toluenesulfonyl - 4,6 - benzylidene - p methylobtained. The main bulk reacted with e-toluglucoside.-One and three-tenths grams of 3-#-tolueneenesulfonyl chloride with difficulty, giving a crys- sulfonyl-0-methylglucoside, obtained as described above, talline derivative in which the p-toluenesulfonyl was treated with benzaldehyde and zinc chloride for twenty group must necessarily occupy position 3. This, (2) Haworth, J . Chcm. Soc., 273 (1926).
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(1) Oldham and Rutherford, T H I S JOURNAL, 64, 366 (1932).
(3) Freudenberg, Bey., 66, 929 (1922).
May, 1939
hours and the product was recrystallized from absolute alcohol as prisms melting a t 174-176' with decomposition and having [ a ] D in chloroform -93.3' for c, 5.653. It was almost insoluble in hot and cold alcohol but soluble in other solvents. Calcd. for C~H2408S: OCHs, 7.2. Found: OCHa, 6.4. On attempted methylation, the melting point merely rose to 179-182'. As it was shown later that the methylated compound melted a t 135-136", it was assumed that methylation had been prevented by steric hindrance. 3 p Toluenesulfonyl 2,4,6 trimethyl a methylp Toluenesulfonyl - diacetone glucose glucoside.-3 was boiled with methyl alcohol containing 2% of hydrogen chloride. The following changes in rotation occurred :
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1113
SYNTHESIS OF 2,4,6-TRIMETHYLGLUCOSE
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0 . 5 hour -21.3
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- -
6 . 5 hours +17.9
5 hours +15.9
and ether, sparingly soluble in benzene and soluble in other solvents. Calcd. for C22H2608S: OCHs, 13.7. Found: OCHs, 13.9. 2,4,6 Trimethyl 3 p toluenesulfonyl 8 methylglucoside.-The benzylidene residue was hydrolyzed in a manner already described. The following changes in [ a ]occurred: ~
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Min. [a]D
Min. [a]D
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- - -
0 -84.5
30 -43.0
50 -30.0
120 -12.7
140 -10.9
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160 9.7
70 -21.2
95 -13.1
215 8.4
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In the last four values, allowance was made for change in concentration. The product was isolated and methylated until there was no further change in the refractive index. After recrystallization from absolute alcohol, the fully methylated substance separated as cubes melting a t 103-104°, soluble in all solvents, except cold alcohol, petroleum ether and water, and showing [ a ]in~chloroform +1.9 for c, 5.068. It proved to be identical in melting point, mixed melting point and rotation with the product obtained by the ptoluenesulfonation of ,the supposed 2,4,6-trimethyl-pmethylglucoside already described.'
In the last two calculations, allowance was made for change in concentration due to the loss of the acetone groups. The solution was neutralized and the product was isolated in the usual manner. Methylation with silver oxide followed until the refractive index became constant a t 1.4999. On standing, the product partly crystallized; the crystals were isolated from the siruR and, after recrystallization, melted a t 123-124" with [ a ] ~in, chloroIn conclusion, the authors wish to express form, +53.6' for c, 2.64. Calcd. for ClVH180aS: OCHs, their thanks to Principal Sir James C. Imine, 31.8. Found: OCHs, 31.6. LL.D., D.C.L., F.R.S., for his constant and 4,6 Benzylidene 2 -methyl 8 methylg1ucoside.-On kindly interest in the work and for much valuable treating 6.4 g. of 2-methyl-8-methylglucoside with benzaldehyde and zinc chloride, 6.1 g. of crystalline benzylidene criticism and advice. compound, m. p. 169-171°, was isolated. After recrysSummary tallization from absolute alcohol, the product separated in needles, m. p. 170-171", and having [ a ] D in chloroform 2-Monomethyl-~-methylglucoside was con-69.2" for c, 4.1826. It was fairly soluble in acetone, verted to 2,4,6-trimethyl-3-~-toluenesulfonyl-~chloroform and hot alcohols but insoluble in ether, petroleum ether and cold alcohols. Calcd. for C16HzoOa: methylglucoside and shown to be identical with the compound obtained on p-toluenesulfonation OCH,, 20.9. Found: OCHs, 21.4. 4,6 Benzylidene 2,3 methyl p methylg1ucoside.of the supposed 2,4,6-trimethyl-p-methylglucoSixth-tenths gram of the substance was twice methylated side (referred to in a previous communication), and the product recrystallized from alcohol, 0.4 g. of thus establishing the constitution of this comcrystals, melting a t 132-135", being obtained. The meltpound. In addition, the following new coming point was unchanged on admixture with an authentic specimen of benzylidene-2,
[email protected] are described : 3-p-toluenesulfonyl-4,64,6 Benzylidene 3 p toluenesulfonyl 2 methylbenzylidene-&methylglucoside,
[email protected] and seven-tenths grams of fonyl-2,4,6-trimethyl-a-methylglucoside, 4,6-benbenzylidene-2-methyl-@-methylglucoside was treated twice zylidene-2-methyl-~-methylglucoside, 4,&benzyliwith p-toluenesulfonyl chloride and 3.79 g. of crude proddene-3 p toluenesulfonyl2 -methyl-P-methylgluuct was isolated (a yield of 94% of the theoretical amount). After being twice recrystallized from absolute alcohol, the coside. crystals separated in large prisms, melting a t 135-136". THE UNIVERSITY OF ST.ANDREWS It was almost insoluble in hot alcohols, petroleum ether SCOTLAND RECEIVED JANUARY 30, 1939
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