DECEMBER 1957
1727
NOTES
the possibility of the establishment of equilibrium between the isomers, and upon the presence in the laboratory of seed crystals of the two forms. Water does not seem to be the determining factor, but might have some effect in accelerating the interconversion of the isomers. The sensitivity of these LAWRENCE ROSEN,JAMESW. WOODS, AND WARDPIGMANreactions to acid catalysts6 suggests that accidental traces of acids may also produce variable rates of reReceived May 13, 1957 establishment of equilibria during crystallization.
Reactions of Carbohydrates with Nitrogenous Substances. V. The Supposed Influence of Water on the Preparation of N-p-Tolyl-DGlucosylamine192
Two isomers (A and 13) of N-phenyl-D-ribosylamine and of N-p-tolyl-D-glucosylamine have been obtained. For the ribose derivatives, the reaction temperature during preparation was considered originally to be the factor determining the particular isomer obtained.a Later Ellis and Honeyman4 provided evidence that for a number of glycosylamines the presence or absence of water was the factor determining the isomer that was formed. For N-ptolyl-D-glucosylamine, Isomer A( [a]: 209 4 -45", methanol) was reported to be the isomer formed under anhydrous conditions. Isomer B ( [aiD- 100 (variable) -45', methanol) was obtained in the presence of water. In our laboratory, N-p-tolyl-D-glucosylamine is usually prepared by refluxing D-glucose with a 33% molar excess of p-toluidine in ordinary commercial absolute methyl alcohol (Baker's reagent grade). The reaction mixture is then concentrated under reduced pressure and successive crops are collected. Water shouid be present, since it is formed in the reaction. I n our earlier work, the usual form of N-ptolyl-D-glucosylamine that was obtained was levorotatory (Isomer B4tS),in conformity with the results of Ellis and Honeyman. I n more recent work, we have obtained the dextrorotatory Isomer A,"K as the first crop from repeated preparations, even when water was deliberately added to the reaction system. Successive crops from the same preparation appeared to be mixtures of both isomers,*since the initial specific rotation in methanol varied from -206" to -89', and all crops mutarotated to a constant value of approximately -45'. We infer from these results that, as might be expected, the particular crystalline isomer or mixture of isomers which is obtained in this laboratory depends upon the composition of the reaction mixture at and during the time of crystallization, upon
+
-
(1) This work was supported by a grant from the National Science Foundation. (2) Previous paper, this series: L. Rosen, J. W. Woods, and W. Pigman, Chem. Ber., 90, 1038 (1957). (3) L. Berger and J. Lee, J . Org. Chem., 11, 75 (1946). (4) G. P. Ellis and J. Honeyman, J . Chem. floc., 1490 (1952). They report the stereoisomer which is obtained under anhydrous conditions as Isomer A, the other isomer being Isomer B. (5) G. P. Ellis and J. Honeyman, Advances i n carbohydrate C h . ,10,95 (1955). I n this review article the isomeric forms, A and B, of N-p-tolyl-D-glucosyle are designated as N-p-tolyl-a- and N-p-tolyl-&D-~ucosyl~ne respectively (seep. 147).
EXPERIMENTAL
Anhydrous methanol was prepared by treating methyl alcohol absolute, Baker reagent, with magnesium turnings.7 The specific rotations of N-p-tolyl-D-glucosylamine were determined using a 2 dm. tube. Anhydrous methanol was used as the solvent. The readings were made a t 20', but on occasion in order to increase the rate of mutarotation, the anhydrous solutions of N-p-tolyl-n-glucosylamine were kept a t 37' to 38' between readings. Anhydrous D-glucosk (Cerelose, Corn Products) was used, and the p-toluidine (Eastman, White Label) was recrystallized before use. All melting points were accompanied by decomposition (browning) and were determined on a Fisher-Johns block and are uncorrected. The following are different preparations of N-p-tolyl-Dglucosylamine. All crops were dried to constant weight in vacuo over calcium chloride and sodium hydroxide. Preparation A: Anhydrous D-glucose (15 g., 0.083 mole) and p-toluidine (12 g., 0.11 mole) were refluxed 150 min. in 175 ml. methanol. The light tan clear solution was concentrated under reduced pressure at room temperature to a thin sirup (27 ml.), to which 10 ml. ethanol was added, and worked in. The sirup was allowed to stand overnight. The f i s t crop of crystals was collected and washed twice with ethanol to yield 7.4 g. (33%). A second crop (3rd day) (4.7 g., 21%) and a third crop (8th day) (3.8 g., 17%) were also collected from the mother liquor and washed and dried as above. X o further crops were collected due to extensive browning of the mother liquor. The physical constants were: Crop 1, m.p. 133-134" (dec.), [a]? f 206.4' (5 rnin.) + -44.9' (con59.3' stant) (c 1.0); Crop 2, m.p. 127-131' (dec.) [a]? -43.7' (constant) (c 1.1); Crop 3, m.p. 126-130' (7 min.) -43.5' (constant) (c 1.4). (dec.), [a]kO-28.7'(6min.)+ Preparation B: Anhydrous D-glucose (18 g., 0.10 moie) and p-toluidine (14 g., 0.13 mole) were refluxed 165 min. in a solvent composed of, 150 ml. anhydrous methanol and 2.0 ml. water (0.11 mole). The reaction mixture was concentrated under reduced pressure at room temperature to 35 ml. Two crops were collected: the fist (3.6 g., 13%)after the sirup stood overnight, and the second (12.2 g., 45%) on the third day. The physical constants were: Crop 1, m.p. 134-43.8' (constant) (c 135' (dec.), [ala" 200' (6 min.) 0.34); Crop 2, m.p. 127-130' (dec.), [a]? $31.6" (5 min.) + -44.2' (constant) (c 0.50). Preparation C: This was made identically to preparation B but in another laboratory after careful washing of the equipment. The first crop (11.1 g., 41%) was collected after 36 hr. and the second crop (6.0 g., 22%), 4 days later. Physical constants follow: Crop 1, m.p. 119-122' (dec.), [a]'," -84.2' (6 rnin.) + -43.6' (constant) (c 1.1); Crop 2, m.p. 117-119' (dec.) [a]? -89.4' (4 min.) 4 -44.2' (constant) (c 1.1).
-
+
+
-
(6) H. S. Isbell and H. L. Frush, J . Research Nail. Bur. &UndaTdS,46,132 (1951). (7) L. F. Fieser. Experiments in Oraanic chemistrv. 2nd Edition, p. 360, D. C: Heath and Company, New"York, N. Y., 1941.
1728
NOTES
Preparation D: Anhydrous D-glucose (30 g., 0.17 mole), and p-toluidine (24 g., 0.22 mole) were refluxed 180 min. in 200 ml. methanol. After 2 days at room temperature, the brownish solution was concentrated under reduced pressure between 35-50' to a thick sirup, approximately 25 ml. Crystallization occurred at once and after 2 days a t room temperature, a crop was collected, washed, and dried in the usual manner. The crop (28 g., 62%) had the following 14.0" physical constants: m.p. 126-128" (dec.): [a]? (6 min.) -.c -44.7' (constant) (c 0.35).
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DEPARTXENT OF BIOCHEMISTRY UNIVERSITY OF ALABAMA MEDICAL CENTER 3, ALA. BIRMINGHAM
Reactions of N-Bromoamides and N-Bromoimides with Styrene' ROBERT E. BUCKLES AND WILLIAM J. PROBST Received Mag 13, 1957
N-Bromoacetamide has been reported213to react rapidly with styrene to give the dibromide. N Bromosuccinimide, however, gave little or no reaction with ~ t y r e n e I. ~ n all reactions including decomposition N-bromosuccinimide was found qualitatively to be less reactive than N-bromoacetamide. This type of result has been related to the tendency of N-bromosuccinimide to brominate the allyl position so successfully.3For this reason a number of Nbromoamides and N-bromoimides have been tested as to their reactivity with styrene. The results are summarized in Table I.
VOL.
22
hydantoin the N,N'-dibromodiamides were of intermediate reactivity except for N,N'-dibromomalonamide which was very unreactive. N-Rromoglutarimide appeared to be consumed by a slow reaction, but only a small yield of the dibromide was obtained after an extended reaction period. Of the N-bromo compounds which were relatively unreactive to styrene l-bromo-5,5-dimethylhydantoin4 and 1,3-dibrom0-5,5-dimethylhydantoin6 have been reported as successful brominating agents for allyl and benzyl positions. N-Bromophthalimide was reporteda as brominating the allyl position but giving dibromide and a 1:1 adduct as by-products. N-bromoglutarimide was found in the present investigation to react with cyclohexene to give 3-bromocyclohexene in 66% yield in contrast to its reporteda unreactivity. The reaction of styrene with N,N-dibromobenzenesulfonamide evidently gave rise to a 1:1adduct analogous to that reported' for N,N-dibromo-p-toluenesulfonamide. The products isolated, however, were N-benzenesulfonylstyreneimide, when the rea,ction mixture was treated with base, and N-(2bromo-1-phenylethy1)-N-(1-bromo-2-phenyl -ethyl) benzenesulfonamide when excess styrene was present. The structures of these compounds were assigned on the basis of analogous derivatives described7 for N,N-dibromo-p-toluenesulfonamide. EXPERIMENTAL
N-Bromo compounds. Samples of the N-bromo compounds used were kindly supplied by Dr. Thomas D. Waugh,
TABLE I STYRENE I N BOILING CHLOROEORM
ItEACl'IONS 01", ~ T - B R O M OCOMPOUNDS WITH
_.
N - l h m o Compound Namr
i\'-Bromophenylacetamide E-Bromo-a-toluamide N-Bromobenzamide N,X '-Di bromosuccinamide N,N'-Dibromoterephthalamide N,N'-Dibromooxamide 1-Bromo-5 5-dimethylhydantoin N,N'-Dibromomalonamide N-Bromophthalimide .V-Bromoglutarimide 1,3-Dibromobarbituric acid 1,3-Dibromo-5,5-dimethylhyd3ntoin a
Mole
Reaction Time, hrs.
0.025 0.01 0.025 0.018 0.018 0.025 0.04 0.025 0.025 0.025 0.01 0.025
0.5 1 .o 1.25 4.5 10 24 34 25 24
-Amide or imide
% Yield N-Bromo comDd.
91 59 50 86 0 0
53 0 0
0 0 0 0 67 42 0
97 92
60
29
0
24 24
0
95 97
0
Dibromidea
53 23 52 30 31 32 30 0 0
6 0 0
Yield of dibromidp based on the amount of N-bromo compound consumed during the reaction.
The -V bromoimides were the least reactive in general uhile the simple N-bromoamides were the
(4) 0. 0. Orazi and J. Mcscri, Anales asoc. quim. argentina, 37,192,263(1949). (5) 0. 0. Orasi and J. Meseri, Anales asoc. quim. argen_-_ -. (1) Taken from part of the Ph.D. dissertation of William tina, 38,5 (1950). (6) I
