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Vol. 68
his modification should not be considered a really fundamental improvement over the BET theory.
acetylation, yielded pentaacetyl-N-methyl-d-glucosamine; m. p. 160.5-161.5° (micro-block), [CX]"D + l o l o . The properties of this compound DEPARTMENT OF CHEMISTRY UNIVERSITY OF ROCHESTER TERRELL. L. HILL are identical with those of the pentaacetyl derivaN. Y. ROCHESTER, tive described above except for the sign of rotaRECEIVED DECEMBER 10, 1945 tion. With these data and the reported configuration it is concluded of carbon atom 2 of d-gl~cosamine,~ STREPTOMYCES ANTIBIOTICS. V. N-METHYLthat the configuration a t carbon atom 2 of the I-GLUCOSAMINE FROM STREPTOMYCIN hexosamine is also that of 1-glucose and the degraSir: dation product is N-methyl-Z-glucosamine. Streptomycin has been degraded to a new ( 5 ) Haworth, Lake and Peat, J . Chem. SOC.,271 (1939). product which has been established as N-methyl-lFREDERICK A . KUEHL,J R glucosamine. EDWXH. FLYNN Acid hydrolysis of methyl streptobiosaminide MERCKRESEARCH LABORATORIES FREDERICK W. HOLLY RALPH hfOZIh-GO dimethyl acetall followed by acetylation yielded a MERCK& Co , I s c . SEW JERSEY ?&4RL FOLKERS pentaacetyl derivative of a hexosamine; m. p. RAHTVAY, RECEIVED FEBRUARY 26, 1946 160.5-161.3' (micro-block), [ c u ] ~ ~ D- 100' (c, 0.7 in chloroform). Anal. Calcd. for C17H25Nolo: C, 50.62; H, 6.25; N, 3.47; CH,CO, 53.3; NEIGHBORING GROUPS AND REACTIVITY mol. wt., 403. Found: C, 50.51; H, 6.24; IT, .3.76; CI&CO, 49.2; mol. wt., 414 (cryoscopic in Sir: benzene). The hydrochloride of the hexosamine Heretofore, we have stressed the stereochemical was obtained from the pentaacetyl derivative by consequences of participation by neighboring hydrolysis with hydrochloric acid; in. p. 160-163' groups' such as OAc, Br, OCH3, etc., in replace(micro-block), [ a I z 5 D - 103' (initial), -88' (final) ment reactions. We have recently completed rate ic, 0.6 In water). Anal. Calcd. for C71-I15iY05~ measurements which bring out the striking connecHCI: C, .3G,GO; H, '7.02; CHON,6.5. Found: tion between reactivity and this participation. C, 36.65; H, 6.&6; CH3N, G.S. Treatment of the First order rate-constants of solvolysis a t '73' hydrochloride with silver oxide gave the free base in glacial acetic acid of a series of 2-substituted as a colorless gum; [ c ~ ] ~-65' ~ D (c, 1.O in methacyclohexyl p-brgmobenzenesulfor7ates give the nol). Acetylation of the free base in the pres- following relative reactivities : unsubstituted, ence of methanol gave the N-acetyl derivative ; 1.00; trans-2-OXc, 0.240; tram-2-Br, 0.101; m. p. 1153-166' (micro-block), [ a I z 5 -51' ~ (c, trans-2-OCH3, 0.057; trans-2-C1, 4.9 X 0.4 in water). cis-2-OL%c, 3.8 X cis-2-OS02C6H4Br,7.7 X The phenylosdzone prepared from the hexostrans-2-OS02CsH4Br,6.9 X Similarly, amine melted a t 205' ( ~ a p i l l . ) . ~4 phenylosotri- acetolysis rates a t 23.6' of cyclohexyl p-tolueneazole, prepared3 from this osazone, melted a t the sulfonates give the relative reactivities : transsame ternperature (196-197') as the correspond- 2-1, 1800; unsubstituted 1.00. ing derival ive of d-glucose, and the speciiic rotaThe effects of a halogen substituent similar tion was of equal magnitude but opposite in sign. to those above are seen also in the rough values Oxidation of the free hexosamine with mercuric of relative reactivities of alcohols to fuming oxide gave an acid which had the same melting hydrobromic acid or concentrated hydrochloric point (m. p. 230-232') reported for N-methyl-d- acid a t room temperature. One reactivity seglucosaniic acid.4 Again, the rotation was of the quence obtained in this way is: tmns-2-iodosame magnitude but opposite sign. cyclohexanol 1000; cyclohexanol 1; trans-2Hydrolysis of the product of the reaction be- bromocyclohexanol 0.0s; fm?zs-3-chlorocvclotween I-arabinose, inethylainitle and hydrogen hexanol 1.6 X cyanide 'yave an acid which was identical with the In the relatively reactive substitutcd cyclo"natural" acid described above. IVhen the syn- hexyl compounds (which are typical of most of thetic acid was converted to the lactone, reduced the cases where stereochemical evidence for and acetylated, the product was found to be participation exists) the neighboring group supidentical with the pentaacetyl derivative of the plies a large driving force for the r,ite-detcrmining "natural" hexosamine. Thus, the configurations ionization of the departing group. This parabout C3, C4,and C5of the hexosamine are those a t tially neutralizes or completely overbalances carbons 2, 3, and 4 of 2-arabinose (or carbons 3, 4 (as for I) the rate-retarding intluctive effect. and 5 of I-glucose). The sequence I > Br > C1 is to be expected. A s 11ethyla tion of d-glucosamine, followed by in the case of the acetoxy group, the driving force (1) Brink, Kuehl and Folkers, Sczence, 102, 506 (1945). is supplied from the trans-positiotl and poorly (2) I-Glucose phenylosazone, m p 205O, Fischer, B e y , 23, 374 if a t all from the cis-position. In the case of thc (1890) J O U R V A L , 67. 93" (lQ45) (3) Haskins Hann and Hudson, THIS (4) Votoipk and Luke4. Ciwm L ~ c l v29, 308 (1915)
(1) Winstein and 5cxmour Trrrs J o r r R v i r p r e t i o u q articlrq in t h e ceric,
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