Sept., 1936
OPEN
CHAIN DERIVATIVES OF &MANNOSE
ICONTRIBUTION FROM THE CHEMICAL
1'781
LABORATORY O F THE OHIO STATE UNIVERSITY]
Open Chain Derivatives of &Mannose BY M. L. WOLF~OM AND L. W. GEORGES Application of the controlled hydrolysis, with was essentially the aldehydo-pentaacetate. Mild mercuric chloride and cadmium carbonate, to acetylation of mannose semicarbazone formed the acetylated sugar mercaptals' having the cis-con- same crystalline semicarbazone pentaacetate as figuration on carbon atoms two and three, such was obtained by the reaction between the deas mannose, rhamnose and a-glucoheptose, has oximated product and semicarbazide. Removal led to impure sirupy products instead of the of the semicarbazide group from this substance desired crystalline aldehydo-sugar acetates. The with nitrous acid yielded a sirupy pentaacetate new synthesis of aldehyde-sugar acetates reported which could be oximated to produce a crystalline from this Laboratory2 offered a different method of aldehydo-mannose oxime pentaacetate identical approach which has now been applied to d-man- with that obtained from the selective hydrolysis nose. The desired aldehydo-mannose penta- of the oxime hexaacetate of Deulofeu and coacetate was not obtained in crystalline form but a workers. The relationships between these comsirupy product was secured which was less im- pounds are shown in Fig. 1. It would appear pure than that produced by de-mercaptalation. from these results and from those of Deulofeu This sirup was characterized by a number of and co-workers, that d-mannose shows a procrystalline derivatives, of an open chain structure, nounced tendency to react in its open chain which are of interest and which can be produced by form. direct acetylation methods. Fig. 1 Deulofeu and co-workersahave Interrelationships in the aldehydo-mannose series shown that the low temperature HC=NOH acetylation of mannose oxime d-mannose +mannose oxime +HC=NOAc I I gives the open chain or aldehydo(CHOAC)~ + (CHOAC)~ I 1 mannose oxime hexaacetate in CHzOAc CHzOAc good yield. The assignment of aldehydo-mannose aldehydo-mannose oxime hexaacetate oxime pentaacetate an open chain structure to this HC( SEt)z compound was based upon its I transformation to the acetylated ( CHOAC)~ I nitrile on heating, a reaction CHlOAc mannose characteristic of the open chain semicarbazone HC=N--NHCONH, mannose HC=O diethyl mercaptal 1 aldose oxime hexaacetate~.~In I ( CHOAC)~ ( CHOAC)~ the work herein reported, the 0-acetyl of the oxime group has CH~OAC ----f CHzOAc aldehydo-mannose aldehydo-mannose been selectively hydrolyzed and semicarbazone pentaacetate the resulting crystalline oxime pentaacetate pentaacetate has been deoximated with nitrous acid to produce the aldehydoExperimental mannose pentaacetate as a sirup. This sirup was Preparation of Aldehydo-d-mannose Oxime Hexaacecharacterized by two crystalline derivatives, man- tate.-This substance was prepared by the low temperanose diethyl mercaptal pentaacetate and aldehydo- ture acetylation of mannose oxime as described by Deulofeu and c o - ~ o r k e r s except ,~ that mechanical stirring was mannose semicarbazone pentaacetate. The for- employed and the reaction was satisfactorily completed in mation of these two carbonyl derivatives without twelve hours a t 2' instead of in eight days a t 0 " ; m. p. loss of acetyl groups indicated that the sirup 91-92'; ( C X ) ~ &-8.5" D (6, 4 ; CHCI,). Deulofeu and co-
.1
(1) M. L. Wolfrom, THIS J O U R N A L , 61, 2188 (1929). (2) M. L. Wolfrom, L. W. Georges and S. Soltzberg, ibid., 66, 1794 (1934) ( 3 ) V. Deulofeu. P. Cattaneo and G. Mendivelzua. J . Chem. S u c . , 147 (1934) JOURNAL, 63, 625 (4) M. L. Wolfrom and A. Thompson, THIS (1931).
if
I
workers record the constants: rn. p. 94"; ( c x ) ~ ~ -8.3" D (CHCL). Aldehydo-d-mannose Oxime Pentaacetate.-Aldehydod-mannose oxime hexaacetate (7.5 8 . ) and 6.5 g. of oxalic acid dihydrate were dissolved in 80 cc. of warn1 methanol and the solution refluxed for thirty minutes. The solvent
1782
M. L.WOLFROM AND L. W.GEORGES
Vol. 58
was removed under reduced pressure and the crystalline residue was washed with several 50-cc. portions of cold water to remove the oxalic acid; yield 4.9 g.; m. p. 119122'; (a)D 4-14' (CHClJ. Pure material was obtained by digestion with ether followed by recrystallization from the minimum amount of hot ethanol by the addition of water; m. p. 122-123'; ( ~ ) P @ D +15' (c, 4; CHCl,).
11.2 cc. of 0.1 N NaOH per 100 mg. Found: N, 9.12; acetyl, 11.3 cc. Aldehydod-mannose semicarbazone pentaacetate was also obtained in good yield by the direct acetylation of mannose semicarbazone.8 An amount of 6 g. of mannose semicarbazone was added to a solution of pyridine (36 cc.) and acetic anhydride (18 cc.) and the mixture shaken meAnal. Calcd. for CsH~O~N(COCH&.:N, 3.45; acetyl, chanically at room temperature for four hours. The semi12.35 cc. of 0.1 N NaOH per 100 mg. Found: N, 3.53; carbazone dissolved and the solution was kept at ice box acetyl (Freudenbergs method), 12.3 cc. temperature for twelve hours and was then poured into 800 Further acetylation of this substance under mild condi- cc. of ice and water. The crystalline product that separated was removed by filtration and washed with cold t ions produced aldehydo-d-mannose oxime hexaacetate. ' in a pre- water; yield 5 g.; m. p. 176-179' (dec.); (a)naD $8.9' The pentaacetate (4.4 g.) was dissolved at 0 viously cooled solution of acetic anhydride (13 cc.) and (c, 2; CHCLS). Pure material was obtained on one recryspyridine (26 cc.) and maintained a t 0' for one hour. The tallization from hot water; m. p. 178-180' (dec.) (m. p. product was obtained in crystalline form by pouring into unchanged on admixture with product from the de-oxima300 cc. of ice and water; yield 3.8 g.; m. p. 89-90'. Pure tion); (a)"D f9.3' (c, 2.5; CHCla). Splitting of Aldehydo-d-mannose Semicarbazone Pentamaterial was obtained by recrystallization from a small amount of hot ethanol by the addition of water; yield 2.5 acetate with Nitrous Acid.-Aldehyh-d-mannose semicarbazone pentaacetate (3.2 g.) obtained from the acetylag.; m. p. 91-92'; (u)*'D -8.4" (c, 4; CHCla). De-oximation of Aldehydo-d-mannose Oxime Penta- tion of mannose semicarbazone was dissolved in 40 cc. of acetate.-Aldehyde-d-mannose oxime pentaacetate (1.6 hot ethanol and a warm solution of 10 g. of sodium nitrite g.) was de-oximated with nitrous acid as described by Wol- in 200 cc. of hot water added. The solution was then from, Georges and Soltzbergz for the corresponding glucose placed in a water-bath maintained at 70' and treated with compound. The sirup (1.2 9.) obtained after chloroform hydrochloric acid and additional sodium nitrite as deremoval resisted crystallization and was purified by pre- scribed by Wolfrom, Georges and Soltzberg2 for the decipitation from acetone solution by the addition of petro- oximation of aldehyde-glucose oxime pentaacetate. The leum ether. The product reduced Fehling's solution and sirup so obtained was dissolved in 30 cc. of hot water, cooled to room temperature and treated with a solid mixgave a Schiff free aldehyde test. ture of hydroxylamine hydrochloride (0.6 9.) and potasAnal. Calcd. for CBH&(COCHa)r: acetyl, 12.8 CC. of sium acetate (1.2 g.). Crystals formed after several hours; 0.1 N NaOH per 100 mg. Found: acetyl, 12.24 cc. m. p. 118-120'. These were recrystallized from hot That the sirup was moderately pure aldehydo-d-mannose ethanol by the addition of water; m. p. 121-123" (m. p. pentaacetate was proved by the preparation of two crystal- unchanged on admixture with the previously described line derivatives. Treatment of the sirup with ethyl mer- preparations of aldehydo-mannose oxime pentaacetate); captan and zinc chloride according to the procedure of (a)21D+13 * '1 (c, 2.3; CHCla). The isolation of this Wolfrom and Thompson' yielded crystalline mannose di- product from the oximated sirup indicated that the sirup ethyl mercaptal pentaacetate; m. p. 5132' (unchanged was essentially aldebydo-d-mannose pentaacetate. on admixture with the product obtained on acetylation of summary mannose diethyl mercaptal);' (a)% +32' (c, 4; CHCls). Pine records the constants: m. p. 51-52'; (a)"D 4-31' 1. Aldehyde-d-mannose semimrbazone penta(CHCls). acetate and aldehyde-d-mannose oxime pentaAldehydo-d-mannose Semicarbazone Pentaacetate.acetate have been synthesized in crystalline condiAn amount of 2.4 g. of the sirupy aldehydo-d-mannose pentaacetate, obtained by the de-oximation procedure, was tion. Proof is furnished for the structure of these dissolved in 35 cc. of hot water, the solution cooled rapidly compounds. t o room temperature and treated with a solid mixture of 2. Mild acetylation of d-mannose semicarbasemicarbazide hydrochloride (0.95 8.) and potassium ace- zone produces aldehydo-d-mannose semicarbazone tate (1.5 g . ) . The semicarbazone separated in crystalline form; yield 1.3g., m. p. 173-175" (dec.); (U)~'D+9.4' (c, pentaacetate in good yield. 3. Nitrous acid treatment of either aldehyde2.5; CHCLJ. Pure material was obtained on recrystallizad-mannose semicarbazone pentaacetate or aldetion from hot water; m. p. 177-178' (dec.); (.)"a 4-9.2' (c, 2.5; CHCb). hydo-d-mannose oxime pentaacetate produces Anal. Calcd. for C,HloO&(COCHs)~: N, 9.40; acetyl, uldehydo-d-mannose pentaacetate as a sirup char(5) K. Freudenberg and M. Harder, Ann., 48% 230 (1923). ( 6 ) M. L. Wolfrom and A. Thompson, THISJOURNAL, 66, 882 (1934). (7) N. W. Pirie, Bwchem. J . , 80, 374 (1936).
acterized by several crystalline derivatives. COLUMBUS, OHIO
RECEIVED JULY 17, 1936
(8) Maquenne and Goodwin, Bull. soc. chim., [3] 81, 1075 (1904).
