2840 OLDHAM TRANSFORMATIONS OF THE SUGAR NImTES. CCCXCII.-Transforrnation~ of the Sugar Nitrates. By JOHN WALTER HYDE OLDHAM. ALTHOUGH the nitrates of the sugar group are as's rule definitely crystalline and eaaily adaptable to synthetical operations little use seems to have been made of them since they were studied by Will and Lenze (Ber. 1898 31 68) and Koenigs and Knorr (Ber. 1901, When 2 3 5-trimethyl glucosan dissolved in chloroform is acted on by fuming nitric acid under the conditions described in the experimental part tt.imethy1 glucose dinitrate is obtained. The result is striking particularly M the action of the same reagent on 1 6-diacetyl2 3 5-trimethyl glucose yielded a syrup which failed to crystallise. Trimethyl glucose dinitrate has no action on Fehling’s solution either before or after acid hydrolysis.The nitrate group in position 1 can be replaced by methoxyl by boiling with methyl alcohol in presence of barium carbonate the reaction yielding trimethyl methyZglucoside 6-mononitrate. This mononitrate is converted on hydrolysis into the same trimethyl methylglucoside as is obtained from trimethyl glucosan and the nitrate group waa definitely allocated to the 6 position by the fact that on treatment with sodium iodide the same trimethyl methylglucoside iodohydrin wtts readily produced as that already obtained from Fischer’s acetodibromoglucose (Irvine and Oldham this vol. p. 2729). This sequence of changes indicatea that the nitrate group possesses considerable reactivity yet the compound was recovered unchanged (as wm also methylglucoside 6-mononitrate) when heated with alcoholic ammonia as described by Wallach (Ber.1881 14 422). In the parallel case of triacetyl glucosan the action of fuming nitric acid was more complex and a yellow syrup showing a high nitrogen content was invariably produced together with trkwtyl glucose 1 6-dinitrateY which wm isolated in fair yield. The com-pound had likewise no action on Fehling’s solution before or after acid hydrolysis but was readily converted into derivatives of different types. On boiling in glacial acetic acid solution with sodium acetate it was converted into tetra-acetyl glucose 6-mono-nitrate ; and this on hydrolysis yielded a tetra-acetyl glucose isomeric with that already obtained by Fischer in that the sixth hydroxyl group in place of the ikst is unsubstituted.Further although triacetyl glucose dinitrate reacted with methyl alcohol only with great difficulty yields of 5cr-sO~0 of the corresponding triacetyl rnethylglucoside 6-mononitrate were obtained. This compound was converted into triacetyl methylglucoside on hydrolysis and into 34 957) OLDHAM TRANSFORMATIONS OF THE SUGAE "RATES. 2841 triaCetyl methylglucoside 6-icniohydrin on trestment with d u r n iodide in acetone in the manner described by Irvine and Oldham iKethyZgZuca&le 6-mononitrate obtained by the action of ammonia on the corresponding acetyl derivative could not be isolated as it could not be separated from acebmide. By the action of dimethyl-amine and removal of the acetodimethylamide however the mono-nitrate of the parent glucoside w a isolated &s a syrup which failed to crystallise.By means of the silver oxide reaction this compound was converted into the trimethyl methylglucoside 6-mononitrate already described thus estabhhing the constitution of the complete series of new derivatives. Triacetyl methylglucoside 6-iodohydrin, on treatment with dimethylamine in the manner already described, gave a somewhat poor yield of m&7&lwide 6-iodohydrin. Finally, incidental evidence was obtained in the come of large-scale pre-parations of triacetyl methylglucoside 6-mononitrate that degrad-ation to the pentose seriea had taken place to a limited extent. Synthetical and constitutional studiea based on the method of nitrate formation now communicated are in progress.(loc. cit.). E x P E R I M E N T A L. 2 3 5-Trimethyl Glucose 1 6-Dinitrate.-A solution of trimethyl glucosan (5 g.) in a mixture of 60 C.C. of fuming nitric acid and 40 C.C. of chloroform containing a few grams of phosphorus pentoxide was kept for 19 hours at the ordinary temperature. The specific rotation increased from -64" to + 140.7" calculated on the change in concentration due to the addition of two nitrate groups. The mixture was poured slowly with constant stirring into ice the lower layer separated washed once with ice-cold water and taken to dryness below 60" in a vacuum. The dinitrate crystallised from absolute alcohol in colourless needles m. p. 86" (Found OMe, 30.3; N 9.1. C,H,,OI& reqces OMe 29-8; N 9.0).The compound is sparingly soluble in alcohol insoluble in water or light petroleum and soluble in other solvenfs. [.ID + 149.3" in chloroform (c 2.3193) + 151.7" in acetone (c 1.463) + 144-8" in methyl alcohol (c 1.508) and + 147.2" in a mixture of 60% of fuming nitric acid and 40% of chloroform by volume (c 2.915). Trimethyl Methylglucoside 6-Mommitrak-The dinitrate WM boiled in 5% solution in methyl alcohol for 4 hour in presence of barium carbonate. The product isolated in the usual manner (yield W%) was drained on a tile and recrystallised from light petroleum; it then melted at 53-54" % of the superfused sub-stance = 1.4565 (Found C 42.7; H 6.7; OMe 44.1 ; N 4.95. C,&,,O$ requires C 42.7 ; H 6-8 ; OMe 44.1 ; N 5.0%). Th 2842 OLDHAM TRANSFORMATIONS OF THE SUGAR NITRATES.mononitrate is insoluble in water but soluble in all other solvents. [=ID - 5.2" in chloroform (c 2=0653) - 4.4" in acetone (c 3.5845), and - 1.3" in methyl alcohol (c 3-3413). Conversion of Trimethyl Methylglucoside 6-Mo?wnitrate into priwm%yl MethyZqlucoside.-The compound was hydrolysed by boiling with iron dust in glacial acetic acid in not more than 5% concentration until a few drops of the liquid gave no trace of blue colour on standing for some time with a strong solution of diphenyl-amhe in concentrated sulphuric acid. (This reaction is given by all these compounds and constitutes an extremely delicate test for the presence of a nitrate group.) The solution was then filtered the reaidue washed with glacial acetic acid and the iiltrate poured info water containing a fair quantity of dissolved sodium acetate the object of which was to suppress the hydrogen chloride set free by the chloroform with which the solution was repeatedly extracted.The trimethyl methylglucoside thus removed on recrystallisation from light petroleum showed the correct melting point and mixed melting point. The yield waq good. Conversion into the Cmaprmding ITodohydrin.-On treating the mononitrate with sodium iodide in the manner already described (%e and Oldham this vol. p. 2729) a good yield of crystals was obtained m. p. 31-33" which showed no depression on mixing with a sample of the authentic iodohydrin. Preparation of Triacetyl Glucose 1 g-Dinitrate.-The best con-ditions as yet found are the following Triacetyl glucosan (5 g.) was dissolved in a mixture of 30% of chloroform with 70% of redistilled nitric acid * by volume solid nitrogen pentoxide (10 g.) added and the whole made up to 100 C.C.with chloroform and kept at the ordinary temperature for about 110 hours. The specific rotation of the solution was then about + 138". Sometimes the liquid separates into two layers; should these not disappear towards the end of the reaction the system can be made homogeneous by the addition of a small measured amount of fuming nitric acid. The product was isolated in the manner described for the corresponding methylated derivative and washed with cold absolute alcohol (yield about 65%). On recrystallisation from hot absolute alcohol this yield was diminished by nearly half and the product melted at 132-133".The substance is insoluble in water light petroleum or cold ethyl alcohol sparingly soluble in ether or cold methyl alcohol, * In this paper the expression " fuming nitric acid " refers to the product obtained by distilling ordinary concentrated nitric acid over its own volume of concentrated sulphuric acid. " Redistilled nitric acid " refers to a product, d J.54 obtained by distilling "fuming nitric acid" over twice its volume of concentrated sulphuric acid OLDHAM TBANSFORXATIONS OF THE SWGB XITBATES. 2843 and soluble in other solvents. The rotation of the pure compound in a mixture of fuming nitric acid and chloroform similax to that used in the preparation wag [ah + 144.2" for c = 5.0. The substance has not been mlpd as it is diilicult to obtain a perfectly pure specimen, but in view of the derivatives into which it can be transformed there can be little doubt that it consists of triacetyl glucose 1 6-dinitrate.Tetra-cmtyl CZumse 6-blonondtPate.-The dinitrate was boiled for 1-14 hours with a mixture of acetic acid acetic anhydride and sodium acetate. If the dinitrate waa pure scarcely any colour ww developed; but if not the solution coloured deeply. In the former case the reaction was practically quantitative as waa shown by the specific rotation falling from + 144" to + 23.3" the corresponding value of the pure substance in acetic acid being + 23.2". The product was poured into water when about 80% of it separated almost immediately in a cryatalline condition; the remainder, however sometimes took several days to separate.The product after recrystallisation from absolute alcohol melted at 142-143", reduced Fehling's solution strongly on boiling ww insoluble in water or light petroleum sparingly soluble in ether or alcohol and soluble in other solvents (Found C 42-55; H 5.0; N 3-65. glacial acetic acid (c 2.494) and + 27.2" in chloroform (c 2-038). Tetra-acetyZ GZucose.-The 6-mononitrate waa hydrolysed with iron dust in glacial acetic acid exactly as described in the case of the corresponding methylated compound. Tetra-acetyl gZme crystal-lised from ether in colourless needles m. p. 1266-1276" [.ID + 9.8" in chloroform (c 0-816) (Found C,H40, after allowance for the alkali used by the reducing sugar 68.7. Calc. C2Ha02, 68.9 %).The substance is insoluble in cold water or light petroleum, sparingly soluble in ether soluble in hot water and in organic solvents generally. "he above reaction is rather uncertain as sometimes the product failed to crystallise. TriaCetyZ Methylglucoside 6- Mononitrate.-Triacetyl glucose di-nitrate unlike both acetonitroglucose and the corresponding methylated derivative reacted only with great diEculty with methyl alcohol in presence of barium carbonate even when a small quantity of pyridine was added as recommended by Koenigs and h o r n (h. cit.). On boiling the mixture for 24 hours the specific rotation of the solution became constant at + 5.0". The solution WM atered and the solid well washed with chloroform. The washings were used to dissolve the residue left on evaporation of the methyl-alcoholic filtrate in order to purify it from trams of barium nitrate.After removal of the chloroform the red residue crystallised twice C&,O1& requires C 42.7; H 4.8; N 3.6%). [.ID + 23.2" in VOL. CXXVII. 5 2844 OLDELAX TRANSFORMATIONS OF THE SUGAR NITRATES. from absolute alcohol melted at 1336--1346" (yield 50-60%), and was insoluble in water or light petroleum sparingly soluble in ether or cold ethyl or methyl alcohol and soluble in other solvents (Found C 42.8; H 5.35; N 3.8; OMe 8.6; CH3-C02H 66.0. C,H190,,N requires C 42.7 ; H 5.2 ; N 3.8 ; OMe 8.5 ; CH3*C02H, 65.7%). [a], - 14.3" in chloroform (c 5.964) and - 14.1" in acetone (c 206913). If the substance is boiled with methyl-alcoholic sodium methoxide the specific rotation falls to - 115" allowance being made for the change in concentration due to loss of acyl groups, which corresponds to the formation of about 80% of Fischer's anhydro-methylglucoside.Trkeetyl .M&hylglutmide.-On hydrolysing the nitrate with iron dust in glacial acetic acid in t'he manner already described t r k t y Z methylglutmide was obtained in good yield in colourless crystals, melting after recrystallisation from ether a t 136134.5'; [a]= in chloroform = - 19.1" for c = 1.514 (Found OMe 9-5; CH3*CO&I 54.6. c13H&g requires OMe 9.6 ; CH3*C02H 56.2%). The compound is insoluble in cold water or light petroleum but soluble in other solvenh including hot water. Met h ylgluwside 6 - Mononit rate. -Tr iacet y 1 met hylgluc oside 6 -mononitrate was treated with a 5% methyl-alcoholic solution of dimethylamine and the acetodimethylarnide produced was distilled off in a vacuum at 100"; the residual syrup failed to crystalbe (Found N 5.9; HNO, 25.7.C,H130& requires N 5.85; €€NO3, 26.3%). A specimen of the substance was twice methylated by the silver oxide reaction ; the product crystallised on nucleation with tri-methyl methylglucoside 6-mononitrate obtained as described above. &r draining on a tile and recrystallisation from light petroleum, the compound showed the correct melting point and mixed melting point thus proving the constitution of this series of substances. Triacetyl Methylglucmide 6-Iodohydrin.-For the sake of compari-son triacetyl methylglucoside 6-mononitrate was treated with sodium iodide in acetone in the manner already described.The product after recrystallisation. from aqueous alcohol consisted of colourless needles m. p. 111-112~5" which were insoluble in water or light petroleum but soluble in other solvents. The yield was poor [Found OMe 7.4; I 28.0; CH,*CO,H (I being calculated as CH3*C0,H) 564. C,Hl9O8I requires OMe 7.2; I 29.5; CH3*C0,H 55.8y0). The specific rotation in chloroform was + 0-9" for c = 3.027. -Methylglumside 6-Iodohydrin.-On treatment with dimethyl-amine in the manner already described the precedmg triacetyl derivative was converted into the parent glucoside in bad yield. The product which consisted when pure of colourless crystals bu WEEKS LEAD DIEYDRIDE AND LEAD TE-RZDE.2846 was usually slightly pink melted at 157-158" was insoluble in ether or light petroleum very sparingly soluble in chloroform, slightly more soluble in acetone and soluble in other solvents. The best recrystallking medium was a mixture of chloroform and ethyl acetate (Found OMe 10.3; I 41.7. C,H130,1 requires OMe, 10.1; I 41.7%). Acetonitropentose.-On taking to dryness the mother-liquors from the recrystallisation of triacetyl methylglucoside 6-mononitrate, boiling for 4 hour with acetic anhydride and sodium acetate and pouring into water a precipitate wits obtained which after very many recrystallisations from absolute alcohol melted at 168-169". The compound did not reduce Fehlmg's solution and was a t first thought to be the a-form of triacetyl methylglucoside 6-mononitrate. It contained no methoxyl however and the analytical figures are in close agreement with those required for a triacetyl pentose mononitrate (Found C 41.2; H 4.7; N 4.2. C,lH,,Ol,,N requires C 41.1 ; H 4-7 ; N 4.4%). The substance had the same solubilities as triacetyl glucose dinitrate and showed spec& rotation in chloroform = + 92-0" for c = 1.214. [.ID in chloroform = - 16.1" for c = 1.677. The author wishes to express his indebtedness to the Carnegie Trust and also to Principal Sir James C. Irvine for much valuable advice and for the kindly interest he has always shown in the work. UNITED COLLEGE OF ST. SALVATOR AND ST. LEONARD, UNIVERSITY OF ST. ~ D R E W S . [Received October 26th 1925.