[ CONTRIBUTION NO. 46 FROM
TEE
RESEARCH LABORATORIES OF HOFFMANN-LAROCHE, INC.]
ARYLAMINE-N-GLYCOS IDES. PART I. ARY LAMINE-N-DRIBOPYRANOSIDES AND N-D-RIBOFURANOSIDES LEO BERGER
AND
JOHN LEE
Receiaed October 22, 1946
In the course of an investigation of the synthesis of N-ribityl-3,4-xylidine, an intermediate in the synthesis of vitamin Ba, a product was obtained from the condensation of 3,4-xylidine and D-ribose which did not correspond to the xylidine riboside obtained by Kuhn (1). A detailed study of this condensation product and related compounds indicated that a new form of N-riboside, N-ribopyranoside, was obtained. The synthesis, properties, and chemical potentialities of this form of N-pentoside form the basis of this paper, the first in a series of studies. The condensation of aryl and alkyl amines with monosaccharides (also disaccharides) is well known and appears in the early literature. Schiff (2) first reported the condensation of aniline and toluidine with anhydrous D-glucose in 1870. Sachsse (3) prepared mono- and di-anilides of lactose in 1871 and Sorokin (4) prepared various anilides of other monosaccharides in 1886. The structure of these condensation products was an open question. Schiff’ and Straus ( 5 ) favored a “Schiff base” amine-aldehyde condensation product type linkage. Sorokin and Marchlewski (6) proposed an N-glycoside formula in 1894. In a series of papers, the first of which was published in 1908, Irvine and co-workers (7) demonstrated that the condensation product of glucose and aniline was an N-glycoside and not a Schiff’s base. Arylamine-N-glycosides are prepared by mixing a sugar and an amine in a solvent (usually a lower alcohol) and heating the mixture for several hours. Upon concentration of the solvent, the N-glycoside usually crystallizes. Other solvents such as water, benzene, or various mixtures, are often used. Various catalysta are employed such as HC1, NHICl, excess base, etc. Most N-glycosides are rather unstable, some decomposing in a few hours. Several species when absolutely pure remain unchanged for several months if kept cold. They usually crystallize with one or more molecules of water, alcohol, or even amine of crystallization (8). As a general class, N-glycosides are labile and undergo rearrangement as well as hydrolysis. The rearrangement of N-glycosides to isoglucosamines (the Amadori rearrangement) ivas studied and reported by Kuhn and co-workers (9) and Weygand (10) in a series of papers from 19:36 through 1940. In connection with the synthesis of riboflavin, vitamin Br, the preparation of ribitylxglidine, which involved the condensation of an aryl amine and a pentose and subsequent reduction, gave impetus to the study of the preparation and properties of ?;-glycosides. Kuhn and Birkofer (1) prepared 3,4-xylidine-~75
76
LEO BERGER AND JOHN LEE
riboside by refluxing a mixture of D-ribose and 3,4-xylidine for 2 hour. The 172'; product obtained had the following characteristics: M.p. 118'; [CY]:' (c = 0.5y0 in pyridine, without mutarotation). Preparation of the above compound according to the directions of Kuhn and Birkofer yielded a product with the following characteristics: M.p. 128-130'; [a]:4+171.7' --+ +56.5"; (c = 0.5% in pyridine). However, if the condensation of 3,4-xylidine and D-ribose was carried out a t room temperature in alcohol or aqueous alcohol, catalyzed with a trace of acid, an isomeric product was obtained which had the following characteristics: M.p. 110-112"; [a]i5+94.5' --+ f53.0"; (c = 1.0% in pyridine).' Similarly, two isomeric products were obtained when aniline and ribose were condensed according to the two procedures. The product obtained from the hot alcoholic condensation had the following characteristics: M.p. 138-140'; [al32d f176.5' --+ +156.6"; (c = 3% in pyridine). The product obtained from the cold alcohol condensation had the following characteristics: M.p. 125-127'; f63.4' --+ +48.6'; (c = 1.0% in pyridine). It was found that the product obtained from the cold alcoholic condensation (lower melting and less positive rotation) could be converted quantitatively to the other form by refluxing for an hour in alcohol. It was also found that the transformation would also take place slowly a t room temperature in the presence of traces of acid or basic catalysts, or other impurities. In a study of the chemical nature of various aromatic X-ribosides, Buhn and Strobele (11) concluded that the products they had obtained were N-ribofuranosides, for acylation yielded triacetyl products, and tritglation indicated that the terminal hydroxyl group was free. The isomeric products obtained by us could possibly be the &furanoside, a- or @-pyranoside, a Schiff's base, or the Amadori rearrangement product. The direction of the mutarotation in pyridine (in the same direction and from positive to negative in both forms) and the different end-points reached on completion of the mutarotation (as shown by the isomeric aniline ribosides) eliminate the possibility of an a-,@-furanosidepair or a Schiff's base structure for these ribosides. Both forms reduced hot Fehling's solution but did not give the dichlorophenol indophenol test for isoglucosamines (1). Hydrogenation of both forms under various conditions of pH and temperature gave the same ribitylamine indicating that Amadori rearrangement had not taken place. Thus a-xylidine-N-Dribofuranoside, when hydrogenated in alcohol with Raney nickel, gave ribityl-29.0'; (c = 5% in pyridine), -37.5'; xylidine, (1, 12);m.p. 144"; (c = 5y0 in 2 N HCl). tu-Xylidine-N-D-ribopyranosidein anhydrous dioxane
+
1 The optical rotation of aromatic K-ribosides are more characteristic and reproducible than the melting point. As these compounds have a strong tendency t o crystallize with solvent of crystallization, the melting point alone cannot be used as a criterion of purity, or t o distinguish between pyranoside or furanoside forms. (Note difference in the melting point and similarity of the optical rotation of 3,4-xylidine-N-~-riboside obtained by Kuhn and Birkofer and our preparation of this compound.) The optical rotation, elementary analysis, moisture, and melting point all must be taken into account.
ARYLAMINE-K-GLYCOSIDES. I
77
(which did not convert the pyranoside to the furanoside even a t reflux temperature for several hours) on hydrogenation gave the identical ribitylxylidine. Similarly, both aniline ribosides gave the same ribitylaniline, m.p. 125-127"; loll:5 -42.3O; (c = 2.0% in pyridine). The direction of the mutarotation in both forms indicated an a-pyranoside structure for the product obtained a t room temperature and an a-furanoside structure for the product prepared in hot solution (on the assumption that the product prepared according to Kuhn is a furanoside). H H H H
I
l
l
1
1
B H L /
HOHz C-C-C-C-C-NH-Aryl
Furanoside: High m.p., more positive rotation, mutarotation (negative), a form
0H H H H
i l l 1 Hz C-C-C-C-C-NH-Aryl I l l
1
0
OHOHOH
1
Pyranoside : Low m.p., less positive rotation, mutarotation (negative), CY form
_ I
That these designations were probably correct was confirmed by a study similar to that of Kuhn and Strobele. The two aniline ribosides were acylated in pyridine to yield triacetyl products further indicating an N-glycoside structure. Both were tritylated in pyridine. The product obtained from the cold condensation (pyranoside) did not yield any identifiable tritylation product while the product obtained from the hot alcoholic condensation (furanoside), reacted under identical conditions, yielded a tritylated product as expected, and in agreement with the structure assigned by Kuhn. Methylation of both aniline ribosides with methyl iodide and active silver oxide in acetone solution gave a mixture of partially methylated syrups. Subsequent, remethylations of these syrups gave red oils, and analysis indicated that partial decomposition had taken place. Methylation of the aniline ribosides and the triacetyl aniline ribosides with methyl sulfate in alkaline solution mas not possible, as warm alkali hydrolyzed the ribosides. Both isomers were instantly decomposed to tars with dilute periodate solution in an attempt to apply the method of Jackson and Hudson (13), and Lythgoe and Todd (14), for distinguishing between furanosides and pyranosides. The result was not entirely unexpected, as amino alcohols possessing a primary or secondary amino group react readily with the periodic acid reagent (15). Lythgoe and Todd record a similar experience with 4- or 6-glycosidaminopyrimidines. Hydrolysis of both forms with water, water catalyzed with acids, or bases, or aldehydes such as formaldehyde and benzaldehyde, regenerated the original amine and ribose. This was further evidence that the products obtained were not Amadori rearrangement products. The triacylated products prepared from the isomeric N-ribosides and their
78
LEO BERGER AND JOHN LEE
hydrogenation products are assigned the tentative structures of 2 ,3,4- or 2,3,5triacyl derivatives depending upon whether they were derived from the pyranoside or the furanoside form. It is assumed, however, that acyl migration did not take place in the course of acylation of the ribosides and their subsequent hydrogenation, although the similarity of the optical rotations of the two tribenzoylribitylanilines may indicate that ring opening and acyl migration had occurred in one of the ribosides. a-Aniline-D-ribopyranoside and a-aniline-D-ribofuranoside were both more stable than the corresponding xylidine ribosides. Hanaoka (16) reported similar results in his studies on the rate of hydrolysis of various aniline and substituted aniline N-glycosides. Traces of impurities, high temperature, and moisture TABLE I PROPERTIES OF ARYLAMINE-N-GLYCOSIDES RIBOSIDE
MXLTING POINT,
ROTATION
'C"
~-.4niline-N-~-ribopyranoside (3 H20)
125-127
a-Aniline-N-D-ribofuranoside
138-140
[a]: f63.4" c = 1.0%
+
+48.6"
in pyridine (48 hrs.)
[a1 +176.5"
-+
156.6'
c = 3.0% in pyridine (24 hrs.)
~t-3,4-Xylidine-N-~-ribopyranoside110-112
[a] 4-94.5" -+ $53.0" c = 1.0% in pyridine (48 hrs.)
a-3,4-Xylidine-N-~-ribofuranosj.de128-130
[a]! $171.7" -+ +56.5' c = 0.5% in pyridine (24 hrs.)
a-3,4-Xylidine-N-~-ribof uranosjde
[a]: +172' c = 0.5% in pyridine without mutaro-
118
(Kuhn, 1)
tation a
All melting points are uncorrected.
accelerated the decomposition of the ribosides. a-Aniline-D-ribopyranoside and -furanoside have been kept for over six months in a sealed container in the refrigerator at 5". EXPERIMENTAL
a-Aniline-N-D-ribopyranoside. A solution of 1.44 g. of crystalline D-ribose in 20 cc. of distilled water was prepared. The pH was adjusted to 4.0 with 3 N HlSOl.2 One cubic centimeter of aniline in 10 cc. of absolute alcohol was added and the mixture stirred for 10 min. at 25". The reaction mixture was then set in a refrigerator a t 5" overnight (crystallized out in one hour). The crystalline precipitate was filtered off and washed with cold 2 Acid catalysts accelerated the condensation but did not alter the direction nor affect the yield. The condensation a t pH 6.0 t o 8.0 (pH of base) gave excellent yields of the pyranoside but required several hours condensation a t room temperature before being set in the refrigerator for crystallization.
ARYLA4MINE-N-GLYCOSIDES.
I
79
alcohol and finally with ether. There was obtained 2.07 g. (96%) of colorless shining platelets, melting at 125-127". The product contained 0.5 mole of water of crystallization; [a]: +63.4" -+ f48.6"; (c = 1.0% in pyridine; 48 hrs.). Anal. Calc'd for C11H16NOd.) HsO: C, 56.41; H, 6.84; N, 5.98. Found: C, 56.71; H , 6.77; N, 5.78. Under certain conditions the product may crystallize with different amounts of solvent of crystallization. This causes variations in the melting point and rotation, but when the latter is corrected on the basis of the above compound, it will correspond. The purity of N-ribosides can be determined accurately by the ordinary Fehling titration method employed for sugars. The N-ribosides hydrolyze quantitatively under the conditions employed and the sugar liberated reduces Fehling solution in the normal manner. For maximum accuracy in this titration, samples should contain or liberate 21 .O t o 38.0 mg. of ribose for every 10 cc. of mixed Fehling solution used. The general procedure is as follows : About 50 mg. of ribos,ide is suspended in 10 cc. of mixed Fehling solution diluted with 15 cc. of distilled water in a 250-cc. Erlenmeyer flask. The flask is covered with a watch glass and set on a hot plate a t 200-300" for exactly five minutes of boiling. The flask is cooled and 20 cc. of 10% KI (freshly prepared) and 20 cc. of 3 N H & 0 4 are added. The liberated iodine is titrated with 0.1 N thiosulfate with soluble starch as an indicator in the usual manner. The titration of the Fehling solution is always run along with the test substance. The ribose liberated is calculated as follows: (a - b) 3.37 = mg. riboses a = cc. of 0.1 N thiosulfate used for Fehling solution alone. b = I X . of 0.1 N thiosulfate used for test substance. a-Aniline-N-D-ribopyranoside : Ribose. Calc'd: 66.70% Found :66.80% 66.70% 66.70% CY-Aniline-N-D-ribofuranoside.(a) By direct condensation. A solution of 15.0 g. of D-ribose in 150 cc. of warm alcohol was prepared. Ten grams of aniline was added with stirring. The mixture was refluxed for two hours. On cooling, a-aniline-N-D-ribofuranoside crystallized out; the reaction was set in the refrigerator to complete the crystallization, and the white mass of crystals that formed was filtered off, washed with cold alcohol and ether, and air dried. There was obtained 19.0 g. (84.5%) of shining plates melting a t 138140"; [a]: f176.5" + f156.6"; (c = 3% in pyridine; 24 hours). Anal. Calc'd for C11H11N04:C, 58.66; H , 6.66; N, 6.22. Found: C, 58.72; H , 6.66; N, 6.16. Ribose. Calc'd: 66.70% Found :66.80% (b) By conversion of a-aniline-N-D-ribopyranoside.Ten grams of a-aniline-N-D-ribopyranoside (m.p. 125-127'; [a] +63.4" + +48.6") was dissolved in 80 cc. of boiling absolute alcohol and refluxed for one hour. The reaction flask was cooled, scratched with a glass rod, and set in the refrigerator for crystallization. After several hours the crystalline mass was filtered off, washed with alcohol and ether t o yield 9.9 g. of a-aniline-N-D-ribofuranoside, m.p. 137-139"; (a];f177" + f156.5"; (c = 1.5% in pyridine; 24 hours). The conversion of a-aniline-N-D-ribopyranoside t o the furanoside is influenced by traces of impurities (both acidic and basic such as amine salts, amines, acids, etc.), water, or other hydroxylated solvents, heat, and sunlight. While attempting to remove the last traces of water of crystallization from a-aniline-N-D-ribopyranosidevia high vacuum desiccation over Pz06,for 7 days, a 70% conversion to the furanoside occurred. Original pyranoside: m.p. 125-127"; [CY]+63" -+ 49"; (c = 1% in pyridine; analysis indicated 4 mole of HzO).
--
* Factor determined with pure crystalline D-ribose.
80
LEO BERGER AND JOHN LEE
Dried pyranoside (7 days) :m.p. 120-123'; [a]+144", initial; (e = 1%in pyridine). Anal. Calc'd for CllHtsNO (anhydrous) : C, 58.66; H, 6.66. Found: C, 58.75; H, 6.67. +186' initial; (c = 1%in pyridine; complete Refluxed in alcohol for twenty minutes; [CY]: conversion). An attempt was made t o recrystallize a-aniline-N-D-ribopyranoside from warm alcohol as rapidly as possible t o avoid conversion to furanoside. One such crystallization lowered the melting point t o 121-123' and the rotation to [a]: +137.7" indicating over a 50% conversion t o the furanoside. cu-d,4-Xylidine-N-~-ribopyranoside. A solution of 1.44 g. of crystalline D-ribose in 20 cc. of distilled water was prepared and the pH was adjusted t o 4.0 with 3 N H2S04. T o this solution 1.3 g. of 3,4-xylidine dissolved in 10 cc. of ethyl alcohol was added, with stirring at 25" for ten minutes. The reaction mixture was then placed in the refrigerator overnight for crystallization. The crystalline product obtained was filtered off, washed with a small amount of cold alcohol and dry ether,to yield 1.2 g. (49%) of a colorless crystalline product; m.p. 110-112°; [a]: +94.5" -+ +53.0°; (c = 1.0% in pyridine). Anal. Calc'd for ClsHloNOl: N, 5.53. Found: N, 5.44. a-3,4-Xylidine-N-~-ribofuram)side (1). (a) By direct condensation. D-Ribose (8.8 g.) was dissolved in 100 cc. of absolute methanol containing 7.1 g. of 3,4-dimethylaniline and the solution was refluxed for forty minutes. The solution was cooled, seeded, and placed in the refrigerator for complete crystallization. The white crystalline product was filtered off, washed with cold methanol and ether, and air dried. There was 8.8 g. (60%) of a-3,4xylidine-N-riboside melting at 127-129"; [CY]: +172" -+ 56.0"; (c = 0.5% in pyridine; 72 hours). (b) By conversion of a-3,4-tiimethylaniline-N-D-ribopyranoside.a-3,4-Xylidine-N-~ribopyranoside (0.5 g.), m.p. 110-112'; [CY]: +94.9", was refluxed with 5 cc. of absolute alcohol for one hour. The flask was cooled, scratched, seeded, and set aside for crystallization in the refrigerator. Forty-five hundredths gram of shiny papery crystals was filtered off, washed with cold alcohol and ether; m.p. 128-130"; [a]: +171.7" + +56.5"; (c = 0.5% in pyridine; 48 hours). 2 , 9 , 4-Triacetyl-CY-aniline-N-D -ribopyranoside, Twelve grams of a-aniline-X-D-ribopyranoside was dissolved in 100 cc. of dry pyridine, cooled t o O", and 36.0 cc. of acetic anhydride was slowly added with stirring. Upon completion of the addition, the solution was kept a t room temperature for one day. Heating for one hour at 40-50" completed the reaction. The reaction mixture was poured into 500 cc. of cold water with stirring, and the syrupy mass that separated was extracted with ether. The ether solution was washed neutral, dried over anhydrous XaSSOa overnight. The solvent was then removed t o yield 14.0 g. (75%) of a hard yellow-orange glass which could not be crystallized. The product was readily soluble in all organic solvents, but insoluble in water and petroleum ether. Anal. Calc'd for CI,H$1NOT: 0 , 58.15; H, 5.98; N , 3.99; Acetyl, 36.75. Found: C, 58.48; H, 6.18; N , 4.00; Acetyl, 33.2, 33.5.' 2,S,6-Triacetyl-a-aniline-N-~ -ribofuranoside. six grams of a-aniline-ru'-D-ribof urano side was dissolved in 50 cc. of dry pyridine, cooled to O", and 18 cc. of acetic anhydride was added slowly with stirring. Upon completion of the addition, the solution was kept a t room temperature for a day. One hour's heating a t 40-50" completed the reaction. The reaction mixture was poured into 250 cc. of cold water with stirring and the syrupy mass that separated was extracted with ether. The ether solution was washed neutral, dried overnight over anhydrourl Na2SOI. The solvent was then removed t o yield 8.3 g. (89%) of a hard yellow glass which began t o soften and flow a t 60". The product could not 4 Micro acetyl determination of the compounds in this series gave consistently low but reproducible values.
ARYLAMINE-N-GLYCOSIDES. I
81
be crystallized. The product was readily soluble in all organic solvents, but insoluble in water and petroleum ether. -4nal. Calc'd for CI'IHZINO~: C, 58.15; H I 5.98; N, 3.99; Acetyl, 36.75. Found: C, 57.92; H, 6.31; N, 4.04; Acetyl, 33.7.4 d,S,d-Tribenzoyl-D-ribitylaniline. Fourteen grams of a-aniline-N-D-ribopyranoside was dissolved in 150 cc. of dry pyridine, cooled t o O", and 28.7 g. of benzoyl chloride (3 moles excess) was slowly added with stirring. The acylation proceeded slowly. I n about 35-40 minutes pyridine hydrochloride started t o precipitate out. Upon completion of the addition, the reaction was kept a t room temperature for a day and worked u p in the usual manner. A yellowish sticky glass, weighing 33 g. (quantitative yield) which could not be crystallized was obtained. The product was soluble in all organic solvents and separated as a thick oil from concentrated alcohol solution. Fifteen grams of the above glass was dissolved in 120 cc. of ethyl alcohol, 1.5 g. of Raney nickel was added, and the reaction mixture was hydrogenated a t 500 lbs. at 60"for two hours. The alcohol solution was filtered from the catalyst and evaporated t o dryness. Fifteen grams of a glassy product was obtained which could not be crystallized. The product did not form a hydrochloride in ether solution with hydrogen chloride gas. Anal. Calc'd for C ~ ~ H Z ~ NCO, 71.25; ,: H, 5.38; N, 2.60. Found: C, 71.41; H, 5.43; N, 2.46. [CY]: -20.3"- i l ; (e = 1.67% in pyridine). d,5,S-Tribenzoyl-~-ribitylaniline. Fourteen grams of a-aniline-N-D-ribofuranoside was acylated in 150 cc. of dry pyridine with 28.7 g. of benzoyl chloride at 0" as previously. I n about 15-20 minutes pyridine salts started t o precipitate out.' The reaction was worked u p as previously t o yield 34.0 g. of a yellow amorphous brittle solid which could not be crystallized. The product did not melt but liquefied a t about 50". Fifteen grams of the glassy solid was dissolved in 120 cc. of ethyl alcohol, 1.5 g. of Raney nickel added, and the mixture hydrogenated at 500 lbs. a t 60" for two hours. The alcohol solution was filtered from the catalyst and evaporated to dryness i n vacuo t o yield a light fluffy amorphous glass in quantitative yield. The product could not be crystallized. A n a l . Calc'd for CszHtsNO7: C , 71.25; H, 5.38; N, 2.60. Found: C, 71.38; H , 5.40; PI', 2.50. [a]: -22.1'; (c = 8.0% in pyridine). D-Ribitylaniline. (a) From CY-aniline-iV-D-ribopyranoside.Four grams of a-aniline-ND-ribopyranoside was suspended in 25 cc. of anhydrous dioxane and 0.3 g. of Raney nickel added. The mixture was hydrogenated a t 65-75' at 500 lbs. for two hours. The catalyst was filtered off and the solution was concentrated in vacuo t o 3 volume. The solution was scratched with a glass rod and set in the refrigerator for crystallization. Three and five-tenths grams (88yo)of a colorless crystalline product was obtained which melted a t 125-127'; [ C Y -42.3"; ]: (c = 2.7% in pyridine). Anal. Calc'd for CllHlrNOa: C, 58.19; H , 7.49; N , 6.17. Found: C, 58.49; H, 7.26; N, 6.24. (b) From or-aniline-N-D-ribofuranoside.Four grams of a-aniline-1S-D-ribofuranoside was suspended in 25 cc. of absolute alcohol and hydrogenated a t 60" at 500 lbs. for three hours in the presence of 0.3 g. of Raney nickel. The reaction was worked up as above to yield 3.60 g. (90%) of ribitylaniline, melting a t 125-127'; [CY] -42.7"; (c = 2.5% in pyridine). N-D-Ribityl-5,d-dimethylaniline(ribitylxylidine). (a) From a-S,4-xylidine-N-~-ribopyranoside. Eight-tenths of a gram of a-xylidine-N-D-ribopyranosidewas dissolved in 25 cc. of anhydrous dioxane and 0.1 g. of Itaney nickel was added. The mixture was hydrogenated a t 60" for three hours a t 50 lbs. The catalyst was filtered from the solution, the solution concentrated and set aside for crystallization. There was obtained 0.72 g. 6 The furanoside acylated more rapidly than the corresponding pyranoside as expected in view of the primary hydroxyl group present in the furanoside.
82
LEO BERGER AND JOHN LEE
of ribitylxylidine, m.p. 143-144' (mixed with an authentic sample, gave no depression). [a]: -29.0'; (c = 5% inpyridine); [a]::-37.5' (c = 5% in 2 N HCl). (b) From a-S,4-xylidine-N-D-ribofuranoside ( 1 ) . Twenty-five and three-tenths grams of a-xylidine-N-D-ribofuranosidewas suspended in 125 cc. of absolute alcohol and 2.5 g. of Raney nickel was added. The mixture was hydrogenated a t 500 lbs. a t 60" for one hour. The catalyst was filtered from the hot solution and the filtrate was set aside for crystallization; yield, 23.0 g. (90%) of colorless shiny platelets melting sharply a t 144'; [a]: -37.5'; (c = 5% in 2 N HCI). Tritylation experiments with a-taniline-N-D-ribopyranoside and a-anitine-N-D-furanoside. a-Aniline-N-D-ribopyranosideand a-aniline-N-D-ribofuranoside(dried in high vacuum over Pz05a t 25' for 24 hours) were tritylated with trityl chloride (dried over anhydrous CaClz for 24 hours) in dry pyridine solution a t room temperature for five hours and a t 5' for two days. Five grams of the riboside was mixed with 6.2 g. of trityl chloride in 25 cc. of dry pyridine in a small ground-glass-stoppered bottle. The resultant brown solutions were poured into water in a fine stream. The furanoside reaction mixture yielded a light brown amorphous product. This reaction product was dissolved in ether, extracted with dilute acid and finally washed neutral with water. The dried ether solution on evaporation yielded a small amount of crystalline matter (0.7 9.) of an undetermined by-product. Trituration of the residual syrup with alcohol removed the remainder of the crystalline matter. The alcoholic solution was treated with Norit and concentrated to dryness invacuo. The resultant glass was dissolved in dry ether and precipitated with Skellysolve "B" to yield a light brown amorphous solid. The product was redissolved in ether and again precipitated with Skellysolve "B" to yield a tan amorphous powder which could not be obtained in crystalline form. The product on analysis corresponded to a monotrityl-a-aniline-D-riboside with water of crystallization. Anal. Calc'd for CaoH,oNO, 1.75 H20: C, 72.20; H , 6.25; N, 2.82. Found: C, 72.06; H , 6.29; N, 2.96. The pyranoside reaction mixture yielded a reddish oil which was dissolved in ether and worked up as previously. Concentration of the dried ether solution gave a tarry product which could not be purified nor could any product be isolated. The above experiments were repeated with identical results. The furanoside yielded a tan amorphous product as previously which again gave analysis for the monotrityl product with water of crystallization. Anal. Calc'd for C ~ O H Z ~ N O 1.75 , H20: C, 72.20, H, 6.52. Found: C, 72.00; H , 6.27. The pyranoside reaction mass yielded intractable tars.
+
+
ACKNOWLEDGMENT
The microanalyses were performed in the Microanalytical Division of these laboratories under the direction of Dr. Al Steyermark. SUMMARY
1. Condensation of aryl amines with ribose in alcohol or aqueous alcohol (catalyzed with traces of acid) a t low temperatures yields a-arylamine-N-Dribopyranosides. If the reactants are condensed at the reflux temperature of the solvent, a-arylamine-N-D-ribofuranosidesare formed. 2. a-Arylamine-N-D-ribopyranosidesare converted quantitatively to the corresponding furanosides in boiling alcohol solution. 3. Hydrogenation of both the arylamine ribopyranoside and the corresponding arylamine ribofuranoside yields the identical ribitylamine.
ARYLAMINE-N-GLY COSIDES.
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83
4. Bcylation of the furanoside and pyranoside forms yields triacyl derivatives. Hydrogenation of these triacyl arylamine ribosides yields triacyl ribityl amines. NUTLEY,N. J. REFERENCES (1) RUHNAND BIRKOFER, Ber., 71, 621 (1938). (2) SCHIFF,Ann., 164, 30 (1870). (3) SACHSSE, Ber., 4, 834 (1871). (4). SOROKIN, Ber., 19, 513 (1886). (5) SCHIFFAND STRAUS, Ber., 27, 1287 (1894). (6) SOROKIN AND MARCHLEWSKI, J. prakt. Chem., [iil 60, 95 (1894). (7) IRVINE AND MOODIE, J. Chem. SOC.,93, 94 (1908). IRVINE AND GILMOUR, J. Chem. S O C .93, , 1429 (1908). IRVINE AND GILMOUR, J. Chem. SOC.,96, 1545 (1909). IRVINE AND MCNICOLL, J. Chem. SOC.,97, 1449 (1910). IRVINE AND HYND,J. Chem. SOC.,99, 161 (1911). (8) MITTSAND HIXON,J . Am. Chem. Soc., 66, 483 (1944). (9) KUHNAND DANSI,Ber., 69, 1745 (1936). KUHNAND WEYGAND, Ber., 70, 769 (1937). KUHNAND BIRKOFER, Bey., 71, 621 (1938). (10) WEYGAND, Ber., 7 3 , 1259, 1278, 1284 (1940). E , 70, 773 (1937). (11) KUHNAND S T R ~ B E LBer., (12) KARRERet al., Helv. Chim. Acta, 18, 1133 (1935). AND HUDSON, J. Am. Chem. SOC.,69, 994 (1937). (13) JACKSON (14) LYTHGOE AND TODD, J. Chem. SOC.,593 (1944). (15) JACKSON, “Organic Reactions,” John Wiley, New York, N. Y., 1944, Volume 11,p. 343. (16) HANAOKA, J. Biochem. (Japan), 31, 95 (1940).
