5860
NOTES
the paper is dried and sprayed with a freshly prepared solution of alkaline hydroxylamine (made by mixing equal volumes of N methanolic hydroxylamine hydrochloride and 1.1 N methanolic potassium hydroxide). After drying in air for about 10 minutes, the paper is sprayed (wetting of the paper should be avoided) with an aqueous solution containing 1-295 ferric chloride and 1% hydrochloric acid. A blue or mauve color is quickly formed in those areas containing the esters or lactones or ester lactones. RF VALUESOF CERTAINLACTONES AND ESTERS Compound
(b) Using methyl ethyl ketone-water" Mannosaccharo-l,4- 3,6-dilactone 3-Methyl-~-erythrono-y-lactone 2,3,6-Trime thyl-L-rhamnono-y-lactone 2,3,~T~methyl-~-galactono-y-~actone
ketone" and with methyl ethyl ketone-petroleum ether (see Table 1). (11) L. Boggs, L. S. Cuendet, I. Ehrenthal, R. Koch and F. Smith, Ndurc, 166, 520 (1950).
DIVISIONOF AGRICULTURAL BIOCHEMISTRY UNIVERSITY OF MINNESOTA ST.PAUL,MINNESOTA RECEIVEDJUNE 22, 1951
A617-Steroids. XI.' The Maleic Anhydride Adduct Products of A5~7~g(11Wteroidal Hormones BY ROSE ANTONUCCI, SEYMOUR BERNSTEIN,DOMINICJ. GIANCOLA AND KARLJ. SAX
TABLEI (a) Using 1-butanol-ethanol-water10 D-Xylono-y-lactone L-Rhamnono-y-lactone D-Glucono-y-lactone D-Gaiactono-y -lactone D-Mannono-y-lactone D-Glucoheptono-y-lactone D-Gluconob-lactone Methyl 8-D-glucofururonoside Mannitol hexaacetate Arabitol pentaacetate
VOl. 73
RF
0.41 .50 .32 .35 .25 .13 .22 .30 .85 .85 0.60 .73 1.00 0.90
In Paper VIP of this series the preparation of A5J~g(11)-andr~~tatriene-3/3-ol-17-one acetate (I) and A5J~s(11)-pregnatriene-3@-ol-20-one acetate (11) was described. R
R
I ,zH
111," R(H) = 0 IV,' R = COCHs
I, R(H) = 0 11, R = COCHa
"MA=
-CH-C
I
-CH-C
I n this note, we wish to recordIthe preparation of the maleic anhydride adduct products of these two ester .91 trienes, and also to describe the pyrolysis of one 2,3,4T~methyl-~-glucosaccharo-l,5-lactone methyl of the adductsa Compounds I and I1 readily reester .94 acted with maleic anhydride in xylene4 at reflux 2,3.5-Trimethyl-~-glucosaccharo-1,4-lactone methyl temperature, and 111and IV were obtained in good ester 1.00 yield. The maleic anhydride adduct (IV) of (c) Using methyl ethyl ketone-petroleum ether-water" pregnatriene-3P-ol-2O-one acetate was pyrolyzed in 2,3,5-Trimethyl-~-rhamnono-y-lactone 0.88 such a manner that the pyrolysis and evaporative 2,3,5-Trimethyl-~-galactono-y-lac tone .58 distillation were carried out simultaneously (0.16 2,3,5-Trimethyl-~-glueosaccharo-l,4-lactone methyl mm. pres~ure,~ 200-313'). These conditions led to ester .88 co-distillation of a considerable amount of I V with 2,4-Dimethyl-D-galactosaccharo-3,6-lactone methyl ester .59 the desired triene (11). Compound I1 was easily separated from I V by treatment of the distillate This hydroxamic acid test can also be used for the detection of certain amides and methylamides of sugar acids and with ether; the adduct product was insoluble. The triene (11)so obtained was identical with an authenesters of amino acids. tic sample of 11. Free acids are not directly detectableg but by Experimental hanging the chromatograms for 10 to 15 minutes Maleic Anhydride Adduct (111) of Aa,7,g(11)-Androstatiin a closed jar containing a dish of ethereal diazo- ene-3pol-17-one Acetate.-A mixture of 1 g. of As~7*g(1*)-anmethane, the acids are converted into methyl drostatriene-3~-ol-l7-one acetate (I), 0.4 g. of maleic anesters and the latter may then be detected as hydride and 50 ml. of xylene was refluxed for 18 hours. The solvent and excess maleic anhydride were removed in described above. With this hydroxamic acid test it has been shown (1) Paper X, R. Antonucd, S. Bernstein, D. J. Giancola and K. J. that butanol-ethanol-water can be employed for Sax, J . Org. Chcm., in process of publication. (2) R. Antonucci, S. Bernstein, D. J. Giancola and K.J. Sax, ibid., the separation of certain sugar lactones. This (1951). particular solvent is not convenient for the separa- 18,(3)1159 The addition of maleic anhydride to a A~~'A1Wriene (dehydrotion of the acetates of sugar alcohols since their ergosterg1 acetate). and the pyrolyda of the resulting adduct have been RF values are very similar. The test has shown described previously; -e Windaua and LUttringhaus. Ber., 64, 850 that methylated lactones and methylated ester (1931), and Honigmann, Ann., 60% 89 (1934). (4) Benzene waa 80t used in place of xylene in the reaction. but lactones may be separated like the methyl sugars probably would be successful; see Bergmann and Stevens, J . Org. with butanol-ethanol-water,'O with methyl ethyl Chcm., l S , 10 (1948). 3,4,6-Trimethyl-~-mannono-6-lactone 2,4-Dimethyl-~-galactosaccharo-3,6-lactone methyl
,86
A5J1g(11)-
(9) C/. 0. Brante, Nolure, 168, 851 (1940). (10) L. Hough, J. K. N. Jon= and W. R. Wadman, ibid., 184, 448 (1948); J . Chem. Soc., 2611 (1949).
( 5 ) Subsequently, experience in this Laboratory with other similar compounds has shown that a pressure of 1-2 mm. would be preferable for this type of pyrolysis.
NOTES
Dec., 1951
vacuo. The residue was worked with ether, and filtered.
5861
not exclusively one or the other as claimed by the
This gave 1.1 g. of crude adduct product, m.p.' 230' un- previous workers.lJ This was actually found to sharp, dec., and with previous softening. Three recrystallibe the case although the 4-isomer was formed in zations from dilute acetic acid gave 0.57 g. of 111, m.p. 244246.5' dec., X$&810. none (possible maximum at 267 mp, E larger amounts. The addition of dioxane to the 500), [ C Y ] % +124", [a]"ap+190°(19 mg. i n 2 m l . of chloro- Grignard solution did not seem to alter the ratio form solution, l-dm. semi-micro tube, gave QD +1.18', L Y H ~ of the isomers; however, its presence did greatly +1.80°), f f x g / f f D 1.53, [MID +326. increase the over-all yield of the benzylpyridines. Anal.' Calcd. for C Z ~ H Z(424.47): ~O~ C, 70.74; H, 6.65. This is in keeping with the observations made on Found: C, 70.52; H, 6.83. quinoline.3 Maleic Anhydride Adduct (IV) of As,7,0(11)-Pregnatriene38-01-20-one Acetate.-A mixture of 3.0 g. of As~i~8(11)-preg- The 2- and 4-benzylpyridines were separated by natriene-3j3-01-20-one acetate (11), 1.2 g. of maleic anhy- carefully fractionating them through an efficient dride and 150 ml. of xylene was refluxed for 19.5 hours. column. Mixed melting points of the picrates The product was worked up as above, wt. 3 g., m.p. 263of these isomers and those obtained from authentic 264', dec. above m.p. Recrystallization from acetic acid gave 2.53 g. of IV, m.p. 264265" dec. above map. From 2- and 4-benzylpyridine prepared by the method the mother liquors there was obtained an additional 100 mg. of Crook and McElvain4 completed the identificaof IV, m.p. 263" dec. above m.p.; [ c Y ] ~ +117', D [aIz6Hg tion. +151' (22.1 mg. in 2 ml. of chloroform solution, I-dm. Experimental semi-micro tube, gave a~ +1.29", C Y H+1.67"), ~ Q H ~ / O I D 1.29, Authentic 2and 4Benzylpyridine.-The method used for [ M I D +529. preparing these compounds was essentially that described Anal. Calcd. for Cz~Ha20s(452.53): C, 71.66; H, 7.13. by Crook and McElvain.4 The reaction product was Found: C, 71.48; H, 7.10. fractionated through a Todd column with a vacuum jacketed Pyrolysis of the Maleic Anhydride Adduct (IV)of AK*i,9(11)- 5-mm. wire spiral. Approximately 25.5 g. of the 2-isomer Pregnatriene-3 8-01-20-one Acetate.-Compound IV (0.5 g.) was collected boiling 275-278'" at 753 mm., nmJD1.5792b; was pyrolyzed and evaporatively distilled in the following dm4 1.055,Kband 5.1 g. of the 4-isomer boiling 284-287'' at manner. A pressure of 0.18 mm. was maintained. The 753 mm., n1O.b 1.5810; d% 1.062.bb A picrate of the 2-benzylpyridine prepared in the usual material was heated for about 5 hours from room temperature to313'. Thesolid sublimatewhichappeared at22O0, became manner melted a t 141-142' (lit. 141.5-142"*). A picrateof considerable a t 250'. Thesublimate was slurried with ether, the 4-isomer melted at 140.5-141" (lit. 141-142°*). A and the insoluble starting material (IV) was removed by mixed melting point was depressed to 115-118'. Reaction of Benzylmagnesium Chloride with Pyridine.filtration; wt. 0.20 g., m.p. 261-264' dec. The ether filtrate was washed with water, dried, and concentrated. The In a one-liter three-neck flask fitted with a reflux condenser, solution was allowed to stand a t room temperature overnight. stirrer and dropping funnel was placed 24.3 g. (1.0 g. atom) During this time a very small amount of material was de- of magnesium turnings and 65 ml. of anhydrous ether. To posited as a film on the walls of the flask. It was separated this was added dropwise and with stirring a solution of 126 by decantation. The ether decantate was concentrated g. (1.O mole) of benzyl chloride in 185 ml. of anhydrous ether. with simultaneous addition of methanol until all of the ether When all the benzyl chloride solution had been added, stirwas removed. Addition of water gave 60 mg. of impure 11. ring was continued for 30 minutes. Then 54 g. (0.67 mole) Recrystallization from dilute methanol gave pure 11, wt 20 of freshly distilled anhydrous pyridine was added dropwise. mg., m.p. 143-144', 312,324 and 339 mg, e 10800, A vigorous reaction set in. When all the pyridine had been added, the mixture was refluxed on a steam-cone for 24 hours 12200, 7600, respectively. with constant stirring. After the mixture had cooled it was immersed in an ice-bath, and an ice-cold 20% ammoniun (6) All melting points are uncorrected and were determined with unchloride solution was added dropwise to decompose the calibrated Anschiitz thermometers. (7) We are indebted to Messrs. Louis M. Brancone, Samuel &I. Grignard complex. The aqueous hydrolyzate was extracted with ether and the ether extracts were in turn Modes and Edward B. Ruffing,Jr., for the microanalytical data. treated with 5% sulfuric acid. This acid extract was neuLEDERLE LABORATORIES DIVISION tralized with 5% potassium hydroxide and this solution was AMERICAN CYANAMID COMPANY extracted with ether. These h a 1 ether extracts were dried RECEIVED AUGUST13, 1951 over Drierite, and then the solvent was removed. The rePEARL RIVER,NEW YORK sidual liquid was distilled through a Claisen head, and the fraction boiling over 100" (15 mm.) was collected. This was then distilled through a Todd column with a vacuum The Reaction of Benzylmagnesium Chloride and jacketed 5-mm. wire spiral. Approximately 2 g. of the 2isomer boiling 274-277' a t 759 mm. was obtained, n% Dibenzylmagnesium with Pyridine 1.5790 and 6 g. of the 4-isomer boiling 277-279" at 759 mm., npD 1.5810. The over-all yield of benzylpyridines was BY ROBERTA. BENKESERAND DEXTERS. HOLTON about 8% of which about 20% was estimated to be the 2In 1932 Bergmann and Rosenthall reported that isomer and 80% the &isomer. The identity of these isoby mixed melting points with authentic dibenzylmagnesium reacts with pyridine to form mers wasofestablished the picrates. 2-benzylpyridine. In 1946 Veer and Goldschmidta samples Reaction of Dibenzylmagnesium with Pyridine.-The disputed this work and claimed that 4-benzyl- benzylmagnesium chloride was prepared exactly as depyridine is fcrmed exclusively and not the 2- scribed before. Then 150 ml. of freshly purifieds dioxane added to the Grignard reagent and the mixture was isomer. The picrates of both of these isomers was stirred for 30 minutes. To this suspension was added drophave about the same melting point ( 1 4 0 - 1 4 2 O ) , wise 64 g. (0.8 mole) of anhydrous pyridine after which the and hence care must be exercised in identifying mixture was refluxed on a steam-cone for 24 hours with constant stirring. The reaction was worked up as described them. and the fractionation again was made through the Since the reaction of quinoline with dibenzyl- before column. Approximately 9 g. of the 2-isomer and 33 g. magnesium is reported to yield largely the 2-iso- Todd of the 4-isomer were obtained with identical physical coni t seemed likely that pyridine should give a t stants as those shown above. This represents a total yield
Xz&slO.
least a mixture of the 2- and 4-benzyl isomers and
( I ) E. Bergmann and W. Rosenthal, J . prakl. Chem., 121 186, 267 (1932). (2) W. L. C. Veer and St. Goldschmidt, F2c. f m v . (him., 66, 793 (1946). ' (3) H. Gilman and G.C. Gainer, THISJOURNAL, 71, 2327 (1949).
(4) R. E. Crook and S. M. McElvain, ibid., S I , 4007 (1930). (58) See P. C. Teague, ibid., 69, 714 (1947); also E. H . Huntress and H. C. Walter, ibid., TO, 3704 (1948). (5b) A. Tschitschibabin, J . Russ. Phys. Chrm. Soc., 83, 255 (1901). (6) L. F. Fieser, "Experiments in Organic Chemistry," D. C. Heath and Co., New York, N. Y.,1941, p. 369.
