May 5 , 19.55
NOTES
2559
118". 9ptical rotation of these samples varied from f 5 0 Preparation of Methylenebisamides t o +80 . Cholest-4-ene-78-01 Benzoate (VI).-A solution of 31 g. B Y CHARLES W. SAUER A N D ROBERT J. BRUNI of the crude reduction product in a mixture of 500 ml. of pyriJUNE 2, 1954 RECEIVED dine and 66 ml. of benzoyl chloride was stored a t 10" for 24 hours. The reaction mixture then was poured into a solution Rnudsen2 has reported the preparation of methof 80 ml. of 12 N hydrochloric acid in 1 1. of water. The benzoate was extracted with a total of 1250 ml. of Skelly- ylenediformamide from paraformaldehyde and forinamide in 30yo.yield. I n searching for a method solve B and this non-aqueous extract washed with dilute hydrochloric acid, water, 10% sodium bicarbonate, and to improve this yield, we investigated the use of finally water. The neutral yellow hexane solution was trioxane, monochlorodimethyl ether, di-(chlorodried over Drierite and shaken during one-half hour with methyl) ether and hexamethylenetetramine as a 250 g. of alumina. The alumina was filtered off to give a source of the methylene group. The only one colorless filtrate. IVhen evaporated the filtrate deposited 24.7 g. of white solid which was crystallized from an ethergiving the desired product was the last of these. methanol pair. The product, weighing 13.5 g. ( 3 3 3 ) , conThe literature3 contains numerous references to sisted of glistening, thick needles, m.p. 158-160 , [ a l Z a ~ the use of hexamethylenetetramine as a source of +94" (c 0.558). Anal. Calcd. for C % J H ~ ~ 0C2, :83.21; H , 10.27. Found: formaldehyde. All of these reactions are reported C , 83.35; H , 10.11. to take place under conditions in which formaldeCholest-4-ene-7pol (I).-To 0.68 g. of the benzoate V I hyde is liberated from the hexamethylenetetramwas added 50 ml. of a 95% ethanol solution containing 4.0 g. ine prior to formation of the final product; while of potassium hydroxide. The resulting solution was refluxed for five hours. After this time water was added t o it is difficult to visualize the formation of formaldethe hot solution until turbidity was produced. After over- hyde under the conditions of the reactions reported night cooling the solution hd: deposited 0.43 g. (86%) of here. Descude4 has reported the reaction of hexsmall prisms, m.p. 122-124 . Recrystallization from ace- amethylenetetramine with benzamide a t 200' to tone-water gave needles, m.p. 122.5-124, [ a ] " ~+90 (c give azotrimethylenetribenzamide, but no product 0.628). Anal. Calcd. for C2,HJ60: C , 83.89; H , 12.00. Found: resembling the methylenedibenzamide we have obtained from hexamethylenetetramine and benzC , 83.67; H , 11.78. The acetate was prepared in the usual fashion giving amide. mica-like plates, m.p. 96-97", [cz]*'D +78" ( c 2.200). The reaction of formamide with hexamethyleneAnal. Calcd. for ClsH4n02: C, 81.25; H , 11.29. Found: tetramine gave a low (30 to 5ooj0) yield of methylC, 81.09; H , 11.07. enediformamide, as had the Knudsen procedure. The tosylate was prepared in a fashion similar to that preHowever, reuse of the mother liquor as solvent for viously described." The tosylate was precipitated from the succeeding runs gave yields of 70 to lOOyobased on pyridine solution with water and the solid recrystallized from acetone-water. The stocky rod: melted 125.5-126' added formamide and hexamethylenetetramine, ~ . dec. typical of tosylates, [ a l Z 7+27.6 which was not the case when paraformaldehyde Anal. Calcd. for CsrHbnOaS: C, 75.51; H , 9.69. Found: was used instead of hexamethylenetetramine. C, 75.71; H , 9.58. Normally for the reaction, the mother liquor from Cholest-4-ene-3-one-7p-01 Benzoate (VII).-During a pea run was refreshed with amounts of hexamethylriod of 1.5 hours, 6.0 g. of chromic acid was added t o a suspension of 13.4 g. of the benzoate VI in 280 ml. of glacial enetetramine and formamide equivalent to the acetic acid. The solution was kept between 52 and 54". amount of methylenediformamide obtained in the Stirring a t this temperature was continued for one-half hour previous run. No determination was made of the after the addition was complete. When the solution was optimum number of runs for reuse of the mother cooled, 8 ml. of ethanol was added t o destroy the excess chromic acid and the mixture was evaporated t o dryness. liquor, but it is a t least 15 to 20. A typical reaction After washing with water, the residue was extracted with is outlined in Table I, which gives some yields ob300 ml. of ether and this ether extract washed with water, tained by this method. Other experiments reusing 10% sodium bicarbonate, and again water. The resulting the mother liquor up to 15 times have been run. ethereal solution was filtered through a short column of Infrared spectra of the products from paraformalalumina and the filtrate was evaporated t o a solid residue. This residue was crystallized from 95'%oethanol to give 2.0 dehyde and from hexamethylenetetramine were g. (14.5%) of white solid, m.p. 142-153 Four recrystalli- compared, and no significant differences were obzations from ethanol gave 1.2 g. of fine needles melting a t lS8-l;aS0 with partial resolidification followed by remelting served. The reaction of hexamethylenetetramine with a t 168 . Chromatography of this material on a 6 X 1 cm. column of 60-100 mesh Florisil gave the pure keto-benzoate amides has been extended t o the formation of 1'11,m.p. 165-167", / c z ~ ~+79"(c ~ D 1.368). methylenediacetamide, methylenebis-(malonamAnal.' Calcd. for Ci4H480~: C: 80.90;' H , 9.58. Found: ide), and methylenedibenzamide from acetamide, C, 80.66; H, 4.40. malonamide and benzamide, respectively. Their Oppenauer Oxidation of Cholest-5-en3p,'I~-diol7-Benzoate.-A mixture of 1.0 g. of the 7-benzoate, 1.0 g . of alumi- preparation is given in the Experimental section. num isopropoxide, 35 ml. of dry cyclohexanone and 35 ml. Experimental of dry toluene was refluxed gently for one hour. After this Methylenediformamide A.-A mixture of 540 g. (12 time 0.3 ml. of acetic acid was added and steam was passed moles) of formamide and 70 g. (0.5 mole) of hexamethylenethrough the mixture for 1.5 hours. The resulting solution tetramine is heated a t a pot temperature of 140' for 5 hours. was extracted with ether which, after washing, was evapoThe mixture is cooled t o ice temperature and the product is rated t o 610 mg. of a yellow oil. Purification of this oil by chromatography produced mostly oily residue, but gave 80 collected on a filter and washed with 90 g. (2 moles) of formmg. of cholest-5,7-diene3-one as a crystalline material, un(1) This work was done under Contracts DA-19-020-ORD-12 and depressed upon admixture with authentic dienone. DA-19-020-ORD-47 with t h e Office of the Chief of Ordnance and has been released by t h e O 6 c e of Public Information, Department of HALLLABORATORY OF CHEMISTRY Defense, for publication. WESLEYAN UNIVERSITY (2) P. Knudsen, Bcr., 47, 2698 (1914). MIDDLETOWN, COXNECTICUT
.
(11) R . H. Baker and Q. R . Petersen. THISJOURNAL, 73, 4080 (1951).
(3) J. F. Walker, "Formaldehyde," 2ad Edition, Reinhold Publ. Corp., New York, N.Y.,1953, p. 416 el rep. (4) M. Descude, Ann. chim. phrt., [7149, 533 (1903).
NOTES
2360
amide. The product may be recrystallized from ethanol. Before recrystallization, it is desirable to elute the crude product with ethanol saturated with methylenediformamide from previous recrystallizations. Decolorizing charcoal is used to remove colored material when necessary. Methylenediformamide melts a t 142-14'. B.-The formamide mother liquor (from A in the first pass or B in the later passes) is treated with Darco G60 to decolorize it, and then it is combined with the wash formamide (90 g.) and 23 g. (0.167 mole) of hexamethylenetetramine and the above procedure is repeated. T h e yields of crude product from a typical series of runs are recorded i n Table I.
mide (MDF)3 in acetic anhydride by anhydrous nitric acid produced methylenedi- (nitroformamide), which on hydrolysis gave rnethylenedinitran~inein nearly quantitative yield. Since this new procedure gave substantially SUperior yields to previous methods for the preparation of nitramines, variables influencing yield have been investigated. The use of this reaction for the preparation of other nitramines also is being investigated and will be reported later. In initial work on the nitration process, all of our TABLE T studies were made using a 9/4/1 ratioi.$ of anhy~r~'rH~'I.ESEDIFORMAMrnE FROM ~ ~ E X A M E T H U L E N E 1 E T R . 4 - drous nitric acid to acetic anhydride to methylenediforniamide, with a nitration and aging temperaMISE WITH 100% EXCESS FORMAMDE Slother ture of 0". The yield of rriethylenedi-(nitroforlll:~quor Formmide) was found to increase with aging time until :1 from EIexamine. amide. Yield, T o t a l yield c,, R u n run mole nioles G. G. c-formic acid or from formamide, was 82.555. ilnal. Calcd. for C 7 H l P O 4 S I C, : 38.89; H, 5.59; S , 25.92. Found: C, 39.12, 38.90; H, 5.72, 5..50; S,25.55, 25.73. Methy1enedibenzamide.-This compound was prepared from benzamide and hexamethylenetetramine in refluxing quinoline. T h e product, melting a t 216-220' after recrystallization from isopropyl alcohol, did not depress the melting point of an authentic sample of methylenedihenzamide. ARTHUR D. LITTLE,I N C MEMORIAL DRIVE CAMBRIDGE 42, MASS.
Nitramines.
I. Methylenedinitramine'
B Y CHARLES \V. SAVER A N D ROBERT P FOLLETT RECEIVED J V Y E 2, 1934
Recently it became necessary to prepare a quantity of methylenedinitramine. This compound has been prepared previously from hydrolysis of 1,8dinitro-1,3,3-triazacyclohexane.?-nitrate with barium hydroxide and isolation through its barium salt, and also from methylenediacetaniide by nitration to methylenedi-(nitroacetamide) followed by hydrolysis.2 Since the formyl group has been found very useful where a labile protecting group is desired, as in the synthesis of amino acids, the use of methylenediformamide instead of methylenediacetamide for the synthesis of this compound was investigated. Nitration of a suspension of methylenediforma(1) This work was done under Contracts DA-19-020-ORD-12 and DA-19-020-ORD-47 with t h e Office of t h e Chief of Ordnance and has been released for publication b y t h e Office of Public Information, Dep d r t m e n t of Defense. ( 2 ) A. H Lamberton, Quart. Rem., 6 , 75 (1951).
TABLE
I
1SFI.UESCE OF SITRATIOX TEMPERATURE IVITIf T I M E OU Y1Er.D OF
Mole of
MDF
~LIETHUI.ENEUINITRAMI~~E
Nitration" temp., OC.
Agina temp., O C .
Aging time, hr.
0
2
1
10 10 10
10 10 10 15-30
1
Crud;, yield.
95 97 7 100 4 93 3 99 25-30 a An acid/anhydride/MDF ratio of 9/4/1 was used. Formic acid was added for the hydrolysis, and the methylenedinitramine was isolated by azeotropic distillation with xylene at reduced pressure.
1 0.5 0.5 0.5 1
-
and Lamberton4 for the nitration of methylenediacetamide. With acetic anhydride-nitric acid mixtures, decreasing amounts of nitroamide were obtained when the amount of water in the nitric acid used was increased; this, however, could be overcome by the pre-addition of enough anhydride to the acid to react with the water present. Any decrease in the ratio of acetic anhydride or nitric acid to methylenediformamide, or the substitution of ammonium nitrate for a portion of the nitric acid, was found to cause a decrease in the yield of methylenedinitramine. However, when trifluoroaceticanhydride was substitutedfor acetic anhydride, the ratio of acid to anhydride to methylenediforniamide could be reduced to 3/3/1 to obtain a quantitative yield. No decrease in yield was obtained with acetic anhydride-nitric acid mixtures when the order of addition was changed. Contrary to (3) P. Knudsen, Ber., 4'7, 2699 (1914); C. W. Sauer and R J . Bruni, THISJOURNAL, 1 7 , 2259 (19.55). ( 4 ) R. C . Brian a n d A . H. Lamberton, J. Chem. SOL.,1635 ( 1 9 4 9 ) . (5) H e a t of reaction d a t a f o r t h e nitration reaction were calculated b y Dr. G . R. Handrick, Arthur D. L i t t l e , Inc., from heat of comhustion d a t a obtained b y a new method which will be given in detail in a forth4(CH80)?0 !IHIiOp + coming publication. CHz(NHCHO)? CHz(X(N0z)CHO)n 6CHaCOOH 5HNOs ZCH?C(O)ONO? f 30.4 kcal./mole (heat evolved). T h e h e a t evolved on nitration was determined experimentally b y Dr. J. W. l.awrence, Atlav Powder Cn., as 29.5 kcal./mole.
+
+
+
+
+
