Trinitro-phenylethyl Amines from TNT

Downloaded by HENKEL KGAA on September 2, 2009 | http://pubs.acs.org Publication Date: November 1, 1946 | doi: 10.1021/ja01215a063 2348 HERMAN BRUSON GEORGE BUTLER A. AND B. steam-bath for eighteen hours. After adding water, the non-aqueous layer was separated, combined with the ether extracts of the water washings, dried and distilled. The forerun consisted of an almost theoretical recovery of the excess hexamethylene dibromide, b. p. 112-114' at 12 mm. The bromoester boiled at 204-205' at 4 mm., n 2 * 1.5283. It weighed 126 g., an 82% yield. ~ Anal. Calcd. for C1,HnOlBr: Br, 21.76. Found: Br, 21.57. w-Morpholinohexyl 1-Phenylcyclohexanecarboxylate.T o 123.5 g. (0.34 mole) of the foregoing bromoester in 200 cc. of dry benzene, 59.0 g. (0.68 mole) of rnorpholine was added slowly. The reaction mixture was then stirred and refluxed five and one-half hours, after which the benzene layer was washed with water then extracted with acid. The base which was regenerated by the addition G f alkali was extracted with ether and dried. Removal of the solvent, followed by distillation of the residue, gave 108 g. (86%) of the aminoester, b. p. 228-230" a t 4 mm., n2'D 1.5166. By method Ia, an 87% yield of this base was obtained. The hydrochloride melted at 121-122' after crystallization from ethyl acetate. 7-Bromopropyl 1-Phenylcyclopropanecarboxylate.-A solution of 25 g. (0.138 mole) of l-phenylcyclopropanecarboxylic acid chloride in 20.5 g. (0.148 mole) of trimethylene bromohydrin was heated on the steam-bath overnight. The reaction mixture was washed successively with water and sodium bicarbonate, then dried and distilled. The main fraction weighed 25.2 g., (65%) and boiled a t 151-1.53' a t 3 mm.. n " ~1.5364. Vol. 68 Anal.1a Calcd. for C1,HlsOzBr: C, 55.12; H, 5.34. Found: C, 55.96; H, 5.42. r-Morpholinopropyl 1-Phenylcyclopropanecarboxylate. -The foregoing bromide, 11.3 g. (0.041 mole), was converted to the morpholino derivative as described above for the w-morpholinohexyl ester. The product boiled at 173-175' at 2 mm., n Z 6 ~ 1.5193. The yield was 8.5 g. or 73%. The hydrochloride, m. p. 168-169', was crystallized from absolute alcohol. Acknowledgment.-The author is indebted to Mr. E. F. Shelberg and Mr. L. F. Reed of the Microanalytical Department of these laboratories for the microanalyses and to Mr. Wm. B. Brownell for his assistance in preparing some of the intermediates. Summary A series of basic esters derived from l-phenylcyclopropanecarboxylic acid and l-phenylcyclohexanecarboxylic acid has been described. Preliminary pharmacological data indicate that several of these esters possess pronounced antispasmodic properties. (13) Fractionation of this material did not improve the analysis. NORTH CHICAGO, ILLINOIS [CONTRIBUTION ROHM FROM AND HAAS RECEIVED JULY 13, 1946 CO., INC.] Trinitro-phenylethyl Amines from TNT' BY HERMAN BRUSON GEORGE BUTLER A. AND B. ylol diethylamine in boiling i-amyl alcohol, but could isolate no definite compounds from the reaction of these amine ethers with 2,4,6-trinitrotoluene. Kermack and Muir4 obtained 2,4-dinitrophenylethyl-N-diethylamine by treating equivalent quantities of 2,4-dinitrotoluene1 diethylamine, and formaldehyde in boiling ethanol. They also described the formation of 1,3-dipiperidino-2(2,4-dinitrophenyl)-propane5 by the reaction of one mole of 2,4-dinitrotoluene with two moles each No, of piperidine and formaldehyde. NOz It also has been reported that the alkaloid berberine6condenses with TNT to give an orange red compound but its properties are not described. Berberine in its pseudo-base form conNO, tains an >N-CHOHgrouping, but whether Vender2 prepared 2,4,5-trinitrophenylethanol this combines with TNT by loss of water or by by treating 2,4,5-trinitrotoluene with aqueous the formation of a simple addition product is not formaldehyde in the presence of potassium carbonate, but described no Mannich-type bases. clear. condensation of TNT with formaldehyde The McLeod and Robinson3described the formation of and secondary amines takes place readily a t 2,4-dinitrophenylethyl-N-diethylamine a yelas to loo", depending low oil from the reaction of equivalent weights of temperatures from about 0 together equivalent upon the amine, by mixing 2,4-dinitrotoluene and the i-amyl ether of meth- weights of the reactants. In the cases of the lower, (1) This paper i s based on work done for the Office of Scientific more reactive amines, low temperatures are suitResearch and Development under OSRD Contract No. OEM sr-643 able to complete the reaction, but in the cases of with the Rohm P U Haas Co. ~ While attempting to utilize 2,4,6-trinitrotoluene in the preparation of combustible plastics, la it was found that this compound would undergo the Mannich reaction with formaldehyde and secondary amines to give 2,4,6-trinitrophenylethyl amines accorciing to the reaction ( l a ) Bruson and Butler, U. S. Patent 2,400,806 (1946). (2) Vender, Gars. chi?& ifat., 45, 11, 97 (1915). (3) McLeod and Robinson. 1. Chcm. Soc.. 11%1470 (1921). (4) Kermack and Muir, J . Chcnt. Sac., 300 (1933). ( 5 ) Mannich and Stein, Bet., 58, 2659 (1925). (6) Robinson and Robinson, J . Chcm. Soc.. 111, 958 11917). TRINITRO-PHENYLETHYL AMms FROM T N T Nov., 1946 2349 the higher, less reactive amines, higher tempera- liquids for this purpose are dioxane, benzene, altures are advantageous. Small amounts of al- cohol or water. kali metal hydroxides accelerate the condensation. The Mannich reaction with TNT as a compoIn view of the tendency for T N T to ignite in con- nent was applied to the following secondary atact with free bases, it is necessary to carry out mines. the condensation in an inert solvent or a liquid Morpholine, piperidine, diethanolamine, Nsuspending medium for the reactants. Suitable methylaniline, dibenzylamine, dimethylamine, diTABLE I PROPERTIES AND ANALYSES 2,4.6-TRIXlTROPHENYLETHYL AMINESO Z N - ~ C H ~ C H Z R OF I NOz Analyses, % 7 M. p., Downloaded by HENKEL KGAA on September 2, 2009 | http://pubs.acs.org Publication Date: November 1, 1946 | doi: 10.1021/ja01215a063 -N< linipirical forniiiln 1: 1 Benzeneethanol CuHi407N4 41.2 4.30 17.18 44.3 4.41 17.00 14 0 Ethanol CtsHigO~N4 48.2 4.94 17.29 48.3 5.06 17.15 8 7 Benzene Czi0N tH684 .. .. 16.29 .. .. 16.28 175 Ethanol CsiON lH4s4 52.1 4.05 16.16 52.1 4.15 16.08 14 0 Ethanol ClzON sHos~ 60.5 4.60 12.83 60.5 4.85 12.86 170 Xylene CawiN aHOna 42.6 3.55 19.86 43.3 3.68 19.90 "C. CHzCH . Recrystallized from 135 R - . CHzCH I)CHI CH,CH* -NCO) -(&H, -N(Z >- -NCzCrz -(H-B) C& HH -N< CHaCHz Calcd. c N H Found H C N TABLE I1 N2 O I PROPERTIES ANALYWS 2,4,6-TRINITROPIIEENYLETHYL AND OF AMINE HYDROCHLORIDES NOz M. p., 'C. R - Analyses, % Empirical formula Recryst. from Calcd. IOU.C1 N 136 19 1 -C. NH (( C z I I>H2) HC-z CHnCHi 220 (dec.) Ethanol GHss4l ozONC 7.80 12.26 8.39 11.97 2 TABLE I11 PROPERTIES AND ANALYSES OF PICRATES OF 2,4,6-TRINITROPHENYLETIIYL 7 Analyses, % - Empirical formula c Cnlcd. H N 11 7 CoiOa7 iHsiN 41.2 3.44 17.72 161 c6iO47 iIriN 38.9 3.06 128-130 162 c&7 i& 6N 37.7 M. p., O C . R - -N< CHiCH >I AMINES NOz NO2 Found H N 41.1) 3.45 17.55 17.65 38.6 3.14 17.70 3.32 17.10 C Z ~ H ~ O ~5~ .N T 3.46 0 5 14.71 37.5 50.3 3.09 3.48 17.15 14.79 19.18 37.8 2.73 19.18 c CH,CH, -N< CHzCHz )i'---h CHXH C . >200 CHT a&i 2&t 37.6 2.54 . 17.45 11.23 17.00 16.10 10.18 15.61 13.85 9.14 13.34 C o i O N C 11.10 iHas~I Ethanol Ethylenedichloride CIZHI~O~N&I 10.20 CdzONC iIse4l 8.78 Benzene 183 Found Ion. C1 N ROBERT DUSCE~NSKY L.ALLENDOLAN AND 2350 ethylamine, di-n-butylamine, dicyclohexyIamine and piperazine. The latter combined with two each Of formaldehyde and TNT to & bis-(2,4,6-me ' trophenylethyl) -NlN'-piperazine. NO2 0 3 N - q - C H 2 C H ~ - - N < CHn-CHz )N-CHnCHz -4 Downloaded by HENKEL KGAA on September 2, 2009 | http://pubs.acs.org Publication Date: November 1, 1946 | doi: 10.1021/ja01215a063 Hn-CHz In general the reaction is applicable to secondary amines that readily form an N-methylol derivative with formaldehyde. Diphenylamine and similar very weakly basic amines which do not readily form N-methylol derivatives with formaldehyde fail to react. The formaldehyde used is preferably in the form of an aqueous 30-37% solution, but may also be used in the form of paraformaldehyde. Experimental 2,4,6-Trinitrophenylethyl-N-morpholine.-The preparation of this compound is given as a typical example of the general procedure used for the preparation of these cornpounds. To a stirred solution of 11.5 g. (0.05mole) of 2,4,6-trinitrotoluene and 25 g. of dioxane cooled to 5 O , there was gradually added 4.5 g. (0.05mole) of morpholine, 1 g. of 2% sodium hydroxide solution, and 4.5 g. (0.05 mole) of 37% aqueous formaldehyde, the additions being made in the order given. The temperature of the reaction mixture was maintained between 5 and 10" while the various reagents were added and for a period of one hour thereafter. The mixture was warmed at 40-50' for one hour, then cooled to 10" and mixed with 100 g. of cold water containing 0.5 g. of concentrated hydrochloric acid. Stirring was continued and the mixture cooled until the product crystallized out. I t was filtered, washed and dried in the air. The material thus obtained amounted to 15.5g. (95% [CONTRIBUTION FROM THE VOl. 68 of theory) and melted at 125'. After recrystallization f o a 1:l mixture of benzene and ethanol, i t formed rm tancolored needles melting at 136". The picrate of the above compound melts at 181'. It was prepared by &ig equivalent quantities of the compound and picric acid in hot alcoholic iolution. This procedure was typical of that used for the NO: preparation of all picrates described. In those cases in which the product obtained was an o l or was difficult to crysi -NOz tallize, the reaction product was taken up in ether, dried over anhydrous calcium chloride and the hydrochloride o the f N 4 amine precipitated by passing dry hydrogen chloride into the solution. The salt was purified by recrystallization to obtain the pure hydrochloride of the tertiary amine. In most cases, the theoretical yield of the crude reaction product was approached with little or no loss by decomposition or by-products. Dioxane was used as solvent in all the preparations. Tables I, I1 and I11 include the compounds prepared, physical properties and analyses. ~ Acknowledgment.-The authors wish to express their appreciation to Mr. Clyde W. Nash of the Rohm and Haas Analytical Laboratories, Bristol, Pa., for the microanalyses reported here. Summary 2,4,6-Trinitrotoluene (TNT) undergoes the Mannich reaction with formaldehyde and Nrnethylol-forming secondary amines to give 2,4,6trinitrophenylethyl-N-t-amines. The following secondary amines were used : dimethylamine, diethylamine, dibutylamine, dicyclohexylarnine, dibenzylamine, diethanolamine, N-methylaniline, morpholine, piperidine and piperazine. Piperazine condensed with two moles each of formaldehyde and TNT. PHILADELPHIA, PA. RECEIVED JULY 26, 1946 RESEARCH LABORATORIESHOFFMANN-LA OF ROCHE, INC.] Studies in the Imidazolone Series. The Synthesis of a Lower and a Higher Homolog of Desthiobiotin and of Related Substances1 BY ROBERT DUSCHMSKY L. ALLEN AND DOLAN In a previous paper,'" it was shown that FriedelCrafts acylations of 4-methyl-2-imidazolone (I, R = CHs), followed by hydrogenation of the obtained ketones (II), lead to imidazolidone compounds, the keto group being first reduced to methylene (I11 and IV). H d I co\H R-C=CH I i - Po\ NH HN I I R-C=C-COR I1 ' -+- (1) Presented before a'session of the Division of Organic Chemis- try, 109th Meeting of the American Chemical Society, Atlantic City, New Jersey, April 10, 1946. (la) Duschinsky and Dolan. THIS JOURNAL 67, 2069 (1946). HN RC L I Po\ NH NH 1 C---CHzR' - i HN I R-CH--CH-CHnR' I11 Iv In the present paper it is reported that 2-imidazolone (I, R = H) and 4-ethyl-2-imidazolone (I, R = CzHb) react in a similar manner. Curiously enough, Compounds having dif€erent properties are described in the literature as 2imidazolone. In 1892 Marckwald reported the synthesis of imidazolone from amino acetal (V) v i a ureido acetal (VI), and described it as a substance H~NCH&H(OC~HI)~ + (V) HnNCONHCHEH(OGH,)t (VI) +J (R H)