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The Mannich reaction consists in the condensation of ammonia or a primary or secondary amines, usually as the hydrochloride, with formaldehyde and a compound containing at least one hydrogen atom of pronounced reactivity. The essential feature of the reaction is the replacement of the active hydrogen atom by an aminomethyl or substituted aminomethyl group. The product from acetophenone, formaldehyde, and a secondary amine salt is an example. The product to be expected from a Mannich reaction involving an ammonium salt is a primary amine. The mechanism of the Mannich reaction has not been established.

l,3-Dimethyl-5,6-diaminouracil was condensed with nitrous acid, thionyl chloride, glyoxal, oxalic acid, diacetyl and benzil, respectively. It was also treated with dilute hydrochloric acid whereupon l,l',3,3'-tetramethylhydurilic acid or 1,3,6,8tetramethyl-2,4,7,9-tetraketodecahydrodipyrimido[4,5-b,4',5'-e]pyrazine or a mixture of both compounds was obtained.During our synthesis of potential diuretics, we studied a number of reactions in which 1,3-dimethyl-5,6-diaminouracil (III), a key intermediate in the manufacture of theophylline, was condensed with nitrous acid, thionyl chloride, glyoxal, oxalic acid, diacetyl and benzil, respectively.In order to obtain the required diamine III, N,N'dimethylurea (I) and cyanoacetic acid were condensed in the presence of acetic anhydride to form N,N'-dimethyl-N-cyanoacetylurea which was converted by sodium hydroxide into l,3-dimethyl-6aminouracil; nitrous acid reacted with the uracil to form l,3-dimethyl-5-nitroso-6-aminouracil monohydrate (II). Since we used the continuous process described by Campbell and Campbell,3 only compound II was isolated; sodium hydrosulfite4 transformed II into III. Traube6 stated that the diamine III condensed with nitrous acid to form "l,3-dimethyl-4,5-aziminouracir'6 and assigned formula IV to this compound; neither the yield nor the melting point was reported, and the compound was characterized only by solubility data and a nitrogen analysis. When we repeated Traube's experiment, we obtained a product which, presumably, was identical with the product obtained by him. However, our analytical data did not correspond exactly to that calculated for formula IV.7 Acylation of IV with acetic anhydride and also with benzoyl chloride yielded the monoacyl derivatives (V). The complete analytical data obtained in the case of both acyl derivatives corresponded very closely to the calculated data. Although formula V indicates that these derivatives are 7-acyl compounds, the acyl group might be attached to the 8or 9-nitrogen atom.Interaction of the diamine III with thionyl chloride yielded a product to which we assigned formula VI.8 It was assumed that the diamine had reacted with thionyl chloride in the same manner as ophenylenediamine. In the latter instance, the structure of the heterocyclic produced, piazthiol, was established by physical chemical measure-(1) This paper represents part of a dissertation submitted by H. C. Godt, Jr., in partial fulfillment of the requirements for the Ph.D. degree in the University of Michigan.(2) Monsanto Chemical Company Fellow.(3) K. N. Campbell and B. K. Campbell, U. S.

This paper deals with the synthesis of 3-chloromethylthianaphthene, thianaphthene-2-and thianaphthene-3-acetic acid and certain derivatives which were prepared from them.We have found that thianaphthene can be chloromethylated very readily.3 Since conversion ©f the chloromethyl into the cyanomethyl derivative and hydrolysis of the latter substance yielded a thianaphthene-acetic acid (m. p. 108-109°) which melted at the same temperature as the thianaphthene-3-acetic acid (m. p. 109°) described by Crook and Davies,4 chloromethylation of thianaphthene must produce the 3-chloromethyl derivative as would be expected. Furthermore, we have prepared an acid (m. p. 141-142°) which must be thianaphthene-2-acetic acid since it was obtained from thianaphthene-2-carboxylic acid, the structure of which has been established,6 by the Amdt-Eistert reaction.It was discovered that the structures of several thianaphthene carboxylic acids can be determined by a very simple, direct procedure Thus when thianaphthene-2-carboxylic acid was heated at 75°for a short time with Raney nickel, in sodium carbonate solution, /3-phenylpropionie acid was obtained in 93% yield. y-Phenylbutyric acid was formed, in good yield, from thianaphthene-2acetic acid, and thianaphthene-3-acetic acid was converted into /3-phenylbutyric acid. A study of the general applicability of this process for a vari-CH -COOH Raney nickel ->-CH2 I CHj-COOH ety of thiophene and thianaphthene derivatives is in progress.6 2-(3-Thianaphthenylmethyl) -imidazoline was(1) This paper represents part of a dissertation to be submitted to the Horace H. Rackham School of Graduate Studies by Mr. Sheets in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the University of Michigan.(2) Monsanto Chemical Company Fellow.(3) Hansch and Lindwall (/. Org. Chem., 10, 381 (1945)) stated that they were unable to chloromethylate thianaphthene.(4) Crook and Davies, J. Chem. Soc., 1697 (1937). Although these investigators named their acid, incorrectly, thianaphthene-2acetic acid, its preparation from 3-bromothianaphthene, by a series of steps which include the Grignard and Arndt-Eistert reactions, establishes its structure as the 3-acetic acid.(5) Weissgerber and Kruber, Ber., 63, 1551Ber., 63, (1920.