Reactions of 1,3-Dimethyl-5,6-diaminouracil

Abstract

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.

An X-ray crystallographic study of C-5 and C-6 substituted 1,3-dimethyl-6-aminouracil architectures

“…Synthesis and spectral characterization 1,3-dimethyl-6-aminouracil (L 1 ) as a key precursor was prepared according to the procedure described in literature [21]. Condensation reaction of L 1 with benzaldehyde, p-chlorobenzaldehyde, 2-furaldehyde and formaldehyde at room temperature in aqueous/ alcoholic medium gave di-pyrimidine derivatives (L 2 -L 5 ) respectively.…”

“…This uracil precursor also has sp 3 ring carbon which motivated us to go for design and control of these organic architectures by simple crystal growth. Keeping these in mind, we have examined the favourability of different hydrogen bonds and non-covalent interacting motifs for the 5,6-substituted uracil, a system of biological relevance [21] and a preliminary report is presented in this manuscript which deal with the synthesis, spectroscopic characterization and X-ray crystallographic structural analysis of 1,3-dimethyl-6-aminouracil (L 1 ) along with its 5-substituted derivatives viz. 6,6'-diamino-1,1',3,3'-tetramethyl-5,5'-(benzylidene)bis -[pyrimidine-2, 4(1H,3H)-dione] (L 2 ), 6,6'-diamino-1,1',3,3'-tetramethyl-5, 5'-(4-chloro-benzylidene)bis[pyrimidine-2,4(1H,3H)-dione] (L 3 ), 6,6'-diamino-1,1',3,3'-tetramethyl-5,5'-(furayl)bis[pyrimidine-2,4(1H,3H)-dione] (L 4 ), 6,6'-diamino-1,1',3,3'-tetramethyl-5,5'-(formyl)bis[pyrimidine-2,4(1H,3H)-dione] (L 5 ) and an amidine side chain derivative 6-[(dimethylamino) methyleneamino]-1,3-dimethylpyrimidine-2,4(1H,3H)-dione dihydrate (L 6 ).…”

1,3,7-Triethyl-substituted xanthines—possess nanomolar affinity for the adenosine A1 receptor

“…31 Subsequently, the target xanthines (3)(4)(5) were synthesized as reported in the literature. 30 The 1,3-dialkyl-5,6-diaminouracils (6a, b) were reacted with the appropriate commercially available carboxylic acid, such as 4-phenylbutanoic acid (7), phenylpropanoic acid (8) and phenoxyacetic acid (9), in the presence of the coupling reagent N-(3-dimethylaminopropyl)-N 0 -ethylcarbodiimide (EDAC) at room temperature.…”

“…The 1,3-dialkyl-5,6-diaminouracils (6a, b) were synthesized following the protocol developed by Blicke and Godt. 31 The test compounds 3a, 3b, 3c, 3d, 5a, 5b, 5c, 5d 30 and 4a 42 were prepared as described in literature. The analytical results of the compounds 4b, 4c and 4d are documented in Supplementary material.…”

Synthesis of a New Series of 1H‐Imidazol‐1‐yl Substituted 8‐Phenylxanthines as Adenosine Receptor Ligands

“…Oxidative cyclization of the resulting imine intermediate using SOCl 2 afforded the xanthines in good yields. Synthesis of 5,6-diamino-1,3-dimethyluracil (1), a key intermediate to the synthesis of all the 8-substituted xanthine derivatives, was performed according to the general method as reported earlier [19] [20].…”