Studies on the series of azoles and azines. 65. Mass spectra of 5-arylidene-, 5-ethoxycarbonylmethylene-hydantoins and their derivatives

The mass spectra of 5-m- and p-substituted benzylidenehydantoins, their thio analogs and 5-carbethoxymethylenehydantoins with a substituent at the -carbon atom of the side chain were studied. The fragmentation of the molecular ions of 5-arylidenehydantoins proceeds in one direction, splitting of the X=C-NR-C=O fragment, irrespective of the substituent in the benzene ring. The peak intensity of the fragmentary ions formed from the molecular ions is linearly dependent on the -constants of the substituent. The direction of the fragmentation of 5-ethoxycarbonylmethylenehydantoins markedly depends on the substituent at the -carbon atom in the side chain that determines the stability of the hydantoin ring and the carboethoxyl group. The fragmentation of these compounds under electron impact proceeds by five paths, related to splitting of fragments O=C₍₂₎NCH₍₄₎=O, C₂H₄, C₂H₅O, C₂H₅OH, and COOC₂H₅.See [1] for Communication 64.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 625–631, May, 1988.     

Mass spectra of substituted uracils

The mechanisms for the major fragmentations obtained with selected substituted uracils are discussed. Interpretation of data was facilitated by use of metastable peaks, high-resolution data, and low-voltage spectra. The major fragmentation obtained with N-alkyl substituted uracils, when the alkyl group contains 2 or more carbons, is due to cleavage of the alkyl substituent. This cleavage is accompanied by a rearrangement of 1 or 2 hydrogens from the alkyl group to the uracil ring. Possible mechanisms for the rearrangements are discussed. It was found that the molecular ion of 1- and 3-alkyl substituted uracils (where the alkyl group has 2 or more carbons) does not undergo the expected ‘retro Diels-Alder Reaction’. Instead, the odd-electron ion formed by loss of the alkyl substituent with a single hydrogen rearrangement undergoes this reaction (loses HNCO). Since it is formed as a secondary reaction product, the relative abundance of the ‘retro Diels-Alder’ fragment is low compared to what is obtained in the spectra of the simple uracils. The ‘retro Diels-Alder Reaction’ can be used to differentiate between 2- and 4-thiouracils, and between 1- and 3-methyl and phenyl substituted uracils. It was found that 1- and 3-alkyl substituted uracils (alkyl group of 2 or more carbons) can be differentiated by the mass of the M-alkyl fragment since the 3-substituted compounds give predominantly a double hydrogen rearrangement and the 1-substituted compound gives mainly a single hydrogen rearrangement. In addition the intensity of the molecular ion, relative to the M-alkyl ion, is considerably stronger in the 1-substituted uracils.     

Synthesis of 1-(dihydroxypropyl)-5-substituted uracils

Novel 1-(dihydroxypropyl)-5-substituted uracils were synthesized in the reaction of 1-(4-nitrophenyl)-5-substituted uracil derivatives with appropriate aminopropanediols under mild conditions. In the case of 3-amino-1,2-propanediol both racemic and enantiomerically enriched products were obtained. These compounds may be considered as new building blocks for oligonucleotide synthesis.     

Syntheses of various 5-(bromoaryl)-substituted uracils

The Suzuki Pd(0)-catalyzed coupling between arylboronic acids and aryl bromides or iodides in weakly alkaline medium, previously further developed by us, has been used for regioselective preparation of 5-(2′-bromo-5′-furyl)-, 5-(2′-bromo-4′-furyl)-, 5-(2′-bromo-5′-thienyl)-, 5-(2′-bromo-4′-thienyl)-, 5-(4′-bromo-2′-thiazolyl)-, 5-(3′-bromophenyl)-, 5-(6′-bromo-2′-pyridyl)- and 5-(4′-bromo-2′-pyrimidyl)-substituted 2,4-di-t-butoxypyrimidines. In the coupling between 2,4-di-t-butoxy-5-pyrimidineboronic acid and the nine different aryl dibromides that were tried as coupling partners, only the 2,4- and 2,5-dibromothiazoles did not give satisfactory yields, 15% and 0%, respectively. The other seven aryl dibromides gave the desired 5-(bromoaryl)-2,4-di-t-butoxypyrimidines in 58-89% yield. Attempts to synthesise 2,4-di-t-butoxy-5-(2′-bromo-4′-thienyl)pyrimidine from 2-bromo-4-iodothiophene failed. Dealkylation of the 5-(bromoaryl)-2,4-di-t-butoxypyrimidines in 2.5 M hydrochloric acid gave the corresponding 5-(bromoaryl)uracils in almost quantitative yields.     

Mass spectra of some azoles

The principal electron-impact fragmentation patterns of 3,4,5-triphenyl-1,2,4-triazole, 2,5-diphenyl-1,3,4-thiadiazole, their perfluorinated analogues and 2,5-di(pentafluorophenyl)-1,3,4-oxadiazole have been established from metastable ion evidence and precise mass measurements. Although ions produced by expulsion of nitrogen from the molecular-ions of these compounds are of low abundance, the simultaneous expulsion of nitrogen and a C₇X₅ radical (X = H or F) gives rise to abundant ions.     

Studies on the series of azoles and azines. 66. Synthesis,spectra and structure of 5-arylazo- and 5-arylideneamino-2,4,6-triaminopyrimidines and their 6-hydroxy analogs

5-Arylazo and 5-arylideneamino-2,4,6-triaminopyrimidines and their 6-hydroxy analogs were obtained by azo coupling of 2,4,6-triamino- and 2,4-diamino-6-hydroxypyrimidines with aryldiazonium salts, and also by the reaction of benzaldehydes with 2,4,5,6-tetraamino- and 2,4,5-triamino-6-hydroxypyrimidines, respectively. According to spectral data, in solvents with different polarity, these compounds exist preferentially in the triamino- or diaminohydroxy form. The main paths of the mass spectrometric fragmentation of the compounds studied have been determined.See [1] for Communication 65.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 659–667, May, 1988.     

A silicon-mediated synthesis of novel 5-substituted 2,4-dimethoxypyrimidines and 5-substituted uracils

A highly efficient and general method for the synthesis of 5-(2-acylethynyl)-2,4-dimethoxypyrimidines starting from 2,4-dimethoxy-5-/2-(trimethylsilyl)ethynyl/pyrimidine is described. The 5-(2-acylethynyl)-2,4-dimechoxypyrimidines have been converted to 5-(2-acyl-1-iodovinyl) uracils and 5-(2-acylethynyl) uracils.     

Mass spectra of 5-fluorouracil derivatives. N-1-substituted sulfonyl derivatives

The electron impact mass spectra of 1-sulfonyl substituted derivatives of 5-fluorouracil were investigated. The substituents were CH₃SO₂ (compound I), CH₃(CH₂)₃SO₂ (II), C₆H₅SO₂ (III) and p-CH₃C₆H₄SO₂ (IV).     

Synthesis and antimicrobial activity of some novel 5-alkyl-6-substituted uracils and related derivatives

6-chloro-5-ethyl-, n-propyl- and isopropyluracils 5a-c were efficiently prepared from the corresponding 5-alkybarbituric acids 3a-c via treatment with phosphorus oxychloride and N,N-dimethylaniline to yield the corresponding 5-alkyl-2,4,6-trichloro-pyrimidines 4a-c, which were selectively hydrolyzed by heating in 10% aqueous sodium hydroxide for 30 minutes. The reaction of compounds 5a-c with 1-substituted piperazines yielded the corresponding 5-alkyl-6-(4-substituted-1-piperazinyl)uracils 6a-j. The target 8-alkyltetrazolo[1,5-f]pyrimidine-5,7(3H,6H)-diones 7a-c were prepared via the reaction of 5a-c with sodium azide. Compounds 6a-j and 7a-c were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Compound 6h displayed potent broad-spectrum antibacterial activity, while compound 6b showed moderate activity against the Gram-positive bacteria. All the tested compounds were practically inactive against Candida albicans.     

Syntheses of various 5-(3′-substituted phenyl)uracils

The Suzuki Pd(0)-catalysed coupling between arylboronic acids and aryl bromides or iodides in weakly alkaline medium has been used for the preparation of 5-(3′-chlorophenyl)-, 5-(3′-iodophenyl)-, 5-(3′-aminophenyl)-, 5-(3′-azidophenyl)-, 5-(3′-methylthiophenyl)- and 5-(3′-styryl)-substituted 2,4-di-t-butoxypyrimidines. In the coupling between 2,4 di-t-butoxy-5-pyrimidineboronic acid and the six different aryl halides that were used as coupling partners, only 1-azido-3-bromobenzene did not give satisfactory yields, 18%. The other five aryl halides gave the desired 5-(3′-substituted phenyl)-2,4-di-r-butoxypyrimidines in 41–92% yield. Dealkylation of these five 5-(3′-substituted phenyl)-2,4-di-t-butoxypyrimidines in 2.5M hydrochloric acid gave the corresponding 5-(bromoaryl)uracils in almost quantitative yields. 5-(3′-Azidophenyl)uracil was prepared in 43% yield directly from 5-(3′-aminophenyl)-2,4-di-r-butoxypyrimidine.     

Mass spectra of some 3-substituted coumarins

The electron impact mass spectrometric fragmentation pathways for some 3-substituted derivatives of coumarin, benzo[f]coumarin, thieno[3,2-f]coumarin, thieno[2,3-h]coumarin and azacoumarin, viz nitriles, carboxamides, thiocarboxamides and esters were investigated. The initial cleavage of the pyrone ring is found to be largely dependent on the stability, under electron impact, of the attached functional group.     

Incorporation of 5-substituted uracil derivatives into nucleic acids—I: Synthesis of some 5-substituted uracils

5-(1-Hydroxyethyl)uracil, prepared by the reduction of 5-acetyluracilwith sodium borohydride, has been dehydrated with formic acid to give 5-vinyluracil and a dimer of 5-vinyluracil. trans 1,3-bis (uracil-5-yl)but-1-ene. These compounds have also been prepared with a tritium label in an identified position and with a high specific activity such that their incorporation into nucleic acids can be monitored.     

Mass spectra of 4-substituted 2-phenylpiperidines

The major transformations in the mass spectral decomposition of 4-substituted 2-phenylpiperidines follow a similar pattern and primarily involve cleavage of the piperidine ring and loss of alkene molecules containing functional groups.Permskii Pharmaceutical Institute, Perm 614000. Translated from Khimiya Geterosiklicheskikh Soedinenii, No. 5, pp. 634–640, May, 1994. Original article submitted April 15, 1994.     

Regioselective direct C-H arylations of protected uracils. Synthesis of 5- and 6-aryluracil bases

A new regioselective synthesis of 5- and 6-aryluracil bases based on direct C-H arylations of diverse 1,3-protected uracils has been developed. Benzyl-protected uracils were selected as the most practical in terms of stability during the arylation and facile cleavage of the benzyl groups. Pd-catalyzed C-H arylations in the absence of CuI gave preferentially 5-aryl-, whereas the reactions in the presence of CuI gave 6-aryl-1,3-dibenzyluracils. Final deprotection either by transfer hydrogenolysis over Pd/C or by treatment with BBr(3) gave the desired free arylated uracil bases in good yields.     

Investigation of azoles and azines. 75. Structure of 2-aryl-1,3-oxazine-4,6-diones in the gas phase

The mass-spectrometric fragmentation of a number of potentially tautomeric 2-aryl-1,3-oxazine-4,6-diones and model substances that fix the possible tautomeric forms was studied. The characteristic fragmentation pathways that are peculiar to one or another tautomer and the characteristic ions that make it possible to identify them in tautomeric mixtures were ascertained. It is shown that in the gas phase 2-aryl-1,3-oxazine-4,6-diones exist in mixtures of 4-hydroxy, 6-oxo, dipolar-ionic, and dicarbonyl forms; the amounts of the latter two forms increase with intensification of the electron-acceptor properties of the substituent in the para position of the benzene ring.See [1] for Communication 74.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 552–556, April, 1990.