Mass spectra of some 4,5-dihydroimidazole derivatives

The mass spectra of a series of 4,5-dihydroimidazole derivatives were determined. Deuterium labelling and high resolution mass spectrometry were utilized in order to elucidate the mechanism of a number of fragmentations. The most significant ions arise from the following processes: (1) elimination of the C-4 substituent; (2) cleavage of the 1,2-N? C and 4,5-C? C bonds with or without hydrogen migration; (3) cleavage of the 1,5-N? C and 2,3-C? N bonds with charge retention on the N-1? C-2 moiety.

1 In this paper the standard numbering of the imidazole ring (see structures) is retained for the fragment ions.

Anomalous behaviour is shown by the t-butoxy derivative; the reasons for this behaviour are discussed.     

Synthesis and antitumor evaluation of some 1,3-disubstituted tetrahydropyrimido[4,5-c]isoquinolines

Cyclocondensation of 6-amino-2,4-dioxopyrimidine or 2,4,6-triaminopyrimidine with 1-cyclohexenecarbox-aldehyde 13 afforded regiospecifically, tricyclic, angular 1,3-disubstituted tetrahydropyrimido[4,5-c]isoquin-olines 5 and 6 respectively. In addition, 2,4,6-triaminopyrimidine when condensed with 2-chloro-1-cyclohex-enecarboxaldehyde 14 , regiospecifically afforded the angular isomer 6 . However, the cyclocondensation of 2,6-diamino-4-oxopyrimidine with 13 was regioselective and afforded a mixture of the linear and angular tetrahydropyrimidoisoquinolines 2 and 4 . The growth of leukemia L-1210 cells in culture were inhibited 50% by 6 at 9 × 10^?8 M. Compounds 4 and 5 were not significantly active.     

Synthesis of 2-amino-4,5-disubstituted 3,5-dicyano-4,5-dihydrofurans

A new reaction was found for the preparation of difficult-to-obtain polyfunctional dihydrofurans, viz., the reaction of tetracyanoethylated ketones with hydrogen peroxide in the presence of a base.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1027–1030, August, 1985.     

Synthesis of some pyridazino[4,5-b]quinoxaline derivatives

Several derivatives of the little-studied pyridazino[4,5-b]quinoxaline heterocyclic system, the structural isomer of benzopteridine, were synthesized in order to study their biological activity. 6,7-Dimethylquinoxaline-2,3-dicarboxylic acid and a number of its derivatives were also obtained.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 274–278, February, 1972.     

Tautomerism of some imidazo[4,5-b]pyridine derivatives

It was shown by means of UV and IR spectroscopy and the ionization constants that the tautomeric equilibrium of 2-amino- and 2-mercapto derivatives of 3-methyl-3H-imidazo[4,5-b]pyridine is shifted to favor the amino and thione forms, respectively.     

Mass spectra of 4,5-disubstituted 1,2,3-thiadiazoles

The schemes of the fragmentation of 4-substituted 5-arylamino-1,2,3-thiadiazoles were established on the basis of electron-impact mass spectra and high-resolution mass-spectrometric data, and the effect of substituents on the fragmentation pathways was analyzed. It is shown that the cyclization of the [M-N₂]⁺ ions formed in the fragmentation of compounds that contain a thiocarboxamido group in the 4 position proceeds with the participation of the most nucleophilic heteroatom.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 118–122, January, 1988.     

Synthesis of some 2,4-disubstituted tetrahydropyrimido[4,5-b]quinolines as potential antitumor agents

Cyclocondensations of two 2,4-disubstituted 6-aminopyrimidines with 2-chloro-1-cyclohexenecarboxaldehyde afforded in each case a new regiospecific synthesis of tricyclic, linear disubstituted 6,7,8,9-tetrahydro-pyrimido[4,5-b]quinolines 2 and 3 in excellent yields. The linear structures and hence the regiospecificity of the synthesis were established using ¹H nmr and ¹³C nmr. The growth of leukemia L1210 cells in culture was inhibited 50% by 2 at 30 × 10^?6M and 48% by 3 at 100 × 10^?6M.     

Syntheses and reactions of some 4,5-dihaloimidazole-2-carboxylic acid derivatives

The preparation of 5H,10H-diimidazo[1,2-a:1′,2′-d]pyrazine-5,10-dione ( 2a ) and its 2,3,7,8-tetrabromo- and 2,3,7,8-tetrachloro- analogs ( 2b and 2c , respectively) is reported. These dimers, when allowed to react with various anilines, afford imidazole-2-carboxamides ( 3a-c ).     

Pyridazines. XLI synthesis of novel pyrido[3,4-d]pyridazine derivatives from 4,5-disubstituted pyridazines

Pyrido[3,4-d]pyridazines 2–5, 21 bearing one, two, or three aryl substituents in the pyridine moiety are shown to be conveniently accessible from 4-aroyl-5-methylpyridazines or 4,5-diaroylpyridazines, respectively, by condensation reactions with appropriate C-N fragments. In addition, the novel pyridazine-annelated pyridones 24, 25 were found to be easily available from ethyl 5-methyl-4-pyridazinecarboxylate.     

The synthesis of some 2,4-disubstituted derivatives of quinolone-3-carboxylic acids and carbonitriles

In order to prepare the 2-chloro derivative of oxolinic acid, ethyl 1-ethyl-1,4-dihydro-2-hydroxy-6,7-methylenedioxy-4-oxo-3-quinolinecarboxylate was treated with phosphorus oxychloride. The compound obtained was the 4-chloro-2-oxo-quinoline. The structure was confirmed by ¹³C nmr and mass spectral techniques. The 2-halocarbonitrile was obtained by a Sandmeyer reaction but could not be hydrolysed into the acid.     

1,4-disubstituted pyridazino[4,5-d] pyridazines

1,4-Bis(methyIthio)pyridazino[4,5-d]pyridazine (IV) was synthesized from 4,5-pyridazinedi-carboxylic acid in three steps. By employing IV as an intermediate, various 1,4-disubstituted pyridazino[4,5-d]pyridazine derivatives of classes 1,4-N,S; 1,4-N,O; 1,4-O,S; and 1,4-O,O were prepared by one-step or two-step nucleophilic substitution reactions. Steric, polar and resonance effects were observed in some of these reactions and are discussed.     

Mass-spectrometric investigation of some 2,6-dimethyloxazolo[4,5-d]pyrimidine derivatives

The fragmentation of the molecular ions of 4-chloro- and 4-alkylamino -2,6-dimethyloxazolo[4,5-d]pyrimidines involves splitting out or fragmentation of the substituent in the 4 position or cleavage of the oxazole ring. The compositions of the fragment ions were determined on the basis of the high-resolution mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1255–1258, September, 1982.     

Nuclear magnetic resonance spectra of some 2,6-disubstituted spiro[3.3]heptane derivatives

Analysis of the full splitting pattern of the 100 MHz ¹H-NMR spectra of diethyl - 2,6 -dibromospiro[3.3]heptane - 2,6 - dicarboxylate (3) in chloroform and benzene and the 220 MHz ¹H-NMR spectrum of dimethylspiro[3.3]heptane - 2,6 - dicarboxylate (2) in naphthalene has been carried out. Puckering of the cyclobutane rings is revealed. Reasonable agreement with an X-ray study on Fecht acid (1) and with the data from the ¹C-NMR spectra of compounds 2 and 3 has been obtained. The temperature dependency of the ¹H-NMR spectra of 2, 3 and the symmetrically substituted tetraethylspiro[3.3]heptane - 2,2,6,6 - tetracarboxylate (4) has been investigated and is discussed in terms of conformational interconversion.     

Fully automated continuous flow synthesis of 4,5-disubstituted oxazoles

[Structure: see text] A multipurpose mesofluidic flow reactor capable of producing gram quantities of material has been developed as an automated synthesis platform for the rapid on-demand synthesis of key building blocks and small exploratory libraries. The reactor is configured to provide the maximum flexibility for screening of reaction parameters that incorporate on-chip mixing and columns of solid supported reagents to expedite the chemical syntheses.     

Synthesis of 3,6-disubstituted pyridazine derivatives

The synthesis of pyridazine functionalized with dioximes side chains are described. Several 3,6-disubsti-tuted pyridazine derivatives were prepared and their structures determined by spectroscopic methods (nmr, ir and ms).     

Synthesis of some new 4,5-substituted-4H-1,2,4-triazole-3-thiol derivatives

In this study appropriate hydrazide compounds, furan-2-carboxylic acid hydrazide (1) and phenylacetic acid hydrazide (2) were converted into 1,4-substituted thiosemicarbazides 4a-e and 5a-e and 4-amino-5-(furan-2-yl or benzyl)-4H-1,2,4-triazole-3-thiols 7 and 10. The 1,4-substituted thiosemicarbazides were then converted into 5-(furan-2-yl or benzyl)-4-(aryl)-4H-1,2,4-triazole-3-thiols 8a-e and 9a-e. In addition, the azomethines 11a-d and 12a-d were prepared from the corresponding arylaldehydes and the 4-amino-5-(furan-2-yl or benzyl)-4H-1,2,4-triazole-3-thiols 7 and 10. The structures of all the synthesized compounds were confirmed by elemental analyses, IR, (1)H-NMR and(13) C-NMR spectra.     

One-pot two-step microwave-assisted reaction in constructing 4,5-disubstituted pyrazolopyrimidines

[reaction: see text] A microwave-assisted reaction was developed to facilitate the construction of 4,5-disubstituted pyrazolopyrimidines. This one-pot two-step process involves a sequential S(N)Ar displacement of the C4 chloro substituent with various anilines and amines, followed by a Suzuki coupling reaction with different boronic acids. Using microwave irradiation leads to high product conversion, low side product formation, and shorter reactions.     

Liquid crystalline 1,4-disubstituted cyclohexenylene derivatives

The influence of the positions of the 1,4-cyclohexenylene fragment and its carbon-carbon double bond in the molecular core, on the mesomorphic behaviour and physical properties of 1,4-disubstituted cyclohexenylene derivatives is discussed and rationalized in terms of existing theories.