New heterocyclic ring systems. XI. Azadithiasteroid analogues

Synthesis of the title compounds has been achieved starting from 4-oxo-3,4-dihydro-2H,5H-thiopyrano[3,2-c][1]benzothiopyran 6,6-dioxide (III), which was converted to glyoxylate (IV), β-ketoester (V), difluoride complex (VII) and β-diketone (XII) gave with hydrazine, hydroxyl-amine and glycine ethyl ester several azadithiasteroid analogues.     

Reaction of heterocyclic diazonium salts with hydrazones

Depending on the nature of the heteroring and the hydrazone, a formazan or a heterylazophenylhydrazone are formed in the reaction of an aryl hydrazone with the diazonium salt obtained from a heterocyclic amine. Disproportionate to form a triphenylformazan is also possible.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1062–1064, August, 1972     

Derivatives of heterocyclic α-iminocarboxylic acids. 1. Syntheses of hydrazides of heterocyclic α-iminocarboxylic acids and their hydrazones

By the interaction of esters of L-proline, L-thioproline, pipecolic acid, and tetrahydro-1,4-thiazine-3-carboxylic acid with hydrazine, the corresponding hydrazides were obtained, which react with equimolar quantities of carbonyl compounds to form hydrazones consisting of mixtures of rotational isomers relative to the amide bond.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1277–1282, September, 1993.     

New heterocyclic ring systems. IX. Polyazadithiasteroid analogues

The synthesis of the novel tricyclic ring 5-rnethyl-4-oxo-2,3,4,5-tetrahydrothiopyrano[3,2-c]-[1,2]benzothiazine 6,6-dioxide (III) is described. By the reaction of hydrazine and hydroxylamine with the glyoxylate (IV) and ester (V) obtained from III, several polyazadithiasteriod analogues have been synthesized.     

Synthesis of heterocyclic propellanes. Preparation and transannular reactions of 5-ethoxycarbonylmethylene-cyclooctanone and the corresponding oximes and hydrazones

5-Ethoxycarbonylmethylene-cyclooctanone ($\text{3}$) is prepared by Wittig monoolefination of dione $\text{1}$ with phosphorus ylide $\text{2}$. Thermal transannular cyclization of oxime $\text{6}$ and phenylhydrazone $\text{12}$ of the ketone $\text{3}$ affords 3-oxa-2-aza- and 2,3-diaza[3.3.3] propellanes $\text{7}$ and $\text{14}$ respectively. Irradiation of ketone $\text{3}$, its oxime $\text{9}$, and its dimethylhydrazone $\text{16}$ furnish 9-oxa-, and 9-aza[3.3.2] propellanes $\text{11}$, $\text{10}$, and $\text{17}$, respectively. In addition to the propellane $\text{14}$, phenylazobicyclo compound $\text{13}$ is also obtained from phenylhydrazone $\text{12}$. The acetyl derivatives $\text{8}$ and $\text{15}$ of propellanes $\text{7}$ and $\text{14}$ are also prepared and studied.     

Thallation-iodination studies of heterocyclic systems

The thallation-iodination of 3-carbonylindoles ( 4a-f ) results in orientation control with substitution occurring at the 4-position ( 6a-f ). Also described is the dithallation of N-methylpyrrole-2-carboxaldehyde ( 2 ).     

New heterocyclic ring systems. XIII. 7,11-Dithiaazasteroid analogues

Synthesis of the tittle compounds has been achieved starting with the new tricyclic ring, 6-methyl-4-oxo-3,4-dihydro-2H,6H-thiopyrano[3,2-c][2,1]benzothiazine 5,5-dioxide (III). This compound was converted to the glyoxylate VI, the β-ketoester IX, a difluoride complex XIII and an enamino ketone XXIV which, by hydrazine, hydroxylamine and glycine treatment, gave 7,11-dithiaazasteroid analogues. Some unexpected products were also obtained from the ketone XVIII and the β-diketone XIX by treatment with chloroacetone and hydrazine respectively.     

Cyclization of ylidenemalononitriles. VII. Studies on sulfur-containing heterocyclic systems

Ring closure of ylidenemalononitrile adducts has been extended to the syntheses of isomeric sulfur heterocycles. The malononitrile derivatives of thiochromanone, thiochromone and iso-thiochromanone have been synthesized, and results of the acidic ring closure experiments on these compounds are reported. The thiochromanone adducts gave an interesting disproportionation reaction, and experiments designed to support the proposed route are presented.     

The directing effect of annelated rings in aromatic systems—XI : Bromination of bicyclic phenols with heterocyclic annelated rings

Bicyclic phenols of type 1 with annelated rings containing a N or an O heteroatom (X = N or O) as well as the ring opened analogs have been brominated and the product distribution determined. The results indicate that while most annelated rings have a directing effect to the ar-β position of the molecule, a 6-membered annelated ring is an exception and it facilitates substitution in the ar-α position.     

Studies on the synthesis of heterocyclic compounds. XI. Cleavage of 1,3-benzodioxoles by magnesium bromide-acetic anhydride

The cleavage reaction of some 1,3-benzodioxole derivatives with magnesium bromide and acetic anhydride has been studied. The reactions have been carried out in acetonitrile solution at room temperature. In all of the 1,3-benzodioxoles studied, the opening of the heterocyclic ring with formation of bromides, alkenes and their corresponding products of hydrolysis have been observed. The competitive electrophilic substitution on the benzene ring was very limited and was insignificant when a large excess of the cleavage reagent was used. The structures of newly prepared compounds have been determined by elemental analysis, spectroscopic data and comparison with authentic samples.     

Synthesis of fused purinoquinazolines. Three new heterocyclic ring systems

The Ullmann reaction of 8-aminotheophylline or 8-aminocaffeine with 2-chlorobenzoic acid and of 8-bromotheophylline with ethyl-2-aminobenzoate afforded derivatives of three new heterocyclic systems: purino[7,8-α]quinazoline-5,9,11(6H,8H,10H)-trione, purino[8,9-b]quinazoline-2,4,11(1H,3H,5H)-trione and purino[8,7-b]quinazoline-2,4,6(1H,3H,11H)-trione, respectively.     

Synthesis of new condensed heterocyclic systems

Two new diamines — [1,3-bis(5-phenyl-1,2,4-triazol-3-yl)-4,6-diamino]benzene and [1,3-di-(2-benzimldazolyl)-4,6-diamino]benzene — were synthesized from 4,6-dinitroisophthalic acid. Newheterocyclic systems — 3,5,9,11-tetraphenyl[benzo[1,2-a; 4,5-a]bis(1,2,4-triazolo[4,3-c]pyrimidine)] and 2,16-diphenyl[benzo[1,2-a;4,5-a']bis(pyrimido[1,6-a]benzimidazole)]—were obtained by reaction of the diamines with benzoyl chloride and subsequent cyclization.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1274–1277, September, 1977.     

Studies in the heterocyclic series. XI. Reactions of 2-Amino-3-hydroxypyridine with 2-Chloro-3-nitropyridine

The reactions of 2-amino-3-hydroxypyridine and 2-chloro-3-nitropyridine in various solvents and in the presence of certain catalysts were studied. A dilute acid-catalysed procedure led to a 45% yield of 3-hydroxy-3-nitro-2,2-dipyridylamine which was also obtained by refluxing in alcoholic potassium hydroxide for several hours. The diarylamine was converted to 1,9-diazaphenoxazine by base-catalysed intramolecular condensation in refluxing DMSO. The same diazaphenoxazine was obtained directly by prolonged base-catalysed reaction of the starting pyridine compounds in DMSO. From a study of the infrared spectrum of the diarylamine precursor, it was found that strong NHO hydrogen bonding is responsible for the failure of the cyclization step in either aqueous or alcoholic base. This problem was overcome by the use of DMSO as the reaction solvent. Structural assignments were made by a study of their ultraviolet, infrared, nmr and mass spectra and the mechanistic pathways were also discussed.     

Investigation of condensed heterocyclic pyrimido systems

2-Phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimtdine-5,7-dione reacts with several nucleophilc reagents via a scheme involving nucleophilic addition with opening of the dioxopyrimidine ring at the C-N bond in the 7–8 positions. The reaction may serve as a method for the synthesis of some asymmetrical pyrazolyl derivatives of malonic acid.See [1] for communication I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1145–1147, August, 1971.     

Catalytic asymmetric hydrogenation of heterocyclic ketone-derived hydrazones, pronounced solvent effect on the inversion of configuration

An enantioselective hydrogenation of hydrazones derived from heterocyclic ketones was developed with up to 85% ee. The enantiomeric purity was enriched to >99% ee by crystallization from EtOAc in >80% yield. Optimization studies have revealed a notable solvent effect that resulted in inversion of enantioselectivity from 85% ee in MeOH to −27% ee in DCE. The hydrazone geometry and possible hydrogenation via endocyclic alkene were examined as possible factors for the inversion of enantioselectivity.     

Molecular associations in acacia gums

The tendency of polysaccharides to associate in aqueous solution has long been recognised. Molecular associations can profoundly affect their performance in a given application due to its influence on the molecular weight, shape and size. This will ultimately determine how the molecules will interact with each other, with other molecules and with water. There are several factors, such as hydrogen bonding, hydrophobic association, ion mediated association, electrostatic interaction, concentration dependence and the presence of proteinaceous components, which affect this behaviour. Our objective is to highlight the role of the proteinaceous component, present in acacia gum, to promote associations when the gum is subjected to various processing treatments such as maturation, spray drying and irradiation. The results demonstrate the ability of the proteinaceous component to promote hydrophobic associations which influence the size and proportion of the arabinogalactan high molecular weight component (AGP). Heat treatment in solid state (maturation) increases the hydrophobic character of the gum and hence its emulsification performance. Spray drying also involves aggregation through hydrophobic association but changes the surface properties of peptide moieties to become more hydrophilic compared to the association promoted by the maturation treatment in the solid state. Irradiation induced cross-linking, in the presence of unsaturated gas, was used to introduce C–C bonds into the carbohydrate moiety and thus confirms the hydrophobic association prompted by the heat used in the maturation and spray drying. This association can be reversed by treatments, such as filtration or high pressure homogenisation. The results reported here reconcile the contradiction about structure of gum arabic proposed by the wattle-blossom and twisted hairy rope models and shows that the AGP fraction is basically an aggregated fraction made up of AG units stabilized by low molecular weight highly proteinaceous components.

New heterocyclic ring systems. XII. Synthesis of [1,4]thiazinocarbazoles

Five [1,4]thiazinocarbazoles have been synthesized from 6-, 7- and 8-amino-2H[1,4]benzo-thiazin-3(4H)ones by the Jaap-Klingemann reaction with 2-hydroxymethylenecyclohexanone followed by Fischer indolisation of the resulting hydrazones. The structures of the hitherto unknown ring systems have been confirmed by pmr spectral data.     

Research on heterocyclic compounds. XXIII. Phenyl derivatives of fused imidazole systems

The reaction of various heteroarylamines with ethyl 2-benzoyl-2-bromoacetate was used to obtain some imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, imidazo[2,1-b]thiazoles and imidazo[2,1-b]benzothiazoles characterized by the presence of a phenyl moiety on the imidazole ring. In the case of thiazole and benzothiazole derivatives, unexpected by-products were isolated and their structures elucidated.     

Neutral homoaromaticity in some heterocyclic systems

[reaction: see text] Neutral homoaromaticity has been evaluated in heterocyclic systems related to the bicyclo[3.2.1]octane skeleton with replacement of CH(2) at C-2 in bicyclo[3.2.1]octa-3,6-diene with X = BH, AlH, Be, Mg, O, S, PH, NH (12); replacement of CH at C-3 in bicyclo[3.2.1]octa-3,6-dien-2-yl anion with PH, S, NH, O (13); and replacement at C-2 and C-3 with N and O (14). Stabilization energies (SE) are evaluated using density functional theory and homodesmotic equations at the B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d) level for series 12-14. Stabilization energies are compared with diamagnetic susceptibility exaltations, Lambda, CSGT-B3LYP/6-31G(d)//B3LYP/6-31G(d), and nucleus-independent chemical shifts (NICS), GIAO-B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d). Analysis of frontier orbitals and geometries, B3LYP/6-31G(d)//B3LYP/6-31G(d), and proton affinities of 2-azabicyclo[3.2.1]octa-3,6-diene, pyrrole, and related model systems, B3LYP/6-311+G(2d,2p)//B3LYP/6-31G(d), provide complementary evidence supporting the division of the substrates evaluated into antihomoaromatic (12, X = BH, AlH, and Be), nonhomoaromatic (12, X = O, S, NH, PH), and homoaromatic (13, X = S, PH, NH, O and 14 X = ON), with 12 (X = Mg) appearing as transitional between anti- and nonhomoaromatic.