Derivatives of pyrido[2,3‐b][1,4]diazepine and of the dipyrido[1,2‐a:2′,3′‐b]imidazole heterocyclic system

With a continuing interest in heteropolycyclic systems which may show biological activities, we studied the reaction of 3‐amino‐2‐(methylamino)pyridine with diethyl 1,3‐acetonedicarboxylate in order to develop pyridodiazepinone derivatives. From the reaction mixture, we separated dipyrido[1,2‐a:2′,3′‐d]imidazole derivatives ( 3 and 4 ) besides two isomeric pyrido[2,3‐b][1,4]diazepine derivatives ( 5 and 6 ) in which the complex structural differentiation was achieved through nmr experiments and chemical evidence. Several attempts to elaborate isomers 5 and 6 have not yet given significant results.     

Identification of some isomeric 3,5-unsymmetrically substituted 1-aroyl-pyrazole derivatives by NMR spectroscopy

The ¹H and ¹³C nmr chemical shifts are used for the structural assignment of isomeric 1-aroyl-4,5-dihydro-5-hydroxy-4,4-dimethyl-1H-pyrazoles 1 unsymmetrically substituted with phenyl or methyl in the 3,5-positions of the pyrazole ring. The ¹H nmr spectra of 1-aroyl- or 1-acetyl-4-methyl-1H-pyrazoles 2 are useful in structure elucidation of unsymmetrically 3- or 5-methyl substituted derivatives.     

Synthesis and structure of some asymmetrically substituted furoxans. I

From the mixture of isomeric esters obtained by heating 3-methy 1-4-furoxancarboxylie acid ethyl ester, some furoxan derivatives have been prepared; their structures were assigned on the basis of nmr spectroscopy.     

Thiophene systems. 7. Pyrido[3,2-b]thieno[3,4-e][1,4]diazepine derivatives with potential cns activity

Pyrido[3,2-b]thieno[3,4-e][1,4]diazepines ( 1a-d ) were synthesized to investigate their potential CNS activity. Synthesis of the desired ring system was effected by condensation of 2,3-diaminopyridine ( 3 ) with methyl tetrahydro-4-oxo-3-thiophenecarboxylate ( 4 ). Structural assignment of the major condensation product 5 was determined by comparison of ¹H nmr absorptions of 5 with those of related methyl lactam derivatives 11 and 14. A discussion of the possible mechanism leading to 5 in preference to isomeric lactam 6 is presented. Biological evaluation of 1a-d revealed no interesting properties.     

Reactivity of 2-methyl-4-(1-pyrrolidinyl)-2H-1,2-benzothiazine 1,1-dioxide towards p-toluenesulphonyl azide

The 2-methyl-2H-1,2-benzothiazin-4-(3H)-one 1,1 dioxide ( 2 ), obtained according to a new, one-pot method, is transformed into the pyrrolidino enamine 3 . Reaction of p-toluenesulphonyl azide with 3 gives, via an unstable triazoline adduct which loses nitrogen, the two isomeric tosylamino derivatives 4 and 5 . The structures have been assigned by exhaustive nmr analysis and some aspects on their formation and chemical behaviour are discussed.     

Synthesis and spectra of 12-(o- and p-R-phenyl)-9,9-dimethyl-7,8,9,10,11,12-hexahydro and 8,9,10,11-tetrahydrobenz[a]acridin-11-ones. Structure correction of 1,2,3,4,5,6-hexahydro and 1,2,3,4-tetrahydro-2,2-dimethyl-5-aryl-6-aza-9,10-benzophenanthren-4-ones. II

It has been reported that the reaction of β-naphthylamine, dimedone and the appropriate aromatic aldehyde in ethanol gave 1,2,3,4,5,6-hexahydro-2,2-dimethyl-5-aryl-6-aza-9,10-benzophenanthren-4-ones, III , which upon treatment with chromic anhydride, yielded the corresponding tetrahydro derivatives, IV . However, the attempted preparation of these compounds resulted instead of the formation of isomeric acridin-11-ones, V and VI . Structures were confirmed by ir, ¹H nmr, ms and X-ray spectroscopy.     

3-Aminoacetylthiazolidine-4-carboxylate esters and their l-thia-4-azaspiro[4.5]decane-3-carboxylate derivatives. Synthesis and stereochemical properties

Dimethyl thiazolidine-2,4-dicarboxylate 2 and ethyl l-thia-4-azaspiro[4.5]decane-3-carboxylates 3-5 were obtained as a diastereoisomeric mixture while their 3-aminoacetyl derivatives were isolated in only one isomeric form. These reactions of N-acylation were stereoselective, which can be explained by an interconversion of the diastereoisomers via a seco intermediate. The ¹H nmr analysis of amides 6 and 11 exhibited the presence of both cis and trans amide bond conformations, whereas only one cis conformation was observed for spiro amides 8-10 and 13-15.     

Free radical 4‐nitrophenylation of thieno[2,3‐b]pyridine. Part 2: Isolation and structural studies of three samples of mono (4‐nitrophenyl) products; relative yields of the five possible isomers

From the crude mixtures of isomeric 4‐nitrophenylthieno[2,3‐b]pyridines ( 3 ) previously reported [1] were isolated three analytically pure samples, viz. the 2‐isomer (yellow needles, mp 258°, 3a ), the 6‐isomer (red prisms, mp 182°, 3e ), and a ternary mixture of the 2‐, 3‐, and 4‐isomers (orange needles, mp 213°, 3a:3b:3c = 1.3:1.0:0.5). The 258° compound was identified as either 3a or 3b by its ¹H nmr spectrum and definitively as the former by its x‐ray crystallographic analysis. The isomeric identities of the 182° and 213° samples were established from their ¹H nmr spectra only. No 5‐isomer ( 3d ) was identified. Semi‐quantitatively, relative isomeric yields fit the pattern 2‐ (64%)>>6‐ (14%)≥3‐ (12%)>4‐ (6%)≥5‐(≤4%). Crystallographic data for 3a are presented.     

Synthesis and stereochemistry of new trihydrodiazabicyclo-[3.m.n]alkano[4′,5′:1,2]pyrido[3,4-b]indole ring system

The classical Pictet-Spengler reaction of tryptamine with the isomeric N-benzylpiperidones 3a, 3b and N-benzylpyrrolidone 3c yielded the spiro derivatives of 1,2,3,4-tetrahydro-β-carboline 5a, 5b and 5c . Cyclocon-densation of the spirotetrahydrocarboline with chloroacetic chloride and the subsequent reductive debenzylation afforded the new ring systems of trihydrodiazabicyclo[3.m.n]alkano[4′,5′:1,2]pyrido[3,4-b]indoles 8a , 8b , and 8c . The structures of the bicyclic systems 8a, 8b , and 8c were determined by using both, high-resolution ¹H and ¹³C nmr techniques and force field and MNDO calculations.     

Synthesis and spectra of 7-(o- and p-R-phenyl)-10,10-dimethyl-8,9,10,11-tetrahydrobenz[c]acridin-8-ones. Structure correction of 1,2,3,4-tetrahydro-2,2-dimethyl-5-aryl-6-aza-7,8-benzophenanthren-4-ones

It has been reported that dimedone added to α-arylidennaphthylamines in ethanol with formation of 1,4-addition products derivatives of 5-aryl-5,6,7,8,9,10-hexahydrobenzo[c]phenanthridin-7-ones, III , which are easily oxidized by chromic anhydride to the corresponding tetrahydro derivatives, IV . However, the attempted preparation of these compounds resulted instead of the formation of isomeric acridin-8-ones V and VI . Structures were confirmed by ir, ¹ H nmr, ms and X-ray spectroscopy.     

Studies on v-triazoles. Part V. Acylation,alkylation and sulphonation reactions of ethyl 5-(4-hydroxyphenoxy)-1H-v-triazole-4-carboxylate

The alkylation of 5-(4-hydroxyphenoxy)-1H-v-triazolecarboxylate ( 1 ) under alkaline conditions was shown to yield exclusively isomeric N-2 and N-3 alkylation products, the structures of which were assigned by ir, ¹H nmr and, ³C nmr spectroscopy. Acylation and sulphonation under similar conditions resulted in exclusive attack at the phenolic oxygen of 1 , possibly by the migration of an initially formed N-derivative.     

Studies on quinoline derivatives and related compounds. II. Synthesis of 5-substituted 1-ethyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid

The cyclization of m-substituted anilinomethylenemalonates ( 1 ) in the presence of polyphosphate ester and some other cyclizing agents gave mixtures of the isomeric ethyl 5- ( 2 ) and 7-substituted 4-hydroxy-3-quinolinecarboxylates ( 3 ), which led to mixtures of the corresponding quinolinecarboxylic acids ( 4 and 5 ) by hydrolysis. The proportions of 4 and 5 in the mixtures were determined on the basis of their nmr spectra. Novel 5-chloro- ( 8a ), 5-methyl- ( 8b ) and 5-nitro-1-ethyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids were prepared and evaluated for antimicrobial activities. No significant activity, however, was noted.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 17. Thieno[3′,2′:4,5]thieno[2,3-c]naphtho-[2,1-f]quinoline and thieno[3′,2′:4,5]thieno[2,3-c]-naphtho[1,2-g]quinoline

The synthesis of two previously unknown novel polycyclic heterocyclic ring systems via photocyclization is described. The structural assignment of the isomeric ring systems, 4 and 5 , was achieved by the total assignment of their ¹H and ¹³C nmr spectra by the concerted usage of two-dimensional nmr methods.     

Synthesis of C-glycosylindazoles by 1,3-dipolar cycloaddition of α-Diazoketoses to benzynes

A number of C-glycosylindazoles were prepared by 1,3-dipolar cycloaddilion of several α-diazoketoses to benzyne. When the cycloaddition reaction was carried out with benzyne derivatives the two possible isomeric indazoles were obtained in most of the cases. Structural assignments were made on the basis of nmr data.     

Spectroscopic identification of some derivatives of 3,4-diamino-4H-1,2,4-triazole and 3-Hydrazino-4H-1,2,4-triazole

Spectroscopic methods (ir, ¹H- and ¹³C-nmr, ms and uv) have been used for the structural elucidation and identification of different isomeric 1,2,4-triazole derivatives, obtained by cyclisation reactions from appropriate diaminoguanidines. The four compounds 3,4-diamino-4H-1,2,4-triazole, 3-hydrazino-4H-1,2,4-triazole, 3-amino-4-(2,6-dichlorobenzylideneamino)-4H-1,2,4-triazole and 3-(2,6-dichlorobenzylidenehydrazino)-4H-1,2,4-triazole, were chosen as representative structures to illustrate the general spectroscopic properties for 3,4-diamino- and 3-hydrazino-substituted 4H-1,2,4-triazoles and the corresponding hydrazones, with different substituents in the 5-position of the triazole ring (alkyl-, aralkyl-, mercapto-, hydroxy- and amino-groups). Nmr and uv spectroscopy were found to be the best methods for confirmation of the different series of hydrazones, while ir and nmr were found to be suitable for the structural elucidation of compounds in the series of 3,4-diamino- and 3-hydrazino-4H-1,2,4-triazoles, respectively.     

Nitro derivatives of 1-picrylbenzotriazole

The synthesis of the isomeric 4,6-, 5,6-, and 5,7-dinitro-1-picrylbenzotriazoles has been accomplished. The nmr spectra of these compounds and the mononitro derivatives of 1-picrylbenzotriazole were determined and the substituent effects of the nitro and picryl groups on the chemical shifts of the various benzotriazole protons are discussed.     

Synthesis of 4,4-disubstituted piperidine analogs of (±)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide

Condensation of (±)-1-benzyl-3-methyl-4-piperidone ( 1 ) with aniline followed by trapping of the intermediate imine with cyanide generated a mixture of isomeric nitriles 2A and 2B , the structures of which were established unambiguously by obtaining an X-ray crystal structure on nitrile 2B . Subsequent elaboration of the nitrile intermediates provided analogs of (±)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide having a second substituent (carbomethoxyl, carboethoxyl, methoxymethyl) at the piper-idine 4-position. The conversion of the carboxamide intermediates 3A and 3B to the carboalkoxyl intermediates 5A, 5B and 6A was accomplished utilizing a modified esterification procedure. Proton nmr data are presented for both the final products and the key synthetic intermediates.     

Benzofuran systems. Synthesis and biological examination of 1-(3-benzofuranyl)-2-phenylethanones

Novel 1-(3-benzofuranyl)-2-phcnylethanones 4a-d have been prepared by acetylation of 2-alkylbenzo-furans 2a-c with phenylacetyl chlorides 3a-b . The methoxy derivatives 4b-d have been demethylated to the corresponding phenols 5b-d with pyridinium hydrochloride. An attempt to obtain the derivatives of 4d and 5a iodinated in the phenyl ring has been undertaken. The novel compounds have been characterized by ir and nmr spectra and their biological activity examined.     

Synthesis of some isomeric 4-ethoxycarbonyl-3-and 5-(1- and 2-hydroxyalkyl)-1,3- and 1,5-dimethylpyrazoles from 3-(2H)furanones and 2,3-dihydro-4-pyrones

The title compounds were prepared by reaction of 3-(2H)furanones and 2,3-dihydro-4-pyrones with methylhydrazine or alternatively by methylation of the corresponding N-unsubstituted pyrazoles. ¹³C and ¹H nmr were used to assign the isomeric 3-methyl or 5-methyl structures.     

Recent work on the synthesis of 3,6-dibenzoylcarbazole

By heating carbazole ( 1 ) with aluminum trichloride and benzoyl chloride four benzoylcarbazole derivatives were obtained: N-benzoylcarbazole ( 2 ), 1-benzoylcarbazole ( 3 ), 3-benzoylcarbazole ( 4 ) and 3,6-dibenzoylcarbazole ( 5 ). The complete characterization of benzoylcarbazole derivatives 2–5 was performed by physical and spectroscopical methods (mp, tlc R_f, glc T_r, uv, ir, ¹H nmr, ¹³C nmr and ms).