Synthesis of new hetero[1,2,4]thiadiazin‐3‐one S,S‐dioxides and oxazolo[3,2‐b]hetero[1,2,4]thiadiazine S,S‐dioxides as potential psychotropic drugs

A series of 2‐substituted 2H‐thieno[3,4‐e][1,2,4]thiadiazin‐3(4H)‐one 1,1‐dioxides ( 2 ), 2‐substituted 2H‐thieno[2,3‐e][1,2,4]thiadiazin‐3(4H)‐one 1,1‐dioxides ( 3 ), 2‐substituted 4,6‐dihydropyrazolo[4,3‐e]‐[1,2,4]thiadiazin‐3(2H)‐one 1,1‐dioxides ( 4 ), 2‐substituted 2,3‐dihydrooxazolo[3,2‐b]thieno[3,4‐e]‐[1,2,4]thiadiazine 5,5‐dioxides, ( 5 ), 6‐substituted 6,7‐dihydro‐2H‐oxazolo[3,2‐b]pyrazolo[4,3‐e][1,2,4]thia‐diazine 9,9‐dioxides ( 6 ) and 7‐substituted 6,7‐dihydro‐2H‐oxazolo[3,2‐b]pyrazolo[4,3‐e][1,2,4]thiadiazine 9,9‐dioxides ( 7 ) were synthesized as potential psychotropic agents.     

Synthesis of a novel series of 6‐chloro‐1,4,2‐benzodithiazine 1,1‐dioxide derivatives with potential biological activity

A novel series of 6‐chloro‐1,4,2‐benzodithiazine 1,1‐dioxide derivatives 2‐19 with alkyl, aryl or het‐eroaryl substituents at position 3 have been synthesized by the reaction of 4‐chloro‐2‐mercaptobenzenesul‐fonamides with aldehydes, aldehyde acetals or acid anhydrides. 6‐Chloro‐3‐(2‐hydroxyphenyl)‐7‐methyl‐2,3‐dihydro‐l,4,2‐benzodithiazine 1,1‐dioxide (7) exhibited remarkable activity on the leukemia CCRF‐CEM cell line (GI₅₀<10 nM) and moderate activity against the other 49 human tumor cell lines derived from nine different cancer type.     

An easy route to 2‐substituted‐2,3‐dihydro‐5(7)H‐oxazolo[3,2‐a]pyrimidin‐5‐ones and 7‐ones starting from the corresponding 2‐amino‐2‐oxazolines

The isomeric 2‐substituted‐7(5)‐methyl‐2,3‐dihydro‐5(7)H‐oxazolo[3,2‐a]pyrimidin‐5‐ones 3a‐b and 7‐ones 2a‐b,7a were synthesized by cyclocondensation from the 5‐substituted‐2‐amino‐2‐oxazolines 1a‐b with biselectrophiles. In boiling ethanol, the reaction of 1a‐b with acetylenic esters led to a mixture of 2a‐b,7a with a small amount of (E)‐2‐N‐(2‐ethoxycarbonylethylene)‐5‐substituted‐2‐iminooxazolines 5a‐b . The ring annulation between 1a‐b and diketene gave the 2‐substituted‐7‐hydroxy‐7‐methyl‐2,3,6,7‐tetrahydro‐5H‐oxazolo[3,2‐ a ]pyrimidin‐5‐ones 4a‐b which can be easily dehydrated to provide the 2‐substituted‐7‐methyl‐2,3‐dihydro‐5H‐oxazolo[3,2‐a]pyrimidin‐5‐ones 3a‐b .     

Hydriodic Acid‐Mediated Cyclization of α‐Substituted Secondary 2‐Ethenylbenzamides: Synthesis of 2‐Substituted 2,3‐Dihydro‐3,3‐dimethyl‐1H‐isoindol‐1‐ones and 3,3‐Disubstituted (E)‐1‐(Arylimino)‐1,3‐dihydroisobenzofurans

A new and facile method for the preparation of 2‐substituted 2,3‐dihydro‐3,3‐dimethyl‐1H‐isoindol‐1‐ones 3 and 3,3‐disubstituted (E)‐1‐(arylimino)‐1,3‐dihydroisobenzofurans 6 has been developed. Thus, treatment of N‐alkyl(or aryl)‐2‐(1‐methylethen‐1‐yl)benzamides 2 with concentrated hydriodic acid (HI) in MeCN at room temperature afforded 3 . Similar treatment of N‐aryl‐2‐(1‐phenylethen‐1‐yl)benzamide 5 with concentrated HI at 0° afforded 6 .     

A Facile Synthesis of Oxoindenothiazine and Dioxospiro(indene‐2,4′‐thiazine) Derivatives from (Substituted ethylidene)hydrazinecarbothioamides

(E)‐2‐[2‐(1‐Substituted ethylidene)hydrazinyl]‐5‐oxo‐9b‐hydroxy‐5,9b‐dihydroindeno[1,2‐d][1,3]‐thiazine‐4‐carbonitriles and (E)‐5‐oxo‐[(E)‐(1‐substituted ethylidene)hydrazinyl]‐2,5‐dihydroindeno[1,2‐d][1,3]thiazine‐4‐carbonitriles have been obtained from the reaction of 2‐(substituted ethylidene)hydrazinecarbothioamides with 2‐(1,3‐dioxo‐2,3‐dihydro‐1H‐inden‐2‐ylidene)propanedinitrile ( 1 ) in ethyl acetate solution. However, (Z)‐6′‐amino‐1,3‐dioxo‐3′‐substituted‐2′‐[(E)‐(1‐phenylethylidene)hydrazono]‐1,2′,3,3′‐tetrahydrospiro(indene‐2,4′‐[1,3]thiazine)‐5′‐carbonitriles were observed during the reaction of N‐substituted‐2‐(1‐phenylethylidene)hydrazinecarbothioamides with ( 1 ). The structure assignment of products has been confirmed on the basis of ¹H‐, ¹³C‐NMR, and mass spectrometry, as well as theoretical calculations.     

Synthesis and Functionalization of 8‐Methyl‐2h‐pyrimido [2,1‐c][1,2,4]triazine‐3,6(1h,4h)‐dione

6‐Methyl‐2‐methylthio‐4‐oxopyrimidin‐3(4H)‐yl)acetohydrazide on heating in benzylamine undergo cyclization to 8‐methyl‐2H‐pyrimido[2,1‐c][1,2,4]triazine‐3,6(1H, 4H)‐dione, which under treatment with bromine in glacial acetic acid was converted to 7‐bromo substituted derivative and at reflux with Lawesson's reagent yielded 3‐thioxo compound. The latter reacted with primary and secondary amines to give 3‐amino substituted pyrimidotriazines and on alkylation—the corresponding S‐alkyl derivatives.     

The Pseudo‐Michael Reaction of 2‐Hydrazinylidene‐1‐Arylimidazolidines with Diethyl Ethoxymethylenemalonate

The pseudo‐Michael reaction of 2‐hydrazinylidene‐1‐arylimidazolidines with diethyl ethoxymethylenemalonate (DEEM) was investigated. The reaction yields the chain adduct, namely diethyl{[2‐(1‐arylimidazolidin‐2‐ylidene)hydrazinyl]methylidene}propanedioates. This is contrary to the pseudo‐Michael reaction of DEEM with 1‐aryl‐4,5‐dihydro‐1H‐imidazol‐2‐amines that does not allow isolation of chain derivatives and leads to cyclic imidazo[1,2‐a]pyrimidine derivatives while even at thermodynamic control. At first cyclization of diethyl{[2‐(1‐arylimidazolidin‐2‐ylidene)hydrazinyl]methylidene}propanedioates leads to ethyl 1‐aryl‐5(1H,8H)oxo‐2,3‐dihydro‐imidazo[2,1‐c][1,2,4]triazepine‐6‐carboxylates. 1,5‐Sigmatropic shift, following the cyclization, caused isomerization of 5(1H,8H)oxo‐2,3‐dihydro‐imidazo[2,1‐c][1,2,4]triazepine‐6‐carboxylates to ethyl 1‐aryl‐5(1H)hydroxy‐2,3‐dihydroimidazo[2,1‐c][1,2,4]triazepine‐6‐carboxylates. Presence of both isomers in the reaction product was detected in the NMR spectra. The structure of all the compounds was confirmed with spectroscopic studies (¹H NMR and MS). The structure of diethyl{[2‐(1‐phenylimidazolidin‐2‐ylidene)hydrazinyl]methylidene}propanedioate was also confirmed by X‐ray crystallography. In the addition reaction, thermodynamics and HOMO–LUMO orbitals of the reactants were studied by using quantum chemical calculations.     

Quinolone analogues 2. A facile synthesis of novel 3‐substituted 1‐alkyl‐4‐oxo‐1,4‐dihydropyridazino[3,4‐b]quinoxalines

The reaction of the 2‐(1‐alkylhydrazino)‐6‐chloroquinoxaline 4‐oxides 1a,b with diethyl acetone‐dicarboxylate or 1,3‐cyclohexanedione gave ethyl 1‐alkyl‐7‐chloro‐3‐ethoxycarbonylmethylene‐1,5‐dihydropyridazino[3,4‐b]quinoxaline‐3‐carboxylates 5a,b or 6‐alkyl‐10‐chloro‐1‐oxo‐1,2,3,4,6,12‐hexahydroquinoxalino[2,3‐c]cinnolines 7a,b , respectively. Oxidation of compounds 5a,b with nitrous acid afforded the ethyl 1‐alkyl‐7‐chloro‐3‐ethoxycarbonylmethylene‐4‐hydroxy‐1,4‐dihydropyridazino‐[3,4‐b]quinoxaline‐4‐carboxylates 9a,b , whose reaction with base provided the ethyl 2‐(1‐alkyl‐7‐chloro‐4‐oxo‐1,4‐dihydropyridazino[3,4‐b]quinoxalin‐3‐yl)acetates 6a,b , respectively. On the other hand, oxidation of compounds 7a,b with N‐bromosuccinimide/water furnished the 4‐(1‐alkyl‐7‐chloro‐4‐oxo‐1,4‐dihydropyridazino[3,4‐b]quinoxalin‐3‐yl)butyric acids 8a,b , respectively. The reaction of compound 8a with hydroxylamine gave 4‐(7‐chloro‐4‐hydroxyimino‐1‐methyl‐1,4‐dihydropyridazino[3,4‐b]quinoxalin‐3‐yl)‐butyric acid 12 .     

Synthesis of novel 6,7‐dihydro‐5H‐pyrimido[4,5‐e][1,4]diazepin‐8(9H)‐ones

A new method was developed for the synthesis of 6,7‐dihydro‐5H‐pyrimido[4,5‐e][1,4]diazepin‐8(9H)‐one derivatives. The key to construct the pyrimido[4,5‐e][1,4]diazepine core is the intramolecular amidation of N‐((4‐amino‐6‐chloropyrimidin‐5‐yl)methyl)‐substituted amino acid esters. This methodology was validated through the preparation of 13 representative 6,7‐dihydro‐5H‐pyrimido[4,5‐e][1,4]diazepin‐8(9H)‐ones in moderate to good yields. J. Heterocyclic Chem., (2011).     

2‐Triazolylpyrimido[1,2,3‐cd]purine‐8,10‐diones via 1,3‐dipolar cycloadditions to 2‐ethynylpyrimido[1,2,3‐cd]purine‐8,10‐dione

This paper presents the synthesis of a series of 5,6‐dihydro‐4H,8H‐pyrimido[1,2,3‐cd]purine‐8,10(9H)‐dione ring system derivatives with a [1,2,3]triazole ring bonded in position 2. The procedure is based on cycloaddition of substituted alkyl azides to the terminal triple bond of 5,6‐dihydro‐2‐ethynyl‐9‐methyl‐4H,8H‐pyrimido[1,2,3‐cd]purine‐8,10(9H)‐dione ( 4 ). This cycloaddition produced two regioisomers ?5,6‐dihydro‐9‐methyl‐2‐(1‐substituted‐1H‐[1,2,3]triazol‐5‐yl)‐4H,8H‐pyrimido[1,2,3‐cd]purine‐8,10(9H)‐dione ( 7 ) and 2‐(1‐substituted‐1H‐[1,2,3]triazol‐4‐yl) derivative 8 . The required 2‐ethynyl deriva tive 4 was obtained from the starting 2‐unsubstituted compound 1 by bromination to yield the 2‐bromo derivative 2 , which was converted by Sonogashira reaction to trimethylsilylethyne 3 and finally, the protective trimethylsilyl group was removed by hydrolysis.     

Novel Compounds with a Viologen Skeleton and N‐Heterocycles on the Peripheries: Electrochemical and Spectroscopic Properties

The present article deals with novel compounds comprising a redox‐active group as core and a nucleobase in the peripheries, linked covalently via a spacer. The new derivatives 1,1′,1″‐(benzene‐1,3,5‐triyltrimethanediyl)tris{1′‐[3‐(3,4‐dihydro‐5‐methyl‐2,4‐dioxopyrimidin‐1(2H)‐yl)propyl]‐4,4′‐bipyridinium} hexafluorophosphate ( 1 ), 1,1′,1″‐(benzene‐1,3,5‐triyltrimethanediyl)tris{1′‐[2‐(4‐chloro‐7H‐pyrrolo[2,3‐d]pyrimidine‐7‐yl)ethyl]‐4,4′‐bipyridinium} hexachloride ( 2a ) 1

1 The numbering of the pyrrolo[2,3‐d]pyrimidine system follows the IUPAC rules and is different from that of the purine ring system.

, and 1,1′,1″‐(benzene‐1,3,5‐triyltrimethanediyl)tris{1′‐[2‐(2‐amino‐4‐chloro‐7H‐pyrrolo[2,3‐d]pyrimidine‐7‐yl)ethyl]‐4,4′‐bipyridinium} hexabromide ( 2b )¹) were synthesized by nucleobase‐anion alkylation and linked to the 4,4′‐bipyridinium core. UV and CV analyses of these compounds were performed and revealed significantly different properties.     

Synthesiss of novel 3‐(2‐thienyl)‐1,2‐diazepino[3,4‐b]quinoxalines with algicidal activity

The reaction of the quinoxaline N‐oxide 1 with thiophene‐2‐carbaldehyde gave 6‐chloro‐2‐[1‐methyl‐2‐(2‐thienylmethylene)hydrazino]quinoxaline 4‐oxide 5 , whose reaction with 2‐chloroacrylonitrile afforded 8‐chloro‐2,3‐dihydro‐4‐hydroxy‐1‐methyl‐3‐(2‐thienyl)‐1H‐1,2‐diazepino[3,4‐b]quinoxaline‐5‐carbonitrile 6 . The reaction of compound 6 with various alcohols in the presence of a base effected alcoholysis to provide the 5‐alkoxy‐8‐chloro‐2,3,4,6‐tetrahydro‐1‐methyl‐4‐oxo‐3‐(2‐thienyl)‐1H‐1,2‐diazepino[3,4‐b]‐quinoxalines 7a‐d . The reaction of compounds 7a and 7b with diethyl azodicarboxylate effected dehydrogenation to give the 5‐alkoxy‐8‐chloro‐4,6‐dihydro‐1‐methyl‐4‐oxo‐3‐(2‐thienyl)‐1H‐1,2‐diazepino[3,4‐b]‐quinoxalines 8a and 8b , respectively. Compounds 8a and 8b were found to show good algicidal activities against Selenastrum capricornutum and Nitzchia closterium.     

An efficient and regiospecific preparation of trifluoromethyl substituted 4‐( 1H‐pyrazol‐1 ‐yl)‐7‐chloroquinolines

A new series of 4‐[3‐alkyl(aryl)(heteroaryl)‐5‐hydroxy‐5‐trifluoromethyl‐4,5‐dihydro‐1H‐pyrazol‐1‐yl]‐7‐chloroquinolines, where [alkyl = CH₃; aryl = C₆H₅, 4‐CH₃C₆H₄, 4‐FC₆H₄, 4‐ClC₆H₄, 4‐BrC₆H₄, 4‐CH₃OCgH₄, 4‐NO₂CgH₄, 4‐biphenyl, 1‐naphthyl; heteroaryl = 2‐furyl and 2‐thienyl] has been regiospecifi‐caly obtained from the reaction of 7‐chloro‐4‐hydrazinoquinoline with 4‐substituted‐l,1,1‐trifluoro‐4‐methoxybut‐3‐en‐2‐ones in 61 ‐ 96 % yield. Subsequently, dehydration reaction of 4,5‐dihydropyra‐zolylquinolines under acid conditions furnished a new series of 4‐(3‐substituted‐5‐trifluoromethyl‐1H‐pyra‐zol‐1‐yl)‐7‐chloroquinolines in 73 ‐ 96 % yield.     

Eight 7‐benzyl‐3‐tert‐butyl‐1‐phenylpyrazolo[3,4‐d]oxazines,encompassing structures containing no intermolecular hydrogen bonds,and hydrogen‐bonded structures in one,two or three dimensions

7‐Benzyl‐3‐tert‐butyl‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₂H₂₅N₃O, (I), and 3‐tert‐butyl‐7‐(4‐methylbenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₇N₃O, (II), are isomorphous in the space group P2₁, and molecules are linked into chains by C—H...O hydrogen bonds. In each of 3‐tert‐butyl‐7‐(4‐methoxybenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₇N₃O₂, (III), which has cell dimensions rather similar to those of (I) and (II), also in P2₁, and 3‐tert‐butyl‐1‐phenyl‐7‐[4‐(trifluoromethyl)benzyl]‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₄F₃N₃O, (IV), there are no direction‐specific interactions between the molecules. In 3‐tert‐butyl‐7‐(4‐nitrobenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₂H₂₄N₄O₃, (V), a combination of C—H...O and C—H...N hydrogen bonds links the molecules into complex sheets. There are no direction‐specific interactions between the molecules of 3‐tert‐butyl‐7‐(2,3‐dimethoxybenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₄H₂₉N₃O₃, (VI), but a three‐dimensional framework is formed in 3‐tert‐butyl‐7‐(3,4‐methylenedioxybenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₅N₃O₃, (VII), by a combination of C—H...O, C—H...N and C—H...π(arene) hydrogen bonds, while a combination of C—H...O and C—H...π(arene) hydrogen bonds links the molecules of 3‐tert‐butyl‐1‐phenyl‐7‐(3,4,5‐trimethoxybenzyl)‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₅H₃₁N₃O₄, (VIII), into complex sheets. In each compound, the oxazine ring adopts a half‐chair conformation, while the orientations of the pendent phenyl and tert‐butyl substituents relative to the pyrazolo[3,4‐d]oxazine unit are all very similar.     

Simple and Efficient Synthesis of Novel 3‐Substituted 2‐Thioxo‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones and Their Reactions with Alkyl Halides and α‐Glycopyranosyl Bromides

A series of 3‐substituted 2‐thioxo‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones 4a – e were synthesized from the reaction of 3‐aminonaphthalene‐2‐carboxylic acid 1 with isothiocyanate derivatives 2a – e . The alkylation of 4a – e with alkyl halides gave 3‐substituted 2‐alkylsulfanyl‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones 5a – o . S‐Glycosylation was carried out via the reaction of 4a – e with glycopyranosyl bromides 7a and 7b under anhydrous alkaline conditions. The structure of the compounds was established as S‐nucleoside and not N‐nucleoside. Conformational analysis has been studied by homonuclear and heteronuclear two‐dimensional NMR methods (2D DFQ‐COSY, heteronuclear multiple quantum coherence, and heteronuclear multiple bond correlation). The S site of alkylation and glycosylation was determined from the ¹H and ¹³C heteronuclear multiple quantum coherence experiments.     

Reactions of 4,5‐Dihydro‐1,4‐Benzothiazepin‐3(2H)‐one 1,1‐Dioxide and 1,5‐Dihydro‐4,1‐Benzothiazepin‐2(3H)‐one 4,4‐Dioxide Derivatives with Vilsmeier Reagent and DMFDMA

The regioselectivity of the interaction between isomeric 4,5‐dihydro‐1,4‐benzothiazepin‐3(2H)‐one 1,1‐dioxide and 1,5‐dihydro‐4,1‐benzothiazepin‐2(3H)‐one 4,4‐dioxide derivatives with the Vilsmeier reagent and DMFDMA (N,N‐dimethylformamide dimethylacetal) has been investigated. The structures of synthesized compounds are confirmed by ¹H, ¹³C NMR, elemental analysis, and X‐ray data.     

The reaction of 3,4‐diamino‐1,2,5‐oxadiazoles with formaldehyde

The compounds 5,6‐dihydro‐4H‐imidazo[4,5‐c][1,2,5]oxadiazole ( 3a , R?H), 4,6,10,12‐tetramethyl‐5,6,11,12‐tetrahydro‐4H,10H‐bis(1,2,5)oxadiazolo[3,4‐d:3′,4′‐I][1,3,6,8]tetraazecine ( 4b , R?CH₃), N³,N³′‐methylenebis‐3,4‐diamino‐1,2,5‐oxadiazole ( 5a , R?H) and N³,N³′‐methylenebis(N,N′‐dimethyl‐3,4‐diamino‐1,2,5‐oxadiazolee) ( 5b , R?CH₃) were synthesized from the reaction of formaldehyde with 3,4‐diamino‐1,2,5‐oxadiazole and N,N′‐3,4‐dimethylamino‐1,2,5‐oxadiazole in an acetonitrile.     

Selenium heterocycles XLIV. Syntheses of 8,9‐dihydro‐1,2,3‐thiadiazolo[4,5‐a]‐4,7‐dihydroxynaphthalene and 1,2,3‐selenadiazolo[4,5‐a]‐4,7‐dimethoxynaphthalene

The reaction of thionyl chloride with the semicarbazone 2 gave 4,5‐dihydro‐6,9‐dihydroxynaphtho‐[1,2‐d][1,2,3]thiadiazole ( 3 ) instead of 4,5‐dihydro‐6,9‐dimethyoxynaphtho[1,2‐d][1,2,3]thiadiazole ( 4 ). Selenium dioxide oxidation of compound 2 gave 4,5‐dihydro‐6,9‐dimethyoxynaphtho[1,2‐d][1,2,3]selenadiazole ( 5 ). Oxidation of compound 5 with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone afforded 6,9‐dimethyoxynaphtho[1,2‐d][1,2,3]selenadiazole ( 6 ).     

Synthesis of Indolo[3,2‐b]carbazoles via an Anomeric‐Based Oxidation Process: A Combined Experimental and Computational Strategy

Indolo[3,2‐b]carbazole is a molecule of great biological significance, as it is formed in vivo after consumption of cruciferous vegetables. The reaction of 1H‐indole and various aldehydes in the presence of a catalytic amount of N,2‐dibromo‐6‐chloro‐3,4‐dihydro‐2H‐benzo[e][1,2,4]thiadiazine‐7‐sulfonamide 1,1‐dioxide as an efficient and homogeneous catalyst in acetonitrile at 50°C produces 6,12‐disubstituted 5,7‐dihydroindolo[2,3‐b]carbazole with an in good to excellent yield. The presented technique offers a fast and robust method, by the use of inexpensive commercially available starting materials toward 6,12‐disubstituted 5,7‐dihydroindolo[2,3‐b]carbazole. A new anomeric‐based oxidation was kept in mind for the final step of the indolo[2,3‐b]carbazoles synthesis. The suggested anomeric‐based oxidation mechanism was supported by experimental and theoretical evidences.     

Synthesis and Characterization of New Heterocyclic Compounds Containing Thienylbenzo[h]Quinoline Moiety

In this paper the reaction of 2‐(2′‐thienylmethylene)‐3,4‐dihydronaphthalen‐2(1H)‐one ( 1 ) with cyanothioacetamide gave a mixture of 3‐cyano‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]quinolin‐2(1H)‐thione ( 2 ) and the related disulfide 3 . Compound 2 was reacted with some halo compounds namely; ethyl chloroacetate, chloroacetamide, chloro(N‐(p‐chlorophenyl))acetamide, N¹‐chloroacetylsulfanilamide, and 2‐chloromethyl‐1H‐benzimidazole to produce a series of 2‐(substituted)methylthio‐3‐cyano‐5,6‐dihydro‐4‐(2′‐thienyl)benzo[h]quinolines 4a , 4b , 4c , 4d , 4e and 11 . Upon heating the latter compounds with sodium ethoxide, they underwent intramolecular Thorpe–Zeigler cyclization to furnish the corresponding 2‐(substituted)‐3‐amino‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]thieno[2,3‐b]quinolines 5a , 5b , 5c , 5d , 5e and 12 . (3‐Cyano‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]quinolin‐2‐ylthio)acethydrazide ( 8 ) and the related isomer, 3‐amino‐5,6‐dihydro‐4‐(2′‐thienyl)thieno[2,3‐b]benzo[h]quinoline‐2‐carbohydrazide ( 9 ), were also synthesized. Most of the aforementioned compounds were used as key intermediates for synthesizing other benzo[h]quinolines, benzo[h]thieno[2,3‐b]quinolines as well as benzo[h]pyrimido[4′,5′:4,5] thieno[2,3‐b]quinolines. The structure of all synthesized compounds was confirmed by spectroscopic measurements and analytical analyses.