A simple synthesis of 4‐chloro‐5‐hydroxy‐1H‐benzo[g]indoles

The reaction of methyl 2‐(3‐chloro‐1,4‐dioxo‐1,4‐dihydronaphthalen‐2‐yl)propenoate ( 2a ) with primary amines gave 4‐chloro‐5‐hydroxy‐3‐methoxycarbonyl‐1H‐benzo[g]indoles 5a‐f as major compounds and 3‐methoxycarbonyl‐4,9‐dioxo‐2,3,4,9‐tetrahydro‐1H‐benzo[f]indoles 6a‐d as minor ones. Whereas the reaction of 3‐(3‐chloro‐1,4‐dioxo‐1,4‐dihydronaphthalen‐2‐yl)‐3‐buten‐2‐one ( 2b ) with primary amines afforded the corresponding 1H‐benzo[g]indoles 5g‐i as major products and 3‐acetyl‐4,9‐dihydro‐4,9‐dioxo‐1H‐benzo[f]indoles 7g, h as minor products.     

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.     

Reaction of 2,3‐Dichloro‐1,4‐Naphthoquinone with 1‐Phenylbiguanide and 2‐Guanidinebenzimidazole

When 2,3‐dichloro‐1,4‐naphthoquinone (DCHNQ) ( 1 ) is allowed to react with 1‐phenylbiguanide (PBG) ( 2 ), 4‐chloro‐2,5‐dihydro‐2,5‐dioxonaphtho[1,2‐d]imidazole‐3‐carboxylic acid phenyl amide ( 4 ), 6‐chloro‐8‐phenylamino‐9H‐7,9,11‐triaza‐cyclohepta[a]naphthalene‐5,10‐dione ( 5 ) and 4‐dimethyl‐amino‐5,10‐dioxo‐2‐phenylimino‐5,10‐dihydro‐2H‐benzo[g]quinazoline‐1‐carboxylic acid amide ( 6 ) were obtained. While on reacting 1 with 2‐guanidinebenzimidazole (GBI) ( 3 ) the products are 3‐(1H‐benzoimidazol‐2‐yl)‐4‐chloro‐3H‐naphtho[1,2‐d]imidazole‐2,5‐dione ( 7 ) and 3‐[3‐(1H‐benzoimidazol‐2‐yl)‐ureido]‐1,4‐dioxo‐1,4‐dihydronaphthalene‐2‐carboxylic acid dimethylamide ( 8 ).     

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.     

7‐Halogenated 7‐Deazapurine 2′‐Deoxyribonucleosides Related to 2′‐Deoxyadenosine, 2′‐Deoxyxanthosine,and 2′‐Deoxyisoguanosine: Syntheses and Properties

A series of 7‐fluorinated 7‐deazapurine 2′‐deoxyribonucleosides related to 2′‐deoxyadenosine, 2′‐deoxyxanthosine, and 2′‐deoxyisoguanosine as well as intermediates 4b – 7b, 8, 9b, 10b , and 17b were synthesized. The 7‐fluoro substituent was introduced in 2,6‐dichloro‐7‐deaza‐9H‐purine ( 11a ) with Selectfluor (Scheme 1). Apart from 2,6‐dichloro‐7‐fluoro‐7‐deaza‐9H‐purine ( 11b ), the 7‐chloro compound 11c was formed as by‐product. The mixture 11b / 11c was used for the glycosylation reaction; the separation of the 7‐fluoro from the 7‐chloro compound was performed on the level of the unprotected nucleosides. Other halogen substituents were introduced with N‐halogenosuccinimides ( 11a → 11c – 11e ). Nucleobase‐anion glycosylation afforded the nucleoside intermediates 13a – 13e (Scheme 2). The 7‐fluoro‐ and the 7‐chloro‐7‐deaza‐2′‐deoxyxanthosines, 5b and 5c , respectively, were obtained from the corresponding MeO compounds 17b and 17c , or 18 (Scheme 6). The 2′‐deoxyisoguanosine derivative 4b was prepared from 2‐chloro‐7‐fluoro‐7‐deaza‐2′‐deoxyadenosine 6b via a photochemically induced nucleophilic displacement reaction (Scheme 5). The pK_a values of the halogenated nucleosides were determined (Table 3). ¹³C‐NMR Chemical‐shift dependencies of C(7), C(5), and C(8) were related to the electronegativity of the 7‐halogen substituents (Fig. 3). In aqueous solution, 7‐halogenated 2′‐deoxyribonucleosides show an approximately 70% S population (Fig. 2 and Table 1).     

Facile Chemoselective synthesis of 2‐(2‐(Methoxycarbonyl)‐3‐oxo‐2,3‐dihydrobenzofuran‐2‐yl)benzoic acids and 3H,3’H‐Spiro[benzofuran‐2,1′‐isobenzofuran]‐3,3′‐dione derivatives

Oxidation of some derivatives of 4b,9b–dihydroxyindeno[1,2‐b]benzofuran‐10‐one have been investigated in detail using lead(IV) acetate in acetic acid under reflux conditions and periodic acid in aqueous ethanol at room temperature. We realized that during the first 5–15 minutes of the oxidation reactions in lead(IV) acetate/acetic acid system, 3H,3’H‐spiro[benzofuran‐2,1′‐isobenzofuran]‐3,3′‐dione derivatives have been synthesized chemo selectively, while, if the reaction mixtures stirred for additional 3 hours, the main products would be 2‐(2‐(Methoxycarbonyl)‐3‐oxo‐2,3‐dihydrobenzofuran‐2‐yl)benzoic acids. Moreover, room temperature oxidation of 4b,9b–dihydroxyindeno[1,2‐b]benzofuran‐10‐ones by periodic acid (H₅IO₆), leads to the formation of 3H,3’H‐spiro[benzofuran‐2,1′‐isobenzofuran]‐3,3′‐dione derivatives in good to excellent yields.     

Facile Synthesis of Novel 3‐(4‐phenylisothiazol‐5‐yl)‐2H‐chromen‐2‐one Derivatives as Potential Anticancer Agents

A series of 3‐(4‐phenylisothiazol‐5‐yl)‐2H‐chromen‐2‐one ( 6a – l ) derivatives has been efficiently synthesized by straightforward sequential reactions. Tandem Vilsmeier Hack reaction/cyclization/bromination/Suzuki cross‐coupling reactions were successfully applied to the preparation of title compounds in good‐to‐high yields. In the synthetic sequences, 3‐chloro‐3‐(2‐oxo‐2H‐chromen‐3‐yl)acrylaldehydes ( 2 ) were found to react with ammonium thiocyanate to yield the corresponding 3‐(isothiazol‐5‐yl)‐2H‐chromen‐2‐ones ( 3 ). These derivatives were brominated with N‐bromo succinamide to yield the corresponding regioselective 3‐(4‐bromoisothiazol‐5‐yl)‐2H‐chromen‐2‐one ( 4 ). Finally, compound 4 was treated with various phenyl/pyrazole/7H –pyrrolo[2,3‐d]pyrimidinyl boronic acids 5a – l in the presence of K₂CO₃ and Pd catalyst in dimethylformamide to yield the corresponding title derivatives 6a – l . All the synthesized compounds were characterized by analytical and spectral studies. All the final compounds were screened against different cancer cell lines (A549, PC3, SKOV3, and B16F10), and among these compounds, 6b , 6g , 6h , and 6l displayed moderate cytotoxic activity against the tested cell lines.     

Facile One‐pot,Three‐component Synthesis of Novel Bis‐heterocycles Incorporating 5H‐chromeno[2,3‐b]pyridine‐3‐carbonitrile Derivatives

Novel bis‐chromeno[2,3‐b ]pyridine derivatives were synthesized with good yields by a clean and efficient methodologies involving one‐pot three‐component synthesis of bis‐aldehydes, malononitrile dimer, and dimedone in the presence of piperidine as a catalyst in EtOH. Depending on the length and position of the spacer in the bis‐aldehyde derivatives 1 , the reactions proceeded to give either the bis(2,4‐diamino‐tetrahydro‐5H‐chromeno[2,3‐b ]pyridine‐3‐carbonitriles) 4 or bis(4‐amino‐2,6‐dioxo‐hexahydro‐2H‐chromeno[2,3‐b ]pyridine‐3‐carbonitriles) 5 . All of the new compounds have been characterized by spectral data.     

Regioselective Synthesis of Amino Substituted Indazolo[2,1‐b]phthalazine‐triones and Pyrazolo[1,2‐b]phthalazine‐2‐carbonitriles Catalyzed by 2‐1′‐Methylimidazolium‐3‐yl‐1‐ethyl Sulfate

The regioselective reactions of luminol with 1,3‐cyclohexanedione (or malononitrile) and aromatic aldehydes catalyzed by 2‐1′‐methylimidazolium‐3‐yl‐1‐ethyl sulfate were developed to synthesize 7‐amino‐3,4‐dihydro‐2H‐indazolo[2,1‐b]phthalazine‐1,6,11(13H)‐triones and 3,9‐diamino‐5,10‐dihydro‐5,10‐dioxo‐1H‐pyrazolo[1,2‐b]phthalazine‐2‐carbonitriles in good to excellent yields in short times.     

Derivatives of 2,3‐dihydroimidazo[1,5,4‐ef][1,2,5]‐benzothiadiazepin‐6(4h,7h)‐thione 1,1‐dioxide,a new heterocyclic system related to tibo

The synthesis of derivatives of 2,3‐dihydroimidazo[1,5,4‐ef][1,2,5]benzothiadiazepin‐6(4H,7H)‐thione 1,1‐dioxide is reported starting from N‐substituted ethyl 2‐(5‐chloro‐2‐nitrobenzenesulfonamido)‐2‐alkyl‐acetates. Fundamental steps of the synthetic pathway were: i) intramolecular cyclization of N‐substituted 2‐(2‐amino‐5‐chlorobenzenesulfonamido)‐2‐alkylacetic acids in the presence of N‐(3‐dimethyl‐aminopropyl)‐N′‐ethyl carbodiimide hydrochloride‐N,N‐dimethylaminopyridine complex; ii) building of imidazole ring from 2‐alkyl‐8‐chloro‐2,3‐dihydro‐3‐methyl‐1,2,5‐benzothiadiazepin‐4(5H)‐one 1,1‐dioxide to achieve 2‐alkyl‐9‐chloro‐2,3‐dihydro‐3‐methylimidazo[1,5,4‐ef][1,2,5]benzothiadiazepin‐6(4H,7H)‐one 1,1‐dioxide; iii) preparation of thiocarbonyl derivative by treatment with Lawesson's reagent. Introduction of a 3‐methyl‐2‐butenyl chain at position 2 of above imidazobenzothiadiazepinone required protection at the 7 position with thermally removable tert‐butoxycarbonyl moiety, due to the fact that alkylation of unprotected structure proved to be regioselective for the 7 position.     

Synthesis and Reactions of the Novel 6‐ethyl‐4‐hydroxy‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carboxaldehyde

The novel 6‐ethyl‐4‐hydroxy‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano[3,2‐c]quinoline‐3‐carboxaldehyde ( 2 ) was efficiently synthesized from Vilsmeier–Haack formylation of 3‐(1‐ethy1‐4‐hydroxy‐2‐oxo‐(1H)‐quinolin‐3‐yl)‐3‐oxopropanoic acid ( 1 ). The aldehyde 2 was allowed to react with some nitrogen nucleophiles producing a variety of hydrazones 3 – 7 . Reaction of aldehyde 2 with hydrazine hydrate and hydroxylamine hydrochloride afforded pyrazole and isoxazole annulated pyrano[3,2‐c]quinoline‐2,5(6H)‐dione, respectively. The reactivity of aldehyde 2 was examined toward some active methylene nitrile, namely, malononitrile, ethyl cyanoacetate, and cyanoacetamide leading to 2‐iminopyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines 10 – 12 , respectively. Also, some novel pyrazolo[4″,3″:5′,6′]pyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines ( 13 , 14 ) and thiazolo[5″,4″:5′,6′]pyrano[2′,3′:4,5]pyrano[3,2‐c]quinolines ( 15 , 16 ) were synthesized. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

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 .     

Studies with Heterocyclic β‐Enaminoniriles: A Simple Route for the Synthesis of Polyfunctionally Substituted Thiophene,Imidazo[1,2:1′,6′]pyrimido[5,4‐b]thiophene and Thieno[3,2‐d]pyrimidine Derivatives

Reaction of 3,5‐diaminothiophene‐2‐carbonitrile derivatives 3a‐c with ethoxycarbonylmethyl isothiocyanate and/or N‐[bis(methylthio)methylene]glycine ethyl ester led to formation of 7‐substituted‐8‐amino‐5‐thioxo‐6H‐imidazo[1,2:1′,6′]pyrimido[5,4‐b]thiophene‐2(3H)‐one derivatives 6a‐c and 7‐substituted‐8‐amino‐5‐(methylthio)imidazo[1,2:1′,6′]pyrimido[5,4‐b]thiophene‐2(3H)‐one 7a‐c , respectively. Also, the synthetic potential of the β‐enaminonitrile moiety in 3a‐c has been explored; it proved to be a promising candiate for the synthesis of 1,6‐disubstituted‐2,4‐diamino‐7,8‐dihydro‐8‐oxopyrrolo[1,2‐a]thieno[2,3‐e]pyrimidine derivatives 10a‐f and pyrido[2′,3′:6,5]pyrimido[3,4‐a]benzimidazole derivatives 12a,b .     

An Efficient Ugi‐Azide Four‐Component Approach for the Preparation of Novel 1‐(1H‐tetrazol‐5‐yl)‐10‐chloro‐1,2,3,4‐tetrahydropyrazino[1,2‐a] Indoles

The synthesis of novel 1‐(1H‐tetrazol‐5‐yl)‐10‐chloro‐1,2,3,4‐tetrahydropyrazino[1,2‐a] indole derivatives starting from the initially prepared 1‐(2‐bromoethyl)‐3‐chloro‐1H‐indole‐2‐carbaldehyde is described. A variety of likely biologically relevant pyrazino[1,2‐a] indole‐based 1,5‐disubstituted tetrazoles was obtained in moderate to high yields via an Ugi‐azide reaction. These reactions presumably proceed by the imine formation, intramolecular cyclization to iminium ion, and nucleophilic addition tandem reactions, respectively.     

Synthesis and Crystal Structures of Two 9‐(2‐Bromoethyl)‐Substituted 7‐Deazapurines

The 7‐(2‐bromoethyl) derivatives, 2a and 2b , of 4‐chloro‐7H‐pyrrolo[2,3‐d]pyrimidine ( 1a ) and 4‐chloro‐7H‐pyrrolo[2,3‐d]pyrimidin‐2‐amine ( 1b ) were synthesized by nucleobase anion alkylation (NaH, DMF) and crystallized. X‐Ray analyses of both compounds were performed, and they revealed significantly different positioning of the side chain relative to the heterocyclic ring, depending on the substituent (H or NH₂) at C(2).     

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.     

Syntheses of 2,3‐dicyano‐5a,8a‐dihydro‐5a‐hydroxycyclopentano[1′,2′:4,5]pyrrolo[2,3‐b]pyrazines and 2,3‐dicyanocyclohexano[1′,2′:4,5]pyrrolo‐[2,3‐b]pyrazines

Previously synthesized 2‐(3′‐chloro‐5′,6′‐dicyanopyrazin‐2′‐yl)cyclopentan‐1‐one 1 , obtained from the reaction of 2,3‐dichloro‐5,6‐dicyanopyrazine with 1‐pyrrolidino‐1‐cyclopentene, was further reacted with primary alkylamines to give mixtures of diastereomer of 5‐alkyl‐2,3‐dicyano‐5a,8a‐dihy‐dro‐5a‐hydroxycyclopentano[1′,2′:4,5]pyrrolo[2,3‐b]pyrazines 3a‐h in high yield. The reaction of 2‐alkylamino‐3‐chloro‐5,6‐dicyanopyrazine with 1‐pyrrolidino‐1‐cyclohexene gave 5‐alkyl‐2,3‐dicyanocyclopentano[1′,2′:4,5]pyrrolo[2,3‐b]pyrazines 5a‐b together with 5‐alkylamino‐2,3‐dicyano‐6‐pyrrolidinopyrazines 6a‐b . The products prepared are all of interest as potential pesticides and new fluorescent chromophores.     

Synthesis and Antimicrobial Activity of Novel Heterocycles Utilizing 3‐(1,4‐Dioxo‐3,4‐dihydrophthalazin‐2(1H)‐yl)‐3‐oxopropanenitrile as Precursors

The reaction of 3‐(1,4‐dioxo‐3,4‐dihydrophthalazin‐2(1H)‐yl)‐3‐oxopropanenitrile 1 and salicyladehyde furnished coumarin derivatives 4 and 5 . Coupling reaction of 1 with aryl diazonium chlorides and benzene‐1,4‐bis (diazonium) chloride gave the corresponding hydrazones 6a , b and bishydrazone 9 , respectively. Hydrazones 6 underwent intramolecular cyclization upon treating with hydrazine hydrate to give 3‐aminopyrazoles 7 . Pyranyl phthalazine 13 was prepared from the reaction of 1 with ethyl 2‐cyano‐3‐ethoxyacrylate 10 . Enaminonitrile 14 was reacted with hydrazine hydrate/phenylhydrazine and hydroxylamine to afford the corresponding pyrazoles 16 and oxime 17 . The antimicrobial evaluation revealed pyrazole derivatives 7a , b and 16a , b displayed a broad spectrum activity against most strains. 3‐Aminopyrazole derivative 7b showed potent antibacterial activity against all tested microorganisms.     

Novel regioselective synthesis of 3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐one containing compounds

A variety of 3″,5″‐diaryl‐3″H,4′H‐dispiro[cyclohexane‐1,2′‐chromene‐3′,2″‐[1,3,4]thiadiazol]‐4′‐ones 3a‐c were synthesized regioselectively through the reaction of 4′H,5H‐trispiro[cyclohexane‐1,2′‐chromene‐3′,2″‐[1,3,4]oxadithiino[5,6‐c]chromene‐5″,1″′‐cyclohexan]‐4′‐one ( 1 ) with nitrilimines (generated in situ via triethylamine dehydrohalogenation of the corresponding hydrazonoyl chlorides 2a‐c ) in refluxing dry toluene. Single crystal X‐ray diffraction studies of 3a,b add support for the established structure. Similarly, 3′,5′‐diaryl‐2,2‐dimethyl‐3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐ones 5a‐c were obtained in a regioselective manner through the reaction of 2,2,5′,5′‐tetramethyl‐4H,5′H‐spiro[chromene‐3,2′‐[1,3,4]oxadithiino[5,6‐c]chromen]‐4‐one ( 4a ) with nitrilimines under similar reaction conditions. On the other hand, reaction of 2,5′‐diethyl‐2,5′‐dimethyl‐4H,5′H‐spiro[chromene‐3,2′‐[1,3,4]oxadithiino‐[5,6‐c]chromen]‐4‐one ( 4b ) with nitrilimines in refluxing dry toluene afforded the corresponding 3′,5′‐diaryl‐2‐ethyl‐2‐methyl‐3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐ones 5d‐f as two unisolable diastereoisomeric forms.     

New 1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidine derivatives II

The 7‐chloro‐3‐(2‐chlorobenzyl)‐ and 7‐chloro‐3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐d]pyrimidines ( 1 and 4 ), by nucleophilic replacement with some hydrazides, gave the corresponding 7‐hydrazidoderivatives ( 2a‐e and 5a‐e ). These, by heating in Dowtherm, underwent an intramolecular cyclization to form the new tricyclic 7‐substituted‐3‐(2‐chlorobenzyl)‐ and 3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidines ( 3a‐d and 6a‐d ). The 7‐hydrazino‐3‐(2‐chlorobenzyl)‐ and 7‐hydrazino‐3‐(2‐fluorobenzyl)‐triazolo‐pyrimidines ( 9a and 9b ) were also prepared via the corresponding mercapto ( 7a and 7b ) and thiomethyl ( 8a and 8b ) derivatives.