Facile synthesis of pyrrolo[2,1‐c][1,4]benzodiazepine‐5,11‐dione dimer

Efficient synthesis of biological important pyrrolo[2,1‐c][1,4]benzodiazepine‐5,11‐dione dimer linked through the C‐2 positions by fumarate group is described.     

A new entry to pyrazolo[4,3‐e][1,4]diazepines. Facile synthesis of pyrazolo [4,3‐e][1,4]diazepin‐5,8‐diones, 5,6,8‐triones and pyrazolo[4,3‐e]pyrrolo‐[1,2‐a][1,4]diazepin‐5,10‐diones

A facile approach to pyrazolo[4,3‐e][1,4]diazepin‐5,8‐diones and pyrazolo[4,3‐e]pyrrolo[1,2‐a][1,4]‐diazepin‐5,10‐diones is reported. Strategy involved the utility of α‐amino acid as a three‐atom segment in the construction of diazepine skeleton on the preformed pyrazole ring.     

Synthesis of N1‐substituted coumarino[4,3‐c] pyrazoles

3‐Acyl‐4‐hydroxy‐2‐oxo‐2H‐chromen derivatives 1a‐d were condensed with (7‐hydroxy‐2‐oxo‐2H‐chromen‐4‐yl)‐acetic acid hydrazide 2 , (4‐methyl‐2‐oxo‐2H‐chromen‐7‐yloxy)‐acetic acid hydrazide 3 , and (7‐hydrazinocarbonylmethoxy‐2‐oxo‐2H‐chromen‐4‐yl)‐acetic acid hydrazide 4 , to give corresponding 3‐alkyl‐1‐[2‐(7‐hydroxy‐2‐oxo‐2H‐chromeno‐4‐yl)‐acetyl]‐1H‐chromeno[4,3‐c]pyrazole‐4‐one 5a‐d , 3‐alkyl‐1‐[2‐(4‐methyl‐2‐oxo‐2H‐chromeno‐7‐yloxy)‐acetyl]‐1H‐chromeno[4,3‐c]pyrazole‐4‐one 6a‐d , and 1‐{4‐[(3‐alkyl‐1H‐chromeno[4,3‐c]pyrazole‐4‐one‐1‐yl)‐carbonylmethyl]‐2‐oxo‐2H‐chromen‐7‐yloxy‐acetyl}‐3‐alkyl‐1H‐chromeno[4,3‐c]pyrazole‐4‐one 7a‐d.     

Straightforward Synthesis and Properties of Highly Fluorescent [5]‐ and [7]‐Helical Dispiroindeno[2,1‐c]fluorenes

This work presents a general approach for synthesis of substituted [5]‐helical dispiroindeno[2,1‐c]fluorenes based on Rh‐catalyzed intramolecular cyclotrimerization of triynes. This approach was further extended for the first synthesis of configurationally stable [7]‐helical dispiroindeno[2,1‐c]fluorenes. A series of variously substituted derivatives was prepared and their photophysical and electrochemical properties were evaluated. Their fluorescence emission maxima were in the region of 351–428 nm and quantum yields up to 88 % are the highest measured among the full‐carbon helical compounds.     

Synthesis of novel 1‐substituted [1,3]thiazolo[3,2‐a]‐[1,5]benzodiazepine derivatives from 1,5‐benzodiazepine‐2‐thiones and α‐halogen carbonyl compounds

A number of substituted 4H,5H,6H‐thiazolo[3,2‐a][1,5]benzodiazepinium salts 2a‐h, 5, 9 , which are based on the novel thiazolobenzodiazepine system, were prepared by condensation‐cyclization of 1,5‐benzodiazepine‐2‐thiones 1a‐f, h, 4 with α‐haloketones, as well as with α‐bromoacetaldehyde diethyl acetal. The structure and stereochemistry of the ring system obtained were investigated by ¹H and ¹³C nmr spectroscopy: the additional heterocyclic nucleus was found to appreciably influence the conformational mobility of the heptatomic ring. Upon treatment of salt 2d with alkali the presence of the base enamine structure in solution has been postulated.     

Chemical and Electrochemical Syntheses of Benzo[b](1,4)‐diazepine‐7,8‐diones

Electrochemical and chemical syntheses of benzodiazepinediones were carried out from the reaction of catechols with N,N′‐dialkylproylenediamine in aqueous solution at room temperature, using CV and controlled‐potential coulometry with K₃Fe(CN)₆ as an oxidant.     

Azinoiminophosphorane mediated 4H,8H‐1,2,4‐triazolo[1,5‐C]‐[1,3]oxazepin‐4‐ones and 5,6‐dihydro‐7H, 12H‐naphtho[2,1‐f]‐[1,2,4]triazolo[1,5‐c][1,3]oxazepin‐7‐ones synthesis

The aza‐Wittig reactions of benzaldehyde‐, acetophenone‐ and benzophenone 1‐[(triphenylphosphor‐anylidene)amino]ethylidenehydrazones ( 1 ) with 2,3‐furandiones 6 provide a new route to 4H,8H‐1,2,4‐triazolo[1,5‐c][1,3]oxazepin‐4‐ones 14 or 5,6‐dihydro‐7H,12H‐naphtho[2,1‐f|[1,2,4]triazolo[1,5‐c]‐[1,3]oxazepin‐7‐ones 17 via the thermal reaction of the expected azinoimine vinylogous lactones.     

A novel and direct synthetic route to substituted 1,5‐dihydro‐4H‐[1]benzopyrano[4,3‐b]pyridine‐4,5‐diones

The condensation of 4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one and substituted 2‐hydroxybenzaldehydes with ammonium acetate gave the title heterocycles. Synthesis of 1,5‐dihydro‐2‐methyl‐4H‐[1]naphtho‐[1′,2′:5,6]pyrano[4,3‐b]‐pyridine‐4,5‐dione is also described. A reaction mechanism is discussed.     

Furopyridines. XXVI. Reactions of cyanopyridine derivatives of furo[2,3‐b]‐, ‐[3,2‐b]‐, ‐[2,3‐c]‐ and ‐[3,2‐c]pyridine

Bromination of α‐cyanopyridine derivatives of furopyridines 1a‐d gave the 2,3‐dibromo‐2,3‐dihydro compounds 2a‐d in excellent yields. Treatment of 2a‐d with sodium hydroxide in methanol yielded compounds formed through the dehydrobromination and solvolysis of the nitrile. N‐Oxidation of 1a and 1b gave N‐oxide in much poor yield, while 1c and 1d gave the N‐oxide 13c and 13d in good yields. The nucleophilic reactions (cyanation, chlorination and acetoxylatoin) of 13c through a Reissert‐Henze type reaction gave poor results, which would be caused by the strong electron withdrawing effect of the cyano group.     

Synthesis of novel benzo[h] [1,6]naphthyridines via a rearrangement of hexahydro‐5H‐pyrrolo [2,1 ‐c] [1,4]benzodiazepines

Heating of hexahydro‐5H‐pyrrolo[2,1‐c][1,4]benzodiazepine‐2,5,11‐trione in boiling phosphoryl chloride led to a rearranged product like 3,5‐dichlorobenzo[h][1,6]naphthyridine. This structure was established from X‐ray diffraction analysis.     

Synthesis and Evaluation of Bioactivity of Thiazolo[3,2‐b]‐[1,2,4]‐triazoles and Isomeric Thiazolo[2,3‐c]‐[1,2,4]‐triazoles

Synthesis of 2‐(o‐nitrophenyl)‐6‐arylthiazolo[3,2‐b]‐[1,2,4]‐triazoles 4 and its isomer 3‐(o‐nitrophenyl)‐5‐arylthiazolo[2,3‐c]‐[1,2,4]‐triazoles 6 has been achieved starting from the appropriate 1‐(o‐nitrobenzoyl)‐3‐thiosemicarbazide 1 . Compound 1 on condensation with α‐haloketones gives 2‐(o‐nitrobenzoyl)hydrazino‐4‐arylthiazole hydrobromide 5 , which, on cyclization with POCl₃, affords thiazolo[3,2‐b]‐[1,2,4]‐triazoles 6 and not the isomeric thiazolo[3,2‐b]‐[1,2,4]‐triazoles 4 . This has been established by an unequivocal synthesis of 4 through polyphosphoric acid cyclization of 5‐aroylmethylmercapto‐3‐o‐nitrophenyl‐[1,2,4]‐triazole 3 . Compound 3 was synthesized by condensation of α‐haloketones with 5‐mercapto‐3‐(o‐nitrophenyl)‐[1,2,4]‐triazole 2 , obtained cyclization of 2‐(o‐nitrobenzoyl)hydrazinecarbothioamide 1 with NaOH. The antibacterial and antifungal activities of some of the compounds have also been evaluated.     

Synthesis of substituted pyrimido[4,5‐b] and [5,4‐c]‐[1,8]naphthyridines

Ethyl 1‐ethyl‐7‐methyl‐4‐oxo‐1,4‐dihydro[1,8]naphthyridine‐3‐carboxylate ( 1 ), precursor of nalidixic acid, has been converted in two steps through ([1,8]naphthyridin‐3‐yl)carbonylguanidine derivatives into substituted pyrimido[4,5‐b] and [5,4‐c][1,8]naphthyridines.     

Synthesis,Modification, and Anticonvulsant Activity of 3′‐R1‐Spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazolin]‐2,2′(7′H)‐diones Derivatives

Previously unknown 3′‐R¹‐5‐R²‐spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazoline]‐2,2′‐(7′H)‐diones and their N‐substituted analogues were obtained via reaction of 6‐R¹‐3‐(2‐aminophenyl)‐1,2,4‐triazin‐5‐ones with isatin and its substituted derivatives. It was shown that alkylation of 3′‐R¹‐5‐R²‐spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazolin]‐2,2′‐(7′H)‐diones by N‐R³‐chloroacetamides or chloroacetonitrile in the presence of а base proceeds by N‐1 atom of isatin fragment. The spectral properties (¹H and ¹³C NMR spectra) of synthesized compounds were studied, and features of spectral patterns were discussed. The high‐effective anticonvulsant and radical scavenging agents among 3′‐R¹‐5‐R²‐spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazolin]‐2,2′(7′H)‐diones and their N‐substituted derivatives were detected. It was shown that compounds 2.2 , 2.8 , and 3.1 exceed or compete the activity of the most widely used in modern neurology drug—lamotrigine on the pentylenetetrazole‐induced seizures model. The aforementioned fact may be considered as a reason for further profound study of synthesized compounds using other pathology models.     

Synthesis of substituted amino‐cycloalkyl[b]thieno‐[3,2‐e]pyridines

An efficient two respectively three steps procedure for the synthesis of cycloalkyl[b]thieno[3,2‐e]‐pyridine amines was developed and in general good to very good yields were obtained.     

Synthesis of [1,4]benzodioxino[2,3‐c and 2,3‐d]pyridazinones

Reaction of chloropyridazin‐3‐one 1, 5 and 10 with catechol in the presence of potassium carbonate gave the corresponding [1,4]benzodioxino[2,3‐e and/or 2,3‐d]pyridazinones 2, 7, 8 and 11 .     

1,2,3‐Trimethoxy‐5,11‐dihydro­indolo[1,2‐b]isoquinoline‐5,11‐dione

The title compound, C₁₅H₁₉NO₅, crystallizes in the monoclinic space group P2₁/c with four mol­ecules in the asymmetric unit, which differ from each other in the orientation of their methoxy groups. Of the three methoxy groups in each molecule, one lies close to the plane of the mol­ecule and the other two have an out‐of‐plane conformation where they point in opposite directions. In the crystal structure, four different types of π‐stacks are observed and the mol­ecules pack in two different types of stacking sheets, with alternating mol­ecules A and B in one ribbon and alternating mol­ecules C and D in the other. The supramolecular structure is supported by C—H⋯O and π–π inter­actions.     

3‐Bromo­methyl‐3‐ethyl‐3,4,6,7,8,8a‐hexa­hydro‐1H‐pyrrolo­[2,1‐c][1,4]­oxazine‐1,4‐dione

In the title compound, C₁₀H₁₄BrNO₃, the six‐membered lactone ring is in a boat conformation, with the two carbonyl groups cis to one another across the boat basal plane. C—H⋯O hydrogen bonds and weak C—H⋯Br interactions stabilize the crystal structure.     

One‐pot Two‐step Reaction for Synthesis of Poly‐substituted Pyrano[3,2‐c]pyridones and Spiro[indoline‐3,4′‐pyrano[3,2‐c]pyridine]‐2,5′(6′H)‐diones in Water

An efficient four‐component approach for the synthesis poly‐substituted pyrano[3,2‐c]pyridones and spiro[indoline‐3,4′‐pyrano[3,2‐c]pyridine]‐2,5′(6′H)‐diones in water has been established. During the reaction, the products were readily achieved through one‐pot two‐step reaction using solid acid as catalyst. The advantages of atom and step economy, the recyclability of heterogeneous solid acid catalyst, easy workup procedure, and the wide scope of substrates make the reaction a powerful tool for assembling pyrano[3,2‐c]pyridone skeletons of chemical and medical interest.