Polycyclic N‐Heterocyclic Compounds,Part 69: Synthesis of 5‐amino‐1,2‐dihydro[1]benzofuro[3,2‐d]furo[2,3‐b]pyridines and their transformations to related compounds

Reaction of 3‐(3‐cyanopropoxy)[1]benzofuran‐2‐carbonitriles with potassium tert‐butoxide gave 5‐amino‐1,2‐dihydro[1]benzofuro[3,2‐d]furo[2,3‐b]pyridines and 5‐amino‐2,3‐dihydro[1]benzofuro[3,2‐b]oxepin‐4‐carbonitriles as new ring systems. Reactions of the 5‐chloro derivative, obtained from 5‐amino‐1,2‐dihydro[1]benzofuro[3,2‐d]furo[2,3‐b]pyridine, produced a dihydrofuran ring‐opened compound and 5‐substituted compounds. J. Heterocyclic Chem.,(2011).     

Synthesis of oxazolo[3,2‐b]hetero[1,2,4]thiadiazine S,S‐dioxides

Six bromomethyl derivatives of the new 2,3‐dihydrooxazolo[3,2‐b]thieno[3,4‐e][1,2,4]thiadiazine 5,5‐dioxides, 2,3‐dihydrooxazolo[3,2‐b]thieno[2,3‐e][1,2,4]thiadiazine 5,5‐dioxides and 6,7‐dihydrooxazolo‐[3,2‐b]pyrazolo[4,3‐e][1,2,4]thiadiazine 9,9‐dioxides heterocyclic ring systems were synthesized. These compounds are good intermediates for the preparation and development of promising antiviral and psy‐chotropic drugs. The structures of the products are supported by different nmr spectroscopic methods and mass spectrometry.     

Synthesis of thieno[2,3‐b][1,5]benzoxazepine derivatives

A new series of 4‐(4‐methylpiperazin‐1‐yl)thieno[2,3‐b][1,5]benzoxazepines 1a‐k has been synthesized from 4‐bromo‐2‐methylthiophene 6 or ethyl 2‐amino‐4,5‐dimethyl‐3‐thiophencarboxylate 10 . Preparation of the key intermediate thieno[2,3‐b][1,5]benzoxazepine‐4(5H)‐ones 4a‐i, 4k were carried out by treatment of 2‐bromo‐N‐(2‐hydroxyphenyl)‐3‐thiophencarboxamides 5a‐i, 5k with potassium carbonate in DMSO. Compounds 1 are thienoanalogues of loxapine, a potent antipsychotic drug. Of these compounds, the neu‐roleptic activity of 2‐methyl‐4‐(4‐methylpiperazin‐l‐yl)thieno[2,3‐b][1,5]benzoxazepine 1a (R¹, R³=H, R²=CH₃) demonstrated potent antipsychotic activity.     

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.     

Syntheses of New Unsymmetrical 2,5‐Disubstituted‐1,3,4‐oxadiazoles and 1,2,4‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles Bearing Thieno[2,3‐c]pyrazolo Moiety

New series of (thieno[2,3‐c]pyrazolo‐5‐yl)‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazoles 10a , 10b , 10c and (thieno[2,3‐c]pyrazol‐5‐yl)‐1,3,4‐oxadiazol‐3(2H)‐yl)ethanones 6a , 6b , 6c has been synthesized from thieno[2,3‐c]pyrazole‐5‐carbohydrazide 3 by multistep reaction sequence. (5‐Aryl‐1,3,4‐oxadiazol‐2‐yl)‐1H‐thieno[2,3‐c]pyrazoles 4a , 4b , 4c were also synthesized from thieno[2,3‐c]pyrazole‐5‐carbohydrazide 3 by cyclization with various aromatic carboxylic acids. The hydrazide 3 was obtained by reaction of thieno[2,3‐c]pyrazole‐5‐carboxylate 2 with hydrazine hydrate in good yield, and compound 2 was obtained by the reaction of 5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde 1 and 2‐ethyl thioglycolate in presence of sodium alcoholate in good yield.     

Utility of Pyridine‐2(1H)‐thiones in the Synthesis of Novel Bis‐Thieno[2,3‐b]pyridines and Their Fused Azines

The starting materials pyridine‐2(1H)‐thiones are prepared and reacted with halogen‐containing reagents in ethanolic sodium acetate solution to give the corresponding 2‐S‐alkylpyridines, which cyclized upon their boiling in methanolic sodium methoxide solution at reflux to give the corresponding thieno[2,3‐b]pyridines in excellent yields. Bis (thieno[2,3‐b]pyridine‐2‐carboxamides), incorporating 2,6‐dibromophenoxy moiety, are prepared by the bis‐O‐alkylation of thieno[2,3‐b]pyridine‐2‐carboxamide derivatives. Two synthetic routes are designed to prepare the target molecules pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4(3H)‐ones, pyrido[3′,2′:4,5]thieno[3,2‐d][1,2,3]triazin‐4(3H)‐ones, and their bis‐analogues using thieno[2,3‐b]pyridine‐2‐carboxamides and their bis‐analogues. The structure of the target molecules is elucidated using elemental analyses as well as spectral data.     

Polycyclic N‐Heterocyclic Compounds. Part 80: Synthesis and Evaluation of Effects on In Vitro Pentosidine Formation of 5,6‐Dihydro[1]benzothieno[3′,2′:2,3]thiepino[4,5‐d]pyrimidine and Related Compounds

Reaction of 3‐(3‐cyanopropylthio)[1]benzothiophene‐2‐carbonitrile with tert‐BuONa gave 5‐amino‐1,2‐dihydro[1]benzothieno[3,2‐d]thieno[2,3‐b]pyridine and 5‐amino‐2,3‐dihydro[1]benzothieno[3,2‐b]thiepin‐4‐carbonitrile. The latter compound served as a convenient scaffold for the synthesis of the new heterocycles, [1]benzothieno[3′,2′:2,3]thiepino[4,5‐d]pyrimidines. All of our new tetracyclic products were evaluated for in vitro inhibitory activity on the formation of pentosidine, which is one of representative advanced glycation end products.     

A Convenient One‐Pot Synthesis of Thieno[2′,3′:4,5]Pyrimido[1,2‐b]‐[1,2,4,5]Tetrazines

A novel series of thieno[2′,3′:4,5]pyrimido[1,2‐b][1,2,4,5]tetrazin‐6‐one derivatives 14 were prepared from the reaction of 3‐amino‐2‐thioxo‐1,2,3,5,6,7‐hexahydro‐4H‐cyclopenta[4,5]thieno[2,3‐d]pyrimidin‐4‐one 3 or its methylthio 4 with hydrazonoyl chlorides 9 . The mechanism of the studied reactions has been discussed and further evidence for the assigned structure of the products is based on alternative synthesis. A single crystal X‐ray analysis of compound 14e has been carried out.     

Ring‐ring interconversions. Part 3. On the effect of the substituents on the thiazole moiety in the ring‐opening/ring‐closing reactions of nitrosoimidazo[2,1‐b][1,3]thiazoles with hydrochloric acid

The reaction of 6‐(4‐chlorophenyl)‐5‐nitrosoimidazo[2,1‐b][1,3]thiazole 1b , 6‐(4‐chlorophenyl)‐2‐methyl‐5‐nitrosoimidazo[2,1‐b][1,3]thiazole 1c , 6‐(4‐chlorophenyl)‐2,3‐dimethyl‐5‐nitrosoimidazo‐[2,1‐b][1,3]thiazole 1d and 2‐(4‐chlorophenyl)‐3‐nitrosobenzo[d]imidazo[2,1‐b][1,3]thiazole 1e with hydrochloric acid has been carried out in order to investigate the effect of substituents on the thiazole ring in a recently reported ring‐ring interconversion reaction. In every case the corresponding [1,4]‐thiazino[3,4‐c][1,2,4]oxadiazol‐3‐ones 2b‐e have been obtained. In particular, the benzoderivative 1e furnished the 4‐(4‐chlorophenyl)‐4‐hydroxy‐4H‐benzo[5,6][1,4]thiazino[3,4‐c][1,2,4]oxadiazol‐1‐one 2e , containing a new tricyclic system with a quasi‐planar geometry whose pharmacological potentialities appear promising.     

One ‐ pot synthesis of novel sulfur and selenium heterocycles by directed ortho‐lithiation

A procedure for the synthesis of benzo[e][1,3]thiazine‐2,4‐diones from benzamides by directed lithiation and sequential treatment with sulfur and phosgene is reported. Use of thiophosgene afforded 2‐thioxo‐2,3‐dihydro‐benzo[e][1,3] thiazin‐4‐ones. Application of this methodology to benzenesulfonamides afforded the previously unknown 1,1‐dioxo‐1,2‐dihydro‐1,4‐dithia‐2‐aza‐naphthalen‐3‐one ring system with phosgene and the 1,2‐dioxo‐2‐phenyl‐2,3‐dihydrobenzo[e][1,4,2]dithiazine‐3‐one ring system with thiophosgene. Use of selenium in place of sulfur afforded the novel analogous selenium heterocycles, however in the case of benzamides the use of selenium and phosgene afforded benzo[d]isoselenazol‐3‐ones unexpectedly.     

An interesting synthesis of thieno[2,3‐d][1,2,3]thiadiazole via decomposition/recyclization of 3‐methoxycarbonyl‐1H‐thieno‐[2,3‐e][1,3,4]thiadiazine 4,4‐dioxide

Attempted hydrolysis of the ester of 3‐methoxycarbonyl‐1H‐thieno[2,3‐e][1,3,4]thiadiazine 4,4‐dioxide ( I ) under acidic conditions gave the ring‐contracted thieno[2,3‐d][1,2,3]thiadiazole ( V ) instead of the expected carboxylic acid. In addition to a discussion of the reaction, a plausible mechanism is presented.     

Reactions of hydrazonoyl halides 43 : Synthesis of some new 2,3‐dihydro‐1,3,4‐thiadiazoles,pyrazoles, pyrazolo[3,4‐d]‐pyridazines,thieno[2,3‐b]pyridines,pyrimidino[4′,5′:4,5]thieno[2,3‐b]‐pyridines and pyrrolo[3,4‐d]pyrazoles

2,3‐Dihydro‐1,3,4‐thiadiazoles, pyrazoles, pyrazolo[3,4‐d]pyridazines, thieno[2,3‐b]pyridines, pyrim‐idino[4′,5′:4,5]thieno[2,3‐b]pyridines and pyrrolo[3,4‐d]pyrazoles were obtained in a good yields by treatment of hydrazonoyl halides with each of alkyl carbodithioates, 3‐(dimethylamino)‐1‐naphtho[1,2‐d]furan‐2‐ylprop‐2‐en‐1‐one and N‐arylmalemides.     

Polycyclic N‐Heterocyclic Compounds. Part 84: Reaction of N‐(pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4‐yl)amidines or N‐(pyrido[2′,3′:4,5]furo[3,2‐d]pyrimidin‐4‐yl)amidines with Hydroxylamine Hydrochloride

The reactions of nine N‐(pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4‐yl)amidines ( 3 ) with hydroxylamine hydrochloride produced new cyclization products. These were formed via ring cleavage of the pyrimidine component followed by a 1,2,4‐oxadiazole‐forming ring closure to give N‐[2‐([1,2,4]oxadiazol‐5‐yl)thieno[2,3‐b]pyridin‐3‐yl]formamide oximes ( 11 ). Reaction of six N‐(pyrido[2′,3′:4,5]furo[3,2‐d]pyrimidin‐4‐yl)amidines ( 12 ) with hydroxylamine hydrochloride gave similar results. Effects of the newly synthesized compounds on pentosidine formation were also evaluated.     

A facile synthesis of new thieno[2,3‐b][1,4]thiazine derivatives starting from 2‐acylamino‐3,3‐dichloroacrylonitriles

Readily available 2‐acylamino‐3,3‐dichloroacrylonitriles are sequentially treated with methyl mercaptoacetate in the presence of sodium methylate and with sulfuric acid to furnish the methyl ester of 7‐amino‐2‐oxo‐3H‐thieno[2,3‐b][1,4]thiazine‐6‐carboxylic acid. Treating it first with triethyl orthoformate and then with ammonia or primary amines, the pyrimidine‐4‐one nucleus is annelated to the thienothiazine system, which is corroborated by spectroscopic methods and X‐ray diffraction analysis. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:411–415, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20232     

Synthesis of dihydrothieno[2,3‐b]pyridines based on titanium(IV) chloride‐mediated michael reactions of 2‐amino‐4,5‐dihydro‐3‐thiophenecarbonitriles with α,β‐unsaturated ketones

2‐Arnino‐4,5‐dihydro‐3‐thiophenecarbonitriles 1a‐c reacted with α,β‐unsaturated ketones (e.g. methyl vinyl ketone 2 and benzalacetone 3 ) in the presence of titanium(IV) chloride to give the corresponding Michael adducts 4a‐c and 5a‐c. Thermal treatment of compounds 4a‐c and 5a‐c with titanium(IV) chloride caused intramolecular cyclocondensation to yield the corresponding tetrahydrothieno[2,3‐b]pyridines 6a‐c and 7a‐c. Aromatization of 6a‐c and 7a‐c with potassium tert‐butoxide in refluxing tert‐butyl alcohol pro ceeded smoothly to afford the corresponding dihydrothieno[2,3‐b]pyridines 8a‐c and 9a‐c.     

Synthesis of dihydrofuro[2,3‐b]pyridines by the reaction of 2‐amino‐4,5‐dihydro‐3‐furancarbonitriles with α,β‐unsaturated carbonyl compounds

The reactions of 2‐amino‐4,5‐dihydro‐3‐furancarbonitriles 1a‐d with α,β‐unsaturated carbonyl compounds in the presence of sodium ethoxide (0.1 equivalent) gave the corresponding Michael adducts 2a‐d , 3a‐d and 4a‐d. Compounds 2a‐d and 3a‐c reacted with sodium alkoxide (1 equivalent) to yield the corresponding 7a‐alkoxyhexahydrofuro[2,3‐b]pyridines 5a‐d, 6a‐d, 7a‐c and 8a‐c . Treatment of 5a‐d, 6a‐d, 7a‐c and 8a‐c with potassium tert‐butoxide produced the corresponding dihydrofuro[2,3‐b]pyridines 9a‐d and 10a‐c . The reaction of 4a‐c with sodium ethoxide (1 equivalent) afforded the corresponding dihydro‐furo[2,3‐b]pyridines 11a‐c .     

Alternating narrow band gap copolymers derived from indeno[1,2‐b]fluorene and thiophene‐cored‐thieno[3,4‐b]pyrazine derivatives—Synthesis,characterization and comparative studies of photochemical stability

Alternating narrow band gap (NBG) conjugated polymers derived from 6,6′,12,12′‐tetraoctylindeno[1,2‐b]fluorene (IF) and 2,3‐dimethyl‐5,7‐dithien‐2‐yl‐thieno[3,4‐b]pyrazine (DTTP), 2,3‐diphenyl‐5,7‐dithien‐2‐yl‐thieno[3,4‐b]pyrazine (DPTP) or 2,3‐dioctyl‐5,7‐dithien‐2‐yl‐thieno[3,4‐b]pyrazine (DOTP), named as PIF‐DTTP, PIF‐DPTP, and PIF‐DOTP, respectively, were synthesized by Suzuki coupling reaction and characterized. The photochemical stabilities of the copolymers and copolymer derived from IF and 5,7‐dithien‐2‐yl‐thieno[3,4‐b]pyrazine (DTP) were investigated by the UV absorptions, PL spectra, FT‐IR spectra, and photovoltaic properties of the copolymers as a function of UV irradiation time. The studies revealed that the degradation of thieno[3,4‐b]pyrazine (TP) ring under UV irradiation can be retarded or eliminated by introducing phenyl group into the 2,3‐positions of TP ring, and indicated that 2,3‐diphenylthieno[3,4‐b]pyrazine could be used as durable electron deficient moiety to achieve donor–acceptor NBG‐conjugated polymers. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis and total 1H-NMR assignment of naphtho[1′,2′:4,5]thieno[2,3-c][1,10]phenanthroline and naphtho[2′,1′:4,5]-thieno[2,3-c] [1,10]phenanthroline

Naphtho[1′,2′:4,5]thieno[2,3-c][1,10]phenanthroline and naphtho[2′,1′:4,5]thieno[2,3-c][1,10]phenanthroline, two novel polycyclic heterocyclic ring systems, have been synthesized in four steps from known starting materials. The total ¹H nmr spectral assignments were made using a COSY experiment to identify the spin systems.     

Reaction of 4,5,6‐triaminopyrimidine and 2,4,5,6‐tetraaminopyrimidine with 3‐dimethylaminopropiophenones. Synthesis of new 4‐aryl‐2,3‐dihydropyrimido[4,5‐b][1,4]diazepines

Several new 6‐amino‐ and 6,8‐diamino‐4‐aryl‐2,3‐dihydropyrimido[4,5‐b][1,4]diazepines were obtained from the reaction of 4,5,6‐triaminopyrimidine 1a and 2,4,5,6‐tetraaminopyrimidine 1b with one equivalent of 3‐dimethylaminopropiophenones 2 in absolute ethanol. Structure analysis of 6‐amino‐ and 6,8‐diamino‐4‐aryl‐2,3‐dihydropyrimido[4,5‐b][1,4]diazepines 3a‐i , determined by detailed nmr measurements, reveals a high regioselectivity of this reaction.     

Synthesis of a New Series of Imidazo[1,5-d]pyrido[2,3-b][1,4]thiazines as Potential Ligands for the GABA Receptor Complex

Summary.  Starting from 2-chloro-3-nitropyridine, 1H-pyrido[2,3-b][1,4]thiazin-2(3H)-one was synthesized. This compound was reacted with potassium tert-butoxide and diethyl chlorophosphate to give the intermediate 1H-pyrido[2,3-b][1,4]thiazin-2-ylphosphate derivative, which in turn afforded the 1,2,4-oxadiazolylimidazo[1,5-d]pyrido[2,3-b]pyrazine derivatives. The title compounds are potential ligands for the γ-aminobutyric acid A/benzodiazepine receptor complex. Corresponding author. E-mail: thomas.erker@univie.ac.at Received February 22, 2002. Accepted March 6, 2002