Synthesis of new functionalized imidazo[2,1‐b]thiazoles and thiazolo[3,2‐a]pyrimidines

5‐Oxo‐5H‐[1,3]thiazolo[3,2‐a]pyrimidine‐6‐carboxylic acid ( 4 ), and 6‐methylimidazo[2,1‐b]thiazole‐5‐carboxylic acid ( 17 ) were reacted with amines 6a‐i by the reaction with oxalyl chloride and N, N‐di methyl‐formamide as a catalyst into primary and secondary amide derivatives 7‐14 and 19‐22. From compound 24 N,N'‐disubstituted ureas 26, 27 and perhydroimidazo[1,5‐c]thiazole 29 derivatives of imidazo[2,1‐b]thiazole were prepared. By nmr analysis of compound 29 , the existence of two stereoisomers resulting from both optical, due to centre of chirality at C7′a, and conformational isomerism, due to restricted C5? N6′ bond rotation were proved.     

Imidazo[2,1‐b]thiazoles,imidazo[2,1‐b]imidazoles and Pyrrolo[1,2‐c]imidazoles. synthesis,structure and evaluation of benzodiazepine receptor binding

As a continuation of our studies on bicyclic heterocycles with benzodiazepine receptor affinity, derivatives with a 5:5 bicyclic skeleton, namely imidazo[2,1‐b]thiazoles, imidazo[2,1‐b]imidazoles and pyrrolo[1,2‐c]imidazoles were prepared. The compounds possessed an aromatic substituent with different spatial arrangement and distance to the bicyclic skeleton. X‐ray structure analysis was performed for Z‐2‐(4‐chlorobenzylidene)‐5,5‐diphenyl‐2,3,5,6‐tetrahydroimidazo[2,1‐b]imidazoline‐3,6‐dione ( 6a ) and 5‐amino‐6‐cyano‐7‐phenyl‐1‐oxo‐3‐thioxo‐2,3‐dihydro‐1H‐pyrrolo[1,2‐c]imidazole ( 20a ). In contrast to the previously described arylideneimidazo[2,1‐b]thiazepinones the smaller heterocyclic ring systems investigated in this study were devoid of meaningful benzodiazepine receptor affinity as well as anti‐convulsant activity.     

Synthesis of Pyrazolo[1,5‐a][1,3,5]triazine,Pyrazolo[1,5‐a]pyrimidine,and Imidazo[1,2‐b]pyrazole Derivatives Based on Imidazo[2,1‐b]thiazole Moiety

3(5)‐Aminopyrazole derivative ( 6 ) has been synthesized by the reactions of the versatile unreported 2‐cyano‐N ′‐(1‐(3‐methyl‐6‐phenylimidazo[2,1‐b ]thiazol‐2‐yl)ethylidene)acetohydrazide ( 3 ) with phenyl isothiocyanate in KOH/DMF solution followed by reaction with methyl iodide and hydrazine hydrate. Reaction of compound 6 with some 1,3‐dicarbonyl compounds yielded pyrazolo[1,5‐a ]pyrimidine derivatives ( 14 – 17 ). Alkylation of compound 6 with various halo reagents, followed by intramolecular cyclization, yielded the corresponding imidazo[1,2‐b ]pyrazole derivatives 27 , 29 , 31 , and 33 . All newly synthesized compounds were elucidated by considering the data of both elemental analysis and spectral data.     

Catalyst‐Free Convergent Approach for the Synthesis of Spiro[imidazo[2,1‐b][1,3]oxazine‐7,3′‐indoline

Strategies to address mounting environmental concerns with current approaches include an operationally simple and highly efficient one‐pot three‐component approach for the synthesis of spiro[imidazo[2,1‐b][1,3]oxazine‐7,3′‐indoline derivatives, which has been developed via Huisgen zwitter ion intermediate. The significant advantages of this protocol are short reaction time, excellent yields, and facile formation of three new bonds in one operation from easily available starting materials.     

Modular synthesis of pyrrolo[2,1‐b]thiazoles and related monocyclic pyrrolo structures

A modular synthesis of selectively‐substituted pyrrolo[2,1‐b]thiazoles (Δ⁶ isomeric form) has been implemented, involving a distinctive bicyclization reaction of a mucobromic acid derivative followed by a Suzuki‐Miyaura coupling. A novel process of Δ⁶ to Δ⁷ isomerization of the pyrrolothiazole structure was uncovered that appears to involve a 1,4‐addition‐1,2‐elimination mechanism. Preparation of 1,5‐dihydropyrrol‐2‐one structures, selectively substituted at the 3‐ and 4‐positions, was also achieved using the mucobromic acid synthon in a reductive amination process. J. Heterocyclic Chem., (2011).     

Synthesis of Imidazo[2,1‐b][2H‐1,3,4]thiadiazines and 1,2,4‐Triazolo[3,4‐b][2H‐1,3,4]thiadiazines

Imidazo[2,1‐b][2H‐1,3,4]thiadiazines were prepared by cyclization of 2‐amino‐5‐(4‐chlorophenyl)‐6H‐1,3,4‐thiadiazine with α‐haloketones. 1,2,4‐Triazolo[3,4‐b][2H‐1,3,4]thiadiazines were prepared by cyclization of 4‐amino‐5‐sulfanyl‐l,2,4‐triazoles with phenacyl bromides.     

Reaction of cyclic imidates with α,β‐unsaturated esters: Synthesis of new pyrrolo[2,1‐b]‐1,3‐oxazine and pyrido[2,1‐b]‐1,3‐oxazine derivatives

The cycloaddition reaction of cyclic imidates, 2‐benzyl‐5,6‐dihydro‐4H‐1,3‐oxazines 1a , 1b , 1c , 1d , 1e , 1f , with dimethyl acetylenedicarboxylate 2 , trimethyl ethylenetricarboxylate 4 , or dimethyl 2‐(methoxymethylene)malonate 6 afforded new fused heterocyclic compounds, such as methyl (6‐oxo‐3,4‐dihydro‐2H‐pyrrolo[2,1‐b]‐1,3‐oxazin‐7‐ylidene)acetates 3a , 3b , 3c , 3d , 3e , 3f (71–79%), dimethyl 2‐(6‐oxo‐3,4,6,7‐tetrahydro‐2H‐pyrrolo[2,1‐b]‐1,3‐oxazin‐7‐yl)malonates 5b , 5c , 5d , 5e , 5f (43–71%), or methyl 6‐oxo‐3,4‐dihydro‐2H,6H‐pyrido[2,1‐b]‐1,3‐oxazine‐7‐carboxylates 7a , 7b , 7c , 7d , 7e , 7f (32–59%), respectively. In these reactions, 1a , 1b , 1c , 1d , 1e , 1f (cyclic imidates, iminoethers) functioned as their N,C‐tautomers (enaminoethers) 2 to α,β‐unsaturated esters 2 , 4, and 6 to give annulation products 3 , 5 , and 7 following to the elimination of methanol, respectively. J. Heterocyclic Chem., (2011).     

Synthesis of Some Novel Thiazolo[3,2‐a]pyrimidine and Pyrimido[2,1‐b][1,3]thiazine Derivatives and their Antimicrobial Evaluation

A 2‐(2‐Mercapto‐4‐(4‐phenoxyphenyl)‐6‐(thiophen‐2‐yl)‐1,6‐dihydropyrimidin‐5‐yl) acetic acid was used as a reactive key precursor to design various pyrimidine derivatives such as thiazolo[3,2‐a]pyrimidines and pyrimido[2,1‐b][1,3]thiazines. The chemical structures of the newly synthesized products were confirmed by their elemental analyses and spectral data (IR, ¹H NMR, ¹³C NMR, and mass spectra). The antibacterial and antifungal activities of some of the synthesized products were also evaluated, and it was found that compounds 3, 5, 9 , and 11 exhibited potent activity against tested microorganisms in comparison with standard drugs.     

Microwave‐Assisted Synthesis of Pyrrolo[2,1‐b]thiazoles Linked to a Carbohydrate Moiety

Herein, we describe the synthesis of pyrrolo[2,1‐b]thiazoles substituted on C‐2 or C‐5 with a protected carbohydrate moiety. The new fused bicyclic heterocycles were obtained via thiazole intermediates, and the N‐alkylation step was assisted by microwave irradiation. The new products were completely characterized by physical and spectroscopic techniques. The cytotoxicity and antiviral activity against Junín virus of the methylated derivates was also evaluated.     

Synthesis of Heterocyclic Analogs of α‐aminoadipic Acid and its Esters Based on Imidazo[2,1‐b][1,3]Thiazole

A method for the preparation of heterocyclic analogs of α‐aminoadipic acid and its esters based on the imidazo[2,1‐b][1,3]thiazole ring system was developed. In this method, free‐radical bromination of ethyl 6‐methylimidazo[2,1‐b][1,3]thiazole‐5‐carboxylate with NBS afforded a versatile building block, ethyl 6‐bromomethylimidazo[2,1‐b][1,3]thiazole‐5‐carboxylate. Coupling of ethyl 6‐bromomethylimidazo[2,1‐b][1,3]thiazole‐5‐carboxylate with Schöllkopf's chiral auxiliary followed by acidic hydrolysis generated ethyl 6‐[(2S)‐2‐amino‐3‐methoxy‐3‐oxopropyl]imidazo[2,1‐b][1,3]thiazole‐5‐carboxylate. A similar procedure using diethyl (Boc‐amino)malonate yielded racemic 2‐amino‐3‐[(5‐ethoxycarbonyl)imidazo[2,1‐b][1,3]thiazol‐6‐yl]propanoic acid.     

Nef‐Isocyanide ‐Based One‐pot Two‐step Three Component Dihydrobenzo[4,5]Imidazo[2,1‐b]thiazoles Synthesis

The reactive imidoyl chloride adducts generated in situ from the reaction of isocyanide and acyl chlorides were trapped by 2‐mercaptobenzimidazoles to yield highly functionalized dihydrobenzo[4,5]imidazo[2,1‐b]thiazoles in good yields.     

A synthetic entry into the quino[2,1-b][1,3]benzoxazine ring system

The double ring closure of N-(2-hydroxybenzyl)anthranilic acids 1 with acetic anhydride or its acyclic analogous (RCH₂CO)₂O 2b and 2e lead to the formation of novel 12H-quino[2,1-b][1,3]benzoxazin-5-ones. The structure of the obtained compounds was proved with the use of their ir, mass, ¹H and ¹³C nmr spectra. Homo- and heteronuclear two-dimensional nmr experiments were performed to unambiguously assign all proton and carbon chemical shifts.     

Catalyst‐free one‐pot regioselective synthesis of benzo[d]imidazo[2,1‐b]thiazoles by heating or grinding

Eco‐friendly, efficient, and simple one‐pot catalyst‐free new procedures have been reported for the synthesis of benzo[d]imidazo[2,1‐b]thiazoles by condensation of phenylglyoxal, cyclic enolizable carbonyl compounds, and 2‐aminobenzothiazole at 80°C or by grinding the components at room temperature in glycerol. Cyclic enolizable carbonyl compounds employed in the protocol include dimedone, cyclohexa‐1,3‐dione, cyclopenta‐1,3‐dione, 5‐methylcyclohexa‐1,3‐dione, and 4‐hydroxy‐6‐methyl‐2‐pyrone. All the reactions were complete in ~30 min. The structures of all the products were confirmed by spectral data. The structures of compounds IVl and IVe have also been confirmed by X‐ray crystallographic studies. This protocol offers advantages such as short reaction time, easy workup, high yields and an environmentally benign methodology.     

Cyclic poly(ε‐caprolactone) synthesized by combination of ring‐opening polymerization with ring‐closing metathesis,ring closing enyne metathesis,or “click” reaction

This article described the synthesis of cyclic poly(ε‐caprolactone) (PCL) via ring‐closing metathesis (RCM), ring closing enyne metathesis (RCEM), and “click” reaction of different difunctional linear PCL. Linear PCL precursors were prepared by ring‐opening polymerization (ROP) of ε‐caprolactone in bulk using 10‐undecen‐1‐ol or propargyl alcohol as the initiator, followed by reacting with corresponding acyl chloride containing vinyl or azido end group. The subsequent end‐to‐end intramolecular coupling reactions were performed under high dilution conditions. The successful transformation of linear PCL precursor to cyclic PCL was confirmed by Gel permeation chromatography, ¹H NMR, and Fourier transform infrared measurements. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3022–3033, 2009     

2‐Nitroso‐1,3‐diphenyl‐1,2,3,4‐tetrahydrobenzo[b][1,6]naphthyridine

The title compound, C₂₄H₁₉N₃O, crystallizes in the centrosymmetric space group P2₁/a with one mol­ecule in the asymmetric unit. The tetra­hydro­pyridine ring has a boat conformation. The dihedral angle between the fused pyridine rings is 16.2 (1)°. The equatorial and axial orientations of the two phenyl groups with respect to the tetra­hydro­pyridine ring are confirmed. The nitroso group is coplanar with the attached C—N—C group. The interplanar angle formed between the fused tetra­hydro­pyridine and benzene planes is 13.4 (1)°. The crystal packing is stabilized by an intermolecular C—H⃛O hydrogen bond, which forms a C(9) graph‐set chain running along the [001] direction.     

Structure elucidation of [1,3]oxazolo[4,5‐e][2,1]benzisoxazole and naphtho[1,2‐d][1,3]‐ and phenanthro[9,10‐d]oxazoles using gradient selected gHMBC,gHMQC and gHMQC‐TOCSY NMR techniques

Structure elucidation of compounds in the benzisoxazole series ( 1 – 6 ) and naphtho[1,2‐d][1,3]‐ ( 7 – 10 ) and phenanthro[9,10‐d][1,3]oxazole ( 11 – 14 ) series was accomplished using extensive 2D NMR spectroscopic studies including ¹H–¹H COSY, long‐ range ¹H–¹H COSY, ¹H–¹³C COSY, gHMQC, gHMBC and gHMQC‐TOCSY experiments. The distinction between oxazole and isoxazole rings was made on the basis of the magnitude of heteronuclear one‐bond ¹J_{C2, H2} (or ¹J_{C3, H3}) coupling constants. Complete analysis of the ¹H NMR spectra of 11 – 14 was achieved by iterative calculations. Gradient selected gHMQC‐TOCSY spectra of phenanthro[9,10‐d][1,3]oxazoles 11 – 14 were obtained at different mixing times (12, 24, 36, 48 and 80 ms) to identify the spin system where the protons of phenanthrene ring at H‐5, H‐6 and at H‐9 and H‐7 and H‐8 were highly overlapping. Copyright © 2003 John Wiley & Sons, Ltd.     

Facile Access to Polycyclic Fused Azo[2,1‐b] [1,3]‐benzothiazinone via Iron‐Catalyzed Cascade Reaction

FeCl₃‐catalyzed cross‐coupling of o‐iodobenzoic acids with azole‐2‐thiols and amidation followed by in situ acidic condensation delivered azo[2,1‐b][1,3]‐benzothiazinones. A simple “one‐pot” operation is conducted for this reaction. This reaction avoids the use of expensive catalytic reagents and provides the desired products containing different azole rings and substituents in good yields.     

An efficient microwave‐assisted synthesis furo[3,4‐b]‐[4,7] phenanthroline and indeno[2,1‐b][4,7]phenanthroline derivatives in water

A series of furo[3,4‐b][4,7]phenanthroline and indeno[2,1‐b][4,7]phenanthroline derivatives were synthesized via a three‐component reaction of aromatic aldehydes, 6‐aminoquinoline and either tetronic acid or 1,3‐indanedione in water, under microwave irradiation without use of any catalyst. This green procedure offers several advantages including operational simplicity, clean reaction, and increased safety for small‐scale high‐speed synthesis.     

Microwave assisted synthesis of thiazolo[3,2‐b][1,2,4]‐triazoles containing 1,8‐naphthyridine moiety

A simple and efficient protocol for the synthesis of 5‐aryl‐2‐(2‐substituted‐1,8‐naphthyridin‐3‐yl)‐thiazolo[3,2‐b][1,2,4]triazoles ( 4 ) is achieved by cyclocondensation of 3‐(2‐substituted‐1,8‐naphthyridin‐3‐yl)‐1,2,4‐triazoles ( 3 ) with α‐halogenoketones in anhyd. methanol under microwave irradiation. The products are obtained in good yields and in a state of high purity.