Synthesis of quaternary 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazolium salts

The reaction of dihydroimidazole-2-thiol with N-(3-chloro-2-oxopropyl)phthalimide gave 2-[3-(4,5-dihydroimidazol-2-ylsulfanyl)-2-oxopropyl]-1,3-dioxo-1H-isoindole which underwent intramolecular heterocyclization to dihydroimidazothiazole system by the action of a dehydrating agent. Treatment of 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazole with concentrated hydrochloric acid led to the formation of dihydroimidazo[2,1-b]thiazol-3-ylmethanamine. Water-soluble quaternary 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazolium salts were obtained by alkylation of 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazole with alkyl halides.     

Dérivés de l'imidazo(2,1-b) thiazoles—VIII. Etude PMR (ASIS,LIS et NOE) du (tétrahydro-2,3,5,6 imidazo(2,1-b) thiazolylidine-3) acétate d'éthyle

The condensation between 2-mercapto imidazoline and γ-bromo acetylacetic ethyl ester gives the bromhydrate of (5,6-dihydroimidazo(2,1-b) thiazolyl-3) acetic ethyl ester. Under action of basis this compound gives the 2,3,5,6-tetrahydroimidazo(2,1-b) thiazolylidene-3) acetic ethyl ester with allylic transposition. The transoïde configuration and s trans conformation are determined by PMR study (ASIS, LIS and NOE). The structure is different of thise of 3-phenacylidene-2,3,5,6-tetrahydroimidazo(2,1-b) thiazole that have an s cis conformation.     

Synthese von pyridylphenyl-imidazo[2,1-b]thiazolen

The synthesis of the isomeric 6(5)-phenyl-5(6)-pyridyl-2,3-dihydroimidazo[2,1-b]thiazoles are described. Only the synthesis of 5-phenyl-6-(2-pyridyl)-2,3-dihydroimidazo[2,1-b]thiazole failed.     

Synthesis,X-ray crystal structure determination and antiinflammatory activity of the regioisomers: 5-phenyl-6-(4-pyridyl)-2,3-dihydroimidazo[2,1-b]thiazole and 6-phenyl-5-(4-pyridyl)-2,3-dihydroimidazo[2,1-b]thiazole. A structural reassignment

A regiospecific synthesis of 6-phenyl-5-(4-pyridyl)-2,3-dihydroimidazo[2,1-b]thiazole ( 2 ) was accomplished by treatment of 6-phenyl-2,3-dihydroimidazo[2,1-b]thiazole ( 10 ) with the reactive complex of pyridine and ethyl chloroformate followed by oxidation with chromium(VI) oxide. Reaction of 4-phenyl-5-(4-pyridyl)imidazole-2-thione ( 12 ) with 1,2-dibromoethane in the presence of base also gave 2 together with its regioisomer 3 . The structures of 2 and 3 were confirmed by X-ray crystallography. Evaluation, on oral administration, in a one hour arachidonic acid-induced mouse ear inflammation assay, showed the inhibition of edema by 2 (48%) and 3 (34%) to be less than that of the 6-(4-fluorophenyl) analog 1 (SK&/F 86002) (69%), a known antiinflammatory agent.     

Heteroarylation of 6-Aryl-2,3-dihydroimidazo[2,1-b]thiazole with N-(Ethoxycarbonyl)heteroaromatic Salts

The ethyl chloroformate salts of a variety of benzo-fused six membered π-deficient heteroaromatics, including quinoline, isoquinoline, 4-chloroquinoline, 3-bromoquinoline, phthalazine, and quinazoline, reacted with 6-aryl-2,3-dihydroimidazo[2,1-b]thiazole at the 5-position. The dihydroheteroaromatic adducts were oxidized by o-chloranil, sulfur, or electrochemical methodology to form the 5-heteroaromatic-6-aryl-2,3-dihydroimidazo[2,1-b]thiazoles, 10-15 . In each example, the regiochemistry of addition to the heteroaromatic ring was established.     

Dérives de l'imidazo[2,1-b]thiazole. V. Transposition allylique observée au cours de la synthése d'(imino-2 alkyl-3 thiazolinyl-4) acetates d'ethyle et de (dihydro-5,6 imidazo[2,1-b]thiazolyl-3) acetates d'éthyle

Ethyl (6-phenyl-5,6-dihydroimidazo[2,1-b]thiazol-3-yl) acetate hydrobromide shows an allylic transposition in alkaline medium and gives ethyl (6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazol-3-ylidene)acetate. This compound possesses an exocyclic double bond which is stable upon acidification. The intermediate ethyl (2-imino-3-alkylthiazolin-4-yl)-acetates undergo an analogous transposition upon treatment with base, which is reversible upon acidification. These transpositions were observed in the pmr data. The steric constraint and π p π conjugation are discussed in this work.     

2-Oxobenzo[h]chromene: a novel entry for the synthesis of functionalized angular polycyclic azaarenes

An efficient and short synthesis of (5,6-dihydrobenzo[h]pyrido[2,1-b]quinazolin-2-ylidene)acetonitriles, (5,6-dihydrobenzo[h]pyrazino[2,1-b]quinazolin-2-ylidene)acetonitriles and (5,6-dihydrobenzimidazo[1,2-b]benzo[f]isoquinolin-7-yl)acetonitriles in good yields is delineated through base catalyzed ring transformation of 4-(piperidin-1-yl)-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with 2-amino-pyridine, 2-aminopyrazine and (imidazo-2-yl)acetonitrile.     

Imidazo[2,1-b]thiazole carbamates and acylureas as potential insect control agents

Imidazo[2,1-b]thiazole carbamates and acylureas were prepared by reaction of 5-hydroxymethylimidazo-[2,1-b]thiazole and imidazo[2,1-b]thiazole-5-carboxyamide with arylisocyanates. The products formed depend from the substituent bonded at the 6 position of the imidazothiazole moiety, and from the reaction conditions.     

Synthetic applications of aryl radical building blocks for cyclisation onto azoles

2-(2-Bromophenyl)ethyl groups have been used as building blocks in radical cyclisation reactions onto azoles to synthesise tri- and tetra-cyclic heterocycles. 2-(2-Bromophenyl)ethyl methanesulfonate was used to alkylate azoles (imidazoles, pyrroles, indoles and pyrazoles) for the synthesis of the radical precursors. Cyclisations of the intermediate aryl radicals yield new 6-membered rings attached to the azoles. The aryl radicals undergo intramolecular homolytic aromatic substitution onto the azole rings. Tributylgermanium hydride has been used with success to replace the toxic and troublesome tributyltin hydride. Initial studies show that the protocol can be used on solid phase resins. The molecular and crystal structures of methyl 5,6-dihydroimidazo[5,1-a]iso-quinoline-1-carboxylate and methyl 5,6-dihydroimidazo[2,1-a]isoquinoline-3-carboxylate were determined by X-ray crystallography.     

Solid-phase synthesis of fused [2,1-b]quinazolinone alkaloids

Solid-phase synthesis of fused [2,1-b]quinazolinone alkaloids has been developed for the preparation of vasicinone and deoxyvasicinone by two approaches. The derivative of polymer-supported p-nitrophenyl carbonate was attached to anthranilic acid and then coupled with various bromo-lactams. This resin-linked bromo intermediate upon acetylation, hydrolysis and resin cleavage gave the cyclized [2,1-b]quinazolinones (vasicinone). Alternatively, resin-linked azido-benzoic acids were coupled with bromo-substituted lactams followed by cyclization in an aza-Wittig reductive cyclization process giving the bromo-substituted quinazolinone intermediates, with subsequent acetylation, hydrolysis and resin cleavage affording the fused [2,1-b]quinazolinones.     

Synthèse d'hétérocycles en catalyse par transfert de phase

A general study of the chemical behavior of heterocyclic anions, dianions and dianionic reagents under phase transfer catalysis conditions allowed us to synthesize various heterocyclic compounds such as imidazo[2,1-b]thiazole and derivatives; imidazo[2,1-b]thiazine and imidazo[2,1-b]benzothiazepine. Reaction conditions e.g., catalyst, solvent, temperature, etc., are indicated.     

Metaboliten der 1,5-Dihydroimidazo[2,1-b]chinazolin-2(3H)-one. Synthese und Reaktionen einiger 1,5-Dihydro-3-hydroxyimidazo[2,1-b]chinazolin-2(3H)-one

Metabolites of 1,5-Dihydroimidazo[2,1-b ]quinazolin-2(3H)-ones. Preparation and Reactions of Some 1,5-Dihydro-3-hydroxyimidazo[2,1-b]quinazolin-2(3H)-ones Hydroxylated 1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-ones 2–4 and 6 were isolated as metabolites of imidazoquinazolinones 1a and 1b , respectively. The synthesis of 1,5-dihydro-3-hydroxy-3-methylimidazo[2,1-b]quinazolin-2(3H)-ones 3 , 4 , and 6 , and the preparation of some derivatives thereof is described.     

Novel nitroimidazo[2,1-b]oxazole formation from reaction of 2,4(5)-dinitroimidazole with oxiranes

A novel reaction for the synthesis of 2,3-dihydroimidazo[2,1-b]oxazoles has been described by condensation of 2,4(5)-dinitroimidazole with a series of oxiranes.     

Arylidene imidazothiazoles. Synthesis,structure and benzodiazepine receptor binding

A series of arylidene imidazo[2,1-b]thiazoles was synthesized, in order to investigate the influence of different spatial arrangements of the arylidene substituent towards the bicyclic structure of imidazo[2,1-b]-thiazole on benzodiazepine receptor affinity. 1,2- And 2,3-cyclized derivatives of mono- and di-substituted Z-5-arylidene-2-thiohydantoins were investigated. As an example of E isomers E-5-benzylidene-2,3-dihydroimidazo[2,1-b]thiazol-6(5H)-one was obtained. The spatial arrangement of the arylidene sub stituent toward the bicyclic structure as well as the character of isomers had little influence on the benzo diazepine receptor affinity of the compounds. It seems that the greatest influence on biological activity has the nature and the number of substituents on the phenyl ring. All investigated imidazo[2,1-b]thiazoles were less active than previously described arylidene imidazo[2,1-b]thiazepinones.     

NBS mediated protocol for the synthesis of N-bridged fused heterocycles in water

A facile and environmental friendly protocol for the synthesis of N-bridged fused bicyclic compounds such as imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazo[2,1-b]thiazole, from commercially available starting materials has been developed. The reaction proceeds via NBS mediated in situ formation of α-brominated intermediate of corresponding aromatic ketones, 1,3-diketones, β-keto esters, followed by trapping with suitable nucleophiles to provide these versatile imidazole fused bicyclic heterocycles in good yields under metal-free conditions.     

Oxone®-mediated direct arylselenylation of imidazo[2,1-b]thiazoles,imidazo[1,2-a]pyridines and 1H-pyrazoles

Oxone mediated reaction of imidazo[2,1-b]thiazole, imidazo[1,2-a]pyridine and 1H-pyrazole derivatives with diaryl diselenides is presented here. The methodology represents an efficient and simple protocol for carrying out the selective synthesis of 5-arylselanyl-imidazo[2,1-b]thiazoles, 3-arylselanyl-imidazo[1,2-a]pyridines and 4-arylselanyl-1H-pyrazoles in high yields using a stable, nontoxic and cheap oxidant. The reactions were conducted at 60?°C in air using acetonitrile as solvent. Alternatively, the use of ultrasound irradiation is presented as a tool for fast and efficient energy transfer that significantly reduced the reaction time.     

Research on heterocyclic compounds. XXIII. Phenyl derivatives of fused imidazole systems

The reaction of various heteroarylamines with ethyl 2-benzoyl-2-bromoacetate was used to obtain some imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, imidazo[2,1-b]thiazoles and imidazo[2,1-b]benzothiazoles characterized by the presence of a phenyl moiety on the imidazole ring. In the case of thiazole and benzothiazole derivatives, unexpected by-products were isolated and their structures elucidated.     

Iodine-promoted direct sulfenylation of 2,3-dihydroimidazo[2,1-b]thiazoles with disulfides

A novel and facile method for the direct sulfenylation of 2,3-dihydroimidazo[2,1-b]thiazoles with disulfides has been developed. The transformation is promoted by iodine under metal-free conditions, providing the corresponding products in moderate to good yields.     

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.     

Concerning the preparations of some pyridylimidazothiazole derivatives

The preparations of some 4-pyridylimidazo[2,1-b]thiazole and -imidazo[5,1-b]thiazole derivatives are described. In some of the cyclizations to form the imidazothiazole ring systems, trifluoroacetic anhydride, the dehydration reagent employed, participated in the reaction leading to products bearing a trifluoromethyl or trifluoroacetyl substituent.