An efficient diastereoselective synthesis of spiro pyrido[2,1-b][1,3]oxazines via a novel pyridine-based three-component reaction

The zwitterions generated from pyridine and dialkyl acetylenedicarboxylate (DAAD) reacted with benzofuran-2,3-diones to form highly substituted spiro pyrido[2,1-b][1,3]oxazines in good to high yields without using a catalyst.     

Intramolecular amidation: synthesis of novel imidazo[2,1-b][1,3,4]thiadiazole and imidazo[2,1-b][1,3]thiazole fused diazepinones

Novel heterocyclic systems 2-alkyl/aryl-9-(2-hydroxybenzylidene)-7,9-dihydro-8H-[1,3,4]thiadiazolo[2′,3′:2,3]imidazo[4,5-d][1,2]diazepin-8-one and 9-(2-hydroxy-benzylidene)-3,3-dimethyl-3,4,7,9-tetrahydro-2H-11-thia-4b,6,7,10-tetraazaindeno[1,2-a]azulene-1,8-dione are synthesized via an intramolecular amidation reaction. An interesting ring opening and cyclization of 2-alkyl/aryl-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde and 6,6-dimethyl-8-oxo-2-(2-oxo-2H-chromen-3-yl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole-3-carbaldehyde are discussed.     

An efficient one-pot synthesis of pyrimido[2,1-b][1,3]thiazine derivatives by reaction of activated acetylenes, thiouracils, and isocyanides

The reactive 1:1 zwitterionic intermediate, formed by the addition of isocyanides to dialkyl acetylenedicarboxylates, was trapped by thiouracils to yield a ketenimine intermediate, which cyclized and then rearranged to afford pyrimido[2,1-b][1,3]thiazines in good yields.     

Gas-phase thermolysis of 1-acylnaphtho[1,8-de][1,2,3]triazines. Interesting direct routes towards condensed naphtho[1,8-de]heterocyclic ring systems

FVP pyrolysis of 1-acylnaphtho[1,8-de][1,2,3]triazines at 500 °C and 10⁻² Torr gave exclusively the corresponding 2-substituted naphtho[1,8-de][1,3]oxazines. The latter was also obtained by static pyrolysis but in lower yield along with the corresponding N-(naphthalen-1-yl)acylamides. The reaction was studied kinetically and mechanistically.     

Efficient one-pot synthesis of 2-oxo-1,9a-dihydro-2H-pyrido[1,2-a]pyrimidine derivatives

Pyridines react smoothly with dialkyl acetylenedicarboxylates in the presence of isocyanates to produce dialkyl 2-oxo-1,9a-dihydro-2H-pyrido[1,2-a]pyrimidine 3,4-dicarboxylates in excellent yields.     

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.     

Intermolecular cycloaddition of nonstabilized azomethine ylides generated from 1,3-thiazolidine-4-carboxylic acids: synthesis of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles

The 1,3-dipolar cycloaddition of dimethyl acetylenedicarboxylate with nonstabilized azomethine ylides, generated via the decarboxylative condensation of 1,3-thiazolidine-4-carboxylic acids with aldehydes, afforded 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazole derivatives. 2-Substituted-1,3-thiazolidine-4-carboxylic acids led to the stereoselective formation of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles. Quantum-chemistry calculations were carried out allowing the rationalization of the observed stereoselective formation of the anti-dipole.     

A novel synthesis of new 2-aryl-6-(arylamino)-1H-imidazo[1,2-b]pyrazole-7-carbonitrile derivatives

New 2-aryl-6-(arylamino)-1H-imidazo[1,2-b]pyrazole-7-carbonitriles are synthesized in good yields, via cyclocondensation of 5-amino-1-(2-oxo-2-arylethyl)-3-(arylamino)-1H-pyrazole-4-carbonitriles, which are prepared by the reaction of 5-amino-3-arylamino-1H-pyrazole-4-carbonitriles and α-bromoacetophenone derivatives in the presence of K₂CO₃ using acetone as the solvent.     

Microwave assisted synthesis of novel imidazo [2,1-b]thiazole derivative attached to quinoxalinones

3-(6-Phenylimidazo[2,1-b]thiazol-5-yl)quinoxalin-2(1H)-ones (qunoxalinone) (6a-q) have been synthesized by the reaction of ethyl 2-oxo-2-(6-phenylimidazo[2,1-b]thiazol-5-yl)acetates (4a-e) with suitably substituted o-phenylenediamines (5a-f) under microwave heating. The ethyl 2-oxo-2-(6-phenylimidazo[2,1-b]thiazol-5-yl)acetates (4a-e) were prepared by the reaction of 6-phenylimidazo[2,1-b]thiazoles (3a-e) with ethyl chlorooxoacetate in refluxing 1,4-dioxane whereas the thiazoles (3a-e) were synthesized by the reaction of 2-bromo-1-phenylethanones (2a-e) with thiazol-2-amine in refluxing acetone.     

First construction of 12H-thiochromeno[2,3-b]quinolines and 5H-benzo[7,8]thiocino-[2,3-b]quinolines via intramolecular Friedel-Crafts reaction of Morita-Baylis-Hillman adducts

An acid-promoted intramolecular Friedel-Crafts reaction of the Morita-Baylis-Hillman adducts 3 derived from 2-arylthioquinolin-3-carbaldehydes 2 was investigated. Interestingly, promoted by sulfuric acid, the substrates with electron-donating groups on the aromatic ring gave six-membered fused-ring 12H-thiochromeno[2,3-b]quinolines 4 with good yields, while those with electron-withdrawing groups afforded eight-membered fused-ring 5H-benzo[7,8]thiocino[2,3-b]quinolines 5 in moderate yields. Using triflic acid instead of sulfuric acid, only products 4 could be obtained under the similar condition.     

One pot synthesis of imidazo[2,1-b]thiazoles and benzo[d]thiazolo[3,2-a]imidazoles

A series of imidazo[2,1-b]thiazole and benzo[d]thiazolo[3,2-a]imidazole analogues were synthesized by stirring an equimolar mixture of dibenzoylacetylene with imidazole/thiazole derivatives in toluene or acetonitrile at room temperature. The products were generated in good yields and characterized by standard analytical techniques such as IR, ¹H NMR, ¹³C NMR and mass spectrometry. The structure of products 19, 20, 22, 24 and 25 were also unambiguously confirmed by single crystal X-ray analysis.     

Solvent-free sonochemical one-pot three-component synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones

A rapid and efficient one-pot three-component protocol for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones 4 and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 6 has been developed by domino coupling of phthalhydrazide, 1,3-diketones, and aldehydes under solvent-free conditions at 80 °C as well as under solvent-free ultrasound irradiation at room temperature promoted by (S)-camphorsulfonic acid.     

Synthesis of bridgedhead azolo[3,2-a]pyrimidines and imidazo[2,1-b]thiazines through ring transformation of 2H-pyran-2-ones

Suitably functionalized 3-carbomethoxy/cyano-2H-pyran-2-ones are excellent synthons for the synthesis of arenes and heteroarenes of therapeutic importance. The compounds 6-aryl-3-cyano-4-methylsulfanyl-2H-pyran-2-ones have been transformed into bridgedhead azolopyrimidines and imidazothiazines through thermal and base-induced ring transformation reactions with aminoazoles and imidazolidin-2-thiones, respectively.     

Novel synthesis of 2,2-dialkyl-3-dialkylamino-2,3-dihydro-1H-naphtho[2,1-b]pyrans

2,2-Dialkyl-3-dialkylamino-2,3-dihydro-1H-naphtho[2,1-b]pyrans were prepared from 2-naphthol, a secondary amine, and 3-hydroxy-2,2-dialkylpropanal in the presence of a catalytic amount of p-toluenesulfonic acid. This one-pot reaction involves retro-aldol disintegration of 3-hydroxy-2,2-dialkylpropanal followed by formation of a Mannich base intermediate from 2-naphthol, a secondary amine, and formaldehyde (retro-aldol product). This Mannich base then disproportionates into a quinone methide intermediate and the secondary amine is regenerated. It then forms an enamine intermediate with 2,2-dialkylacetaldehyde (another retro-aldol product). Finally, the quinone methide intermediate undergoes electrocyclic ring closure with enamines to produce the title compounds.     

Zinc triflate-catalyzed synthesis of pyrazino[2,1-b]quinazoline-3,6-diones

Using zinc triflate, the direct one-pot double cyclodehydration of linear tripeptides to the total synthesis of pyrazino[2,1-b]quinazoline-3,6-diones (1a-l) on solid support was achieved with good overall yields in short reaction time. These syntheses of the pyrazino[2,1-b]quinazoline-3,6-diones were conveniently achieved in only three steps, starting from the amino acid-bound Wang resin.     

Iron fluoride: the most efficient catalyst for one-pot synthesis of 4H-pyrimido[2,1-b]benzothiazoles under solvent-free conditions

A new iron fluoride assisted convenient and efficient strategy for the preparation of 4H-pyrimido[2,1-b]benzothiazoles derivatives in solvent-free media is described. The reactions can be performed at low-catalyst loadings with excellent functional group tolerance. The catalyst can be readily recovered and reused for next reaction for at least three runs without any significant impact on the yields of the products. The easy recovery of the catalyst and high yield of the products make the protocol attractive, sustainable, and economic.     

Reaction between isocyanides and dialkyl acetylenedicarboxylates in the presence of 2,4-dihydro-3H-pyrazol-3-ones. One-pot synthesis of highly functionalized 7-oxo-1H,7H-pyrazolo[1,2-a]pyrazoles

The reactive 1:1 intermediate produced in the reaction between isocyanides and dialkyl acetylenedicarboxylates was trapped by 2,4-dihydro-3H-pyrazol-3-ones to yield highly functionalized 7-oxo-1H,7H-pyrazolo[1,2-a]pyrazoles in fairly good yields.     

An efficient synthesis of 4,5-dihydronaphtho[2,1-b]furan through a novel ring transformation of 2H-pyran-2-one

An innovative route for the synthesis of substituted naphtho[2,1-b]furan has been delineated through a ring transformation reaction of suitably functionalized 2H-pyran-2-ones by reaction with 6,7-dihydro-5H-benzofuran-4-one, in good yield.     

A rapid and convenient synthesis of novel 1-imino-2,3-dihydro-1H-pyrazino[2,1,-b]quinazolin-5-ones

Exploring original approaches for the synthesis of therapeutic agents having a quinazoline part, we discovered that novel 3,4-dihydro-2H-pyrazino[2,1,-b]quinazolines (3) may be rapidly and easily obtained via the chemistry of 4,5-dichloro-1,2,3-dithiazolium chloride (1). Our synthetic approach of this reaction is described with the aim of obtaining a well-controlled access to this very rarely described pyrazino[2,1,-b]quinazoline skeleton.     

Chemistry of cyclopropenones: synthesis of new pyrrolo[2,1-b]-1,3,4-oxadiazoles

2,3-Diphenylcyclopropenone (1) reacts with ylidene-N-phenylhydrazine-carbothioamides 2a-e to form the pyrrolo[2,1-b]-1,3,4-oxadiazoles 5a-e.