Uncatalyzed solventless Diels-Alder reaction of 2-amino-3-nitroacrylate: synthesis of new epimeric 2-amino-3-nitro-norbornene- and norbornane-2-carboxylic acids

A highly diastereoselective Diels-Alder reaction between cyclopentadiene and ethyl (Z)-2-N-Boc-amino-3-nitroacrylate in neat conditions affords the ethyl 2-t-butoxycarbonylamino-3-endo-nitro-bicyclo[2.2.1]hept-5-ene-2-exo-carboxylate: a new constrained carbocyclic amino acid. Catalytic hydrogenation of this cycloadduct gave the corresponding reduced norbornane derivative. A preliminary investigation into the chemistry of these two amino acids was performed. In particular, the epimerization to their corresponding 3-exo-nitro compounds by treatment both with acid and base was studied. From this study, valuable information on the endo/exo process at the C-3 carbon atom, as well as on the stability of the different stereomers, was obtained. The stability is closely related to the presence or the absence of the double bond in the ring and to the substitution pattern. Finally, deprotection of the amino acid function has been performed.     

Reactivity of 3-formyl- and 3-cyanothiochromones toward some N- and C-nucleophiles. Novel synthesis of 3-substituted 2-aminothiochromones

The reactions of 3-formylthiochromone with o-phenylenediamines, o-aminobenzenethiol, and indoles proceeded at the aldehyde group to give 3-(benzimidazol-2-yl)thiochromone, 3-(benzothiazol-2-yl)thiochromone, and 3-di(indol-3-yl)methylthiochromones, respectively. 3-Formyl- and 3-cyanothiochromones react with primary aromatic amines and phenylhydrazine to give the corresponding anils and phenylhydrazones of 3-formyl- and 2-amino-3-formylthiochromones. The reaction of 3-cyanochromones with o-phenylenediamines gave 2-amino-3-[(2-aminophenyl)iminomethyl]-4H-chromen-4-ones.     

Reactivity of allenoates toward aziridines: [3+2] and formal [3+2] cycloadditions

The reactivity of buta-2,3-dienoates toward aziridines is reported. Allenoates react as 2π-component in the [3+2] cycloaddition with the azomethine ylide generated from cis-1-benzyl-2-benzoyl-3-phenylaziridine affording 4-methylenepyrrolidines in a site-, regio-, and stereoselective fashion. Under conventional thermolysis, cis- and trans-2-benzoyl-1-cyclohexyl-3-phenylaziridines showed a different reactivity. These aziridines participate in formal [3+2] cycloadditions with allenes via C-N bond cleavage of the three-membered ring leading to functionalized pyrroles.     

Fluoroalkyl-containing 2-arylhydrazono-1,3-dicarbonyl compounds in the reactions with ethylenediamine and polyethylenepolyamines

Acyclic N,N′-(poly)ethylene-bis(2-arylazo-1,3-aminovinylketones) are the main products in the reactions of fluoroalkyl-containing 2-arylhydrazono-1,3-diketones with ethylenediamine, diethylenetriamine and triethylenetetramine. Nickel(II) and copper(II) chelates were obtained from N,N′-ethylene-bis(2-arylazo-1,3-aminovinylketones). 2-Arylhydrazono-3-fluoroacyl esters formed N,N′-ethylenediamides of 2-arylhydrazono-3-fluoroacylpropionic acids with ethylenediamine. Interaction of 2-arylhydrazono-3-fluoroacyl esters with diethylenetriamine and triethylenetetramine resulted in and decomposition products.     

Facile synthesis of 2-carboxanilido-3-arylquinazolin-4-ones from N1-(2-carboxyphenyl)-N2-(aryl)oxalamides

A simple and efficient approach for the synthesis of novel 2-carboxanilido-3-arylquinazolin-4-ones via the one-pot condensation of readily available N¹-(2-carboxyphenyl)-N²-(aryl)oxalamides with various aromatic amines is described. Notably, this methodology allows us to synthesize 3-aryl-quinazolin-4-ones using aromatic amines with various substituents, both electron-donating and electron-withdrawing, which ensures structural diversity of the products and an atomic-economic process.     

Synthesis of new 3,3-dimethoxyazetidine-2-carboxylic acid derivatives

Cyclization of γ-amino-α-bromocarboxylic esters resulted in an efficient synthesis of new 3,3-dimethoxyazetidine-2-carboxylates, that is, methyl N-t-butyl-3,3-dimethoxyazetidine-2-carboxylic ester and 3,3-dimethoxyazetidine-2-carboxylic acid, or 3-bromo-4,4-dimethoxypyrrolidin-2-ones, depending on the substituent at nitrogen. Reduction of the 3,3-dimethoxyazetidine-2-carboxylates gave the corresponding 3,3-dimethoxy-2-(hydroxymethyl)azetidines. These novel cyclic amino acid derivatives, available on multigram scale, have a suitably protected carbonyl function at the 3-position, which enables further functionalization.     

A new general approach to 4-substituted-3-halo-2-quinolones

A general procedure for the preparation of 4-substituted-3-halo-2-quinolones (halo = F, Cl, Br) utilizing 2-halo diethylphosphonoacetic acids (halo = F, Cl, Br) and o-aminophenylketones as the starting materials is described. The title compounds are obtained by an intramolecular Horner-Wadsworth-Emmons olefination of halogen-containing N-acyl-o-aminophenylketones. The transformation process is generally applicable under mild conditions.     

Unexpected dimerization during hydrogenation of 2-(2-pyridylmethylene)-3(2H)-benzofuran-3-ones

Palladium catalyzed hydrogenation of 2-(2-pyridylmethylene)-3(2H)-benzofuran-3-ones (1-3) gave besides the expected 2,α-dihydro products 8-10 pentacyclic dimers formed by an attack of a semihydrogenated species on the substrate.     

Structural revision in the reactions of 3-cyanochromones with primary aromatic amines. Improved synthesis of 2-amino-3-(aryliminomethyl)chromones

3-Cyanochromones react with primary aromatic amines to give 2-amino-3-(aryliminomethyl)chromones as the sole products or as their mixtures with Z- and E-3-anilino-2-salicyloylacrylonitriles, depending on the reaction conditions. With aliphatic amines, 2-amino-3-(alkyliminomethyl)chromones are obtained in good yields. The reaction of 3-cyanochromone with o-phenylenediamine is reinvestigated and proof for the product structure and a possible reaction pathway are presented.     

Facile stereoselective synthesis of cis- and trans-3-alkoxyazetidin-2-ones

A highly stereoselective synthesis of cis- and trans-3-alkoxy-3-phenyl/benzylthioazetidin-2-ones is described. The reaction of α-chlorosulfide-β-lactams with various alcohols catalyzed by a Lewis acid such as ZnCl₂ in the presence of molecular sieves (3-4 Å) leads to cis-3-alkoxy-3-phenyl/benzylthio-β-lactams whereas treatment of potassium 2-alkoxy-2-phenylthioethanoate with appropriate Schiff's base using POCl₃ in the presence of triethylamine leads to the formation of trans-3-alkoxy-3-phenylthioazetidin-2-ones as major products.     

Convenient and efficient stereoselective synthesis of (2Z)-2-(chloromethyl)alk-2-enoates using iron(III) or indium(III) chloride

The stereoselective synthesis of (2Z)-2-(chloromethyl)alk-2-enoates has been achieved efficiently and in high yields and in short reaction times from Baylis-Hillman adducts, 3-hydroxy-2-methylene-alkanoates, by treatment with FeCl₃ or InCl₃ at room temperature.     

Chrysanthemyl 2-acetoxy-3-methylbutanoate: the sex pheromone of the citrophilous mealybug, Pseudococcus calceolariae

Headspace volatiles collected from virgin females of the citrophilous mealybug, Pseudococcus calceolariae, contain three compounds not present in the headspace of control samples. The main female-specific compound is identified as [2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropyl]methyl 2-acetoxy-3-methylbutanoate (chrysanthemyl 2-acetoxy-3-methylbutanoate). The other two compounds are identified as [2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropyl]methanol (chrysanthemol) and [2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropyl]methyl 2-hydroxy-3-methylbutanoate (chrysanthemyl 2-hydroxy-3-methylbutanoate). Traps baited with 100 μg and 1000 μg of chrysanthemyl 2-acetoxy-3-methylbutanoate captured 4- and 20-fold more males than traps baited with virgin females.     

Efficient stepwise and one pot three-component synthesis of 2-amino-4-(2-oxo-2H-chromen-3-yl)thiophene-3-carbonitriles

Environmentally benign conditions have been developed for the synthesis of 2-amino-4-(2-oxo-2H-chromen-3-yl)thiophene-3-carbonitriles (3) starting from 3-acetyl-2H-chromen-2-one (1) through the intermediacy of 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)malononitrile (2) using the Knoevenagel condensation followed by the Gewald reaction. Alternatively, 3 could also be prepared in a one pot method by treating equimolar amounts of 1, malononitrile, and elemental sulfur. The merits of this preparation are mild reaction conditions, easy work-up procedure, and good yields.     

General synthesis of mono-, di-, and tri-acetylated indoles from indolin-2-ones

Having developed the one-pot triacetylation of indolin-3-ones, we have now devised a simple two-step reaction sequences to produce di- and mono-acetylated indoles from indolin-2-ones. The indolin-2-ones were first subjected to acetylation in the presence of acetic anhydride and a catalytic amount of N,N-dimethylaminopyridine to give 2-acetoxy-1,3-diacetylindoles. Subsequently, an enzyme-assisted deacetylation resulted in the chemoselective deprotection of the acetoxy group to produce 1,3-diacetyl-2-hydroxyindoles. However, a chemical deacetylation of 2-acetoxy-1,3-diacetylinoles under mild basic or acidic conditions resulted in the formation of 3-acetyl-2-hydroxyindoles.     

An efficient synthesis of optically active 3-amino-3-alkyl-2-oxetanones

An efficient two-step synthesis of p-toluenesulfonic acid salts of optically active 3-amino-3-alkyl-2-oxetanones is reported that involves cyclization of N-Boc-α-alkylserines under Mitsunobu reaction conditions followed by deprotection of the amino group with trifluoroacetic acid in the presence of anhydrous p-toluenesulfonic acid.     

Base-catalyzed cyclization reaction of 2-chloroquinoline-3-carbonitriles and guanidine hydrochloride: a rapid synthesis of 2-amino-3H-pyrimido[4,5-b]quinolin-4-ones

t-BuOK-catalyzed cyclization of 2-chloroquinoline-3-carbonitriles with guanidine hydrochloride provided simple and rapid synthesis of 2-amino-3H-pyrimido[4,5-b]quinolin-4-ones in very short reaction time with good yield. Other 1,3-binucleophiles are found to react at the same rate. This methodology could be extended with their 3-formyl and 3-ester derivatives for the synthesis of pyrimido annulated quinolines.     

A versatile synthesis of 2-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones

A mild and general strategy for the synthesis of 2-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones is described. The seven-membered lactam is prepared by intramolecular amide bond formation from the intermediate amino acid, which is obtained either by reductive alkylation of a variety of amines with N-Boc,N-Me-ortho-formyl-Phe and Phth-ortho-formyl-Phe, or by reductive amination of a variety of aldehydes with N-Boc-ortho-aminomethyl-Phe.     

A new, one-pot, multi-component synthesis of imines of 3-amino-2-arylimidazo[1,2-a]pyridines, 3-amino-2-arylimidazo[1,2-a]pyrazines, and 3-amino-2-arylimidazo[1,2-a]pyrimidines

An efficient, one-pot, multi-component synthesis of 3-amino-2-arylimidazo[1,2-a]pyridines, 3-amino-2-arylimidazo[1,2-a]pyrazines, and 3-amino-2-arylimidazo[1,2-a]pyrimidines is described. Heating a mixture of a 2-aminopyridine, 2-aminopyrazine or 2-aminopyrimidine, a benzaldehyde, and imidazoline-2,4,5-trione under solvent-free conditions afforded imine derivatives of the title compounds in excellent yields. Single-crystal X-ray analysis conclusively confirms the structure of these bridgehead bicyclic 5-6 heterocycles.     

Formation of new 4-isocyanobut-2-enenitriles by thermal ring cleavage of 3-pyridyl azides

A new thermal ring cleavage of 3-pyridyl nitrenes for the formation of 4-isocyanobut-2-enenitrile products is reported. Thermolysis of 4-(thien-3-yl)-3-pyridyl azide 1 and 3-azido-4-(1-TIPS-1H-pyrrol-3-yl)pyridine 5 afforded two new isonitrile-nitrile products by ring cleavage; 4-isocyano-2-(thiophen-3-yl)but-2-enenitrile (3, 27%) and 4-isocyano-2-(1-TIPS-1H-pyrrol-3-yl)but-2-enenitrile (7, 20%), in addition to our previously reported pyrido[3,4-b]thienopyrrole (2, 29%) and pyrido[3,4-b]pyrrolo[3,2-d]pyrrole (6, 71%) products. Minor amounts of 2-(thien-3-yl)-1H-pyrrole-3-carbonitrile (4, 6%), formed by ring contraction, were also isolated after thermolysis of azide 1. Isonitriles 3 and 7 underwent degradation into amine 3b and formamide 7a by acidic hydrolysis. The nature and chemistry of compounds 3, 4 and 7 were investigated.     

Efficient and selective deprotection method for N-protected 2(3H)-benzoxazolones and 2(3H)-benzothiazolones

Cyclic carbamate flanked with heterocyclic or aliphatic moieties are frequently used in medicinal chemistry. The synthesis of derivatives bearing a free NH often requires the use of a protection method. A literature search reveals very few protection/deprotection methods for cyclic carbamates. In this paper, we described different methods applicable to 2(3H)-benzoxazolone and 2(3H)-benzothiazolone.