The synthesis of 2-aryl-3-oxa-1-azaspiro [4.4]non-1-enes

A series of 2-aryl-3-oxa-1-azaspiro[4.4]non-1-enes was prepared by cyclization of the corresponding β-acylamino alcohols (V) with thionyl chloride. Structure proofs for the β-acylamino alcohols and the spiro compounds are given. Infrared and p.m.r. data are reported.     

Synthesis of 3,7,9-triazatricyclo[6.2.1.01,5]undeca-2,4-dienes by reaction of 2-oxa-7-azaspiro[4.4]nona-3,6,8-trienes with sodium hydroxide

Russian Journal of Organic Chemistry -     

Synthesis and Antimycobacterial Activity of New 2-Hydroxy-N-(3-oxo-1-thia-4-azaspiro[4.4]non-4-yl)/(3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2,2-diphenylacetamide Derivatives

Summary. 2-Hydroxy-2,2-diphenylacetohydrazide (2), cyclic ketones, and mercaptoalkanoic acids were converted into 2-hydroxy-N-(3-oxo-1-thia-4-azaspiro[4.4]non/[4.5]dec-4-yl)-2,2-diphenylacetamide derivatives (3, 4) in a one pot procedure. Compounds 3 and 4 were tested for in vitro antimycobacterial activity against M. tuberculosis H37Rv. The compounds were found to provide 0–86% inhibition of mycobacterial growth in the primary screen conducted at 6.25 μg/cm³.     

Synthesis and Antimycobacterial Activity of New 2-Hydroxy- N -(3-oxo-1-thia-4-azaspiro[4.4]non-4-yl)/(3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-2,2-diphenylacetamide Derivatives

2-Hydroxy-2,2-diphenylacetohydrazide (2), cyclic ketones, and mercaptoalkanoic acids were converted into 2-hydroxy-N-(3-oxo-1-thia-4-azaspiro[4.4]non/[4.5]dec-4-yl)-2,2-diphenylacetamide derivatives (3, 4) in a one pot procedure. Compounds 3 and 4 were tested for in vitro antimycobacterial activity against M. tuberculosis H37Rv. The compounds were found to provide 0–86% inhibition of mycobacterial growth in the primary screen conducted at 6.25 μg/cm³.     

Hydrolysis and acylation of imino group in E/Z-isomers of 3,4-dialkyl-8-amino-1-imino-6-morpholin-4-yl-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles

Acid-catalyzed hydrolysis of 3,4-dialkyl-substituted 8-amino-1-imino-6-morpholin-4-yl-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles under mild conditions led to the formation of 8-amino-6-morpholin-4-yl-1-oxo-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles, and their acylation afforded N-(8-amino-9-cyano-6-morpholin-4-yl-2-oxa-7-azaspiro-[4.4]nona-3,6,8-trien-1-ylidene)acetamides. The NMR spectra of compounds synthesized in contrast to the spectra of initial N-unsubstituted imins contained no doubled proton and carbon signals.     

Spiro heterocyclization of 4-aryl-4-oxobutane-1,1,2,2-tetracarbonitriles to 3H-pyrrole derivatives, 2-oxa-7-azaspiro[4.4]nona-3,6,8-trienes

4-Aryl-3-methyl-4-oxobutane-1,1,2,2-tetracarbonitriles reacted with morpholine to give 8-amino-3-aryl-1-imino-4-methyl-6-(morpholin-4-yl)-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles.     

Synthesis and Crystal Structure of 4-(Dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane

<正>The title compound 4-(dichloroacetyl)-1-oxa-4-azaspiro[4. 5] decane (CAS number 71526-07-3, C10H15Cl2NO2, Mr= 252.13) was obtained by the reaction of dichloroacetic acid with 1-oxa-4-azaspiro[4. 5] decane. The crystal is of monoclinic, space group P21ln with the unit cell constants: a = 5.9619(4),b= 10.0066(8), c = 20.0986(4) A,β = 90.194(3)°, V= 1199(4) A3,Z = 4, Dc= 1.397 g/cm3, F(000) = 528, μ(MoKα) = 0.522 mm-1, R = 0.0611 and wR = 0.1656 for 1276 observed reflections (I > 2σ(I)). X-ray analysis reveals that the cyclohexyl adopts a chair conformation and the compound is a chiral one.     

Condensation of 4-benzamido-3-oxothiophan with acrolein. synthesis of 1-benzamido-4-hydroxy-6-thiabicyclo[3.2.1]-octan-8-one and 6-benzoyl-7-hydroxy-2-thia-6-azaspiro[4.4]-nonan-4-one

It is shown that acrolein adds to the 4 position (rather than to the 2 position) of 4-benzamido-3-oxothiophan under the influence of catalysts with basic character; the aldehyde group of the intermediate compound reacts with the amino group (if the reaction is carried out in chloroform) to give 6-benzoyl-7-hydroxy-2-thia-6-azaspiro[4.4]nonan-4-one or (if the reaction is carried out in a mixture of alcohol and chloroform) 1-benzamido-4-hydroxy-6-thiabicyclo-[3.2.1]octan-8-one as a result of intramolecular aldol condensation.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1620–1624, December, 1978.     

Synthesis of 3-Amino-2,2-dimethyl-8-thia-1-azaspiro[4.5]decane

The synthesis of 3-amino-2,2-dimethyl-8-thia-1-azaspiro[4.5]decane is described. Key steps include the addition of prenyl magnesium bromide to a 4-methoxybenzylimine without reversal of stereochemistry and the iodine-initiated aminocyclization to form the azaspirocycle.     

Regioselective synthesis of diaryl sulfides by [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-dienes

Functionalized and sterically encumbered diaryl sulfides were prepared based on [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-dienes.     

The synthesis of 1-thia-6-oxa-6alambda(4)-seleno-3-azapentalene and a 3H-1,2,4-dithiazole

The reaction of thiocarbamoyl isoselenocyanate with a carbanion gave 1-thia-6-oxa-6alambda(4)-seleno-3-azapentalene, which has a hypervalent selenium, as the major product. The by-products 3-diacylmethylidene-5-dimethylamino-3H-1,2,4-dithiazole and thiocarbamate thioanhydride were also formed.     

One-pot synthesis of 2-oxa-7-azaspiro[4.4]nonane-8,9-diones using Mn(III)-based oxidation of 4-acylpyrrolidine-2,3-diones

2-Oxa-7-azaspiro[4.4]nonane-8,9-diones were newly synthesized in good yields by the Mn(III)-based reaction of a mixture of 1,1-diarylethenes and 4-acylpyrrolidine-2,3-diones. Under the stated reaction conditions, the pyrrolidinedione ring remained intact and became one of the two rings of the 2-oxa-7-azaspiro[4.4]nonanedione scaffold. The procedure was simple and the product was easily separated. The structure determination and the mechanism for the formation of the 2-oxa-7-azaspiro[4.4]nonanediones were also discussed.     

A synthesis of 6-functionalized 4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidines

6-Unsubstituted 7-R-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines (R = H or Me) were synthesized via two pathways: (a) deacylation of the corresponding 5-acetyl Biginelli-like precursors in KOH/H₂O and (b) reduction of the corresponding 1,2,4-triazolo[1,5-a]pyrimidines using LiAlH₄. The products could be easily formylated at position 6, which is promising for the further synthesis of functionalized 6-substituted derivatives of 4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines. In contrast, 6-acetyl-7-(4-(N,N-dimethylaminophenyl))-5-methyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine undergoes a cascade process in KOH/H₂O, leading to the formation of a 4,5,8,9-tetrahydro[1,2,4]triazolo[5,1-b]quinazoline derivative.     

Synthesis of 2-azaspiro[4.4]nonan-1-ones via phosphine-catalysed [3+2]-cycloadditions

The phosphine-catalyzed [3+2]-cycloaddition of the 2-methylene γ-lactams 4 and 5 and the acrylate 6 with the ylides derived from the ethyl ester, the amide or the chiral camphor sultam derivative of 2-butynoic acid (7a-c) give directly, or indirectly after reductive cyclization, spiro-heterocyclic products. The acid 32 underwent Curtius rearrangement and then acid hydrolysis to give two novel spiro-cyclic ketones, 41 and 42.     

“4,7-lactams”, intermediates for penems synthesis. II. Total synthesis of (+)-2,2-dimethyl-9-oxo-3-oxa-6-thia-1-azabicyclo [5.2.01,7]nonane

The total synthesis of chiral “4,7-lactam” $\text{4}$ has been accomplished starting from 4-acetoxyazetidinone. An independent route from methyl penicillanate has been used to test the efficiency of the foregoing synthesis.     

Synthesis of new 3<Emphasis Type="Italic">H</Emphasis>-pyrrole derivatives from 3-aryl-2-oxa-7-azaspiro[4.4]nona-3,6,8-trienes

8-Amino-3-aryl-1-imino-4-methyl-6-(morpholin-4-yl)-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles reacted with acetic anhydride to give different products, depending on the solvent. The reaction in tetrahydrofuran gave the corresponding N-acyl derivatives at the imino group, whereas in pyridine 5-amino-2-morpholin-4-yl-3-(1-aryl-1-oxopropan-2-yl)-3H-pyrrole-3,4-dicarbonitriles were formed as a result of opening of the furan ring.     

Synthesis of dialkyl 5-(aryl)-1-phenyl-1H-prazole-3,4-dicarboxylates via a one-pot and four-component reaction

A number of new dialkyl 5-(aryl)-1-phenyl-1H-prazole-3,4-dicarboxylate derivatives have been prepared regiospecifically in moderate to good yield from the cyclocondensation reaction of dialkyl (E)-2-(dialkoxyphosphoryl)-3-(aroyl)-2-butenedioate, derived from the reaction between trimethyl phosphite, an acetylenic ester, and an aroyl chloride, with phenylhydrazine. The reaction is four-component and is carried out under reflux conditions in dry toluene.