Reactions of 4-amino-4-azatricyclo[5.2.1.0<Superscript>2,6-<Emphasis Type="Italic">endo</Emphasis></Superscript>]dec-8-ene-3,5-dione with dicarboxylic acid anhydrides

Reactions of 4-amino-4-azatricyclo[5.2.1.0^2,6-endo ]dec-8-ene-3,5-dione (hydrazinolysis product of endic anhydride) with succinic, maleic, cis-cyclohexane-1,2-dicarboxylic, endic, phthalic, and 1,8-naphthalic anhydrides were studied. Procedures for the preparation of the corresponding hydrazido acids and bis-imides were proposed. Their reactions with peroxyformic acid, depending on the substrate nature, led to the formation of both epoxy hydrazido acids and epoxy imides. The unsaturated adducts reacted with p-nitrophenyl azide to give the corresponding triazole derivatives.     

New derivatives of 2-(3,5-Dioxo-4-azatricyclo[5.2.1.0<Superscript>2,6-<Emphasis Type="Italic">endo</Emphasis></Superscript>]dec-8-en-4-yl)acetic acid. Synthesis and reactivity

New urea, carbamates, and carboxamides of the norbornene series were synthesized on the basis of 4-isocyanatomethyl-4-azatricyclo[5.2.1.0^2,6-endo ]dec-8-ene-3,5-dione, and their behavior in reactions with various electrophiles was studied. The structure of the isolated compounds was confirmed by the IR and ¹H NMR spectra.     

Features of reactions between (3,5-dioxo-4-azatricyclo-[5.2.1.0<Superscript>2-<Emphasis Type="Italic">endo</Emphasis>,6-<Emphasis Type="Italic">endo</Emphasis></Superscript>]dec-8-en-4-yl)carboxylic acids and <Emphasis Type="Italic">p</Emphasis>-nitrophenyl azide

Reactions were performed of (3,5-dioxo-4-azatricyclo[5.2.1.0^{2-endo,6-endo} ]dec-8-en-4-yl)carboxylic acids and their derivatives with p-nitrophenyl azide. A significant fact of the involvement of the carboxy group into the formation of aziridine ring was established and the intermolecular character of this process was confirmed. The structure of compounds synthesized was proved by IR and ¹H NMR spectra.     

Synthesis of 5-(Benzylamino)-<Emphasis Type="Italic">exo</Emphasis>-3-azatricyclo-[5.2.1.0<Superscript>2,6</Superscript>]decan-4-one derivatives

5-(Benzylamino)-exo-3-azatricyclo[5.2.1.0^2,6]decan-4-one derivatives were synthesized in up to 94% yield by condensation of norbornane-fused 3-aminopyrrolidin-2-one with aromatic aldehydes.     

Synthesis of novel 4<Emphasis Type="Italic">H</Emphasis>-furo[3,2-c]pyran-4-ones and 4<Emphasis Type="Italic">H</Emphasis>-furo[3,2-<Emphasis Type="Italic">c</Emphasis>]chromen-4-ones

It was found that the condensation of two equivalents of 4-hydroxy-6-methyl-2H-pyran-2-one or 4-hydroxycoumarin with arylglyoxals in boiling formic acid leads to 4H-furo[3,2-c]-pyran-4-ones or 4H-furo[3,2-c]chromen-4-ones, respectively.     

Synthesis of 6-methyl-8<Emphasis Type="Italic">H</Emphasis>-dibenzo[<Emphasis Type="Italic">a</Emphasis>,<Emphasis Type="Italic">g</Emphasis>]quinolizin-8-imines <Emphasis Type="Italic">via Reissert</Emphasis> compounds

Alkylation of Reissert compounds derived from 3-methylisoquinolines with several 2-cyanobenzylbromides followed by hydrolytic cleavage provided the corresponding 1-benzyl-3-methylisoquinolines. Treatment of the latter with methylmagnesiumiodide caused cyclization to the title compounds rather than formation of 2-acetylbenzylisoquinolines.     

Synthesis of 3-N-substituted <Emphasis Type="Italic">exo</Emphasis>-3,4 diazatricyclo[5.2.1.0<Superscript>2,6</Superscript>]dec-4-enes

Treatment of exo-3,4-diazatricyclo[5.2.1.0^2,6]dec-4-ene with methyl acrylate, acrylonitrile, ethylene oxide, acetic acid and nitrosonium cation gave a series of 3-N-substituted exo-3,4-diazatricyclo[5.2.1.0^2,6]dec-4-enes. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 533–537, April, 2007.     

Reaction of N-substituted <Emphasis Type="Italic">exo</Emphasis>-2-hydroxy-5-oxo-4-oxatricyclo[4.2.1.0<Superscript>3,7</Superscript>]nonane-<Emphasis Type="Italic">endo</Emphasis>-9-carboxamides with acetic acid

Acylation of N-substituted exo-2-hydroxy-5-oxo-4-oxatricyclo[4.2.1.0^3,7]nonane-endo-9-carboxamides on heating in boiling glacial acetic acid gave the corresponding trans-diacetoxy imides of the norbornane series. The effect of the reaction time on the product composition was studied in the reaction with exo-2-hydroxy-N-(4-methylphenyl)-5-oxo-4-oxatricyclo[4.2.1.0^3,7]nonane-endo-9-carboxamide. The structure of the resulting norbornane-2,3-dicarboximides was confirmed by IR, ¹H NMR, and mass spectra, and the structure of N-(2,5-dimethylphenyl)-exo-2,endo-3-diacetoxybicyclo[2.2.1]heptan-endo-5,endo-6-dicarboximide was additionally proved by X-ray analysis.     

Synthesis of Novel <Emphasis Type="Italic">D</Emphasis>-<Emphasis Type="Italic">Seco</Emphasis>-Pregnenes

Summary. A new synthetic route was developed for the preparation of trans-3-hydroxy-16,17-seco-pregna-5,17(20)-dien-16-al, using Grob fragmentation as the key step. This seco-steroid contains a formyl group and an unsaturated side-chain in a sterically favourable position, and is therefore a promising starting material for the synthesis of novel condensed steroid heterocycles.Received March 22, 2003; accepted April 22, 2003 Published online September 25, 2003     

Molecular and crystal structure of ethylene acetal of <Emphasis Type="Italic">endo</Emphasis>-<Emphasis Type="Italic">endo</Emphasis>-3-trityloxymethylbicyclo[3.3.1]nonane-2-on-7-ol

Molecular structure of ethylene acetal of 3-trityloxymethylbicyclo[3.3.1]nonane-2-on-7-ol (3) was determined by X-ray investigation. It was revealed that 3 has endo-endo-configuration and adopt chair-boat-conformation. The distortion of rings was evaluated by calculation of the Zefirov–Palyulin and Cremer–Pople puckering parameters. Failure of esterification of 3 was rationalized in terms of steric hindrance and intramolecular hydrogen bonding.

Cyclofunctionalization of 6-alkenylsulfanylpyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]-pyrimidin-4(5<Emphasis Type="Italic">H</Emphasis>)-ones with arenesulfenyl chlorides

Reactions of 6-allylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one with arenesulfenyl chlorides in chloroform gave products of addition of the latter at the exocyclic double bond, while analogous reactions in acetic acid in the presence of LiClO₄ were accompanied by intramolecular electrophilic cyclization involving the N⁷ atom. 6-Cinnamylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one reacted with arenesulfenyl chlorides in acetic acid in the absence of electrolyte to produce fused pyrazolo[4′,3′: 5,6]pyrimido[2,1-b][1,3]thiazine derivatives. Introduction of a bulky phenyl group into position 1 of the pyrazolo[3,4-d]pyrimidine system reduces the yield of the corresponding intramolecular cyclization product at N⁷ as a result of concurrent formation of acyclic addition product. DOI     

Synthesis and structures of benzo[<Emphasis Type="Italic">cd</Emphasis>]furo[2,3-<Emphasis Type="Italic">f</Emphasis>]indol-4(5<Emphasis Type="Italic">H</Emphasis>)-one derivatives

A procedure was developed for the synthesis of derivatives of the new heterocyclic system, benzo[cd]furo[2,3-f]indole, based on the cyclodehydration of 6-acylmethyloxy-1-alkyl-benzo[cd]indol-2(1H)-ones. Either 7- or 8-aryl derivatives of benzo[cd]furo[2,3-f]indol-4(5H)-ones can be prepared depending on the reaction conditions. The molecular and crystal structures of 7- and 8-phenylbenzo[cd]furo[2,3-f]indol-4(5H)-ones were established by X-ray diffraction.     

Catalytic hydrogenation of methyl 3,4-diazatricyclo-[5.2.1.0<Superscript>2,6</Superscript>]dec-4-ene-5-carboxylate

The hydrogenation at Raney nickel of the pyrazoline ring in methyl exo-3,4-diazatricyclo-[5.2.1.0^2,6]dec-4-ene-5-carboxylate takes place quantitatively with the preferential formation of the trans isomer of 5-amino-exo-3-azatricyclo[5.2.1.0^2,6]decan-4-one. The 3-methoxycarbonylmethyl-, 3-acetyl-, and 3-nitroso-substituted esters are not hydrogenated under these conditions.     

New Strategy of the Synthesis of 3,4-Dihydropyrimido[1,2-<Emphasis Type="Italic">a</Emphasis>]benzimidazol-2(1<Emphasis Type="Italic">H</Emphasis>)-ones

A new procedure has been developed for preparative synthesis of 3,4-dihydropyrimido[1,2-a]-benzimidazol-2(1H)-ones by thermal intramolecular heterocyclization of 3-[2-(propylsulfanyl)- and 2-(benzylsulfanyl)-1H-benzimidazol-1-yl]propanehydrazides and 3-[2-(benzylsulfanyl)-1H-benzimidazol-1-yl]-propanamide.     

Structure and Reactivity of Bicyclo[2.2.1]hept-2-ene-<Emphasis Type="Italic">endo</Emphasis>-5,<Emphasis Type="Italic">endo</Emphasis>-6-dicarboxylic (endic) Acid Hydrazide

Establishing of the structure of hydrazinolysis product obtained from bicyclo[2.2.1]hept-2-ene-endo-5, endo-6-dicarboxylic (endic) acid was performed by preparation of the compound under alternative conditions followed by comparison of the characteristics and spectral parameters of the resulting substances, and also by quantum-chemical calculations by the density functional method of the chemical shifts in ¹H and ¹³C NMR spectra of different reaction products. The X-ray diffraction analysis of the hydrazide was also carried out. The compound obtained was assigned a structure of N-aminobicyclo[2.2.1] hept-2-ene-endo-5,endo-6-dicarboximide. The products were prepared by its reactions with arylsulfonyl chlorides, benzoyl chlorides, m-tolyl and p-toluene-sulfonyl isocyanates, phenyl isothiocyanate, with o-nitrobenzaldehyde, and oxiranes (1,2-epoxycyclohexane and 2,3-epoxypropylcarbazole). The aromatic sulfonamides, carboxamides, and ureas were epoxidized by performic acid obtained in situ from the formic acid and hydrogen peroxide. Products of [3+2]-cycloaddition of aryl azides to the strained double bond in the N-aminobicyclo[2.2.1] hept-2-ene-endo-5,endo-6-dicarboximide and its derivatives. The structures of compounds obtained were confirmed by their IR, 1H and 13C NMR spectra.     

Stereochemistry of dihydroxylation of <Emphasis Type="Italic">N</Emphasis>-arylbicyclo[2.2.1]-hept-5-ene-<Emphasis Type="Italic">endo</Emphasis>- and -<Emphasis Type="Italic">exo</Emphasis>-2,3-dicarboximides

Stereochemistry of the oxidation of N-arylbicyclo[2.2.1]hept-5-ene-endo-and-exo-2,3-dicarboximides at the double bond with peroxyacetic acid generated in situ in the presence of sulfuric acid and with an anhydrous dioxane solution of peroxyacetic acid was studied. In both cases, the reaction was stereospecific, regardless of the substituent in the N-aryl group and configuration of the imide ring, but the reaction direction depended on the presence of water in the system. In the first case, the corresponding trans-5,6-dihydroxy derivatives were formed, while in the second, exo-5,6-epoxy derivatives. The oxidation of N-arylbicyclo[2.2.1]-hept-5-ene-endo-and-exo-2,3-dicarboximides with a solution of potassium permanganate in aqueous acetone gave the corresponding N-aryl-cis-5,6-dihydroxybicyclo[2.2.1]heptane-endo-and-exo-2,3-dicarboximides. The exo,cis,exo and exo,cis,endo configurations of the synthesized compounds were determined by ¹H NMR spectroscopy.     

Reaction of 2-alkylthio-6-amino-pyrimidin-4(3H)-ones with ethyl bromopyruvate. Synthesis of furo-[2,3-<Emphasis Type="Italic">d</Emphasis>]-pyrimidine and furo[3,2-<Emphasis Type="Italic">e</Emphasis>]imidazo-[1,2-<Emphasis Type="Italic">c</Emphasis>]pyrimidine carboxylates

Reaction of 2-alkylthio-6-aminopyrimidin-4(3H)-ones with ethyl bromopyruvate to give ethyl 2-alkyl-thio-4-aminofuro[2,3-d]pyrimidine-5-carboxylates has been shown to proceed under neutral or acidic conditions. The obtained furo[2,3-d]pyrimidines underwent further cyclocondensation reaction with ethyl bromopyruvate to afford diethyl 5-alkylthiofuro[3,2-e]imidazo[1,2-c]pyrimidine-2,9-dicarboxy-lates. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 440–443, March, 2009.     

Synthesis of epothilones molecule fragment (15<Emphasis Type="Italic">R</Emphasis>)-C<Superscript><Emphasis Type="Italic">13</Emphasis></Superscript>-C<Superscript><Emphasis Type="Italic">21</Emphasis></Superscript> from D-mannitol

Efficient synthesis of an epothilone molecules fragment (15R)-C¹³-C²¹ was carried out from D-mannitol through its conversion into methyl 2,3-O-cyclohexylidene-D-glycerate followed by the cyclopropanation of the ester group with ethylmagnesium bromide in the presence of titanium(IV) isopropoxide and the transformation of the obtained cyclopropanol into the corresponding 2-substituted allyl bromide. The coupling of the latter catalyzed by copper with 2-methylthiazolyl-4-magnesium bromide, the shift of a double carbon-carbon bond in the product obtained into the position, conjugated with the thiazole ring, and the common transformation of the protected 1,2-diol function afforded the target compound in 15% yield.