Isoquinoline derivatives

The condensation of 1-(p-alkoxyphenyl)-1-aminomethylcyclopentanes with dimethoxyphenylacetic acid has given the corresponding amides (III) which were isolated in the form of two isomers. The Bischler-Napieralski cyclization of the amides XIII converted them into 7-alkoxy-1-(3, 4-dimethoxybenzyl)-4-spirocyclopentane-3,4-dihydroisoquinolines (V), and reduction with the aid of lithium aluminum hydride into the amines IV. The reduction of the dihydroisoquinolines V gave the tetrahydro derivatives VI.For part I, see [1].     

Reduction studies on benzaza[3.3.3]propellanc derivatives

Sodium borohydride reduction of 3-methyl-2,3-dioxo-7,8-benzo-3-aza[3.3.3]propellan-6-one (1b) gave 2,4-dioxo-3-methyl-7,8-benzo-3-aza[3.3.3]propellan-6-ol, while lithium aluminum hydride reduction gave 3-methyl-7,8-benzo-3-aza[3.3.3]propellan-6-ol, which on oxidation, gave the corresponding ketone. This ketone formed the corresponding thioketal upon reaction with 1,2-ethanedithiol. Raney nickel desulfurization of the thioketal provided 3-methyl-6,7-benzo-3-aza[3.3.3]propellane. The same compound was also obtained in poor yield by forming the thioketal of Ib followed by lithium aluminum hydride reduction and Raney nickel desulfurization of the product. Desulfurization of the thioketal of Ib gave 2,4-dioxo-6,7-Benzo-3-aza[3.3.3]propellane.     

Esters of heterocyclic γ-amino alcohols

Reduction of cis-3-cyano-4-hydroxypiperidines with lithium aluminum hydride (LAH) gave cis-3-aminomethyl-4-hydroxypiperidines, which were converted to cis-3-dimethylaminomethyl-4-hydroxypiperidines by methylation with formaldehyde and formic acid. Acylation of the methylated compounds with benzoyl and cinnatnoyl chlorides gave the corresponding esters. Condensation of cis-3-aminomethyl-4-hydroxypiperidines with formaldehyde gave perhydropyrido[3,4-e][1,3]oxazines, which were converted to 3-methylaminomethyl-4-hydroxypiperidines by means of LAH. The cis isomers of the corresponding O,N-diacyl derivatives of these amino alcohols were obtained by acylation with acetic anhydride and benzoyl and cinnamoyl chlorides.See [1] for communication V.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1363–1368, October, 1978.     

Isoquinoline derivatives

The corresponding amides were obtained by condensation of 1-(p-alkoxyphenyl)-1-aminomethylcyclopentanes with p-alkoxyphenylacetyl chlorides; the cyclization of the amides with subsequent reduction yielded 1-(4-alkoxybenzyl)-7-alkoxy-1,2,3,4- tetrahydroisoquinoline-4-spirocyclopentanes. The amides were converted to secondary amines by reduction. The IR and UV spectra of the intermediate and final compounds were studied. The purity of the compounds obtained was verified by chromatography.For Communication II, see [2].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1381–1383, October, 1970.     

Rapid reductive-carboxylation of secondary amines. One pot synthesis of tertiary N-methylated amines

Various tertiary N-methylated amines were synthesized by using a new reductive-carboxylation approach. Secondary amines, on carboxylation with carbon dioxide under moderate reaction conditions, afforded their corresponding carbamate esters, which, on $\text{in situ}$ lithium aluminum hydride reduction, gave desired tertiary N-methylated amines in high yield.     

Isoquinoline derivatives

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline-4-spirocyclopentane was obtained by condensation of 3,4-dimethoxyphenyl-1-(aminomethyl)cyclopentane with formalin. The corresponding amides, which were reduced to tertiary amines, were synthesized by reaction of the latter with the acid chlorides of substituted benzoic and phenylacetic acids. Substituted dibenzo[a,-g]quinolizines, isoindolo[1,2-a]isoquinolines, and 1-(3,4-dimethoxyphenyl)-1-[(6,7-dimethoxy-1, 2,3,4-tetrahydro-2-isoquinolinyl)methyl]cyclopentane were synthesized, respectively, by condensation of 1-aryl (or aralkyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-4-spirocyclopentanes and their open analog -1-(3,4-dimethoxyphenyl)-1-(3,4-dimethoxyphenylethylaminomethyl)cyclopentane — with formalin.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 679–682, May, 1973.     

Isoquinoline derivatives

Amides IV, which are converted to 1-diphenylmethyl-4,6,7-substituted 1,2,3,4-tetrahydroisoquinolines (II) by cyclization and subsequent reduction with lithium aluminum hydride, were obtained by condensation of diphenylacetyl chloride with the corresponding substituted phenylethylamines (III). Amines VI, the open analogs of the tetrahydroisoquinolines, were synthesized by reduction of IV.See [3] for Communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1670–1673, December, 1970.     

Synthesis of 1,2,3‐Triazole Substituted Isoxazoles via Copper (I) Catalyzed Cycloaddition

The synthesis of a series of 3,5‐disubstituted isoxazole‐4‐carboxylic esters containing N‐substituted 1,2,3‐triazoles ( V ) starting from various benzaldehydes ( I ) is reported. Benzaldehydes undergo oximation with hydroxylamine hydrosulfate. Later, chlorination followed by condensation with methylacetoacetate and the hydrolysis of the resulting ester afforded respective carboxylic acid ( II ), which on chlorination with PCl₅ gave the corresponding acid chlorides ( III ). The coraboxylic acid chlorides ( III ) on propargylation gave propargylic esters ( IV ) and these on click reaction gave the title compounds ( V ).     

Acetals of lactams and acid amides. 36. Some reactions of enamines of the isoquinoline series and synthesis of pyrimido[4,3-a]isoquinolines

The reactions of 1-methylene-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives with acyl chlorides were investigated. 2-Oxopyrimido[4,3-a]isoquinoline derivatives were obtained by the reaction of 1-carbamidomethylene-6,7-dimethoxy-1,2, 3,4-tetrahydroisoquinoline with dimethylformamide and dimethylacetamide diethylacetals. The reaction of the latter with phosphorus oxychloride and then with primary amines was used to synthesize a number of hydrochlorides that are derivatives of 2-iminopyrimido[4,3-a]isoquinoline.See [1] for Communication 35.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1095–1099, August, 1982.     

Substituted 2,3,4,5-tetrahydro-1H-3-benzazepine and 2,3,4,5-tetrahydro-1H-naphth[1,2-d] azepine derivatives

The multi-step synthetic procedures to prepare a number of 2,3,4,5-tetrahydro-1H-benzazepine derivatives 1 through a series of intermediates are described. The condensation of arylaldehydes 2 with 2-nitropropanes 3 gave nitroalcohols 4 which were reduced to alcohol amines 5 . The condensation of 5 with arylacetaldehydes 6 gave imino derivatives 7 which on reduction with borohydride gave secondary amines 8 . By employing different methods, alcohol amines 5 were condensed with arylacetic acids 9 to give amides 10 which were then reduced to amines 8 . On treatment with mineral acids, amines 8 were cyclized to the target compounds 1 . Biological activities of 1 are also briefly discussed.     

Carboxamides and amines having two and three adamantane fragments

New carboxamides having two and three adamantane fragments were synthesized from adamantanecarboxylic acid chlorides and adamantane-containing amines. The amides were reduced to the corresponding amines, and the latter were converted into N-p-nitrophenylsulfonyl and N-p-tolylsulfonylcarbamoyl derivatives by treatment with p-nitrobenzenesulfonyl chloride and p-toluenesulfonyl isocyanate, respectively. The structure of the newly synthesized compounds was confirmed by IR and ¹H NMR spectroscopy. Some carboxamides turned out to be inactive in the reduction with lithium tetrahydridoaluminate, which was discussed in terms of the results of semiempirical quantum-chemical calculations.     

Syntheses of substituted 2-(l-methyl-2-imidazolyl)quinolines

Reaction of methyllithium with 1-methy1-2-imidazolecarboxaldehyde afforded the corresponding alcohol 2. Oxidation of compound 2 with manganese dioxide gave 2-acety1-1-methylimidazole ( 3 ). Using compound 3 and substituted isatins 4 , the corresponding quinoline-4-carboxylic acids ( 5 ) were prepared. The reaction of acid imidazolides of 5 with appropriate amines yielded the amides 6 . Carbamic acid esters 10 were prepared by the Curtius rearrangement in good yield. Substituted quinolin-4-amines 13 were obtained by the acid hydrolysis of compound 10 (R₁ = t-Bu). Alkylation of amines 13 with diakylaminoalkyl chlorides gave compounds 14 .     

Asymmetric synthesis and antimicrobial activity of some new mono and bicyclic beta-lactams

Reaction of the amino acid D-phenylalanine ethyl ester (4) with cinnamaldehyde gave chiral Schiff base 5, which underwent an asymmetric Staudinger [2+2] cycloaddition reaction with phthalimidoacetyl chloride to give the monocyclic beta-lactam 6 as a single stereoisomer. Ozonolysis of 6 followed by reduction with lithium aluminum tri(tert-butoxy) hydride afforded the hydroxymethyl beta-lactam 8. Treatment of 8 with methansulfonyl chloride gave the mesylated monocyclic beta-lactam 9, which was converted to the bicyclic beta-lactam 10 upon treatment with 1,8-diazabicyclo[5,4.0] undec-7-ene (DBU). Deprotection of the phthalimido group in beta-lactams 6 and 10 by methylhydrazine and subsequent acylation of the free amino beta-lactams with different acyl chlorides in the presence of pyridine afforded mono and bicyclic beta-lactams 14a-d and 15a-d respectively. The compounds prepared were tested against Escherichia coli, Staphilococcus citrus, Klebsiella pneumanie and Bacillus subtillis. Some of these compounds showed potential antimicrobial activities.     

3-Cyanopyridine-2(1H)-thiones and 3-cyano-2-(methylthio)pyridines in the synthesis of substituted 3-(aminomethyl)pyridines

The reactions of substituted 3-cyanopyridine-2(1H)-thiones and 3-cyano-2-(methylthio)pyridines with lithium aluminum hydride in anhydrous diethyl ether afforded the corresponding 3-aminomethyl derivatives, which were used in the synthesis of the corresponding amides.     

4,5-Dibenzyloxybenzyne as a synthon for diels-alder reactions. The synthesis of 6,7-dihydroxy-1,4-ethano-1,2,3,4-tetrahydroisoquinolines as rigid analogs of adrenergic agents. Assignment of proton and carbon-13 NMR parameters using homonuclear and heteronuclear two-dimensional chemical shift correlation NMR spectroscopy

The synthesis of several rigid analogs of catecholamine type of adrenergic agents is reported. Their synthesis began with a Diels-Alder cycloaddition of 4,5-dibenzyloxybenzyne (generated from 4,5-dibenzyloxyan-thranilic acid) to 1-(2-trans-phenylvinyl)-2-pyridone and 1-benzyl-3-benzyloxy-2-pyridone. The unsaturated amides so produced were reduced first with hydrogen and palladium and then with lithium aluminum hydride to provide 6,7-dihydroxy-1,4-ethano-1,2,3,4-tetrahydroisoquinolines. Homonuclear and heteronuclear two-dimensional chemical shift correlation nmr spectroscopy confirmed the structure of the bridged tetra-hydroisoquinolines and led to the unambiguous assignment of the ¹H and ¹³C nmr chemical shifts of key compounds.     

Synthesis and reactions of 2,2-[60]fullerenoalkanoyl chlorides

2,2-[60]Fullerenoalkanoyl chlorides (1a-d) were easily and securely prepared from the corresponding 2,2-[60]fullerenoalkanoic acids (2a-d) by the reaction with thionyl chloride in an unusual mixed solvent, CH2Cl2/dioxane. The characterization of 1a-d by 1H and 13C NMR, FT-IR, and MALDI-TOF-MASS was conducted for the first time. The 2,2-[60]fullerenoalkanoyl chlorides thus obtained were readily converted to the corresponding amides and esters in moderate to excellent yields by the condensation with amines and alcohols, respectively. Upon applying the condensation, [60]fullerene-biomolecule hybrids were easily prepared.     

Preparation of C-(aminomethyl)cellulose

Conclusions The reaction of keto-6-O-tritylcellulose with nitromethane, followed by reduction of the condensation product with aluminum lithium hydride, gave C-(aminomethyl)cellulose with a degree of substitution equal to 0.35.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 879–881, April, 1971.     

Synthesis of 2-ethoxy-2-carbethoxy-δ5 -dihydropyrans and their derivatives

Acrolein and methyl vinyl ketone undergo diene condensation with ethyl -ethoxyacrylate to give the corresponding 2-ethoxy-2-carbethoxy-⁵-dihydropyrans in 50–60% yields. The reduction of the latter with lithium aluminum hydride gave the hydroxymethyl derivatives of dihydropyrans, while ammonolysis gave amides of 2-ethoxy-⁵-dihydropyran-2-carboxylic acids.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 452–453, April, 1972.     

Fluorocyclohexanes Part XIV [1] 1-H-decafluorocyclohexylamine

1-$\text{H}$-Decafluorocyclohexylamine (V) has been prepared from decafluorocyclohexene (I). (I) gave the corresponding epoxide (II) by reaction with alkaline hydrogen peroxide, reaction of (II) with fluoride ion in sulpholane yielded decafluorocyclohexanone (III). This then gave decafluorocyclohexylidene imine (IV), lithium aluminium hydride reduction affording the desired 1-$\text{H}$-decafluorocyclohexylamine (V).     

The reduction and hydrolysis of some 7,7-diethylpyrazolo[1,2-a]-pyridazine-6,8(7H)dione derivatives

The chemistry of several of the Diels-Alder adducts formed by the reaction of 4,4-diethylpyrazoline-3,5-dione ( 1 ) with conjugated dienes was studied with respect to reduction (hydride and catalytic) and reaction with base. Reaction of the 2,3-dimethyl-1,3-butadiene adduct with lithium aluminum hydride followed by hydrogenation gave 1,3,5,6,7,8-hexahydro-cis-endo-6,7-dimethyl-2,2-diethylpyrazolo[1,2-a]pyridazine ( 11 ). Attempted conversion of this compound to 3,3-diethyl-cis-7,8-dimethyl-1,5-diazacyclononane ( 12 ) gave instead a compound which has been tentatively identified as N-(2,3-dimethyl-4-aminobutyl)-2-ethyl-2-methylbutanaldimine ( 14 ). Lithium aluminum hydride reduction of 4,4-diethylpyrazolidine-3,5-dione ( 22 ) or the adducts formed from 1 and cyclopentadiene or 1,3-cyclohexadiene gave good yields of 4,4-diethylpyrazolidine ( 21 ). This later reduction gave a new and efficient synthetic route to the pyrazolidine ring system. Lithium aluminum hydride reduction of 5,6,7,8-tetrahydro-5,8-ethano-2,2-diethylpyrazolo[1,2-a]pyridazine-1,3(2H)dione ( 26 ) followed by hydrogenolysis led to a high yield of 4,4-diethyl-2,6-diazabicyclo[5.2.2]undecane ( 28 ) which is the first reported example of this ring system. Reaction of several of the adducts with ethanolic potassium hydroxide resulted in the opening of the five-membered ring.