Ring-chain isomerism and reactions of 2-(1-anthraquinonecarbonyl)-1,2,3,4-tetrahydrophthalazine

The ring isomer of the corresponding acyl derivative — 5,9-dioxo-17a-hydroxy-9,10,11,16-17,17a-hexahydro-5H-dibenzo[d,e,h]phthalazino[2,3-a]cinnoline — was obtained by acylation of 1,2,3,4-tetrahydrophthalazine with anthraquinone-1-carboxylic acid chloride. Treatment of the product with thionyl chloride or hydrogen chloride gave the deeply colored 5,9-dioxo-9,10,11,16-tetrahydro-5H-dibenzo[d,e,h]phthalazino[2,3-a]cinnolinium chloride. The possibility of charge transfer between the chloride anion and the phthalazinium cation is examined as a reason for the deep coloration. This compound very readily undergoes hydrolytic oxidative cleavage at the C-N bond to give 2-(2-formylbenzyl)-3,7-dioxo-2,3-dihydro-7H-dibenzo[d,e,h]cinnoline.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1411–1415, October, 1977.     

Synthesis of Hexa- and Octahydropyrido[3'2':4,5]thieno[3,2-d]pyrimidines

The reaction of N-methylmorpholinium 4-(2-chlorophenyl)-5-cyano-2-oxo-1,2,3,4-tetrahydropyridine-6-thiolate with chloroacetamide in DMF in the presence of an excess of KOH gave 3-amino-2-carbamoyl-4-(2-chlorophenyl)-6-oxo-4,5,6,7-tetrahydrothieno[2,3-b]pyridine. Refluxing the latter with acyl chlorides in AcOH or heating in formic acid gave hexahydropyrido[3',2':4,5]thieno[3,2-d]pyrimidine derivatives and reaction with cyclohexanone gave a spiro-linked octahydropyrido[3',2':4,5]thieno[3,2-d]pyrimidine.     

3-acyl-1,2,3,4-tetrahydropyridine-2,4-diones: Synthesis and chemical properties

N-Substituted 6-methyl-1,2,3,4-tetrahydropyridine-2,4-diones reacted with aliphatic carboxylic acid chlorides in the presence of pyridine or triethylamine to give the corresponding 4-O-acyl derivatives which underwent O,C-migration of the acyl group by the action of 2 equiv of triethylamine and a catalytic amount of 2-hydroxy-2-methylpropanenitrile. Reactions of 3-acyl-6-methyl-1,2,3,4-tetrahydropyridine-2,4-diones thus formed with aliphatic and aromatic amines gave the corresponding enamino derivatives at the side acyl group. Enamino derivatives at the C⁴ =O group were obtained by transformation of 3-acyl-1,2,3,4-tetrahydropyridine-2,4-diones into 3-acyl-4-methoxy-6-methyl-1,2-dihydropyridin-2-ones via alkylation with dimethyl sulfate and subsequent treatment with amines.     

Synthesis of 2-aryl-5H-[1,3,4]-thiadiazolo[2,3-b]quinazolin-5-ones

3-Amino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-ones were converted into 2-aryl-5H-[1,3,4]thiadiazolo[2,3-b]quinazolin-5-ones on treatment with carboxylic acids and POCl₃. 3-Arylmethylidenamino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-ones also cyclized to 2-aryl-5H-[1,3,4]thiadiazolo[2,3-b]quinazolin-5-ones when oxidized with potassium chlorate in acetic acid, but on heating they were deaminated to give 2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one and aryl nitriles. __________ Translated from Khimiya Geteotsiklicheskikh Soedinenii, No. 5, 787–791, May, 2006.     

Synthesis of enantiomers of 6-nitro- and 6-amino-2-methyl-1,2,3,4-tetrahydroquinolines

Enantiomers of 2-methyl-6-nitro-1,2,3,4-tetrahydroquinoline have been obtained by kinetic resolution of racemic 2-methyl-1,2,3,4-tetrahydroquinoline in acylation with acyl chlorides of N-protected amino acids followed by regioselective nitration of the diastereoisomeric amides and acidic hydrolysis. The introduction of a trifluoroacetyl protecting group into the position 1 of the enantio pure nitro compound followed by the reduction led to (S)-6-amino-2-methyl-1-trifluoroacetyl-1,2,3,4-tetra-hydroquinoline in a high yield.     

Synthesis of (6,7-dichlorononafluoro-5,6,7,8-tetrahydronaphthalen-2-yl)acetic acid and its transformation into perfluorinated 2-methylnaphthalene and 6-methyl-1,4-dihydronaphthalene

2,3-Dichlorodecafluorotetralin reacted with ethyl cyanoacetate to give ethyl 2-cyano-2-(6,7-dichlorononafluoro-5,6,7,8-tetrahydronaphthalen-2-yl)acetate which was hydrolyzed to (6,7-dichlorononafluoro-5,6,7,8-tetrahydronaphthalen-2-yl)acetic acid. The latter was treated with PCl₅ on heating to obtain 2,2-dichloro-(6,7-dichlorononafluoro-5,6,7,8-tetrahydronaphthalen-2-yl)acetyl chloride which was converted to 2,3-dichlorononafluoro-6-trifluoromethyl-1,2,3,4-tetrahydronaphthalene by the action of SbF₅. The reduction of 2,3-dichlorononafluoro-6-trifluoromethyl-1,2,3,4-tetrahydronaphthalene with zinc in 1,4-dioxane gave perfluoro-6-methyl-1,4-dihydronaphthalene, and in DMF, perfluoro-2-methylnaphthalene.     

Preparation and reactions of some 1,2,3,4-Tetrahydro-2,3-disubstituted 7(or 8)hydroxy-1,4-dioxopyrazino[1,2-a] indoles

1,2,3,4-Tetrahydro-2,3-disubstituted 7(or 8) hydroxy-1,4-dioxopyrazino[1,2-a]indoles have been prepared by the condensation of 6(or 5)benzyloxyindole-2-carbonyl chloride with d1-N- alkylamino acid ethyl esters in the presence of triethyl amine followed by the hydrogenolysis over palladium-carbon. Methylation and alkaline hydrolysis of 1,2,3,4-tetrahydro-2-benzy1-1,4-dioxopyrazino[1,2-a]indole are discussed.     

Synthesis of Multifunctionalized 1,2,3,4‐Tetrahydropyridines, 2,3‐Dihydropyridin‐4(1H)‐ones,and Pyridines from Tandem Reactions Initiated by [5+1] Cycloaddition of N‐Formylmethyl‐Substituted Enamides to Isocyanides: Mechanistic Insight and Synthetic Application

Tandem reactions for the efficient synthesis of multifunctionalized 1,2,3,4‐tetrahydropyridines, 2,3‐dihydropyridin‐4(1H)‐ones, and pyridine derivatives have been developed and reaction mechanisms have been investigated. Synthetic cascades are initiated by the Zn(OTf)₂‐mediated [5+1] cycloaddition of N‐formylmethyl‐substituted tertiary enamides to isocyanides, thus leading to the versatile heterocyclic enamino imine intermediates. Interception of the intermediates by diastereoselective reduction of imine functionality with Me₄NBH(OAc)₃ afforded 1,6‐disubstituted trans‐3‐hydroxy‐4‐arylamino‐ or ‐alkylamino‐1,2,3,4‐tetrahydropyridines, whereas acylation of the imino group followed by acidic hydrolysis produced 1,6‐disubstituted 3‐acyloxy‐2,3‐dihydropyridin‐4(1H)‐ones. Aerobic oxidation led to the aromatization followed by intermolecular acyl‐group transfer from the pyridinium nitrogen to the 3‐hydroxy moiety, thereby yielding substituted 3‐acyloxy‐4‐aminopyridines. Synthetic potentials of the resulting products have been demonstrated by expedient and highly stereoselective synthesis of cis,cis‐4,5‐dihydroxy‐2‐phenylpiperidine and trans,trans‐4‐amino‐5‐hydroxy‐2‐phenylpiperidine compounds, which are important in medicinal chemistry, through simple and practical reduction reactions.     

Synthesis of the 1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridine ring system

As part of an on-going research project, we required an efficient method for the preparation of compounds containing the 1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridine ring nucleus. The parent compound 1 has not been described in the literature, and there is only one reference to the N-methyl analog 2 [1]. A series of structurally related compounds, the 2-substituted-4-hydroxy-1,2,3,4-tetrahydrobenzofuro[2,3-c]pyridines, has been described [2].     

Chemical modification of the alkaloid 2,3-tetramethylene-3,4-dihydroquinazol-4-one

The 1,2-dihydro derivative of 2,3-tetramethylene-3,4-dihydroquinazol-4-one was produced by reduction and characterized using NMR spectra. 1-Acyl-1,2,3,4-tetrahydroquinazol-4-ones and ureas were synthesized by acylation of 2,3-tetramethylene-1,2,3,4-tetrahydroquinazol-4-one with acid chlorides and arylisocyanates, respectively. The molecular structures of 1-acetyl-and-m-chlorophenylaminocarbonyl-2,3-tetramethylene-1,2,3,4-tetrahydroquinazol-4-ones were established using x-ray structure analyses. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 364–370, July–August, 2007.     

A comparative study on the acylative kinetic resolution of racemic fluorinated and non-fluorinated 2-methyl-1,2,3,4-tetrahydroquinolines and 3,4-dihydro-3-methyl-2H-[1,4]benzoxazines

The acylative kinetic resolution of racemic 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline, 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine, and their non-fluorinated analogues with (S)-naproxen and N-phthaloyl-(S)-amino acyl chlorides has been carried out. It has been shown that the presence of fluorine atoms in the aromatic fragment of a heterocyclic amine results in the increasing stereoselectivity of acylation with (S)-naproxen acyl chloride and in a decrease in the efficiency of acylative kinetic resolution using N-phthaloyl-(S)-amino acyl chlorides. A method for the preparation of enantiopure (S)-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (ee >99%) was developed.     

The syntheses of polycyclic molecules containing b-carboline units by the photochemically induced ring closure of enamides

The syntheses of 5-methyl-5,8,9,14-tetrahydroindolo(2,3-$\text{c}$)indolo (2,3-$\text{g}$) quinolizin-6-one and 15-methyl-7,8,13,15-tetrahydroindolo ( 3,2-$\text{c}$) indolo(2,3-$\text{g}$)quinolizin-5-one from the photochemical cyclisation of i-methylene-2-(N-`methylindole-2'-carbonyl) 1,2,3,4-tetrahydro-B-carboline and 1-methylene-2- (N-`methylindole-3' carbonyl) 1,2,3,4,-tetrahydro-B-carboline are described. Attempts to prepare indolo(2,3-$\text{c}$)isoquinolines from the photochemical cyclisation of 2-benzamidoindoles were unsuccessful.     

Investigation of the products of the reaction of epichlorohydrin with aromatic amines

The action of hydrogen halides on 7a,8-dihydro-7H-azirino[1,2-]benz[g]indole gives 2-halomethyl-2,3-dihydro-1H-benz[g]indoles and 3-halo-1,2,3,4-tetrahydrobenzo[h]quinolines, which were converted to the corresponding N-nitroso derivatives and then to the isonitroso derivatives. 2-(Benzoxymethyl)-2,3-dihydro-1H-benz[g]indole hydrohalides were obtained by heating 1-benzoyl-2-halomethyl-2,3-dihydro-1H-benz[g]indoles. The reaction of 3-halo-1,2,3,4-tetrahydrobenzo[h]quinolines with thionyl chloride at room temperature gives 3-halo-6-chloro-1,2,3,4-tetrahydrobenzo[h]quinolines, while refluxing with thionyl chloride gives 6-chlorobenzo[h]quinoline.See [1] for communication XVI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 342–346, March, 1973.     

Synthesis of new pyrido[2,3-d]pyrimidine derivatives

The mutual condensation of 4-aminouracil or 2,4-diamino-6-hydroxypyrimidine with bisacetonitrile and aldehydes was used to synthesize 2,4-dioxo-5-R-7-methyl-6-cyano-1,2,3,4,5,8-hexahydropyrido[2,3-d]pyrimidine and 2-amino-4-oxo-5-R-7-methyl-6-cyano-3,4,5,8-tetrahydropyrido[2,3-d]pyrimidine derivatives, which were oxidized with chromic anhydride to the corresponding 2,4-dioxo-5-R-7-inethyl-6-eyano-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine and 2-amino-4-oxo-5-R-7-methyl-6-cyano-3,4-dihydro[2,3-d]pyrimidines. The IR and UV spectra of the synthesized compounds were recorded.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 422–425, March, 1972.     

Borane-Catalyzed Tandem Cyclization/Hydrosilylation Towards Enantio- and Diastereoselective Construction of trans-2,3-Disubstituted-1,2,3,4-Tetrahydroquinoxalines

Recent years have witnessed marked progress in the efficient synthesis of various enantioenriched 1,2,3,4-tetrahydroquinoxalines. However, enantio- and diastereoselective access to trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines remains much less explored. Herein we report that a frustrated Lewis pair-based catalyst generated via in situ hydroboration of 2-vinylnaphthalene with HB(C₆F₅)₂ allows for the one-pot tandem cyclization/hydrosilylation of 1,2-diaminobenzenes and 1,2-diketones with commercially available PhSiH₃ to exclusively afford trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines in high yields with excellent diastereoselectivities (>20 : 1 dr). Furthermore, this reaction can be rendered asymmetric by using an enantioenriched borane-based catalyst derived from HB(C₆F₅)₂ and a binaphthyl-based chiral diene to give rise to enantioenriched trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines in high yields with almost complete diastereo- and enantiocontrol (>20 : 1 dr, up to >99 % ee). A wide substrate scope, good tolerance of diverse functionality and up to 20-gram scale production are demonstrated. The enantio- and diastereocontrol are achieved by the judicious choice of borane catalyst and hydrosilane. The catalytic pathway and the origin of the excellent stereoselectivity are elucidated by mechanistic experiments and DFT calculations.     

Benzo-1,2,3,4-tetrazine 1,3-dioxides annulated with tetraazapentalene systems 3. Annulation at the C(7)—C(8) bond

Thermolysis of 7-azido-8-(2H-1,2,3-triazol-2-y1)-1,2,3,4-benzotetrazine 1,3-dioxide and 7-azido-8-(l H-1,2,3-triazol-l-yl)-1,2,3,4-benzotetrazine 1,3-dioxide afford new heterocyclic systems, viz., 7,11-dehydro-7H, 11H [1,2,3]triazolo[l′,2′:2,3][1,2,3]triazolo[4,5-f]-[1,2,3,4]benzotetrazine 1,3-dioxide and 7,9-dehydro-7 H, 9H [1,2,3]triazolo[2′,1′:2,3]-[1,2,3]triazolo[4,5-f][1,2,3,4]benzotetrazine 1,3-dioxide, respectively, and their thermal stability has been studied.     

Synthesis and structures of pyridoannelated 1,2,3,4-tetrazine 1,3-dioxides

Treatment of 2- and 4-amino-3-(tert-butyl-NNO-azoxy)pyridines with nitrating agents (N₂O₅or NO₂BF₄) afforded the first representatives of pyridoannelated 1,2,3,4-tetrazine di-N-oxides, viz., pyrido[2,3-e][1,2,3,4]tetrazine 1,3-dioxide (9), 7-nitropyrido[2,3-e][1,2,3,4]tetrazine 1,3-dioxide (10), and pyrido[3,4-e][1,2,3,4]tetrazine 2,4-dioxide (11). These compounds were studied by ¹H, ¹³C, and ¹⁴N NMR spectroscopy. The 1:1 complex of compound 10 with benzene was studied by X-ray diffraction analysis.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2471–2477, November, 2004.     

A Concise Synthesis of 2‐Amino‐1,2,3,4‐tetrahydronaphthalene‐6,7‐diol (‘6,7‐ADTN’) from Naphthalene‐2,3‐diol

2‐Amino‐1,2,3,4‐tetrahydronaphthalene‐6,7‐diol ( 2 ; 6,7‐ADTN) was synthesized starting from naphthalene‐2,3‐diol in seven steps and with an overall yield of 44%. Methylation of naphthalene‐2,3‐diol with dimethyl sulfate, followed by Friedel? Crafts acylation with AcCl, gave 2‐acetyl‐6,7‐dimethoxynaphthalene. 2‐Acetyl‐6,7‐dimethoxynaphthalene was converted to 6,7‐dimethoxynaphthalene‐2‐carboxylic acid by a haloform reaction. Birch reduction of the carboxylic acid with 4 mol‐equiv. of Na in liquid ammonia afforded 1,2,3,4‐tetrahydro‐6,7‐dimethoxynaphthalene‐2‐carboxylic acid, from which 2 was obtained by a Curtius reaction, followed by hydrogenolysis and demethylation.     

Chemical Modification of Plant Alkaloids. 4. Reaction of Cotarnine with Bifunctional NH- and CH-Acids

1-Substituted 1,2,3,4-tetrahydroisoquinoline systems were prepared by reaction of cotarnine with the NH-and CH-acids methyl- and acyl derivatives of pyrazole and 1,3-dicarbonyl reagents. Depending on the structure and reaction conditions, bifunctional pyrazole nucleophiles can give substitution products at the N atom, methyl, or acyl group; 1,3-diketones, at the terminal methyl. Rearrangements occurring during the reaction of cotarnine with bifunctional substrates were studied. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 360–364, July–August, 2005.     

Synthesis of 1-substituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones

1,2-Disubstituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones are prepared for the first time through an activated Pictet-Spengler reaction of the corresponding imines of 2-(1,4-dimethoxynaphth-2-yl)ethylamine in the presence of an acyl chloride and AlCl(3) followed by an oxidation with silver(II) oxide in nitric acid. Depending on the reaction conditions the N-trichloroacetyl protecting group could be cleaved off, converted to an N-methoxycarbonyl group or transformed to an N-(2-oxoacetamide) moiety. The synthesized 1,2-disubstituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones constitute a new class of quinones, which has not been reported yet.