Pyrrolopyridazines. II. Synthesis of the novel pyrrolo[3,2-c]pyridazine ring system

The first derivatives of the pyrrolo[3,2-c]pyridazine ring system, ethyl pyrrolo[3,2-c]pyridazine-6-carboxylate 2-oxide (5) and ethyl 3-chloro-6-methylpyrrolo[3,2-c]pyridazine-7-glyoxalate 1-oxide ( 12 ), were obtained in good yields from the cyclization of 4-ethoxymethyl-eneamino-3-methylpyridazine 1-oxide (3) and 3-chloro-5-(α-ethoxyethylideneamino)-6-methylpyridazine 1-oxide (14, R ? Cl, R₁ ? OMe), respectively, with diethyl oxalate and potassium ethoxide in ether.     

Diazepines II. A new synthesis of 4h-pyrrolo[ 1,2-α] -[1,41] benzodiazepine

A convenient synthesis of a 4H-pyrroIo[1,2-α][1,4 ]benzodiazepine is described. 2,5-Di-methoxy-2-melhyl-5-phthalimidomethyltetrahydrofuran ( 3 ) was prepared starting from 2-methyl-5-phthalimidomelhylfuran ( 1 ). The condensation of 2-amino-5-chlorobenzophcnone with 3 to give 5-chloro-2-(2-methyl-5-phthalimidomethylpyrro]-1-yl)benzophenone ( 4 ), the treatment of which with hydrazine hydrate afforded 8-chloro-1-methyl-4H-pyrrolo[1,2-α] [1,4]benzodiazepine ( 5 ).     

An influence of a basic side chain moiety on the tautomer ratio between the enamine and methylene imine forms in azole condensed quinoxalines

The reaction of 7-chloro-4-(2-cyano-2-hydroxyvinyl)tetrazolo[1,5-α]quinoxaline 2a with 4-aminopyridine, p-toluidine or p-aminophenol gave 7-chloro-4-(4-pyridylcarbamoylmethylene)-4,5-dihydrotetrazolo[1,5-α]-quinoxaline 7a , 7-chloro-4-(p-tolylcarbamoylmethylene)4, 5-dihydrotetrazolo[1,5-α]quinoxaline 8a or 7-chloro-4-(p-hydroxyphenylcarbamoylmethylene)-4,5-dihydrotetrazolo[1,5-α]quinoxaline 9a , respectively. The reaction of 7-chloro-4-(2-cyano-2-hydroxyvinyl)-1,2,4-triazolo[4,3-α]quinoxaline 2b with 4-aminopyridine, p-toluidine or p-aminophenol afforded 7-chloro4-(4-pyridylcarbamoylmethylene)-4,5-dihydro-1,2,4-triazolo-[4,3-α]quinoxaline 7b , 7-chloro-4-(p-tolylcarbamoylmethylene)-4,5-dihydro-1,2,4-triazolo[4,3-α]quinoxaline 8b or 7-chloro-4-(p-hydroxyphenylcarbamoylmethylene)-4,5-dihydro-1,2,4-triazolo[4,3-α]quinoxaline 9b , respectively. The reaction of compound 2a with 2-aminopyridine or 3-aminopyridine provided 7-chloro-4-(2-pyridyl-carbamoylmethylene)-4,5-dihydrotetrazolo[1,5-α]quinoxaline 10 or 7-chloro-4-(3-pyridyl-carbamoylmethylene)-4,5-dihydrotetrazolo[1,5-α]quinoxaline 11 , respectively. Compounds 7a,b (4-pyridylcarbamoyl) predominated as the enamine tautomer A in a trifluoroacetic acid solution, while compounds 8a,b (p-tolylcarbamoyl) and compounds 9a,b (p-hydroxyphenylcarbamoyl) coexisted as the enamine A and methylene imine B tautomers in a trifluoroacetic acid solution. Moreover, the ratio of the enamine tautomer A elevated in an order of compound 11 (3-pyridylcarbamoyl), compound 10 (2-pyridylcarbamoyl) and compound 7a (4-pyridylcarbamoyl), reflecting an order of the increase in the pKa values of the aminopyridine side chain moieties. In general, the ratio of the enamine tautomer A was higher in the basic carbamoyl derivatives 7–11 than in the neutral ester derivatives 3a,b . From these results, the basic side chain moiety of the tetrazolo[1,5-α]quinoxalines 7a-11 or 1,2,4-triazolo[4,3-α]quinoxalines 7b-9b was found to increase the ratio of the enamine tautomer A in trifluoroacetic acid media.     

C-Metallierte chirale Aloxide als d2- und d3-Reagenzien für die Synthese enantiomerenreiner Produkte (EPC-Synthese)

C-Metallated Chiral Alkoxides as d²–-and d³ -Regents for the Synthesis of Enantiomerically Pure Compounds (EPC-Synthesis) The chloroalcohols (S)-1 -chloro-2-propanol ( 1 ), (S)-1 -chloro-2-methyl-2-pentanol ( 4 ), (R)-3-chloro-2-methyl-1 -propanol ( 7 ), (R)-4-chloro-2-butanol ( 10 ), and (2R, 3R)- 4-chloro-3-methyl-2-butanol (14), really available from the esters of lactic, 3-hydroxy-2-methylpropanoic, and 3-hydroxybutanoic acid are subjected to sequential metallation first with BuLi (or MeMgCl) and then with lithium naphthalenide (or Li metal powder) to give solutions of the highly reactive C -metallated alkoxides 15, 22, 26, 27 , and 28 , respectively. - These chiral d²- and d³ -reagents may be added to aldehydes (non-diastereoselectively), ketones, and CO₂ to give 1, 3- or 1 4-dioles ( 18-21, 24, 29-33 ) or δ-lactones ( 35, 36 ). Thiolations with dibenzyl disulfide (→ 16, 34 ) and a deuteration (→ 17 , (S)-(1-²H)propan-2-ol) were also carried out. Independent synthesis of (S)-1-benzylthio-2-propanol ( 16 ) and comparison of the specific rotations establish that no loss enantiomeric purity occurs on the metallation route. The results described represent and extension of the applicability of simple chiral building blocks to EPC-synthesis.     

Neue Phellandren-Derivate aus dem Wurzelöl von Angelica archangelicaL

New Phellandrene Derivatives from the Root Oil of Angelica archangelica L . 2-Nitro-1,5-p-menthadiene ( 5 ), trans- and cis-6-nitro-1(7), 2-p-menthadiene ( 6 and 7 ), trans-1(7), 5-p-menthadien-2-yl acetate ( 9 ) and a formal phellandrene derivative, 7-isopropyl-5-methyl-5-bicyclo [2.2.2]octen-2-one ( 16 ), have been identified in the root oil of Angelica archangelica L . Starting from (?)-(R)-α-phellandrene ( 1 ) (R)- 5 , (4R, 6S)- 6 /(4R, 6R)- 7 , (2S, 4R)- 9 and (1R, 4R, 7R)- 16 as well as (2S, 4R)- 11 , (2R, 4R)- 12 and (2R, 4R)- 10 have been prepared.     

Synthesis and calcium channel antagonist activity of new symmetrical and asymmetrical 4-[2-chloro-2-(4-chloro-6-methyl-2-oxo-2H-pyran-3-yl)vinyl]-substituted 1,4-dihydropyridines

New symmetrical 4-[2-chloro-2-(4-chloro-6-methyl-2-oxo-2H-pyran-3-yl)vinyl]-substituted 1,4-di-hydropyridines were synthesized in moderate to good yields via the modified Hantzsch reaction of β-dicarbonyl compounds with (Z)-3-chloro-3-(4-chloro-6-methyl-2-oxo-2H-pyran-3-yl)acrolein in the presence of an excess amount of NH₄OAc. Also, the reaction of β-dicarbonyl compounds with (Z)-3-chloro-3-(4-chloro-6-methyl-2-oxo-2H-pyran-3-yl)acrolein in the presence of enamino esters and ketones was performed, and asymmetrical 4-[2-chloro-2-(4-chloro-6-methyl-2-oxo-2H-pyran-3-yl)vinyl]-substituted 1,4-dihydropyridines were obtained in moderate to good yields at room temperature. The calcium channel blocking activity of these compounds was assessed. They demonstrated moderate to weak effects, although one compound had a comparable effect (IC₅₀ =1.40×10⁻⁷ M) with respect to the reference drug Nifedipine.     

Synthesis of 1,2-diazepino[3,4-b]quinoxalines and pyrido[3′,4′:9,8][1,5,6]oxadiazonino[3,4-b]quinoxalines via a 1,3-dipolar cycloaddition reaction

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 8 with furfural, 3-methyl-2-thiophene-carbaldehyde, 2-pyrrolecarbaldehyde, 4-pyridinecarbaldehyde and pyridoxal hydrochloride gave 6-chloro-2-[2-(2-furylmethylene)-1-methylhydrazino]quinoxaline 4-oxide 5a , 6-chloro-2-[1-methyl-2-(3-methyl-2-thienyl-methylene)hydrazino]quinoxaline 4-oxide 5b , 6-chloro-2-[1-methyl-2-(2-pyrrolylmethylene)hydrazino]quinoxa-line 4-oxide 5c , 6-chloro-2-[1-methyl-2-(4-pyridylmethylene)hydrazino]quinoxaline 4-oxide 5d and 6-chloro-2-[2-(3-hydroxy-5-hydroxymethyl-2-methyl-4-pyridylmethylene)-1-methylhydrazino]quinoxalme 4-oxide 5e , respectively. The reaction of compound 5a or 5b with 2-chloroacrylonitrile afforded 8-chloro-3-(2-furyl)-4-hydroxy-1-methyl-2,3-dihydro-1H-1,2-diazepino[3,4-b]quinoxaline-5-carbonitrile 6a or 8-chloro-4-hydroxy-1-methyl-3-(3-methyl-2-thienyl)-2,3-dihydro-1H-1,2-diazepino[3,4-b]quinoxaline-5-carbonitrile 6b , respectively, while the reaction of compound 5e with 2-chloroacrylonitrile furnished 11-chloro-7,13-dihydro-4-hydroxy-methyl-5,14-methano-1,7-dimethyl-16-oxopyrido[3′,4′:9,8][1,5,6]oxadiazonino[3,4-b]quinoxaline 7.     

Unequivocal syntheses of 6-methyl- and 6-phenylisoxanthopterin

Although 6-methyl- ( 1 ) and 6-phenylisoxanthopterin ( 2 ) have previously been synthesized, the requirement of high purity necessary for immunological testing has necessitated our development of the first reported synthesis of these compounds by unequivocal methods. In the process of so doing four new pyrazines, ethyl 3-amino-5-chloro-6-methyl-2-pyrazinecarboxylate ( 11 ), N,N-dimethyl-N'-(6-chloro-3-cyano-5-phenylpyrazin-2-yl)methanimidamide ( 16 ), 2-amino-3-ethoxycarbonyl-5-phenylpyrazine 1-oxide ( 19 ), and ethyl 3-amino-5-chloro-6-phenyl-2-pyrazinecarboxylate ( 20 ) were synthesized. Four new pteridines, 7-methoxy-6-methyl-2,4-pteridinediamine ( 7 ), 7-methoxy-6-phenyl-2,4-pteridinediamine ( 17 ), 2-amino-7-ethoxy-6-methyl-4(3H)-pteridinone ( 12 ), and 2-amino-7-ethoxy-6-phenyl-4(3H)-pteridinone ( 21 ) have also been synthesized enroute to these isoxanthopterins.     

Diterpenoide Chinomethane,vinyloge Chinone und ein Phyllocladan-Derivat aus Plectranthus purpuratus HARV. (Labiatae)

Diterpenoids from Leaf Glands of Plectranthus purpuratus: p-Quinomethanes, Extended Quinones, p-Acylcatechols and a Novel Phyllocladanon Derivative From the complex mixture of terpenoids from the title plant, the following novel diterpenoids have been isolated: 11-hydroxy-19-(3-methyl-2-butenoyloxy)- and 11-hydroxy-19-(3-methylbutanoyloxy)-5,7,9 (11), 13-abietatetraen-12-one ( 1a / 1b ), 11-hydroxy-19-(3-methyl-2-butenoyloxy)- and 11-hydroxy-19-(3-methylbutanoyl-oxy)-7,9(11), 13-abietatrien-6,12-dione ( 2a / 2b ), 6α, 11-dihydroxy-19-(3-methyl-2-butenoyloxy)- and 6α, 11 -dihydroxy-19-(3-methylbutanoyloxy)-7,9 (11), 13-abieta-trien-12-one ( 3a / 3b ), 11,12-dihydroxy-19-(3-methyl-2-butenoyloxy)- and 11,12-di-hydroxy-19-(3-methylbutanoyloxy)-8,11,13-abietatrien-7-one ( 4a / 4b ), and (16R)-17,19-diacetoxy-16-hydroxy-13β-kauran-3-one (=(16R)-17,19-diacetoxy-16-hydro-xyphyllocladan-3-one; 10 ). Compounds 2 and 3 are derivates of taxodione and taxodone, respectively, 4 is a derivative of cryptojaponol. The structure of 10 is Wised on a single-crystal- X -ray analysis and CD . data.     

NMR study on the tautomeric equilibria between the hydrazone imine and diazenyl enamine forms in side chained quinoxalines: Solvent effects and temperature dependence

The reaction of 7-chloro-4-ethoxycarbonylmethylene-4,5-dihydro-1,2,4-triazolo[4,3-a]quinoxaline 6 with 4-ethoxycarbonyl-1-methyl-1H-pyrazole-5-diazonium chloride or 4-cyano-1,3-dimethyl-1H-pyrazole-5-diazonium chloride gave 7-chloro-4-[α-(4-ethoxycarbonyl-1-methyl-1H-pyrazol-5-ylhydrazono)-ethoxycarbonylmethyl]-1,2,4-triazolo[4,3-a]quinoxaline 8a or 7-chloro-4-[α-(4-cyano-1,3-dimethyl-1H-pyrazol-5-ylhydrazono)ethoxycarbonylmethyl]-1,2,4-triazolo[4,3-a]quinoxaline 8b , respectively, while the reaction of 7-chloro-4-ethoxycarbonylmethylene-4,5-dihydrotetrazolo[1,5-a]quinoxaline 7 with 4-ethoxycarbonyl-1-methyl-1H-pyrazole-5-diazonium chloride or 4-cyano-1,3-dimethyl-1H-pyrazole-5-diazomum chloride provided 7-chloro-4-[α-(4-ethoxycarbonyl-1-methyl-1H-pyrazol-5-ylhydrazono)ethoxycarbonylmethyl]tetrazolo[1,5-a]quinoxaline 9a or 7-chloro-4-[α-(4-cyano-1,3-dimethyl-1H-pyrazol-5-ylhydrazono)ethoxycarbonylmethyl]tetrazolo[1,5-a]quinoxaline 9b , respectively. Compounds 8a,b and 9a,b showed the tautomeric equilibria between the hydrazone imine C and diazenyl enamine D forms in dimethyl sulfoxide and/or trifluoroacetic acid, and the effects of solvent and temperature on the tautomer ratios of C to D were studied by the nmr measurements in a series of mixed trifluoroacetic acid/dimethyl sulfoxide media (compounds 8a,b and 9a,b ) and at various temperatures (compounds 8a,b ).     

Novel heterocycles. Synthesis of 2,3-dihydro-6-methyl-2-phenyl-4H,6H-pyrano[3,2-c][2,1]benzothiazin-4-one 5,5-dioxide and related compounds

The reaction of 2-chloro-4-(methylsulfonyl)benzoyl chloride ( 5 ) with 1-methyl-1H-2,1-benzothiazin-4-(3H)-one 2,2-dioxide ( 4 ) gave the O-benzoyl compound, 1-methyl-2,2-dioxido-1H-2,1-benzothiazin-4-yl 2-chloro-4-(methylsulfonyl)benzoate ( 6 ), which rearranged to give the C-benzoyl isomer, [2-chloro-4-(methylsulfonyl)phenyl] (4-hydroxy-1-mefhyl-2,2-dioxido-1H-2,1-benzothiazin-3-yl)methanone ( 7 ). The O-cinnamoyl compound 13 that resulted from the addition of 2,4-dichlorocinnamoyl chloride ( 11 ) to compound 4 rearranged to give the C-cinnamoyl compound, 3-(2,4-dichlorophenyl)-1-(4-hydroxy-1-methyl-2,2-dioxido-1H-2,1-benzothiazin-3yl)-2-propen-1-one ( 15 ). On the other hand, 1-methyl-2,2-dioxido-1H-2,1-benzothiazin-4-yl 3-phenyl-2-propenoate ( 19 ) (from cinnamoyl chloride ( 17 ) and compound 4 ) rearranged to give 2,3-dihydro-6-methyl-2-phenyl-4H,6H-pyrano[3,2-c][2,1]benzothiazin-4-one 5,5-dioxide ( 21 ), an example of a hitherto unknown ring system. Additional examples of this novel heterocycle were prepared from 1-methyl-7-(trifluoromethyl)-1H-pyrido[2,3-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 23 ) and 1-methyl-1H-thieno[3,2-c][1,2]thiazin-4(3H)-one 2,2-dioxide ( 8 ).     

Stereoselective synthesis of (R)- and (S)-Ipsdienols, pheromone components of bark beetles of the Ips family

(R)- and (S)-Ipsdienols, components of pheromones of bark beetles of the Ips family, were synthesized with high enantiomeric purity (>98%) from 8-chloro-2-methyl-6-methylideneoct-2-en-4-ol prepared from ethyl 3-chloropropionate via cyclopropanation according to Kulinkovich. 8-Chloro-2-methyl-6-methylideneoct-2-en-4-ol was converted into the corresponding hydrogen phthalate whose stereoisomeric salts with (R)- and (S)-1-phenylethanamines were separated by crystallization, and subsequent hydrolysis of the latter and dehydrohalogenation with potassium tert-butoxide gave targeted (R)- and (S)-ipsdienols.     

Reactions of 3-chloro-6-hydrazinopyridazine with michael-retro-michael reagents

Although pyrazole formation results from treatment of 3-chloro-6-hydrazinopyridazine ( 2 ) with both ethoxymethylenemalononitrile and ethyl (ethoxymethylene)cyanoacetate, 6-chlorotriazolo[4,3-b]pyridazine ( 5 ) was produced (75% yield) when 2 was treated with diethyl ethoxymethylenemalonate. Treatment of 2 with diethyl acetylmalonate ( 8 ) gave both 6-chloro-3-methyltriazolo[4,3-b]pyridazine ( 10 ) and 5-hydroxy-3-methyl-1-(6-chloro-3-pyridazinyl)-1H-pyrazole-4-carboxylic acid ethyl ester ( 12 ). Pyrazole 12 was initially isolated as a salt of triazolopyridazine 10 .     

Synthesis and antimalarial effects of 5,6-dichloro-2-[(4-||4-(diethylamino)-i-methylbutyl] amino||-6-methyl-2-pyrirnidinyl)amino] benzimidazole and related benzimidazoles and lH-imidazo[4,5-b] pyridines

A group of fifty-five 2-[(4-11[(dialkylamino)alkyI]amino11-6-methyl-2-pyrimidinyl)amino]-benzimidazoles (VII) was synthesized in 3-88% yield by the condensation of the requisite 2-[(2-benzimidazolyl)amino]-4-chloro-6-methylpyrimidine (VI) with the appropriate polyamine in ethanol-hydrochloric acid or neat with excess amine containing potassium iodide. The 2-[(2-benzimidazolyl)amino]-6-methyl-4-pyrirnidinol precursors (V), obtained in 11-51% yield by cyclization of 2-(cyanoamino)-4-hydroxy-6-methylpyrimidine with a suitably substituted o-phenylenediamine, were chlorinated with phosphorus oxychloride to give the intermediate 2-[(2-benzimidazolyl)amino]-4-chloro-6-rnethylpyrimidines (VI) (27-99%). Oxidation of 5,6-dichloro-2-[(4-11[4-(diethylamino)-l-methylbutyl] amino 11-6-methyl-2-pyrimidinyl) amino ]benzimidazole ( 29 ) with m-chloroperbenzoic acid gave the distal N⁴'-oxide ( 31 ) (19%). Fusion of 2,3-uiaminopyridine with 2-(cyanoamino)-4-hydroxy-6-methylpyrimidine provided 2-[(4-hydroxy-6-tnethyl-2-pyrimidinyl)amino]-lH-imitlazo[4,5-b]pyrimidine (VIII) (30%), which upon chlori-nation with phosphorus oxychloride (63%) followed by amination with i N, N-diethylethylene-diamine afforded 2-(4-11[2-(diethylamino)ethyl] amino 11-6-methyl-2-pyrimidinyl)-lH-imidazo [4,5-b]pyridine (X) (8%). Thirty-eight of the novel 2-[(4-amino-6-methyl-2-pyrimidinyl)amino]-benzimidazoles possessed “curative” activity against Plasmodium berghei at single subcutaneous doses ranging from 20.640 mg./kg. Orally, thirty-one compounds exhibited suppressive activity against P. berghei comparable with or superior to the reference drugs 1-(p-chlorophenyl)-3-(4-11[2-(diethylarnino)ethyl]amino 11-6-methyl-2-pyrimidinyl)guanidine (I) and quinine hydrochloride, while twelve of them were 5 to 28 times as potent as I and quinine hydrochloride. Eight compounds also displayed strong suppressive activity against P. gallinaceum in chicks. 5,6-Dichloro-2-[(4-112-(diethylamino)ethyl]amino11-6-methyl-2-pyrimidinyl] benzimidazole (18) showed marked activity against a cycloguanil-resistant line of P. berghei, and the most promising member of the series, namely 5,6-dichloro-2-[(4-11[4-(diethylamino)-l-methylbutyl]amino11-6-methyl-2-pyrimidinyl)amino]benzimidazole ( 29 ) (Q = 28), was designated for preclinical toxico-logical studies and clinical trial. Structure-activity relationships are discussed.     

Epimeric Isopavine N-Oxides from Roemeria refracta

Roemeria refracta DC. (Papaveraceae) of Turkish origin yielded two novel epimeric N-oxides, (?)-(5R, 11S,14R)-reframidine N-oxide ( = (?)-(5R, 11S,14R)-11,12-dihydro-14-methyl-11,5-(iminomethano)-5H -cyclohepta[1, 2-f: 4, 5-f′]bis[1,3]benzodioxole 14-oxide; 1 ) and (?)-(5R, 11S, 14S)-reframidine N-oxide ( = (?)-(5R, 11S, 14S)-11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxole 14-oxide; 2 ). The isolated (?)-roelactamine ( = (?)-11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxol-15-one, 4 ) is the first natural isopavinoid incorporating a lactam group. The epimeric (?)-15-(2-oxopropyl)reframidines ( = (?)-1-[11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxol-15-y1]propan-2-ones; 5/6 ) and the epimeric (?)-ethyl (reframidin-15-yl)acetates ( = (?)-ethyl [11, 12-dihydro-14-methyl-11, 5-(iminomethano)-5H-cyclohepta[1, 2-f:4, 5-f′]bis[1, 3]benzodioxol-15-y1]acetates; 7/8 ) are probably artifacts. (±)-Coclaurine ( 9 ), (±)-N-methylcoclaurine ( 10 ), (?)-roemeridine ( 11 ), and N-feruloyltyramine ( 12 ) are also isolated from R. refracta together with the previously reported bases. Specific ¹³C-NMR assignments are reported for the first time for the isopavines.     

4-hydroxy-2-quinolones 151. Reaction of 4-chloro-3-ethoxycarbonyl-2-oxo-1,2-dihydroquinolines with p-toluenesulfonylhydrazide

The reaction of ethyl 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylate with p-toluene-sulfonylhydrazide at room temperature in the system DMSO/K₂CO₃ gives 5-methyl-2-(toluene-4-sulfonyl)-1,2-dihydro-5H-pyrazolo[4,3-c]quinoline-3,4-dione, alkylation of which using ethyl iodide gives the 1N-substituted derivative. For Communication 150 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 59-66, January, 2009.     

Study on the Reaction of CIS-1-Acetyl-2-Aryl-6,6-Dimethyl-5,7-Dioxospiro-[2,5]-4,8-Octadiones with Methanol

Cis-l-acetyl-2-aryl-6,6-dimethyl-5,7-dioxo-spiro-[2,5]-4,8-octadiones 3a-d (X=p-CH₃, p-Cl, H, p-NO₂) reacted with anhydrous methanol in a sealed tube at 80°C to form trans, cis-α-carbomethoxy-β-(α′-methoxy-α′-aryl)-γ-methoxy-γ-methyl-γ-butyrolactones 4a-d and cis, cis-α-carbomethoxy-β-(α′-methoxy-α′-aryl)-γ-methoxy-γ-methyl-γ-butyrolactones 5a-d in good yield.     

Synthesis of mesoionic triazolo[4,3-a]quinoxalines

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 1 or 6-chloro-2-(1-methylhydrazino)-quinoxaline 5 with phenyl isothiocyanate under reflux in N,N-dimethylformamide gave 7-chloro-3-methyl-1,2,4-triazolo[4,3-a]quinoxalin-3-ium-1-thioate 4 , which was also obtained by refluxing of 6-chloro-2-[1-methyl-2-(N-phenylthiocarbamoyl)hydrazino]quinoxaline 4-oxide 2b or 6-chloro-2-[1-methyl-2-(N-phenylthiocarbamoyl)hydrazino]quinoxaline 6 in N,N-dimethylformamide.     

Synthesis and some transformations of 6(8)-substituted 4-hydrazino-2-methylquinolines

6(8)-Substituted 4-hydrazino-2-methylquinolines were synthesized by reaction of the corresponding 4-chloro-2-methylquinolines with hydrazine hydrate. Reactions of the title compounds with ethyl acetoacetate and acetone gave 2,4-dimethyl-1H-pyrrolo[3,2-c]quinolines and 4-(5-ethoxy-3-methyl-1H-pyrazol-1-yl)-2-methylquinolines.     

Synthesis and transformations of (±)-trans-4aβ(H), saα(H)-octahydro-4α,7β-dimethyl-2H-1-benzopyran-2-one

Hydrogenation of 4,7-dimethylcoumarin ( 1 ) in alkaline medium has been shown to furnish a mixture of (±)-trans-4aβ(H),8aα(H)-octahydro-4α,7β-dimethyl-2H-1-benzopyran-2-one ( 2 ), (±)-trans-4aβ(H),8aα(H)-octahydro-4α,7α-dimethyl-2H-1-benzopyran-2-one ( 3 ) and (±)-cis-4aα(H),8aα(H)-octahydro-4α,7α-dimethyl-2H-1-benzopyran-2-one ( 4 ) in 40:25:35:ratio, respectively. The stereochemistry of the major hydrogenation product 2 , has been established by transforming it to p-menthane derivatives e.g. (±)-2 (R)-[2′(R)hydroxy-4′(R) methylcyclohex-(1′S)-yl]propan-1-ol ( 20 ) and (±)-trans-3α,6β-dimethyl-3aβ(H),7aα(H)-octahydrobenzofuran ( 12 ). Starting from a mixture of lactones 2, 3 and 4 , lactone 3 has been obtained in pure state employing a sequence of reactions.