New general synthesis of tetrahydro-1,2,4,5-tetrazin-3(2H)-one derivatives and stable 3,4-dihydro-3-oxo-1,2,4,5-tetrazin-1(2H)-yl radical derivatives

Reactions of 2-chloroformylhydrazones of aromatic aldehydes or ketones 2 with various hydrazines were converted to monocarbonohydrazone derivatives 3 or 5 and/or tetrahydro-1,2,4,5-tetrazin-3(2H)-one derivatives 6 , 7 . By oxidation with lead dioxide, compounds 6 were transformed into stable 3,4-dihydro-3-oxo-1,2,4,5-tetrazin-1(2H)-yl radical derivatives 8 .     

Synthesis of 3-acylamino-2-oxazolidinone derivatives through cyclic transformations of 5-aryl (or benzyl)-1,3,4-oxadiazol-2(3H)-one derivatives

New 3-acylamino-2-oxazolidinone derivatives 3 were obtained in good yields by reaction of 5-aryl (or benzyl)3-(2-hydroxyethyl)1,3,4-oxadiazol-2(3H)ones 1 with sodium ethylate. Treatment of ethyl 5-aryl-2-oxo-1,3,4-oxadiazole-3(2H)-acetates 7 with aromatic aldehydes in the presence of sodium ethylate or sodium hydride afforded 3-acylamino-5-aryl-4-ethoxycarbonyl-2-oxazolidinone derivatives as two trans- 5 and cis- 6 racemics. Only RS,SR-racemates were obtained with acetophenone under the same conditions.     

Benzoxazol-2 (3H)-one and 1,3,4-oxadiazol-2(3H) -one derivatives from substituted enaminones and ketoenamines

Enaminones and ketoenamines bearing a hydrazine type substituent undergo side chain thermal cyclization, the former into benzoxazol-2 (3H)-one derivatives and the latter into 1, 3, 4-oxadiazol-2 (3H)-one derivatives. Factors affecting such reactions are discussed.     

1,4-Benzodioxin-2(3H)-one and some of its derivatives

The methods of synthesis of 1,4-benzodioxin-2(3H)-one have been reexamined. Frequently quoted in the literature the method of Ghosh has been found to give impure (2-hydroxyphenoxy)acetic acid rather than the lactone. Using various methods some simple derivatives of the title lactone substituted in the benzene ring have been prepared and characterized. The bromination of the lactone with NBS gives predominantly 7-bromo-1,4-benzodioxin-2(3H)-one under electrophilic conditions, while 6-bromo-1,4-benzodioxin-2(3H)-one is obtained as a major isomer under photolytic conditions.     

Synthesis of 1-(2-hydroxyphenyl)-2,4-imidazolidinedione derivatives through cyclic transformations of ethyl 2-oxo-3(2H)-benzoxazoleacetate derivatives

A series of ethyl 2-oxo-3(2H)-benzoxazoleacetate derivatives 2 have been synthesized. By reaction with ammonia, primary amines or hydrazine, these compounds 2 were transformed into 1-(2-hydroxyphenyl)-2,4-imidazolidinedione derivatives 4, 5 and 6 , respectively. Some of these new hydantoins 4 , treated with phosphorus oxychloride, gave 3H-2-oxoimidazo[2,1-b]benzoxazole derivatives 9 . Ethyl 2-oxo-3(2H)-benzoxazolepropionate ( 10 ) was prepared by a Michaël reaction of ethyl acrylate with 2-benzoxazolone ( 1a ). With 10 , no cyclic transformation was observed in the presence of ammonia or alkylamine.     

Ring transformations of 1,3,4-oxadiazol-2(3H)-one derivatives into 1-amino and 1,3-diamino-2,4-imidazolidinedione (hydantoin) derivatives

Some ethyl 5-aryl(or benzyl)-2-oxo-1,3,4-oxadiazole-3(2H)-acetates were prepared and treated with ammonia, primary amines or hydrazine to give 1-amino-2,4-imidazolidinedione or 1,3-diamino-2,4-imidazolidinedione derivatives. The 1,3-bis(benzylideneamino)-2,4-imidazolidinedione was obtained by reacting ethyl bromoacetate with the 1,5-dibenzylidenecarbonohydrazide sodium salt.     

Synthesis of 3,5-disubstituted 1-amino-1,3,5-triazine-2,4,6-triones (or 1-aminocyanurates) by cyclic transformation of 1,3,4-oxadiazol-2(3H)-one derivatives

The 5-aryl(or methyl)-3-phenylcarbamoyl-1,3,4-oxadiazol-2(3H)-ones 2 , in the presence of sodium hydride in anhydrous dimethylformamide, were transformed into 1-benzamido(or acetamido)-3,5-diphenyl-1,3,5-triazine-2,4,6-trione derivatives 7 in poor yields. However, compounds 7 were obtained in better yields when the sodium salts of 5-aryl(or methyl)-1,3,4-oxadiazol-2(3H)-ones 1 were treated with two equivalents of aryl(or ethyl)isocyanates. Acidic hydrolysis of 1-acetamido-3,5-diphenyl-1,3,5-triazine-2,4,6-trione ( 7i ) provided the corresponding free N-amino derivative 9 . Nitrous deamination of 9 gave the known 3,5-diphenyl-1,3,5-triazine-2,4,6-trione ( 11 ). This cyclic transformation is the first one to be reported providing 1,3,5-triazine-2,4,6-trione derivatives.     

Synthesis of 3-arylamino-4(3H)quinazolinone derivatives from 1-acetyl- or 1-ethoxycarbonylmethylene-2-arylhydrazines

By reacting 1-acetyl- or 1-ethoxycarbonylehloromethylene-2-arylhydrazines ( 2a-c ) with anthranilic acids (1a-b) the corresponding C-acetyl- or C-ethoxyearbonylcarbohydrazonamide derivatives (3a-d) were obtained. Ring closure of the carbohydrazonamides with acetic anhydride afforded 2-carboethoxy- or 2-acetyl-3-arylamino-4(3H)quinazolinones ( 4a-d ). The ester derivatives undergo basic hydrolysis with decarboxylation to 3-arylamino-4(3H)quinazolinones ( 5a-b ).     

Cyclic transformations of 5-aryl(or benzyl)-3-(2-bromoethyl- 1,3,4-oxadiazol-2(3H)-ones into 1-aminoimidazolidin-2-one and 5,6-dihydro-4H-1,3,4-oxadiazine derivatives

5-Aryl(or benzyl)-3-(2-bromoethyl)-1,3,4-oxadiazol-2(3H)-ones 3 have been prepared. They were reacted with secondary alkylamines without any change of the heterocycle to give amino derivatives 6 , but with primary alkylamines, cyclic transformation occurred to give 1-acylamino-3-alkylimidazolidin-2-ones 7 . In the presence of sodium alcoholate, bromo compounds 3 were transformed into 2-aryl(or benzyl)-4-alkoxycarbonyl-5,6-dihydro-4H-1,3,4-oxadiazines 9 .     

Synthesis of 5-aryl-3-carbazoyl-1,3,4-oxadiazol-2(3H)-one. Derivatives and their ring transformation into 5-benzamido-1,2,4-triazolidine-3,5-dione derivatives

Some 5-aryl-3-carbazoyl-1,3,4-oxadiazol-2(3H)-one derivatives 6 and 9 have been synthesized in two ways. The expected thermal ring transformation into 2,5-disubstituted 1,3,4-oxadiazoles did not occur but, by acid hydrolysis of 5-aryl-3-[3-benzylidene-2-methyl(or phenyl)carbazoyl]-1,3,4-oxadiazol-2(3H)-ones 6 , a new ring transformation took place and the corresponding 4-benzamido-1-methyl(or phenyl)-1,2,4-triazolidine-3,5-dione derivatives 11 were formed. The 4-amino-1-phenyl-1,2,4-triazolidine-3,5-dione ( 19 ) has been prepared and its structure was confirmed by some reactions.     

Synthesis of azolo[a]pyridines from 5-(bromomethyl)hept-4-en-3-one and 5-bromopent-3-en-2-one derivatives

Alkyl derivatives of 1H-imidazo[1,2-a]pyridin-4-ium, 5H-pyrido[1,2-a]benzimidazol-10-ium, 1H-[1,2,4]-triazolo[4,3-a]pyridin-4-ium, and 3-methylthiazolo[3,2-a]pyridin-4-ium bromides were obtained in two stages from (4Z)-5-(bromomethyl)-2,2,6,6-tetramethylhept-4-en-3-one, 5-bromo-4-methylpent-3-en-2-one, or (3E)-5-bromopent-3-en-2-one by alkylation of 1-alkyl-1H-imidazoles, 1-alkyl-1H-benz-imidazoles, 1-methyl-1H-1,2,4-triazole, and 4-methylthiazole and subsequent cyclization of the quaternary azolium salts in the presence of bases.     

1,3-Dipolar cycle-addition of 2-diazoalkanes to pyridazin-3(2H)-one derivatives. The formation of 3H-pyrazolo[3,4-d]pyridazin-4(5H)-one and 3H-pyrazolo[3,4-d]pyridazin-7(6H)-one derivatives

1,3-Dipolar cycloadditions of diazoalkanes to pyridazin-3(2H)-ones 1–7 and pyridazin-3(2H)-thiones 8 and 9 are regioselective producing 3H -pyrazolo[3,4-d]pyridazin-4(5H)-ones 15–19, 27–29 and 34–38 as the major products. In some instances, the isomeric 3H-pyrazolo[3,4-d]pyridazin-7(6H)-ones, such as 20 and 23 were isolated as the minor products. From 3 and 6 the primary 3a,7a-dihydro cycloadducts 25 and 26 , and rearranged 1,2-dihydro intermediate 31 were isolated. From 10 and 1-diazoindane the isomeric exo- and endospiro products 39 and 40 were formed.     

Pyrimidine derivatives. IX . Synthesis of bromosubstituted 5-nitro-2,4(1H,3H)-pyrimidinedione derivatives

The following 5-nitro-2,4(1H,3H)-pyrimidinediones possessing bromo substituted side chains at the 1- and 6-positions were prepared by bromination of 3,6-dimethyl-1-(ω-hydroxyalkyl)-5-nitro-2,4(1H,3H)-pyrimidinediones 4a and 4b and its nitrates 2a and 2b . The three of mono-bromo derivatives are: 1-(ω-acetoxyalkyl and ω-hydroxyalkyl)-6-bromomethyl-3-methyl. 6a, 6b, 7a and 7b and 1-(ω-bromoalkyl)-3,6-dimethyl-2,4(1H,3H)- pyrimidinediones 8a and 8b . The one type dibromo derivatives are: 1-(ω-bromoalkyl)-6-bromomethyl-3-methyl-2,4(1H,3H)-pyrimidinediones 5a and 5b .     

Synthesis of tetronic acid enamine. Dienamine derivatives from 3-(2H)furanones

The synthesis of 5-aryl (or alkyl) aminomethylene-3-(1-amino or 1-alkylaminoethylidene)-2,4-dioxo-(3H,5H)furans and 5-arylaminomethylene-3-(1-hydroxyethylidene)-2,4-dioxo-(3H,5H)furans (new 3-acetyltetronic acid derivatives) are described. The stereochemistry of these compounds from the ¹H nmr data is discussed.     

Ni-Catalyzed desilylative annulation of benzamides and acrylamides with alkynylsilanes: Access to 3-Methyleneisoindolin-1-one and 5-Methylene-1H-pyrrol-2(5H)-one derivatives

Abstract

The nickel-catalyzed desilylative annulation of C(sp²)–H bonds of benzamides and acrylamides with alkynylsilanes assisted by 8-aminoquinolyl directing group has been reported. A variety of benzamides and acrylamides were compatible in this protocol to construct various 3-methyleneisoindolin-1-one and 5-methylene-1H-pyrrol-2(5H)-one derivatives with Z-configuration selectivity in moderate to high yields.     

A mass spectrometric investigation on some 3-[2-(Nitroxy)alkyl]-2H-1,3-benzoxazin-4-(3H)-one derivatives

The electron ionization mass spectrometric behaviour of ten 3-[2-(nitroxy)alkyl]-2H-1,3-benzoxazin-4-(3H)-one derivatives has been studied by means of metastable ion studies. By mass-analysed ion kinetic energy spectrometry of the related molecular ions, clear differences have been evidenced between the 5-methyl derivative and the other compounds, consisting of a highly favoured loss of NO₂ radical. The same methodology has allowed easy characterization of isomeric compounds.     

Metaboliten der 1,5-Dihydroimidazo[2,1-b]chinazolin-2(3H)-one. Synthese und Reaktionen einiger 1,5-Dihydro-3-hydroxyimidazo[2,1-b]chinazolin-2(3H)-one

Metabolites of 1,5-Dihydroimidazo[2,1-b ]quinazolin-2(3H)-ones. Preparation and Reactions of Some 1,5-Dihydro-3-hydroxyimidazo[2,1-b]quinazolin-2(3H)-ones Hydroxylated 1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-ones 2–4 and 6 were isolated as metabolites of imidazoquinazolinones 1a and 1b , respectively. The synthesis of 1,5-dihydro-3-hydroxy-3-methylimidazo[2,1-b]quinazolin-2(3H)-ones 3 , 4 , and 6 , and the preparation of some derivatives thereof is described.     

A simple and efficient approach for the synthesis of a novel class aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives via intramolecular nucleophilic substitution reaction

In this study, we synthesized a new series of substituted aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives (6-24) in yields ranging from 42 to 70% with an interesting mechanism that involves internal nucleophilic substitution followed by an S_N2-type nucleophilic substitution. First, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanone (3) was synthesized from the reaction of 5-methyl-1,3,4-thiadiazole-2-thiol (1) with 2-bromo-1-(4-chlorophenyl)ethanone (2) in the presence of potassium hydroxide. Then, 1-(4-chlorophenyl)-2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethanol (4) was synthesized by a reduction reaction of this compound using NaBH₄. Finally, 5-methyl-3-alkyl-1,3,4-thiadiazol-2(3H)-one derivatives (6-24), which are the target compounds, were synthesized from the reaction of this compound (4), which is a secondary alcohol with various alkyl halides (5a-n) in the presence of sodium hydride (NaH). This study presents an interesting reaction mechanism related to the synthesis of aliphatic 1,3,4-thiadiazol-2(3H)-one derivatives that is not recorded in the literature.     

Synthesis of perhydro-2(1H)-quinoxalinones and perhydropyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives

The novel trans-bicyclic-perhydro-2(1H)-quinoxalinones 4, 6 and 7 and the tricyclic-perhydropyrrolo[1,2-a]-quinoxalin-4(5H)-one derivatives 8 and 9 are prepared via a ring opening and spontaneous ring closing reaction of the aziridines 2 and 3 with the α-amino acids glycine, L-alanine, L-proline and L-phenylalanine. This methodology was used to prepare 5 and 10 which are novel rigid analogues of the kappa opioid compound 1. Treatment of aziridine 3 with methyl carbamate gave the cyclic urea 11.     

Heterocyclization reactions of azinoisocyanates. Synthesis of 2H-1,2,4-triazol-3(4H)-one derivatives

The reaction of 1-aminoethylidenehydrazones 9 with di-tert-butyl dicarbonate and 4 -dimethylaminopyridine led to the corresponding azinoisocyanates 10 , which underwent thermal rearrangement under the reaction conditions to give 4-(tert-butoxycarbonyl)-5-methyl-2H-1,2,4-triazol-3(4H)-ones 14 . However, amidrazone 17 gave 2-(2-tert-butoxycarbonyloxy-2-phenyl)ethyl-4-(tert-butoxycarbonyl)-5-methyl-2H-1,2,4-triazol-3(4H)-one 22 and N-aziridinyliminocarbamate 18 under the similar conditions.