The photolysis of 1-(4,5-dihydro-1H-imidazol-2-yl)benzotriazole

1-(4,5-Dihydro-1H-imidazolo-2-yl)benzotriazole was photolyzed at 254 nm yielding 1,2-dihydro-4H-imidazo-[1,2-a]benzimidazole.     

Novel routes to 1-aryl-1,4-dihydro-3(2H)-isoquinolinones and 2-substituted or 2,3-disubstituted benzofurans by intramolecular cyclizations

N-(α-Benzotriazolylalkyl)arylacetamides, readily available from an arylacetamide, an aldehyde and benzotriazole, undergo intramolecular cyclization under acidic conditions to give 1-aryl-1,4-dihydro-3(2H)-isoquinolinones in good to excellent yields. Similarly, 2-(benzotriazol-1-yl)-2-(o-hydroxyphenyl)ethanols, obtained by lithiation of 2-(benzotriazol-1-ylmethyl)phenols followed by quenching with aldehydes or ketones, eliminate a molecule of water and a molecule of benzotriazole yielding 2-substituted and 2,3-disubstituted benzofurans.     

Synthesis of (R)-3,4-dihydro-2H-pyran-2-carboxaldehyde: application to the synthesis of potent adenosine A2A and A3 receptor agonist

Synthesis of potent adenosine A_2A and A₃ receptor agonist from the modification of adenosine-5′-N-ethylcarboxamide (NECA) has been reported. Diastereoisomer possessing an (R)-3,4-dihydro-2H-pyranyl (DHP) moiety exhibited the highest affinity at the A_2A and A₃ receptors. The key steps involve the synthesis of (R)-3,4-dihydro-2H-pyran-2-carboxaldehyde (7), which was obtained through the enzyme-catalyzed kinetic resolution of (±)-2-acetoxymethyl-3,4-dihydro-2H-pyran (5).     

New synthesis of chalcogenolactones. 1H,3H-benzo[c]selenophen-1-one, 1H,3H-benzo[c]tellurophen-1-one and the related 3,4-dihydro-1H-2-benzoselenin-1-one and 3,4-dihydro-1H-2-benzotellurin-1-one

The synthesis of three new basic heterocyclic systems namely, 1H,3H-benzo[c]tellurophen-1-one (2-tellurophthalide), 3,4-dihydro-1H-2-benzoselenin-1-one (3,4-dihydro-2-isoselenocoumarin) and 3,4-dihydro-1H-2-benzotellurin-1-one (3,4-dihydro-2-isotellurocoumarin), is reported through the cyclisation of o-(bromoalkyl)benzoyl chlorides.     

Synthesis of new CF3-containing 3,4-dihydro-2H-pyrans

The reactions of vinyl sulfides with -sulfonylvinyl trifluoromethyl ketones afforded CF₃-containing 3,4-dihydro-2H-pyrans. An attempt to synthesize 1,1,1-trifluoro-3-(methylthio)but-3-en-2-one resulted in its dimerization into a CF₃-containing 3,4-dihydro-2H-pyran.     

Unambiguously confirmed structure of 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one

To determine the structures of two isomeric products, 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (2) and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (3) obtained by condensation of 2,3-diaminopyridine (1) with ethyl benzoylpyruvate [1–3], these compounds were hydrolyzed to give 2-methyl-4H-pyrido[2,3-b]pyrazin-3-one (4) and 3-methyl-1H-pyrido[2,3-b]pyrazin-2-one (5) , respectively [4,5]. Both hydrolysates 4 and 5 were hydrogenated to afford 2-methyl-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (6) and 3-methyl-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (7) . The latter compound was identical with an unequivocally synthesized compound providing proof for the structures of all these compounds.     

Spiro[(2,3-dihydro-2-oxo-imidazo[1,2-a]pyridine)-3,3-(3,4-dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine 1,1-dioxide)]-A novel product derived from piroxicam

A novel compound, spiro[(2,3-dihydro-2-oxo-imidazo[1,2-a]pyridine)-3,3-(3,4-dihydro-2-methyl-4-oxo-2H-1,2-benzothiazine 1,1-dioxide)] (3) , was isolated during an attempt to convert 4-hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide ( 1 ) (Piroxicam) to an O-trifluoromethanesulfonyl ester. A possible mechanism is offered to explain this unusual transformation.     

Synthesis of 5,6-dihydro-2H-thiopyrans

Synthesis of 5,6-dihydro-2H-lhiopyrans by mild dehydromesylation of the corresponding tetrahydro-4H-thiopyran-4-mesylates using commercial grade Woelrn W-200 (activity, Super 1) neutral alumina is described. Cis- and trans-stereoisomers of 2,6-diphenyl-5,6-dihydro-2H-thiopyrans were prepared for the first lime without isomerization.     

Synthesis and anticonvulsant activity of 3-alkyl-3,4-dihydro-2(1H)-quinazolinones

Previously we reported the potent anticonvulsant activity of 3-dimethylamino-3,4-dihydro-2(1H)-quinazolinone. In this report, a series of 3-alkyl-3,4-dihydro-2(1H)-quinazolinones was synthesized in three steps from isatoic anhydrides or an anthranilic acid. Structure/activity investigations revealed optimal activity for the 3-isopropyl and 3-cyciohexyl analogs. These compounds were effective against seizures induced by maximal electroshock.     

A facile synthesis of 1-alkylthio and acylthio-2,3-dihydro-1H-naphtho[2,1-b]thiopyrans and 4-alkylthio and acylthio-3,4-dihydro-2H-naphtho[1,2-b]thiopyrans

The reaction of 3-(2-naphthylthio)propionaldehyde ( 3 )and its (1-naphthylthio)isomer (7)with a variety of thiols and thio acids in the presence of sulfuric acid at room temperature afforded 1-alkylthio and acylthio-2,3-dihydro-1H-naphtho[2,1-b]thiopyrans 5 and 4-alkylthio and acylthio-3,4-dihydro-2H-naphtho[1,2-b]thiopyrans 9 in excellent yield.     

Preparation of 3,4-dihydro-2H-1,3-benzoxazines

N,N-Di(butoxymethyl)alkylamines react with phenols under mild conditions to yield substituted 3,4-dihydro-2H-l,3-benzoxazines.     

4-Substituted-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones. III (2,3). Solvolytic-reductive transformation of 4-(2-keto)-benzoxazin-2-ones into oxazin-2-ones

A series of 4-(2-keto-substituted)-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones 1 (Table I) was synthesized by condensation of 3-alkyl-3,4-dihydro-4-hydroxy-2H-1,3-benzoxazin-2-ones 4 with ketones 5 having active alpha hydrogens. In the presence of alcoholic potassium borohydride, compounds 1 underwent reductive transacylation to give 1,3-oxazin-2-one derivatives 3 (Table III, a,b,c). When the other side of the ketone possessed substituents other than hydrogen, there were always also normal reduction products, i.e., secondary alcohols 2 (Table II) in addition to 3.     

Ab initio molecular orbital study of energies and conformers of 3,4-dihydro-1,2-dithiin, 3,6-dihydro-1,2-dithiin, 4H-1,3-dithiin,and 2,3-dihydro-1,4-dithiin

Optimized geometries and energies for 3,4-dihydro-1,2-dithiin ( 1 ), 3,6-dihydro-1,2-dithiin ( 2 ), 4H-1,3-dithiin ( 3 ), and 2,3-dihydro-1,4-dithiin ( 4 ) were calculated using ab initio 6-31G* and MP2/6-31G*//6-31G* methods. At the MP2/6-31G*//6-31G* level, the half-chair conformer of 4 is more stable than those of 1 , 2 , and 3 by 2.5, 3.5, and 3.6 kcal/mol, respectively. The half-chair conformers of 1 , 2 , 3 , and 4 are 2.9, 7.1, 2.0, and 5.6 kcal/mol, respectively, more stable than their boat conformers. The calculated half-chair structures of 1 – 4 are compared with the calculated chair conformer of cyclohexane and the half-chair structures for cyclohexene, 3,4-dihydro-1,2-dioxin ( 5 ), 3,6-dihydro-1,2-dioxin ( 6 ), 4H-1,3-dioxin ( 7 ), and 2,3-dihydro-1,4-dioxin ( 8 ). © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1064–1071, 1998     

Synthesis of 3-amino-3,4-dihydro-2(1H)-quinazolinones as potential anticonvulsants

Thirteen 3-amino-3,4-dihydro-2(1H)-quinazolinones have been synthesized from ethyl chloroformate and o-aminobenzylhydrazines. The latter compounds were obtained from the metal hydride reduction of either o-aminobenzhydrazides or o-acylaniline hydrazones. All compounds were evaluated in mice in the maximal electroshock (MES) seizure and pentylenetetrazole (sc Met) seizure threshold tests for anticonvulsant activity and in the rotorod test to determine neurotoxicity. Five of the compounds showed activity in one or both tests at a dose of 300 mg/kg or lower. The most active compound is 3-dimethylamino-3,4-dihydro-2(1H)-quinazolinone.     

A Short and Efficient Synthesis of Novel N-(2,3-dihydro-2-oxo-5-phenyl-1 H -1,4-benzodiazepin-3-yl)-2-carboxamides

 Several novel N-(2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-2-carboxamides were prepared by acyl coupling of 2-aminobenzophenones with α-(benzotriazol-1-yl)-N-acylglycines followed by displacement of the benzotriazole ring with ammonia and cyclization of the resulting monoacyl aminals. In addition to high yields and shorter reaction sequences due to avoiding deprotection and acylation of the protected 3-amino-1,4-benzodiazepin-2-one intermediates, the present approach did not involve the use of toxic and odoriferous materials as is the case with other methods.     

A Short and Efficient Synthesis of Novel N-(2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-2-carboxamides

Summary.  Several novel N-(2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-2-carboxamides were prepared by acyl coupling of 2-aminobenzophenones with α-(benzotriazol-1-yl)-N-acylglycines followed by displacement of the benzotriazole ring with ammonia and cyclization of the resulting monoacyl aminals. In addition to high yields and shorter reaction sequences due to avoiding deprotection and acylation of the protected 3-amino-1,4-benzodiazepin-2-one intermediates, the present approach did not involve the use of toxic and odoriferous materials as is the case with other methods. Received September 20, 2000. Accepted (revised) November 29, 2000     

Ring transformation of 6-methyl-3,4-dihydro-2H-1,3-oxazine-2,4-diones

Ring transformation of 6-methyl-3,4-dihydro-2H-1,3-oxazine-2,4-dione (Ia) and its N-sub-stituted derivatives, such as 3-methyl (Ib), 3-ethyl (Ic), and 3-benzyl (Id) derivatives is described. Reaction of Ia with hydrazine hydrate gave 1-amino-6-methyluracil (II), while Id reacted with hydrazine hydrate to give 3-hydroxy-5-methylpyrazole (III). Reaction of Ia,b,d with ethyl acetoacetate in ethanol in the presence of sodium ethoxide afforded ethyl 3-acetyl-6-hydroxy-4-methyl-2(1H) pyridone-5-carboxylate derivatives (IVa,b,d). On the other hand, reaction of Ib,c,d with ethyl acetoacetate in tetrahydrofuran in the presence of sodium hydride did not give IV, but gave 3-acetyl-1-alkyl-5-(N-alkylcarbamoyl)-6-hydroxy4-methyl-2(1H) pyridone (VIb,c,d). Mechanisms for the formation of compounds IV and VI are discussed.     

Preparation and reactions of 3,4-dihydro-2H-pyran-2-ones

The Michael reaction of ethyl cinnamates with deoxybenzoin gave ethyl 3,4,5-triaryl-5-oxopentanoates which were hydrolysed to the corresponding acids. The latter could be cyclized to the respective 3,4-dihydro-2H-pyran-2-ones which underwent ring opening with several nucleophiles to the corresponding acid derivatives. However, their reaction with ammonium acetate led to the formation of 3,4-dihydro-2-pyridones. The 3,4-dihydro-2-pyrones and pyridones were dehydrogenated to the corresponding 2-pyrones and 2-pyridones by fusion with sulfur.     

A convenient synthesis of 3,4-dihydro-2-methyl-3-oxo-2H-1,4-benzoxazine-2-carboxylic acids and 3,4-dihydro-2-methyl-3-oxo-2H-pyrido[3,2-b]-1, 4-oxazine-2-carboxylic acid

A convenient one pot synthesis of ethyl 3,4-dihydro-2-methyl-3-oxo-2H-1,4-benzoxazine-2-carboxylates and 3,4-dihydro-2-methyl-3-oxo-2H-pyrido[3,2-b]-1,4-oxazine-2-carboxylates and their conversion into the respective carboxylic acids are described.     

2,3,4,9-Tetrahydro-1H-pyrido[3,4-b]indoles. II. Reversible transformation of 1-alkyl-2-(4,9-dihydro-3H-pyrido[3,4-b]indol-1-yl)cyclohexanol into 1-alkylidene-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoles

Treatment of 2-(4,9-dihydro-3H-pyrido[3,4-b]indol-1-yl)-1-methylcyclohexanol ( 2a ) with acetic anhydride or methyl isocyanate gave 2-acetyl-2,3,4,9-tetrahydro-1-(6-oxoheptylidene)-1H-pyrido[3,4-b]indole ( 3 ) or 1,3,4,9-tetrahydro-N-methyl-1-(6-oxoheptylidene)-2H-pyrido[3,4-b]indole-2-carboxamide ( 4 ), respectively. Simpler analogues, 1-alkyl-4,9-dihydro-3H-pyrido[3,4-b]indoles, 7 , subjected to identical reaction conditions, gave 2-acetyl-1-alkylidene-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoles 8 and 1,3,4,9-tetrahydro-N-methyl-1-alkyli-dene-2H-pyrido[3,4-b]indole-2-carboxamides 9 , respectively. A limited lanthanide shift reagent study to determine stereochemical assignments was also performed.