A study of the Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one derivatives

Summary The Claisen rearrangement of 7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 a) gave 7-hydroxy-8-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (3 a) and 2,3-dihydro-2,6-diphenyl-3-methyl-(7H)furo[2,3-h]-1-benzopyran-7-one (7 a). 2-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (2 b) afforded4 b and7 b. 8-Methyl-7-(3-phenyl-2-propenyloxy)-3-phenyl-(4H)-1-benzopyran-4-one (12) gave only the alkali soluble product 7-hydroxy-8-methyl-6-(1-phenyl-2-propenyl)-3-phenyl-(4H)-1-benzopyran-4-one (13).3 a,4 b, and13 were further cyclized in acidic medium to9 a,10 b, and14 followed by dehydrogenation.This paper is dedicated to Dr. F. M. Dean, Department of Organic Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool, U. K., on his retirement     

Substituted γ-Lactones. 35 . Reduction of 4-aroyl-3-hydroxy-2(5H)-furanones

The reduction of 4-aroyl-3-hydroxy-2(5H)-furanons 1a-c was investigated using different reducing agents. Sodium borohydride reacts with type 1 compounds by loss of water to yield 4-(arylmethylene)-2,3(4H,5H)-furandiones 2a-c . Platinum or charcoal supported by pallodium chloride transforms 1a to 4-benzyl-3-hydroxy-2(5H)-furanone ( 3). Compounds 2a and 2b react with o-phenylenediamine to give 3-(E-(1′-hydroxymethyl-2′-aryl)ethenyl]-2-quinoxalinones 4a and 4b . The lactone 3 under the same conditions splits out formaldehyde and forms 3-(2′-phenylethyl)-2-quinoxalinone ( 6 ). The structure assignments of the novel compounds are based on elemental analysis and nmr as well as ir spectroscopic data.     

Crystal structure,dissociation and zwitterion formation in 2,6-diaryl-1(3)-oxo-3(1)-hydroxy-5(7)-imino-7(5)-amino-1 H,5H-(3-H,7H)-pyrazolo[1,2-a]pyrazoles

Single crystal X-ray analysis and quaternization of 2,6-diphenyl-1(3)-oxo-3(1)-hydroxy-5(7)-imino-7(5)-1H,-5H[3H,7H)-pyrazolo[1,2-a]pyrazole is described. The dissociation constants are determined and compared with those of 4-phenyl-1,2-dimethyl-3(5)-oxo-5(3)-hydroxypyrazole and 4-phenyl-3,5-diaminopyrazole. The quaternization of the latter compound is also described. The influence of electron donating substituents at the cationic moiety on the electronic spectra of such paraionic systems is discussed. The title products exist in the solid state as zwitterions and probably as covalent species in solution.     

Pyridinethiones. XI. Diastereoselective aldol condensations with 2(1H)-pyridones, 2(1H)-pyridinethiones,and the crystal structure of 3-(1-hydroxy-2-methyl-3-oxo-3-(4-chlorophenyl)propyl-1-isoprpyl-2(1H)-pyridinethione

Aldol condensation of 3-formyl-2(1H)-pyridinethiones and the corresponding pyridones with ketones such as acetophenones in aqueous base yields 3-hydroxy-1-propanones in high yields. Reaction with propiophenone showed this reaction to be highly diastereoselective as only the erythro-isomer is formed at room temperature. This assignment was based on an X-ray crystallographic investigation of the compound given in the title. Aldol condensations of a number of related 3-acetyl-2(1H)-pyridinethiones with benzaldehyde yielded the corresponding trans-vinyl ketones.     

Synthesis of benzo-halogenated 4-hydroxy-2(1H)-quinolones

Malondianilides 3 derived from dichloro substituted anilines 2 undergo cyclization to afford 4-hydroxy-2(1H)-quinolones 4 in very good yields using methane sulfonic acid-phosphorus pentoxide as catalyst. 3,4-Dichloro anilines 5 can be shown to yield two isomers, 7 and 8 , whereas 3-substituted anilines 9 afford merely 7-substituted 4-hydroxy-2(1H)-quinolones 11.     

Synthesis of 1H-pyrazolo[3,4-c]isoquinolin-1-ones by the condensation of cyclohexanone derivatives with 3-amino-1-phenyl-1H-pyrazol-5(4H)-one

The synthesis of 1H-pyrazolo[3,4-c]isoquinolin-1-ones was carried out by reacting 3-aryl(heteryl)-2,4-diacetyl-5-hydroxy-5-methylcyclohexanones with 3-amino-1-phenyl-1H-pyrazol-5(4H)-one. The structure of the 7-acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-dimethyl-2-phenyl-6-(fur-2-yl)-1H-pyrazolo[3,4-c]isoquinolin-1-one obtained was proved by X-ray diffraction analysis.     

Dioxomolybdenum(VI) complexes containing 1-alkyl-2-ethyl-3-hydroxy-4-pyridin-4(1H)-ones

Dioxomolybdenum(VI) complexes derived from ethyl maltol (2-ethyl-3-hydroxy-4-pyrone) and 1-alkyl-2-ethyl-3-hydroxy-4-pyridin-4(1H)-ones have been prepared and characterized using physical methods including ¹H- and ¹³C-n.m.r. spectroscopy, i.r., elemental analysis, and X-ray diffraction for the pyrone and 3-methylpyridine pyridinone derivatives. The octahedral complexes have the general formula cis-MoO₂L₂ where L = the deprotonated pyrone or pyridinone ligand.     

Five-membered 2,3-dioxoheterocycles: LXVII. Pyrroledione-pyrroledion recyclization of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates under the action of arylamines. Crystal and molecular structure of (z)-isopropyl 2-hydroxy-4,5-dioxo-1-phenyl-3-[phenyl(phenylamino)-methylene]pyrrolidine-2-carboxylate

Reactions of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates with aromatic amines involve a pyrroledione-pyrroledione recyclization to form isopropyl 1-aryl-2-hydroxy-4,5-dioxo-3-[phenyl(arylamino)methylene]pyrrolidine-2-carboxylates. The crystal and molecular structure of (Z)-isopropyl 2-hydroxy-4,5-dioxo-1-phenyl-3-[phenyl(phenylamino)methylene]pyrrolidine-2-carboxylate was proved by XRD analysis.     

Acetylenchemie, 14. Mitt.: PTC-Umsetzung von 9(10H)-Acridinon mit 3-Chlor-3-phenyl-1-propin und 3-Brom-1-phenyl-1-propin

Summary Reaction of 9(10H)-acridinone (2) with 3-chloro-3-phenyl-1-propyne under PTC conditions affords 1-methyl-2-phenyl-6H-pyrrolo[3,2,1-de]acridin-6-one (1 b), 10-(2-chloro-1-methyl-2-phenyl-ethenyl)-9(10H)-acridinone (4), 10-(3-phenyl-1-propynyl)-9(10H)-acridinone (7), and 10-(4-methylene-2,3-diphenyl-2-cyclobuteneylidenemethyl)-9(10H)-acridinone (5). The structure of the last compound which crystallizes in the triclinic system with the space group , was confirmed by X-ray diffraction. Under the same conditions 10-(3-phenyl-2-propynyl)-9(10H)-acridinone (3) and 10-(3-phenyl-1-propynyl)-9(10H)-acridinone (6) were obtained from 9(10H)-acridinone (2) and 3-bromo-1-phenyl-1-propyne.

     

Enzymatic resolution of trans-2,3-dihydro-3-hydroxy-2-phenyl-4H-1-benzopyran-4-one (trans-flavanon-3-ol) by lipase

trans-2,3-Dihydro-3-hydroxy-2-phenyl-4H-l-benzopyran-4-one (trans-flavanon-3-ol) was resolved to acetate of (2S,3S)-(-)-trans-flavanon-3-ol and (2R,3R)-(-)-trans-flavanon-3-ol by an enzymatic transesterification with vinyl acetate in the presence of Pseudomonas cepacia lipase.     

Ein einfacher Zugang zu 4-hydroxy-2,5-dimethyl-3(2H)-furanon (furaneol), einem Aromabestandteil von Ananas und Erdbeere

Furaneol®

1 Registered trade mark of Firmenich SA.

[4-hydroxy-2,5-dimethyl-3(2H)-furanone ( 1 )], a flavour component of pineapple and strawberry, has been prepared by a two-step synthesis starting with readily available 3-hexyne-2,5-diol. By the same method 4-hydroxy-5-methyl-3(2H)-furanone ( 2 ) and 2-ethyl-4-hydroxy-5-methyl-3(2H)-furanone ( 3a ) have been prepared from 2-pentyne-1,4-diol and 3-heptyne-2,5-diol, respectively.     

Natural product chemistry. Part 158. Reactions of ethyl 4-hydroxy-1-methyl-3-quinolin-2(1H)-onecarboxylate with 1,4-dibromo-2-methyl-2-butene

Ethyl 4-hydroxy-1-methyl-3-quinolin-2(1H)-onecarboxylate ( 1 ) which is obtained conveniently by the condensation of N-methylisatoic anhydride with diethyl malonate [4], was reacted with 1,4-dibromo-2-methyl-butene ( 2 ) to give the main products 3 and 4 and the dimeric derivatives 5 and 6 .     

Further reactions of 3-hydroxy-1(3H)-isobenzofuranone with amines

The reaction of 3-hydroxy-1(3H)-isobenzofuranone (III) with 2-phenylethylamines has been shown to give either monoalkylated VI or dialkylated VII products (prodrugs) depending on the number of equivalents of III used. The monoalkylated products disproprotionated to the dialkylated products unless they were stabilized as salts. In addition, the reaction of III with cytosine and adenine resulted in the formation of N⁴ and N⁶-alkylated products, respectively. The alkylated 2-phenylethylamines, and cytosine and adenine are representative of a new type of prodrug approach to modifying the physical chemical properties of these two important classes of drugs.     

Über die Einwirkung von Ammoniak auf 5-Chlor-2-(N-methyl-jodmethansulfonamido)-benzophenon

Zusammenfassung 5-Chlor-2-(N-methyl-jodmethansulfonamido)-benzophenon (6 b) reagiert mit flüss. NH₃ zu 6-Chlor-4-hydroxy-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazin-2,2-dioxid (7), mit NH₃ in absol. Alkohol zu 6-Chlor-4-hydroxy-3-jod-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazin-2,2-dioxid (9). Der Mechanismus dieser Reaktionen wird diskutiert.

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The reaction of ammonia with 5-Chloro-2-(N-methyl-iodo-methanesulfonamido)-benzophenone

The reaction of 5-chloro-2-(N-methyl-jodomethanesulfon-amido)-benzophenone (6b) with liquid or absol. alcoholic ammonia leads to 6-chloro-4-hydroxy-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazine-2,2-dioxid (7) and 6-chloro-4-hydroxy-3-jodo-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazine-2,2-dioxid (9) resp. The mechanism of these reactions is discussed.

     

Mechanism of the condensation reaction between 1-aryl- and heteroaryl-1,4-dihydro-3(2H)-isoquinolinones and aldehydes

4-Benzylidene-1-phenyl-1,4-dihydro-3(2H)-isoquinolinone, the intermediary product of the carbonyl condensation reaction between 1-phenyl-1,4-dihydro-3(2H)-isoquinolinone and benzaldehyde, rearranges in the presence of an equivalent quantity of sodium hydride into 4-benzyl-1-phenyl-3(2H)-isoquinolinone. As the possibility of the migration of the hydrogen at C-1 in the form of a proton or a hydrogen atom (radical reaction) was excluded, the mechanism of the rearrangement could be depicted as an intermolecular hydride anion migration. In case of the 1-(4-pyridyl)- and 1-(3-pyridyl)-1,4-dihydro-3(2H)-isoquinolinones, however, the rearrangement can be carried out also in polyphosphoric acid and in this case a proton loss-proton gain mechanism was proved.     

Transformation of 4-(1-dimethylaminoethylidene)-2-phenyl-5(4H)-oxazolone into methyl 2-benzoylamino-3-oxobutanoate. The synthesis of 1-substituted 4-benzoylamino-3-methyl-5(2H)-pyrazolones

Methyl 2-benzoylamino-3-oxobutanoate ( 3 ) was prepared from hippuric acid (1) which was converted with N,N-dimethylacetamide and phosphorus oxychloride into 4-(1-dimethylaminoethylidene)-2-phenyl-5(4H)-oxazolone ( 2 ) followed by hydrolysis with hydrochloric acid in methanol. Compound 3 was treated with hydrazines 4 to give 4-benzoylamino-3-methyl-1H-pyrazol-5(2H)-one ( 6a ) and its 1-substituted derivatives 6b-j . The corresponding hydrazones 5f, i, j were isolated as intermediates.     

Structural reassignment of the alleged 6-hydroxy-1,2,4-triazine-3,5-(2H,4H)dione

The reaction of 6-amino-1,2,4-triazine-3,5-(2H,4H)clione with sodium hydroxide or nitrous acid has been shown to give 5-hydroxy-1,2,4-triazole-3-carboxylic acid instead of 6-hydroxy-1,2,4-triazine-3,5-(2H,4H)dione as reported in the literature. The triazolecarboxylic acid was also obtained from the aminotriazine and hydrochloric acid.     

Pyrimidines. 24. Analogues and derivatives of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP)

Preparation of a number of derivatives of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) including the 2-dialkylaminoalkylamino-, 2-hydroxyalkylamino-, 2-ethoxycarbonylamino- and 2-alkylaminocarbonyl-amino- groups substituted on the pyrimidine ring as well as preparation of 1-(alkylaminoalkyl)-4,6-dioxo-8-phenyl-2,3,4,6-tetrahydro-1H-pyrimido[1,2-α]pyrimidines and 3,5-dioxo-7-phenyl-1,2,3,5-tetrahydroimidazo-[1,2-α]pyrimidines with or without the bromo-substitution are reported.     

Synthesis of 2-amino-3-hydroxy- and of 2,3-diamino-3H-1,4-benzodiazepines

A new synthesis of 7-chloro-2,3-diamino-5-phenyl-3H-1,4-benzodiazepines is described, which allows for the preparation of compounds bearing the same or different substituents at the 2 and 3 positions, starting from 2-amino-7-chloro-3-hydroxy-5-phenyl-3H-1,4-benzodiazepines.     

Eine überraschende Ringerweiterung von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin zu 4,5-Dihydropyridin-2(3H)-on-Derivaten

An Unexpected Ring Enlargement of 3-(Dimethylamino)-2,2-dimethyl-2H-azirine to 4,5-Dihydropyridin-2(3H)-one Derivatives The reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1a ) and 4,4-disubstituted 2-(trifluoromethyl)-1,3-oxazol-5(4H)-ones 7 in MeCN at 70° afforded 5-(dimethylamino)-3,6-dihydropyrazin-2(1H)-ones 10 (Scheme 4), whereas no reaction could be observed between 1a and 2-allyl-4-phenyl-2-(trifluoromethyl)-1,3-oxazol-5(2H)-one ( 8a ) or 4,4-dibenzyl-2-phenyl-1,3-oxazol-5(4H)-one ( 9 ). The formation of 10 is rationalized by a mechanism via nucleophilic attack of 1a onto 7 . The failure of a reaction with 9 shows that only activated 1,3-oxazol-5(4H)-ones bearing electron-withdrawing substituents do react as electrophiles with 1a . The amino-azirine 1a and 2,4-disubstituted 1,3-oxazol-5(4H)-ones 2b – e in refluxing MeCN undergo a novel ring enlargement to 4,5-dihydropyridin-2(3H)-ones 11 (Scheme 5). Several side products were observed in these reactions. Two different reaction mechanisms for the formation of 11 are proposed: either 1a undergoes a nucleophilic addition onto the open-chain ketene tautomer of 2 (Scheme 6), or 2 reacts as CH-acidic compound (Scheme 7).