Synthesis of 3-(2H-Indazol-2-yl)-2H[1]-Benzopyran-2-Ones

Hitherto unknown 3-(2H-Indazol-2-yl)-2H[1] benzopyran-2-ones (4a-f) have been synthesized under the trithyl phosphite (TEP) mediated reaction conditions of 3-[[(2-nitro-phenyl)-methylene]amino]-2H-1-benzopyran-2-ones (3a-f), obtained by the condensation of 3-amino coumarins (1a-f) with 2-nitro-benzaldehyde (2).     

Preparation of 1,5-disubstituted pyrrolidin-2-ones

1,5-Disubstituted pyrrolidin-2-ones 18a-g, 19a-h, and 20a-f were synthesized in good to excellent yields via the nucleophilic substitution of 5-(benzotriazol-1-yl)-1-substituted-pyrrolidin-2-ones 9 with allylsilanes, organozinc reagents, and phosphorus compounds. Compounds 9 and 5-(benzotriazol-2-yl)-1-substituted-pyrrolidin-2-one isomers 10 are readily prepared in total 70-84% yields from 2, 5-dimethoxy-2,5-dihydrofuran (7), primary amines 8, and benzotriazole; 9 and 10 react identically with nucleophiles.     

Eine neue lactonsynthese via 2-oxazolin-5-one als zwischenprodukte

Treatment of N-acyl-aminoacid dimethylamides of type 8 with HCl in toluene leads to lactones of type 9 in good yields via the intermediate formation of 2-oxazolin-5-ones.     

Synthesis of Several 2-Azafluorenones and 5H[1]Benzopyrano[3,4-c]Py Riding-Ones

Convenient syntheses of 2-azafluorenones 5a-f and 5H[1]benzopyrano[3,4-c]pyridin-5-ones 6a-b were performed by using intramolecular cyclization of 4-arylnicotinic acids 4a-F. 4a-f were obtained via permanganate oxidation from the corresponding of 4-arylpyridines 3a-f in good yields.     

Synthesis and reaction of 6-substituted 3-methoxycarbonyl-4-methylthio-2H-pyran-2-one derivatives

Reaction of aryl and styryl methyl ketones 1a-m with dimethyl bis(methylthio)methylenemalonate ( 2 ) in the presence of potassium hydroxide in dimethyl sulfoxide gave the corresponding methyl 6-aryl- and 6-styryl-4-methylthio-2-oxo-2H-pyran-3-carboxylates 3a-m . 6-Aryl derivatives 3a-d,g were treated with sodium methoxide in methanol to give the corresponding 6-aryl-4-methoxy-2H-pyran-2-ones 8a-d and 9. Phenylcoumalin ( 7a ) and paracotoin ( 7b ) were synthesized by the desulfurization of 6-aryl-4-methylthio-2H-pyran-2-ones 4a,b. Similarly, anibine ( 8e ) was also synthesized from 3g . Treatment of 3 with hydrogen peroxide or 3-chloroperoxybenzoic acid gave the corresponding 4-methylsulfiny-2H-pyran-2-ones 10a-f in good yields. Displacement reactions of 10a-f with nucleophilic reagents are also described.     

A facile preparation of 4-(1-Acetyl-4(1H)-pyridylidene)-2-oxazohn-5-ones

4-(1-Acetyl-4(1H)-pyridylidene)-2-oxazolin-5-ones were prepared by the reaction of acylglycines with pyridine and acetic anhydride under oxygen. Acidic and alkaline hydrolysis of 2-oxazolin-5-ones provided oxazole derivatives, pyridine derivatives, and carboxylic acids.     

Studies on the synthesis of amino acids XIII. Dibenzylation of 2-phenyl-2-oxazolin-5-one

4,4-Dibenzyl-2-phenyl-2-oxazollin-5-ones are prepared by one step reaction of 2-phenyl-2-oxazolin-5-one with magnesium methyl carbonate (MMC) and benzylhalides. It is a novel and convenient method for the synthesis of α,α-disubstituted α-amino acids by hydrolysis of 4,4-dibenzyl-2-phenyl-2-oxazolin-5-ones.     

Selektive Umfunktionalisierung der terminalen Amidgruppe offenkettiger Polyamide via 2-Oxazolin-5-one als Zwischenstufen. Vorläufige Mitteilung

Selective Modification of the Terminal Amide Group of Linear Polyamides via 2-Oxazolin-5-ones as Intermediates Treatment of aqueous or alcoholic solutions of diamides of type 2 with HCl leads to the formation of amide-acids and amide-esters of type 3 (Scheme 1 and Table). It has been shown, that 2-oxazolin-5-ones of type 4 are intermediates of this selective transformation of the disubstituted terminal amide group. The selectivity of the transformation is demonstrated by the reaction sequence shown in Scheme 3. No selectivity has been observed in the acid-catalyzed hydrolysis of triamide 9 with a monosubstituted terminal amide group (Scheme 4). Hydrolysis of the optically active dipeptide derivatives (+)-(L )- 13 and (+)-(L )- 15 with HBr in nitromethane at 60–80° yields the pure enantiomer (+)-(L )- 14 and (+)-(L )- 16 , respectively (Scheme 5), i.e., no racemization takes place under the reaction conditions. These results show the usefulness of the dimethylamide group as a protecting group for carboxylic acids for example in the peptide synthesis.     

The convenient synthesis of benzimidazole derivatives catalyzed by I2 in aqueous media

In the presence of catalytic amount of iodine, in THF‐H₂O, the condensation of aldehydes with 1,2‐phenylenediamine gave the benzimidazole derivatives under mild conditions in good yields. The method can be used for the synthesis of 2‐substituted benzimidazoles or 1,2‐disubstituted benzimidazoles.     

The first synthesis of phosphonoacrolein. Application to Diels-Alder reaction as heterodiene

The first synthesis of phosphonoacrolein 3 was made in quantitative yield by acidic treatment of beta-ethoxy-alpha-(methoxymethyl)vinylphosphonate 2, derived from a beta-ethoxy-alpha-phosphonovinyl anion and MOMCl. The phosphonoacrolein 3 easily underwent a hetero-Diels-Alder reaction with electron-rich alkenes 4a-f or alkynes 9a-c under mild conditions, and phosphono-substituted pyrans 5a-d, 6e,f or pyranopyrans 11a-c were obtained in good to excellent yields. The reaction of 3 with cyclopentadiene and cyclohexadiene led to mixtures of [2 + 4] and [4 + 2] cycloadducts 7a, 8a and 7b, 8b in modest yields. The cycloaddition reaction between 3 and pyranopyran 13 or dibromocarbene and 13 resulted in [4 + 2] or [2 + 1] cycloadducts 14 or 15 in good yields.     

Studies in spiroheterocycles,Part XV. Investigation of the reaction of 3-(2-oxocycloalkylidene)-indol-2-ones with thiourea and urea derivatives

The reaction of 3-(2-oxocycloalkylidene)indol-2-one 1 with thiourea and urea derivatives has been investigated. Reaction of 1 with thiourea and urea in ethanolic potassium hydroxide media leads to the formation of spiro-2-indolinones 2a-f in 40–50% yield and a novel tetracyclic ring system 4,5-cycloalkyl-1,3-diazepino-[4,5-b]indole-2-thione/one 3a-f in 30–35% yield. 3-(2-Oxocyclopentylidene)indol-2-one afforded 5′,6′-cyclopenta-2′-thioxo/ oxospiro[3H-indole-3,4′(3′H)pyrimidin]-2(1H)-ones 2a,b and 3-(2-oxocyclohexylidene)indol-2-one gave 2′,4′a,5′,6′,7′,8′- hexahydro-2′-thioxo/oxospiro[3H-indole-3,4′ (3′H)-quinazolin]-2(1H)-ones 2c-f . Under exactly similar conditions, reaction of 1 with fluorinated phenylthiourea/cyclohexylthiourea/phenylurea gave exclusively spiro products 2g-1 in 60–75% yield. The products have been characterized by elemental analyses, ir pmr. ¹⁹F nmr and mass spectral studies.     

2,5,5-Trimethyl-2-oxazolin-4-one,its perchlorate,and α-acetoxyisobutyronitrile by acetylation of acetone cyanohydrin

Acetone cyanohydrin (1) yields on acylation and ring closure with anhydrides and perchloric acid. 2-oxazolin-4-onium perchlorates 5a, 5c or 5d. The same perchlorates (5a, 5b) may be obtained under similar conditions from acyloxy-nitriles (2) or -amides (4). Perchlorates 5 may be deprotonated in pyridine to 2-oxazolin-4-ones (6), but in aqueous solution they undergo ring opening to acyloxy-amides 4a.c.d. or to N-benzoyl-α-hydroxy-isobutyramide 7b.     

A Convenient One-Pot Synthesis of Indane-1,2,3-triones by Oxidation of Indan-1-ones with N-Bromosuccinimide-dimethyl Sulfoxide Reagent

Indane-1,2,3-triones (2a-f) have been synthesized via bromination of indan-1-ones (1a-f), followed by oxidation of the resulting brominated indan-1-ones with dimethyl sulfoxide in one pot in good yields.     

Generation and fate of free radicals of Δ2-oxazolin-5-ones

The reaction of Δ² -oxazolin-5-ones 1a and 1b with nickel peroxide in benzene produces the corresponding 4,4-dehydrodimers 5a and 5b as the main products in yields over 75%. Under the same conditions, the 2-aryl -4-methyl - Δ²-oxazolin-5-ones 1c, 1d and 1e yield five products. In the case of 1c, the constituents of the product mixture were separated and identified as two 4,4-dehydrodimers ( meso and d] pair isomers) 5c and 5c', (40.7%), 2,4-dehydrodimer 6c (34.9%), acetylanisoylimide 8c (8.5%) and anisamide (15.9%). Adequate mechanistic schemes are discussed to account for the products formed.     

Thermische Reaktionen mit 3-Phenyl-2H-azirinen; 1, 3-dipolare Cycloadditionen und En-Reaktionen

Benzonitrile p-nitrobenzylide ( 5 ) undergoes 1,3-dipolar cyclo-additions in the presence of 3-phenyl-2H-azirines ( 1 ), yielding in benzene at 0° 2-(p-nitrophenyl)-4,5-diphenyl-1,3-diazabicyclo[3.1.0]hex-3-enes ( 7 , scheme 2). Under the basic conditions of the reaction mixture, 7 a and 7 b are partially converted to 2-(p-nitrophenyl)-4,5-diphenyl-1,6-dihydropyrimidines ( 8a, b ) which are dehydrogenated by oxygen to the corresponding pyrimidines 9a and 9b , respectively. 3-Phenyl-2H-azirines ( 1 ) form, on heating at 145° in xylene in the presence of the azalactone 32 (2,4-diphenyl-Δ²-oxazolin-5-one), 4-(aziridin-2′-yl)-2,4-diphenyl-Δ²-oxazolin-5-ones ( 33 , scheme 11). 33 arises from an ene reaction of the enol form of 32 with 1 . Similar ene reactions are observed with the azirines 1 and dimedone ( 37 , scheme 12). Under the ene reaction conditions (xylene, 145°), the non-isolated intermediate primary adducts ( 38a and 38b ) undergo rearrangements of the vinylcyclopane-cyclopentene type to give 6,6-dimethyl-4-oxo-1,3-diphenyl-4, 5, 6, 7-tetrahydroisoindole ( 40 ) and 6, 6-dimethyl-4-oxo-3-phenyl-4, 5, 6, 7-tetrahedroindole ( 42 ), respectively.     

A novel synthesis of precocenes. Efficient synthesis and regioselective O-alkylation of dihydroxy-2,2-dimethyl-4-chromanones

The reactions of trihydroxybenzenes 1a-c and 3-methylbut-2-enoic acid ( 2 ) in a zinc chloride/water/phosphoryl chloride system afford either the new trihydroxyphenylbutenone derivatives 3b,c or dihydroxy-2,2-dimethyl-4-chromanones 4a-c in good yields. Compounds 3b,c can be cyclized in high yields to 4b,c in 5% sodium hydroxide solution. Regioselective O-alkylation of 4a-c leads to 5a-f in good yields. O-Alkylation of 5a-f , followed by reduction and dehydration, results in the formation of precocene 3 ( 7d ) and its regioisomer 7a-c,e,f . Methylation of 4a-c gives 6g-i . Subsequent reduction and dehydration affords precocene 2 ( 7h ) and its regioisomers 7g,i .     

Reaction of E-2-arylidene-1-indanones,Z-aurones,Z-1-thioaurones and Z-2-arylidene-2,3-dihydro-1H-indol-3-ones with diazomethane

1,3-Dipolar cycloaddition of E-2-arylidene-1-indanones 1a-h and Z-aurones 3a-c with diazomethane provided trans-spiro-1-pyrazolines 2a-h and 4a-c , respectively, as sole products. However, the same cycloaddition of Z-1-thioaurones 5a-f afforded a mixture of Z-α-methyl-1-thioaurones 6a-f and trans-cyclopropane derivatives 7a-f as a result of the spontaneous denitrogenation of the initially formed 1-pyrazolines. Similar reaction of Z-2-arylidene-2,3-dihydro-1H-indol-3-ones 8a,b and diazomethane yielded trans-cyclopropanes 9a,b . Structure and stereochemistry of the compounds synthesized have been elucidated by nmr spectroscopic measurements.     

Photochemistry of arylidene-beta-ionones: a highly efficient route to novel tricyclic ketones through intramolecular, exoselective photochemical (4 + 2) cycloadditions, occurring only in an aqueous-organic solvent

(E,E)-Arylidene-beta-ionones (1a-f) are converted to 1,7,7-trimethyl-3-(E-2'-arylethenyl)-2-oxabicyclo[4.4.0]deca-3,5-dienes (3a-f, approximately 90%) by irradiating in anhydrous solvents. Irradiation of (3a-f) in aqueous methanol results in Z,E-arylidene-beta-ionones (2), through retro-electrocyclization, which undergoes an intramolecular, exo-selective [4 + 2] photocycloaddition leading to 11-(exo)-aryl-1,7,7-trimethyl-tricyclo[4.4.0.1(2,4)]undec-5-ene-3-ones (8a-f, 60-80%). The latter rearrange over silica gel to afford, quantitatively, 5-aryl-7,11,11-trimethyl-tricyclo[5.4.0.0(3,6)]undec-1-ene-4-ones (5a-f). Irradiation of 1a-f in aqueous methanol leads to 8a-f, except in case of 1c,f wherein formation, respectively, of tricyclic ketones 9c (55%) and 9f (80%), derived from photodeconjugation in 2, followed by intramolecular [4 + 2] cycloaddition, is observed.     

Formation of carbon-carbon single bonds from isocyanates and cyclic pentaoxyphosphoranes—VI : Synthesis of 4-oxazolones and 4-thiazolones,and a new type of chapman rearrangement

The reaction of 4,5-dimethyl-2,2,2-trimethoxy-2,2-dihydro-1,3,2-dioxaphospholene with carbomethoxy, carbopropoxy and N,N-diphenylcarbamyl isocyanates yields, respectively, 2-methoxy-, 2-propoxy- and 2- diphenylamino-5-acetyl-5-methyl-2-oxazolin-4-one. The reaction with carbophenoxy isocyanate gives two products in a proportion which depends on experimental conditions: 2-phenoxy-5-acetyl-5-methyl-2-oxalin-4-one (1:1 stoichiometry) and 1,3-dicarbophenoxy-5-acetyl-5-methyl-hydantoin (1:2 stoichiometry). The 2-substituted 4- oxazolones are hydrolyzed to 5-acetyl-5-methyl-oxazolidin-2,4-dione. The alkyl group of the 2-alkoxy-4-oxazolones migrates to the adjacent nitrogen to give 3-alkyl-5-acetyl-5-methyl-oxazolidin-2,4-diones. The dioxaphospholene reacts with 2-substituted 2-thiazolin-4,5-diones to give 2-substituted 5-acetyl-5-methyl-2-thiazolin-4-ones, including rhodanine derivatives.     

N-nitration of secondary amines with 4-chloro-5-methoxy-2-nitropyridazin-3-one

N-Nitration of 4-chloro-5-substituted-pyridazin-3-one with copper nitrate trihydrate in acetic anhydride gave the corresponding 4-chloro-2-nitro-5-substituted-pyridazin-3-one. 4-Chloro-5-alkoxy-2-nitropyridazin-3-ones such as 5-methoxy (2b) and 5-ethoxy (2d) derivatives showed excellent nitro group transfer potentiality. N-Nitration of some secondary amines with 2b gave the corresponding N-nitramines under mild neutral condition in good yields.