Bildung von 5,6-Dihydro-1,3(4H)-thiazin-4-carbonsäure-estern aus 4-Allyl-1,3-thiazol-5(4H)-onen

Formation of Methyl 5,6-Dihydro-l, 3(4H)-thiazine-4-carboxyiates from 4-Allyl-l, 3-thiazol-5(4H)-ones . The reaction of N-[1-(N, N-dimethylthiocarbamoyl)-1-methyl-3-butenyl]benzamid ( 1 ) with HCl or TsOH in MeCN or toluene yields a mixture of 4-allyl-4-methyl-2-phenyl-1,3-thiazol-5(4H)-one ( 5a ) and allyl 4-methyl-2-phenyl-1,3-thiazol-2-yl sulfide ( 11 ; Scheme 3). Most probably, the corresponding 1,3-oxazol-5(4H)-thiones B are intermediates in this reaction. With HCl in MeOH, 1 is transformed into methyl 5,6-dihydro-4,6-dimethyl-2-phenyl-1,3(4H)-thiazine-4-carboxylate ( 12a ). The same product 12a is formed on treatment of the 1,3-thiazol-5(4H)-one 5a with HCl in MeOH (Scheme 4). It is shown that the latter reaction type is common for 4-allyl-substituted 1,3-thiazol-5(4H)-ones.     

4-Substituted-3-alkyl-3,4-dihydro-2H-1,3-benzoxazin-2-ones. IV (2-4). Keto-Enol tautomerism of β-keto ester derivatives. Reaction of β-dicarbonyl compounds with diamines

A series of α-[3-alkyl-3,4-dihydro-2-oxo-2H-1,3-benzoxazin-4-yl]-β-keto ester derivatives 1 (Table I) were synthesized by the condensation of 3-alkyl-3,4-dihydro-4-hydroxy-2H-1,3-benzoxazine-2-ones 3 (2) with β-keto esters 4 in the presence of traces of mineral acids under azeotropic conditions. Condensation of 1 with hydrazines 5 gave pyrazolone derivatives 2 (Table II). Condensation of β-diketone derivatives 6 with hydrazines 5 and with 1,2-benzenediamine ( 8 ) resulted in the formation of pyrazoles ( 7a-c ) and diazepine derivatives 12 (Table III) and 13 , respectively.     

Reaktion von Phenyldiazomethan mit 1,3-Thiazol-5(4H)-thionen: Basenkatalysierte Ring-Öffnung des Primäradduktes

Reaction of Phenyldiazomethane with 1,3-Thiazole-5(4H)-thiones: Base-Catalyzed Ring Opening of the Primary Adduct Reaction of 1,3-thiazole-5(4H)-thiones 1 and phenyldiazomethane ( 2a ) in toluene at room temperature yields the thiiranes trans- and cis-1,4-dithia-6-azaspiro[2.4]hept-5-enes (trans- and cis- 4 ; Scheme 2). With Ph₃P in THF at 70°, these thiiranes are transformed stereospecifically into (E)- and (Z)-5-benzylidene-4,5-dihydro-1,3-thiazoles 5 , respectively. In the presence of DBU, 1 and 2a react to give 1,3,4-thiadiazole derivatives 6 or 7 via base-catalyzed ring opening of the primary cycloadduct (Scheme 3). In the case of 2-(alkylthio)-substituted 1,3-thiazole-5(4H)-thiones 1c and 1d , this ring opening proceeds by elimination of the corresponding alkylthiolate, yielding isothiocyanate 7 . The structures of (Z)- 5c and 6b have been established by X-ray crystallography.     

Synthese von 4-Benzylthio- und 4-(Arylthio)-1,3-oxazol-5(2H)-onen

Synthesis of 4-(Benzylthio)-and 4-(Arylthio)-1,3-oxazole-5(2H)-ones Following a known procedure, 4-(benzylthio)-1,3-oxazol-5(2H)-one ( 4a ) was synthesized starting from sodium cyanodithioformate ( 1 ) and cyclohexanone (Scheme 1). The structure of the intermediate 4-(benzylthio)-1,3-thiazol-5(2H)-one ( 3a ) was established by X-ray crystallography. An alternative route was developed for the synthesis of 4-(arylthio)-1,3-oxazol-5(2H)-ones which are not accessible by the former reaction. Treatment of ethyl cyanoformate ( 5 ) with a thiophenol in the presence of catalytic amounts of Et₂NH and TiCl₄, followed by addition of a ketone and BF₃.Et₂O in a one-pot-reaction, gave 4f–i in low-to-fair yields (Scheme 3). Both synthetic pathways-complementary as for benzyl–S and aryl-S derivatives–seem to be limited with respect to variation of substituents of the ketone.     

New domino‐reaction for the synthesis of N4‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines and 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine

The model morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide (1) reacts with phenacyl bromides to afford N⁴‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines (4) or N⁴‐(4,5‐diphenyl‐1,3‐oxathiol‐2‐yliden)‐2‐phenyl‐4‐aminoquinazoline ( 5 ) by a thermodynamically controlled reversible reaction favoring the enolate intermediate, while the 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine ( 8 ) was produced by a kinetically controlled reaction favoring the C‐anion intermediate. ¹H nmr, ¹³C nmr, ir, mass spectroscopy and x‐ray identified compounds ( 4 ), ( 5 ) and ( 8 ).     

Herstellung enantiomerenreiner Derivate von 3-Amino- und 3-Mercaptobuttersäure durch SN2-Ringöffnung des β-Lactons und eines 1,3-Dixoanons aus der 3-Hydroxybuttersä ure

Preparation of Enantiomerically Pure Derivatives of 3-Amino- and 3-Mercaptobutanoic Acid by S_N2 Ring Opening of the β-Lactone and a 1,3-Dioxanone Derived from 3-Hydroxybutanoic Acid From (S)-4-methyloxetan-2-one ( 1 ), the β-butyrolactone readily available from the biopolymer ( R )-polyhydroxybutyrate (PHB) and various C, N, O and S nucleophiles, the following compounds are prepared:(s)-2-hydroxy-4-octanone ( 3 ), (R)-3-aminobutanoic acid ( 7 ) and its N-benzyl derivative 5 , (R)-3-azidobutanoic acid ( 6 ) (R)-3-mercaptobutanoic acid ( 10 ), (R)-3-(phenylthio)butanoic acid ( 8 ) and its sulfoxide 9 . The (6R)-2,6-dimethyl-2-ethoxy-1,3-dioxan-4-one ( 4 ) from (R)-3-hydroxybutanoic acid undergoes S^N2 ring opening with benzylamine to give the N-benzyl derivative (ent- 5 ) of (S)-3-aminobutanoic acid in 30?40% yield.     

Halocyclization of 2-(2-{4-[allylamino(thioxo)methyl]piperazin-1-yl}ethyl)-1<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">de</Emphasis>]isoquinoline-1,3(2<Emphasis Type="Italic">H</Emphasis>)-dione

Cyclization of 2-(2-{4-[allylamino(thioxo)methyl]piperazin-1-yl}ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione by the action of iodine, bromine, or sulfuryl chloride gave 2-(2-{4-[4,5-dihydro-5-(halomethyl)-thiazol-2-yl]piperazin-1-yl}ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione hydrohalides which were converted into 2-{2-[4-(5-methylthiazol-2-yl)piperazin-1-yl]ethyl}-1H-benzo[de]isoquinoline-1,3(2H)-dione.     

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.     

Synthesis of (4Z)‐4‐(Arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones by the Reaction of Ethyl (2Z)‐3‐Aryl‐2‐isothiocyanatoprop‐2‐enoates with Organolithium Compounds

A convenient one‐pot method for the preparation of (4Z)‐4‐(arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones 2 and 3 from ethyl (2Z)‐3‐aryl‐2‐isothiocyanatoprop‐2‐enoates 1 , which can be easily prepared from ethyl 2‐azidoacetate and aromatic aldehydes, has been developed. Thus, these α‐isothiocyanato α,β‐unsaturated esters were treated with organolithium compounds, including lithium enolates of acetates, to provide 5‐substituted (4Z)‐4‐(arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones, 2 , and 2‐[(4Z)‐(4‐arylmethylidene)‐5‐ethoxy‐2‐thioxo‐1,3‐oxazolidin‐5‐yl]acetates, 3 .     

Five-Membered 2,3-Dioxo Heterocycles: XLVI. Reaction of 5-Aryl-4-quinoxalinyl-2,3-dihydrofuran-2,3-diones with Aldehydes and Ketones. Molecular and Crystalline Structure of 5-(3-p-Tolylquinoxalin-2-yl)-4H-1,3-dioxine- 2-spiro-2'-adamantan-4-one

Aroyl(quinoxalinyl)ketenes generated by thermolysis of 5-aryl-4-(3-arylquinoxalin-2-yl)-2,3-di-hydrofuran-2,3-diones act as dienes in [4 + 2]-cycloaddition at the carbonyl group of aldehydes and ketones to afford 2-substituted 6-aryl-5-(3-arylquinoxalin-2-yl)-4H-1,3-dioxin-4-ones. The structure of 5-(3-p-tolylquino-xalin-2-yl)-4H-1,3-dioxine-2-spiro-2'-adamantan-4-one was proved by X-ray analysis.     

Stereoselective Synthesis of Alkyl Z -2-(2-Amino-4-oxo-1,3-thiazol-5(4 H )-yliden)Acetates in Solventless Conditions

Tiourea reacts with dialkyl acetylenedicarboxylates in solventless conditions to form 1:1 adducts, which undergo a cyclization reaction to produce alkyl Z-2-(2-amino-4-oxo-1,3-thiazol-5(4H)-yliden)acetates in fairly good yields. The stereochemistry of the ethyl Z-2-(2-amino-4-oxo-1,3-thiazol-5(4H)-yliden)acetate was established by the use of X-ray single crystal structure analysis. The reaction is completely stereoselective.     

Synthesis and microbial screening of 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives

The present investigation describe the synthesis of 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives. Quinolin-8-ol was transformed by five step synthetic procedures into 8-Benzyloxy-5-(2-bromo-acetyl)-1H-quinolin-2-one. Subsequently, 8-Benzyloxy-5-(2-bromo-acetyl)-1H-quinolin-2-one condensed with 1,3-Diphenyl-1H-pyrazole-4-carbothioic acid amide in the presence of acetonitrile to afford 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives. Synthesized compounds were screened for their antimicrobial activity against gram-positive and gram-negative bacteria. Most of the synthesized compounds are found to be active against tested bacterial strains and fungal strain.     

A convenient one‐pot synthesis of new 3‐(4‐aryl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2‐yl)‐2H‐chromen‐2‐ones

Anhydrous zinc bromide catalysed reactions of arylidine‐3‐acetyl coumarins ( 1a‐c ) and 5,6‐benzoanalogs of arylidine 3‐acetyl coumarins ( 4a,4b ) with 1,3‐cyclohexanedione gives ‐(4‐aryl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2yl)‐2H‐chromen‐2‐ones ( 3a, 3c ) and 5,6‐benzoanalogs of 3‐(4‐aryl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2yl)‐2H‐chromen‐2‐one ( 5a,5b ). Under similar conditions arylidine‐3‐acetylcoumarins ( 1a, 1b,1d, 1e, 1f ) and 5,6‐benzoanalog of arylidine 3‐acetyl coumarin ( 4b ) react with 5,5‐dimethyl‐1,3‐cyclohexanedione (dimedone) yielding 3‐(4‐aryl‐7,7‐dimethyl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2‐yl)‐2H‐chromen‐2‐ones ( 3d‐3h ) and the 5,6‐benzoanalog of 3.(4‐aryl‐7,7‐dimethyl‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromen‐2‐yl)‐2H‐chromen‐2‐one ( 5c ).     

Cascade synthesis of 2-amino-5-(4-methoxyphenyl)-4-phenyl-1,3-thiazole by reaction of 4-chloro-<Emphasis Type="Italic">N</Emphasis>-[2,2-dichloro-1-(4-methoxyphenyl)-2-phenylethyl]benzenesulfonamide with thiourea

4-Chloro-N-[2,2-dichloro-1-(4-methoxyphenyl)-2-phenylethyl]benzenesulfonamide reacted with thiourea on heating in DMF in the presence of sodium carbonate to give 5-(4-methoxyphenyl)-4-phenyl-1,3-thiazole-2-amine. A probable reaction scheme includes cyclization of the initial N-dichloroethyl amide to N-sulfonyl-2,3-diaryl-2-chloroaziridine which undergoes isomerization with opening of the three-membered ring to 1-arylsulfonylamino-2-chloro-2-(4-methoxyphenyl)-1-phenylethene. The subsequent heterocyclization in the reaction with thiourea is accompanied by aromatization via elimination of the arenesulfonamide fragment.     

Synthesis of 1-[3-methyl-2(3H)-benzazolon-5- or 6-yl]-4-{4-[cis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl-methyl)-1,3-dioxolan-4-yl]methyleneoxyphenyl}piperazines

Reactions of 3-methyl-6-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzoxazolone, 3-methyl-6-[4-(4-hydroxy-phenyl)-1-piperazinyl]-2(3H)-benzothiazolone and 1,3-dimethyl-5-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzimidazolone with cis-{[2-(2,4-dichlorophenyl) -2-(1H-imidazol-1-ylmethyl)]-1,3-dioxolan-4-yl}methyl meth-anesulfonate in the presence of sodium hydride furnish the title compounds.     

Reaction of N-(4-Pyridylrnethyl)benzamide N-oxides and N-[(α-acetoxy)-4-pyridylmethyl]benzamides with 1,3-diphenyl-1,3-propanedione

Reaction of N-(4-pyridylmethyl)benzamide N-oxides 2 with 1,3-diphenyl-1,3-propanedione in the presence of acetic anhydride afforded 1,1-dibenzoyl-2-(4-pyridyl)-2-(benzoylamino)ethanes 4 in low yield. Treatment of N-[(α-acetoxy)4-pyridylmethyl]benzamides 3 with 1,3-diphenyl-1,3-propanedione in the presence of triethylamine and chloroform as a solvent provided 4 in high yield. Reaction of 4 with nucleophiles as hydrazine, methyl and phenylhydrazine gave the corresponding pyrazoles 5 .     

Zur Photodimerisierung von 3-Phenyl-2H-azirinen. Vorläufige Mitteilung

Irradiation of 3-phenyl-2H-azirine ( 2 ) in benzene solution with a high-pressure mercury lamp yields 4,5-diphenyl-1,3-diazabicyclo[3,1,0]hex-3-ene ( 4 ) and not 3-phenylimino-4-phenyl-1-azabicyclo[2,1,0]pentane ( 1 ), as had been reported previously by others [2]. 2-Methyl-3-phenyl-2H-azirine ( 3 ) yields on irradiation a 2:1 mixture of 2-exo, 6-exo- and 2-exdo, 6-exo-dimethyl-4,5-diphenyl-1,3-diazabicyclo[3,1,0]hex-3-ene (2-exo,6-exo- and 2-endo, 6-exo- 5 ). Irradiation of 2,3-diphenyl-2H-azirine ( 8 ) leads to the formation of 2,4,5-triphenyl-imidazole ( 9 ) and tetra-phenylpyrazine ( 10 ). The suggested reaction path for the generation of 9 and 10 is shown in Scheme 2.     

NMR experiments on acetals—XXXIX: Conformational insights through NMR studies at 300 MHz of 2-methyl-4-halogenomethyl-1,3-dioxolanes

NMR spectra of cis- and trans-2-methyl-4-halogeno-methyl-1,3-dioxolanes have been analysed at 300 MHz. Some of the extracted parameters facilitate easy distinction between these 1,3-dioxolanes and the corresponding structurally isomeric 2-Methyl-5-halogeno-1,3-dioxanes. Criteria enabling configurational assignments to be made for the cis-trans isomers of the dioxolane series are tested. The Me-2 group causes an upfield shift (0·2 to 0·3 ppm) of a trans proton at position 5, but the reversed shift for the corresponding cis proton. This competes with, or even overwhelms the effect of the CH₂X-4 substituent, which by virtue of its pronounced preferential rotameric orientation and in comparison with a simple Me-group, has no large upfield effect on the shift of the syn-adjacent proton. Shift criteria and coupling constants J_{H-4, H-5} in cis- and trans derivatives allow further conformational insights into these 1,3-dioxolanes.     

Reaction of ketenes with N,N-disubstituted 2-aminomethylenecycloalkanones. V. Synthesis of N,N-disubstituted 4′-aminospiro [1,3-dithiane-2,3′-(5′,6′-polymethylene-3′,4′-dihydro-α-pyrones)]

The reaction of 2-carbonyl-1,3-dithiane, a sulfene prepared in situ from 2-chloroearbonyl-1,3-dithiane and triethylamine, with N,N-disubstituted 2-aminomethylvnecycloalkanones gave the 1,4-cycloadducts, namely N,N-disubstituted 4′-aminospiro[1,3-dithiane-2,3′-(5′,6′-poly-methylene-3′,4′-dihydro-α-pyrones)].     

Preparation and radical ring-opening polymerization of 2-substituted-4-methylene-1,3-dioxolanes

2-Methyl-2-phenyl-4-methylene-1,3-dioxolane ( IIa ), 2-ethyl-2-phenyl-4-methylene-1,3-dioxolane ( IIb ), 2-phenyl-2-(n-propyl)-4-methylene-1,3-dioxolane ( IIc ), 2-phenyl-2-(i-propyl)-4-methylene-1,3-dioxolane ( IId ), 2-(n-heptyl)-2-phenyl-4-methylene-1,3-dioxolane ( IIe ), 2-methyl-2-(2-naphthyl)-4-methylene-1,3-dioxolane ( IIf ), and 2,2-diphenyl-4-methylene-1,3-dioxolane ( IIg ) were prepared and polymerized in the presence of a radical initiator. IIa–IIf were found to undergo vinyl polymerization with ring-opening reaction accompanying the elimination of ketone groups in bulk. IIg was found to undergo the quantitative ring-opening reaction accompanying the elimination of benzophenone in solution to obtain polyketone without any side reaction.