Synthesis,studies and in vitro antibacterial activity of some 5-(thiophene-2-yl)-phenyl pyrazoline derivatives

In the present investigation, a novel series of pyrazolines 2a–2d were synthesized by the cyclization of various -1-[2-(alkoxy) phenyl]-3-(thiophen-2-yl) prop-2-en-1-one 1a–1d with N-substituted phenyl hydrazine and thiosemicarbazide in the presence of CH₃COOH and NaOH in ethanol which lead to the formation of new pyrazolines. The structures of these compounds were elucidated by, IR, ¹H-NMR, ¹³C-NMR, ESI-MS spectral data and their purities were confirmed by elemental analyes. The in vitro antibacterial activity of these compounds was evaluated against two Gram-positive and two Gram-negative bacteria Aeromonas hydrophila, Yersinia enterocolitica, Listeria monocytogenes, and Staphylococcus aureus by microdilution method and then the minimum inhibitory concentration (MIC) of these compounds was determined. The results showed that compounds 1-[2-(benzyloxy) phenyl]-5-(thiophen-2-yl)-1-phenyl-4,5-dihydro-1H-pyrazol-4-yl (2b) and 1-[2-(naphthalen-2-ylmethoxy) phenyl]-5-(thiophene-2-yl)-1-phenyl-4,5-dihydro-1H-pyrazole-4-yl (2d) showed most promising antibacterial activity as compared to the antibiotics gentamicin and tetracycline in (Table 1, Table 2).     

New derivatives of 4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazole, 4,5-dihydro-1,2-oxazole,and pyrimidine prepared proceeding from (<Emphasis Type="Italic">E</Emphasis>)-3-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-one

Condensation of acetylferrocene with 5-phenyl(4-methylphenyl)-1,2-oxazole-3-carbaldehydes afforded (Е)-3-[5-phenyl(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-ones. Reactions of (Е)-3-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-one with semicarbazide, thiosemicarbazide, and hydroxylamine led to the formation of 5-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-3-ferrocenyl-4,5-dihydro-1H-pyrazole- 1-carboxamide, 5-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-3-ferrocenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide, and 5-(4-methylphenyl)-3'-ferrocenyl-4',5'-dihydro-3,5'-bi-1,2-oxazole respectively. Reactions of (Е)-3-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-one with guanidine and thiourea result in 4-[5-(4-methyl-phenyl)-1,2-oxazol-3-yl]-6-ferrocenylpyrimidin-2-amine and -2-thione respectively.     

Five-membered 2,3-dioxo heterocycles: LXIII. Cascade recyclization of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates with cyclic enamines. Crystalline and molecular structure of 1′-benzyl-6′,6′-dimethyl-3-[(Z)-phenyl(phenylamino)methylidene]-6′,7′-dihydro-3H-spiro[furan-2,3′-indole]-2′,4,4′,5(1′H,5′H)-tetraone

Isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates reacted with N-substituted 3-amino-5,5-dimethylcyclohex-2-en-1-ones to give the corresponding 1′-substituted (Z)-6′,6′-dimethyl-3-[phenyl(arylamino)methylidene]-6′,7′-dihydro-3H-spiro[furan-2,3′-indole]-2′,4,4′,5(1′H,5′H)-tetraones. The structure of 1′-benzyl-6′,6′-dimethyl-3-[(Z)-phenyl(phenylamino)methylidene]-6′,7′-dihydro-3Hspiro[furan-2,3′-indole]-2′,4,4′,5(1′H,5′H)-tetraone was proved by X-ray analysis.     

Synthesis and Antimicrobial Activity of Some New 5-Arylazothiazole,Pyrazolo[1,5-a] Pyrimidine, [1,2,4]Triazolo[4,3-a]Pyrimidine,and Pyrimido[1,2-a]Benzimidazole Derivatives Containing the Thiazole Moiety

1-(2-(4,5-Dihydro-3-(4-methyl-2-phenylthiazol-5-yl)-5-phenylpyrazol-1-yl)-4-substituted thiazol-5-yl)-2-phenyldiazene were synthesized from hydrazonoyl halides and 3-(4-methyl-2-phenyl-1,3-thiazol-5-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide in ethanolic triethylamine. Also, pyrazolo[5,1-a]pyrimidines, 2,3,6-trisubstituted pyridines, and pyrazolo[3,4-d]pyridazines were obtained from sodium salt of 3-hydroxy-1-(4-methyl-2-phenylthiazol-5-yl)prop-2-en-1-one and different heterocyclic amines. All structures of the newly synthesized compounds were elucidated by elemental analysis, spectral data, and alternative synthetic route whenever possible. The newly synthesized compounds were tested towards different microorganisms.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Electrophilic cyclization of <Emphasis Type="Italic">N</Emphasis>-allyl(propargyl)-5-amino-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-4-carboxamides. Synthesis of 4-[(dihydro)oxazol-2-yl]-1<Emphasis Type="Italic">H</Emphasis>-pyrazol-5-amines

N-Allyl-5-amino-1H-pyrazole-4-carboxamides in reactions with polyphosphoric acid, with N-halosuccinimides in chloroform, and with (chlorosulfanyl)benzenes in nitromethane in the presence of lithium perchlorate underwent cyclization involving the N-allylamide fragment to give 4-[5-methyl(halomethyl)-4,5-dihydrooxazol-2-yl]-1H-pyrazol-5-amines and 2-(5-amino-1H-pyrazol-4-yl)-5-[(arylsulfanyl)methyl]-4,5-dihydro-1,3-oxazolium perchlorates, respectively. Analogous reactions of N-propargyl-5-amino-1H-pyrazole-4-carboxamides with polyphosphoric acid afforded 4-(5-methyloxazol-2-yl)-1H-pyrazol-5-amines, and with (chlorosulfanyl) benzenes, 2-(5-amino-1H-pyrazol-4-yl)-5-[(arylsulfanyl)methylidene]-4,5-dihydro-1,3-oxazolium perchlorates.     

Reaction of acetylenedicarboxylic acids esters with 4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazole-1-carbothioamides and 3,4,5,6-tetrahydro-2<Emphasis Type="Italic">H</Emphasis>-1,2,4-triazepine-3-thiones

The reactions of dimethyl acetylenecarboxylate with 3,4,5,6-tetrahydro-2H-1,2,4-triazepine-3-thiones and 4,5-dihydro-1H-pyrazole-1-carbothioamides are convenient methods for the synthesis of 7,8-dihydrothiazolo[3,2-b][1,2,4]triazepin-3-ones derivatives and methyl esters of (2Z)-[2-(4,5-dihydro-1H-pyrazol-1-yl)-4-oxo-1,3-thiazol-5(4H)-ylidene]acetic acids, respectively. The reaction of methyl propynoates with 4,5-dihydro-1H-pyrazole-1-carbothioamides or with 5,5,7-trimethyl-2,4,5,6-tetrahydro-3H-1,2,4-triazepine-3-thione gives 2-(4,5-dihydro-1H-pyrazol-1-yl)-4H-1,3-thiazin-4-ones.     

In vitro microbial studies of new pyrazolyl quinazolin-4(3H) ones

A series of new 2-[2-(2,6-dichlorophenyl)amino]phenyl methyl-3-[(5-substituted phenyl)-1,5-dihydro-1H-pyrazol-3-yl-amino]-6-iodoquinazolin-4(3H) ones (6a–m) have been synthesized by the reaction of 2-[2-(2,6-dichlorophenyl)amino]phenyl methyl-3-substituted phenyl acryl amido-6-iodoquinazolin-4(3H) ones with hydrazine hydrate in the presence of glacial acetic acid. The chalcone (5a–m) have been prepared by the condensation of 2-[2-(2,6-dichlorophenyl)amino]phenyl methyl-3-acetamido-6-iodoquinazolin-4(3H) one with different substituted aromatic aldehyde. The compound 1 on treatment with 5-iodoanthranilic acid in pyridine undergoes cyclisation gave 2-[2-(2,6-dichlorophenyl)amino]phenyl methyl-6-iodo-3,1-benzoxazin-4(3H) one (2). Treatment on benzoxazine with hydrazine hydrate gave 3-amino-2-[2-(2,6-dichlorophenyl)amino]phenyl methyl-6,8-dibromo quinazolin-4(3H) one (3) followed by acetylation synthesized 2-[2-(2,6-dichlorophenyl)amino]phenyl methyl-3-acetamido-6,8-dibromoquinazolin-4(3H)-one (4). The structure of synthesized compounds has been elucidated by IR, ¹H NMR, ¹³C NMR and elemental analysis. The products were screened for antibacterial and antifungal activity. Among the series containing some of the compounds showed promising results against standard drugs.     

Synthesis of 2-thioxoimidazolines via reaction of 1-unsubstituted 3-aminoquinoline-2,4-diones with isothiocyanates

3-Alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones react with alkyl/aryl isothiocyanates to give 3a-alkyl/aryl-1,2,3,3a-tetrahydro-9b-hydroxy-2-thioxo-5H-imidazo[4,5-c]quinolin-4(9bH)-ones in high yields. These compounds rearrange in boiling acetic acid or concd hydrochloric acid to give novel 4-(2-aminophenyl)-1H-imidazole-2(3H)-thiones, 1,3-bis(2-(2,3-dihydro-2-thioxo-1H-imidazol-5-yl)phenyl)ureas and minor N-(2-(2,3-dihydro-2-thioxo-1H-imidazol-4-yl)phenyl)acetamides. In the presence of ethanol, the starting compounds rearrange in boiling acetic acid to give ethyl 2-(2,3-dihydro-2-thioxo-1H-imidazol-4-yl)phenylcarbamates. All compounds were characterized by their ¹H, ¹³C, IR and MS spectra and some of them also by ¹⁵N NMR data. The structures of two compounds were supported by single-crystal X-ray diffraction.     

Five-membered 2,3-dioxo heterocycles: LXXII. Recyclization of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates by the action of aliphatic amines

Reactions of isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates with alkylamines involve pyrroledione-pyrroledione recyclization with formation of isopropyl 1-aryl-2-hydroxy-4,5-dioxo-3-[phenyl(alkylamino)methylidene]pyrrolidine-2-carboxylates.     

Synthesis,Structure and Cytotoxicity Testing of Novel 7-(4,5-Dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-Imine Derivatives

The appropriate 1-arylhydrazinecarbonitriles 1a–c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a–c, which are subsequently converted into the corresponding amides 4a–e, 8a–c, sulfonamides 5a–n, 9, ureas 6a–I, and thioureas 7a–d. The structures of the newly prepared derivatives 3a–c, 4a–e, 5a–n, 6a–i, 7a–d, 8a–c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-[1,1′-biphenyl]-4-sulfonamide (5l) inhibits the growth of the cervical cancer SISO and bladder cancer RT-112 cell lines with IC₅₀ values in the range of 2.38–3.77 μM. Moreover, N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-phenyl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-4-phenoxybenzenesulfonamide (5m) has the best selectivity towards the SISO cell line and induces apoptosis in this cell line.     

Microwave synthesis,characterization and antimicrobial study of new pyrazolyl-oxopropyl-quinazolin-4(3H)-one derivatives

Heterocyclic compounds containing pyrazolyl-oxopropyl-quinazolin-4(3H)-one are reported to possess significant biological activity. Syntheses of 6-bromo-2-(3-chloro-2-oxopropyl)-3-(4-fluorophenyl)quinazolin-4(3H)-one 2 6-bromo-3-(4-fluorophenyl)-2-(3-hydrazinyl-2-oxopropyl)quinazolin-4(3H)-one 3 and 6-bromo-2-(3-(3-(4-(1-(2-chlorophenyl)-3-methyl-1H-pyrazol-5(4H)-ylideneamino)phenyl)-5-(substituted phenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxopropyl)-3-(4-fluorophenyl)quinazolin-4(3H)-one 5a–j using microwave irradiation have been described. These compounds have been characterized on the basis of the UV, IR, ¹H NMR, ¹³C NMR, Mass and elemental analysis. Compounds have been evaluated for their antimicrobial activity.     

Reaction of methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrole-2-carboxylates with arylhydrazines. synthesis of isomeric 5-arylcarbamoyl-4-aroyl- and 5-aryl-4-aryloxamoyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazoles

Methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with arylhydrazines to give methyl 3-aroyl-1-aryl-2-(2-arylhydrazinyl)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylates which underwent thermal recyclization into isomeric methyl 1-aryl-5-(arylcarbamoyl)-4-aroyl-1H-pyrazole- 3-carboxylates and methyl 1,5-diaryl-4-[2-oxo-2-(arylamino)acetyl]-1H-pyrazole-3-carboxylates.     

Synthesis and screening of some novel substituted indoles contained 1,3,4-oxadiazole and 1,2,4-triazole moiety

A series of novel 3-[5-(1H-indol-3-yl-methyl)-2-oxo-[1,3,4]oxadiazol-3-yl]propionitrile(5),3-[4- amino-3-(1H-indol-3-yl-methyl)-5-oxo-4,5-dihydro-[1,2.4]triazol-1-yljpropionitrile(6),3-[5-(1H- indol-3-yl-methyl)-2-thioxo-[1,3,4]oxadiazol-3-yl]propionitrile(7) and 3-[4-amino-3-(1H-indol-3-yl-methyl) -5-thioxo-4,5-dihydro-[1,2,4]triazol-l -yljpropionitrile(8) were synthesized in good yields from the intermediate(1H-indol-3-yl)-acetic acid N’-(2-cyanoethyl)hydrazide(4).The chemical structures of the newly synthesized compounds were elucidated by their IR,~1H NMR and MS.Further,all the compounds were screened for their antimicrobial activity against Gram-positive,Gram-negative bacteria and also tested their ability toward anti-inflammatory activity.     

Synthesis,antimicrobial evaluation,and docking studies of some novel benzofuran based analogues of chalcone and 1,4-benzodiazepine

A series of novel {5-[4-hydroxy-3-(4-phenyl-2,3-dihydro-1H-benzo[b][1,4]diazepin-2-yl)benzyl]- benzofuran-2-yl}(phenyl)methanones (5a–5g) were prepared by the condensation of (E)-3-{5-[(2- benzoylbenzofuran-5-yl)methyl]-2-hydroxyphenyl}-1-phenylprop-2-en-1-one (chalcone) (4a) with various substituted o-phenylene diamines in the presence of oxalic acid as catalyst. The structures of all compounds were characterized by FTIR, ¹H NMR, ¹³C NMR, and MS. The representative examples were screened in vitro for antimicrobial activity. Among all compounds 4g and 5g showed potent antibacterial activity, 4b and 5g showed good antifungal activity. The data was further compared with structure based investigations using docking studies with the crystal structure of adenosine-5'-(β,γ-imido)triphosphate (2ONJ) from Staphylococcus aureus for antibacterial activity and trypsin (1FY5) protein from Fusarium oxysporum for the antifungal activity. The score values estimated by genetic algorithm were found to have a good correlation with the experimental inhibitory potencies.     

Synthesis and Some Transformations of 7-(Fur-2-yl)-1-methyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazolo[4,3-<Emphasis Type="Italic">g</Emphasis>][1,3]benzothiazole

N-Methylation of 5-nitro-1H-indazole in a KOH–DMSO system resulted in a mixture of 1-methyl-5(6)-nitroindazoles in a ratio of 1: 2. Reduction of the isomers with tin in concentrated hydrochloric acid afforded pure 1-methyl-1H-indazole-6-amine. Condensation of the latter with furoyl chloride in 2-propanol yielded N-(1-methylindazol-6-yl)furan-2-carboxamide, treatment of which with an excess of P2S5 in anhydrous pyridine gave the corresponding carbothioamide. 7-(Fur-2-yl)-1-methyl-1H-pyrazolo[4,3-g][1,3]benzothiazole was synthesized by Jacobson oxidation of N-(1-methylindazol-6-yl) furan-2-carbothioamide with potassium ferricyanide in an alkaline medium. Some transformations of 7-(fur-2-yl)-1-methyl-1H-pyrazolo[4,3-g][1,3]- benzothiazole such as formylation and acylation were performed.     

Synthesis of 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids

Nitration of 2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one gave its 5-nitro derivative which was subjected to alkylation with dimethyl sulfate, diethyl sulfate, and benzyl(dimethyl)phenylammonium chloride. The resulting 1,3-dimethyl-, 1,3-diethyl-, and 1,3-dibenzyl-5-nitro-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones were reduced to the corresponding 1,3-dialkyl-5-amino-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones, and the latter reacted with itaconic acid to produce 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids. 1-(2-Oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acid was obtained by analogous reaction with 5-amino-2,3-dihydro-1H-imidazo[4,5-b]-pyridin-2-one.     

Synthesis,structure elucidation and plants growth promoting effects of novel quinolinyl chalcones

The readily synthesized 3-(4-Hydroxy-1-methyl-1,2-dihydro-2-oxoquinolin-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyd (5) and 3-(2-Oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde (6) were utilized as a convenient starting precursor materials for synthesis of novel enone system 4-hydroxy-1-methyl-3-(4-(2H-2-oxo-chromen-3-yl)prop-2-enoyl)-1-phenyl-1H-pyrazol-4-yl)quinolin-2(1H)-one (7) and4-hydroxy-1-methyl-3-(2E)-3-(3-(2-oxo-2H-chromen-3-yl)-1-phenyl-1H-pyrazol-4-yl)acryloyl)quinolin-2(1H)-one (8). Simple homonuclear NOE experiment (NOESY 1D) method was performed for structure elucidation of the novel quinolinyl chalcones. The synthesized compounds have been estimated for their effect of growth on some selective crop of plants (Hibiscus, Mint and Basil).     

Five-membered 2.3-dioxo heterocycles: LXVIII. Three pathways in the reaction of methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with 3-amino-5,5-dimethylcyclohex-2-en-1-one

Methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 3-amino-5,5-dimethylcyclohex-2-en-1-one having no substituent on the nitrogen atom to give 3-aroyl-4-arylamino-6′,6′-dimethyl-6′,7′-dihydro-5H-spiro[furan-2,3′-indole]-2′,4′,5′(1′H,5′H)-triones or methyl 12-aroyl-11-aryl-9-hydroxy-5,5-dimethyl-3,10-dioxo-8,11-diazatricyclo[7.2.1.0^2,7]dodec-2(7)-ene-1-carboxylates. The latter underwent thermal recyclization to 3′-aroyl-1′-aryl-4′-hydroxy-6,6-dimethyl-6,7-dihydrospiro[indole-3,2′-pyrrole]-2,4,5′(1H,1′H,5H)-triones.     

Syntheses, characterization, X-ray crystal structures and emission properties of five oxovanadium(V) complexes with pyridyl/pyrimidyl-pyrazole derived ditopic ligands

Four oxovanadium(V) complexes of heterocycle based ditopic ligands PyPzOAP (N-[amino(pyridin-2-yl)methylidene]-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-3-carbohydrazonic acid), PyPzOAPz (N-[amino(pyrazin-2-yl)methylidene]-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-3-carbohydrazonic acid), PymPzOAP (N-[amino(pyridin-2-yl)methylidene]-1-(4,6-dimethylpyrimidin-2-yl)-5-methyl-1H-pyrazole-3-carbohydrazonic acid) and PyPzCAP (5-methyl-1-(pyridin-2-yl)-N′-[1-(pyridin-2-yl)ethylidene]-1H-pyrazole-3-carbohydrazide) and a binuclear (di-μ-oxo) oxovanadium(V) complex of the ligand PymPzCAP (1-(4,6-dimethylpyrimidin-2-yl)-5-methyl-N′-[1-(pyridin-2-yl)ethylidene]-1H-pyrazole-3-carbohydrazide) have been investigated. The ligands act as uninegative NNO tridentates donors for the VO₂⁺ ion exhibiting their monotopicity. The ligands show varying emission properties due to the presence of fluophoric groups like 1-(2-pyridyl)pyrazole or 1-(2-pyrimidyl)pyrazole. The vanadium(V) complexes show fluorescence quenching with respect to the used ligands to a varying extent. The complexes were characterized by UV-Vis, IR, cyclic voltammetry and X-ray crystallography.     

New atropoisomeric alkenylphenylglycine derivatives: Synthesis of (5R*)- and (5S*)-isomers of (1R*,3aR*,4S*,11S*)-3a,5,9,11-tetramethyl-4,5-dihydro-3aH-1,4-methano[1,3]oxazolo[3,2-a]quinolin-2-one

We synthesized methyl ester of N-(1-methylbut-2-en-1-yl)-N-phenylglycine which underwent acid catalyzed aromatic amino Claisen rearrangement to provide methyl-N-[2-(1-methylbut-2-en-1-yl)phenyl]glycinate. A mixture of syn- and anti-atropisomeric methyl-N-acetyl-N-[4-methyl-2-(1-methylbut-2-en-1-yl)phenyl]glycinates was obtained either by the reaction of this ester with acetyl bromide or by the reaction of the sodium salt of N-acetyl-2-(1-methylbut-2-en-1-yl)-4-methylaniline with methyl bromoacetate. Upon saponification of the synthesized ester mixture the syn-atropisomer of N-acetyl-N-[4-methyl-2-(1-methylbut-2-en-1-yl)phenyl]glycine was isolated by fractional crystallization. Treatment of the obtained acids with acetic anhydride, ethyl chloroformate, dicyclohexylcarbodiimide or isopropenylacetate leads to compounds of 4,5-dihydro-3aH-methano[1,3]oxazolo[3,2-a]quinolin-2-one structure.