The synthesis of 3-alkyl-5-trifluoromethyl-1H- pyrazole-1-carboxamides, 3-alkyl-5-trifluoromethyl-1H-pyrazole-1-thiocarboxamides, and 2-(3-alkyl-5-trifluoromethyl-1H-pyrazol-1-yl)-thiazoles derivatives are reported. [3 + 2] cyclocondensations for a series of long alkyl chain 1,1,1-trifluoro-4-methoxyalk-3-en-2-ones and semicarbazide or thiosemicarbazide were carried out in ethanol, an eco-friendly medium. The series of trifluoromethyl-1H-pyrazol-1-yl-thiocarboxamide following a [3 + 2] cyclocondensation with 2-bromoacetophenone were converted into two series of 2-(3-alkyl-5-trifluoromethyl-1H-pyrazol-1-yl)-thiazoles. Good yields (69-96%) of the isolated products were obtained. The structures of the new long alkyl chain 1H-pyrazoles and 2-(1H-pyrazol-1-yl)thiazoles were characterized using 1H, 13C, and 19F nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization tandem mass spectrometric (ESI MS/MS) data. Moreover, some of the products were evaluated for their antimicrobial activity against Gram-negative Escherichia coli American Type Culture Collection (ATCC) 35218, Salmonella enteritidis ATCC 13076, and Pseudomonas aeruginosa ATCC 15692; and Gram-positive Staphylococcus aureus ATCC 6538, methicillin resistant Staphylococcus aureus (MRSA clinical isolate), Streptococcus sp. (clinical isolate), and Candida albicans ATCC 14053 and Candida krusei ATCC 6258 fungi. All the tested 1H-pyrazoles exhibited antibacterial and antifungal activities at the tested concentrations. The compounds from series 4 were found to be powerful against MRSA.

A series of functionalized 1,1,1-trihalo-4-methoxy-3-alken-2-ones [CX3C(O)CR1=CROMe, where X = F or Cl; R = n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-tridecyl, (CH2)2CH=C(Me)2, (CH2)2Ph, (CH2)2-(4-HOC6H4), (CH2)2-(4-MeOC6H4), (CH2)2CO2Me, (CH2)3CO2Me, CH(SMe)CH3, CH2(2-MeOC6H4), and R1 = H, and R = H and R1 = n-decyl] were synthesized from respective alkyl methyl ketones or aldehyde via acetal acylation using trifluoroacetic anhydride and trichloroacetyl chloride. 1,1,1-Trihalo-4-methoxy-3-alken-2-ones with acid-compatible substituents were easily hydrolyzed to respective trihalomethyl-1,3-diketones. The 1,1,1-trihalo-4-methoxy-3-alken-2-ones and/or respective trihalomethyl-1,3-diketones were reacted regiospecifically with hydroxylamine hydrochloride, leading to isoxazole derivatives, and with hydrazines, leading to respective 1H-pyrazole derivatives. The structures of all compounds were assigned based on nuclear magnetic resonance (NMR) and mass spectrometric data. This method represents an efficient pathway for the regioselective trihaloacetylation of asymmetrically substituted alkyl methyl ketones and highly self-condensing aldehydes. Moreover, this approach allows the introduction of biologically recognizable moieties, such as those from levulinic acid, sulcatone (prenyl), benzylacetone, anisylacetone, and raspberry ketone, as synthetic molecular targets.

The synthesis of 5-[2-(trifluoromethylheteroaryl)-ethyl]-1,3,4-oxadiazoles derived from levulinic acid is reported. Cyclocondensations [4 + 1] between four different 5-[2-(trifluoromethylheteroaryl)propionylhydrazides derived from methyl 7,7,7-trifluoro-4-methoxy-6-oxo-4-heptenoate obtained from levulinic acid, and electrophilic orthoesters RC(OR1)3 (where R = H, Me, Ph) and CS2 were carried out in a mild medium. Good yields (69-96%) of isolated products were obtained. The structures of the new ethylene-spaced biheterocycles were characterized using 1H and 13C nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization coupled to tandem mass spectrometric (ESI MS/MS) data.

Neste trabalho relatamos a ciclocondensação entre a 2-metil-7-trifluorometilpirazolo[1,5-a]pirimidino-5-propanoil hidrazida derivada da 2-metil-5-(metilpropanoato-3-il)-7-trifluorometilpirazolo[1,5-a]pyrimidina e doze versáteis 1,1,1-trifluoro-4-alcóxi-3-alquen-2-onas [F3CC(O)C(R²)=C(R¹)OMe onde R¹ = H, Me, (CH2)2CHCMe2, (CH2)2Ph, (CH2)2CO2Me, Ph, 4-MeC6H4, 4-MeOC6H4, EtO e R² = H; R¹, R² = -(CH2)4-, -(CH2)5-; R¹ = Ph e R² = Me]. A estrutura molecular dos produtos 5-[(5-trifluorometil-5-hidroxi-4,5-diidro-1H-pirazol-1-il)-1-propan-1-ona-3-il]-2-metil-7-trifluorometilpirazolo[1,5-a]pirimidinas, novos bihetererociclos contendo o espaçador propionil, foram atribuídas com base nos dados de ressonância magnética nuclear (NMR) de ¹H, 13C e 19F, e espectrometria de massas (MS).

Twelve new 5-[(5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazol-1-yl)-1-propan-1-one-3-yl]-2-methyl-7-trifluoromethylpyrazolo[1,5-a]pyrimidines were prepared by cyclocondensation between 2-methyl-7-trifluoromethylpyrazolo[1,5-a]pyrimidine-5-propanoyl hydrazide derived from 2-methyl-5-(methylpropanoate-3-yl)-7-trifluoromethylpyrazolo[1,5-a]pyrimidine and a series of versatile 1,1,1-trifluoro-4-alkoxy-3-alken-2-ones [F3CC(O)C(R²)=C(R¹)OMe where R¹ = H, Me, (CH2)2CHCMe2, (CH2)2Ph, (CH2)2CO2Me, Ph, 4-MeC6H4, 4-MeOC6H4, EtO and R² = H; R¹, R² = -(CH2)4-, -(CH2)5-; R¹ = Ph and R² = Me]. The structures of new propionyl-spaced biheterocycles were derived from ¹H, 13C, and 19F nuclear magnetic resonance (NMR) spectroscopy and mass spectrometric (MS) data.

A síntese eficiente de novas 1,1,1-tricloro-4-metoxi-3-alquen-2-onas graxas [Cl3CC(O)C(R²)=C(R¹)OMe, onde R¹ = n-hexil, heptil, nonil, undecil, tridecil e R² = H] e 1,1,1-tricloro-2,4-alkanediones [Cl3CC(O)CHR²C (O) R¹, onde R¹ = n-pentil e R² = Me, R¹ = Et e R² = n-butil, R¹ = n-butil e R² = n-propil] é apresentada, com bons rendimentos (85-95%) a partir da acilação dos respectivos acetais com cloreto de tricloroacetila. As 1,1,1-tricloro-4-metoxi-3-alquen-2-onas e 1,1,1-tricloro-2,4-alkanediones graxas reagem com cloridrato de hidrazina produzindo os respectivos 1H-pirazol-5-carboxilatos, uma classe de novos ésteres metílicos (FAMEs) e etílicos (FAEEs) graxos não comuns. As estruturas moleculares dos compostos sintetizados foram confirmadas por análise elementar e ressonância magnética nuclear (NMR) de ¹H e 13C. As 1,1,1-tricloro-4-metoxi-3-alquen-2-onas graxas e seus derivados 1H-pirazol-5-carboxilatos são novos oleoquímicos com propriedades diferenciadas e potencialmente interessantes.

The efficient synthesis of new fatty 1,1,1-trichloro-4-methoxy-3-alken-2-ones [Cl3CC(O)C(R²)=C(R¹)OMe, where R¹ = n-hexyl, heptyl, nonyl, undecyl, tridecyl and R² = H] and 1,1,1-trichloro-2,4-alkanediones [Cl3CC(O)CHR²C(O)R¹, where R¹ = n-pentyl and R² = Me, R¹ = Et and R² = n-butyl, R¹ = n-butyl and R² = n-propyl] in good yields (85-95%) from acetal acylation with trichloroacetyl chloride is reported. The fatty 1,1,1-trichloro-4-methoxy-3-alken-2-ones and 1,1,1-trichloro-2,4-alkanediones were reacted with hydrazine hydrochloride, leading to respective 1H-pyrazole-5-carboxylates, unusual class of fatty acid methyl (FAMEs) and ethyl (FAEEs) esters. Their structures were confirmed by elemental analysis and ¹H and 13C nuclear magnetic resonance (NMR). The fatty 1,1,1-trichloro-4-methoxy-3-alken-2-ones and 1H-pyrazole derivatives are new oleochemicals with potentially interesting and differential properties.

Neste trabalho, a ciclocondensação dos precursores 7,7,7-trifluoro-4-metoxi-6-oxo-4 heptenoato de metila e 7,7,7-trichloro-4-metoxi-6-oxo-4-heptenoato de metila, a partir do ácido levulínico com amidinas [NH2CONH2, NH2CR(NH) (R = H, Me, Ph, NH2, SMe e 1H-pirazol-1-il), 5-amino-3-metil-1H-pirazol e 2-aminotiazol] para obtenção de 3-(6-trifluormetilpirimidina-4-il) propanoatos de metila com estrutura análoga a mediadores glutamatérgicos é relatada. A síntese de 3-(6-trifluormetilpirimidina-4-il)propanohidrazidas também é relatada. A versatilidade desse método foi demostrada através da síntese de quatorze 3(pirimidinil)propanoatos inéditos em rendimentos razoáveis a bons (38-92%). As estruturas moleculares dos produtos foram atribuídas com base nos dados de ressonância magnética nuclear (NMR) de ¹H e 13C e cromatografia de gases acoplada à espectrometria de massas (GC-MS).

The cyclocondensation of methyl 7,7,7-trifluoro-4-methoxy-6-oxo-4-heptenoate and methyl 7,7,7-trichloro-4-methoxy-6-oxo-4-heptenoate, derived from levulinic acid with amidines [NH2CONH2, NH2CR(NH) (R = H, Me, Ph, NH2, SMe and 1H-pyrazol-1-yl), 5-amino-3-methyl1H-pyrazol and 2-aminothiazole] into pyrimidine and pyrimidine-like derivatives as a new type of glutamate-like 3-(trihalomethylatedpyrimidinyl)propanoate is reported. Preparation of 3-(trihalomethylatedpyrimidinyl) propanohydrazides is also described. The synthetic potential of this straightforward protocol was established by the synthesis of fourteen new 3-(pyrimidinyl) propanoates in regular to good yields (38-92%). The structural assignments were based on the analysis of their ¹H and 13C nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) data.

Cinco derivados de 4-trifluorometil-2-(5-aril-3-stiril-1H-pirazol-1il)-pirimidinas e seis 5-aril-3-estiril-1-carboxamidino-1H-pirazois previamente sintetizados foram avaliados de acordo com suas propriedades antioxidantes e antimicrobianas. Estas atividades foram avaliadas por ensaios de DPPH e HRP/luminol/H2O2 quimioluminescência e suas atividades antimicrobianas (CIM). Os resultados foram bons para alguns compostos da série em certas concentrações em comparação direta com padrões.

Five previously synthesized 4-trifluoromethyl-2-(5-aryl-3-styryl-1H-pyrazol-1yl)-pyrimidines and six 5-aryl-3-styryl-1-carboxamidino-1H-pyrazole derivatives were screened for their antioxidant proprieties. The antioxidant activities were evaluated by using the DPPH and the HRP/luminol/H2O2 chemiluminescence assay systems and for their antimicrobial activity (MIC). The results were good for those series in some concentration in comparison with the standards.

Este trabalho mostra a síntese, em bons rendimentos (57-95%), de duas séries de 1-alquil(aril)amino-2-oxo-5-(2-oxo-3,3,3-trialopropiliden)-pirrolidinas 5 e 6, a partir dos intermediários 4-[alquil(aril)amino]-6-oxo-7,7,7-trialo-4-hepteno-atos de metila 3 e 4 obtidos por substituição da metoxila-beta nos precursores 4-metoxi-6-oxo-7,7,7-trialo-4-heptenoatos de metila 1 e 2, pela série de aminas primárias RNH2, onde R = PhCH2, PhCH2CH2, Ph, 4-MeC6H4, 4-MeOC6H4, 4-ClC6H4, 4-BrC6H4, 2-piridnil, 5-metil-3-isoxazolil, 4-NH2C6H4. A estrutura molecular dos produtos inéditos foi atribuída a partir dos dados de RMN ¹H, 13C e espectrometria de massas. A configuração geométrica dos compostos 3d e 5b foi confirmada pelos dados de difração de raios-X em monocristal.

Reactions of methyl 4-methoxy-6-oxo-7,7,7-trihalo-4-heptenoates 1 and 2 with primary amines RNH2, where R = PhCH2, PhCH2CH2, Ph, 4-MeC6H4, 4-MeOC6H4, 4-ClC6H4, 4-BrC6H4, 2-pyridyl, 5-methyl-3-isoxazolyl, 4-NH2C6H4 affording methyl 4-[alkyl(aryl)amino]-6-oxo-7,7,7-trihalo-4-heptenoates 3, 4, in good yields (57-95%), which suffer quantitative intramolecular cyclocondensation to produce 1-alkyl(aryl)-5-(2-oxo-3,3,3-trihalopropylidene)pyrrolidin-2-ones 5, 6, are reported. The structures of the isolated new products were assigned by means of ¹H,13C NMR measurements and mass spectrometry. The Z and E configuration of compounds 3d and 5b respectively were established from X-ray crystallography.

Este trabalho mostra as reações entre 2-trifluoracetil-1-metoxi-1-cicloalquenos (1a-1e) ou 2-trifluoracetilcicloalcanonas e bromo molecular, para produção de ômega-bromo-2-trifluoracetilcicloalcanonas (3a-3e, 4a). Ficou demonstrado que o grupo 2-trifluoracetil determina o sítio de bromação no C-omega, carbono vizinho à carbonila endocíclica. Os produtos 2-trifluoracetilcicloalcanonas e ômega-bromo-alfa-trifluoracetilcicloalcanonas foram ciclocondensados com cloridrato de hidroxilamina, formando os respectivos 5-trifluormetil-5-hidroxido-3,4-polimetileno-4,5-diidroisoxazóis (5c-5e e 6c-6e).

The reactions of a serie of the 2-trifluoroacetyl-1-methoxy-1-cycloalkenes (1a-1e) and 2-trifluoroacetylcycloalkanones (2a-2e) with molecular bromine to obtain omega-bromo-alpha-trifluoroacetylcycloalkanones (3a-3e, 4a) is reported. Was determined that 2-trifluoroacetyl group have established the C-omega as reactive site. The 2-trifluoroacetylcycloalkanones and omega-bromo-alpha-trifluoroacetylcycloalkanones were reacted with hydroxylamine hydrochloride leading to respective 5-trifluoromethyl-5-hydroxy-4,5-dihydro-3,4-polimethyleneisoxazole derivatives (5c-5e and 6c-6e).