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.

A series of twelve novel 2-(pyrazol-1-yl)pyrimidine derivatives was easily obtained under ultrasonic conditions by the cyclocondensation reaction of 1-carboxamidino-pyrazoles with 4-methoxyvinyl-trifluoromethyl ketones using ethanol as an environment-friendly solvent in the presence of potassium hydroxide. Comparison of the ultrasound-promoted reaction with classical methodology shows that the former is faster and gives better yield. The products were isolated in excellent purity grades without purification by chromatography or recrystalization.

A green method was developed for the synthesis of chalcones using glycerin as solvent. Subsequently, the potential microbiology activity of these molecules was evaluated by testing them against the Gram-positive bacteria Staphylococcus aureus (S. aureus) ATCC 19095 and Enterococcus faecalis (E. faecalis) ATCC 4083, the Gram-negative bacteria Escherichia coli (E. coli) ATCC 29214 and Pseudomonas aeruginosa (P. aeruginosa) ATCC 9027, and the fungus Candida albicans (C. albicans), which includes ATCC 62342 and three clinical strains of C. albicans from human oral cavities. The results showed that some chalcones exhibited moderate inhibitory activity, the most prominent being those acting against the fluconazole-resistant strains of C. albicans.

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.

Uma série de novas pirazolinas N-acil trialometiladas derivadas de ésteres metílicos de ácidos graxos foi sintetizada por reação de ciclocondensação entre hidrazidas graxas e 4-alcóxi-1,1,1-trialometil-3-alquen-2-onas. Ciclizações eficientes e regioespecíficas catalisadas por BF3·MeOH levaram aos produtos desejados em rendimentos de bons a excelentes e alto grau de pureza.

A series of new fatty N-acyl trihalomethylated pyrazoline derivatives from fatty acid methyl esters was synthesized by the cyclocondensation of respective fatty hydrazides with 4-alkoxy-1,1,1-trialomethyl-3-alquen-2-ones. Efficient and regiospecific cyclizations catalyzed by BF3·MeOH gave the desired products in good to excellent yields and at high purity.

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 descreve a síntese de dois novos trifluoracetilceteno O,N-acetais [CF3C(O) CH=C(OEt)(NS(O)R2), onde R = CH3, Ph], obtidos da reação de 4,4-dietóxi-1,1,1-trifluorbut-3- en-2-ona [CF3C(O)CH=C(OEt)2] com S,S-dimetil- e S-metil-S-fenil-sulfoximida [HN=S(O)R2], na presença de trietilamina, com rendimentos de 60-72%, e suas aplicações na obtenção de pirazóis, isoxazóis e pirimidinas S,S-dimetilsulfoximido substituídos, em 55-89% de rendimento, a partir de reações de 4-etóxi-4-(S,S-dimetilsulfoximido)-1,1,1-trifluorbut-3-en-2-ona com hidrazinas, hidrazidas, cloridrato de hidroxilamina e acetilguanidina.

Two new trifluoroacetylketene O,N-acetals [CF3C(O)CH=C(OEt)(NS(O)R2), where R = CH3, Ph] derived from the reaction of 4,4-diethoxy-1,1,1-trifluorobut-3-en-2-one [CF3C(O)CH=C(OEt)2] with S,S-dimethyl- and S-methyl-S-phenyl-sulfoximide [HN=S(O)R2], in the presence of triethylamine, have been obtained, in 60-72% yields, and applied in the synthesis of S,S-dimethylsulfoximido-substituted pyrazoles, isoxazoles and pyrimidines, in 55-89% yields, from the reactions of 4-ethoxy-4-(S,S-dimethylsulfoximido)-1,1,1-trifluorobut-3-en-2-one with hydrazines, hydroxylamine hydrochloride and acetylguanidine.

Uma nova série de nove 3-fosfato-(4,4,4-trifluor-butil)-carbamatos de etila (compostos fosfato-carbamato), foram obtidos através da reação de (4,4,4-trifluor-3-hidroxibut-1-il)-etil carbamatos com oxicloreto de fósforo seguido de adição de álcoois. Os produtos foram caracterizados por espectroscopia de RMN de ¹H, 13C, 31P e 19F, CG-EM e análise elementar. Todos os compostos sintetizados foram testados para a inibição da enzima acetilcolinesterase (AChE) usando o método de Ellman. Todos os compostos analisados contendo os grupos carbamato e fosfato em sua estrutura, mostraram inibição enzimática, sendo que o composto contendo o grupo dietóxi (2b) apresentou a maior atividade inibitória. Estudos de modelagem molecular foram realizados para obter informações detalhadas entre o sítio ativo da enzima acetilcolinesterase e os compostos candidatos a inibição, obtendo-se valiosas informações estruturais com relação à inibição de enzima acetilcolinesterase.

A series of nine new [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters (phosphate-carbamate compounds) was obtained through the reaction of (4,4,4-trifluoro-3-hydroxybut-1-yl)-carbamic acid ethyl esters with phosphorus oxychloride followed by the addition of alcohols. The products were characterized by ¹H, 13C, 31P, and 19F NMR spectroscopy, GC-MS, and elemental analysis. All the synthesized compounds were screened for acetylcholinesterase (AChE) inhibitory activity using the Ellman method. All compounds containing phosphate and carbamate pharmacophores in their structures showed enzyme inhibition, being the compound bearing the diethoxy phosphate group (2b) the most active compound. Molecular modeling studies were performed to investigate the detailed interactions between AChE active site and small-molecule inhibitor candidates, providing valuable structural insights into AChE inhibition.

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.

Neste trabalho é apresentada a síntese, em rendimentos razoáveis (50-67%), de novos sistemas biheterocíclicos, duas 6-(2-heteroaril)-4-trifluormetil-2-(1H)-pirimidinonas (2a,b) e uma série de dez 6-(2-heteroaril)-4-trifluormetilpirimidinas (3a,b -7a,b) a partir da ciclocondensação de 1,1,1-trifluor-4-(2-heteroaril)-4-metoxi-3-buten-2-onas com uréia e amidinas. As estruturas de todos os compostos foram atribuídas pelos dados de análise elementar, espectrometria de massas e dados de RMN ¹H e 13C. Os dados de RMN ¹H e 13C são mostrados de maneira sistemática. Também apresentamos os dados de difração de raios-X de um monocristal da 2-amino-6-(tien-2-il)-4-trifluormetilpirimidina (5b).

The synthesis of biheterocyclic systems 6-(2-furyl)-pyrimidines and 6-(2-thienyl)pyrimidines in reasonable yields (50-67%), two 6-(2-heteroaryl)-4-trifluoromethyl-2-(1H)pyrimidinones (2a,b) and a series of ten 6-(2-heteroaryl)-4-trifluoromethylpyrimidines (3a,b 7a,b) from the cyclocondensation of 1,1,1-trifluoro-4-(2-heteroaryl)-4-methoxy-3-buten-2-ones with urea and amidines is reported. Structures of all compounds have been elucidated by elemental analysis, mass spectrometry and ¹H, 13C NMR measurements. The ¹H and 13C NMR data are systematically reported. The X-ray diffraction data for monocrystal from 2-amino-4trifluoromethyl-6-(thien-2-yl)-pyrimidine (5b) are reported.

A preparação, com bons rendimentos (70-98%), de doze novos ésteres etílicos de 5-triclorometil-4,5-diidro-1H-1-pirazóis, usando-se ambientalmente boas técnicas induzidas por microondas, é descrita. Estes compostos foram sintetizados a partir da reação de ciclocondensação de 1,1,1-tricloro-4-alcoxi-3-alquen-2-onas [CCl3C(O)C(R²)=C(R¹ )OR, onde R, R² = H, alquila; R¹ = H, alquila e arila] com metil carboxilato hidrazina. As vantagens obtidas pelo uso de irradiações de microondas na ausência de solventes, em relação ao método convencional foram demonstradas.

Twelve novel 5-trichloromethyl-4,5-dihydro-1H-1-pyrazole ethyl esters have been synthesized in good yields (70-98%) by using environmentally benign microwave induced techniques. The compounds were synthesized from the cyclocondensation of 1,1,1-trichloro-4-alkoxy-3-alken-2-ones [CCl3C(O)C(R²)=C(R¹ )OR, where R, R² = H, alkyl; R¹ = H, alkyl and aryl] with hydrazine methyl carboxylate. The advantages obtained by the using of microwave irradiation under solvent-free conditions, rather than a conventional method, were demonstrated.