Juliana L. Malavolta

A straightforward and efficient synthesis of 3-(pyrimidinyl)propanoates from levulinic acid

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.

Efficient synthesis of new biheterocyclic 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

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.

Synthesis and Structure of Novel 1-Aryl-4,4,4-trichloro-1,3-butanediones

Abstract Novel 1-aryl-4,4,4-trichloro-1,3-butanediones in good yields (80–97%) were synthesized in one pot through acetal acylation with trichloroacetyl chloride followed by acid hydrolysis. Structures of all compounds were elucidated by elemental analysis, mass spectrometry, and 1H/13C nuclear magnetic resonance (NMR) measurements. The 1H/13C NMR data showed that trichloromethyl-β-diketones 2a–k in solution are predominantly ketoenol. However, the spectroscopic data from 4,4,4-trichloro-2-methyl-1-phenyl-1,3-butabedione (2l) with methyl substituent between carbonyls showed a bias toward the diketo form in solution. X-ray diffraction of monocrystals from 2g and 2i showed that these compounds are cis-ketoenol tautomers. Supplemental materials are available for this article. Go to the publishers online edition of Synthetic Communcations® to view the free supplemental file. GRAPHICAL ABSTRACT

From Levulinic Acid to Biheterocycles: Synthesis of 1-[(5-Hydroxy-5-trifluoromethyl-3-substituted-4,5-dihydro-1H-pyrazol-1-yl)-3-(5-trifluoromethyl-1H-pyrazol-3-yl)propan-1-ones

Abstract We develop an efficient method to synthesize novel propionyl-spaced bisheterocyclic compounds. It entails cyclocondensation of 3-(5-trifluoromethyl-1H-pyrazol-3-yl)propanoyl hydrazide obtained from levulinic acid, with 1,1,1-trifluoro-4-methoxy-3-alken-2-ones proceeding regiospecifically to 1-[(5-trifluoromethyl-5-hydroxy-3-substituted-4,5-dihydro-1H-pyrazol-1-yl)-3-(5-trifluoromethyl-1H-pyrazol-3-yl)propan-1-one derivatives. GRAPHICAL ABSTRACT

Synthesis of fatty trichloromethyl-β-diketones and new 1H-pyrazoles as unusual FAMEs and FAEEs

A sintese 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] e apresentada, com bons rendimentos (85-95%) a partir da acilacao 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 esteres metilicos (FAMEs) e etilicos (FAEEs) graxos nao comuns. As estruturas moleculares dos compostos sintetizados foram confirmadas por analise elementar e ressonância magnetica 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 sao novos oleoquimicos com propriedades diferenciadas e potencialmente interessantes.

Heterocyclization of ω-Bromo-2-trichloroacetyl Cycloalkanones to Isoxazole Derivatives

Abstract A new series of brominated 3,4-polymethylene-5-hydroxy-5-trichloromethyl-4,5-dihydroisoxazoles (2a–d) has been regiospecifically obtained from the reaction of ω-bromo-2-trichloroacetylcycloalkanones with hydroxylamine in 79–87% yield. Dehydration of the 5-hydroxydihydroisoxazoles 2a–d can be effected with concentrated sulfuric acid at 25 °C to give the regioisomeric brominated 3,4-polymethylene-5-trichloromethylisoxazoles (3a–d). In contrast, the dehydration of 5-hydroxydihydroisoxazoles with sulfuric acid in ethanol solution at 65 °C, for transformation of trichloromethyl to carboxyl group, was reproducible only with 9-bromo-3-trichloromethyl-3,3a,4,5,6,7,8,9-octahydrocycloocta[c]isoxazole-3-ol, 2d, leading to isoxazolecarboxylate 4d. The structural assignments of all isolated products are based on the analysis of their 1H and 13C NMR spectral data.

Strategies for the Efficient Synthesis of Biheterocyclic 5-[2-(Trifluoromethylheteroaryl)-ethyl]-1,3,4-oxadiazoles from Levulinic Acid

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(OR)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 H and C nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization coupled to tandem mass spectrometric (ESI MS/MS) data.

Straightforward and Clean Ultrasound-Promoted Synthesis of 2-(4,5-Dihydro-1H-pyrazol-1-yl)pyrimidines

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.