Simón E. López

The synthesis of substituted 2-aryl 4(3 H )-quinazolinones using NaHSO 3 /DMA. Steric effect upon the cyclisation-dehydrogenation step

A number of 2-aryl substituted 6-pyrrolidino-4(3H)-quinazolinones are reported. They were synthesised in four steps starting from commercially available 5-chloro-2-nitrobenzoic acid. The key cyclisation-dehydrogenation step between 2-amino-pyrrolidinobenzamide 5 and different benzaldehydes employs NaHSO3 as the dehydrogenating agent in hot DMA. This last reaction shows a strong dependence on the position of the substituent at the aromatic ring of the benzaldehyde used. Thus, the 2-substituted benzaldehydes, in contrast to 3- and 4-substituted compounds give a poor yield of desired products or a mixture.

Direct microwave promoted trifluoroacetylation of aromatic amines with trifluoroacetic acid

A simple microwave-promoted procedure has been developed for the direct preparation of trifluoroacetanilides. An equimolar mixture of substituted anilines and trifluoroacetic acid was microwave irradiated at short reaction times, giving the corresponding anilides in high yields and purity.

Trifluoroacetylation in Organic Synthesis: Reagents, Developments and Applications in the Construction of Trifluoromethylated Compounds

This review covers the trifluoroacetylation reaction in organic synthesis and its importance for the construction of trifluoromethylated compounds. Developed reagents for trifluoroacetylation are described, as well as their characteris- tics and preparation, giving emphasis on their applications and limitations in organic synthesis. Trifluoroacetylation, al- though commonly employed for the protection of functional groups (amines, alcohols, thiols), may be a useful tool for the further introduction of a trifluoromethyl group into an organic molecule. Its application, mainly in the synthesis of trifluoromethyl-heterocycles such as benzothiadiazines, pyrazoles, benzodiazepines, thieno-thiazines, isoxazoles and pyrimidines, is also covered.

Synthesis of 2-trifluoromethyl-1(substituted aryl)-4(1H)-quinolones using trifluoroacetamidoyl chlorides

A simple two-step procedure for the preparation of 2-trifluoromethyl-1(substituted aryl)-4(1H)-quinolones utilizing electrophilic trifluoroacetamidoyl chlorides as the starting materials is described. The cyclization of trifluoromethyl enaminone intermediates with potassium carbonate in hot dimethylformamide produce the trifluoromethylated 4(1H)-quinolones in good to excellent yields.

A convenient route to 2-substituted benzothiazole-6-carboxylic acids using nitrobenzene as oxidant

Various substituted benzothiazole-6-carboxylic acids (4a–i) have been prepared by the condensation of 4-amino-3-mercaptobenzoic acid and aldehydes in nitrobenzene as oxidant. Compound 4i was found to be a good candidate as an inhibitor of β-hematin formation in vitro.

Synthesis, dopaminergic profile, and molecular dynamics calculations of N-aralkyl substituted 2-aminoindans

Brain dopaminergic system has a crucial role in the etiology of several neuropsychiatric disorders, including Parkinsons disease, depression, and schizophrenia. Several dopaminergic drugs are used to treat these pathologies, but many problems are attributed to these therapies. Within this context, the search for new more efficient dopaminergic agents with less adverse effects represents a vast research field. The aim of the present study was to synthesize N-[2-(4,5-dihydroxyphenyl)-methyl-ethyl]-4,5-dihydroxy-2-aminoindan hydrobromide (3), planned to be a dopamine ligand, and to evaluate its dopaminergic action profile. This compound was assayed as a diastereoisomeric mixture in two experimental models: stereotyped behavior (gnaw) and renal urinary response, after central administration. The pharmacological results showed that compound 3 significantly blocked the apomorphine-induced stereotypy and dopamine-induced diuresis and natriuresis in rats. Thus, compound 3 demonstrated an inhibitory effect on dopaminergic-induced behavior and renal action. N-[2-(-Methyl-ethyl)]-4,5-dihydroxy-2-aminoindan hydrobromide (4) was previously reported as an inotropic agent, and in the present work it was also re-evaluated as a diastereoisomeric mixture for its possible central action on the behavior parameters such as stereotypy and dopamine-induced diuresis and natriuresis in rats. Our results indicate that compound 4 produces an agonistic response, possibly through dopaminergic mechanisms. To better understand the experimental results we performed molecular dynamics simulations of two complexes: compound 3/D(2)DAR (dopamine receptor) and compound 4/D(2)DAR. The differential binding mode obtained for these complexes could explain the antagonist and agonist activity obtained for compounds 3 and 4, respectively.

HYDROCHLORINATION OF 2,3-ACETYLENIC ACIDS WITH THIONYL CHLORIDE IN DIMETHYLFORMAMIDE

ABSTRACT The reaction of 2,3-acetylenic acids (1a–d) with thionyl chloride in DMF under mild conditions gave E,Z-3-chloro-2-alkenoic acids (2a–d) or esters (3a–d) depending on treating the reaction mixture with either water or alcohols.

Microwave-Assisted Direct Synthesis of 4H-1,2,4-Benzothiadiazine 1,1-Dioxide Derivatives

Abstract We describe a rapid and convenient methodology for the preparation of diverse 3-aryl and 3-trifluoromethyl 4H-1,2,4-benzothiadiazine-1,1-dioxides in a one-pot microwave-promoted reaction between 2-aminobenzenesulfonamides and benzaldehydes, trifluoroacetic acid or benzoic acids. GRAPHICAL ABSTRACT

AN IMPROVED PROCEDURE FOR THE PREPARATION OF N-ARYL SUBSTITUTED 4H-1,4-BENZOTHIAZINE 1,1-DIOXIDE DERIVATIVES

Abstract An improved procedure for the synthesis of N-aryl substituted 4H-1,4-benzothiazine 1,1-dioxide 2-carboxylic acid-esters derivatives is reported. In this new, efficient methodology. silver nitrate was used as a catalyst for the cyclization of N-aryl-phenylsulfonyl-acrylates 6–11 using potassium carbonate in dimethylformamide to the corresponding title compounds in high yields.

1H and 13C NMR spectral characterization of some antimalarial in vitro 3-amino-9-methyl-1H-pyrazolo[3,4-b]-4-quinolones

We report the 1H NMR and 13C NMR chemical shifts and J(H,H), J(H,F) and J(C,F) coupling constants of nine 3‐amino‐9‐methyl‐1H‐pyrazolo[3,4‐b]‐4‐quinolone derivatives, all of them active against Plasmodium falciparum in vitro. They were characterized and assigned on the basis of 1H, 13C and 13C 1H (short‐ and long‐range) correlated spectra. Copyright