José Salazar

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.

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.

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

Synthesis, β-hematin inhibition studies and antimalarial evaluation of dehydroxy isotebuquine derivatives against Plasmodium berghei.

Diverse dehydroxy-isotebuquine derivatives were prepared by using a five step synthetic sequence in good yields. All these new 4-aminoquinolines were evaluated as inhibitors of haemozoin formation, where most of them showed a significant inhibition value (% IHF >97). The best inhibitors were tested in vivo as potential antimalarials in mice infected with Plasmodium berghei ANKA chloroquine susceptible strain, three of them (11b, 11d and 11h) displayed an antimalarial activity comparable to that of chloroquine.

SYNTHESIS AND PRELIMINARY CYTOTOXIC EVALUATION OF NOVEL 3,4-DIHYDRO-2H-1,2,4-BENZOTIADIAZINE-1,1-DIOXIDE DERIVATIVES

The preparation of novel 3,4-dihydro-2//-l,2,4-benzothiadiazine-l,l-dioxide derivatives through the condensation of halogenated 2-aminobenzenesulfonamides and benzaldehydes using sodium hydrogen sulfite is described. Contrary to previous reports for non substituted 2aminobenzenesulfonamides, sodium hydrogen sulfite does not effect the dehydrogenation of 3,4-dihydro compounds to the corresponding 3,4-unsaturated 2//-l,2,4-benzothiadiazines. The preliminary cytotoxic evaluation of some of these new compounds toward several human tumor cell lines is also reported.

A Facile Synthesis of (E,Z)‐3‐Chloro‐2‐propenamides, Acids, and Esters from 2,3‐Acetylenic Acids with Oxalyl Chloride in DMF

Abstract A simple route is described for the synthesis of E and Z 3‐chloro‐2‐propenamides (4a‐e), esters (3a) and acids (2a‐c) by the reaction of 2,3‐acetylenic acids with oxalyl chloride in DMF followed by treatment of the corresponding 3‐chloro‐2‐propenoyl chloride derivative with amines, alcohol and water.

UNEXPECTED DESULFONATION OF α-PHENYLSULFONYL ENAMINOACRYLATES DURING THEIR CYCLISATION TO NEW N-ARYL 4H-1,4-BENZOTHIAZINE-l,l-DIOXIDES

Abstract An unexpected desulfonation of α-phenylsulfonyl-enaminoacrylates occurred during their cyclisation to novel 6,7-dichloro-N-aryl-4H-1,4-benzothiazine-1,1-dioxides using potassium carbonate and silver nitrate in DMF. This last cyclisation step was not completed in five hours of reaction but, instead of higher yields of the desired cyclic 4H-benzothiazines, a mixture of the above mentioned target compounds and desulfonated N-formyl-2-aryl-enanii-noacrylates were obtained.

Synthesis of 3-Hydroxy-2-Phenyl-1,8-Naphthyridin-4(1H)-one derivatives

As part of our research program directed towards the design and synthesis of novel heterocycles with potential cytotoxic activity, we synthesized some 2-phenyl-3-hydroxy-l,8-naphthyridin-4(li/)-one derivatives, structurally related to the antimitotic 2-phenyl-1.8-naphthyridin-4(l//)-ones. To the best of our knowledge, this is the first example of preparation of 3-hydroxy derivatives from the 1,8-napththyridine nucleus. A preliminary cytotoxic evaluation of two of these compounds is also included. The 1,8-naphthyridines are an interesting class of members of the diazanaphthalene series [1,2]. Attention on these heterocycles in the last fifteen years have been focused on the preparation of biologically important 3-carboxylic acid l,8-naphthyridin-4(l//)-one antibacterials related to nalidixic acid [3]. Recently a number of 2-phenyl-l,8naphthyridin-4(l//)-ones 1 were prepared and tested for their cytotoxic activity towards a large number of cancer cell tumor lines [4]; these compounds were also capable of inhibit tubulin polymerization, demonstrating their potential as novel antimitotic agents [5]. A 3-hydroxy substitution on the isosteric 2-phenyl flavones and 2-phenyl 4(l//)-quinolones 2 has proved its value for the antimitotic activity [6], Thus, an hydroxy group located at C-3 of 2-phenyl-1,8naphthyridine-4(l//)-ones 5a-f may lead for novel cytotoxic compounds. Ο Ο 1 2 5«-f A limited number of procedures have been reported for the related and relatively unexplored 3-hydroxy-4(l//)quinolones; these include a cyclization-dehydratation of an a-alcoxy-2-N-acylamino substituted acetophenone by an intramolecular anion nucleophilic attack [6] and a cyclization of phenacyl anthranylate esters in hot polyphosphoric acid to a 3//-benc(eXl,4)oxacepin-5-one whose in situ rearrangment give the more stable 3-hydroxy-4( 1 //)-quinolone [7-8]. The simplicity of this last have attracted our attention due to the readily available 2-amino-nicotinic acid as a source of starting material for the required phenacyl nicotinic esters, necessary for a possible rearrangement to novel 3-hydroxyl,8-naphthyridin-4(lW)-ones (Scheme 1). Results and discussion Starting from 2-amino-nicotinic acid 3, its potassium salt was formed and reacted with substituted a bromoacetophenones to obtain the corresponding phenacyl nicotinic esters 4a-f by nucleophilic displacement. These esters were then poured on to preheat (50 °C) polyphosphoric acid and heated at 120 °C for two hours, giving the required 3-hydroxy-l,8-naphthyridin-4(l//)-ones 5a-f in good yields (Table 1). Although not isolated, we supposed a 2phenyl-1.5-dihidropyrido[2,3-e][l,4]-oxazepin-5-one as a reaction intermediate which then rearrange to the 3-hydroxy-

GAS-PHASE THERMOLYSIS OF SULFUR COMPOUNDS. PART VII. 4,6-DITHIA-1-OCTENE, 4,6-DITHIA-1,8-NONADIENE AND 4,6-DITHIA-6-PHENYL-1-HEXENE

Abstract Under stirred-flow conditions, the title compounds pyrolyze to yield propene and the ethyl, allyl and benzyl dithioformates, respectively, as reaction products. The first order rate coefficients of these unimolecular decompositions followed the Arrhenius equations 4,6-dithia-1-octene k (sec−1)=1010.85 ± 0.18exp (-142 ± 2 kJ/mol RT) 4,6-dithia-1,8-nonadiene k (sec−1)=1010.45 ± 034exp (-132 ± 4 kJ/mol RT) 4,6-dithia-6-phenyl-1-hexene k (sec−1)=1010.09 ± 043exp (-130 ± 5 kJ/mol RT) The activation parameters are discussed in relation to those of other allyl sulfides. These suggest that a sulfur atom can stabilize the transition state to the same extent as a π-electron system.