An Effective Route toward Dithieno[3,2-b:2',3'-d]thiophene-based Hexaheteroacenes

A series of 12H-benzo[4'',5'']thieno[2'',3'':4',5']thieno[2',3':4,5]thieno[3,2-b]indoles was efficiently prepared in three step starting from available benzo[b]thieno[2,3-d]thiophen-3(2H)-ones. To this end, these fused ketones were treated with the Vilsmeier reagent and hydroxylamine hydrochloride, thus giving 3-chlorobenzo[b]thieno[2,3-d]thiophene-2-carbonitriles, which then reacted with methyl thioglycolate to form methyl 3-aminobenzo[4',5']thieno[2',3':4,5]thieno[3,2-b]thiophene-2-carboxylates in accordance with the Fiesselmann thiophene synthesis protocol. Finally, the desired N,S-heterohexacenes were obtained by the conversion of these fused 3-aminothiophene-2-carboxylates to the corresponding 3-aminothiohene intermediates, which play role of synthetic equivalents of thiophen-3(2H)-ones, followed by their acid-promoted reaction with arylhydrazines in accordance with the Fischer indolization reaction.

Synthesis, Antibacterial, and Molecular Docking Study of Novel 2-Chloro-8-Methoxy-3-Aryl-[1,3] Benzoxazine Derivatives using Vilsmeier Reagent

Reducing of ethyl 4-((2-hydroxy-3-methoxybenzylidene)amino)benzoate (1) afford ethyl 4-((2-hydroxy-3-methoxybenzyl)amino)benzoate (2). Reaction of this compound with Vilsmeier reagent affords novel 2-chloro-[1,3] benzoxazine ring (3). The corresponding acid hydrazide of compound 3 was synthesized from reaction of compound (3) with hydrazine hydrate. Newly series of hydrazones (5a–i) were synthesized from reaction of acid hydrazide with various aryl aldehydes. Antibacterial activity of the hydrazones was secerned utilizing gram-negative and gram-positive bacteria. Compound (5b) and (5c) exhibited significant antibacterial ability against both gram-negative and gram-positive bacteria, while the compounds (5a) showed mild antibacterial activity. Compounds (5d–i) did not display notable activity. The molecular docking of synthesised compounds were tested inside the pocket of bacterial gyrase enzyme target site by using MOE 2015 software, which acts as Adenosine triphosphate (ATP)-binding domain bacterial gyrase enzyme pocket and novobiocin was used as reference.

Synthesis of TFA-protected α-Amino Acid Chloride via a Vilsmeier Reagent for Friedel–Crafts Acylation

α-Amino acid chlorides are reactive coupling agents in amide (peptide) formation. The Vilsmeier reagent ((chloromethylene)dimethylammonium chloride) offers a convenient way to prepare α-amino acid chlorides for peptide synthesis. Its use with N-trifluoracetyl (TFA)-protected isoleucine and allo-isoleucine is described. The 1H-NMR of the α-proton signal offers a convenient way to monitor the chirality retention in the acid chloride forming reaction and subsequent Friedel-Crafts acylation of arenes which result in α-amino acid aryl-ketone with no loss of chirality.

A Leopard Cannot Change Its Spots: Unexpected Products from the Vilsmeier Reaction on 5,10,15-Tritolylcorrole

The reaction of 5,10,15-tritolylcorrole with 3-dimethylaminoacrolein (3-DMA) and POCl3 gives a further example of the rebel reactivity of this contracted macrocycle. While no evidence was obtained for the formation of the expected β-acrolein corrole, the inner core substituted N21,N22-3-formylpropylcorrole and the 10-acrolein isocorrole were the reaction products. By increasing the temperature or the amount of the Vilsmeier reagent, the 10-isocorrole became the unique reaction product. The formation of the isocorrole by electrophilic attack of the Vilsmeier reagent to the 10-position of the corrole is unprecedented in the porphyrinoids field and it could pave the way for a novel route to the preparation of stable isocorroles.

Vilsmeier reagent, NaHSe and diclofenac acid chloride: one-pot synthesis of a novel selenoindolinone with potent anticancer activity

An effective and straightforward synthesis of 3-seleno functionalized indolinone (5) involving Vilsmeier reagent is presented.

A Novel Synthesis of N-Sulfonylformamidines from N-Sulfonyl­sulfonamides

N-Sulfonylformamidines were synthesized from N-sulfonylsulfonamides by reacting with p-toluenesulfonyl chloride (TsCl) and N,N -disubstituted formamides. In this reaction, it was expected that mixing TsCl with the N,N-disubstituted formamide would generate an iminium salt (Vilsmeier reagent). The reaction avoids the use of metal catalysts and hazardous reagents, and the desired N-sulfonylformamidines were obtained in 60% to quantitative yields.