Vilsmeier Reaction Research Articles

ChemInform Abstract: FormylBODIPYs: Privileged Building Blocks for Multicomponent Reactions. The Case of the Passerini Reaction.

Eleven formyl-containing BODIPY dyes were prepared by means of either the Liebeskind–Srogl cross-coupling reaction or the Vilsmeier reaction. These dyes were used as components in the Passerini reaction to give highly substituted BODIPY dyes. A joined spectroscopic and theoretical characterization of the synthesized compounds was conducted to unravel the impact of the structural rigidity/flexibility on the photophysical signatures. These dyes were tested as fluorescent trackers for phagocytosis. Additionally, they proved to be useful to stain different blood cells with an intense and stable signal at a very low exposure time.

Synthesis of Some New Heterocyclic Compound Derivative from 2-Chloro-3-Formyl-1,8,-Naphthyridine

2-Chloro-3-formyl-1,8-naphthyridine ( 1 ) has been synthesized in a Vilsmeier-Haack type reaction route. Starting from ( 1 ) a number of novel 1,8-naphthyridines were also synthesized. The structures of synthesized compounds were confirmed by their spectral and physical data. Some of the newly synthesized compounds exhibited antibacterial activity.

Synthesis of Novel 3-Acetyl-2-aminothiophenes and Investigation of their Behaviour in the Reaction with Vilsmeier–Haack Reagent

Through an investigation into the behaviour of 3-acetyl-2-aminothiophene in the reaction with Vilsmeier–Haack reagent, an efficient method for the synthesis of 4-chlorothieno[2,3-b]pyridine derivatives has been established. Gewald’s classical synthesis starting from cyanoacetone, ketones and elemental sulphur has been applied to produce the starting materials.

Synthesis and Antimicrobial Activities of Novel 2‐[substituted‐1H‐pyrazol‐4‐yl] Benzothiazoles, Benzoxazoles, and Benzimidazoles

In an endeavor to find a new class of antimicrobial agents, a series of novel substituted benzimidazole, benzoxazole, and benzothiazole derivatives 6 containing pyrazole moiety have been synthesized by reaction of 3‐aryl‐4‐formyl pyrazole 4 with substituted phenylenediamine or o‐aminophenol or o‐aminothiophenol 5. Reaction of phenyl hydrazine or 2‐hydrazinopyridine 1 with substituted acetophenones 2 gave the corresponding hydrazones 3, which on Vilsmeier–Haack reaction with POCl3–DMF gave substituted 3‐aryl‐4‐formyl pyrazoles 4. All final compounds 6a, 6b, 6c, 6d, 6e, 6f, 6g, 6h, 6i, 6j, 6k were evaluated for in vitro antibacterial activities against Escherichia coli and Staphylococcus aureus strains and in vitro antifungal activity against Candida albicans and Aspergillus niger strains by using serial dilution method. The antimicrobial activities were expressed as the minimum inhibitory concentration in µg/mL. The compound containing benzimidazole and benzoxazole moiety gave better antibacterial and antifungal activities than benzothiazole compounds.

Synthesis of novel 17-(4′-formyl)pyrazolylandrosta-5,16-dienes and their derivatives as potent 17α-hydroxylase/C17,20-lyase inhibitors or antiproliferative agents depending on the substitution pattern of the heteroring

A series of novel 17-(4′-formyl)pyrazolylandrosta-5,16-dienes were efficiently synthesized in two steps from pregnadienolone acetate with monosubstituted hydrazines via the cyclization/formylation sequence of the primarily formed hydrazones on treatment with the Vilsmeier-Haack reagent. The products were further transformed by deacetylation and subsequent reduction in order to enlarge the compound library available for pharmacological studies. Moreover, 4′-formylpyrazoles containing H or Me on the heteroring-N were subjected to oxime formation and Ac2O-induced dehydration to furnish the corresponding 4′-cyano derivatives in good yields. The antiproliferative activities of the structurally related steroidal 17-exo-pyrazole derivatives were tested in vitro on four human adherent breast cancer cell lines (MCF7, T47D, MDA-MB-231 and MDA-MB-361): the microculture tetrazolium assay revealed that seven compounds exerted better cell growth-inhibitory effects on some or all these cell lines than those of the reference cisplatin. With regard to the well-known structural features that a potent C17,20-lyase inhibitor should possess, some relevant derivatives were tested in vitro from the aspects of their inhibitory effects on rat testicular enzyme, and one of them proved to exert noteworthy enzyme-inhibitory action, with an IC50 (26 nM) of the same order of magnitude as that of abiraterone.

Total Synthesis of the Proposed Structure of Marineosin A.

A total synthesis of a proposed structure of marineosin A has been achieved. The key steps involve Lewis acid catalyzed spirocyclizaton, ring-closing metathesis, Paal-Knorr pyrrole synthesis, and a Vilsmeier-Haack type reaction with Tf2O.

Synthesis, structural studies and antituberculosis evaluation of new hydrazone derivatives of quinoline and their Zn(II) complexes

The quinoline hydrazone ligands were synthesized through multi-step reactions. The 2-hydroxy-3-formylquinoline derivatives (1a–1c) were prepared from acetanilide derivatives as starting materials using Vilsmeier–Haack reaction. Then the condensation of 2-hydroxy-3-formylquinoline derivatives with hydrazide derivatives (2a–2c) yielded quinoline hydrazone ligands (3a–3i). The synthesis of a new series of Zn(II) complexes carried out by refluxing with these quinoline hydrazone ligands (3a–3i) is reported. The molecular structures of the ligands (3a–3i) and the Zn complexes were characterized by elemental analysis and spectral studies like FT-IR, 1H and 13C NMR, MS, UV–Visible and fluorescence. The preliminary results of antituberculosis study showed that most of the Zn(II) complexes 4a–4i demonstrated very good antituberculosis activity while the ligands 3a–3i showed moderate activity. Among the tested compounds 4e and 4g were found to be most active with minimum inhibitory concentration (MIC) of 8.00μM and 7.42μM respectively against Mycobacterium tuberculosis (H37 RV strain) ATCC No-27294 which is comparable to “first and second line” drugs used to treat tuberculosis.

Synthesis and Crystal Structures of Stable 4-Aryl-2-(trichloromethyl)-1,3-diaza-1,3-butadienes

A simple and convenient method to generate 4-aryl-substituted 1H-2-(trichloromethyl)-1,3-diaza-1,3-butadienes from aryl(chlo­ro)methaniminium salts (best known as Vilsmeier–Haack reagents) and trichloroacetamidine has been developed. These 4-aryl-1H-1,3-diaza­butadienes are isolable, relatively stable during silica gel chromatography, and can be crystallized. The analysis by X-ray diffraction demonstrated that in the solid state these 1,3-diazabutadienes have an s-cisoid conformation. The principal characteristic of these 1,3-diazabutadienes is their reactivity towards electron-deficient acetylenes, reacting under mild reaction conditions to produce 4-aryl-2-(trichloromethyl)pyrimidines in good yields.

ChemInform Abstract: A Facile Synthesis of Diformylated Pyrroles by Dehydroxylation of N‐Aryl‐5‐hydroxy‐γ‐lactam Derivatives under Vilsmeier Reaction Conditions.

A simple and efficient methodology for the conversion of substituted trans-1,4-diaryl-5-hydroxypyrrolidin-2-ones to diformylated N-arylpyrroles by treatment with Vilsmeier–Haack reagent has been developed.

Microwave assisted selective synthesis of (E)-1-(4-Chloro-7-hydroxy-2-aryl-2H-chromen-6-yl)-3-arylprop-2-en-1-ones and their antimicrobial activity

A series of new (E)-1-(4-chloro-7-hydroxy-2-aryl-2H-chromen-6-yl)-3-arylprop-2-en-1-ones (2a–2f) have been synthesized by selective mono cyclization of 4,6-dicinnamoyl resorcinols (1a–1f) using Vilsmeier–Haack reagent under conventional heating and microwave irradiation. The structures of the synthesized compounds have been elucidated by elemental analysis, IR, 1H NMR, 13C NMR and Mass spectral data. The synthesized compounds were tested in vitro for antimicrobial activity.

Synthesis of new hydroquinolinecarbaldehydes

A number of new N-alkyl-6(8)-formylhydroquinolines have been synthesized. The Vilsmeier—Haack reaction of 7(8)-substituted N-alkyl-1,2-dihydroand N-alkyl-1,2,3,4-tetrahydroquinolines led to 6-formylhydroquinolines, whereas N-methyl-8-formylhydroquinolines were formed in the case of 6-substituted N-methyl-1,2-dihydroand N-methyl-1,2,3,4-tetrahydroquinolines.

FormylBODIPYs: Privileged Building Blocks for Multicomponent Reactions. The Case of the Passerini Reaction.

Eleven formyl-containing BODIPY dyes were prepared by means of either the Liebeskind-Srogl cross-coupling reaction or the Vilsmeier reaction. These dyes were used as components in the Passerini reaction to give highly substituted BODIPY dyes. A joined spectroscopic and theoretical characterization of the synthesized compounds was conducted to unravel the impact of the structural rigidity/flexibility on the photophysical signatures. These dyes were tested as fluorescent trackers for phagocytosis. Additionally, they proved to be useful to stain different blood cells with an intense and stable signal at a very low exposure time.

Design and synthesis of some new tri-substituted pyrazole derivatives as anticancer agents

A new series of tri-substituted pyrazole derivatives were designed as anti-cancer agents and synthesized, starting with the formylation of semicarbazone via the Vilsmeier–Haack reaction to give 3-(4-bromophenyl)-1H-pyrazole-4-carbaldehyde I which was the precursor of compounds 1–9. The new chemical entities were screened for their anti-cancer activity on various human cancer cell lines, namely: hepatocellular carcinoma HepG2, breast cancer MCF-7, lung carcinoma A549 and prostatic cancer PC3. Most of the synthesized compounds showed remarkable activity on the tested cell lines, while compound 2 had the highest potency against the HepG2 cell line with an IC50 of 9.13 µM compared with doxorubicin (IC50 = 34.24 µM), the reference standard used in this study, and compound 7 was the most active on the rest of the three cell lines; MCF-7, A549 and PC3 (IC50 = 16.52, 6.52 and 9.13 µM, respectively) relative to IC50 = 20.85, 5.93 and 38.02 µM of the standard. Thus, some of the synthesized tri-substituted pyrazole derivatives, specially 2 and 7, have the potential to be developed into potent anticancer agents.

One-Pot Synthesis of Highly Substituted Nicotinic Acid Derivatives Based on a Formylation Strategy of Enamino Keto Esters.

A facile one-pot synthesis of 4-chloro or 4-bromonicotinic acid esters with optional 2- and 2,5-disubstitution on the pyridine ring has been developed from easily accessible enamino keto esters by a formylation followed by in situ intramolecular cyclization strategy under optimized Vilsmeier reaction conditions. The effect of the substituents on the β-carbon and the nature of the keto functionality were explored in detail to understand the mechanism of pyridine ring formation under the described conditions.

ChemInform Abstract: 2,4,6‐Trichloro‐1,3,5‐triazine and N,N′‐Dimethylformamide as an Effective Vilsmeier—Haack Reagent for the Synthesis of 2‐Chloro‐3‐formyl Quinolines from Acetanilides.

AbstractA preformed 2,4,6‐trichloro‐1,3,5‐triazine/dimethylformamide adduct reacts with acetanilines under sonication at room temperature to form quinoline derivatives in short reaction times.

Design, synthesis and characterization of new 1,2,3-triazolyl pyrazole derivatives as potential antimicrobial agents via a Vilsmeier–Haack reaction approach

A new series of 1,2,3-triazolyl pyrazole derivatives were synthesisedviaa Vilsmeier–Haack reaction approach and screened for theirin vitroanti-bacterial, anti-fungal and anti-oxidant activities.

Synthesis of Pyrazolyl Thiobarbituric Acids and their Cytotoxic and Antimicrobial Evaluation

Synthesis, cytotoxic and anti-microbial screening of novel thiobarbituric acid incorporated pyrazole derivatives were performed. Vilsmeier-Haack reaction of different phenyl hydrazones 1(a-e) afforded pyrazole -4- carbaldehydes 2(a-e) in good yields. Knoevenagel condensation of compounds 2(a-e) with thiobarbituric acid gave a series of 5-ylidene derivatives 3(a-e) in reasonable yields. The synthesized compounds were characterized with the help of IR,1HNMR and mass spectral data. The compounds were tested for cytotoxic activity against Vero, MCF-7 and HCT-116 cell lines. Among the tested compounds, 5- ((3 -(4-hydroxyphenyl)-1-phenyl-1H-pyrazol-4- yl)methylene)-2-thioxodihydropyrimidine-4,6-(1H,5H)-dione (3d) was found to be most active molecule with the activity against both MCF-7 and HCT-116 cell lines with IC50 values of 14.0 μM and 18.12 μM. In anti-microbial screening, none of the compounds exhibited anti-bacterial activity.

Ultrasonically Assisted Decarboxylative Bromination of α,β-Unsaturated Carboxylic Acids Under Vilsmeier-Haack Conditions

An efficient method for decarboxylative bromination of cinnamic acids (α,β-unsaturated carboxylic acids or 3-arylpropenoic acids) was achieved under relatively mild conditions using Vilsmeier-Haack reagent and KBr in acetonitrile media. Vilsmeier-Haack reagent is prepared by using 1:1 ratio of oxychloride (SOCl2 or POCl3) and DMF under chilled condition. Ultrasonically assisted reactions underwent smoothly with highly significant rate enhancements and afforded bromostyrenes as products in very good yields even though the reactions were too sluggish.

ChemInform Abstract: A Straightforward Approach Toward Multifunctionalized Pyridazines via Imination/Electrocyclization.

AbstractThe chlorovinyl aldehydes are efficiently prepared from ketones by Vilsmeier—Haack reaction.

Synthesis, biological activity evaluation and molecular docking studies of novel coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes.

A novel series of coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes (4a-o) were synthesized via an efficient, one-pot multicomponent approach involving 3-(2-bromoacetyl)coumarins (1a-g), thiosemicarbazide (2) and substituted acetophenones (3a-c) utilizing Vilsmeier-Haack reaction condition with good yields. The title compounds structure was elucidated by spectroscopic data (IR, NMR and Mass) and elemental analysis. All the synthesized compounds were screened for their in vitro cytotoxic activity against MCF-7, DU-145 and HeLa cell lines and studied detailed about molecular interaction of probable target protein human microsomal cytochrome CYP450 2A6 using docking simulation. These coumarin derivatives were exhibiting moderate to appreciable cytotoxic activities. The compounds 4m and 4n exhibited significant cytotoxic activity with IC50 values having 5.75 and 6.25μM against HeLa cell line. Similarly compound 4n also exhibiting good anti cancer property and antibacterial activity against DU-145 cell line and Gram negative bacterial strains.