Regiospecific Synthesis Research Articles

Direct Multicomponent Synthesis of C3-Arylated Pyrroles under Catalyst-Free Conditions

AbstractAn operationally simple catalyst-free protocol for the direct regiospecific synthesis of C3-arylated/alkenylated pyrroles has been developed. The enamine-intermediate, in situ generated from succinaldehyde and a primary amine, was trapped with activated carbonyls before the Paal–Knorr reaction in a direct multicomponent ‘just-mix’ protocol to furnish pyrroles in good yields. Several C3-substituted N-alkylpyrroles have been prepared under open-flask conditions, avoiding protection-deprotection chemistry.

Reconstructive Approach to the Regiospecific Synthesis of N9‐Alkylated Purines

AbstractA regiospecific synthesis of N9‐alkylated purines as novel acyclic nucleosides was developed. This approach is based on reconstructive methodology involving the construction of a target heterocyclic scaffold on a readily available 5‐aminotetrazole moiety, which is subsequently cleaved under reductive conditions due to azido‐tetrazole tautomerism. It appeared that the rate of reduction for the azide fragment in 6‐nitro‐7‐alkylaminotetrazolo[1,5‐a]pyrimidines is much greater than the rate of nitro group reduction. Treatment of these heterocycles with hydrogen over a palladium catalyst resulted in the formation of triaminopyrimidines in excellent yields through the reduction of both the azide and nitro group. Triaminopyrimidines were transformed into the desired N9‐alkylated purines, and an analog of the marketed drug penciclovir was synthesized by the developed method.

Regiospecific synthesis of N,N’-disubstituted-2-imino-hydantoins derived from cyanamides

The present work developed a new simple method and convenient procedure to synthesize a novel series of 1-(4,6-dimethylpyrimidin-2-yl)-2-imino-3-arylimidazolidin-4-ones 3. The sodium salt of N-(4,6-dimethylpyrimidin-2-yl)cyanamide (1) was selected to use as the starting material to undergo intramolecular cyclization reaction with 2-chloro-N-arylacetamides in boiling acetone for about 12–18 hours. According to this new synthetic route, eleven imino-hydantoins were readily separated in moderate to excellent yields as single products after cooling the reaction without any purification technique. Also, on the basis of the experimental results and analysis data (IR, NMR, elemental analyses, and GC-MS spectra), the reaction is regiospecific as well as a plausible mechanism to form the target products 3 instead of di-imino-oxazolidines 4 and/or 2-imino-2,3-dihydro-oxazoles 5 is proposed.

Molecular Design of Naphthalene- and Carbazole-Based Monomers for Regiospecific Synthesis of Poly(arylenevinylene)s via Co-Catalyzed Hydroarylation Polyaddition.

This study focuses on the development of regiospecific hydroarylation polyaddition of naphthalene- and carbazole-based monomers with diynes under mild reaction conditions at room temperature. A 1-pyrazole substituent serves as an appropriate directing group for a Co-catalyst to efficiently activate the C-H bonds of generally inactive six-membered aromatic hydrocarbons. The 1-pyrazole groups in 2,6-di(1-pyrazolyl)naphthalene adopt planar conformations and act as directing groups, resulting in a smooth hydroarylation reaction. In contrast, the reaction with 1,5-di(1-pyrazolyl)naphthalene do not proceed. The polyaddition reaction of 2,6-di(1-pyrazolyl)naphthalene selectively proceeds at 3,7-positions under mild reaction conditions at 30 °C, and yields corresponding poly(arylenevinylene) (PAV) with high molecular weight. This molecular design is also applicable to the hydroarylation polyaddition of carbazole; the polyaddition reaction of 9-(2-ethylhexyl)-3,6-di(1-pyrazolyl)carbazole selectively occurred at 2,7-positions. The optical and electronic properties of the synthesized compounds are evaluated. The obtained PAVs serve as an emitting material in organic light-emitting diode (OLED). This study aims to develop a Co-catalyzed hydroarylation polyaddition via C-H activation of generally inactive polyaromatic hydrocarbons (PAHs) under mild conditions.

Fabrication of Nanoporous 3D Carbon Nitride from Poly(ionic liquid)s for Regiospecific Synthesis of Benzimidazole Frameworks

Fabrication of Nanoporous 3D Carbon Nitride from Poly(ionic liquid)s for Regiospecific Synthesis of Benzimidazole Frameworks

Eco-friendly and Regiospecific synthesis of Novel (5-oxo-4,4-diphenylimidazolidin-2-ylidene)cyanamide Derivatives

Eco-friendly and Regiospecific synthesis of Novel (5-oxo-4,4-diphenylimidazolidin-2-ylidene)cyanamide Derivatives

Estratégias para a Síntese de Análogos MonoHalogenados da Juglona: Desbloqueando o Potencial de Metodologias de Síntese Regioespecífica

Estratégias para a Síntese de Análogos MonoHalogenados da Juglona: Desbloqueando o Potencial de Metodologias de Síntese Regioespecífica

Identification, synthesis, and characterization of thermal degradants of brivaracetam

Imp-I∼III were observed for the first time after a 4-hour thermal degradation study of brivaracetam at 130 °C. These three degradants were prepared and purified through targeted and regiospecific synthesis, and were further characterized by 1D-NMR and 2D-NMR. After differentiation from other isomers, Imp-I was identified as (2S)-2-((3R)-2,5-dioxo-3-propylpyrrolidin-1-yl)butanamide; Imp-II was identified as (2S)-2-((3R,4S)-3-hydroxy-2-oxo-4-propylpyrrolidin-1-yl)butanamide; and Imp-III was identified as (S)-2-(2-oxo-4-propyl-2,5-dihydro-1H-pyrrol-1-yl)butanamide. Besides, in-silico toxicity prediction confirmed a high probability of non-mutagenicity of the three impurities. By preparing and characterizing the degradants, product stability of Brivaracetam under even extreme conditions was better understood, thus further ensuring product quality.

Straightforward and regiospecific synthesis of 1,3,5,7-tetra-arylated acene bearing different aryl groups

1,3,5,7-Tetra-arylated acene derivatives were synthesised by first introducing aryl groups at the 1,5-positions via cross-coupling reactions and then selectively introducing pentafluorophenyl groups at the 3,7-positions via CDC reactions.

Gold-Catalyzed [4 + 1] Heterocyclization of Hydroxamic Acid and Nonactivated Alkyne: A Protocol to Construct 5-Methyl-1,4,2-dioxazole.

A novel gold-catalyzed [4 + 1] heterocyclization of nonactivated alkyne and hydroxamic acid is developed for the regiospecific synthesis of 5-methyl-1,4,2-dioxazole, which is an important structural motif in various bioactive molecules. The current methodology is characterized by high efficiency, simple operation, mild reaction conditions, and good functional group compatibility. Moreover, gram-scale synthesis and synthetic application toward bioactive molecular skeletons have been realized.

Ultrasonic Preparation and Reactivity of 4,5-dihydro-1H-pyrazole Derivatives

: The regiospecific synthesis of 1H-pyrazole derivatives has been accomplished through the 1,3-dipolar cycloaddition of aryldiazoalkane to but-3-en-2-one. A convenient and inexpensive ultrasound-assisted preparation of cyclopropenes in good yields has been realized. The effect of solvent, ultrasonic power, frequency, reaction time and temperature of cyclopropenation were studied and the order of yield indicates Ultrasound, 25 KHz > Ultrasound, 40 KHz > conventional synthesis method.

(Phenylseleno)acetic acid based precursor for the regiospecific synthesis of 1-phenylseleno-2-alkanones*

A new procedure for the regiospecific synthesis of 1-(phenylseleno)alkan-2-ones starting from (phenylseleno)acetic acid has been developed. When (phenylseleno)acetyl chloride, generated from the corresponding acid, was allowed to react with phenylthio(alkyl)cuprate(I) reagents, 1-(phenylseleno)alkan-2-ones were obtained in fair to good yields.

Photoredox/Cobalt Dual Catalysis Enabled Regiospecific Synthesis of Distally Unsaturated Ketones with Hydrogen Evolution

Photoredox/Cobalt Dual Catalysis Enabled Regiospecific Synthesis of Distally Unsaturated Ketones with Hydrogen Evolution

Catalyst-free direct regiospecific multicomponent synthesis of C3-functionalized pyrroles

An operationally simple catalyst-free protocol for the direct regiospecific synthesis of β-(C3)-substituted pyrroles has been developed. The enamine intermediate, in situ generated from succinaldehyde and a primary amine, was trapped with activated carbonyls before the Paal-Knorr reaction in a direct multicomponent "just-mix" fashion to furnish pyrroles with overall good yields. Several C3-substituted N-alkyl/aryl/H pyrroles have been produced under open-flask conditions with high atom economy and avoiding protection-deprotection chemistry.

Chemo‐ and Regioselective Synthesis of Functionalized 1H‐imidazo[1,5‐a]indol‐3(2H)‐ones via a Redox‐Neutral Rhodium(III)‐Catalyzed [4+1] Annulation between Indoles and Alkynes

AbstractAlkynes generally serve as C2 synthons in transition‐metal‐catalyzed C−H annulations, herein, exploiting electron‐deficient alkynes as unconventional C1 synthons, the chemo‐ and regiospecific synthesis of functionalized 1H‐imidazo[1,5‐a]indol‐3(2H)‐ones via a redox‐neutral rhodium(III)‐catalyzed [4+1] annulation of N‐carbamoyl indoles has been achieved. This process is characterized by high chemo‐ and regioselectivity, broad substrate scope, good tolerance of functional groups, moderate to high yields and mild redox‐neutral conditions, thus affording a robust approach to access valuable 1H‐imidazo[1,5‐a]indol‐3(2H)‐ones.magnified image

Anthradithiophene-based organic semiconductors through regiodirected double annulations

An innovative double annulation regiospecific synthesis of angularly fused anthradithiophene-based scaffolds is reported, carried out with very low values for E factors. Further functionalization affords small molecules as semiconducting organic materials.

Base‐Promoted Regiospecific Synthesis of Fully Substituted 1,2,3‐Triazoles and 1,5‐Disubstituted 1,2,3‐Triazoles

AbstractAn efficient strategy have been developed for the synthesis of fully substituted 1,2,3‐triazoles and 1,5‐disubstituted 1,2,3‐triazoles subsequently by C−C bond cleavage. Regitz diazo‐transfer and C−C bond cleavage process were involved in this reaction to give 1,2,3‐triazoles with good substrate tolerance. This protocol provideed a facile and an expeditious approach for the assembly of diversely structural 1,2,3‐triazoles.

Unraveling the Mechanism of the IrIII -Catalyzed Regiospecific Synthesis of α-Chlorocarbonyl Compounds from Allylic Alcohols.

We have used experimental studies and DFT calculations to investigate the IrIII‐catalyzed isomerization of allylic alcohols into carbonyl compounds, and the regiospecific isomerization–chlorination of allylic alcohols into α‐chlorinated carbonyl compounds. The mechanism involves a hydride elimination followed by a migratory insertion step that may take place at Cβ but also at Cα with a small energy‐barrier difference of 1.8 kcal mol−1. After a protonation step, calculations show that the final tautomerization can take place both at the Ir center and outside the catalytic cycle. For the isomerization–chlorination reaction, calculations show that the chlorination step takes place outside the cycle with an energy barrier much lower than that for the tautomerization to yield the saturated ketone. All the energies in the proposed mechanism are plausible, and the cycle accounts for the experimental observations.

An efficient and regiospecific synthesis of 1,5-diaryl-4-benzothiazolyl-1,2,3-triazoles by organocatalytic 1,3-dipolar cycloaddition reactions

An efficient synthesis of 1,5-diaryl-4-benzothiazolyl-substituted 1,2,3-triazoles by organocatalytic 1,3-dipolar cycloaddition reactions, from easily available benzo[d]thiazole derivatives and substituted azidobenzenes, has been developed. The 1,8-diazabicyclo[5,4,0]undec-7-ene is used as organocatalyst, and the 2-(1,5-diaryl-1H-1,2,3-triazol-4-yl)benzo[d]thiazoles were obtained in good yields (60% − 82%) with regiospecificity. The structures of all synthesized compounds were confirmed by 1H NMR, 13C NMR and HRMS.

A new and green approach for regiospecific synthesis of novel chromeno‐triazolopyrimidin using tungstic acid immobilized MCM‐41 as a reusable catalyst

AbstractA novel, eco‐friendly and fast route has been developed for the synthesis of new and known triazolo[1,5‐a]pyrimidin fused chromone derivatives via a one pot three‐component reaction of 3‐amino‐1,2,4‐triazoles, aromatic aldehydes and 4‐hydroxycoumarin in aqueous medium at room temperature. These reactions are catalyzed by MCM‐41‐HWO4 as a safe and recyclable mesoporous solid acid. It combines successfully the synergistic effect of green chemistry with nanocatalysis. The yields are high and the products were characterized by 1H NMR, 13CNMR spectra and elemental analysis.