Methyl 2-formylbenzoate Research Articles

Synthesis of 3-Benzylphthalide Derivatives by Using a TDAE Strategy

AbstractA one-pot synthesis of new 3-benzylphthalide derivatives was developed by using a strategy based on tetrakis(dimethylamino)ethylene (TDAE). The reactions in the presence of TDAE of substituted benzyl chlorides with methyl 2-formylbenzoate or of substituted methyl-2-formylbenzoates with 4-nitrobenzyl chloride furnished the corresponding isobenzofuran-1(3H)-one products in moderate to good yields.

Methyl-2-formyl benzoate: A Review of Synthesis and Applications

Methyl-2-formyl benzoate is known as a bioactive precursor in organic synthesis of compounds due to its variety of pharmacological activities namely antifungal, antihypertensive anticancer, antiulcer, antipsychotic and antiviral properties. As an active scaffold, methyl-2-formyl benzoate can be considered as a significant structure and an excellent precursor for the search of new bioactive molecules. Methyl-2-formyl benzoate is synthetically a versatile substrate, which can be used as a raw material for the preparation of medical products. Due to its significant in organic synthesis, the objective of this review is to discuss on the various synthetic routes for the preparation of methyl2-formyl benzoate (via two-step and one-step methodologies) and its importance as precursor for the preparation of compounds with pharmaceutical applications. This review is of importance in synthetic fields and pharmaceutical industry.

Stereoselective synthesis of isoindolinones and tert-butyl sulfoxides

A reaction of Grignard reagents with an optically pure N-sulfinylimine derived from methyl 2-formylbenzoate yields enantioenriched isoindolinones and tert-butyl sulfoxides. The products are formed by the addition of the nucleophile to N-sulfinylimine followed by cyclization to form N-tert-butylsulfinylisoindolinone, which readily undergoes substitution with a second equivalent of Grignard reagent. The reaction can be carried out in dichloromethane at room temperature or at elevated temperatures without any loss of stereoselectivity. The use of nucleophiles other than Grignard reagents has also been investigated.

Synthesis of isoindolin-1-one derivatives via multicomponent reactions of methyl 2-formylbenzoate and intramolecular amidation

Four series of heterocyclic compounds were obtained using Ugi-type multicomponent reactions (MCRs) with methyl 2-formylbenzoate as one of the starting materials. A facile and efficient one-pot procedure was suitable for all the MCRs under acidic conditions. This process provided access to four series of complex and potentially biologically active scaffolds.

Catalytic cascade aldol-cyclization of tertiary ketone enolates for enantioselective synthesis of keto-esters with a C-F quaternary stereogenic center.

The first asymmetric catalytic aldol-cyclization reaction of detrifluoroacetylatively in situ generated enolates with methyl 2-formylbenzoate is reported. This reaction tolerates a wide range of substrates, affording fluorinated quaternary stereogenic α,α-dialkyl/cyclo-alkyl-β-ketoesters with good yields, high diastereo- (94% de) and enantioselectivity (96% ee) at room temperature.

New efficient synthesis of isoquinoline-1,3(2H,4H)-diones and isoindolin-1-ones via sequential Ugi/cyclization reaction

A new efficient synthesis of isoquinoline-1,3(2H,4H)-diones or isoindolin-1-ones via sequential Ugi-4CR or Ugi-3CR/cyclization reaction was developed. α-Acylamino amides 5, obtained from Ugi-4CR of methyl 2-formylbenzoate, amines, isocyanates and acids, cyclized to give isoquinoline-1,3(2H,4H)-diones 6 in good yields in the presence of catalytic amount of sodium ethoxide. Ugi-3CR of methyl 2-formylbenzoate, amines and isocyanates in the presence of catalytic amount of H3PO4 produced isoindolin-1-ones 7 directly in one-pot fashion.

Sc(OTf)3-catalyzed three-component cascade reaction: One-pot synthesis of substituted 3-oxoisoindoline-1-carbonitrile derivatives

A facile and efficient approach for the synthesis of N-substituted 3-oxoisoindoline-1-carbonitrile derivatives has been developed, with a Sc(OTf)3-catalyzed three-component Strecker/Lactamization cascade reaction involving methyl 2-formylbenzoate, TMSCN and amines in ethanol at room temperature. Good to excellent yields for a broad scope of amine substrates were achieved.

Highly enantioselective synthesis of 2,3-dihydro-1H-imidazo[2,1-a]isoindol-5(9bH)-ones via catalytic asymmetric intramolecular cascade imidization-nucleophilic addition-lactamization.

Highly enantioselective catalytic asymmetric intramolecular cascade imidization-nucleophilic addition-lactamization of N(1)-alkylethane-1,2-diamine with methyl 2-formylbenzoate catalyzed by a chiral phosphoric acid represents the first efficient method for the preparation of medicinally interesting chiral 2,3-dihydro-1H-imidazo[2,1-a]isoindol-5(9bH)-ones with high yields and excellent enantioselectivities. This strategy has been shown to be quite general toward various methyl 2-formylbenzoates.

ChemInform Abstract: A One‐Pot Preparation of 1,3‐Diarylisobenzofuran.

AbstractA simple, practical and efficient method for the one‐pot synthesis of symmetric (III) and unsymmetric (V), (VII) 1,3‐diarylisobenzofurans is developed using sequential reactions of methyl 2‐formylbenzoate (I) with two identical or different aryl metal species.

Rapid two-step synthesis of benzimidazo[1',2':1,5]pyrrolo[2,3-c]isoquinolines by a three-component coupling reaction.

A two-step, three-component coupling reaction on ionic liquid supported 2-cyanomethylbenzimidazoles, methyl 2-formylbenzoate, and isocyanides under microwave activation is explored. Knoevenagel condensation of 2-cyanomethylbenzimidazole with methyl-2-formylbenzoate in the presence of piperidine catalyst is followed by [4+1] cycloaddition with an isocyanide in the next step. Consequent intramolecular δ-lactam formation allows rapid construction of novel aza-pentacycles, benzimidazo[1',2':1,5]pyrrolo[2,3-c]isoquinolines.

ChemInform Abstract: A Telescoping Synthesis of Chimeric Polyheterocycles Through a Piperidine‐Mediated Multicomponent Reaction.

A new piperidine-catalyzed Groebke–Bienayme–Blackburn (GBB) multicomponent reaction of 2-aminobenzimidazoles, methyl 2-formylbenzoate, and isocyanides has been explored. A facile and straightforward postmodification leads to isoquinolinone-embedded imidazo[1,2-a]benzimidazoles. Insight into a plausible mechanism is discussed and supported by X-ray crystal structure analysis.

A One-pot Preparation of 1,3-Diarylisobenzofuran

Abstract A simple, practical, and efficient method for one-pot synthesis of symmetric and unsymmetrical 1,3-diarylisobenzofurans has been developed by sequential reactions of methyl 2-formylbenzoate with two identical or different aryl metal species.

Development of a copper(II)-catalyzed three-component tandem synthesis of isoindolinone derivatives

Isoindolinone derivatives are important pharmaceutical building blocks in medicinal chemistry. Isoindolo[2,1-a]quinolines are a class of interesting compounds that possess protective effects against N2-induced hypoxia and inhibitory activities against human topoisomerase II and bacterial DNA-gyrase. The conventional methods for synthesizing these compounds are unsatisfactory because of their harsh reaction conditions, complex starting materials, and multistaged purification procedures. This synthesis of the propargyl-isoindolinone core features an aldehyde–alkyne–amine (A3) coupling-based tandem strategy using methyl 2-formylbenzoate, primary aryl amine, and terminal alkyne under Cu(OTf)2 catalysis.

Rhodium-Catalyzed Synthesis of Chiral 3-Substituted Phthalides

The synthesis of phthalides 3 via the addition of arylboronic acids 2 to methyl 2-formylbenzoate 1 and lactonization is reported. Three sets of conditions were identified under ­palladium, platinum, and rhodium catalysis. EDG, EWG, and ortho substituents were all equally well tolerated on the boronic acid, although no electron-poor examples were reported. A rhodium(I)-catalyzed asymmetric version of the reaction using SPINOL ligand 7 was also reported to give chiral phthalides 4, although the enantio­induction was only moderate.

Tandem reversible addition–intramolecular lactonization for the synthesis of 3-functionalized phthalides

A new tandem process based on reversible nucleophilic addition and intramolecular lactonization of methyl 2-formylbenzoate leads to the efficient synthesis of 3-functionalized phthalides, which are important precursors for the synthesis of quinone skeletons via Hauser–Kraus annulation. The reactions are successfully carried out under mild conditions in single operations.

One-Pot Synthesis of Quinoline-Based Tetracycles by a Tandem Three-Component Reaction

A practical one-pot synthetic strategy for the efficient synthesis of a range of structurally interesting and bioactive quinoline-based tetracycles has been developed. A key step in the synthesis is a tandem three-component reaction of heteroaromatic amine, methyl 2-formylbenzoate and (t)butyl isonitrile, followed by TFA-mediated lactamization via intramolecular aminolysis of an adjacent ester. Results related to a kinase-panel screening for several selected compounds are also discussed in this article.

Synthesis and reactivity towards carbon monoxide of an optically active endo five-membered ortho-cyclopalladated imine: X-ray molecular structure of trans-(μ-Cl) 2[Pd(κ 2- C, N-( R)-C 6H 4-CH [dbnd]N-CHMe-Ph)] 2

( R)-1-Phenylethyl-benzylidene-amine ( 1) reacted with Pd(OAc) 2 in acetic acid at 60 °C under nitrogen affording the acetato-bridged dinuclear endo five-membered ortho-cyclopalladated compound (μ-OAc) 2[Pd(κ 2- C, N-( R)-C 6H 4-CH N-CHMe-Ph)] 2 ( 2) in 65% yield. Compound 2 was converted by a metathesis reaction with LiCl into the corresponding chloro-bridged dinuclear cyclopalladated compound (μ-Cl) 2[Pd(κ 2- C, N-( R)-C 6H 4-CH N-CHMe-Ph)] 2 ( 3). 1H NMR of CDCl 3 solutions of compounds 2 and 3 treated separately with py- d 5, ( R)-1-phenylethylamine and racemic 1-phenylethylamine were consistent with the endo cyclopalladated structure and the R absolute configuration of the chiral carbon atoms of compounds 2 and 3. Compounds 2 and 3 reacted with carbon monoxide in methanol affording, as major compounds, methyl 2-formylbenzoate (91% chemical yield) and the epimers of 3-methoxy-2-[( R)-1-phenylethyl]isoindolin-1-one (64% chemical yield) in ca. 20% diastereomeric excess, respectively. The trans isomer of compound 3 crystallized in the P2 1 monoclinic space group with a = 10.430(4) Å, b = 12.082(8) Å, c = 11.168(4) Å and β = 95.20(3)° and presented C–H⋯Cl intramolecular and C–H⋯Pd intermolecular non-conventional hydrogen bonds.

Asymmetric routes towards polyfunctionalized pyrrolidines: application to the synthesis of alkaloid analogues

The Mukaiyama aldol type condensation of t-butyldimethylsilyloxypyrrole 1b with methyl 2-formylbenzoate furnished the aldol adduct 9 with high yield and complete stereoselectivity. An erythro ( anti) configuration was established (X-ray) in sharp contrast with the reaction of 1b with aliphatic aldehydes. Simple chemical transformations were used to transform 9 into original phthalidopyrrolidine compound analogous of bicuculline alkaloids.

ChemInform Abstract: NOTE ON THE SYNTHESIS OF 3‐(ALKYL(ARYL)THIO)ISOINDOLINONES FROM METHYL 2‐FORMYLBENZOATE

Chemischer InformationsdienstVolume 16, Issue 36 Heterocyclic Compounds ChemInform Abstract: NOTE ON THE SYNTHESIS OF 3-(ALKYL(ARYL)THIO)ISOINDOLINONES FROM METHYL 2-FORMYLBENZOATE R. LIEBL, R. LIEBLSearch for more papers by this authorR. HANDTE, R. HANDTESearch for more papers by this author R. LIEBL, R. LIEBLSearch for more papers by this authorR. HANDTE, R. HANDTESearch for more papers by this author First published: September 10, 1985 https://doi.org/10.1002/chin.198536177AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume16, Issue36September 10, 1985 RelatedInformation