37784-67-1

Usage

Uses

Used in Pharmaceutical Industry:
Diethyl (3-thienyl)malonate is used as a key intermediate in the synthesis of various pharmaceuticals for its versatile reactivity and potential biological activities, contributing to the development of new drugs and treatments.
Used in Agrochemical Industry:
Diethyl (3-thienyl)malonate is utilized as a building block in the creation of agrochemicals, playing a crucial role in the development of effective and innovative products for agricultural applications.
Used in Organic Synthesis:
Diethyl (3-thienyl)malonate serves as a valuable intermediate in organic synthesis, enabling the production of a wide range of organic compounds for various industrial and research purposes.

InChI:InChI=1/C11H14O4S/c1-3-14-10(12)9(11(13)15-4-2)8-5-6-16-7-8/h5-7,9H,3-4H2,1-2H3

Upstream product

• 37784-63-7 ethyl-3 thiophene acetate 
• 95-92-1 oxalic acid diethyl ester 
• 10486-61-0 3-thienyl iodide 
• 105-53-3 diethyl malonate 
• 64-17-5 ethanol 
• 21080-92-2 2-(thiophen-3-yl)malonic acid 
• 872-31-1 3-Bromothiophene 
• 7787-70-4 copper(I) bromide 
• 21418-54-2 ethyl 3-thienyl-α-cyanoacetate 
• 13781-53-8 (thiophen-3-yl)acetonitrile 

Downstream Products

• 182952-28-9 2,3-Bis-ethoxycarbonyl-2,3-di-thiophen-3-yl-succinic acid diethyl ester 
• 182952-30-3 benzo[1,2-b;4,5-b']dithiophene-4,4,8,8-tetracarboxylic acid tetraethyl ester 
• 99727-96-5 2-allyl-3-methylthiophene 
• 21080-92-2 2-(thiophen-3-yl)malonic acid 

Relevant academic research and scientific papers

Enantioselective Desymmetrization of 2-Aryl-1,3-propanediols by Direct O-Alkylation with a Rationally Designed Chiral Hemiboronic Acid Catalyst That Mitigates Substrate Conformational Poisoning

Enantioselective desymmetrization by direct monofunctionalization of prochiral diols is a powerful strategy to prepare valuable synthetic intermediates in high optical purity. Boron acids can activate diols toward nucleophilic additions; however, the design of stable chiral catalysts remains a challenge and highlights the need to identify new chemotypes for this purpose. Herein, the discovery and optimization of a bench-stable chiral 9-hydroxy-9,10-boroxarophenanthrene catalyst is described and applied in the highly enantioselective desymmetrization of 2-aryl-1,3-diols using benzylic electrophiles under operationally simple, ambient conditions. Nucleophilic activation and discrimination of the enantiotopic hydroxy groups on the diol substrate occurs via a defined chairlike six-membered anionic complex with the hemiboronic heterocycle. The optimal binaphthyl-based catalyst 1g features a large aryloxytrityl group to effectively shield one of the two prochiral hydroxy groups on the diol complex, whereas a strategically placed "methyl blocker"on the boroxarophenanthrene unit mitigates the deleterious effect of a competing conformation of the complexed diol that compromised the overall efficiency of the desymmetrization process. This methodology affords monoalkylated products in enantiomeric ratios equal or over 95:5 for a wide range of 1,3-propanediols with various 2-aryl/heteroaryl groups.

Arylation of diethyl malonate and ethyl cyanoacetate catalyzed by palladium/di-tert-butylneopentylphosphine

α-Arylated carbonyl derivatives are important structural motifs in many natural products and pharmaceutically active compounds. Although arylation of simple monocarbonyl compounds is a well-established methodology, metal-catalyzed arylation of β-dicarbonyl derivatives is significantly more challenging. The ability of β-dicarbonyl anions to bind to palladium in a κ2-O,O mode, rather than the κ1-C-bound mode required for bond formation, often results in the deactivation of catalyst systems. The C-bound form of the enolate can be favored through the use of sterically demanding ligands. Herein, we report that the sterically demanding di-tert-butylneopentylphosphine (DTBNpP) ligand in combination with Pd(dba)2 provides an effective catalyst for the coupling of aryl bromides and chlorides with diethyl malonate. The Pd/DTBNpP system also catalyzes the coupling of aryl bromides with ethyl cyanoacetate.

Oxidative dimerization of diethyl 3-thienylmalonate by high valent metal salts. Synthesis of benzo[1,2-b:4,5-b']dithiophene derivatives

The oxidation of diethyl 3-thienylmalonate (1) by metal oxidants (Fe(ClO4)3, Mn(OAc)3, MnO2 and CuO) in various solvents at 60 °C affords dimerization products arising from side-chain and nuclear coupling of the intermediate delocalized malonyl radicals 6. Metal to sulphur binding is suggested to play a role in controlling the distribution of dimers 2-5. The higher thermodynamic stability of unsymmetric dimer 3, along with its oxidative intramolecular 1,6-cyclization to 4, allows to develop a new simple synthesis of benzo[1,2-b:4,5-b']dithiophene derivatives 15-18.

Cope Rearrangement in the Thiophene Series

The inability to observe Cope rearrangement at elevated temperature for diethyl α-allylphenylmalonate does not extend to the analogous systems resulting from replacement of the benzene ring by 2- and 3-thiophene nuclei.Thermal rearrangement of diethyl α-allyl-2-thienylmalonate (5) at 250-260 deg C for 12 h produces the expected Cope rearrangement product diethyl (3-allyl-2-thienyl)malonate (6) (49percent) accompanied by ethyl 6-carboethoxy-5,6-dihydro-4H-5-cyclopentathiopheneacetate (7) (28percent).The structural verification of 6 was obtained by degradation to 3-allyl-2-methylthiophene which was compared with an authentic sample obtained by synthesis.The structure of 7 was based on analogy.Similar results were observed with the 3-substituted analogues of 5, both diethyl (2-allyl-3-thienyl)malonate (14) and ethyl 4-carboethoxy-5,6-dihydro-4H-5-cyclopentathiopheneacetate (15) being formed.In this case the structure of 14 was verified by synthesis.Speculative mechanistic considerations are offered regarding the mode of transformation of 6 to 7 and 14 to 15.That the methine proton of the malonate substituent in 6 and 14 is involved in this transformation is seen by the inability of the appropriate methyl-substituted derivative of 6 to undergo thermal cyclization.

Chemical process

An improved process for the preparation of 3-substituted thiophenes. The thiophenes are useful for the preparation of penicillins and cephalosporins. The process is for the preparation of a thiophene of formula (I): STR1 where R1 represents a carboxylic acid group, or an ester or amide thereof or a nitrile group; R2 represents a group suitable for use as an α-substituent in the side-chain of a penicillin or cephalosporin; which comprises treating under basic conditions a compound of formula (II): STR2 wherein X represents halogen or optionally functionalized hydroxyl, Y represents halogen, hydroxyl, or alkoxy; with a source of nucleophilic sulphur ionically bound to a polymeric support.

Preparation of a 3-thienylmalonic acid and the corresponding diesters

Preparation of a 3-thienylmalonic acid or a diester thereof comprising reacting in a polar solvent in the presence of a copper (I) halide a thiophene compound of formula: STR1 wherein X=I or Br, R1 =H or a C1-4 alkyl group, R2 =H or a C1-2 alkyl group and R3 =H or a C1-2 alkyl group, with the proviso that R2 and R3 cannot be an alkyl group simultaneously, with a mono-deprotonated methylene compound of formula: STR2 wherein a cation is present and Z'=Z" is CN or COOR in which R is a C1-4 alkyl group, or Z'=CN and Z"=COOR' in which R' is a C1-2 alkyl group, followed by hydrolysis by methods known per se to get the corresponding free acid.

Process for the preparation of thiophenes

A process for the preparation of 3-substituted thiophenes which involves cyclization of a novel intermediate, avoids the use of previously employed expensive starting materials. The thiophenes are useful for the preparation of penicillins and cephalosporins. The process is for the preparation of a thiophene of formula (I): STR1 where R1 represents a carboxylic acid group, or an ester or amide thereof or a nitrile group; R2 represents a group suitable for use as an α-substituent in the side-chain of a penicillin or cephalosporin; which comprises treating a compound of formula (II): STR2 wherein X represents halogen or optionally functionalized hydroxyl, Y represents halogen, hydroxyl, or alkoxy; with a source of nucleophilic sulphur under basic conditions.