7283-96-7

Usage

Uses

Used in Pharmaceutical Industry:
2-Chloro-5-thiophenecarboxaldehyde is used as a key intermediate in the synthesis of various pharmaceutical compounds. It plays a crucial role in the development of 2-benzylidene-1-tetralone derivatives, which are evaluated as antagonists of A1 and A2A adenosine receptors. These receptors are significant targets for the treatment of various diseases, including neurodegenerative disorders, cardiovascular diseases, and cancer.
Used in Chemical Synthesis:
In the field of chemical synthesis, 2-Chloro-5-thiophenecarboxaldehyde serves as a valuable building block for the creation of complex organic molecules. It is particularly useful in the synthesis of 2-heteroaryl-α-methyl-5-benzoxazoleacetic acids and N,N′-bis[(E)-(5-chloro-2-thienyl)methylidene]ethane-1,2-diamine. These compounds have potential applications in various areas, such as pharmaceuticals, agrochemicals, and materials science.
Overall, 2-Chloro-5-thiophenecarboxaldehyde is a versatile compound with significant applications in the pharmaceutical and chemical synthesis industries. Its unique chemical properties and ability to form various derivatives make it an essential component in the development of new drugs and advanced materials.

InChI:InChI=1/C5H3ClOS/c6-5-2-1-4(3-7)8-5/h1-3H

Upstream product

• 96-43-5 2-thienyl chloride 
• 50-00-0 formaldehyd 
• 68-12-2 N,N-dimethyl-formamide 
• 93-61-8 N-methyl-N-phenylformamide 
• 17249-82-0 2-chloro-5-methylthiophene 
• 98-03-3 thiophene-2-carbaldehyde 
• 554-14-3 2-Methylthiophene 
• 23784-96-5 2-Chloro-5-(chloromethyl)thiophene 
• 636-72-6 2-thiophenemethanol 
• 3437-95-4 2-Iodothiophene 

Downstream Products

• 90797-71-0 (5-chloro-thiophen-2-ylmethyl)-pyridin-2-yl-amine 
• 141247-45-2 3-[1-(5-Chloro-thiophen-2-yl)-meth-(Z)-ylidene]-2-phenyl-chroman-4-one 
• 133531-43-8 5-pyridin-3-yl-thiophene-2-carbaldehyde 
• 943834-85-3 [3-(3-chlorophenyl)-1,2-benzisoxazol-5-yl](5-chloro-2-thienyl)methanol 
• 332099-38-4 ethyl 2-chlorothieno[3,2-b]pyrrole-5-carboxylate 
• 332099-40-8 2-chloro-4H-thieno[3,2-b]pyrrole-5-carboxylic acid 
• 756477-32-4 2-chlorothieno[2,3-c]pyridine 

Relevant academic research and scientific papers

Low cost preparation method of high purity 5-chlorothiophene-2-formyl chloride

The invention relates to a low cost preparation method of high purity 5-chlorothiophene-2-formyl chloride. According to the preparation method, 2-chlorothiophene and a formylation reagent carry out reactions to generate 5-chlorothiophene-2-formaldehyde, then 5-chlorothiophene-2-formaldehyde is oxidized by an oxidant to generate 5-chlorothiophene-2-formic acid, and finally 5-chlorothiophene-2-formic acid and an acyl-chlorination reagent carry out acyl-chlorination reactions to generate 5-chlorothiophene-2-formyl chloride. 5-chlorothiophene-2-formyl chloride can be used as a key intermediate inrivaroxaban preparation. The preparation method has the advantages of cheap and easily-available raw materials, simple technical route, low raw material cost, little discharge amount of wastewater, low salt content of wastewater, environmental friendliness, and high reaction selectivity. The purity of obtained 5-chlorothiophene-2-formyl chloride is high, and the industrial production of high purity rivaroxaban is promoted.

Systematic structure-activity relationship (SAR) exploration of diarylmethane backbone and discovery of a highly potent novel uric acid transporter 1 (URAT1) inhibitor

In order to systematically explore and better understand the structure-activity relationship (SAR) of a diarylmethane backbone in the design of potent uric acid transporter 1 (URAT1) inhibitors, 33 compounds (1a-1x and 1ha-1hi) were designed and synthesized, and their in vitro URAT1 inhibitory activities (IC50) were determined. The three-round systematic SAR exploration led to the discovery of a highly potent novel URAT1 inhibitor, 1h, which was 200-and 8-fold more potent than parent lesinurad and benzbromarone, respectively (IC50 = 0.035 μM against human URAT1 for 1h vs. 7.18 μM and 0.28 μM for lesinurad and benzbromarone, respectively). Compound 1h is the most potent URAT1 inhibitor discovered in our laboratories so far and also comparable to the most potent ones currently under development in clinical trials. The present study demonstrates that the diarylmethane backbone represents a very promising molecular scaffold for the design of potent URAT1 inhibitors.

Method for preparing 5-chlorothiophene-2-carboxylic acid through one-pot synthesis

The invention relates to a method for preparing 5-chlorothiophene-2-carboxylic acid through one-pot synthesis. The method comprises the following steps: leading or adding a chlorinated reagent into 2-thiophenecarboxaldehyde for heat insulation reaction, so as to obtain an intermediate 5-chlorine2-thiophenecarboxaldehyde after the reaction is completed, wherein the intermediate 5-chlorine2-thiophenecarboxaldehyde is directly used for the next reaction without separation; slowly dropping the intermediate 5-chlorine2-thiophenecarboxaldehyde into pre-cooled caustic soda liquid, controlling the reaction temperature to be not higher than 30 DEG C, cooling after the dropping is completed, slowly leading chlorine into the pre-cooled caustic soda liquid for heat insulation reaction after the leading of the chlorine is completed, cooling to 5 DEG C after a center control reaction is completed, adding sodium sulfite for quenching, adding a solvent for extraction and impurities elimination, regulating the pH value of a water phase with concentrated hydrochloric acid, performing suction filtration, recrystallizing a filter cake, and drying, so as to obtain an target compound. According to the method, the defects of the prior art of being high in raw materials, complex in operation and more in three wastes are overcome; the provided method for synthesizing 5-chlorothiophene-2-carboxylic acidis suitable for industrial production.

The Hydrazine–O2 Redox Couple as a Platform for Organocatalytic Oxidation: Benzo[c]cinnoline-Catalyzed Oxidation of Alkyl Halides to Aldehydes

An organocatalytic oxidation platform that capitalizes on the capacity of hydrazines to undergo rapid autoxidation to diazenes is described. Commercially available benzo[c]cinnoline is shown to catalyze the oxidation of alkyl halides to aldehydes in a novel mechanistic paradigm involving nucleophilic attack, prototropic shift, and hydrolysis. The hydrolysis and reoxidation events occur readily with only adventitious oxygen and water. A survey of the scope of viable substrates is shown along with mechanistic and computational studies that give insight into this mode of catalysis.

Sodium hypochlorite pentahydrate (NaOCl·5H2O) crystals; An effective re-oxidant for TEMPO oxidation

The novel oxidant of sodium hypochlorite pentahydrate (NaOCl·5H2O), which is now available for industrial and laboratory use has several advantageous properties. The crystalline material has 44% of NaOCl, contains minimal sodium hydroxide and sodium chloride, and the aqueous solution indicates pH 11-12. Herein, NaOCl·5H2O crystals are examined for use as an oxidant for primary and secondary alcohols, with or without nitroxyl radicals, in the presence or absence of phase-transfer catalysts. The pentahydrate crystals alone (without nitroxyl radicals) demonstrate a powerful oxidizing ability, converting secondary alcohols to the corresponding ketones. In the presence of TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl) or 1-Me-AZADO (1-methyl-2-azaadamantane N-oxy radical), sterically hindered secondary alcohols are oxidized without pH adjustment. A proposed mechanism for the oxidation is discussed.

PROCESS FOR THE PREPARATION OF RIVAROXABAN

Disclosed is a process for the preparation of rivaroxaban and purifying rivaroxaban.

Continuous flow magnesiation of functionalized heterocycles and acrylates with TMPMgCl·LiCl

A flow procedure for the metalation of functionalized heterocycles (pyridines, pyrimidines, thiophenes, and thiazoles) and various acrylates using the strong, non-nucleophilic base TMPMgCl·LiCl is reported. The flow conditions allow the magnesiations to be performed under more convenient conditions than the comparable batch reactions, which often require cryogenic temperatures and long reaction times. Moreover, the flow reactions are directly scalable without further optimization. Metalation under flow conditions also allows magnesiations that did not produce the desired products under batch conditions, such as the magnesiation of sensitive acrylic derivatives. The magnesiated species are subsequently quenched with various electrophiles, thereby introducing a broad range of functionalities. Go with the flow: Flow conditions allow a practical metalation of functionalized heterocycles and various acrylates in the presence of the base TMPMgCl·LiCl (TMP=2,2,6,6-tetramethylpiperidyl). More convenient temperatures and very fast reaction times can usually be achieved by applying the flow conditions. Sensitive acrylic derivatives can be magnesiated under flow conditions. Furthermore, the flow reactions are readily scalable without further optimization.

Chemistry of polyhalogenated nitrobutadienes, part 11: Ipso-formylation of 2-chlorothiophenes under Vilsmeier-Haack conditions

The regioselective ipso-formylation of electron-rich, 3,4-push-pull- substituted 2-chlorothiophenes under Vilsmeier-Haack conditions was performed in good yields. The synthetic scope of this new reaction was explored using various halothiophenes, chloroanilines, and 1-methyl-3-chloroindole. In comparison with their structural C-H analogs the chlorinated thiophenes, anilines, and the indole proved to be less reactive toward electrophilic attack by chloromethyleniminium salts.

Modulating reactivity and diverting selectivity in palladium-catalyzed heteroaromatic direct arylation through the use of a chloride activating/blocking group

(Chemical Equation Presented) Through the introduction of an aryl chloride substituent, the selectivity of palladium-catalyzed direct arylation may be diverted to provide alternative regioisomeric products in high yields. In cases where low reactivity is typically observed, the presence of the carbon-chlorine bond can serve to enhance reactivity and provide superior outcomes. From a strategic perspective, the C-Cl bond is easily introduced and can be employed in a variety of subsequent transformations to provide a wealth of highly functionalized heterocycles with minimal substrate preactivation. The impact of the C-Cl functional group on direct arylation reactivity has also been evaluated mechanistically, and the observed reactivity profiles correlate very well with that predicted by a concerted metalation-deprotonation pathway.

PYRROLIDINE CARBOXAMIDE COMPOUNDS

Pyrrolidine carboxamide compounds are provided. Some such pyrrolidine carboxamide compounds include agonists of sst4 which may be useful for the treatment and prevention of pain and inflammatory disorders.