3-Chloropropionyl Chloride

• CAT Number: R029801
• CAS Number: 625-36-5
• Molecular Formula: C3H4Cl2O
• Molecular Weight: 126.964
• Purity: ≥95%
• Synonyms: Propanoyl chloride, 3-chloro-
• Storage: Store at -20°C
• IUPAC Name: 3-chloropropanoyl chloride
• InChI: InChI=1S/C3H4Cl2O/c4-2-1-3(5)6/h1-2H2
• InChIKey: INUNLMUAPJVRME-UHFFFAOYSA-N
• SMILES: C(CCl)C(=O)Cl

Reference

[1]. Chemistry. 2018 Aug 9;24(45):11779-11784. doi: 10.1002/chem.201802208. Epub 2018 Jul 13.
Atom- and Mass-economical Continuous Flow Production of 3-Chloropropionyl Chloride and its Subsequent Amidation.
Movsisyan M(1), Heugebaert TSA(1), Roman BI(1), Dams R(2), Van Campenhout R(2), Conradi M(2), Stevens CV(1).
Author information: (1)Department of Green Chemistry and Technology, Ghent University, Coupure Links 653, 9000, Ghent, Belgium. (2)Materials Resource Division, 3M (Belgium) BVBA, Haven 1005, Canadastraat 11, 2070, Zwijndrecht, Belgium.
3-Chloropropionyl chloride is a chemically versatile building block with applications in the field of adhesives, pharmaceuticals, herbicides and fungicides. Its current production entails problems concerning safety, prolonged reaction times and the use of excessive amounts of chlorinating reagents. We developed a continuous flow procedure for acid chloride formation from acrylic acid and a consecutive 1,4-addition of hydrogen chloride generating 3-chloropropionyl chloride, as presented in this paper. Up to 94 % conversion was reached in 25 minutes at mild temperatures and pressures. This continuous flow method offers a safer alternative and is highly efficient in terms of consumption of starting product and shorter residence time. Valorization of this building block is exemplified by the synthesis of beclamide, a compound with sedative and anticonvulsant properties. Over 80 % conversion towards this drug was achieved in 1 minute in a continuous flow setup. Further research is needed to telescope the synthesis of 3-chloropropionyl chloride and subsequent beclamide formation without intermediate purification.
DOI: 10.1002/chem.201802208 PMID: 29879290

[2]. Arch Pharm (Weinheim). 1989 Sep;322(9):541-4. doi: 10.1002/ardp.19893220906.
Diethylaminopropionamido-hydroxy-anthraquinones as potential anticancer agents: synthesis and characterization.
Antonello C, Uriarte E, Palumbo M.
A number of new 9,10-anthracenediones were obtained, bearing one or two hydroxyl groups and one positively charged side chain at different positions of the aromatic ring system (compounds 1-5 in Chart 1). These derivatives resemble the anticancer agents mitoxantrone and ametantrone. The synthesis started from dihydroxy- or amino-hydroxy-9,10-anthracenediones, which were converted into the nitro-derivatives. After reduction to the corresponding amines and acylation with 3-chloropropionyl chloride, substitution with diethylamine led to the final diethylaminopropionamido derivatives. The new anthracenediones cause a quite relevant inhibition of cell growth in vitro and will be tested as possible anticancer agents.
DOI: 10.1002/ardp.19893220906 PMID: 2610587 [Indexed for MEDLINE]

[3]. Biotechnol Bioeng. 1990 Jul;36(3):219-23. doi: 10.1002/bit.260360302.
Macroporous and hydrophilic polymer resins modified with isothiocyanate groups for immobilization of enzymes.
Hasegawa M(1), Kitano H, Nishida R, Kobashi T.
Author information: (1)Department of Polymer Chemistry, Kyoto University, Kyoto, Japan.
Hydrophilic and macroporous polymer resins composed of glycerylmethacrylate, styrene, and divinylbenzene were quite easily modified with isothiocyanate groups using a Friedel-Crafts reaction with 3-chloropropionyl chloride and subsequent nucleophilic reaction with KSCN. Alkaline phosphatase and trypsin could be covalently bound to the isothiocyanate-carrying polymer resins, and the immobilized enzymes obtained were sufficiently active and stable due to a covalent bonding via a spacer group between the carrier resins and the enzymes and also due to a hydrophilic environment around the enzymes. A heterogeneity of the immobilized enzyme was taken into account to interpret the thermal denaturation process of the enzyme immobilized onto the resins.
DOI: 10.1002/bit.260360302 PMID: 18595071

[4]. J Med Chem. 1982 Feb;25(2):161-6. doi: 10.1021/jm00344a014.
Synthesis of pseudo cofactor analogues as potential inhibitors of the folate enzymes.
Temple C Jr, Bennett LL Jr, Rose JD, Elliott RD, Montgomery JA, Mangum JH.
Reaction of 5,6,7,8-tetrahydrofolic acid (THF,7) with phosgene, thiophosgene, and cyanogen bromide gave the bridged derivatives, 5,10-(CO)-THF (8), 5,10-(CS)-THF (9), and 5,10-(C = NH)-THF (11), respectively. Catalytic hydrogenation of 10-(chloroacetyl)folic acid (2) gave 5,10-(CH2CO)-THF (12). A similar reaction with 10-(3-chloropropionyl)folic acid (3) gave 10-(ClCH2CH2CO)-THF (14) rather than 5,10-(CH2CH2CO)-THF (13). In the catalytic hydrogenation of 10-ethoxalylfolic acid (5), the initial product 10-(EtO2CCO)-THF (22) rearranged readily to give 5-(EtO2CCO)-THF (21). Acylation of THF with chloroacetyl chloride gave a N5,N10-diacylated product (18 or 19), which could not be converted to 5,10-COCH2)-THF (17). Reductive alkylation of THF with glyoxylic acid and 5-hydroxypentanal, respectively, gave 5-(HO2CCH2)-THF (24) and 5-[HO(CH2)5]-THF (25). Reductive dialkylation of THF with formaldehyde gave 5,10-(CH3)2-THF (27), whereas glyoxal gave 5,10-CH2CH2)-THF (10). Also, both folic acid and 5-(CHO)-THF were reductively alkylated with formaldehyde to give 10-methylfolic acid (6) and 5-(CHO)-10-(CH3)-THF (28), respectively. These compounds were tested as inhibitors of the enzymes involved in folate metabolism and for activity against lymphocytic leukemia P388 in mice.
DOI: 10.1021/jm00344a014 PMID: 7057422 [Indexed for MEDLINE]

[5]. Mol Divers. 2003;7(2-4):185-98. doi: 10.1023/b:modi.0000006802.21361.29.
Microwave-enhanced liquid-phase synthesis of thiohydantoins and thioxotetrahydropyrimidinones.
Yeh WB(1), Lin MJ, Lee MJ, Sun CM.
Author information: (1)Laboratory of Combinatorial Drug Discovery, Department of Chemistry, National Dong Hwa University, Shou-Feng, Hualien-974, Taiwan.
An efficient, microwave-assisted method for the liquid-phase combinatorial synthesis of 3,5-disubstituted thiohydantoins and 3,5-disubstituted 2-thioxotetrahydropyrimidin-4-ones has been developed. In synthesizing thiohydantoins, Fmoc-protected amino acids were coupled with polymer support and then deprotected to give primary amines. While in synthesizing thioxotetrahydropyrimidinones, 3-chloropropionyl chloride was immobilized to the support and subsequently reacted with various amines to form secondary amines. The PEG bound primary/secondary amines then were incorporated with various isothiocyanates to give thiourea intermediates and concomitant cyclization/cleavage steps occurred under mild basic condition. The desired products were then liberated from the soluble matrix in good yield and purity. All reactions described here were performed under microwave irradiation.
DOI: 10.1023/b:modi.0000006802.21361.29 PMID: 14870850 [Indexed for MEDLINE]