α-Halo carboxylic acids and esters are organic compounds with the respective formulas RCHXCO2H and RCHXCO2R' where R and R' are organic substituents. The X in these compounds is a halide, usually chloride and bromide. These compounds are often used as intermediates in the preparation of more elaborate derivatives. They are often potent alkylating agents. The mono halide derivatives are chiral.
Preparation edit
They are often prepared by reaction of the acid or the ester with halogen:
- RCH2CO2R' + Cl2 → RCHClCO2R' + HCl
A related method is the Hell-Volhard-Zelinsky halogenation.
Amino acids are susceptible to diazotization in the presence of chloride, a process that affords chiral 2-chloro carboxylic acids and esters.[1]
Reactions edit
Consistent with these compounds being alkylating agents, the α-halide is readily substituted, e.g. by azide.[2] Similarly, the α-bromocarboxylic acid undergo nucleophilic substitution with ammonia to give the amino acid,[3]
The Darzens reaction involves a ketone or aldehyde with an α-haloester in the presence of a base to form an α,β-epoxy ester, also called a "glycidic ester".[4] The reaction process begins with deprotonation at the halogenated position. In a related reaction, α-halo carboxylic esters can be reduced by lithium aluminium hydride to the α-halo alcohols, which can be converted to the α-epoxides.[5]
α-Halo-esters can be converted to vinyl halides. upon reaction with ketones and chromous chloride.[6]
Applications edit
A prominent α-halo carboxylic acid is chloroacetic acid, which is used to produce carboxymethyl cellulose, carboxymethyl starch, as well as several phenoxy herbicides.[7] 2,2-Dichloropropionic acid ("Dalapon") is an herbicide.[8]
Reference edit
- ^ Koppenhoefer, Bernhard; Schurig, Volker (1988). "(S)-2-Chloroalkanoic Acids of High Enantiomeric Purity from (S)-2-Amino Acids: (S)-2-Chloropropanoic Acid". Organic Syntheses. 66: 151. doi:10.15227/orgsyn.066.0151.
- ^ Roy, Patrick; Boisvert, Michel; Leblanc, Yves (2007). "Preparation of Substituted 5-Azaindoles: Methyl 4-Chloro-1H-Pyrrolo[3,2-C]Pyridine-2-Carboxylate". Organic Syntheses. 84: 262. doi:10.15227/orgsyn.084.0262.
- ^ McMurry J (1996). Organic chemistry. Pacific Grove, CA, USA: Brooks/Cole. p. 1064. ISBN 978-0-534-23832-2.
- ^ Newman, M. S; Magerlein, B. J (1949). "The Darzens Glycidic Ester Condensation". Organic Reactions. 5 (10): 413–440. doi:10.1002/0471264180.or005.10.
- ^ Koppenhoefer, Bernhard; Schurig, Volker (1988). "(R)-Alkyloxiranes of High Enantiomeric Purity from (S)-2-Chloroalkanoic Acids Via (S)-2-Chloro-1-Alkanols: (R)-Methyloxirane". Organic Syntheses. 66: 160. doi:10.15227/orgsyn.066.0160.
- ^ Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, p. 1382, ISBN 978-0-471-72091-1
- ^ Koenig, Günter; Lohmar, Elmar; Rupprich, Norbert (2005). "Chloroacetic Acids". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a06_537. ISBN 978-3527306732.
- ^ Samel, Ulf-Rainer; Kohler, Walter; Gamer, Armin Otto; Keuser, Ullrich (2005). "Propionic Acid and Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a22_223. ISBN 978-3527306732.