Chloroacetyl esters

Preparation of Derivatives. Enoate derivatives were prepared by Homer-Wittig reactions between aldehydes and the ethyl phos-phonate derived from the chloroacetyl ester of (3) in high E) selectivity (97 3). Ester derivatives were obtained by treating alcohol (3) with the corresponding carboxylic acid chloride. ... 

Conversion of disaccharide III.86 into glycosyl acceptor III.87 was achieved in 92% yield hy removal of the chloroacetyl ester with thiourea in pyridine-ethanol. Condensation of acceptor III.87 with imidate III.83 in the presence of trimethylsilyl triflate afforded the crystalline trisaccharide III.88 in 92% yield. Removal of the isopropylidene with aqueous acid followed hy selective benzoylation of C6 gave III.82 (90%, two steps). 

The mixture is reduced with sodium in t -PrOH to give the same proportions (87 13) of two alcohols 21 and 25. This thermodynamically controlled reduction is totally stereospecific, giving the equatorial alcohol in both cases. Presumably the equilibration of the ketone 24 is less successful because the large PhCMe2- group eclipses the carbonyl group when it is equatorial. The two alcohols are easily separated as their chloroacetyl esters. 

The preferred glycosylating synthon of i-lyxo configuration was the azide 69, obtained by nucleophihc displacement of 4-0-triflate with tetrabutyl-ammonium acetate, as shown in Scheme 11. Chloroacetyl ester 71 and tri-... 

Much of the chloroacetyl chloride produced is used captively as a reactive intermediate. It is useful in many acylation reactions and in the production of adrenalin [51-43-4] diazepam [439-15-5] chloroacetophenone [532-27-4] chloroacetate esters, and chloroacetic anhydride [541-88-8]. A major use is in the production of chloroacetamide herbicides (3) such as alachlor [15972-60-8]. 

Chloroacetate esters are usually made by removing water from a mixture of chloroacetic acid and the corresponding alcohol. Reaction of alcohol with chloroacetyl chloride is an anhydrous process which Hberates HCl. Chloroacetic acid will react with olefins in the presence of a catalyst to yield chloroacetate esters. Dichloroacetic and trichloroacetic acid esters are also known. These esters are usehil in synthesis. They are more reactive than the parent acids. Ethyl chloroacetate can be converted to sodium fluoroacetate by reaction with potassium fluoride (see Fluorine compounds, organic). Both methyl and ethyl chloroacetate are used as agricultural and pharmaceutical intermediates, specialty solvents, flavors, and fragrances. Methyl chloroacetate and P ionone undergo a Dar2ens reaction to form an intermediate in the synthesis of Vitamin A. Reaction of methyl chloroacetate with ammonia produces chloroacetamide [79-07-2] C2H ClNO (53). 

The electrophilic ring opening of iV-allyl HHT 53 with chloroacetyl chloride gave N-allyl- -chloromethyl-a-chloroacetamide 54, which was then alkylated with the diethyl ester of a-aminomethylphosphonic acid (AMPA) to generate the imidazolone 55. Subsequent hydrolysis of 55 gave GLYH3 (57). 

Thiazolopyridopyrimidines can be prepared directly from enamino esters such as 151 <2001H(55)115> (Equation 36 cf. Equation 29), or, alternatively, from piperidinones such as 152, thiourea, and chloroacetyl chloride (Scheme 43) <2001IJB213, 2002PS(177)45, 2006JHC75>. 

CH2F CH2 N-ftjX, chlorofluoroethane sulphur-containing compounds, e.g. CH2F CH2 Si2 esters of 1-alkylated fluoroacetic acids, CH-ft F C02iZ and CiZ iZ F C02B acetyl and chloroacetyl fluoride. 

Cyclization of a dipeptide having a hydroxylamine unit at the N-terminus is the second general method for the synthesis of 1-hydroxypiperazine-2,5-diones. Thus, Japanese workers have reported that the N-bromoacetyl derivatives (210) obtained from the corresponding dehydro amino acid esters, on treatment with hydroxylamine, give low yields of 1-hydroxy-3-alkylidenepiperazine-2,5-diones (211) (78BCJ550). The corresponding iodo compounds lead to better yields, whereas the chloroacetyl derivative does not cyclize under these conditions. 

The above observations have been confirmed and extended by Japanese workers (75BCJ2584). The N-bromoacetyl derivative (218) of an a-hydroxylamino ester, on treatment with ammonia in ethanol at room temperature, gave l-hydroxy-6-benzylpiperazine-2,5-dione (219). Under the same conditions, the chloroacetyl derivative gave only the 6-benzyli-denepiperazine-2,5-dione by prior elimination and rearrangement. Treatment of (218) with hydroxylamine gave the 1,4-dihydroxycompound (220). 

Chlorine Trifluoride Chlordacetic Acid Chloroacetic Acid, Ethyl Ester Chloroacetophenone Alpha-chloroacetophenone Omega-chloroacetophenone Chloroacetyl Chloride 5-Chloro-2-Aminotoluene... 

Chloroacetamide derivatives such as N,N-diallyl (5) and N-alkoxymethyl-N-2,6-diethylphenyl (<5) analogs are widely used as upland field herbicides. By modification of chloroacetamide structure, Fujinami et al. found that the N-chloroacetyl-N-phenylglycine esters (7) show varying degrees of inhibitory activity, in particular, against shoot growth of annual grasses 17). They developed Eq. 15 and 16 for the herbicidal activities of various esters where the aromatic substituents are fixed... 

Tadalafil (3, IC-351) was discovered at ICOS and is being developed and marketed as a joint venture with Eli Lilly, D-tryptophan methyl ester (21) was condensed with piperonal by means of trifluoroacetic acid and the C2 carbon of the indole adds to the resulting iminium ion to give a mixture of cis (3-carboline 22 and trans isomer 23 (Scheme 5). The desired cis isomer 22 can be isolated by chromatography or crystallization in 42% yield. Compound 22 was acylated with chloroacetyl chloride to... 

Two general syntheses of 3-pyrrolinones which utilize easily available starting materials are known. One involves acylation and cyclization of /3-aminoacrylates by reaction with chloroacetyl chloride, as shown in reaction (198). The condensation of /3-keto esters with ethyl glycinate (reaction 199) also appears to be a reasonably general route to 3-pyrrolinones. Other methods, which are summarized by Jones and Bean (B-77MI0610), lead to specialized products or require unusual starting materials. 

---