Chloromethyl ketones

Further chlorination of the chloromethyl ketone gives the corresponding trichloromethyl ketone which then undergoes hydrolysis to form chloroform... 

BENZYL CHLOROMETHYL KETONE (2-Propanone, l-chloro-3-phenyl-)... 

This method is general for chloromethyl ketones. Yields of 75-85% may be obtained using hydrocinnamoyl chloride or diphenylacetyl chloride. 

Benzyl chloromethyl ketone has been prepared by the reaction of diazomethane with phenylacetyl chloride. The method of Clibbens and Nierenstein, in which one equivalent of diazomethane is added to the acyl chloride and the chloromethyl ketone obtained directly, could not be duplicated by Bradley and Schwarzenbach or by the submitters. 

Chemical Designations - Synonyms Phenacyl Chloride omega-Chloroacetophenone alpha-Chloroacetophenone Phenyl Chloromethyl Ketone Tear Gas Chloromethyl Phenyl Ketone Chemical Formula CeHjCOCHjCl. 

Bhmingham Metal Company Ltd., 207 Bis(2-chloroisopropyl) ether, 25 Bis(chloromethyl) ether, 25 Bis(chloromethyl) ketone, 25 Bis(2-EthyUiexyl) phthalate, 25 Bismuth and Bismuth Compounds, 25 Bismuth Institute, 256 Bismuth telluride, 26 Bisphenol-A, 26 Bithionol, 26 Bitmac Ltd., 207, 236 Bitoscanate, 26 Bitoumina SA, 167... 

Tosyl-L-phenylalanine chloromethyl ketone (TPCK) specifically inhibits chymotrypsin by covalently labeling His ". 

Substitution of a dipeptide unit by a cychc dipeptide derivative within a peptide chain can induce certain conformational restraints that may alter the biological response via changing receptor selectivity. A facile procedure for synthesis of pyrazinone ring-containing opioid mimetics [21] has been elaborated, based on the cycHzation of readily available dipep-tidyl chloromethyl ketones [22] (Scheme 6). This method affords 2(IH)-pyrazinone derivatives containing substituents with desired functional groups at positions 3 and 6 in high yield. 

It has been shown that the stereochemistry of starting dipeptidyl chloromethyl ketones does not influence the cycHzation reaction, but the chlorine... 

A group of peptide derivatives such as peptide arginals and boronic acid peptide derivatives belong to another class of reversible thrombin inhibitors. One such inhibitor is PPACK (D-Phe-Pro-Arg chloromethyl ketone), which functions as a powerful irreversible thrombin inhibitor by alkylating the histidine residue at the catalytic site of thrombin (58). It, however, is unstable in neutral solution, as it undergoes cyclization and inactivation. However, the D-methyl derivative of D-Phe-Pro-Arg-H (D-Mephe-Pro-Arg-H) called efegatran, with a molecular mass of 515 Da, is a stable selective reversible inhibitor of thrombin with a K. of approximately 100 nM. The basic amino terminus in this compound is responsible for promoting the specificity toward thrombin (63). 

The addition of halomethyl metal reagents provides another Darzens-like route to aziridines <06JOC9373>. Reaction of ICH2C1 with MeLi generates a chloromethyllithium reagent, which then adds to the inline 74. A subsequent intramolecular /V-alkylation provides the aziridine 75. The isolation of a chloromethyl ketone byproduct demonstrated that the chloromethyllithium reagent is operative as opposed to a carbene. 

More specific evidence came from affinity labeling with molecules which could react with specific amino acid group sat or adjacent to the substrate site. These labels were substrate analogues and competitive inhibitors. Substituted aryl alkyl ketones were used. TV-p-toluene-sulphonyl-L-phenylalanine chloromethyl ketone (TPCK) blocked the activity of chymotrypsin. Subsequent sequence analysis identified histidine 57 as its site of binding (see Hess, 1971, p 213, The Enzymes, 3rd ed.). Trypsin, with its preference for basic rather than aromatic residues adjacent to the peptide bond, was not blocked by TPCK but was susceptible to iV-p-toluenesulphonyl-L-lysine chloromethyl ketone (TLCK) (Keil, ibid, p249). 

Fig. 10.9. Stereo view of a 13-mer chloromethyl ketone bound to the active site. The electron density of the peptide directs to the propeller.

The chloromethyl ketone-based inhibitor-complex crystal structures suggested the strand E993-P996 as a recognition strand for the unprimed-substrate residues. 

This ceramide-mediated apoptosis was shown to be inhibited by the simultaneous addition of PKC activators (Ni et at, 1994 Obeid et al, 1993), implying that PS may activate the ceramide-mediated apoptotic pathway. However, the inhibitors of interleukin-1 converting enzyme (ICE)-like proteases (Caspase), such as tosyl-L-lysine chloromethyl ketone (TLCK), and tosyl-L-phenylalanine chloromethyl ketone (TPCK) which inhibit ceramide-mediated apoptosis, had no effect on PS-induced apoptosis (Figure 4). Thus, PS-induced apoptotic pathway appears to be distinct from that mediated by ceramide. Further studies are required to clarify the molecular mechanisms underlying the PS-induced apoptosis. 

Synonyms AI3-52322 BRN 0507950 CAP CAP Caswell No. 179C CCRIS 2370 Chemical mace 1-Chloroacetophenone 2-Chloroacetophenone Q-Chloroacetophenone Chloromethyl phenyl ketone 2-Chloro-l-phenylethanone CN EINECS 208-531-1 EPA pesticide chemical code 018001 Mace NC1-C55107 NSC 41666 Phenacyl chloride Phenyl chloromethyl ketone Tear gas UN 1697. 

Phenyl chloromethyl ketone, see a-Chloroacetophenone 1,4-Phenylenediamine, see p-Phenylenediamine /72-Phenylene dichloride, see 1,2-Dichlorobenzene... 

Reaction of a-chloromethyl ketones with (3-ketoesters and ammonia to assemble pyrroles. 

The active-site-directed inhibitor tosylphenylalanine chloromethyl ketone that specifically and irreversibly inhibits chymotrypsin. This chloroketone inhibitor relies on its toluene sulfonyl (or tosyl) group for binding into the aromatic binding pocket of chymotrypsin s active site. Inactivation occurs by alkylation of histidine-57 (pseudo-first order rate constant 0.2 min ). See Chymo-trypsin... 

Alkylation of sodium tolylsulhnate with bromomethyl or chloromethyl ketones (la-c) under reflux for 2 h in ethanol gave 3-keto sulfones (2a-c) in 62-90% yields after crystallization. (Adapted from Swenson et ah, 2002)... 

Synonyms 2-Chloro-l-phenylethanone phenacyl chloride phenyl chloromethyl ketone tear gas chemical Mace... 

The C=C bond in a 5-(alkylidene)oxazoline 644 is activated for electrophilic reactions similar to that in analogous vinyl acetates. Rohm Haas researchers exploited this property to prepare chloromethyl ketone fungicides 646 (Scheme 8.203). The overall process constitutes an indirect chlorination of a-amido ketones since the 5-(vinylidene)oxazolines were prepared from a-amido ketones. 

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