Haloacetyl, reactions

A three-stage procedure is more versatile and gives higher yields. In this method (Method B), the 2-aminobenzophenone is treated with an a-haloacetyl halide and the resulting haloacetamide 5 converted into an aminoacetamide 6 by reaction with ammonia. Cyclization to the benzo-diazepinone 7 occurrs readily. In some cases the intermediates 5 and 6 are not isolated selected examples are given.193 94... 

Reaction of ot-haloacetyl bromides with amides in the presence of strong acids... 

Haloacetyl Method The haloacetyl method uses supports that contain lodoacetyl or bromoacetyl groups for the immobilization of ligands through sulfhydryl residues. These supports are usually prepared via the reaction of an amine-containing material with iodoacetic or bromoacetic acid in the presence of ethyldimethylaminopropyl carbodii-mide (EDC) at pH 4 to 5. EDC reacts with the carboxylic acid in iodo- or bromoacetic acid... 

Numerous researchers have employed thiols as weak bases in the thioalkylation reaction to ligate unprotected peptides with a haloacetyl group to form thioethers at pH 7 8.5[90 91 131-133 or thioesters at acidic to basic conditions. 108"110 Of these two reactions, thioether formation is often the choice because thioesters suffer from instability in aqueous basic conditions. Haloacetyl derivatives, either as carboxylic acids or active esters, can be attached to either the N-terminal or side-chain amines during the stepwise solid-phase synthesis of either the peptide or the core and are stable to either HF or TFA cleavage conditions. Capping an amino group with a chloroacetyl group is compatible with Fmoc chemistry when used at a terminal step. 

In addition, the reaction product of an amino acid with an affinity label of the haloacetyl type is converted by acid hydrolysis to a carboxymethylamino acid derivative many carboxymethylamino acids are well characterized and therefore readily identifiable in modified enzymes. Haloacetyl derivatives of cysteine, lysine, histidine, methionine, glutamate, aspartate, and tyrosine have been re-... 

A Haloacetyl oxazolidinones form suitable enolate partners in aldol reactions, although complete aldehyde conversion requires the use of a slight excess of imide. Nucleophilic azide displacement of a-halo-P-hydroxy syn aldol adducts affords the corresponding anti a-amino- 3-hydroxy compounds. ... 

Chiral alcohol 73 was synthesized using the Evans aldol reaction and provided the syn-selective aldol adduct (95 5) in 52% yield in the haloacetyl aldol reaction during the total synthesis of (-)-clavosolide B. The chlorine atom was removed by treatment of Zn/NH4C1 in methanol, providing an additional example of an acetate aldol equivalent. 

Martins et al. [202] prepared 3-haloacetyl-4-methylquinolines 110 in good yield via the reaction of 4-alkoxy-3-al-ken-2-ones with 2-aminoacetophenone in the presence of IL and 4-toluene sulfonic acid under microwave irradiation... 

Alternative routes to labeled anri-/3-hydroxy-a-amino acids of the a//o-threonine type are described in Section 11.3.9. They involve aldol reactions of haloacetyl-Evans and -Oppolzer auxiliaries to give iyn-/3-hydroxy-a-halo derivatives, whose a-halo groups are then inverted by nucleophilic displacement with azide ion. ... 

Chiral a-unsubstituted a,)8-unsaturated, isotopically carbon-labeled imides or esters (such as 249 above) needed as starting materials for such applications are best prepared by Horner-Wadsworth-Emmons reaction of e.p. (7 )-or-(5)-A-diethylphosphonoacetyl 4-substituted l,3-oxazolidin-2-ones or bornane-10,2-sultams or of (1R,2S,3R)/ (15,2R,35)-3-[A-phenylsulfonyl-A-(3,5-dimethylphenyl)amino]bornyldiefhylphosphono-acetates (e.g., 252) with aldehydes For purposes of isotopic synthesis, labels could be incorporated either via the haloacetyl group or the aldehyde component, or both, as suggested in Figure 11.87. Entities of the 249-type are also accessible through aldol reaction of the respective homochiral acetyl derivatives 253 with aldehydes, (9-acetylation of the resultant diastereomeric )8-hydroxy intermediates 254 and elimination of HO Ac upon treatment with Both methods avoid the separate preparation of labeled... 

Shin, C., K. Nanjo, and J. Yoshimura Cyclisation Reaction of N-(Haloacetyl)- or N-(Phtaloylglycyl)hydroxyaminoacid Esters with Ammonia. Chemistry Letters 1973, 1039. 

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