Mono bromoacetal

The substitution of chlorine by the direct action of bromine is rarely effected. Aluminium bromide, cupric bromide in alcoholic solution or boron tribromide under pressure, convert many alkyl chlorides into alkyl bromides. Mono-chloroacetic acid heated to 150° in a sealed tube with hydrobromic acid or potassium bromide yields mono-bromoacetic acid. 

Alkylation of 72 with ethyl bromoacetate using K2C03 as the base resulted in the O-, N-dialkylated derivative 105, whereas regioselective mono N-alkylation took place with ethyl iodide in the presence of NaH to give 106. Moreover, 72 smoothly added to methyl acrylate to give 107 (Scheme 7) <2003JHC789>. 

Another example with porphyrinic dipolar species uses pyridinium salt derivatives as precursors of porphyrinic pyridinium ylides (Scheme 18) <05TL5487>. The procedure involves the reaction of porphyrin 58 with methyl bromoacetate, in refluxing chloroform, to give pyridinium salt 59. The latter, in the presence of K2CO3, reacts with 1,4-benzoquinone to yield only the mono-addition compound 60. Notably, when the reaction was performed in the presence of DBU, bis-addition occurred and the porphyrinic dimer 61 was the only isolated addition product. 

When 2,2-disubstituted 1,3-dioxolanes were employed, mono- or poly-chlorination of the side chain was observed on the carbon atom a to the acetal grouping. Incidentally, it should be noted thatN-bromo-succinimide, N-chlorosuccinimide, and trichlorotetrahydrotriazine-trione were found to be effective for the preparation of bromoacetates from O-ethylidene derivatives this might be useful when O-benzyli-dene derivatives are not readily available, or when a problem arises due to the fact thatO-benzoyl groups are, in general, more difficult to remove than O-acetyl groups. 

Haloacetates. In alkaline solution lysine residues can be alkylated in the presence of iodo- or bromoacetate ions (118). Both mono- and di-carboxymethyl derivatives can be formed. Some of the characterized derivatives are listed at the end of Table VI. Number 25, t-CM-Lys-41-RNase, shows a very low activity when measured by a step 2 assay employing C > p as substrate. This same compound is active in the depolymerization of 5S RNA (119) but the evidence presented to show that it is not the result of contamination with native RNase-A can be interpreted to suggest the opposite. 

This method is suitable for the preparation of mono- and di-a-substituted /3-ketoesters. Bromoacetates fail in this reaction. Yields with ethyl a-bromopropionate are considerably lower (30-36% with capronitrile) however, ethyl esters are useful for higher-molecular-weight compounds whose sec-alkyl esters are cracked by distillation. With 3-pentyl a-bromopropionate, the yields are slightly higher (53-60% with capronitrile). Both aromatic and aliphatic nitriles are suitable benzonitrile gives yields comparable to those obtained with capronitrile. Alkyl substitution in the a- and /8-positions (cf. Note 4) of aliphatic nitriles lowers the yield to 29% and 38%), respectively 7-substitution has no effect. 

The limited knowledge of thermal behaviour of halogenated acids has been extended significantly by a pyrolysis (infrared laser-powered) and semiempirical study which has established that mono-, di- and tri-chloroacetic, trifluoroacetic, and bromoacetic acid eliminate HX and that both bromo- and iodo-acetic acid undergo C—X bond homolysis acetic acid undergoes decarboxylation and dehydration under the same conditions.46 The semiempirical calculations of corresponding activation energies are consistent with these conclusions. 

The processes involving the aziridine cycle are very diverse. For instance, reactions of alkylation by alkyl halogenides [63], bromoacetic acid derivatives [29, 30] and acetoxypropene [64], are known. The use of arylboronic acids for synthesis of TV-alkyl derivatives, e.g., compound 45, is described in [63] (Scheme 1.13). The one-step reaction at room temperature of aziridinyl ketones 46 with chloroacetamides 47 and sulfur in the presence of Et3N yields mono-thio-oxamidines 48 [65]. 

The first reported application of this reaction is described by A. N. Pudovlk et al.C 25) who reacted the ethyl esters of bromoacetic acid and chloroacetic acid with various phosphonate esters. His group used molar ratios of the phosphonate and the haloacetate, and obtained a mixture of the mono- and dl-carbethoxy alkylphosphonates. 

V-mono substituted or protected piperazines benzyl bromides, bromoacet-amides, a-bromo ketones11 pyridyl, benzothiazolyl [86, 1211... 

The synthesis of rac-versicolorin A (13) is shown in Scheme 2.18. Resorcinol (107) was MOM-protected and formylated to yield 108. Horner-Wadsworth-Emmons reaction with 109, followed by deprotection and reaction with ethyl bromoacetate gave, after hydrolysis, phenyl acetaldehyde 110. With TIPSOTf and triethylamine, cyclization occurred rapidly, followed by mono deprotection. 

The chelates are prepared in anhydrous DMF or DMSO by ionization of the desired number of hydroxyl groups of the sucrose molecule with stoichiometric cunounts of sodium hydride to form alcoholates which, with metal salts, give the chelates. The etherification of sucrose with alkyl halides or esterification with organic acids caus is hydrolysis. The hydrolysis or diether formation is avoided if sucrose chelate is etherified at moderate temperatures and with only a small excess of allyl halide or sodium bromoacetate, giving 55-69% mono- and 0-2% diallyl ethers respectively, 41-48% mono- and 4-7% dicarboxymethyl ethers of sucrose. 

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