Bromoacetyl derivatives

A method for the preparation of bis(furazanoyl)- and bis(furoxanoyl)furoxans has been developed utilizing the nitrosation of the corresponding bromoacetyl derivatives 121. The resulting a-bromo-a-hydroximinoacetyl intermediates afforded the furoxans 122 on treatment with aqueous sodium carbonate (94IZV485, 94RCB445). An example is shown in Scheme 72. 

Ester group of l-(ethoxycarbonylmethyl)-7-aryl-5-oxo-1,2,3,5-tetrahydro-pyrido[l,2,3-i/e]quinoxaline-6-carboxamides was hydrolyzed and the 1-carboxymethyl moiety was converted to an aminocarbonylmethyl group with 1-methylpiperazine (01MIP12). Bromo atom of l-(2-bromoacetyl) derivatives was substituted by different amines. An amino group in the side chain attached to the position 1 of 7-aryl-5-oxo-l,2,3,5-tetrahydropyr-ido[l,2,3-i/e]quinoxaline-6-carboxamides was acylated, and terc-butoxycarbonyl protecting group of amino group was eliminated. 

Although the primary utility of active halogen compounds is to modify sulfhydryl groups in proteins or other molecules, the reaction is not totally specific. Iodoacetyl (and bromoacetyl) derivatives can react with a number of functional groups within proteins the sulfhydryl group of cysteine, both imidazolyl side chain nitrogens of histidine, the thioether of methionine, and... 

A bromoacetylated derivative of the nonsense codon UpGpA has been synthesized and used to label ribosomal proteins.103... 

An alternative way of making cephapirin is the acylation of 7-aminocephalosporanic acid by bromoacetyl bromide, which gives a bromoacetyl derivative (32.1.2.5), and which is then reacted with 4-mercaptopyridine in the presence of triethylamine, forming the desired cephapirin (32.1.2.4) [75-78]. 

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 third general method involves the cyclization of a linear dipeptide in which the C-terminal amino acid carries the N-hydroxy unit. This was the basis of a method described as far back as 1956 (56JCS4130), in which the bromoacetyl derivative (216) gave the 1-hydroxypiperazinedione (217) on treatment with ammonia. They have also described the formation of 1,4-dihydroxypiperazine-2,5-dione by treatment of (216) with hydroxylamine. 

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). 

Although it is more usual to obtain the halogenoacyl derivatives of pyrrole and indole by direct acylation (see Section 3.05.1.2.6), it is possible to carry out electrophilic halogena-tion of acylindoles <79HC(25-3)357). 3,4-Diacetyl-l,2,5-trimethylpyrrole has also been reported to react with phenyltrimethylammonium tribromide to give the 3,4-bis(bromoacetyl) derivative, which cyclizes in the presence of a zinc-copper catalyst to yield 4,5,6,7-tetrahydro-l,2,3-trimethyl-4,7-dioxoisoindole (74CC1034). 

In the 6j8-bromoacetyl derivative of 3,5a-cyclo-cholestan-6)S-oI, the 6)8-oxygen-19 carbon distance in the crystal is about 3.19 A (private communication from Prof. Dorothy Hodgkin, Oxford), (f. also H. R. Harrison, D. Crowfoot Hodgkin, E. N. Maslen and W. D. S. Motherwell. J. Chem. Soc. C, 1971, 1275). 

Produced as a minor product, together with compound 5. Isolated by chromatography. Isolated by crystallization. Produced together with 32% of a bromoacetyl derivative. 

The postexchange mixture in the tritium-labelling experiment has not been subjected to oxidation, and if the tritiated (saturated) B-ring product had been formed, it probably would not have undergone reoxidation and its bromoacetylated derivative has been separated from 148 in the course of its HPLC purification. 

An alternative method for preparing derivatives of bromoacetate involves using bromoacetyl bromide or bromoacetyl chloride. The synthesis of the N-bromoacetyl derivative of L-arginine methyl ester with bromoacetyl bromide was carried out by Liu (1967). The product N-bromoacetyl-L-arginine methyl ester was a successful affinity label for streptococcal proteinase. L-Arginine methyl ester dihydrochloride (780 mg 3 mmoles) was dissolved in 6 ml of ice-cold 1 N NaHCOj. Over a period of 20 min, freshly distilled bromoacetylbromide, 3... 

Bromoacetyl derivatives of free amino acids can be prepared in a comparable manner. Product in this case can be readily precipitated by acidification of the reaction mixture to pH 2.0 with 1 N HCl. 

An access to optically active P-hydroxy acids uses the bromoacetyl derivatives of chiral oxazolidin-2-ones to react with aldehydes. " 1,3-Diketones are obtained from reaction of a-haloketones with acyl cyanides. ... 

Hydroxymethyl phosphinate 105 was prepared in three steps from hydroxymethyl-//-phosphinic acid 115 [102]. //-Phosphinic acid 115 was silylated to give the P ° intermediate, which reacted in a silyl-Arbusov reaction with the bromoacetyl derivative of aspartic acid to give 116. A deprotective step using hydrogen afforded phosphinic acid 105. From intermediate 116, cyclic phosphinic acid 106 was also accessible in two steps. First, a 5-exo-tet cyclization under... 

During such a cycUzation of ester (308) followed by elimination, they also observed (208, 209) the formation of imidazolidone (310) (Scheme 61). The cyclization of bromoacetyl derivatives (309) finally... 

Figure 1. Conjugation of thiols to maleimides (pathway a) 2-pvridyldithio derivatives (pathway b, R3 = H) 3-nitro-2-pyridyldithio derivatives (pathway b, R3 = NOj), e.g. a Boc-S-(3-nitro-2-pyridylsulphenyl)cysteinyl-psptide or bromoacetyl derivatives (pathway cK...

Different 5-alkyl-2-formyI- and 5-alkyl-2-acetyl-selenophens have been synthesized as well as semicarbazones derived from them. From 2-acetylselenophen, 2-vinylselenophen epoxide has been prepared via the bromoacetyl derivative. In connection with investigations on the direction of enolization in /3-diketones of the selenophen series, compounds such as (663) and (664) have been synthesized. In connection... 

The A -bromo-, chloro-, and fluoro-acetyl derivatives of 2-amino-2-deoxy-D-glucose and -o-galactose have been prepared and tested for cytotoxic activity the per-O-acetylated A -bromoacetyl derivatives in either the glucose or galactose series were most effective against Friend erythroleukemia cells. A -nictotinoyl derivatives of 2-amino-2-deoxy-D-glucose and its ethyl a- and j8-pyranoside have been prepared. ... 

The low reactivity of the bromoacetyl derivatives is also sustained toward their reaction with the solvent. Thus, these reagents decompose slowly and are stable for long reaction periods the low reactivity secures the presence of the reagent for many hours. 

---