Halogenation Processes

The fact that the bromine concentration remains at veiy low levels is important to the success of the allylic halogenation process. The allylic bromination of alkenes must... 

Electrophilic halogenation processes can involve conventional mechanisms with a carbocation intermediate, or pathways that are of the addition-elimination type. Sometimes the process does not go beyond the addition stage there are also examples of halodehalogenation in which the displaced halogen attaches elsewhere in the ring, as in the chlorination of 3-bromobenzo[fe]thiophene to give 2-bromo-3-chlorobenzo[6]thiophene as one of the products (73IJS233). 

Typical halogenation processes for making halobutyl rubbers involves the injection of chlorine or bromine into a solution of butyl rubber. The reactants are mixed vigorously in the halogenation reactor with a rather short resident time, typically less than 1 min, followed by the neutralization of the HC1 or HBr and removal of the unreacted halogen (13). The procedures of halogenation have been described in detail elsewhere (41,42). 

Importantly, this halogenation process can be extended to members of the disaccharide series, and the lactose, maltose, and cellobiose derivatives 61, 62, and 63 afford the crystalline a-glycosyl bromides 64,65, and 66 in almost quantitative yields (see Scheme 10).51 As these O-benzoylated oximes are... 

Other enzymes capable of halogenation processes include a bacterial esterase from Pseudomonas fluorescens (2316), acid phosphatases from the bacteria Shigella flexneri and Salmonella enterica ser. typhimurium (2317), a lactonohydrolase from Acinetobacter calcoaceticus F46 (2318), and hydroperoxide halolyse from the marine diatom Stephanopyxis turris (2319). The biosynthesis of the ubiquitous methyl halides seems to involve methyl transferase enzymes, which have been isolated and purified in the plant Brassica oleracea (S -adenosyl-L-methionine ... 

Harper DB (1995) The Contribution of Natural Halogenation Processes to the Atmospheric Halomethane Burden. In Grimvall A, de Leer EWB (eds) Naturally-Produced Organoha-logens. Kluwer, Dordrecht, p 21... 

Trans-halogenation processes are especially important for the preparation of iodo (except 5-iodo) pyrimidines. Chloro- and bromo-pyrimidines... 

Imidazoles and halogens form charge-transfer complexes, and also rather unstable N-halogeno derivatives which rearrange into G-halogeno products. AM lalogcnoimidazoles may be intermediates in G-halogenation processes. 

As with other halogenation processes, the monoiodination of imidazole has proved to be a difficult process. A number of recent approaches have shown some success. Thus, imidazoles can be monoiodinated at C-2 via the 2-lithio derivative or Grignard reagent. With iodine and iodic acid 5-chloro-l-methylimidazole was converted to a mixture of 12.8% of the 2,4-diiodo compound and 27.5% of the 4-iodo product. The previously undescribed 2-iodoimidazole (119) has been prepared in low yield by the sequence shown in Eq. (27). ... 

Theories and principles of various halogenation processes (including chlorination and chloramination) have been introduced in another chapter, entitled, Halogenation and Disinfection, in Volume 3 of this handbook series (1). This advanced chapter emphasizes the detailed technical information on the process equipment, various applications. 

The halogenation process may be regarded as a carbanion displacement reaction on a halogen molecule in equilibrium with the hypo-halite 18... 

As with other halogenation processes, the monoiodination of imidazole has proved to be a difficult process. A number of recent approaches have shown some success. Thus, imidazoles can be monoiodinated at C-2 via the... 

Figure 14 Biosynthesis of PKS-NRPS hybrid compounds in myxobacteria (b). Biosynthesis of chondramide D (34) in Chondromyces crocatus Cm c5. The DH domain from module 1 (marked with an asterisk) is most likely inactive. During the assembly of the chondramide backbone, an unusual extender unit - a /3-amino acid - is incorporated by NRPS module 6. The precursor is generated by the tyrosine amino mutase (TAM) CmdF, which converts L-tyrosine into R-/3-tyrosine (see box). The function of the terminal phosphoenolpyruvate synthase (PEP) domain is still unknown. Macrocyclization catalyzed by the TE domain yields chondramide C (40), which can be further transformed to the chlorinated derivative chondramide D (34). The halogenation process catalyzed by CmdE may also take place on the assembly line intermediate.

The use of solid catalysts in halogenation processes will avoid corrosion and disposal problems. Work-up procedures to isolate and recover the desired product will also be easier leading to simpler and cleaner process routes. In addition, the use of zeolites as the solid catalysts in nuclear aromatic halogenations might lead to enhanced yields of the para isomer, because of the shape selectivity of the zeolite. 

The fact that the Br2 concentration remains at very low levels is important to the success of the allylic halogenation process. The allylic bromination of alkenes must compete with polar addition of bromine via a bromonium ion intermediate. The reactions differ in their dependence on bromine concentration. The allylic substitution is one-half order in bromine, whereas the addition reaction follows a first- or second-order dependence on [Br2] (see Section 5.3). Therefore a low concentration of Br2 favors substitution over addition. 

Chlorination. A number of methods are available for organizing the material relating to halogenation processes, all of which are necessarily complex. Here, as in other chapters, the principal classification is based on the (halogenating) ag ts employed. The most important methods for preparing chlorine compounds are the following ... 

Although the efficiency of the reaction was poor due to the Wurtz coupling and the p-proton elimination reactions, the block copolymer was synthesized by this transformation mechanism with polydispersity around 1.1 (Scheme 28). Fortunately, the problem related to coupling reactions can be avoided by using Grignard intermediates. Additionally, the P-proton elimination can be achieved by the use of xylene dibromide in the halogenation process. Obviously, such difficulties led to poor transformation efficiency. 

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