Activation by chlorination

Kastnlg and his co-workers(2) appear to have been the first to report that metal acetylacetonates activated by chlorinated hydrocarbons are capable of acting as initiators for the emulsion polymerisation of butadiene. Unfortunately the polymerisation recipes and rates of polymerisation were not published, but the data given for the structure of the polybutadienes obtained indicate that some degree of stereoregulation can be effected by this type of initiating system. This conclusion has not been confirmed by subsequent investigations. 

Aminocephalosporanic acid (7-ACA) is a key intermediate for the synthesis of semisynthetic cephalosporin antibiotics. It is produced from the fermentation product cephalosporin C. Today, 7-ACA is mainly produced via a chemical method. In this process, highly purified cephalosporin C is required as a raw material. The carboxy and amino functions are protected with trimethylsilyl groups. The amide is activated by chlorination with phosphorous pentachloride. The reaction steps are carried out at -40 to -60 °C in chlorinated hydrocarbons as the solvent. After hydrolysis the 7-ACA is isolated. Because of the hazardous chemicals used, the aqueous phase has to be incinerated. 

In a water-free process in dichloromethane as the solvent, trimethylchlorosilane (3 mol per mol Ceph C) is used to protect the carboxy and amino functions with trimethylsilyl groups. N,N-dimethylaniline is used to bind the released HC1. The solution is cooled down to -40 °C to -60 °C and the amide is activated by chlorinating with phosphorous pentachloride humidity has to be avoided. After hydrolysis and phase separation 7-ACA is isolated by crystallization from the aqueous phase with high quality and yield. 

Derivatives of polyisobutylene (6. in Figure 9.1) offer the advantage of control over the molecular weight of the polyisobutylene obtained by cationic polymerization of isobutylene. Condensation on maleic anhydride can be done directly either by thermal activation ( ene-synthesis reaction) (2.1), or by chlorinated polyisobutylene intermediates (2.2). The condensation of the PIBSA on polyethylene polyamines leads to succinimides. Note that one can obtain mono- or disuccinimides. The mono-succinimides are used as... 

Organic fluorine compounds were first prepared in the latter part of the nineteenth century. Pioneer work by the Belgian chemist, F. Swarts, led to observations that antimony(Ill) fluoride reacts with organic compounds having activated carbon—chlorine bonds to form the corresponding carbon—fluorine bonds. Preparation of fluorinated compounds was faciUtated by fluorinations with antimony(Ill) fluoride containing antimony(V) haUdes as a reaction catalyst. 

DicblorobenzotnfIuoride. This compound is produced by chlorination of 4-chloroben2otrifluoride and exhibits sufficient activation to undergo nucleophilic displacement with phenols to form diaryl ether herbicides, eg, acifluorofen sodium [62476-59-9]. 

Peroxide-Ketazine Process. Elf Atochem in France operates a process patented by Produits Chimiques Ugine Kuhhnaim (PCUK). Hydrogen peroxide (qv), rather than chlorine or hypochlorite, is used to oxidize ammonia. The reaction is carried out in the presence of methyl ethyl ketone (MEK) at atmospheric pressure and 50°C. The ratio of H202 MEK NH2 used is 1 2 4. Hydrogen peroxide is activated by acetamide and disodium hydrogen phosphate (117). Eigure 6 is a simplified flow sheet of this process. The overall reaction results in the formation of methyl ethyl ketazine [5921-54-0] (39) and water ... 

The PMBs, when treated with electrophilic reagents, show much higher reaction rates than the five lower molecular weight homologues (benzene, toluene, (9-, m- and -xylene), because the benzene nucleus is highly activated by the attached methyl groups (Table 2). The PMBs have reaction rates for electrophilic substitution ranging from 7.6 times faster (sulfonylation of durene) to ca 607,000 times faster (nuclear chlorination of durene) than benzene. With rare exception, the PMBs react faster than toluene and the three isomeric dimethylbenzenes (xylenes). 

Manufacture. Trichloromethanesulfenyl chloride is made commercially by chlorination of carbon disulfide with the careful exclusion of iron or other metals, which cataly2e the chlorinolysis of the C—S bond to produce carbon tetrachloride. Various catalysts, notably iodine and activated carbon, are effective. The product is purified by fractional distillation to a minimum purity of 95%. Continuous processes have been described wherein carbon disulfide chlorination takes place on a granular charcoal column (59,60). A series of patents describes means for yield improvement by chlorination in the presence of dihinctional carbonyl compounds, phosphonates, phosphonites, phosphites, phosphates, or lead acetate (61). 

Catalytic Oxidation. Catalytic oxidation is used only for gaseous streams because combustion reactions take place on the surface of the catalyst which otherwise would be covered by soHd material. Common catalysts are palladium [7440-05-3] and platinum [7440-06-4]. Because of the catalytic boost, operating temperatures and residence times are much lower which reduce operating costs. Catalysts in any treatment system are susceptible to poisoning (masking of or interference with the active sites). Catalysts can be poisoned or deactivated by sulfur, bismuth [7440-69-9] phosphoms [7723-14-0] arsenic, antimony, mercury, lead, zinc, tin [7440-31-5] or halogens (notably chlorine) platinum catalysts can tolerate sulfur compounds, but can be poisoned by chlorine. 

Pyrolysis. Pyrolysis of 1,2-dichloroethane in the temperature range of 340—515°C gives vinyl chloride, hydrogen chloride, and traces of acetylene (1,18) and 2-chlorobutadiene. Reaction rate is accelerated by chlorine (19), bromine, bromotrichloromethane, carbon tetrachloride (20), and other free-radical generators. Catalytic dehydrochlorination of 1,2-dichloroethane on activated alumina (3), metal carbonate, and sulfate salts (5) has been reported, and lasers have been used to initiate the cracking reaction, although not at a low enough temperature to show economic benefits. 

Two approaches that have been investigated recently for disinfection are mixtures of bromine and chlorine, and mixtures containing bromide or iodide salts. Some evidence exists that mixtures of bromine and chlorine have superior germicidal properties than either halogen alone. It is believed that the increased bacterial activity of these mixtures can be attributed to the attacks by bromine on sites other than those affected by chlorine. The oxidation of bromide or iodide salts can be used to prepare interhalogen compounds or the hypollalous acid in accordance with the following reaction ... 

Replacement of the aromatic hydroxyl groups in isoproterenol by chlorine again causes a marked shift in biologic activity. 

Activity is also retained when the hydroxyl group at the 21 position is replaced by chlorine. Reaction of corticoid 44 with methanesulfonyl chloride proceeds preferentially at the 21-hydroxyl (45) due to the hindered nature of the 11-alcohol. Replacement of the mesylate by means of lithium chloride in DMF affords clobetasol propionate (46) a similar sequence starting with the 17- butyrate ester 47, via mesylate 48, should give clobetasone butyrate, (49) [11]. 

The neutron activation analysis of the polymer reveals that initiation is effected predominantly by chlorine atoms. No retardation or inhibition were detected,... 

Ion exchangers in general and cation resins in particular are liable to chemical attack by chlorine. The very small residual of chlorine in public supply (typically, 0.2mg/l) has only a mineral effect, but if more chlorine has been added it must be removed (e.g. with an activated carbon filter) before ion exchange. 

Sufficient activation was present in 5-ethylamino-2-oxoimidazolo [4,5-6]pyrazine (173) for it to be halogenated in the 6-position by chlorine and bromine in acetic acid or by sulfuryl chloride (69FRP1578366 71BRP1248146). The 2-oxo group could be replaced by chlorine (75KFZ10 76KFZ35). 

The optically active D- and L-em/rn.i-2-morpholmones 1 (only the d-erythro series is depicted) are efficiently brominated with (V-bromosuccinimide to afford the bromo derivatives 2 (X = Br) that serve as versatile precursors for electrophilic glycine templates which permit construction of either d- or L-a-atnino acids in high optical purity71. The corresponding chlorides 2 (X = Cl) are similarly obtained by chlorination of 1 with tert-butyl hypochlorite71. 

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