Halogenation Routes

Tetrabromination to give 169 (E = Br) can be effected in high yield by treating the tetraalkyl ethers of 4 with N-bromosuccinimide, while B,D-di-bromination of the A,C-dialkyl ether 180 (Y = Me = H = t-Bu  

Arduini, A. Pochini, A. Sicuri, A. R. Secchi, A. Ungaro, R. Gazz. Chim. Ital. 1994,124, 129. 

Vreekamp, R. H. Verboom, W. Reinhoudt, D. N. Reel. Trav. Chim. Pays-Bas 1996,115, 363. 

Timmerman, P., Ph.D. Thesis, Universiteit Twente, Enschede, The Netherlands, 1994 (a) p. 78 

Ohseto, F. Yamamoto, H. Matsumoto, H Shinkai, S. Tetrahedron Lett. 1995, 36, 6911. 

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Butadiene is an industrial chemical and is prepared by dehydrogena tion of butane Elimination reactions such as dehydration and dehydro halogenation are common routes to alkadienes... 

Vlayl fluoride [75-02-5] (VF) (fluoroethene) is a colorless gas at ambient conditions. It was first prepared by reaction of l,l-difluoro-2-bromoethane [359-07-9] with ziac (1). Most approaches to vinyl fluoride synthesis have employed reactions of acetylene [74-86-2] with hydrogen fluoride (HF) either directly (2—5) or utilizing catalysts (3,6—10). Other routes have iavolved ethylene [74-85-1] and HF (11), pyrolysis of 1,1-difluoroethane [624-72-6] (12,13) and fluorochloroethanes (14—18), reaction of 1,1-difluoroethane with acetylene (19,20), and halogen exchange of vinyl chloride [75-01-4] with HF (21—23). Physical properties of vinyl fluoride are given ia Table 1. 

Direct halogenation of S-hydroxyquiaoline has been used as a route to 5,7-dihalo derivatives. Compounds of this type reported iaclude... 

The introduction of tritium into molecules is most commonly achieved by reductive methods, including catalytic reduction by tritium gas, PH2], of olefins, catalytic reductive replacement of halogen (Cl, Br, or I) by H2, and metal pH] hydride reduction of carbonyl compounds, eg, ketones (qv) and some esters, to tritium-labeled alcohols (5). The use of tritium-labeled building blocks, eg, pH] methyl iodide and pH]-acetic anhydride, is an alternative route to the preparation of high specific activity, tritium-labeled compounds. The use of these techniques for the synthesis of radiolabeled receptor ligands, ie, dmgs and dmg analogues, has been described ia detail ia the Hterature (6,7). 

The route to 3-bromothiophene utilises a variation of the halogen dance technology (17). Preferably, 2,5-dibromothiophene [3141-27-3] is added to a solution of sodamide in thiophene containing the catalyst tris(2-(2-methoxyethoxy)ethyl)amine (l DA-1) (33) at temperatures marginally below reflux. On completion, quenching exothermically Hberates ammonia gas the organic phase is separated, washed, and distilled, and foremnning thiophene is recycled. Material of 97—98% purity is isolated. 

Acyl halides may also be added to ethylene ia the presence of aluminum chloride to form halogenated ketones. At low temperatures, ethylene reacts with halogens to yield dihaloethanes. At high temperatures, trichloroethylene and perchloroethylene are formed. The most profitable route for chloroethylene is via ethylene dichloride (see Chlorocarbonsandchlorohydrocarbons). 

The halogenation-dehydrohalogenation of ketones and their derivatives is the most widely applied method for the preparation of unsaturated ketones, and the different combinations of alternatives which exist for both steps extend the scope of this approach. Consequently, this route will be discussed in considerable detail. 

The formation of derivatives of this type by free-radical attack has been mentioned previously (see section E above). The most common route to vinylogous halo ketones is by halogenation of dienol acetates or ethers. Both free halogen and A -halo compounds may be employed, and this approach has frequently been used to obtain 6 (axial) halo compounds ... 

The success of the halo ketone route depends on the stereo- and regio-selectivity in the halo ketone synthesis, as well as on the stereochemistry of reduction of the bromo ketone. Lithium aluminum hydride or sodium borohydride are commonly used to reduce halo ketones to the /mm-halohydrins. However, carefully controlled reaction conditions or alternate reducing reagents, e.g., lithium borohydride, are often required to avoid reductive elimination of the halogen. 

Addition of hydrogen halide across fluoroalkenes and fluoroalkylalkenes is an important route to halogen-containing fluoroorganics Both lontc and free radical... 

Many reactions of fluorinated organics with metal halides result in the replacement of fluorine with halogen A general route to 1,1,1-trichloro- or tribromo-fluoroalkanes involves treating primary fluoroalkyl iodides with aluminum trichloride or aluminum tribromide [74], Benzylic [75, 76] or vinylic [72] fluorine can be exchanged for chlorine when treated with aluminum trichloride... 

The mtroducuon of a tnfluoromethanethio group into an aromatic nng has a synthetic importance The reaction of tnfluoromethanethio copper with aryl bro mides and iodides provides a convenient route to the synthesis of aryltn fluoromethane sulfides The reaction is not sensitive to the type of substituents or the aromahc nucleus Selectivity can be achieved accordmg to the type of halogen or the aromatic rmg, because iodides react at lower temperatures than bromides, whereas chlondes do not react [f J] (equation 12) (Table 5)... 

Codeposition of silver vapor with perfluoroalkyl iodides at -196 °C provides an alternative route to nonsolvated primary perfluoroalkylsilvers [272] Phosphine complexes of trifluaromethylsilver are formed from the reaction of trimethyl-phosphme, silver acetate, and bis(trifluoromethyl)cadmium glyme [755] The per-fluoroalkylsilver compounds react with halogens [270], carbon dioxide [274], allyl halides [270, 274], mineral acids and water [275], and nitrosyl chloride [276] to give the expected products Oxidation with dioxygen gives ketones [270] or acyl halides [270] Sulfur reacts via insertion of sulfur into the carbon-silver bond [270] (equation 188)... 

Reactivity and yields are greatly enhanced by the presence of 0.5-1% Na in the Li. The reaction is also generally available for the preparation of metal alkyls of the heavier Group 1 metals. Lithium aryls are best prepared by metal-halogen exchange using LiBu" and an aryl iodide, and transmetalation is the most convenient route to vinyl, allyl and other unsaturated derivatives ... 

Fonnation of C-X bonds is not normally a problem but the Grignaid route can occasionally be useful when normal halogen exchange fuls. Thus iodination of Me3(XH2CI cannot be achieved by reaction with Nal or similar reagents but direct iodinadon of the conesponding Grignaid effects a smooth conversion ... 

X = alkyl, H, halogen, etc. They are usually colourless, crystalline compounds with mp in the range 0-100° for X = H and 50-200° for X = halogen. Synthetic routes, and factors affecting the stability of the adducts have already been discussed (p. 165 and p. 198). In cases where diborane undergoes unsymmetrical cleavage (e.g. with NH3) alternative routes must be devised ... 

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