Polyhalo compounds

A search has not been made for products of displacement of halogen from the benzo-ring in polyhalo compounds, but it is clear that the major mono-substitution occurs in the azine ring. For example, 2,6- and 2,7-dichloroquinoxalines give 70-80% of the 2-amination product with )S-diethylaminoethylamine (150°, 2 hr) or y-(l-piperidyl)-propylamine (220°, 2 hr). 2,3,6-Trichloroquinoxaline gives with... 

Whereas simple haloalkanes play a very important role in synthetic and mechanistic organic chemistry in the ground state, the interest in excited-state reactions centres more on polyhaloalkanes and on vinyl or aryl halides. Chloromethane absorbs only in the far ultraviolet (X-, . 173 nml, but ionger-wavelength absorption occurs for bromo- or iodo-cornpounds (CH, has A, 258 nrn and for polyhalo-compounds (iodoform, CHIj, has A, 349 nm and is coloured yellowi. 

Trichlorosilane in combination with a tertiary amine has been used previously to reduce polyhalo compounds. Both reductions are believed to involve the trichlorosilyl anion, which is isoclcctronic with phosphines. 

All these reactions proceed most likely by initial activation of the iron(0) species by a ligand exchange with the activating additives, such as amines, benzonitrile or DMF (Fig. 7). Thus generated mononuclear iron complexes bearing a labile ligand are activated to form coordinatively unsaturated iron complexes 37A. These species reduce the polyhalo compounds to radicals 38A, which add to olefins 30 or 33. 

Leonel, E., Paugam, J.P., Condon-Gueugnot, S. and Nedelec, J.-Y. (1998) Cyclopropane formation by electroreductive coupling of activated olefins and gem-polyhalo compounds. Tetrahedron 54,3207-3218. 

Reactivity in polyhalo compounds. Regioselective substitutions in di- and trihalogenopyrimidines can be achieved in many cases. Chloro, bromo, and iodo substituents undergo aminolysis at approximately the same rates, whereas a fluoro substituent reacts 60200 times faster. 4(6)-Halo substituents react up to 10 times faster than 2-halo substituents. Electron-donating substituents (e.g., Me, Ph, OMe, NMe2) decrease the rate of aminolysis, whereas electron-withdrawing substituents (Cl, CF3, N02) have the opposite effect. 

Hence, in polyhalo compounds such as 2,4,6-trichloropyrimidine, each successive chlorine atom is replaced more slowly than the last because the groups introduced (e.g., NH2) partially cancel the activating effect of the annular... 

A search has not been made for products of displacement of halogen from the benzo-ring in polyhalo compounds, but it is clear that the major mono-substitution occurs in the azine ring. For example,... 

Reductions. The combination of trichlorosilane and tertiary amines (tri-n-propylamine, tri-n-butylamine used for the most part) has been used by Benkeser to effect some interesting reductions. Thus polyhalo compounds are reduced cleanly and selectively by this combination 1... 

Achieving a selective coupling reaction involving just one particular halogen in a polyhalo-compound can be very useful synthetically. This can take two main forms - competition between identical halogens and between different halogens. 

Nevertheless, if the reactions are conducted carefully, certain functional reagents can be prepared. 1,1-Di- or polyhalo compounds usually give no well-defined products with Mg metal they may even cause explosions (see, however, the exception of the dihalometh-anes, above). 

The tributyltin hydride-mediated carbon-carbon bond formation via radical addition and cyclization of alkyl halides with alkenes has often been a choice for construction of various organic molecules [1], However, the requirement for high-temperature initiators or photo initiation and the difficulties associated with purification of the products from tributyltin halides tend to limit the widespread use of these methods, despite the efforts to make the methods easier [Ic, 2], Recently, nickel-mediated radical additions and cyclizations have been introduced as promising alternatives to the tributyltin hydride methods. These are the nickel powder-acetic acid method for cyclization of haloamides to y-lactams, y -lactams and in-dolones, the borohydride exchange resin-nickel boride method for radical addition, nickel-catalyzed electroreductive cyclization and nickel-catalyzed Kharasch addition of polyhalo compounds. 

Sulfonic acids can also be obtained by the Strecker synthesis from sodium sulfite and aryl halides that contain reactive halogen. Thus o-formylbenzene-sulfonic acid is formed in very good yield when o-chlorobenzaldehyde is heated under pressure with sodium sulfite,354 2-formyl-4-nitrobenzenesulfonic acid is formed on merely boiling 2-chloro-5-nitrobenzaldehyde with alcoholic sodium sulfite solution.355 The nitro group of nitroaryl halides may also be reduced to an amino group (cf. page 626) using polyhalo compounds leads to poly sulfonic acids.356... 

Polyhalo compounds such as CH2C12, CHC13, and CC14 usually give a very complex mixture of various organosilicon compounds on reaction at a silicon-copper catalyst.328 However, 1,1-dichloro-l-silacyclopentane (1,1-di-chlorosilole) is obtained with other products from 1,4-dichlorobutane.329... 

There is no isomerization or rearrangement during such dehalogenations. However, cyclization cannot be entirely avoided on dehalogenation of 1,3-dihalo compounds68 or some polyhalo compounds by, e.g., zinc or aluminum. Roedig and his co-workers69 used alcoholic potassium hydroxide in acetone... 

Stepwise dehalogenation of a polyhalo compound through its Grignard reagent which on treatment with water yields a product containing one halogen atom less ... 

A detailed study of the orientation and reactivity in the nucleophilic replacement reactions of aromatic polyhalo-compounds has been published . This involves study of the stability of the Wheland type intermediates (17, 18) where Nu is a nucleophile. The formation of meta... 

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