With Replacement of a Halogen Atom

Bromine is exchanged for iodine when alkyl 8-bromooctyl tellurium compounds are refluxed with sodium or potassium iodide in acetone. This method was used to introduce into the tellurium compound d. 

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Another widely used method involves hydrolysis of cyanopyrida-zines. These are usually obtained from cyclizations of open-chain cyano compounds (synthesis of 4-cyano-3(2/7)-pyridazinone and its methyl analogs ), since replacement of a halogen atom by cyano group proceeds with pyridazines in low yields or not at all. Many cyanopyridazines have been obtained by dehydration of amides, such as 3- or 4-cyanopyridazine, 3-chloro-6-cyanopyridazine or 6-cyano-2-methyl-3(2.ff)-pyridazinone, and 3-chloro-4-cyano-... 

Reduction of an alkyl halide, either via the Grignard reagent or directly with metal and acid, involves simply the replacement of a halogen atom by a hydrogen atom the carbon skeleton remains intact. This method has about the same applicability as the previous method, since, like alkenes, alkyl halides are generally prepared from alcohols. Where either method could be used, the hydrogenation of alkenes would probably be preferred because of its simplicity and higher yield. 

The replacement of a halogen atom in a compound by a hydroxyl group is an important method of preparing alcohols. As iodides react with water more readily and at a lower temperature than chlorides, they are more frequently used. In order to increase the rate at which the alcohol is formed the alkyl iodide is shaken or heated with water and silver oxide. It is probable that a reaction takes place between the iodide and the silver hydroxide which is formed from the oxide and passes into solution. The equation is as follows —... 

In the previous chapters the preparation and properties of certain important classes of compounds have been discussed, and the principles which are illustrated in their transformations into one another have been emphasized. These principles are of wide application and can be employed in the preparation of compounds of more complex structure than any met with so far. For example, the method of preparing an alcohol by the treatment of an alkyl halide with water or an alkali, is very general in its application. The reaction consists in the replacement of a halogen atom by a hydroxyl group, and such replacement takes place not only with alkyl halides, but with other compounds which contain halogen. Thus, chloroacetic acid can be transformed into hydroxyacetic acid by water —... 

Thiazolo[4,5-b]pyrazines. 2-Amino-3,5-dibromopyrazine refluxed 3 hrs. with a soln. obtained by saturating KOH in methanol with HgS 2-amino-3-mercapto-5-bromopyrazine (Y 96%), 7 g. refluxed 3.5 hrs. with acetic anhydride 6 g. 2-methyl-6-bromothiazolo[4,5-b]pyrazine refluxed 3.5 hrs. with a soln. of Na in methanol -> 2-methyl-6-methoxythiazolo [4,5-b] pyrazine (Y 78%) refluxed 2 hrs. with a soln. of NaOH in water-methanol 2-amino-3-mercapto-5-methoxy-pyrazine (Y 92%).—The above method circumvents the influence of the amino group, which ordinarily hinders replacement of a halogen atom in the 5-position. G. Palamidessi and L. Bernardi, G. 91, 1438 (1961). 

Carbonyl and formyl halides CF O, CCIFO, and CCljO are stable gases and are commercially available. CBr O is a liquid and is prepared by the reaction of tetra-bromomethane with concentrated sulfuric acid. The replacement of a halogen atom by hydrogen decreases the molecular stability. Formyl fluoride, CHFO, is usually generated, as needed, by the fluorination of dry formic acid with NaF. CHClO is unstable, and must be prepared in a flow system. The procedure is to pass formic acid vapor over solid PClj immediately before it is to be used. The bromine compound, CHBrO, is very short lived. It has been prepared in the vapor phase by the photolysis of a bromine-formaldehyde mixture. 

If only the monocarboxybc acid is required, the ester after hydrolysis with potash may be strongly acidified with sulphuric acid and the mixture heated under reflux the mineral acid promotes decarboxylation at a temperature just above 100°. The net result is the replacement of the halogen atom of the alkyl halide by —CH COOH thus in the above example ... 

Very frequently in these reactions 2NO replace 3CO. Alternatively, INO can replace 2CO with simultaneous formation of a metal-metal bond, or INO can replace CO + a halogen atom ... 

The haloalkanes (also called alkyl halides) are alkanes in which at least one hydrogen atom has been replaced by a halogen atom. Although they have important uses, many haloalkanes are highly toxic and a threat to the environment. The haloalkane 1,2-dichlorofluoroethane, CHC1FCH2C1, is an example of a chlorofluorocarbon (CFC), one of the compounds held responsible for the depletion of the ozone layer (see Box 13.3). Many pesticides are aromatic compounds with several halogen atoms. 

The dehalogenases (EC 3.8.1), a subclass of the hydrolases that act on the halide bonds in C-halide compounds, catalyze reactions of hydrolytic de-halogenation (Fig. 11.3,a), i.e., the replacement of a halide atom at a sp3 C-atom with a OH group. Exceptions include thyroxine deiodinase (EC 3.8.1.4), which catalyzes reductive deiodination on phenyl rings, and the bacterial 4-chlorobenzoate dehalogenase (EC 3.8.1.6), which forms 4-hydroxy-benzoate. 

Haloalkanes can be regarded as substituted alkanes in which one or more of the hydrogen atoms is replaced by a halogen atom. They are named in a similar fashion to branched-chain alkanes with the halogen atoms treated like branches. For example, the anaesthetic halothane has the structure shown in the diagram and is called 2-bromo-2-chloro-l,l, 1-trifluoroethane. 

The electrophilic substitution reactions commonly used with aromatic compotmds could not be applied to monosubstituted oxadiazoles 25a, 55 b). The hydrogen atoms in position 3 and 5 of these derivatives could not be replaced by a halogen atom or a nitro group and are also inactive towards Friedel-Craft reagents. 

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