Substitution of halogen

In laboratory methods for the preparation of aliphatic nitro compounds, the V. Meyer reaction [186] consisting in reacting alkyl iodides or bromides with silver nitrite, is widely used. As is well known, the reaction can proceed in two directions, resulting in the formation of a certain quantity of a less stable nitrous ester besides a nitro compound. Instead of silver nitrite mercuric nitrite may be used (Ray [187]). 

Komblum and his co-workers [188, 188a] have recently improved the method used for the preparation of nitroparaffins with longer aliphatic chain (over C8). They reacted an alkyl chloride with sodium nitrite in the solvent (dimethylform-amide) for several hours at low temperature, obtaining a homogeneous solution  

The addition of urea to the reacting system prevents side reactions, e.g. the formation of nitrous esters. The yield amounts to about 60%. 

In aromatic compounds such a reaction is possible only in the case of polybro-mo- or polyiodo-derivatives of phenol. Sodium nitrite and acetic acid may be used for replacing one of the Br or I atoms by the nitro group (Zincke [189], Raiford [190-193])  

Not only salts of nitrous acids but also nitrous acid itself can replace halogen by the nitro group. This has been discovered by Wuster and Scheibe [194] when they reacted sodium nitrite with bromodimethylaniniline in hydrochloric acid  

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With the exception of the nuclear amination of 4-methylthiazole by sodium amide (341, 346) the main reactions of nucleophiles with thiazole and its simple alkyl or aryl derivatives involve the abstraction of a ring or substituent proton by a strongly basic nucleophile followed by the addition of an electrophile to the intermediate. Nucleophilic substitution of halogens is discussed in Chapter V. 

Halogens add to butenediol, giving 2,3-dihalo-l,4-butanediol (90,91). In a reaction typical of aHyhc alcohols, hydrogen haUdes cause substitution of halogen for hydroxyl (103). 

In contrast, substituents in 1,2,4-triazoles are usually rather similar in reactivity to those in benzene although nucleophilic substitution of halogen is somewhat easier, forcing conditions are required. 

The introduction of halogen into organic molecules can be carried out by a variety of addition or substitution reactions. The classical methods for the addition of halogen to double bonds or the substitution of halogen for hydroxyl by hydrohalic acids are too well known to bear repetition here. Discussed below, then, are methods that are of interest because of their stereospecific outcome or because they may be used on sensitive substrates. 

Nucleophilic substitutions of halogen by the addition-elimination pathway in electron-deficient six-membered hetarenes by sulfinate anions under formation of sulfones have been described earlier120. The corresponding electron-poor arenes behave similarly121 (equation 30). A special type of this reaction represents the inverse Smiles rearrangement in equation 31122. 

Substitution of halogens on heteroaromatic rings is a common way to introduce new functionalities. The product from reaction 6 (Scheme 6) was required on a 100-g scale as an intermediate. In the literature, this exchange was done on a 5-g scale using ammonia in ethanol in a sealed tube under pressure for 6 h at 125-130°C with a yield of 76% (Bendich et al. 1954). Because of the lack of a suitable autoclave for high-pressure reactions, we choose the microwave reactor for scale-up trials. Using our Synthos 3000 equipment, we found suitable conditions with only minimal optimization at 170°C for 180 min and obtained the desired product on a 60-g scale in 83% yield. 

Figure 11. Mbssbauer spectra of (CQH5) Sn and (CQH5)3SnCl. Substitution of halogen ligand for CgH., group produces a quadrupole splitting of 2.45 ...

Several other azido esters has been reported, including (7), (8) and (9), which are synthesized along similar routes of ester formation followed by substitution of halogen with azide anion or in the reverse order. 

Nucleophilic substitution of halogen atom in aromatic and heteroaromatic halides with a hydroxyamino group proceeds only in substrates that are activated by a strong electron-withdrawing substituent in the benzene ring (e.g. 27, equation 17). Despite this limitation this reaction is useful for synthesis of arylhydroxylamines and usually provides good yields of products. Along with activated aryl halides and sulfonates, activated methyl aryl ethers such as 28 can be used (equation 18). 

Substitution of halogen atom in non-activated rings such as 33 (equation 23) is substantially more difficult. Palladium couplings are the most promising approach, although... 

Nucleophilic substitution with heteroaryl halides is a particularly useful and important reaction. Due to higher reactivity of heteroaryl halides (e.g. 35, equation 24) in nucleophilic substitution these reactions are widely employed for synthesis of Al-heteroaryl hydroxylamines such as 36. Nucleophilic substitution of halogen or sulfonate functions has been performed at positions 2 and 4 of pyridine , quinoline, pyrimidine , pyridazine, pyrazine, purine and 1,3,5-triazine systems. In highly activated positions nucleophilic substitutions of other than halogen functional groups such as amino or methoxy are also common. 

When electronegative substituents are present, oxadiazoles undergo nucleophilic reactions on the carbon atoms, both in position 3 or 5- The substitution of halogen, alkoxy and trichloromethyl derivatives has. been studied. 5-Halogeno-oxadiazoles react with ahphatic and aromatic primary and secondary amines, to give the corresponding amino-derivatives. With sodium hydroxide and -alcoholate, hydroxy and alkoxy oxadiazoles are obtained 25 a, 55 b). 

Further Substitutions of Halogens These reactions are listed in Table XIII. 

The low efficiency of this initiator limits its utility for polymerization. However, it has been shown to be highly efficacious for grafting onto and substitution of halogenated polymer substrates (55). 

Carbon tetrachloride represents an example of the change to petroleum raw materials in this field. The traditional source of this widely used product has been the chlorination of carbon disulfide, either directly or through the use of sulfur dichloride. Military requirements in World War II caused an increase in demand, and in addition to expansion of the older operations, a new process (28) was introduced in 1943 it involved direct chlorination of methane at 400° to 500° C. and essentially atmospheric pressure. This apparently straight-forward substitution of halogen for hydrogen in the simplest paraffin hydrocarbon was still a difficult technical accomplishment, requiring special reactor construction to avoid explosive conditions. There is also the fact that disposal of by-product hydrochloric acid is necessary here, though this does not enter the carbon disulfide picture. That these problems have been settled successfully is indicated by the report (82) that the chlorination of methane is the predominant process in use in the United States today, and it is estimated that more than 100,000,000 pounds of carbon tetrachloride were so produced last year. 

Highly halogenated alkenes, e.g. 6, react with sulfur tetrafluoride at elevated temperatures in the presence of Lewis acid type fluorides to afford halofluoroalkanes, which result from both addition of fluorine to the C = C bond and substitution of halogen atoms.191... 

Substitution of Halogen with Fluorine Using Mercury(I) Fluoride... 

Substitution of Halogen with Fluorine Using Mercury(II) Fluoride Generated In Situ from Mercury(II) Oxide or Mercury(II) Chloride and Anhydrous Hydrogen Fluoride... 

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