Chlorination, Sandmeyer reaction

The diazonium salts usually decompose when warmed with water to give a phenol and nitrogen. When treated with CuCl, CuBr, KI, the diazo group is replaced by chlorine, bromine or iodine respectively (Sandmeyer reaction). A diazonium sulphate and hydroxyl-amine give an azoimide. The diazonium salt of anthranilic acid (2-aminobenzoic acid) decomposes to give benzyne. ... 

Chlorination of OCT with chlorine at 90°C in the presence of L-type 2eohtes as catalyst reportedly gives a 56% yield of 2,5-dichlorotoluene (79). Pure 2,5-dichlorotoluene is also available from the Sandmeyer reaction on 2-amino-5-chlorotoluene. 3,4-Dichlorotoluene (l,2-dichloro-4-methylben2ene) is formed in up to 40% yield in the chlorination of PCT cataly2ed by metal sulfides or metal halide—sulfur compound cocatalyst systems (80). 

Dichlorotoluene (l,2-dichloro-3-methylben2ene) is present in about 10% concentration in reaction mixtures resulting from chlorination of OCT. It is best prepared by the Sandmeyer reaction on 3-arnino-2-chlorotoluene. 

Dichlorotoluene (l,3-dichloro-2-methylben2ene) is prepared from the Sandmeyer reaction on 2-arnino-6-chlorotoluene. Other methods include ring chlorination of -toluenesulfonyl chloride followed by desulfonylation (81), and chlorination and dealkylation of 4-/ f2 -butyltoluene (82) or... 

Tetrachlorotoluene, C H Cl (mol wt 229.93) (1,2,3,5-tetrachloro-4-methylben2ene), is prepared from the Sandmeyer reaction on 3-arnino-2,4,6-trichlorotoluene. 2,3,4,5-Tetrachlorotoluene (l,2,3,4-tetrachloro-5-methylben2ene) is the principal isomer in the further chlorination of 2,4,5-trichlorotoluene. Exhaustive chlorination of -toluenesulfonyl chloride, followed by hydrolysis to remove the sulfonic acid group yields... 

Sandmeyer Reaction. This general reaction allows the phenol function to be introduced. The technique complements chlorination insofar as it makes it possible to produce chlorophenols chloriaated in the meta position from the corresponding meta-chlotinated anilines. 

Bromination of 136 in methanol gave the 3-bromo derivative, identical with the product of Sandmeyer reaction of the 3-diazonium salt. When the reactive 3-position was blocked, electrophilic bromination would not take place (66JOC265). Chlorination appears to occur by addition [83AHC(34)79], and perhalides are known [84MI25 90AHC(47)1]. Activating substituents are able to induce some bromination in the pyridine ring. 

Treatment of diazonium salts with cuprous chloride or bromide leads to aryl chlorides or bromides, respectively. In either case the reaction is called the Sandmeyer reaction The reaction can also be carried out with copper and HBr or HCl, in which case it is called the Gatterman reaction (not to be confused with 11-16). The Sandmeyer reaction is not useful for the preparation of fluorides or iodides, but for bromides and chlorides it is of wide scope and is probably the best way of introducing bromine or chlorine into an aromatic ring. The yields are usually high. 

Entries 7 and 8 illustrate conversion of diazonium salts to phenols. Entries 9 and 10 use the traditional conditions for the Sandmeyer reaction. Entry 11 is a Sandmeyer reaction under in situ diazotization conditions, whereas Entry 12 involves halogen atom transfer from solvent. Entry 13 is an example of formation of an aryl iodide. Entries 14 and 15 are Schiemann reactions. The reaction in Entry 16 was used to introduce a chlorine substituent on vancomycin. Of several procedures investigated, the CuCl-CuCl2 catalysis of chlorine atom transfer form CC14 proved to be the best. The diazonium salt was isolated as the tetrafluoroborate after in situ diazotization. Entries 17 and 18 show procedures for introducing cyano and azido groups, respectively. 

Halo-de-diazoniations are a series of reactions in which the replacement of the dia-zonio group changes from a heterolytic de-diazoniation in the case of the fluorination (Balz-Schiemann reaction) to transition metal-catalyzed chlorination and bromination (Sandmeyer reaction) and finally to iodination and astatination where no catalyst is necessary due to the favorable redox potentials of I and At- (I- E° = 1.3 V). 

Low-temperature chlorination of dibenzothiophene with elemental chlorine produces a chlorine adduct at the sulfur atom which is readily decomposed to dibenzothiophene 5-oxide. However, nuclear chlorination of dibenzothiophene has still not been studied. 2-Chlorodibenzo-thiophene has been prepared by the Sandmeyer reaction on 2-amino-dibenzothiophene and this route has now been extended to give... 

In pyrazolium salts chlorine can be displaced quite readily by iodide (77BSF171), and Sandmeyer reactions have found application in the preparation of iodopyrazoles from their diazonium salts [90AHC(48)65 90JAP(K)02/304064]. 

There appear to be no direct electrophilic substitutions of compound 2 it is unreactive toward bromine, N-bromosuccinimide, or nitrating agents.49 The sole electrophilic substitution (excluding alkylation) is that of the diazo group in compound 190 by chlorine in a Sandmeyer reaction.65 By contrast,... 

The third chlorine can be introduced via the Sandmeyer reaction. Reduction of the nitro group completes the synthesis of 3,4,5-trichloroaniline. 

Chloroisothiazole is available by chlorinative cyclization of /9-mercaptopropionitrile (see Section I,E). 3-Chloro-5-phenylisothia-zole has been prepared by the Sandmeyer reaction from 3-amino-5-phenylisothiazole118 and also by thermal decomposition of the... 

Amino groups in phenyl substituents form acyl214 and benzyli-dene214,215,217 derivatives the latter are cleaved by hydrochloric acid214,215,217 and hydrazine.214 The amino group may be replaced by a chlorine atom in a Sandmeyer reaction 279 apparently here (in 3-p-aminophenylanthranil), nitrous acid does not affect the usual rearrangement to acridones. 

If for any reason the direct introduction of chlorine is not possible, or the chlorine does not enter the desired position in the molecule, recourse may be had (but rarely ) to the Sandmeyer reaction (see example on page 161). In some cases, the Sandmeyer reaction can be avoided (it is rather bothersome and expensive) by the use of a trick reaction, such as in the preparation of o-chlorotoluene from p-toluene-sulfonic acid2 (page 163). 

The replacement of the diazonium group by chlorine or bromine is accomplished using the Sandmeyer reaction Replacement with fluorine and iodine can be achieved by variations of this reaction. 

A diazonium salt reacts with copper(I) chloride or copper(I) bromide to form an aryl chloride or aryl bromide, respectively. This is called the Sandmeyer reaction. It provides an alternative to direct chlorination and bromination of an aromatic ring using CI2 or Br2 and a Lewis acid catalyst. 

Hanson, P., Jones, J. R., Taylor, A. B., Walton, P. H., Timms, A. W. Sandmeyer reactions. Part 7.1 An investigation into the reduction steps of Sandmeyer hydroxylation and chlorination reactions. J, Chem. Soc., Perkin Trans. 2 2002, 1135-1150. 

Sandmeyer reaction, synthesis, of bromo compound, 36, 39, 45, 48, 52, 75, 217 of chloro compound, 48, 110, 113 of cyano compound, 90, 91, 216 of iodo compound, 182, 183, 184, 185 use of mercuric nitrate in, 52 Saponification of an ester, 113, 152 Schiemann reaction, 165, 167 Schotten-Baumann reaction, 145 Skraup reaction, 28, 85, 193, 204, 235 Sommelet reaction, 281 Sulfenyl chloride, formation from chlorine and disulfide, 214... 

Although chloro and bromo substituents can be placed directly on a benzene ring by halogenation, the Sandmeyer reaction can be a useful alternative. For example, if you wanted to make para-chloroethylbenzene, chlorination of ethylbenzene would lead to a mixture of the ortho and para isomers. 

However, if you started with para-ethylaniline and used a Sandmeyer reaction for chlorination, only the desired para product would be formed. 

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