The Sandmeyer procedure

Amino groups can be exchanged for sulfo or halo groups via diazotization and application of the Sandmeyer procedure. An example is the preparation of zinc(II) 2-chloro-9,16,23-trwer/-butylphthalocyaninc (6).3,9... 

The most frequently used synthesis of isatins is the Sandmeyer procedure, which involves the formation of an isonitrosoacetanilide (3) from an aniline (2), chloral hydrate, and hydroxylamine. The isonitroso-... 

The Sandmeyer procedure for the synthesis of aryl halides from arylamines has been applied, with modification, to the conversion of 5- and 8-aminoquinolines to the iodo and bromo derivative. 8-Aminoquinoline is converted to 8-bromoquinoline in good yield on treatment with /-butyl nitrite in the presence of CuBr in acetonitrile at 60 °C <2003JOC5123> and 5-amino-6-nitroquinoline is converted to the 5-iodo derivative under equally mild conditions using potassium nitrite and copper iodide in DMSO at 60 °C <2005JOC2445>. 

The Sandmeyer procedure and its Gattermann variant (see page 259) often give poor yields when applied to diphenylamines, naphthylamines, or phen-anthrenamines, but good results can be obtained by the method worked out by Schwechten1239 as a variant of the Schiemann reaction (thermal decomposition of diazonium fluoroborates, see below). 

W. A. Waters (Oxford University) Investigations of the extent to which complexes such as (CuCl)+ and undissociated CuCL affect the chain length in the polymerization associated with the Sandmeyer reaction are in progress at Oxford. It is well known that ions that complex well with cupric, e.g., (CN) , can be introduced into aryl nuclei by the Sandmeyer procedure in preference to chloride even when diazonium chlorides have initially been taken. The system, however, is complicated by the fact that the complexing of cuprous and cupric salts alters the redox potential, and this affects the facility of both stages 1 and 3 of the reaction sequence. The effects of introducing polar substituents into the aryl nuclei (Table I) indicates the importance of such effects. 

When aqueous solutions of aromatic and heteroaromatic diazonium salts are treated with cuprous chloride, -bromide, or -cyanide, the corresponding aromatic chlorides, bromides, or cyanides are formed, respectively. In many cases the anions mentioned must be present in excess. This reaction, the Sandmeyer reaction, was discovered by Sandmeyer in 1884. A variant carried out with copper powder and HBr or HC1 was for many years called the Gattermann reaction (Gattermann, 1890). As it is often confused with the Gattermann-Koch reaction (ArH + CO + HC1 ArCHO), and as it is mechanistically not significantly different from Sandmeyer s procedure, the name Gattermann reaction should be avoided. 

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. 

One of the drawbacks of the Sandmeyer reaction is the number of competing side reactions leading to the formation of biaryls, azo compounds and phenols. A recent procedure to maximise the yield of aryl halide involves treatment of the arylamine with t-butyl nitrite and anhydrous copper(n) halide (the chloride or the bromide) in acetonitrile at 65 °C.28 The method is illustrated by the preparation of p-chloronitrobenzene (Expt 6.73) the overall reaction may be represented as ... 

Amino-8-bromophenanthridone can be deaminated smoothly by the action of cold hypophosphorus acid on the diazonium chloride.122 1-Bromophenanthridone is formed in moderate overall yield from the amino compound when the diazonium bromide-mercuric bromide complex is heated at 120° and a number of bromo- and chloro-phen-anthridones have been obtained recently by Sandmeyer procedures.26, 101... 

A general procedure for the synthesis of 5-chloro-l,2,4-thiadiazoles (289) is the reaction of amidines with trichloromethylsulfenyl chloride (329) in the presence of an acid acceptor (Scheme 152) (also see Scheme 102). 3-Halo derivatives (387 X = Cl, Br, I Scheme 153) have been obtained in moderate yields from the corresponding amines (386) using the Sandmeyer-Gatterman reaction (Scheme 153) (60JCS3234) (see Section 4.25.3.3.4). 3-ChIoro-l,2,4-thiadiazolin-2-ones of types (298) and (299) can be prepared by treatment of chlorosulfenylcarbonyl chloride (291) with carbodiimides and cyanamides, respectively (Scheme 154) (70AG(E)54). The isomeric products (270) and (274) are produced by the chlorination of mixtures of isocyanates and isothiocyanates (Scheme 155) (see also Scheme 95). 

The Sandmeyer synthesis has been described as being unapplicable to ortho-hydroxy or 0/7/70-alkoxyanilines. Therefore an alternative procedure for the synthesis of the isonitrosoacetanilides was reported24,25 (Scheme 2). 

For the preparation of chlorides or bromides, the diazonium salt is decomposed with a solution of cuprous chloride or bromide in the corresponding halogen acid (Sandmeyer reaction). It is possible to prepare the aryl bromide from the diazonium chloride or sulfate. A variation Involves the use of copper powder and a mineral acid for the decomposition step (Gattermann reaction). Both procedures are illustrated by the syntheses of the isomeric bromotoluenes and chlorotoluenes. The usual conditions of the Sandmeyer reaction fail in the preparation of the chloro- and bromo-phenanthrenes. However, these compounds can be successfully obtained by the interaction of the diazonium compound with mercuric and potassium halides (Schwechten procedure). Another procedure for formation of aryl bromides involves treatment of the amine hydrobromide with nitrogen trioxide in the presence of excess 40% hydro-bromic acid. The Intermediate diazonium perbromide is then decomposed by heat. ... 

In the preparation of a-naphrhonitrile, somewhat better yields are obtained by substituting nickel cyanide for the usual cuprous cyanide reagent (55% vs. 78%). 5-Cyanoquinoline is prepared satisfactorily by the Sandmeyer reaction, but the 8-isomer could not be obtained by this procedure. ... 

The procedure given was developed by Ghigi from an earlier preparation by Jacobsen. 4-Bromo-< -xylene has also been prepared from 3,4-dimethylamline by the Sandmeyer reaction. ... 

Dinitronaphthalene has been prepared previously from diazotized 4-nitro-l-naphthylamine by a modified Sandmeyer procedure, - from 5,8-dinitrotetralin by dehydrogenation, by the deamination of l,4-dinitro-2-naphthylamine, and by the decomposition of 4-nitro-l-naphthalenediazonium cobaltinitrite. The method described above has been published. ... 

The first examples reported by Sandmeyer date back to 1884. The many various preparative procedures differ mainly in the type and the preparation of the copper-cyanide complex which is used. In the Gattermann procedure KCN in the presence of Cu powder is used. Generally one tries to avoid the formation of HCN on the addition of alkali metal cyanide to the acidic medium by neutralizing the diazo-nium salt solution in advance with sodium or barium carbonate. Cyanogen, which is formed from CN ions on treatment with Cu" salts, is also a harmful by-product. In this case the addition of sodium hydrogen sulfite (equation 19) proved to be of great value. 

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