Reaction Sandmeyer

Haloarenes from the reaction of a diazonium salt with CuX. 

Sandmeyer, T. Ber. Dtsch. Chem. Ges. 1884, 17, 1633. Traugott Sandmeyer (1854—1922) was bom in Wettingen, Switzerland. He apprenticed under Victor Meyer and Arthur Hantzsch although he never took a doctorate. He later spent 31 years at the firm J. R. Geigy, which is now part of Novartis. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 227, Springer-Verlag Berlin Heidelberg 2009 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 242, Springer International Publishing Switzerland 2014 

The conversion of an aromatic diazo compound, generated from the corresponding aniline, to the aryl halide (chloride or bromide) or cyanide is known as the Sandmeyer reaction.  

The reaction begins with conversion of the aniline (1) to the diazo compoimd (2). Usually in the same pot, 2 is then treated with the cuprous halide or cyanide to form the aryl halide or cyanide (3). 

During an unsuccessful attempt to prepare phenylacetylene (5) from diazobenzene (4), Sandmeyer discovered that chlorobenzene (6) could be efficiently prepared from 4 under these reaction conditions. While investigating the formation of this unexpected product, he discovered that the active reagent was cuprous chloride, formed in hydrochloric acid solution. He further postulated that this particular reaction was unique to cuprous chloride, since cupric and ferrous chloride did not exhibit a similar behavior. It would be many years, however, before a more complete understanding of this process could be secured. Sandmeyer s subsequent studies demonstrated that, when reacted with diazobenzene (4), cuprous bromide produced bromobenzene (8) and cuprous cyanide produced cyanobenzene (7). Strictly 

Since its discovery in 1884, the Sandmeyer reaction has undergone numerous 

CoCl) are capable of catalyzing both the reduction and ligand transfer 

Conversion of arenediazonium salts into aryl halides 

The name Sandmeyer reaction is used for the replacement of the diazonium group in an arenediazonium compound by halide or pseudohalide, taking place in the presence of a metal salt. However this is not a strict definition, since the replacement of the diazonium group by iodide, which is possible without a metal catalyst, is also called a Sandmeyer reaction. 

The reaction mechanism is not rigorously known, but is likely to involve the following steps. First the arenediazonium ion species 1 is reduced by a reaction with copper-(I) salt 2 to give an aryl radical species 4. In a second step the aryl radical abstracts a halogen atom from the CuX2 compound 5, which is thus reduced to the copper-I salt 2. Since the copper-(l) species is regenerated in the second step, it serves as a catalyst in the overall process. 

For the in situ preparation of the required arenediazonium salt from an aryl amine by application of the diazotization reaction, an acid HX is used, that corresponds to the halo substituent X to be introduced onto the aromatic ring. Otherwise—e.g. when using HCFCuBr—a mixture of aryl chloride and aryl bromide will be obtained. The copper-(I) salt 2 (chloride or bromide) is usually prepared by dissolving the appropriate sodium halide in an aqueous solution of copper-(II) sulfate and then adding sodium hydrogensulfite to reduce copper-(ll) to copper-(I). Copper-(l) cyanide CuCN can be obtained by treatment of copper-(l) chloride with sodium cyanide. 

The Sandmeyer reaction generally permits the introduction of electron-withdrawing substituents onto an aromatic ring. Arenediazonium salts, as well as the Sandmeyer products derived thereof, are useful intermediates for the synthesis 

electron-withdrawing groups (EWG) or electron-donating groups (EDG) HX HCI, HBr X = Cl, Br, CN 

The mechanism of the Sandmeyer reaction is not completely understood. For a long time it was believed to proceed via aryl cations, but later W.A. Waters and then later J.K. Kochi proposed a radical mechanism which was catalytic for 

The neurotoxic quaterpyridine natural product nemertelline was successfully synthesized by S. Rault et al. using a Suzuki cross-coupiing as the key step. The boronic acid coupling partner, required for the Suzuki reaction, was prepared by first subjecting 3-amino-2-chloropyridine to the conditions of the Sandmeyer reaction followed by a lithium-halogen exchange and trapping the lithiopyridine derivative with triisopropylborate. 

2-bromo-4-chloro-3,6-dimethoxy-aniline benzene precursor. 

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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. ... 

Gattermann s reaction A variation of the Sandmeyer reaction copper powder and hydrogen halide are allowed to react with the diazonium salt solution and halogen is introduced into the aromatic nucleus in place of an amino group. 

The following mechanism of the Sandmeyer reaction has been proposed as a result of a kinetic study, and incidentally accounts for the formation of the azu compounds as by-products. The catalyst is the CuCl ion produced in the dissolution of cuprous chloride in the chloride solution ... 

In the preparation of bromo compounds by the Sandmeyer reaction, the amine is generally diazotised in sulphuric acid solution (or in hydrobromic acid solution), and the resulting aryldiazonium sulphate (or bromide) is treated with a solution of cuprous bromide in excess of hydrobromic acid the addition... 

The Sandmeyer reaction may also be applied to the preparation of nitriles. The solution of the diazonium salt is added to a solution of cuprous cyanide in excess of sodium or potassium cyanide solution (sometimes improved yields are obtained by substituting nickel cyanide for cuprous cyanide), for example CH3 CH, CH3... 

By the hydrolysis of nitriles. The nitriles may be easily prepared either from amines by the Sandmeyer reaction (Section IV,66) or by the action of cuprous cyanide upon aryl halides (compare Section IV,163). Benzyl cyanide... 

Pinacol-pinacolone rearrangement Prileschajew epoxidation reaction Reformataky reaction Reimer-Tiemanii reaction Rosenmund reduction Sandmeyer reaction Schiemaim reaction Schmidt reaction or rearrangement Schotten-Baumann reaction Skraup reaction Sommelet reaction. ... 

Halothiazoles are usually obtained from 2-aminothiazoles through the Sandmeyer reaction. Nevertheless, ammonolysis has sometimes proved useful for the preparation of 2-aminothiazole derivatives. Detweiler et al. (18) obtained 2-(u-pyridinylamino)thiazole (1) from 2-bromothiazole (Scheme 1). The reaction is easier if a nitro group occupies the 5-position of the thiazole ring (19-21). Ethylene diamine derivatives undergo this reaction with 2-haiothiazoles (22-24). 

The Sandmeyer reaction, the substitution of an amino group by an halogen atom that is subsequently substituted after reduction by hydrogen atom. 

The replacement of 2-amino group by a hydrogen can be achieved by diazotization, followed by reduction with hypophosphorous acid (1-8, 13). Another method starting from 2-aminothiazole is to prepare the 2-halo-thiazole by the Sandmeyer reaction (prepared also from the 2-hydroxy-thiazole), which is then dehalogenated chemically or catalytically (1, 9, 10). 

All four 2-halogenothiazoles are known. 2-Chloro (l- ll). 2 bromo (1, 2. 5, 8-10, 12-24), and 2-iodothiazole (8, 10, 25, 26) can be prepared from 2-aminothiazole by Sandmeyer reactions, with yields between 30... 

Some 2-halogeno-5-nitrothiazoles and 2-nitro-5-halogenothiazoles are known. 2-Halogeno-5-nitrothiazoles can be prepared by a Sandmeyer reaction from 2-amino-5-nitrothiazole (1, 85), while 2-nitro-5-halo-genothiazoles can be analogously prepared by decomposition of dia-zonium salts arising from 2-amino-5-halogenothiazoles in presence of nitrite anion (82, 84). 

Reactions that employ copper(I) salts as reagents for replacement of nitrogen m diazo mum salts are called Sandmeyer reactions The Sandmeyer reaction using copper(I) cyanide is a good method for the preparation of aromatic nitriles... 

Sandmeyer reaction using cop per(l) bromide is applicable to the conversion of primary arylamines to aryl bromides... 

Sandmeyer reaction (Section 22 17) Reaction of an aryl dia zonium ion with CuCl CuBr or CuCN to give respec tively an aryl chloride aryl bromide or aryl cyanide (nitrile)... 

Diazotization Routes. Conventional Sandmeyer reaction conditions are not suitable to make fluoroaromatics. Phenols primarily result from high solvation of fluoride ion in aqueous media. 

Physical properties for naphthalene mono-, di-, tri-, and tetracarboxyhc acids are summari2ed in Table 9. Most of the naphthalene di- or polycarboxyLic acids have been made by simple routes such as the oxidation of the appropriate dior polymethylnaphthalenes, or by complex routes, eg, the Sandmeyer reaction of the selected antinonaphthalenesulfonic acid, to give a cyanonaphthalenesulfonic acid followed by fusion of the latter with an alkah cyanide, with simultaneous or subsequent hydrolysis of the nitrile groups. 

Ha.loisoquinolines, The Sandmeyer reaction is commonly used to prepare chloroisoquinolines from the amino compound. The corresponding hydroxy compounds are also used by treatment with chlorides of phosphoms. The addition of bromine to a slurry of isoquinoline hydrochloride in nitrobenzene gives a 70—80% yield of 4-bromoisoquinoline [1532-97-4J. Heating 1-chloroisoquinoline [19493-44-8] with sodium iodide andhydriodic acid gives 1-iodoisoquinoline [19658-77-6] (179). 

Pure monochlorotoluene isomers are prepared by dia2oti2ation of the corresponding toluidine isomers followed by reaction with copper(I) chloride (Sandmeyer reaction). This is the preferred method of obtaining y -chlorotoluene. 

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. 

SnCl2 reduction produced the 4-hydrazinoisoxazole (243). In ethanol the diazonium salt reacted with the 4-aminoisoxazole to produce the linear triazine (244) (Scheme 85). Diazoisoxazoles can also be treated with KI or H20/urea to produce the 4-iodo or 4-hydroxy derivatives (63AHC(2)365). These Sandmeyer reactions have been extended to a variety of isoxazole systems (77JMC934, 63AHC(2)365). 

In contrast to the 3-substituted products above, 4-chloro-, 4-bromo- and 4-iodo-isoxazoles are readily prepared by direct halogenation of the corresponding isoxazoles, from 4-isoxazolediazonium salts by the Sandmeyer reaction, or by reaction of hydroxylamine with a-halo- 8-dicarbonyl compounds (62HC(l7)l, p. 66, 63AHC(2)365). 3,5-Bis(dimethyl-amino)-4-fluoroisoxazole has been synthesized by reaction of (Me2NCO)2CHF with hydroxylamine (78BSB391). 

Benzisothiazole, 5-amino-azo dyes from, 6, 175 oxidation, 6, 154 oxidative degradation, 5, 86 Sandmeyer reaction, 6, 154... 

Pyrimidine-2,4( 1 f/,3H)-dione, 5-amino-6-metfayl-Sandmeyer reactions, 3, 85 Pyrimidine-2,4(lf/,3f/)-dione, 5-benzoyloxyimino-6-methylimino-5,6-dihydroacylation by, 3, 88... 

Triazolo[4,3-a]pyridine, 3-amino-diazonium reactions, 5, 863 Dimroth rearrangement, 5, 861 Sandmeyer reaction, 5, 862 synthesis, 5, 883... 

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