Benzenediazonium Chloride1

[110-34-5]  · C6H5ClN2  · Benzenediazonium Chloride  · (MW 140.57)

(can form azo compounds by coupling with carbon and hetero nucleophiles,1a-c,e,f and a wide variety of benzene derivatives with concomitant dediazoniation;1 substrate for aromatic substitution)

Alternate Name: phenyldiazonium chloride.

Physical Data: no mp (explodes on heating).

Solubility: very sol H2O, cold glacial acetic acid; sol abs. ethanol, acetone; insol diethyl ether, CHCl3, benzene.

Form Supplied in: colorless needles, not commercially available. The dry salt can detonate violently and should, therefore, not be isolated as such. Typically, it is prepared by amine diazotization in water or an organic solvent, and the solution or suspension so obtained is used directly.

Analysis of Reagent Purity: usually none (in situ preparation).

Preparative Methods: 1a,b an aqueous solution of PhN2+Cl- is obtained by adding a stoichiometric amount of NaNO2 at 0-5 °C to the solution obtained from aniline and excess hydrochloric acid in water (eq 1). An excess of nitrite ions at the end of the reaction should be avoided, since they reduce the stability of the diazonium salt solution and can interfere with some further transformations. An excess of HNO2 is detected with starch-KI paper that turns blue immediately on contact with the reaction solution, and can be destroyed with urea or amidosulfuric acid. A large variety of arenediazonium chlorides and sulfates (using H2SO4 instead of HCl) can be prepared by amine diazotization; for less basic and less soluble aromatic amines, the reaction conditions have to be somewhat modified.2 When the diazotization is carried out with an organic nitrite (typically pentyl nitrite) in an organic solvent such as HOAc, ethanol, or dioxane (eq 1),3 the solid diazonium salt either separates from the solution or can be precipitated by addition of a nonpolar solvent. The same is true for diazotization of PhN(SiMe3)2 with NOCl formed in situ from an organic nitrite and Me3SiCl in dry CH2Cl2 (eq 2).4

Handling, Storage, and Precautions: dry benzenediazonium chloride explodes on heating, shock, and friction. It deliquesces in moist air with decomposition, but is rather stable in dry air in the dark and in aqueous solution at 0 °C. The decomposition of aqueous solutions of PhN2+Cl- at several temperatures and pH values has been studied by various authors.5 Less labile than the chloride is the sulfate salt, which does not explode below ca. 100 °C and has a low shock-sensitivity. The salt (PhN2+)2ZnCl42-, obtained from PhN2+Cl- and ZnCl2, is considered as a stabilized diazonium salt, but an explosion hazard on drying has also been reported.6 In other arenediazonium salts, both electron-withdrawing and electron-donating p-substituents as well as m-NO2, m-Br, and m-Cl retard the dediazoniation, whereas m-MeO and m-alkyl groups favor it.1a,d,7 Arenediazonium salts are stabilized both in the solid state and in solution by complex formation with arenesulfonic acids (especially 1- and 2-naphthalenesulfonic acids),1a,8 crown ethers, and polyethylene glycols.1e

Formation of Covalent Azo Compounds.

The arenediazonium ion reacts at the terminal N atom with a wide range of nucleophiles.1a,c,7,9 The most important reaction of this type is the synthesis of diarylazo compounds by coupling with phenols, naphthols, aromatic amines, and similar electron-rich aromatic substrates. Electron-rich heteroaromatic and related CH-acidic heterocyclic compounds as well as heteroarenediazonium salts can also participate in this azo coupling reaction which gives access to a great variety of azo dyes and also to azo compounds that are of interest as pharmaceuticals or liquid crystalline materials.1a,b,f,10,11 In general, the arenediazonium salt is prepared in situ by diazotization of an aromatic amine (see above), and coupled in aqueous solution at pH 3.5-7.0 with another aromatic amine or at pH 5-9 with a phenol derivative. The reaction takes place exclusively at the p- and o-positions (eqs 3 and 4). The different aspects of this aromatic SE reaction (mechanism, reactivity, orientation effects) have been studied extensively.12 In agreement with the electron demand of an aromatic SE reaction, the reactivity sequence for substituted phenols and naphthols as coupling components is O-> NR2 > NHR > OR &AApprox; OH >> Me.1a,12 Whereas 1,3,5-trimethoxybenzene couples with PhN2+, the more electrophilic 4-nitro- and 2,4-dinitrobenzenediazonium ions are needed for azo coupling with 1,3-dimethoxybenzene and anisole, respectively.13 With primary or secondary aromatic amines, N-coupling to give triazenes can compete with or dominate over aromatic C-coupling in weakly acidic, neutral or basic solution. The triazenes can undergo an acid-catalyzed intermolecular rearrangement1a to the diarylazo compounds. This two-step sequence is sometimes preferred over the direct azo coupling process and has found technical application (eq 5).14

Azo coupling reactions with in situ generated arenediazonium salts have also been performed on azulenes,15 2-alkoxy-1,6-methano[10]annulenes,16 and tropolones.1c Since azo compounds can be reductively cleaved into two amine moieties, the azo coupling route allows the regioselective introduction of NH2 into an electron-rich aromatic substrate.17 Furthermore, the chemical stability of the azo group allows modifications on the aromatic nucleus before cleavage (eq 6).18 The transformations of azulene to 1-aminoazulene19 and of tropolone to 5-aminotropolone1c have been realized similarly.

The covalent azo compounds obtained from ArN2+ and CN- or hetero nucleophiles1a,c,7,9 are of lesser synthetic importance. Some of them, e.g. anti-areneazocyanides (Ar-N=N-CN), anti-areneazosulfonates (Ar-N=N-SO3-), and areneazophosphonates (Ar-N=N-P(O)(OR)2) are thermally stable enough to be useful for further transformations, whereas others split off N2 more readily to generate aryl radicals by a homolytic pathway. The latter decomposition mode is involved in some synthetically useful transformations of ArN2+ salts into functionalized aromatics (see below).

Reduction to Arylhydrazines.

Arenediazonium salts can be converted into arylhydrazines preferably with SnCl2/HCl, Na2SO3, or Na2S2O4, or by conversion into Ar-N=N-SO3- or Ar-N=N-P(O)(OR)2 and reduction with Zn/HOAc.20 While reduction with SnCl2 is most convenient for small-scale preparations, Na2SO3 is favored for large batches (eq 7).21

Formation of Arylhydrazones and Formazans.

Arenediazonium salts can be coupled with many active methylene and methine compounds and also with some CH-acidic methyl groups.22 The reactions are usually carried out in aqueous solution buffered with NaOAc. Alcohol, pyridine, or HOAc are sometimes added for better solubility of the reactants. 1,3-Diketones, b-keto aldehydes, b-keto esters, malonic esters, b-cyano esters, b-cyano sulfones, and malononitriles all react at the active CH2 group to give arylhydrazones (eq 8).23 The reaction of PhN2+Cl- with 2 equiv of ethyl acetoacetate yields 3-ethoxycarbonyl-1,5-diphenylformazan24 with elimination of the acetyl group. Other b-keto esters, oxaloacetic esters, b-keto acids, and malonic acid monoesters behave analogously, the latter two with elimination of CO2.22 Acetone (eq 9) and nitromethane also afford formazans, whereas higher nitroalkanes (RCH2NO2) as well as activated methyl compounds such as 2-methylpyridine and 9-methylacridine yield the normal arylhydrazones.22

Methine compounds activated by two electron-withdrawing groups (Z) react with arenediazonium chlorides to give azo compounds that undergo a rapid acid cleavage of the (hetero-)1,3-dicarbonyl system with formation of arylhydrazones (Japp-Klingemann reaction) (eq 10).25 An aqueous base (NaOH) is sometimes added to facilitate the cleavage reaction. Phenylhydrazones derived from acetoacetic esters can be reduced to amino acid esters und utilized in Fischer-type indole syntheses.1c,22 By the same sequence, cyclic b-keto esters are cleaved to acyclic o-carboxy-2-arylhydrazono carboxylic esters and can be converted to o-carboxy-a-amino acids or 3-(o-carboxyalkyl)indoles (eq 11).1c,22,26,27

Functionalized Arenes from Aromatic Amines via Arenediazonium Salts.

The N2+ group of arenediazonium salts can be replaced by H and a variety of functional groups. These straightforward dediazoniation reactions can occur by heterolytic (SN1), homolytic, and (for certain o-substituted ions) aryne mechanisms.1d,7,28 Table 1 lists some of the more important transformations; further examples can be found elsewhere.1c,1f,29 The copper(I)-mediated synthesis of ArCl and ArBr from arenediazonium halides (Sandmeyer reaction) has seen various modifications to improve the yield.30 A particularly efficient approach is the direct conversion of arylamines into ArCl and ArBr with t-butyl nitrite and CuX2 in anhydrous acetonitrile.31

Biaryl Synthesis.

Biaryls can be obtained when a cold aqueous solution of an arenediazonium chloride is added to a mixture of aqueous NaOH (15-40%) or NaOAc and an aromatic solvent (Gomberg-Bachmann reaction39). Benzene and many substituted arenes as well as thiophene and pyridine have been used as coupling partners. There is good evidence that the reaction normally proceeds by a free radical chain mechanism, with aryl radicals as reactive species.7,40 The yields rarely exceed 45%, and positional isomers are sometimes obtained from substituted arenes (eq 12).41 Higher yields result when isolated arenediazonium salts (see Benzenediazonium Tetrafluoroborate) are employed under PTC conditions. In view of the drawbacks mentioned, the Gomberg-Bachmann reaction must give way to more efficient and selective procedures for the synthesis of more highly substituted and functionalized biaryls.42 Appropriately substituted arenediazonium salts (chlorides and sulfates) can undergo intramolecular aryl-aryl coupling to give phenanthrene derivatives (Pschorr cyclization43), often in acceptable yield. Fluorenes, fluorenones, and phenanthridones can be obtained analogously. The cyclization is most often copper-catalyzed (eq 13), but several other methods also exist.42a,43 Copper-mediated cyclization of the isolated arenediazonium BF4 salts in acetone is also in use.44

Arylation of Alkenes.

Arenediazonium chlorides react, in aqueous or H2O-acetone solution and in the presence of CuI or CuII salts, with alkenes by dediazoniation and addition of Ar-Cl across the alkene bond (Meerwein arylation1b,1f,45). Alkenes activated by groups such as acyl, cyano, chloro, aryl, vinyl, and ethynyl are best suited for this reaction (eq 14)45,46 which proceeds via aryl radicals.45 Elimination of HCl may lead to a formal substitution product under the reaction conditions. Instead of using the preformed arenediazonium chloride, the Meerwein arylation product can be obtained directly and in improved yield from an arylamine by treatment with an alkyl nitrite and CuCl2 in acetonitrile or acetone solutions that contain the alkene (eq 15).47

The reductive b-arylation of a,b-unsaturated carbonyl compounds and acrylonitrile can be realized in the presence of an excess of TiCl3 in a solution of water and a water-miscible organic solvent. The best yields have been obtained with methyl vinyl ketone as the substrate (eq 16).48 When steric and electronic effects divert the attacking aryl radical to the position a to the carbonyl, a different result is obtained.49 For the Pd-mediated arylation of unactivated alkenes, see Benzenediazonium Tetrafluoroborate. In contrast to the example in eq 16, simple carbonyl compounds do not undergo an analogous arylation reaction. However, N-benzylanilines result when an arenediazonium salt is decomposed by TiCl3 in aqueous acid in the presence of an aldehyde and a primary aromatic amine.50

1. (a) Zollinger, H. Azo and Diazo Chemistry - Aliphatic and Aromatic Compounds; Interscience: New York, 1961. Zollinger, H. Diazo Chemistry I - Aromatic and Heteroaromatic Compounds; VCH: Weinheim, 1994. (b) Pütter, R. MOC 1965, X/3, 7. (c) Wulfman, D. S. In The Chemistry of Diazonium and Diazo Groups, Part 1; Patai, S., Ed.; Wiley: Chichester, 1978; pp 247-339. (d) Zollinger, H. In The Chemistry of Triple-Bonded Functional Groups, Part 1; Patai, S.; Rappoport, Z., Eds.; Wiley: Chichester, 1983; pp 603-669. (e) Bartsch, R. A. In The Chemistry of Triple-Bonded Functional Groups, Part 2; Patai, S.; Rappoport, Z., Eds.; Wiley: Chichester, 1983; pp 889-915. (f) Engel, A. MOC 1990, E16a, 1052.
2. A representative collection of procedures for PhN2+Cl- and various other arenediazonium salts is found in Ref. 1b. See also: Fierz, H. E.; Blangey, L. Grundlegende Operationen der Farbenchemie, 8th ed.; Springer: Wien, 1952; p 243.
3. (a) Hantzsch, A.; Jochem, E. CB 1901, 34, 3337. (b) Knoevenagel, E. CB 1890, 23, 2994. (c) Friedman, L.; Chlebowski, J. F. JOC 1968, 33, 1633.
4. Weiss, R.; Wagner, K.-G.; Hertel, M. CB 1984, 117, 1965.
5. See: Beilsteins Handbuch der Organischen Chemie, EIII, 4th ed.; Springer: Berlin, 1974; Vol. 16, Part 1, p 506.
6. Muir, G. D. CI(L) 1956, 58.
7. Hegarty, A. F. In The Chemistry of Diazonium and Diazo Groups, Part 2; Patai, S., Ed.; Wiley: Chichester, 1978, pp 511-591.
8. Saunders, K. H. The Aromatic Diazo-Compounds and their Technical Applications, 2nd ed.; E. Arnold & Co.: London, 1949; p 93.
9. Pütter, R. MOC 1965, X/3 511.
10. Lang-Fungmann, S. MOC 1992, E16d, 1.
11. Heterocyclic coupling components: Schwander, H. R. Dyes Pigm. 1982, 3, 133.
12. Szele, I.; Zollinger, H. Top. Curr. Chem. 1983, 112, 1.
13. v. Auwers, K.; Michaelis, F. CB 1914, 47, 1275.
14. Ruggli, P.; Courtin, A. HCA 1932, 15, 75.
15. (a) Gerson, F.; Heilbronner, E. HCA 1958, 41, 1444, and ref. cit. (b) Gerson, F.; Schulze, J.; Heilbronner, E. HCA 1958, 41, 1463. (c) Nozoe, T.; Asao, T.; Kobayashi, M. BCJ 1973, 46, 3266.
16. Neidlein, R.; Radke, C.-M.; Hädicke, E.; Gieren, A. CB 1983, 116, 2881.
17. Schröter, B. MOC 1957, 11/1, 522f.
18. Tarbell, D. S.; Hirschler, H. P.; Hall, T. J. JACS 1953, 75, 1985. The route via the azo compound proved more satisfactory than the one by reduction of 3-nitro-4-methoxybiphenyl.
19. Schulze, J.; Heilbronner, E. HCA 1958, 41, 1492.
20. (a) Müller, N. MOC 1990, E16a (Part 1), 656. (b) Enders, E. MOC 1967, X/2 (Part 2), 180f.
21. Coleman, G. H. OSC 1942, 1, 442. (b) Stephenson, E. F. M. OSC 1955, 3, 475.
22. Parmerter, S. M. OR 1959, 10, 1.
23. Bülow, C.; Neber, P. CB 1912, 45, 3732.
24. Bamberger, E.; Wheelwright, E. W. JPR [2] 1902, 65, 123.
25. Phillips, R. R. OR 1959, 10, 143.
26. (a) Feofilatkov, V. V.; Ivanov, A. ZOB 1943, 13, 457 (CA 1944, 38, 3255). (b) Feofilatkov, V. V.; Semenova, N. K. IZV 1952, 2, 98 (CA 1954, 48, 668).
27. Tietze, L. F.; Eicher, T. Reaktionen und Synthesen im Organisch-chemischen Praktikum und Forschungslaboratorium, 2nd ed.; Thieme: Stuttgart, 1991; pp 332, 402.
28. Zollinger, H. AG(E) 1978, 17, 141.
29. Such transformations are discussed in different volumes of MOC; for cross-references, see: MOC, 1965, X/3 113, and MOC 1990, E16a 1088.
30. (a) Hodgson, H. H. CRV 1947, 40, 251. (b) Cowdrey, W. A.; Davies, D. S. QR 1952, 6, 358. (c) Galli, C. TL 1980, 4515.
31. Doyle, M. P.; Siegfried, B.; Dellaria, Jr., J. F. JOC 1977, 42, 2426.
32. Kornblum, N. OR 1944, 2, 262.
33. (a) (X = Cl) Marvel, C. S.; McElvain, S. M. OSC 1941, 1, 170. (b) (X = Br): Bigelow, L. A. OSC 1941, 1, 80. (c) (X = Br): Hartwell, J. L. OSC 1955, 3, 185.
34. Example: Lucas, H. J.; Kennedy, E. R. OSC 1943, 2, 351.
35. Clarke, H. T.; Read, R. R. OSC 1941, 1, 514.
36. (a) Lambooy, J. P. JACS 1950, 72, 5327. (b) Ungnade, H. E.; Orwoll, E. F. OSC 1955, 3, 130. (c) Cohen, T.; Dietz, A. G.; Miser, J. R. JOC 1977, 42, 2053.
37. (a) Meerwein, H.; Dittmar, G.; Göllner, R.; Hafner, K.; Mensch, F.; Steinfort, O. CB 1957, 90, 841. (b) Yale, H. L.; Sowinski, F. JOC 1960, 25, 1824. (c) Hoffman, R. V. OSC 1990, 7, 508.
38. Smith, P. A. S.; Boyer, J. H. OSC 1963, 4, 75.
39. (a) Bachmann, W. E.; Hoffman, R. A. OR 1944, 2, 224. (b) Dermer, O. C.; Edmison, M. T. CRV 1957, 57, 77.
40. (a) Rüchardt, C.; Merz, E. TL 1964, 2431. (b) Rüchardt, C.; Freudenberg, B. TL 1964, 3623.
41. (a) Hey, D. H.; Nechvatal, A.; Robinson, T. S. JCS 1951, 2892. (b) Ito, R.; Migita, T.; Morikawa, N.; Simamura, O. BCJ 1963, 36, 992.
42. (a) Sainsbury, M. T 1980, 36, 3327. (b) Bringmann, G.; Walter, R.; Weirich, R. AG 1990, 102, 1006; AG(E) 1990, 29, 977.
43. (a) DeTar, D. F. OR 1957, 9, 409. (b) Floyd, A. J.; Dyke, S. F.; Ward, S. E. CRV 1976, 76, 509.
44. Hey, D. H. QR 1971, 25, 483.
45. Rondestvedt, C. S., Jr. OR 1976, 24, 225; OR 1960, 11, 189.
46. Dombrovskii, A. V.; Yurkevich, A. M.; Terent'ev, A. P. ZOB 1957, 27, 3047 (CA 52:8087).
47. Doyle, M. P.; Siegfried, B.; Elliott, R. C.; Dellaria, J. F., Jr. JOC 1977, 42, 2431.
48. (a) Citterio, A. OSC 1990, 7, 105. (b) Citterio, A.; Vismara, E. S 1980, 291.
49. Citterio, A.; Minisci, F.; Vismara, E. JOC 1982, 47, 81.
50. Clerici, A.; Porta, O. TL 1990, 31, 2069.

Gerhard Maas

University of Kaiserslautern, Germany

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