Methanol, diazonium salt reaction

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. 

Broxton and Bunnett (1979) determined the products of the reaction of 4-chloro-3-nitrobenzenediazonium ions with ethoxide ion in ethanol, which is exactly analogous to the reaction in methanol discussed earlier in this section. These authors found 12.8% 4-chloro-3-nitrophenetole, 83% 2-chloronitrobenzene, and 0.8% 2-nitrophenetole. When the reaction was carried out in C2H5OD, the first- and second-mentioned products contained 99% D and 69% D respectively. Dediazoniation in basic ethanol therefore results in a higher yield of hydro-de-diazoniation with this diazonium salt compared with the reaction in methanol. This is probably due to the slightly higher basicity of the ethoxide ion and to the more facile formation of the radical CH3-CHOH (Packer and Richardson, 1975). Broxton and McLeish (1983 c) measured the rates of (Z) — (E) interconversion for some substituted 2-chlorophenylazo ethyl ethers in ethanol. 

Let us now consider the formation of aryl iodides from aryl diazonium salts and potassium iodide in methanol (Singh and Kumar 1972a, 1972b). Electron-donor substituents decelerate the process as compared with benzene diazonium (the substituent is hydrogen), whereas electron acceptor substituents accelerate it. Oxygen inhibits the reaction, and photoirradiation speeds it up. As the authors pointed out, in the case of 4-nitrobenzene diazonium, the reaction leads not only to 4-iodonitrobenzene but also to nitrobenzene, elemental iodine, and formaldehyde. All of these facts support the following sequence of events ... 

The reaction of phenacyltriphenylarsonium bromides (333) with aromatic diazonium salts in methanol containing sodium acetate provides a simple method for synthesizing 3,6-diaroyl-l,4-dihydro-l,2,4,5-tetrazines (334) in good yield (78JOM(155)293). The reaction has been postulated to proceed via the nitrilimine intermediate (335), whose formation can be explained by the sequence shown in Scheme 19. 

In the extensive review of diazotisation, frequent reference is made to the need for close temperature control during processing operations, and to the explosive nature of isolated diazonium salts [1]. Inclusion of methanol in the reaction mixture used to diazotise 2-toluidine, and use of sulfuric acid rather than acetic acid in the ensuing... 

Treatment with diazonium salts proceeds between 0 and — 5 ° in pyridine-methanol solution, and this affords an outstanding reagent for distinguishing between iV-glycosyl derivatives and aminodeoxyketoses. When the reaction is performed in aqueous solution, two isomeric compounds are formed. Depending on the acidity of the medium, the triazine (54) or the azo form (55) preponderates. 

The application of a triazene motif to the development of a photolabile linker was reported by Enders in 2004 [63]. The reaction of a secondary amine with polymer-bound diazonium salt 45 produced the triazene moiety 46. It was stable to a wide range of non-acidic conditions, suitable for other organic reactions. Photocleavage was carried out with 355 nm UV laser irradiation (3co Nd-YAG) in methanol-diethyl ether (Scheme 17.22). 

Quantum yields for the photoelectron transfer process in methanol are generally greater than unity, because the solvent radical takes part in a chain reaction (Scheme 3), the efficiency of which depends on the concentration of the diazonium salt and on the substitution pattern. " Quantum yields for decomposition are around 80 for 4-nitrobenzenediazonium (10 M), 5 for 4-chlorobenzenediazonium (10" M), and about 2 for 4-methylbenzenediazonium (5 XlO" M). Added 2-methyl-2-nitrosopropane acts as a scavenger for phenyl radicals and, under these conditions, the quantum yield for diazonium salt... 

Both diazonium salts and iodonium salts can be effectively used as arylating agents. The aryl group is transferred either heterolyt-ically or homolytically, depending on the choice of salt and reaction conditions. In acid solution diazonium salts decompose relatively cleanly to give products consistent with a polar mechanism. In basic solution the product is a complex mixture resulting from free radical intermediates (6). When either benzenediazonium chloride or fluoborate is decomposed in acidic methanol, the major product, formed in 93% yield, is anisole, and less than 1% biphenyl is isolated. In the same solvent with an acetate buffer, the product contains 85-90% benzene, 4.5% biphenyl, 0.6% azobenzene, some anisole, and 80-90 mole % formaldehyde per mole of diazonium salt decomposed (7). 

In basic solution diazonium salts decompose by a complex process, very probably involving a radical chain reaction (7,29,30). The rates in methanol are strongly sensitive to oxygen and not very reproducible. Oxygen, however, has relatively little effect on the product composition. The reaction order is complex, probably mixed, and details of mechanism are still uncertain and controversial. 

Attempts to trap the diazonium intermediate 2.252 by addition of nitrosyl chloride to a solution of the amine 2.251 in CH2CI2 at — 70°C, followed by addition of a methanol solution of the sodium salt of 2-naphthol, gave no azo compound. (It seems to the present author that the reaction conditions for these trapping experiments have not been studied in sufficient detail to be conclusive.) In their second paper, Curtin et al. (1965 b) selected 3-amino-2-phenyl-l//-inden-l-one (2.256) for... 

---