Ethanol, diazonium salt reaction

The high reactivity of the 5-position in 1.3-selenazoles toward electrophilic substitution was also observed on azocoupling. By reacting molar quantities of an aqueous solution of a diazonium salt with an ethanolic solution of a 2-arylamino selenazole. for example, the corresponding 2-arylamino-5 azoselenazoles are formed in a smooth reaction (100). They deposit from the deeply colored solution and form intenselv red-colored compounds after their recrystallization from a suitable solvent (Scheme 36l. 

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 most cases diazonium salts are not isolated, but are converted into products by reactions that can be carried out in situ. Moreover, it is actually recommended not to isolate these salts, not even for purification purposes, as many of them have a tendency to explode. In addition, the high solubility of most diazonium salts in water makes precipitation from this medium difficult. Therefore, to obtain solid diazonium salts the recommended method for many decades was to carry out diazotizations in ethanol followed by precipitation with ether. As inorganic salts of nitrous acid are scarely soluble in ethanol, Knoevenagel recommended alkyl nitrites (ethyl or isopentyl nitrite) as diazotization reagents as long ago as 1890. Various other solvents have subsequently been used for diazotizations with alkyl nitrites (see Saunders and Allen, 1985, p. 23 ff.), but as a method for obtaining solid diazonium salts this has been superseded by the isolation of diazonium tetrafluoroborates and, to a lesser degree, of hexafluorophosphates. 

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. 

Heck reactions of arenediazonium salts can be conveniently carried out with [Pd(OAc)2] in ethanol. This method was extended to the one-pot sequential diazotation and allylation of aniUnes (Scheme 6.7). The latter were converted to the corresponding diazonium salts at 0 °C with NaNOa + 42 % HBF4. Ethyl acrylate and [Pd(OAc)2] were added and the reaction mixture was heated on a water bath for 1 h. The corresponding cinnamate esters were obtained in 65-80 % yield [22],... 

N-Acetyl-2,5-dimethoxy-4-iodophenylisopropylamine. 5 g of the diazonium salt is prepared as described immediately above and cooled to 0° then added gradually to a solution of 8 g of potassium iodide in 10 ml of water. After reaching room temp the reaction is set until the evolution of nitrogen has stopped. The dark brown viscous semi-solid that will separate is dissolved in ethanol with heat and then eooled. On cooling the title material separates out and is crystallized from ethanol. Yield 1.97 g, mp 167-168°. 

Again the Sandmeyer reaction is frequently used to convert amino- to halo-isoquinolines. The diazonium salt of 5-amino-8-isoquinolinol (14) on treatment with potassium iodide and iodine gives the 5-iodophenol (15). Iodination of the hydrochloride of (15) with iodine monochloride in ethanol gives (16 Scheme 9) (66JMC46). 

Nitration of hydroxypropiophenone (7-1) followed by conversion of the phenol to its methyl ether by means of methyl iodide provides the intermediate (7-2) the nitro group is then reduced to the corresponding amine (7-3) by catalytic reduction. The newly introduced amine is then replaced by a nitrile group by successive conversion to the diazonium salt by means of nitrous acid followed by treatment with cuprous cyanide (7-4). Reaction with aluminum chloride removes the methyl ether to afford the ortho acylphenol (7-5). This is converted to the chromone (7-6) as above by reaction with benzoyl chloride and sodium benzoate. The nitrile is next hydrolyzed to the carboxylic acid (7-7) by means of sulfuric acid. The acid is then converted to its acid chloride by means of thionyl chloride and that treated with 2-(A -piperidyl)ethanol (7-8). There is thus obtained flavoxate (7-9) [8], a muscle relaxant whose name reflects its flavone nucleus. 

Aminobenzo[6]thiophene is prepared from 7-hydroxybenzo[6]-thiophene by means of the Bucherer reaction it may be converted into 7-nitrobenzo[6]thiophene via the diazonium salt.84 5,7-Diamino-3-phenylbenzo[6]thiophene and its 2-carboxylic acid are prepared by reduction of the corresponding dinitro compound.334 Partial reduction of o,7-dinitro-3-phenylbenzo[6]thiophene-2-carboxylic acid with ethanolic ammonium sulfide affords 7-amino-5-nitro-3-phenylbenzo-[6]thiophene-2-carboxylic acid, the amino group of which may be replaced by hydrogen or iodine via the diazonium salt.334 7-Amino-4-methoxybenzo[6]thiophene is mentioned in the patent literature.560... 

Macrae and Wright (96) demonstrated that visible light irradiation of xanthene dyes (eosin, erythrosin, rhodamine B, or RB) in ethanolic solutions of 4-(N,N-diethylamino)benzene-diazonium chloride (as the zinc chloride double salt) resulted in decomposition of the diazonium salt. Electron transfer from the dye excited state(s) to the diazonium salt was postulated and dye-diazonium salt ion pair formation in the ground state was shown to be important. Similar dyes and diazonium salts were claimed by Cerwonka (97) in a photopolymerization process in which vinyl monomers (vinylpyrrolidone, bis(acrylamide)) were crosslinked by visible light. Initiation occurs by the sequence of reactions in eqs. 40-42 ... 

To prepare the solid benzenediazonium chloride or sulphate, the reaction is conducted in the absence of water as far as possible. The source of nitrous acid is one of its organic esters (e.g. pentyl nitrite) and a solution of hydrogen chloride gas in absolute ethanol upon the addition of ether only the diazonium salt is precipitated as a crystalline solid. 

The first irregularity appeared in 1870. It was found that two chlorotoluidines, when diazotized and boiled with ethanol, gave the corresponding ethyl ethers the reaction of a diazonium salt with ethyl alcohol had taken an alternative course. 

Later it was found that the decomposition of benzenediazonium salts with ethanol actually yields phenyl ethyl ether contaminated with a little benzene. This, coupled with the fact that a number of instances of ether formation had been recorded, led to the suggestion that the normal products of reaction between diazonium salts and ethanol are the ethers. 

This gradation is illustrated by the results obtained with the diazonium salts from the isomeric aminobenzoic adds. When the orthQ diazonium nitrate is treated with absolute ethanol only reduction occurs 23 ethyl benzoate is obtained in 63% yield.f The diazonium add sulfate derived from ra-aminobenzoic add is converted into a mixture of ethyl benzoate and ethyl m-ethoxybenzoate, the former preponderating.24 23122 Finally, with the p-diazonium salts the ether reaction is the favored one 22123 from the nitrate the yields of p-ethoxy benzoic add and ethyl benzoate are 60% and 12%, respectively. 

Metals, Metallic Oxides, and Salts. In an effort to facilitate the reduction of diazonium salts by ethanol, a number of metals, oxides, and salts are added to the reaction mixture. Finely divided cop-per, 2 - 37 68- 66- 67 cuprous oxide,6 -44- - f and cupric sulfate °-70 are often employed. 

Very often reduction of diazonium salts by ethanol requires tempera tures in the neighborhood of the boiling point of the alcohol. The reaction may take place with violence so that, once it is started, moderation by external cooling may be necessary.14 28 84... 

The 4-aminopyridine derivative 92, prepared from the reaction of ethyl benzoylacetate and malononitrile dimer 91, undergoes the coupling reaction with aromatic diazonium salts to afford azo derivatives such as 93. Under refluxing conditions in ethanolic sodium hydroxide, these azo compounds cyclize to pyrido[3,2-f]pyridazines and pyrido[3,2-r]-pyridazino[2, 3 - ]quinazolines (Scheme 15) <2005AP329>. 

Carboxyphenyl Phenyl Tellurium2 27.2 g (0.2 mol) of 2-aminobcnzoic acid arc dissolved in a mixture of 25 ml of concentrated hydrochloric acid and 70 ml of water. 13.8 g of sodium nitrite dissolved in 20 ml of water are added dropwisc to the stirred amine solution cooled in an icc/walcr bath. Sodium hydrogen carbonate is added until the solution of the diazonium salt is slightly basic. 23 g (56 mmol) of diphenyl ditellurium are dissolved in a mixture of 30 ml of ethanol and 60 ml of THF. To this solution are added 2.3 g (60 mmol) of sodium borohydride dissolved in 33 ml of 1 M aqueous sodium hydroxide. The diazonium salt solution is quickly added to the warm benzenetellurolate solution. 10 ml of 1 M sodium hydroxide are then added and, after the evolution of nitrogen has ceased, the mixture is heated to complete the reaction. The mixture is poured onto ice and diphenyl ditellurium is extracted with benzene. The aqueous phase is acidified with 1 M hydrochloric acid and the product precipitates in analytically pure form yield 28.2 g (43%) m.p. 185° (from toluene). 

A mixture of 50 g. (0.35 mole) of 2-naphthylamine, 670 ml. of water, and 140 ml. of concentrated hydrochloric acid is diazotized at 0-10° in the usual manner by the addition of 20% aqueous sodium nitrite solution. To the resulting solution of the diazonium salt is added with stirring a cold suspension of mercuric bromide formed by treating 57 g. (0.175 mole) of mercuric nitrate with 83 g. (0.80 mole) of sodium bromide in a total volume of 250 ml. of water. The precipitated yellow complex is removed by filtration, washed with water and acetone, and air-dried. It weighs 137-149 g. The solid is mixed well with 300 g. of powdered sodium bromide, and the mixture is added in several portions to a reflux apparatus heated to 90° in an oil bath. Vigorous evolution of gas follows the addition of each portion. After decomposition is complete, the reaction mixture is extracted with benzene and the benzene solution is washed with dilute acid and alkali. Removal of the solvent followed by two distillations of the residual oil gives a product boiling at 103-104°/4 mm. After one recrystallization from a mixture of 110 ml. of hot ethanol and 4 ml. of water, 38-43 g. (53-59%) of colorless plates of 2-bromonaphthalene, m.p. 55-56.4°, is obtained. 

Benzoselenazole-2-thione 63 is obtained by a four-step procedure starting from o-nitroaniline <2002J(P1)1568, 2001CC1336>. Reaction of potassium selenocyanate with the diazonium salt yields o-nitrophenyl selenocyanate. Treatment of the o-nitrophenyl selenocyanate with sodium in ethanol affords bis(o-nitrophenyl) diselenide. The m situ reduction of this with sodium hydrosulfide gives an intermediate o-aminobenzeneselenoate, which cyclizes with carbon disulfide in basic medium, work-up giving 3/7-benzoselenazole-2-thione 63 (Scheme 22). 

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