Chloride diazonium salts

Diazopyrazoles can be converted into very stable diazonium salts (chloride or bromide) upon treatment with the corresponding concentrated acid at room temperature (76JOC3781 84JHC957). Stable diazonium tetrafluoroborate [87JOC5538], platinichloride, and aurichloride [14JCS(105)435] can be isolated. Only in the case of the unstable 3-diazo-pyrazole was it necessary to operate at low temperature and in non aqueous solvents (61CB1036). 

Chloroformate Chlorosulfonylcarbamate Cyclopropane Diazide 1,2-Diazine Diazoimide Diazoester Diazonium Salt Chloride Diene Diketone Diol... 

Copper 1) chloride, bromide and cyanide were used by Sandmeyer to introduce a chlorine, a bromine atom and a cyanide group respectively into a benzene ring by addition to the phenyl diazonium salt. 

In preparing an aqueous sol ution of a diazonium salt, such as benzene-diazonium chloride, it is usual to dissolve the amine in a slight excess (about 2 2 molecular equivalents) of dilute hydrochloric acid (or alternatively to dissolve the crystalline amine hydrochloride in i 2 equivalents of the acid) and then add an aqueous solution of a metallic nitrite. Nitrous acid is thus generated in situ, and reacts with the amine salt to give the diazonium compound. For a successful preparation of an aqueous solution of the diazonium salt, however, two conditions must always be observed ... 

When an aqueous solution of a diazonium salt is added to an alkaline solution of a phenol, coupling occurs with formation of an azo-compound (p. 188). If ho vc cr the ntiueous solution of the diazonium salt, t. . ., />-bromohenzene diazonium chloride, is mixed with an excess of an aromatic hydrocarbon, and aqueous sodium hydroxide then added to the vigorously stirred mixture, the diazotate which is formed, e.g., BrC,H N OH, dissolves in the hydrocarbon and there undergoes decomposition with the formation of nitrogen and two free radicals. The aryl free radical then reacts with the hydrocarbon to give a... 

Primary aromatic amines differ from primary aliphatic amines in their reaction with nitrous acid. Whereas the latter yield the corresponding alcohols (RNHj — ROH) without formation of intermediate products see Section 111,123, test (i), primary aromatic amines 3neld diazonium salts. Thus aniline gives phcnyldiazonium chloride (sometimes termed benzene-diazonium chloride) CjHbNj- +C1 the exact mode of formation is not known, but a possible route is through the phenjdnitrosoammonium ion tlius ... 

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

Dissolve 3-5 g. of aniline hydrochloride in 20 ml. of absolute ethyl alcohol contained in a 50 ml. conical flask, and add 0-5 ml. of a saturate solution of hydrogen chloride in absolute ethyl alcohol. Cool in ice and add 4 g. (4 -6 ml.) of iso-amyl nitrite (compare Section 111,53) gradually. Allow the mixture to stand for 5-10 minutes at the room temperature, and precipitate the diazonium salt by the gradual addition of ether. Filter ofiF the crystals at the pump on a small Buchner funnel, wash it with 5 ml. of alcohol - ether (1 1), and then with 10 ml. of ether. Keep... 

The diazonium salt solution decomposes on standing and hence must be mixed with the Cuprous chloride solution without delay. Mechanical stirring is an advantage. 

Attention has previously (see Diazonium Sails) been drawn to the fact that unless an excess of hydrochloric (or mineral) acid is used in the diazotisation process, coupling occurs between the diazonium salt and the amine to give diazoamino compounds. Thus phenyldiazonium chloride and aniline yield diazoaminobenzene. This substance may be conveniently prepared by dissolving two equivalents of aniline in three equivalents of hydrochloric acid, and adding one equivalent of sodium nitrite in aqueous solution followed by two equivalents of sodium acetate ... 

Unsymmetrical diaryls may be prepared by treating an aryl diazonium salt solution with sodium hydroxide or sodium acetate in the presence of a liquid aromatic compound. Thus 2-chlorodiphenyl is readily formed from o-chloro phenyl diazonium chloride and sodium hydroxide solution (or sodium acetate solution) in the presence of benzene ... 

Owing to their particular interest two individual reactions will now be discussed separately. The reaction of methoxycarbonylhydrazine and 3-bromo-2,4-pentanedione affords, in addition to the expected pyrazole (608), a pyrazolium salt (609), the structure of which was established by X-ray crystallography (74TL1987). Aryldiazonium salts have been used instead of arylhydrazines in the synthesis of pyrazolines (610) and pyrazoles (611) (82JOC81). These compounds are formed by free radical decomposition of diazonium salts by titanium(n) chloride in the presence of a,/3-ethylenic ketones. 

Thymoquinone has been prepared directly from thymol by sulfonating and oxidizing the sulfonation mixture with manganese dioxide or potassium dichromate the same process has been successfully applied to carvacrol. The oxidation of sa ts of aminothymol with dichromate, ferric chloride, or nascent bromine also leads to satisfactory yields of thymoquinone. The above procedure is based on the observation that the diazonium salt obtained from aminothymol is almost quantitatively con-... 

The 4-chloroben2enediazon1um chloride solution Is prepared as follows finely powdered 4-chloroaniline (5.65 g, 0.044 mol) is suspended in 18 ml of 24% aqueous hydrochloric acid and cooled to O C. Sodium nitrite (3.2 g, 0.045 mol) in water (7 ml) is added dropwise during 45 min at 0-5°C to give a pale yellow solution of the diazonium salt. 

Diazotization of a primary arylamine followed by treatment of the diazonium salt with copper(l) bromide or copper(l) chloride yields the corresponding aryl bromide or aryl chloride. 

Some of the cuprous chloride compounds of the diazonium salts have been isolated and analysed, and coirespond to the formula CoH.-.NjCl.CuoCIo (Hantzsch). The formation of a crystalline copper compound is rendeied very evident in the present preparation.. A modification of Sandmeyer s reaction IS the introduction of precipitated metallic copper in place of the cuprous salt (Gattermann). 

Aldehyde enamines react with aromatic diazonium salts in two ways, depending on the degree of substitution at the enamine earbon (130). Thus the piperidine enamine of butyraldehyde (60) reacted with p-nitrophenyl-diazonium chloride to give the p-nitrophenylhydrazone of the a-keto aldehyde (190). 

Aniline 77 was converted into its diazonium salt with nitrous acid and this was followed by reduction with stannous chloride to afford the corresponding arylhydrazine 78. Condensation of 78 with 3-cyanopropanal dimethylacetal 79 gave the arylhydrazone 80. Treatment of 80 with PPE resulted in cyclization to indole 81. The nitrile group was then reduced to the primary amine by catalytic hydrogenation. Reaction of the amine with excess formalin and sodium borohydride resulted in Imitrex (82). 

The reactivity of the 5-position of 2-aminothiophene in diazo coupling, which is present also in the acylated derivatives, complicates the formation of a diazonium salt from 2-aminothiophene. Thus Steinkopf and Miiller obtained only an azo dyestuff, although they proved, through the isolation of small amounts of 2-thienyl diazonium chloride, the diazotizability of 2-aminothiophene which had earlier been denied. However, recent Russian work claims the preparation of 2-thienyldiazonium chloride by treating the double salt in 10% hydrochloric acid with sodium nitrite. Amazingly high yields (over 90%) of azo compounds were then achieved by coupling the diazonium salt solution with y9-naphtol, w-toluidine or with the 2-aminothiophene double salt. These authors have also studied the... 

Elimination of the hydroxyaminomethyl moiety from nitro oxime 15 by treatment with a diazonium salt gave hydrazone 43 (75LA1029) (Scheme 15). The same product was obtained by coupling the diazonium salt with the compound 16. On heating in aniline, oxime 15 was transformed into Schiff base 42. Acylation of the oxime 15 with benzoyl chloride in pyridine led to a mixture of furazan 44 and dinitrile 45. 

Inclusion of a para acetyl group requires a somewhat different approach to the preparation of these compounds. Reaction of the diazonium salt from p-aminoacetophenone with sulfur dioxide affords the sulfonyl chloride, 203 this is then converted to the sulfonamide, 204, Elaboration via the carbamate with cyclohexyl-amine affords acetohexamide (205). ... 

Replacement of chlorine on the pendant benzoyl group by azide is apparently consistent with antiinflammatory activity. Acylation of indomethacin intermediate with p-nitrobenzoyl chloride leads to the corresponding amide (7). Saponification ( ) followed by reduction of the nitro group gives the amine 9. The diazonium salt (10) obtained on treatment with nitrous acid is then reacted with sodium azide there is thus obtained zidomethacin (11). 

Arylamines are converted by diazotization with nitrous acid into arenediazonium salts, ArN2+ X-. The diazonio group can then be replaced by many other substituents in the Sandmeyer reaction to give a wide variety of substituted aromatic compounds. Aryl chlorides, bromides, iodides, and nitriles can be prepared from arenediazonium salts, as can arenes and phenols. In addition to their reactivity toward substitution reactions, diazonium salts undergo coupling with phenols and arylamines to give brightly colored azo dyes. 

Nucleophilic processes that generate chloroindoles are largely confined to the displacements of oxy functions and Sandmeyer reactions of diazo-nium salts [81 H( 15)547]. A low yield of 2-chloroindole was obtained by a reaction sequence that involved treatment of oxindole with phosphoryl chloride, and then treatment of the Vilsmeier salt with sodium bicarbonate [66JOC2627 86H(24)2879]. It is, however, much better to prepare this compound from 2-lithioindole (92JOC2495). With phosphoryl chloride and dimethylformamide ethyl l-hydroxyindole-2-carboxylate failed to give the expected 3-formyl derivative. Instead there was a 50% yield of the 3-chloro derivative (84CPB3678). Diazonium salts have been used as precursors in... 

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