Diazonium salts. Replacement by

Diazonium salts. Replacement by halogen. Sandmeyer reaction... 

A general method of replacement of the primary aromatic amino group by hydrogen is reduction of aromatic diazonium salts, prepared by diazotization, typically by treatment of the primary amine or its salts with sodium or potassium nitrite in strongly acidic aqueous media. Conversion to the diazonium salts may also be accomplished in nonaqueous media using acetic acid, or using alkyl nitrites (equation 86). Most diazonium salts decompose at temperatures above 0-5 C. Only certain salts such as naphthalene-1,5-sulfonates,tetrafluoroborates ° ° and hexafluorophosphates ° ° are stable at room temperature. 

This reducing agent reagent was introduced by Mai for deamination, that is, for replacement of a diazonium salt group by hydrogen. For the reduction of tetrazotized o-tolidine, Komblum- used about six times the theory of 30% hypophosphorous acid ... 

Nitration of p-cymene by fuming nitric add leads to 2,4-dinitrotoluene.1184 Heating 1,6-dihydro-l-methyl-6-oxonicotinic acid with nitric acid (d 1.52) under reflux gives 1-methyl-3,5-dinitro-2(li/)-pyridone in good yield.1185 2,6-Dibromo-4-nitrosophenol is formed quantitatively from 3,5-dibromo-4-hydroxybenzoic acid and sodium nitrite in aqueous alcohol.166,1183 Nitrous acid replaces hydroxymethyl groups in phenols by nitro groups,1186 and diazonium salts replace them by diazo groups.1187... 

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. ... 

When a solution of a diazonium salt is heated, the diazo group is replaced by hydroxyl and nitrogen is evolved ... 

It IS possible to replace ammo substituents on an aromatic nucleus by hydrogen by reducing a diazonium salt with hypophosphorous acid (H3PO2) or with ethanol These... 

Reductive deamination of primary arylamines The ammo substituent of an arylamine can be replaced by hydrogen by treatment of its de rived diazonium salt with ethanol or with hypophosphorous acid... 

Ciprofibrate (48), a more potent lipid-lowering agent clofibrate, is prepared from Simmons-Smith product by Sandmeyer replacement of the amino group by a hydroxyl via the diazonium salt. Phenol undergoes the Reimer-Thiemann like process common to these agents upon alkaline treatment with acetone and chloroform to complete the synthesis of ci profib-rate (48). 

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. 

In the isomer (156) (and its 4-amino and 4-oxo derivatives) 3-bromination also occurred [82CHE753 87AHC(41)320]. The 4-bromo compound was made in 40% yield from the diazonium salt (82CHE753), whereas a 3-oxo function was replaced by chlorine in the usual way [92JCS(P1)239]. 

MNN is obtained in 3—5% yield by the nitration of naphthalene and is present at this level in coml MNN. It is best prepd by indirect methods for example, by the removal of an amino group from an appropriately substituted nitro-naphthylamine. The amine is treated with Na nitrite and acid to form the diazonium salt which is replaced with a H atom by redn with EtOH (Ref 7). It may also be prepd by treatment of 6-nitro-l, 2,3,4-tetrahydronaphthalene with Br to form a dibromo compn (probably the 1,4-isomer), followed by removal of two moles of H bromide by distn in the presence of base (Ref 10). 2-Naphthalenediazonium fluoroborate... 

Aryl Halides from Diazonium Ion Intermediates. Replacement of diazonium groups by halides is a valuable alternative to direct halogenation for the preparation of aryl halides. Aryl bromides and chlorides are usually prepared by a reaction using the appropriate Cu(I) salt, which is known as the Sandmeyer reaction. Under the classic conditions, the diazonium salt is added to a hot acidic solution of the cuprous halide.99 The Sandmeyer reaction occurs by an oxidative addition reaction of the diazonium ion with Cu(I) and halide transfer from a Cu(III) intermediate. 

CINNOLINES AND QUINOXALINES Replacement of a methine in oxolinic acid (46) by nitrogen is apparently consistent with retention of antibacterial activity. One approach begins with reduction of nitroacetophenone 144 to afford the corresponding aminoketone (145). Treatment of this intermediate with nitrous acid leads to the diazonium salt the diazonium group condenses with the ketone methylene group (as its enol form) to lead to the cyclized product, cinnoline 147. Bromination proceeds at the position adjacent the enol grouping (148) ... 

A secondary reaction yields at the same time phenol ether by the replacement of the diazonium group by alkoxyl. This is clearly analogous to the conversion of diazonium salts to phenols. 

As indicated by Komblum in 1944125 the classical method of hydro-de-diazoniation by treating a diazonium salt in boiling acidic ethanol often leads to ethoxy-de-diazoniation. Kornblum replaced that method by dediazoniation in an aqueous solution of hypophos-phorous acid (H3PO2), in some cases in the presence of a catalyst, e.g. 0.05-0.10 mol% Cu. Experimental evidence indicates that aryl radicals are involved. 

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