Diazonium replacement

How would you prepare /n-hydroxyacetophenone from benzene, using a diazonium replacement reaction in your scheme ... 

The route shown above is one of several ways to synthesize p- bromobenzoic acid and is definitely not the simplest way. (The simplest route is Friedel-Crafts alkylation -> bromination - oxidation). The illustrated synthesis shows the use of the diazonium replacement reaction that substitutes bromine for a nitro group. Oxidation of the methyl group yields the substituted benzoic acid. 

Diazonium salts are quite useful in organic synthesis as the diazonium group can be easily replaced by fluorine, chlorine, bromine, iodine, cyanide, hydroxy, and hydrogen. In these diazonium replacement reactions, nitrogen gas is evolved. 

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 ... 

The diazonium group may be replaced by hydrogen, thus effecting the removal of the primary amino group, deamination, by the following methods ... 

The direct replacement of the diazonium group by hydrogen. These methods are discussed further in Chapter VI. 

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... 

Amino groups in pyridazine A-oxides can be diazotized and the diazonium group further replaced by halogens, hydroxy group or hydrogen. So, 3-, 4-, 5- and 6-bromopyridazine 1-oxides can be prepared from the corresponding amino A-oxides. 

The name Sandmeyer reaction - is used for the replacement of the diazonium group in an arenediazonium compound by halide or pseudohalide, taking place in the presence of a metal salt. However this is not a strict definition, since the replacement of the diazonium group by iodide, which is possible without a metal catalyst, is also called a Sandmeyer reaction. 

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... 

Some time ago Tedder (1957) recommended a process which he called direct introduction of the diazonium group , because it replaces the steps of nitration, reduction, and diazotization of an aromatic compound by a one-pot operation with three equivalents of a nitrosating reagent in acidic solution. The first step (Scheme 2-35) is a C-nitrosation and the following steps (Scheme 2-36) are the reduction of the nitroso-arene. 

H5C20 —C-S K+) to the diazonium salt solution. This leads to replacement of... 

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