Reduction with hypophosphorous acid

The replacement of 2-amino group by a hydrogen can be achieved by diazotization, followed by reduction with hypophosphorous acid (1-8, 13). Another method starting from 2-aminothiazole is to prepare the 2-halo-thiazole by the Sandmeyer reaction (prepared also from the 2-hydroxy-thiazole), which is then dehalogenated chemically or catalytically (1, 9, 10). 

Aminothiazoles are invaluable intermediates for the preparation of 2-unsubstituted-thiazoles by diazotization followed by reduction with hypophosphorous acid. Application of the Sandmeyer reaction leads to 2-halogeno- and 2-cyano-thiazoles. 

Reduction reactions occurring along with substitution chemistry are also well known, and the examples above are such cases. Another simple example involves the [IrCle]2 ion, which undergoes both reduction (with hypophosphorous acid) and substitution in (6.32). 

Amino-l,2,3-benzothiadiazoles can themselves undergo this rearrangement. Thus, diazotization followed by reduction with hypophosphorous acid converts 7-amino-6-chloro-4-methyl-l,2,3-benzothiadiazole (40) into the rearranged 4-chloro-6-methyl compound (41) a small but significant quantity of non-rearranged product (42) is also obtained. When C-4 is... 

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... 

Gravimetric methods more suitable for general use involve the precipitation of metallic gold from tetrachloraurate solutions by reduction with oxaUc acid, SO2, or hydroquinone. Formaldehyde, hydrazine, ferrous sulfate, and hypophosphorous acid also have been used but are considered less efficient (40). 

A large number of polymeric substances, (RAs) or (ArAs), are also known (113). They are usually prepared by the reduction of arsonic acids with hypophosphorous acid (100,114) or sodium dithionite (115). Most of these polymers have not been well characterized. An insoluble, purple material, poly(methylarsinidene) [26403-94-1], (CH As), prepared by the interaction of methylarsine and a dihalomethylarsine, however, has been shown by an x-ray investigation to have a ladderlike polymeric stmcture in which the inter-mng distances correspond to one-electron bonds (116) ... 

Scheme 11.6 gives some examples of the various substitution reactions of aryl diazonium ions. Entries 1 to 6 are examples of reductive dediazonization. Entry 1 is an older procedure that uses hydrogen abstraction from ethanol for reduction. Entry 2 involves reduction by hypophosphorous acid. Entry 3 illustrates use of copper catalysis in conjunction with hypophosphorous acid. Entries 4 and 5 are DMF-mediated reductions, with ferrous catalysis in the latter case. Entry 6 involves reduction by NaBH4. 

Acylamino groups also are useful activating groups and have the advantage that the amino groups obtained after hydrolysis of the acyl function can be removed from an aromatic ring by reduction of the corresponding diazonium salt with hypophosphorous acid, preferably in the presence of copper(I) ions. 

As has already been noted in the section on ethanol deaminations, upon diazotizing some nitroamines in hydrochloric acid, a diazonium salt is obtained in which the nitro group has been replaced by chlorine (pp. 272-273). Consequently, hypophosphorous acid reduction gives a deaminated product Containing chlorine in place of the nitro group. For example, when 5-amino-8-nitroisoquinoline (XVIII) is diazotized with hydrochloric acid and then treated with hypophosphorous acid, 8-chloro-isoquinohne (XIX) is obtained in 60-70% yield instead of 8-nitro-isoquinoline.86... 

In aqueous solution at 0° to +5°, exchange of nuclear bromine for chlorine (pp. 271-272) does not occur. Thus, the diazonium chloride of 2,4,6-tribromoaniline when treated with hypophosphorous acid gives 1,3,5-tribromobenzene in 70% yield, while the hypophosphorous add reduction of the diazonium chloride derived from 2,4,6-tribromo-3-methylaniline is productive of the corresponding tribromotoluene in 91% yield.88 18... 

This is not the only instance where hypophosphorous acid is more effective than ethyl alcohol. For example, whereas deamination of o-toluidine by the hypophosphorous acid procedure affords toluene in 70-75% yield,82 treatment with ethanol gives o-ethoxytoluene in approximately 50% yield.10-13 And while reduction of the diazonium salt of p-amino-phenylarsonic acid by hypophosphorous acid yields phenylarsonic add (ca. 50%),92 ethanol gives p-ethoxyphenylarsonic add (ca. 65%). Although 3,3 -dimethoxybenzidine may be deaminated by either procedure, the yield with hypophosphorous acid is 66-78% 80 81 as compared to approximately 20% when ethanol is used.46 These data, in conjunction with other results, lead to the conclusion that hypophosphorous acid is at least equal to ethanol as a reagent for deaminating an aromatic amine, and that it is usually effective in deaminations which cannot be carried out with ethanol.18 81 82-88187 93 94... 

It would be of interest to attempt this reduction under Bomewhat modified conditions deamination might be achieved by treating the diazonium chloride with hypophosphorous acid at 0° to +5° in the absence of copper. 

An isothiazolo[5,4-6]triazole prepared from a 4,5-diaminoiso-thiazole and nitrous acid suffered reductive cleavage on treatment with hypophosphorous acid (Scheme 41).147... 

White crystalline phosphite, Ge0P(0)0H, is formed from the reduction of Ge02 with hypophosphorous acid. 

Benieneselenol, 6, 28-29. This reagent has been prepared by reaction of selenium with phenybnagnesium bromide (57-71% yield) and by reduction of diphenyl diselenide with hypophosphorous acid or with NaBHa (86% yield). , ... 

Reduction with phosphinic acid (hypophosphorous acid, HjPOj) leads to the replacement of the diazonium group with hydrogen. Thus an... 

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