07-13-03 14:16
No 446887
(Rated as: good read)

I'm posting the preparation of this compound to illustrate the preparation of phenylhydrazines that are used in Fischer synthesis. In many cases a Fischer resction can bee carried out simply by heating together the aldehyde or ketone and phenylhydrazine in acetic acid. But, in this case below we've got a nitro group that is 'in the way' so to say. But, if someone still wants to for some reason proceed and end up with some 5-nitro-indoles or tryptamines after the Fischer synthesis then fine but there are few things to keep in mind. Nitro group is a electron-withdrawing substituent and therefore the Fischer process would bee slowed-down as expected, electron-releasing increase the rate (duh!). But it's possible to bee satisfied indolizing even deactivated systems (with for instance nitro group) with appropriate choice of acid and conditions, if there is interest I can find papers describing such conditions in detail.  


Dissolve 10 g (0.075 mol) of p-nitroaniline in a mixture of 21 mL of concentrated hydrochloric acid and an equal volume of water, and cool rapidly to 0C in order to obtain the hydrochloride of the base in a fine state of division. Diazotise by the gardual addition of a solution of 5.2 g (0.075 mol) of sodium nitrite  in 12 mL of water. Continue the stirring for a few minutes, filter the solution rapidly and add it from a separatory funnel to an ice-cold solution of 41 g (0.156 mol) sodium sulphite (96% Na2SO3*7H2O) in 100 mL of water containing 4 g of sodium hydroxide; stir the mixture during the addition which requires about 5 minutes. (If the diazonium solution is added too rapidly, an orange-red precipitate of sodium p-nitrobenzenediazosulphonate is produced, and is apt to form a resin.) Allow the solution to stand for 5 minutes, acidify with 70 mL of conc. HCl (aq) and heat on a water bath at 25C for 3 minutes, whan yellow needles commence to separate. Allow to stand overnight, filter off the crystals, heat them with 20 mL of conc. HCl (aq) on a water bath for 7 minutes and allow to cool. Filter off the precipitate, consisting of p-nitrophenylhydrazine hydrochloride and sodium salts, dissolve it in water and treat the solution with a conc. solution of sodium acetate: the free base will separate out in an almost pure state (7-8 g, 63-72%). The p-nitrophenylhydrazine may be recrystallised from EtOH and is obtained as light brown crystals, m.p. 158C (decomnp.).

Above preparation of p-nitrophenylhydrazine was found in Vogel's 5:th edition, page 960.

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