RU2002100083A

RU2002100083A - The method of obtaining (nitroxymethyl) phenyl esters of derivatives of salicylic acid

Info

Publication number: RU2002100083A
Application number: RU2002100083/04A
Authority: RU
Inventors: Грациано КАСТАЛДИ; Эрмино ОЛДАНИ; Габриеле РАЦЦЕТТИ; Франческа Бенедини
Original assignee: Никокс С.А.
Priority date: 1999-07-09
Filing date: 2000-06-21
Publication date: 2003-09-27

Claims

1. The method of obtaining compounds of formula (I)

where R ₁ means OCOR ₃ group, where R ₃ means methyl, ethyl or linear or branched C ₃ -C ₅ alkyl, or the residue of a saturated heterocyclic ring having 5 or 6 atoms containing heteroatoms independently selected between O and N;

R ₂ means hydrogen, halogen, linear or branched when possible C ₁ -C ₄ alkyl, linear or branched when possible C ₁ -C ₄ alkoxyl, linear or branched when possible C ₁ -C ₄ perfluoroalkyl, mono- or di- (C ₁ -C ₄ ) alkylamino,

preferably in (I) R ₁ is acetoxy and is in the ortho position with respect to the carboxyl group, R ₂ is hydrogen; oxygen of the ester group is bound to an aromatic ring substituted by a (nitroxy) methylene group in the ortho, meta or para position with respect to the (nitroxy) methylene group; preferably this is the meta-position, said method comprising the following steps: a) reacting a halide of a salicylic acid derivative of the formula (IA)

where Hal = Cl, Br and R ₁ and R ₂ have the above meanings, with hydroxybenzyl alcohol in the presence of a base in an organic solvent or in a mixture of water with a water-miscible or water-immiscible organic solvent to obtain compound (IB) having the following formula

where R ₁ and R ₂ are as defined above,

b) nitration of compound (IB) under anhydrous conditions in an inert organic solvent by means of a mixture formed from fuming nitric acid with an inorganic acid other than nitric acid, or with an organic acid or with an anhydride of one or two organic acids, to obtain a nitroxy derivative of the formula ( I), c) the selection of the final product by adding water to the organic phase, separation of the phases, drying and evaporation of the organic phase.

2. The method according to claim 1, where in stage a) the base is an inorganic or organic base.

3. The method according to claims 1 and 2, where in stage a) the organic solvents are C ₁ -C ₄ aliphatic alcohols, aromatic hydrocarbons, aliphatic esters, chlorinated organic solvents, aliphatic and cycloaliphatic ketones.

4. The method according to claims 1 to 3, where in stage a) the reaction is carried out at a temperature in the range from -20 ° C to + 50 ° C, when using in relation to moles of hydroxybenzyl alcohol in the reaction, the amounts in moles of the acid halide respectively (IA ) in a ratio between 1 and 2, preferably between 1.2 and 1.5, and the amount in moles of base between 0.1 and 2, preferably between 0.5 and 2.

5. The method according to claim 1, where in stage b) the nitration is carried out at a temperature in the range of -20 ° C and + 40 ° C, and the amount in moles of nitric acid is in the ratio between 1 and 6, preferably 1 and 3, in relation to moles of compound (IB), wherein the amount in moles of inorganic acid other than nitric acid or organic acid or organic anhydride, as defined above, is in a ratio between 0.5 and 6, preferably between 1 and 3, with respect to moles of compound (IB).

6. The method according to claim 5, where the nitration is carried out in the presence of an anhydride, which is pre-mixed with hydroxyether (I-B), and the resulting mixture is added to a solution of nitric acid in an inert organic solvent.

7. The method according to claim 6, where the anhydride is acetic anhydride.