A method of obtaining a possibly substituted p-hydroxymandelic connections

 

(57) Abstract:

The invention relates to an improved method for producing a p-hydroxymandelic compounds by condensation in the water, in the presence of an alkaline agent, an aromatic compound containing at least one hydroxyl group and having a free parapolitica, with Glyoxylic acid. The method consists in the condensation of hydroxyl-containing aromatic compounds corresponding to formula I:in which: the position of the couple is a free, x is an integer from 0 to 4, R denotes: - hydrocarbon group with 1-20 carbon atoms selected from the group of alkyl, alkoxyl, hydroxyalkyl, cycloalkyl, aryl, phenoxy, alkoxyalkyl, foralkyl, hydroxyacetanilide; - hydroxyl group; - the group-Cho; - acyl group having from 2 to 6 carbon atoms; a halogen atom; or two groups R, associated with two adjacent carbon atoms; together with these carbon atoms to form benzene; with Glyoxylic acid in the presence of compounds having at least two carboxyl groups corresponding to the formula (II): HOOC-R1-COOH (II) in which R1denotes a valence bond or a hydrocarbon radical, SNIM acyclic aliphatic radical; mono - or polycyclic carbocyclic radical saturated, unsaturated or aromatic; mono - or polycyclic heterocyclic radical is a saturated, unsaturated or aromatic. 32 C.p. f-crystals, 2 tab.

The object of the present invention is a method of obtaining a possibly substituted p-hydroxymandelic compounds and their derivatives.

The following summary of the invention the phrase “possibly substituted p-hydroxyindole connection” refers to aromatic compounds containing at least one group-NON-COOH in paraprotein to the hydroxyl group.

More specifically, the present invention relates to the production of p-hydroxymandelic acid and 3-methoxy-p-hydroxymandelic acid.

One of the classic ways of synthesis of p-hydroxymandelic acids consists in carrying out the condensation in an alkaline medium Glyoxylic acid with phenol and/or corresponding derivatives.

The output of the above acids is limited by the fact that the condensation reaction is not selective and leads to the simultaneous formation of o-hydroxymandelic and dimondale acids.

In addition, the yield of the reaction decreases Irakli Cannizaro in oxalic and glycolic acid.

Order to prevent the above reaction Cannizaro became predominant and destroyed Glyoxylic acid, in the patent FR-A 2132364 proposed to carry out the reaction of condensation in a dilute aqueous medium at low or room temperature.

Given the difficulty of obtaining satisfactory outputs reactions is important to control the various parameters of the process and, in particular, as used for the reaction of Glyoxylic acid.

The most important from an industrial point of view, the process of obtaining Glyoxylic acid is the oxidation of glyoxal with nitric acid. You get a water solution of Glyoxylic acid, which in addition to unreacted glyoxal also contain oxalic acid, organic acids such as formic, acetic and glycolic acid, and nitric acid.

The search for new methods of extraction and purification of Glyoxylic acid continues to the present time.

In particular, in the patent DE-A 1198339 method, which primarily removes nitric acid, then oxalic acid using anion exchange resins and then glyoxal and other impurities using the supersaturation of the solution and the latter is their impurities by extraction with aliphatic or alicyclic alcohols or esters of aliphatic alcohols with a low degree of carbon condensation.

In FR-A 2552426 also described is a method of obtaining aqueous solutions of Glyoxylic acid, not containing other acids, consisting in the processing of the original solution of nitrogen-containing organic compound, mainly tertiary amine, at a temperature not exceeding 50C with subsequent extraction of Glyoxylic acid by exhaustive extraction of the organic phase with water at a higher temperature.

Thus, currently, there is a constant desire to obtain a solution of Glyoxylic acid, freed from the above-mentioned impurities.

In contrast with this trend, found that obtaining the substituted p-hydroxymandelic compounds the condensation of Glyoxylic acid with the corresponding phenol is carried out with a higher yield when the reaction is carried out in the presence of a certain amount of dicarboxylic acid.

A specific object of the present invention is a method of obtaining a possibly substituted p-hydroxymandelic compounds and their derivatives, consisting in carrying out the condensation in water in the presence of an alkaline agent aromatic compounds containing at least one hydroxyl group and ineffective number of connections, having at least two carboxyl functions.

According to the method of the invention using the catalyst of the invention can improve the yield of the reaction.

Another advantage of the method of the invention is that it can be used technical Glyoxylic acid, containing, along with other impurities oxalic acid.

The method of the invention more specifically applies to phenol and substituted phenols having an unsubstituted parapolitica.

The aromatic nucleus contains at least one hydroxyl group, but may also be substituted one or more other groups. Usually, several deputies assumes at least four of the substituents in the aromatic nucleus.

Perhaps the presence of any Deputy, if he does not participate in the reaction of the invention.

Thus, the method of the invention is well suited for hydroxyl-containing aromatic compounds corresponding to the following formula I:

where:

- position pair is free,

- x is an integer from 0 to 4,

- R means:

- utlendingsdirektoratet, foralkyl, hydroxyethoxyethyl;

- hydroxyl group;

group-SNO;

- acyl group having from 2 to 6 carbon atoms;

is a halogen atom, preferably fluorine atom, chlorine or bromine;

two of the groups R, associated with two vicinal carbon atoms may together with these two carbon atoms form a benzene cycle.

Examples of radicals R, which may be substituents in the aromatic nucleus:

- alkyl radicals such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-octyl, 2-ethylhexyl, decyl, octadecyl, eicosyl;

- alkoxy radicals such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, hexyloxy, decyloxy, hexadecylamine, octadecylamine or phenoxy;

- hydroxyalkyl radicals, such as hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxyhexyl, hydroxyacyl;

- cycloalkyl radicals, such as cyclopentyl, cyclohexyl, cycloheptyl;

- alkyl fluoride radicals, such as vermeil, deformity, trifluoromethyl, foradil, 1,1,1-triptorelin, pentafluoroethyl, forproper, terbutyl, tel-di(oksietilenom), hydroxyethyl-three(oksietilenom), hydroxyethoxymethyl-1,2-ene, hydroxyethoxymethyl, hydroxypropionitrile, hydroxyatomoxetine, hydroxybutyl-di(oxybutylene);

- atoms of halogen, such as fluorine, chlorine, bromine or iodine.

In the method of the invention most preferably the use of hydroxyl-containing aromatic compounds corresponding to General formula I, in which:

- x is 0, 1, 2 or 3;

R denotes one of the following:

is a hydrogen atom;

- normal or branched alkyl radical having from 1 to 10, mostly from 1 to 4 carbon atoms;

- normal or branched alkoxy radical having from 1 to 10, mostly from 1 to 4 carbon atoms;

group-HE;

group-SNO;

is a halogen atom;

group-CF3.

Even more preferred compounds selected from compounds of the formula I in which the radicals R, identical or different, denote a hydrogen atom, normal or branched C1-C4is an alkyl radical, such as methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl, normal or branched alkoxy radical, such as Medenine, corresponding to the formula I, can be mentioned:

- compounds corresponding to the formula I, in which x is equal to 0, such as phenol,

- compounds corresponding to the formula I, in which x is equal to 1, such as:

- pyrocatechin

- resorcinol

- o-cresol

- m-cresol

- 2-ethylphenol

- 3-ethylphenol

- 2-propylene

- 2-sec-butylphenol

- 2-tert-butylphenol

- 3-tert-butylphenol

- 2-methoxyphenol (guaiacol)

- 3-methoxyphenol

- 2-ethoxyphenol (quetal)

- 2-isopropoxyphenol

- salicylic aldehyde

- methyl salicylate

- 2-chlorophenol

- 3-chlorophenol

- 3-NITROPHENOL

- compounds corresponding to the formula I, in which x is equal to 2, such as:

- 2,3-dimethylphenol

- 2.5-dimethylphenol

- 3,5-dimethylphenol

- 2-hydroxy-5-acetamido-benzaldehyde

- 2-hydroxy-5-atamido-benzaldehyde

- 2,3-dichlorophenol

- 2.5-dichlorphenol

- 3,5-dichlorphenol

- pyragollole,

- compounds corresponding to the formula I, in which x is equal to 3, such as:

- 2,3,5-trimethyl the formula I, represents a naphthalene radical, such as:

- 1-naphthol

- 2-naphthol

- 1,2-dihydroxynaphthalene

- 1,5-dihydroxynaphthalene

- 2,3-dihydroxynaphthalene

- 2,6-dihydroxynaphthalene

- 2,7-dihydroxynaphthalene

- 6-bromo-2-naphthol

- compounds corresponding to the formula I, which is a sequence of benzene nuclei, such as:

- 2-phenoxyphenol

- 3-phenoxyphenol.

From the above list of compounds preferably used are the following aromatic compounds substituted by at least one hydroxyl group, phenol, o-cresol, m-cresol, 3-ethylphenol, 2-tert-butylphenol, guaiacol and quetal.

In regard to the nature of the catalyst, can be called acid having at least two carboxyl functions and corresponding to the following formula II:

in which R1denotes a valence bond or a possibly substituted hydrocarbon radical containing from 1 to 40 carbon atoms.

More specifically, R1in the formula II denotes a substituted or unsubstituted, saturated or unsaturated, normal or ri, monocyclic or polycyclic carbocyclic radical: or a saturated, unsaturated or aromatic, monocyclic or polycyclic heterocyclic radical.

Particularly well suited for use in the method of the invention compounds with at least two carboxyl functions of the formula II in which R1denotes a valence bond or a bivalent radical containing predominantly from 1 to 15 carbon atoms.

Particularly well suited for use in the method of the invention compounds with at least two carboxyl functions of the formula II in which R1denotes a saturated or unsaturated, normal or branched acyclic aliphatic residue.

More specifically, R1indicates a normal or branched acyclic aliphatic residue mainly containing from 1 to 12 carbon atoms which may be saturated or may contain in the chain one or more unsaturated bonds, predominantly from one to three unsaturated bonds, which can be as simple or conjugated double bonds or triple bonds.

The hydrocarbon chain may be:

(1) the AET hydrogen or a normal or branched alkyl radical with 1-4 carbon atoms, mainly methyl or ethyl, or a radical of type -(CH2)p-COOH, in which R is an integer from 1 to 5;

(2) and/or to have the following placeholders:

HE: -COOH; -CHO; -NO2, -CN; -NH2; -SH; -X; -CF3;

-NH-[(CH2)p-COOH] or-N[(CH2)p-COOH]2,

where X denotes a halogen atom, preferably fluorine atom, chlorine or bromine, and p have the above values.

Suitable for use in the method of the invention are also compounds with at least two carboxyl functions of the formula II in which R1denotes a monocyclic or polycyclic aromatic hydrocarbon residue.

R1mainly refers to aromatic hydrocarbon residue, in particular a residue of benzene, corresponding to the General formula III:

where:

- n is an integer from 0 to 4, mainly from 0 to 3:

- R3denotes one of the following groups or functions:

is a hydrogen atom,

- normal or branched C1-C4is an alkyl radical,

- normal or branched C1-C4-alkoxy radical,

is a halogen atom.

Even more preferred compounds of formula II, in which the radical R1corresponds to the formula III, in which the radicals R3identical or different, denote a hydrogen atom, a methyl radical, a methoxy radical or a group-SNO.

Compounds with at least two carboxyl functions may correspond to the General formula II, in which the radical R1denotes a divalent polycyclic aromatic hydrocarbon residue in which the cycles can form between an ortho-condensed or ortho - and peri-condensed systems. It is possible, in particular, to call Neftyanoy balance, where cycles can be substituted 1-4, mostly 1-3, the radicals R3whose values mentioned above for the substituents of the aromatic hydrocarbon residue of General formula III.

In the formula II compounds having at least two carboxyl functions, R1also means the residue of a saturated carbocyclic radical or may contain 1 or 2 unsaturated bonds in the cycle, usually containing 3-7 carbon atoms, preferably 6 carbon atoms in the cycle; this cycle may be substituted by 1-5 radicals R3preferably 1-3 radicals, p is uly (III).

As preferred examples of radicals R1you can call cyclohexanediamine radicals which can be substituted normal or branched C1-C4-alkyl radicals.

Compounds with at least two carboxyl functions can also meet the General formula II, in which the radical R1denotes a divalent radical formed by the sequence of two to four residues defined above: aliphatic, aromatic or cycloaliphatic. The latter can be linked to either the valence bond or a functional group, which, in particular, may be a group selected from the groups indicated by y

Below are some examples of radicals R1:

-CH2-C6H4-;

-CH2-CH2-C6H4-;

-CH2-O-C6H4-;

-CH2-O-C6H4-CH2-;

-C6H4-C6H4-;

-C6H4-CH2-C6H4-;

-C6H4-O-C6H4-;

-CH2-C6H4-CH2-C6H4-CH2-.

In CA Rainey least two carboxyl functions:

- aliphatic dicarboxylic acids, such as:

- oxalic acid

- malonic acid

- succinic acid

- glutaric acid

- adipic acid

- 2,4-dimethyldiphenyl acid

- Emelyanova acid

- subarova acid

- azelaic acid

- sabotinova acid

- dodecandioic acid

- fumaric acid

- maleic acid

- cycloalkylcarbonyl acids such as cyclohexane-1,4-dicarboxylic acid,

aromatic dicarboxylic acids, such as:

- phthalic acid

- isophthalic acid

- terephthalic acid

- phenyleneoxy acid

- naphthalene-1,5-dicarboxylic acid

- naphthalene-1,6-dicarboxylic acid

- diphenyl-4,4’-dicarboxylic acid

- diphenyl-3,3’-dicarboxylic acid

bis[(4-hydroxycarbonyl)phenyl]the oxide

bis[(3-hydroxycarbonyl)phenyl]the oxide

- 4,4’-(dihydroxyaryl)diphenylsulfone

- 3,3’-(dihydroxyaryl)diphenylsulfone

- dicarboxylic acid pyrimidine is used oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, sabotinova acid, phthalic acid, isophthalic acid and terephthalic acid.

Perfect for use in the method of the invention and aminopolycarboxylate acid. As examples aminoalkanoic acids suitable for use in the method of the invention may be along with other named:

- ethylenediaminetetraacetic acid (EDTA)

- diethylenetriaminepentaacetic acid (DTPA)

- nitriloacetate acid

- N-(2-hydroxyethyl)ethylenediaminetriacetate acid (HEDTA).

From the above aminoalkanoic acids are preferred ethylenediaminetetraacetic acid.

According to the method of the invention, the reaction is carried out in the presence of alkali metal hydroxide, in particular sodium hydroxide or potassium.

For reasons of economic nature, preference is given to sodium hydroxide.

As for the concentrations and quantities of reagents used, the preferred terms are defined below.

According to the method of the invention, Glyoxylic acid is used in the form of a solution. Conc is about 70 wt.%. Thus preferably used commercial solutions, the concentration of which is approximately 50%.

According to the method of the invention, carried out the reaction of Glyoxylic acid with a hydroxyl-containing aromatic compound of the formula I, taken in excess. The molar ratio of hydroxyl-containing aromatic compounds of the formula I to Glyoxylic acid ranges from 1.5 to 4.0 and preferably selected in the range from 2.0 to 3.0.

The concentration of the used solution of alkali metal hydroxide is usually from 10 to 50 wt.%. The concentration of the original solution does not matter. However, because the preferred low concentration of hydroxyl-containing aromatic compounds of the formula I in the reaction medium, for diluting the latter use a dilute solution of alkali metal hydroxide.

The number entered in the reaction medium of the hydroxide of an alkali metal is determined by its number, which is necessary for the formation of a salt with a hydroxyl function hydroxyl-containing aromatic compounds of the formula I, and quantity necessary for the formation of a salt with the carboxyl function Glyoxylic cat salt-forming hydroxyl functions, in this case, the alkali metal hydroxide is injected in an amount necessary for the formation of a salt with all are capable of forming salts with features that can be hydroxyl groups and/or carboxyl functions COOH.

Typically, the amount of alkali metal hydroxide may be varied within wide limits and be equal or close to stoichiometric or be in excess. Generally, the amount of alkali metal hydroxide varies from 80 to 120% of the stoichiometric amount.

The concentration of the hydroxyl-containing aromatic compounds of the formula I is predominantly from 0.5 to 1.5 mol/l and preferably close to the value of 1 mol/L.

In regard to the used amount of the catalyst, the latter is determined by the fact that the molar ratio of the catalyst to hydroxyl-containing aromatic compound of the formula I should be 0.005 to 0.025 and preferably from 0.01 to 0.02.

The amount used of the catalyst, expressed through the ratio of the number of moles of catalyst to the number of moles of Glyoxylic acid, is mainly from 0.5 to 2.5 and preferably from 1% to 2%.

The preferred catalyst is meta oxalic acid. Oxalic acid reaction, thus partially supplied the initial solution. In this case for compliance with the above ratios is necessary to Supplement the amount of oxalic acid by the addition of oxalic or any other dicarboxylic acid.

According to a preferred variant of the invention, using a solution of Glyoxylic acid with the concentration of oxalic acid from 0.6 to 3 and, preferably, from 1.2 to 2.6% by weight of Glyoxylic acid.

The reaction temperature is chosen mainly from 20 to 60 and preferably from 30 to 40C.

The process of the invention is carried out at atmospheric pressure, but in a controlled atmosphere of inert gases, preferably nitrogen or noble gases, preferably in a nitrogen atmosphere.

Below is preferred practical embodiment of the invention.

In reaction medium containing a hydroxyl-containing aromatic compound of the formula I, water and alkali metal hydroxide in an amount necessary for salt formation with the hydroxyl group and the other capable of salt formation functions that may be contained in the compound of formula I administered a solution of Glyoxylic colorazione salt COOH function.

The reaction medium is stirred at a temperature selected within the above temperature range, during the period of time from 1 to 10 hours

Another variant of the invention consists in the addition of the catalyst the reaction is not in aqueous solution of Glyoxylic acid, but at the same time with hydroxyl-containing aromatic compound of formula I.

At the end of the reaction may allocate substituted p-hydroxymandelic acid obtained in salt form using classical separation methods, in particular using crystallization.

The method of the invention is particularly well applicable in the case, when using an aqueous solution of Glyoxylic acid containing monofunctional acids such as acetic, formic and glycolic acid and, in particular, when there is acetic acid at a concentration of from 0.1 to 3%.

The method of the invention yields a possibly substituted p-hydroxymandelic compounds which can be represented by the following formula IV:

in which R and x have the meanings given for formula I.

The products obtained are of particular interest because they are polypropylene hydroxyacylglutathione acid (i.e., hydroxyaryl--oxoxoxo acid) or hydroxyaromatic aldehydes.

The preferred application of the invention to provide hydroxyaromatic aldehydes by oxidation obtained in accordance with the invention, compounds of formula IV.

Oxidation of compounds of formula IV can be carried out in accordance with the described methods in the literature. In particular, it is possible to refer to R. Hebert [Bull. Soc. Chim. France, 27, p. 45-55 (1920)] and Nagai Shigeki et al. [JP-A 76/128934]. The oxidation can be carried out using oxygen or air under pressure in the presence of a suitable catalyst, such as derivatives of chromium, cobalt, copper, vanadium or osmium.

Thus, the invention makes it easy to obtain 4-hydroxybenzaldehyde and vanilla and its analogues, such as 3-ethyl-3-isopropylaniline, by oxidation, respectively, p-hydroxymandelic acid and 3-methoxy-p-hydroxyindole, 3 ethoxy-p-hydroxyindoles and 3 isopropoxy-p-hydroxymandelic acids.

The following examples illustrate the invention without limiting its scope.

In these examples, percentages are given in weight percent (wt.%).

Used in examples of the reducing Eector, equipped with double walls, pH electrode, temperature sensor, refrigerator, input for inert gas and a mechanical stirrer, download:

- 600 g of distilled water,

- to 91.6 (0,687 mol) of 30% aqueous sodium hydroxide solution and

- 93 g (0,750 mol) of guaiacol.

Create an inert atmosphere and raise the temperature of the reaction mixture up to 35S and simultaneously for 2 h type of 50.7 g (0,380 mol) of 30% aqueous sodium hydroxide solution and 55.2 g of a 50% aqueous solution of Glyoxylic acid. Together with Glyoxylic acid is added oxalic acid is used in a quantity amounting to 0.75% by weight solution of Glyoxylic acid.

Used a solution of Glyoxylic acid contains 0.3% oxalic acid, lower carboxylic acids, such as acetic acid (0,9%), and formic and glycolic acid (each in the amount of below 0.1%).

Maintain the reaction mixture at a temperature of 35C for 2 h

At the end of the reaction to determine the concentration of products using high-performance liquid chromatography.

The following results are obtained:

- conversion of 47.3%

- 4-hydroxy-3-methoxymandelic acid:

- selectivity of 5.1%

- 2-hydroxy-3-methoxy-1,5-damentally acid

output 8,0%

- selectivity of 4.0%.

Comparative example 2

Play example 1 with the difference that is not loaded oxalic acid.

The following results are obtained:

- conversion of 46,1%

- 4-hydroxy-3-methoxymandelic acid:

output 76,9%

- selectivity 83,0%

- 2-hydroxy-3-methoxymandelic acid:

output of 5.1%

- selectivity of 5.5%

- 2-hydroxy-3-methoxy-1,5-damentally acid:

output of 7.5%

- selectivity of 4.1%.

Example 3

In this example reproduces the example 1, but using a 50% aqueous solution of Glyoxylic acid containing 0.4 wt.% of oxalic acid. The following results are obtained:

- conversion of 48%

- 4-hydroxy-3-methoxymandelic acid:

output 79.3 percent

- selectivity 83.1% of

- 2-hydroxy-3-methoxymandelic acid:

output 5.6 percent

- selectivity of 5.8%

- 2-hydroxy-3-methoxy-1,5-damentally acid:

output 8,0%

- selectivity of 4.2%.

Examples of the o acids, such as malonic and succinic acid, and EDTA.

Used a solution of Glyoxylic acid contains 0,09% oxalic acid, lower carboxylic acids, such as acetic acid (1%), and formic and glycolic acid (each in the amount of less than 0.3%).

All conditions of the examples and the obtained results are presented in table I.

Examples 9-11

In the following examples, an increased amount of oxalic acid introduced into the process in a solution of Glyoxylic acid.

Using the sequence of operations of example 1, is introduced into the process 50% solution of Glyoxylic acid, the composition of which is given in examples 4-8.

The results are presented in the following table II.

In the above tables abbreviations ortho, steam and di denote:

- 4-hydroxy-3-methoxymandelic acid (= pair)

- 2-hydroxy-3-methoxymandelic acid (= ortho)

- 2-hydroxy-3-methoxy-1,5-damentally acid (= di).

1. The method of obtaining p-hydroxymandelic compounds by condensation in the water, in the presence of an alkaline agent, an aromatic compound containing at least one hydroxyl group is Yu hydroxyl-containing aromatic compounds, corresponding to the formula I

in which position the pair is free;

x is an integer from 0 to 4;

R denotes a hydrocarbon group with 1-20 carbon atoms selected from the group of alkyl, alkoxyl, hydroxyalkyl, cycloalkyl, aryl, phenoxy, alkoxyalkyl, foralkyl, hydroxyacetanilide; a hydroxyl group; a group-SNO; acyl group having from 2 to 6 carbon atoms; a halogen atom; two groups R, associated with two adjacent carbon atoms may together with these two carbon atoms form a benzene cycle with Glyoxylic acid,

in the presence of compounds having at least two carboxyl groups corresponding to the formula (II)

HOOC-R1-COOH (II)

in which R1denotes a valence bond or a hydrocarbon radical containing from 1 to 40 carbon atoms which may be saturated or unsaturated, normal or branched acyclic aliphatic radical; a mono - or polycyclic carbocyclic radical saturated, unsaturated or aromatic; mono - or polycyclic heterocyclic radical is a saturated, unsaturated or aromatic.

2. The way p is equal to 0, 1, 2, or 3; R denotes one of the following groups or functions: normal or branched alkyl radical having from 1 to 10 carbon atoms; normal or branched alkoxyalkyl having from 1 to 10 carbon atoms; the group-HE; group-SNO; fluorine atom, chlorine or bromine; group-CF3.

3. The method according to p. 1 or 2, characterized in that the hydroxyl-containing aromatic compound corresponds to the formula I in which the radicals R, identical or different, represent a normal or branched C1-C4-alkyl, normal or branched C1-C4-alkoxyalkyl, group-SNO or chlorine atom, and x is 0 or 1.

4. The method according to p. 1, characterized in that the hydroxyl-containing aromatic compound of the formula I is a phenol, o-cresol, m-cresol, 3-ethylphenol, 2-tert-butylphenol, guaiacol, svetol and 2-isopropoxyphenol.

5. The method according to p. 1, characterized in that the compound with at least two carboxyl groups correspond to the formula II in which R1indicates a normal or branched acyclic aliphatic radical containing from 1 to 12 carbon atoms which may be saturated or may contain in the chain of 1-3 unsaturated communication which may be (1) interrupted by one of the following groups, denote Y:

in formulas where R2denotes hydrogen or a normal or branched alkyl radical with 1-4 carbon atoms or a radical of type -(CH2)p-COOH, in which R is an integer from 1 to 5;

(2) and/or to have one of the following substituents: -HE; -COOH; -Cho; -NO2, -CN; -NH2; -SH; -X; -CF3; -NH-[(CH2)p-COOH ] or-N[(CH2)p-COOH]2,

where X denotes a halogen atom, preferably fluorine atom, chlorine or bromine, and R has the above significance.

6. The method according to p. 1, characterized in that the compound with at least two carboxyl functions is a compound of formula II in which R1denotes an aromatic hydrocarbon radical of General formula III

in which n is an integer from 0 to 3;

R3denotes one of the following groups or functions: normal or branched C1-C4is an alkyl radical; normal or branched C1-C4-alkoxyalkyl; methylene radical or Ethylenedioxy; group-SNO; phenyl or benzyl radical; a halogen atom.

7. The method according to p. 1, wherein the rule II, in which R1denotes a divalent polycyclic aromatic hydrocarbon radical, in which cycles can form between artecontemporanea or ortho - and pericontusional system.

8. The method according to p. 1, characterized in that the compound with at least two carboxyl groups is a compound corresponding to the formula II in which R1denotes a carbocyclic radical, which is saturated or contains one or two bonds in the cycle containing from 3 to 7 carbon atoms.

9. The method according to p. 8, characterized in that the compound with at least two carboxyl groups is a compound corresponding to the formula II in which R1denotes a carbocyclic radical, which is saturated or contains 1 or 2 unsaturated communication cycle containing 6 carbon atoms.

10. The method according to p. 1, characterized in that the compound with at least two carboxyl groups is a compound of formula (II) in which R1denotes a divalent radical formed by the sequence 2-4 defined above radicals: aliphatic, aromatic or cycloaliphatic connected between EDINENIE with at least two carboxyl groups is a compound corresponding to the formula II, selected from the following compounds: oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, 2,4-dimethyldiphenyl acid, Emelyanova acid, subarova acid, azelaic acid, sabotinova acid, dodecandioic acid, fumaric acid, maleic acid, cyclohexane-1,4-dicarboxylic acid, phthalic acid, isophthalic acid, terephthalic acid, phenyleneoxy acid, naphthalene-1,5-dicarboxylic acid, naphthalene-1,6-dicarboxylic acid, diphenyl-4,4’-carboxylic acid, diphenyl-3,3’-carboxylic acid, bis[(4-hydroxycarbonyl)phenyl]oxide, bis[(3-hydroxycarbonyl)phenyl]oxide, 4,4’-(dihydroxyaryl)diphenylsulfone, 3,3’-(dihydroxyaryl)diphenylsulfone, pyrimidine or imidazoledicarbonitrile acid, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminopentaacetic acid (DTPA), nitryltriacetic acid (NTA), N-(2-hydroxyethyl)ethylenediaminetriacetate acid (HEDTA).

12. The method according to p. 1, characterized in that use an aqueous solution of Glyoxylic acid, which contains a monofunctional acid selected from acetic, oxalic and glycolic acid.

13. The method according to p. 12, the Method according to p. 1, characterized in that the concentration of Glyoxylic acid in aqueous solution is from 15 to 70 wt.%.

15. The method according to p. 14, characterized in that the concentration of Glyoxylic acid in aqueous solution is about 50 wt.%.

16. The method according to p. 1, characterized in that the molar ratio of hydroxyl-containing aromatic compounds of the formula I to Glyoxylic acid is from 1.5 to 4.0.

17. The method according to p. 16, characterized in that the molar ratio of hydroxyl-containing aromatic compounds of the formula (I) to Glyoxylic acid is from 2.0 to 3.0.

18. The method according to p. 1, wherein the amount of alkali metal hydroxide is close to or equal to the stoichiometric quantity necessary for the formation of a salt with all capable of salt formation in groups of hydroxyl-containing aromatic compounds of the formula I and for the formation of salts with the carboxyl group of Glyoxylic acid.

19. The method according to p. 1, characterized in that the concentration of hydroxyl-containing aromatic compounds of the formula I is preferably from 0.5 to 1.5 mol/L.

20. The method according to p. 19, characterized in that the concentration of hydroxyl-containing aromatic soedineniya with at least two carboxyl groups is that the molar ratio of this compound to the hydroxyl-containing aromatic compound of the formula I is 0.005 to 0.025.

22. The method according to p. 21, characterized in that the number of connections with at least two carboxyl groups is such that the molar ratio of this compound to the hydroxyl-containing aromatic compound of the formula (I) is from 0.01 to 0.02.

23. The method according to p. 1, characterized in that the compound with at least two carboxyl groups served fully or partially aqueous solution of Glyoxylic acid.

24. The method according to one of paragraphs.1-21, characterized in that the compound with at least two carboxyl groups injected with an aqueous solution of Glyoxylic acid or in the original reaction medium containing hydroxyl-containing aromatic compound of the formula I, water and alkali metal hydroxide.

25. The method according to p. 1, characterized in that the alkali metal hydroxide is sodium hydroxide.

26. The method according to p. 1, characterized in that the reaction temperature is 20 to 60C.

27. The method according to p. 25, characterized in that the reaction temperature is 30-40C.

28. The method according to p. 1, characterized in that SS="ptx2">

29. The method according to p. 1, wherein the use solution of Glyoxylic acid containing 1-2 wt.% oxalic acid by weight of Glyoxylic acid.

30. The method according to p. 1, further comprising restoring the received parahydroxybenzoic acid to hydroxyarylalkyl acid.

31. The method according to p. 1, further comprising the oxidation obtained parahydroxybenzoic acid to hydroxyacylglutathione acid or hydroxyaromatic aldehyde.

32. The method according to p. 1, further comprising the oxidation of the obtained 3-methoxypropionitrile acid to vanillin.

33. The method according to p. 1, including additional oxidation of the obtained 3-ethoxypropionitrile acid to ethylaniline.

 

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The invention relates to a new process for the preparation of 2,2-dimethyl-5-(2,5-dimethylphenoxy)-pentanol acid of the formula (I)

OCOOH

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The invention relates to a method for aryloxyalkanoic acid of General formula I, where X=-C(Et)=C(Et)-; -CH(Et)-CH(Et) - which is used as a source of products to obtain conjugates with proteins in the development of immunochemical methods for the determination of hormones, and also exhibits antioxidant and anti-inflammatory properties

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< / BR>
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FIELD: chemistry.

SUBSTANCE: invention refers to cis/trans-citral and (iso)piperitenole processes to be then used in perfumery, household chemicals, vitamin synthesis. The process involves isomerisation of cis-trans verbenol in supercritical lower alcoholic vehicles (C1-C3) at temperature 420°C and lower. As a rule, supercritical lower alcoholic vehicles include supercritical methyl or ethyl alcohol, or supercritical 1-propanol. Commonly thermal isomerisation is ensured at temperature 280-420°C and pressure 100-120 atm.

EFFECT: high yield end products with controlled selectivity and high reaction time.

6 cl, 1 tbl, 2 dwg, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of campholene aldehyde which is widely used in perfumery and household chemicals. The method involves conversion of α-pinene epoxide in a supercritical complex solvent consisting of a mixture of carbon dioxide, propanol-2 and water at temperature of 160-240°C and pressure of 130-220 atm. As a rule, the conversion reaction is carried out in a supercritical solvent with molar ratio water/α-pinene epoxide equal to 5-7.9.

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2 cl, 1 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of 2-hydroxy-6-isopropenyl-3-methyl-cyclohex-3-enone, which can be used in asymmetric synthesis, for example in synthesis of chiral ligands which can be used in the pharmaceutical industry. The method involves isomerisation of verbenone epoxide in supercritical carbon dioxide with addition of isopropyl alcohol at temperature 463-513 K and pressure 140-150 atm.

EFFECT: high rate and efficiency of the process with continuous synthesis of the end product and controlled selectivity of synthesis.

2 cl, 1 tbl, 1 dwg, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing cyclopentanone, which is an active synthone for synthesis of drugs, plant protection agents, fragrant compositions, and is also used as a solvent, a BMC monomer, in production of crystalline wafers and engineering plastics. The method involves liquid-phase isomerisation of 1,2-epoxycyclopentane in the presence of a catalyst in a solvent medium and under gas pressure. The isomerisation reaction takes place in the presence of a homogeneous catalyst in form of concentrated 30-40% solution of a MgBr2·2H2O·4N-MP (N-MP = N-methylpyrrolidone) complex in N-methylpyrrolidone, with weight ratio of MgBr2 in the reaction mixture equal to 2-8%, initial concentration of 1,2-epoxycyclopentane equal to 30-45%, at temperature 110-440°C and gas pressure 0.2-0.5 MPa, where said gas is inert nitrogen, in the medium of a mixed N-methylpyrrolidone/xylene solvent in weight ratio (1.5-2)/1, followed by extraction of the catalyst from the reaction products and further reuse without regeneration.

EFFECT: method enables to obtain the end product with high selectivity.

1 ex

FIELD: organic chemistry, chemical technology.

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12 cl, 8 ex

FIELD: chemistry.

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EFFECT: efficient method of producing anionic surfactants.

4 cl, 1 tbl, 15 ex

FIELD: chemistry.

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EFFECT: single-step method enables to obtain desired product with high output.

13 cl, 2 dwg, 3 ex

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