FR2609712A1 - L-amino acids prepn. - from precursor mixt. of keto acid, maleic acid, and ammonia - Google Patents

Abstract

Precursors for the manufacture of amino acids of formula (I) R-CH(NH2)-COOR' (I) where R = straight or branched chain, thatmay be substd., or an aromatic ring,that may be condensed, R' = H, or a group forming a salt or derivative of the amino acid, comprise maleic acid or anhydride, ammonia, and a keto acid or its derivative of formula R-CO-COOR'. USE/ADVANTAGE - (I) is made from the precursor mixture by a process of transamination in the presence of transaminase. The process does not require careful control of the purity of the starting materials and so gives a simple and economical route to (I) on an industrial scale.

Description

PROCESS FOR THE PREPARATION OF HYROXYBIPHENYLS
The present invention relates to a process for producing hydroxybiphenyls. It relates more particularly to a process for the preparation of 4,4'-dihydroxybiphenyl.

 Indeed 4,4'-dihydroxybiphenyl is an intermediate currently sought in the industry of synthetic materials such as polyesters, polyepoxides, polyurethanes, as an antioxidant in resins or in the dyestuffs industry.

 It is known to prepare the hydroxybiphenyls by hydrolysis of the halogenobiphenyls by means of a copper catalysis, such as, for example, with the aid of copper sulphate (according to US Pat. No. 4,475,500) or with the aid of copper oxide (according to US Pat. No. 4,340,748) in aqueous basic medium. The temperature conditions and the autogenous pressure created by such high temperatures as well as the small amount of dobby treated at each operation have prompted those skilled in the art to seek a less dangerous and above all more profitable.

 Numerous processes are still known for the preparation of hydroxyaryl compounds produced in the vapor phase, that is to say at a temperature above 3000 ° C. in the presence of a copper-based catalyst and a rare earth phosphate catalyst. Thus, US Pat. No. 3,752,878 discloses a process for the preparation of hydroxyaryl compounds wherein the aryl group contains one or more benzene rings from equivalent halogenated compounds by hydrolysis in the presence of a lanthanum phosphate or cerium and copper which are precipitated together in the form of mineral polyphosphate. This reaction is carried out in biphasic form. The catalyst is in solid form and the halogenated compound to be hydrolyzed in gaseous form because the reaction is carried out at 5000 ° C. The conversion rate of the starting compound is low and the reaction conditions are too severe to be usable on an industrial scale.

 When it is desired to carry out the hydrolysis at a lower temperature, as for example according to Japanese Patent 69/17372 or the hydrolysis is carried out at about 2000C, in the presence of copper derivatives in the oxidation state two such as copper sulphate, copper dibromide, copper diacetate; the duration of the hydrolysis reaction is particularly long and sometimes reaches 10 hours for a yield not exceeding 25%. This method is therefore not transferable at the industrial level.

 For many years, the industry has been seeking a process for the preparation of economically profitable, non-hazardous hydroxybiphenyls from halobiphenyls.

dans laquelle m et n sont des nombres entiers identiques ou différents, égal å 0,1, 2 ou 3 et dont la somme n+m est supérieure ou égale à 1 et inférieure ou égale à 4, avec une base de formule M(OH) dans laquelle M
p est un métal choisi parmi les métaux alcalins ou alcalino-terreux, p est un nombre entier égal à 1 ou 2 suivant la valence du M, en présence d'un catalyseur à base de cuivre et d'un co-catalyseur choisi parmi les halogénures (fluorures, bromures), les phosphates, les nitrates, les alcoolates alcalins ou alcalinoterreux, de cuivre ou d'argent, les silicates minéraux ou organiques ainsi que leurs précurseurs, les dérivés soufrés organiques et l'oxyde de carbone ou un de ses précurseurs. Les dérivés bromés sont préparés de manière connue par tout homme de l'art par action du brome sur un biphényle & température ambiante pendant quelques heures. La variation de température, de durée, le choix du solvant et le cboix de certains catalyseurs de bromation permettent de fixer un ou plusieurs atomes de brome. The present invention has made it possible to achieve this objective and relates to an industrial process for the preparation of hydroxybiphenyls, characterized in that a bromobiphenyl of general formula (I) is placed in the aqueous liquid phase at a temperature below 3000C. )

in which m and n are identical or different integers, equal to 0.1, 2 or 3 and whose sum n + m is greater than or equal to 1 and less than or equal to 4, with a base of formula M (OH ) in which M
p is a metal selected from alkali or alkaline earth metals, p is an integer equal to 1 or 2 depending on the valence of M, in the presence of a copper-based catalyst and a co-catalyst selected from the group consisting of halides (fluorides, bromides), phosphates, nitrates, alkali or alkaline earth metal alkoxides, copper or silver, inorganic or organic silicates and their precursors, organic sulfur derivatives and carbon monoxide or one of its precursors. The brominated derivatives are prepared in a manner known to those skilled in the art by the action of bromine on a biphenyl at room temperature for a few hours. The variation of temperature, of duration, the choice of the solvent and the coxix of certain bromination catalysts make it possible to fix one or more bromine atoms.

 Among the derivatives of general formula (I), the derivatives in which n + m is equal to 1 or 2 and even more preferably those for which n + m is equal to 2 and especially 4,4'-dibromo biphenyl are preferred. .

 Among the bases of formula N (OH), it is preferred to use strong alkaline bases and especially soda or potassium hydroxide.

 Copper-based catalysts include, but are not limited to, copper metal, copper in the oxidation state such as cuprous oxide, halides, acetate, cyanide, thiocyanate, triflate, cuprous sulfide, as well. that two oxidation state copper derivatives such as oxide, halides, acetates, acetylacetonates, metaborate, isobutyrate, citrate, cyclohexylbutyrate, dimethyldithiocarbamate, hexanoate, gluconate, hydroxide, oxalate, propionate, stearate, sulfate, cupric trifluoroacetylacetonate.

 It is preferred, however, to use the oxides or halides of copper in the oxidation state one or two.

 Among the cocatalysts which make it possible to reduce either the temperature or the duration of the reaction and the object of the protection required for the present invention, it is possible to choose the halides, the phosphates, the nitrates, the silicates, all of these compounds. are for their implementation associated with protons or cations alkaline, alkaline earth metal, for example copper, silver or organic. The silicates can also be prepared in situ in the reaction medium by action, for example, of the strong base on silica or glass. Phosphates can also be prepared in situ from organic phosphates.

 Among the fully organic cocatalysts, mention may also be made, for example, of alcoholates and alcohols containing preferably 1 to 12 carbon atoms, carboxylic acids containing 2 to 12 carbon atoms, sulfur derivatives and carbon monoxide or one of its organic precursors such as formates.

Thus, exemplary co-catalysts of the present invention include diphenylsulfide, dithiophene, potassium fluoride and / or sodium, phosphoric acid, nitric acid, sodium methoxide, formate methyl, glasses, for example the
Pyrex, silica ......

 It is preferred to use fluorides, bromides, phosphates, nitrates, alkali silicates or organic formates.

 It is obvious that when the copper catalyst and the cocatalyst form a single chemical entity, the latter will be used and will play both roles.

 Among the reaction conditions, the temperature is an essential condition from the economic point of view and is the subject of the present process, it is limited to 3000C and preferably between 220 and 250 C. The pressure used is the autogenous pressure obtained a the vaporization reaction temperature of the compounds present may be increased by any inert solvent such as nitrogen or any gas unreactive with the reaction compounds. Since the reaction takes place in an aqueous medium, a mono or polybromobiphenyl is preferably used at a concentration greater than 0.15 mole per liter of water and preferably between 0.15 and 2 moles per liter of water.

A base amount of formula M (OH) liberating p at least 2 equivalents of hydroxyl per atom of bromine is preferably used for hydrolysis and has a concentration in water of between one molar equivalent per liter and ten molar equivalents per liter. .

 The amount by weight of copper-based catalyst is preferably between 0.2 and 5 t relative to the amount of bromobiphenyl introduced.

 The molar amount of cocatalyst is preferably between 0.1 and 100 times the molar amount of catalyst. A large excess quantity would not be harmful to the process of the invention, but this provides no additional benefit. The useful amount will simply be adapted by those skilled in the art to the economics of the process.

 The invention makes it possible to prepare bydroxybiphenyls and among these can be mentioned; 4-hydroxy-biphenyl, 2-hydroxy-biphenyl, 3-hydroxy-biphenyl, 4,4'-dihydroxybiphenyl, 2,2'-dihydroxybiphenyl, 2,4'-dihydroxybiphenyl, trihydroxy -2,4,4'biphenyl, tetrahydroxybiphenyls.

 The invention will be more fully described with the aid of the following examples which should in no way be considered as limiting the invention.

2 g (6,4 mmoles)
- Cu2O 10 mg (0,07 mmoles)
- NaOH 5N 20 ml (100 mmoles
- Cocatalyseur 2 moles par mole de Ou2O
ou 20 mg dans le cas du pyrex
les gaz sont introduits par purge.EXAMPLES 1 TO 16
Operating mode
We introduce into a reactor er. Hastelloy C 276 of 7t ml the following compounds

2 g (6.4 mmol)
- Cu2O 10 mg (0.07 mmol)
5N NaOH (100 mmol)
- Cocatalyst 2 moles per mole of Ou2O
or 20 mg in the case of pyrex
the gases are introduced by purge.

 After purging with argon, closing the autoclave and then optionally introducing gaseous cocatalyst, the autoclave is placed in a stirred oven and heated to 250oC. After a reaction time T, the reactor is brought back to ambient temperature. The reaction mixture is diluted with 20 ml of water (shifted from the reactor), acidified with 25 ml of 4N sulfuric acid and extracted with methyl isobutyl ketone (1 × 20 ml + 5 × 10 ml).

The organic phase is dried over sodium sulphate. The yields are determined by high performance liquid chromatography.

Table of results see next page
Table I

N <SEP> Co-catalysts <SEP> Time <SEP> RR <SEP> (%) <SEP> RR <SEP> (t) <SEP>
<tb><SEP> 4-OH <SEP> 4,4 '<SEP> diOH
<tb><SEP> 1 <SEP> - <SEP> 3 <SEP> h <SEQ> 0.4 <SEP> 52.9
<tb><SEP> 2 <SEP> - <SEP> 5 <SEP> h <SEP> 1.5 <SEP> 85.2
<tb><SEP> 3 <SEP> - <SEP> 7 <SEP> h <SEP> 1.3 <SEP> 90.5 <SEP>
<tb><SEP> 4 <SEP> Ph2S <SEP> 3 <SEP> h <SEP> 0.5 <SEP> 6C, 6
<tb><SEP> 5 <SEP> dithiophene <SEP> 3 <SEP> h <SEP> 0.6 <SEP> 68.8 <SEP>
<tb><SEP> 6 <SEP> XF <SEP> 3 <SEP> h <SEP> 1.7 <SEP> 88.8
<tb><SEP> 7 <SEP> NaF <SEP> 3 <SEP> h <SEP> 1.4 <SEP> 93.3
<tb><SEP> 8 <SEP> H3PO4 <SEP> 3 <SEP> h <SEP> 2.7 <SEP> 91.2
<tb><SEP> 9 <SEP> HNO3 <SEP> 3 <SEP> h <SEP> 1.2 <SEP> 83.6
<tb> 10 <SEP> NaCN <SEP> 3 <SEP> h <SEP> 0.3 <SEP> 58.9
<tb> 11 <SEP> NaOMe <SEP> 3 <SEP> h <SEP> 4.2 <SEP> 83.0 <SEP>
<tb> 12 <SEP> NaBr <SEP> (1 <SEP> mole <SEP> with <SEP> mole <SEP> 3 <SEP> h <SEP> 1.2 <SEP> 84.5
<tb><SEP> of <SEP> Br2 <SEP> (C6H4) 2
<tb> 13 <SEP> HCO2Me <SEP> 3 <SEP> h <SEP> 1.7 <SEP> 90.4
<tb> 14 <SEP> CO <SEP>&<SEP> 6.4 <SEP> t <SEP> in <SEP> N2 <SEP> 3 <SEP> h <SEP> 0.5 <SEP> 62.5
<tb><SEP> 1 <SEP> purge
<tb> 15 <SEP> Pyrex <SEP> 3 <SEP> h <SEP> 1.7 <SEP> 86.9
<tb> 16 <SEP> SiO2 <SEP> 3 <SEP> h <SEP> 1.8 <SEP> 89.4
<Tb>
EXAMPLE 17
The procedure is as described in Example 1, with the introduction of 2,4-dibromo-4,4'-biphenyl (6.4 mmol).
20 ml of 5 N NaOH (100 mmol)
- 10 mg of cuprous oxide (0.07 mmol)
1.4 g of NaBr (14 mmol)
After 3 hours of reaction, a yield of 4,4'-dihydro-4,4'biphenyl of 84.7 t and a yield of 4-hydroxybiphenyl of: 2% is obtained.

EXAMPLE
The reaction is carried out as in Example 1, by hydrolysing a mixture of:
- 2-bromo biphenyl
- 2,4-dibromo biphenyl
- 2,4-dibromo biphenyl
- 2,2'-dibromo biphenyl
tribromo-2,4,4 'biphenyl obtained by bromination bromine biphenyl bromine in dichloromethane in the presence of 1 t ferric chloride for 48 hours.

 The hydrolysis is conducted in the presence of 0.07 mole of cuprous oxide and 2 moles of silica per mole of catalyst, at 2500C in 5N sodium hydroxide.

In 3 hours, a mixture of
- 2-hydroxybiphenyl
2,4-dihydroxybiphenyl
2,4-dihydroxybiphenyl
2,2-dihydroxybiphenyl
2,4,4-trihydroxybiphenyl
The products are identified by nuclear magnetic resonance after isolation by preparative gas chromatography.

EXAMPLE 19
The following tests are carried out under the same conditions as Examples 1 to 16 with
-2 g of 4,4'-dibromobiphenyl
- 100 mg of cuprous oxide
20 ml of 5N NaOH at 2300 ° C., optionally using as butanol cocatalyst.

Table 2

N <SEP> Cocatalysts <SEP> Time <SEP> RR <SEP> (%) <SEP> RR <SEP> (%)
<tb><SEP> 4-OH <SEP> 4,4 '<SEP> diOH
<tb><SEP> 7 <SEP> - <SEP> 7 <SEP> h <SEP> 30 <SEP> traces <SEP> 69.0
<tb><SEP> 2 <SEP> 10 <SEP> ml <SEP> BuOH <SEP> 7 <SEP> h <SEP> 30 <SEP> 1.8 <SEP> 84.0
<Tb>

Claims (5)

 10) Process for the preparation of hydroxybiphenyls, characterized in that a bromobiphenyl of general formula (I) is brought into contact with the aqueous liquid phase at a temperature of less than 3000.degree.

 in which m and n are integers identical or different equal to 0.1, 2 å 3 and whose sum n + m is greater than or equal to 1 and less than or equal to 4, with a base of formula Moto) in which M p is a metal selected from alkali or alkaline earth metals, p is an integer equal to 1 or 2 depending on the valence of the metal M, in the presence of a copper catalyst and a chosen cocatalyst . among the halides, inorganic phosphates and their organic precursors, nitrates, alkali, alkaline-earth, copper or silver alkoxides, mineral or organic silicates and their precursors, organic sulfur compounds, alcohols, carboxylic acids and carbon monoxide or a precursor thereof.  20) The method of claim 1, characterized in that in the formula (I) n + m is equal to 1 or 2.  30) Process according to claim 1 and 2, characterized in that the compound of formula (I) is 4,4'-dibromo-biphenyl.  40) Process according to claim i, characterized in that the copper-based catalyst is selected from the oxides or halides of copper in the oxidation state one or two.  50) Process according to claim 1, characterized in that the co-cetyster is selected from fluorides, bromides, alkaline phosphates, organic formates and alkali silicates.  60) Process according to claim 5, characterized in that the alkali silicates are prepared in situ from silica or glass.  70) A method according to claim 1, characterized in that among the reaction conditions, it is preferred to operate at a temperature between 220 and 2500C.