WO2006104411A1

WO2006104411A1 - Method for producing 2-methyl-1,4-naphthoquinone

Info

Publication number: WO2006104411A1
Application number: PCT/RU2005/000495
Authority: WO
Inventors: Oxana Anatolievna Kholdeeva; Mikele Rossi
Original assignee: Institut Kataliza Imeni G.K. Boreskova Sibirskogo Otdeleniya Rossiiskoi Akademii Nauk
Priority date: 2005-03-28
Filing date: 2005-10-03
Publication date: 2006-10-05
Also published as: RU2278106C1

Abstract

The invention relates to a method for producing 2-methyl-1,4-naphthoquinone by oxidising a 2-methyl-1-naphthol with the aid of oxygen or oxygen-containing gas in an organic solvent medium or in a 2-methyl-1-naphthol melt and intensively agitating at the oxygen or oxygen-containing gas pressure equal to or less than 1 atm and a temperature equal to or less than 20 °C. Said invention makes it possible to attain a high target product yield.

Description

The method of obtaining 2-methyl-l, 4-naphthoxinone

The invention relates to organic synthesis, and in particular, to a method for producing 2-methyl-l, 4-naphthoxinone (MHX, menadione, vitamin K ₃ ). MHX is a synthetic analogue of group K vitamins, which are widely used in medical practice and animal husbandry as drugs to improve blood coagulation, and also play an important role in bone formation.

Most methods for the preparation of 2-methyl-l, 4-naphthoxinone (MHX) are based on the oxidation of 2-methylnaphthalene (MH). In industry, MHX is obtained mainly by stoichiometric oxidation of 2-methylnaphthalene (MH) with chromium (VI) oxide in sulfuric acid with a yield of 40-50% [LF Fiсеr, Compound rоceаdures forrеrеrаrаtiсо, bоmperatorоmagrосhісоmо. Chem. 133 (1940) 391; R.A. Shëldop, Nomogepeus apd heterogepheusus satalutis ohidatiop with rehide reagetts, Tor. Cp Chem. 164 (1993) 21]. At the same time, 18 kg of chromium-containing wastewater is formed per 1 kg of product. A known method of producing MHX, where a solution of Mn ₂ (SO ₄ ) ₃ in sulfuric acid is used as a stoichiometric oxidizing agent; the yield of 2-methyl-l, 4-naphthoxinone is 55% [M. Resiasamu, MV Batt, Facile oxydate of aromatics rips b Mn ₂ (S (Xi) ₃ , Terraheter Letters 46 (1978) 4561]. These methods require the use of large amounts of expensive and toxic oxidizing agents and are unacceptable, both from the point of view of ecology in terms of economics.

Catalytic methods for the oxidation of 2-methylnaphthalene (MH) are known. The catalytic oxidation of MH by ammonium persulfate in the presence of cerium (GV) ammonium sulfate and sodium dodecyl sulfate is known to form a mixture of MHX and 2-methyl-l, 6-naphthoxinone with a yield of up to 73% [J. Skarzewski, Сеrium сatalуzеd resulfatе okhidatiop о rolususlis aromatis hudrosarbops tо quiopopes, Tetrаhedrop 40 (1984) 4997].

Known methods for the oxidation of MH by dichromates in the presence of ruthenium compounds as catalysts [S. Choproop, M. Mishmap, Ohidatiop оf 2-methyl-paphthalepe to 2-methyl-l, 4-paphthoquipo with attopiate dichromate catalysed by RuCl ₃ , Arl. Catal. 62 (1990) 119], KHSO ₅ in the presence of iron and manganese porphyrins [R. Sopg, A. Sorocip, J. Vetadou, V. Mépier, Metalororrhurip-Catalus Ohidatop 2-methylnaphthalene vitamip K ₃ apd 6-methyl-1, 4-naphtholquinone butoptosulfate Chet. 62 (1997) 673] et al. The oxidation of MH with tert-butyl hydroperoxide in the presence of Fe- and Mn-containing phthalocyanines fixed on the surface of mesoporous (MCM-41) and amorphous silicates (SiO ₂ ) has been reported. In this method, the MHX selectivity did not exceed 34% at a conversion of 90% [A. Sorokip, A. Tuel, Metallorhthalosuapipe Fuppiopilized Silis: Satalusts forté Ohidatiop of Aromatis Kompoupds, Satal. Todau 57 (2000) 45].

Of greatest interest is the use of environmentally friendly and cheap oxidizing agents - molecular oxygen and hydrogen peroxide. It is known that MH is oxidized with hydrogen peroxide in a carboxylic acid medium without a catalyst [US 6579994, C07C 46/04, 12/12/02] and in the presence of palladium compounds as a catalyst [US 5637741, C07C 46/04, 06/10/97]. High catalytic activity in the oxidation reaction of methylnaphthalene with hydrogen peroxide H ₂ O ₂ in an environment of acetic acid / acetic anhydride is shown by rhenium complexes, in particular methyl trioxorenium (VII) (CH ₃ ReO ₃ , MTO) [W. Adam, W.A. Nerrmapp, W. Lip, Ch.R. Saha-Möller, RW Fischer, JDG Correia, Nomogepeus satalutis okhidatiop of arpeps apd and pw supupésis of vitamip K ₃ , Apgew. Chem. Ipt. Ed. 33 (1994) 2475; W.A. Jermrmapp, JJ. Naider, RW Fischeher, Rhepshm-Sataluzed Ohidatiof of Arpez - up Improved Supetesis of Vitamip K ₃ , J. MoI. Catal. A: Chem. 138 (1999) 115]. MHX selectivity reaches 60% with an MH conversion of 65%. The disadvantages of this process are 1) the use of concentrated hydrogen peroxide (85%), which is an explosive reagent and 2) the use of a homogeneous catalyst and, accordingly, the difficulties associated with its separation and regeneration. It is known to oxidize MH with hydrogen peroxide in acetic acid using iron salts (Fe (CU ₄ ) ₃ , (CH ₃ COO) ₃ Fe) as a homogeneous catalyst [J. Kowalski, J. Roszupska, A. Sobkowiak, Irop (W) - Ipduced activatiop of hudrogep rehide for ohidatiop of 2-mefhylpaphthalepe ip glacial asetis acid, Catal. Sottup. 4 (2003) 603]. The selectivity of this process does not exceed 36% with a substrate conversion of 85-90%. Famous Method for the oxidation of MH with hydrogen peroxide using Pd (P) acetate fixed on polystyrene-sulfonic resins as a catalyst [S. Yamaguchi, M. Biope, S. Epoto, Ohidopiof 2-methylnaphthalene to 2-methyl-1, 4-naphthoquinone with hydrogen sulfate in the presence of Pd (II) - roustustere sulfulfic acid. Lettt. (1985) 827]. In this process, the MHX selectivity reaches 66% with an MH conversion of 90%. It is also known that MH is oxidized with hydrogen peroxide in the presence of titanium and iron-containing molecular sieves (TS-I, Ti-Veta, Ti-NCL-I, Fe-Veta, Ti-MCM-41) [O.S. Application, L.V. Rierella, A.R. Veltramope, Supеsis оf mepadiopе overeсlivet ohidatiop zеlitеs, J. MoI. Catal. A: Chem. 149 (1999) 255; O.S. Application, A.R. Veltramope, J. Sousse, Studies оf Vitamip K ₃ suptеsis overs Ti- soptipipg mesoropus material, Arrl. Catal. A: Heperal 270 (2004) 77]. The maximum selectivity (54%) at 22% conversion was obtained for Fe-Beta zeolite. A common disadvantage of all processes for obtaining 2-methyl-l, 4-naphthoxinone

(MHX) from 2-methylnaphthalene (MH) is a low selectivity for the target product and, in particular, the formation of 2-methyl-l, 6-naphthoxinone, which is close in physical and chemical properties to MHX, which greatly complicates the process of isolation and purification of MHX. The use of 6-methyl-l, 4-naphthoquinone as a by-product can be avoided by using 2-methyl-1-naphthol (MHJI) as the starting substrate instead of 2-methylnaphthalene (MH). A recently developed highly efficient method for producing MHJI by alkylating a cheap and affordable raw material — 1-naphthol — with methanol in the gas phase in the presence of a catalyst containing a mixture of Mg and Fe (P) / Fe (PI) oxides [WO 2004/014832, B01J23 / 78, 19.02 .04], makes MHJI a more promising starting substrate for MHX than MH.

The oxidation of MHJI KHSO ₅ in the presence of porphyrins of iron and manganese is known [R. Sopg, A. Sorokip, J. Vetadou, V. Mépier, Metalororhurm-Catalus Ohidatiof 2-methylpaphthalepot, K- ₃ , 6-methyl-1, 4-paroxylpropyl, Chet. 62 (1997) 673]. The yield of MHX is maximum in the presence of FeTDCPPS and is 30%. The oxidation of MHJI to MHX by aqueous hydrogen peroxide in the presence of mesoporous titanium silicate catalysts is known. (MHX yield of 46% with MNL conversion of 97%) [SU 2196764, C07C46 / 06, 01.20.03].

Closest to the proposed invention is a method for producing 2-methyl-l, 4-naphthoxinone (MHX) by catalytic oxidation of 2-methyl-l-naphthol (MNL) or its mixture with 2,4-dimethyl-l-naphthol in a two-phase system, in which the oxidizable substance is reacted in a solution of a water-immiscible organic solvent, and the catalyst is an aqueous solution of molybdovanadophosphoric heteropoly acid or its acid salt (HPA-p) containing 10 to 20 vol.% acetic acid, and the oxidation reaction is carried out under intense mixing phases at a temperature of 40 - 7O ⁰ C, the overall composition of the catalyst corresponds to the formula H _a PχMo _y V _n O, where 1 <x <3; 8 <y <16; 40 <b <89; a = 2b - 6y - 5 (x + n); 4 <n <12, n is the number of vanadium atoms. During the reaction, the molar ratio of HPA-p: MH is used, not exceeding 2.5. The maximum yield of 2-methyl-l, 4-naphthoxinone reaches 88% when using an aqueous-acetic acid solution of HPA and a chlorine-containing solvent (SU 2162837, C07C50 / 12, 02.10.01).

The disadvantages of this process are 1) two-stage 2) low productivity (it is impossible to use the concentration of MNL in the reaction mixture greater than 0.1 M) and 3) the use of stoichiometric amounts of hetero-compounds of GPS containing toxic vanadium. Even during the oxidation process in a two-phase system, the organic solvent - water, pollution of the organic phase with vanadium complexes cannot be completely avoided, resulting from the interaction of HPS (or its degradation products) with organic components of the reaction mixture.

The objective of the invention is to provide a method for oxidizing MNL in MHX with oxygen or an oxygen-containing gas, the use of which will significantly simplify the process technology, increase its productivity and increase the purity of the resulting product by eliminating the presence of toxic impurities of transition metals in the product.

The problem is achieved in that the oxidation of 2-methyl-l-naphthol (MNL) in 2-methyl-l, 4-naphthoxinone (MHX) is carried out in the absence of a catalyst in an organic solvent or in an MNL melt at a pressure (P) of oxygen or an oxygen-containing gas of at least 1 atm (preferably P (O ₂ ) of at least 3 atm) and a temperature of at least 2O ⁰ C. The process is carried out with vigorous stirring

As an organic solvent, non-polar and low-polar aromatic and non-aromatic hydrocarbons and chlorine-containing hydrocarbons, or any mixtures thereof, mainly toluene, carbon tetrachloride, cyclohexane, are used.

There are no restrictions on the concentration of oxidation of 2-methyl-l-naphthol (MHJl) for the claimed process, which can significantly increase the productivity of the process compared to the prototype.

The invention is illustrated by the following examples.

Example 1. In a temperature-controlled at 80 ° C glass (“pyrox”) reactor equipped with a magnetic stirrer and a condenser, 55 mg of 2-methyl-1-naphthol MHJI (0.1 mol / L) and 3.5 ml of toluene are placed. The mixture is stirred vigorously at 80 ° C. and an oxygen pressure of 3 atm. After 8 hours, the conversion of MHJl and the yield of 2-methyl-l, 4-naphthoxinone MHX calculated on the reacted MHJI (selectivity) determined by GLC were 76 and 80%, respectively.

Example 2. The process is carried out as in example 1, but instead of toluene take 3.5 ml of CCl ₄ . After 4 hours, the conversion of MHJI and the yield of MHX based on the reacted MHJI (selectivity) were 58 and 80%, respectively.

Example 3. The process is carried out as in example 2, but at an oxygen pressure of 1 atm. After 10 hours, MHJI conversion and MHX selectivity were 43% and 74%, respectively. This example in comparison with example 2 demonstrates that with a decrease in oxygen pressure, the reaction rate is significantly reduced.

Example 4. The process is carried out as in example 2, but at a temperature of 50 ° C. After 10 hours, the conversion of MHJI is 40%, the selectivity for MHX is 74%. This example, in comparison with example 2, demonstrates that with a decrease in the reaction temperature, its rate decreases.

Example 5. The process is carried out as in example 2, but at room temperature (about 20 ° C). After 72 hours, the conversion of MHJI is 43%, the yield of MHX is 84%.

After 171 h, the conversion of MHJI is 80%, the selectivity for MHX is 75%. This process demonstrates the possibility of obtaining MHX in high yield at room temperature.

Example 6. The process is carried out as in example 1, but take ON g MNL (0.2 mol / l) After 7.5 h, the conversion of MNL 83%, the selectivity for MHX 82%. Example 7. The process is carried out as in example 1, but take 220 g of MNL (0.4 mol / l). After 7.5 h, the conversion of MNL 91%, the selectivity for MHX 88%.

Examples 6 and 7 in comparison with example 1 show that increasing the concentration of MNL above 0.1 M leads to an increase in the speed and productivity of the process and does not lead to a decrease in selectivity for MHX.

Example 8. The process is carried out as in example 2, but take 220 g MNL (0.4 mol / l) and carry out the process at room temperature (about 2O ⁰ C). After 119 h, the MNL inversion is 75%, the MHX selectivity is 80%. After 162 hours, the MNL conversion was 87%, and the MHX selectivity was 80%. This example demonstrates that with a 4-fold increase in the concentration of MNL, the selectivity of the process does not deteriorate, and also that at room temperature the selectivity of the process does not deteriorate with an increase in the conversion of MNL.

Example 9. The process is carried out as in example 2, but take 277 g MNL (0.5 mol / l). After 4.5 h, the conversion of MNL 89%, the yield of MHX 70%. Example 10. The process is carried out as in example 9, but without solvent and at a temperature of 75 ° C. After 3.5 hours, the conversion of MNL was 55%, and the yield of MHX was 47%. This example demonstrates the possibility of carrying out the process in the MNL melt, without the use of an organic solvent.

Example 11. The process is carried out as in example 2, but air is used as an oxidizing agent at a pressure of 3 atm. After 10 hours, the MNL conversion and MHX selectivity were 40 and 70%, respectively. This example demonstrates that an oxygen-containing gas, such as air, can be used as an oxidizing agent.

Example 12. The process is carried out as in example 1, but cyclohexane is used as a solvent. After 6 hours, the MNL conversion and MHX selectivity were 41 and 84%, respectively.

Example 13. The process is carried out as in example 2, but chloroform is used as a solvent. After 3 hours, the conversion of MNL and selectivity for MHX are 33 and 45%, respectively. This example demonstrates a decrease in the selectivity of the process with increasing polarity of the solvent.

Example 14. The process is carried out as in example 2, but acetic acid is used as a solvent. After 3 hours, MHJI conversion and MEK selectivity were 14 and 60%, respectively.

Example 15. The process is carried out as in example 2, but ethanol is used as a solvent. After 3 hours, the conversion of MHJI is 6%, the yield of MHX is 0%.

Example 16. The process is carried out as in example 2, but cyclohexanone is used as a solvent. After 3 hours, the conversion of MHJI is 0%, the yield of MHX is 0%.

Example 17. The process is carried out as in example 2, but acetonitrile is used as a solvent. After 5 hours, the conversion of MHJI is 20%, the yield of MHX is 2%. Examples 14-17 demonstrate that the process is not efficient in polar solvents.

The generalized results of the process according to examples 1-17 are shown in the table.

The above examples show that the method of obtaining MHX proposed by the present invention is high-performance, cheap and easy to implement. The application of this method allows to obtain the target product of high purity (without impurities of transition metals) and with a high yield. The organic solvent is separated by distillation and can be used repeatedly. Separation of MHX from by-products (mainly resins) can be carried out by steam distillation. Resins can be burned to form CO ₂ and H ₂ O. Table. Oxidation of 2-methyl-1-naphthol (MHJl) to 2-methyl-l, 4-naphthoxinone (MHX)

a) GLC output calculated on the starting substrate. b) In the melt of MNL. c) Instead of oxygen, air is used.

Claims

Claim

1. A method of producing 2-methyl-l, 4-naphthoxinone by oxidation of 2-methyl-l-naphthol with oxygen or an oxygen-containing gas, characterized in that the process is carried out in an organic solvent or in a 2-methyl-1-naphthol melt.

2. The method according to claim 1, characterized in that non-polar and low-polar aromatic and non-aromatic hydrocarbons and chlorine-containing hydrocarbons, or any mixture thereof, mainly toluene, carbon tetrachloride, cyclohexane, are used as an organic solvent.

3. The method according to p. 1.2, characterized in that the process is carried out with vigorous stirring at a pressure of oxygen or an oxygen-containing gas not lower than 1 atm, preferably not lower than 3 atm.

4. The method according to p. 1.2, characterized in that the process is carried out at a temperature not lower than 20 ° C.