CN86100772A - 2,3-dimethoxy-5-methyl isophthalic acid, 4-benzoquinones synthetic method - Google Patents

Abstract

, methylate through bromination by p-methyl phenol, step Synthetic 2s such as peroxide oxidation, 3-dimethoxy-5-methyl isophthalic acid, the existing patent report of the method for 4-benzoquinones, but in the existing patented method methylation reaction time oversize, the peroxide oxidation yield is low.The present invention to methylate and the peroxide oxidation method carried out significant improvement, adopted phase transfer catalytic technology and new reagent.The time of methylation reaction was shortened in 2 hours by 30 hours; The product yield of peroxide oxidation reaction has improved 30% than former patented method, and the easily separated purification of product, has actual production and is worth.

Description

2,3-dimethoxy-5-methyl isophthalic acid, 4-benzoquinones synthetic method

2,3-dimethoxy-5-methyl isophthalic acid, the 4-benzoquinones (is called for short Q ₀), be the important intermediate of synthetic ubiquinone (ubiquinone) compounds.The Q of relevant reported in literature ₀Synthetic route long, productive rate is low, separates purification difficult, therefore many investigators make every effort to work out a kind of new more economic synthetic method.

The synthetic method of having reported is many, wherein mainly contains following two kinds:

This method final step yield: use Na ₂Cr ₂O ₇-H ₂SO ₄Make oxygenant, yield is 20-30% (W.K.Anslow etc., J.Chem.Soc., 1938,439); With

Make oxygenant, yield is 90% (L.M.Weinstoek etc., J.Chem.Eng.Data, 12,154 (1967)).

This method final step yield; Use 60%H ₂O ₂-CF ₃COOH makes oxygenant, and yield is 68% (the tail Qin in temple is inferior, " openly speciallyying permit communique ", clear and 54-106440); With (NH ₄) ₂S ₂O ₈-CH ₃OH-H ₂SO ₄-H ₂O makes oxygenant, and yield is 54.3% (village difficult to understand Itou Kentaro etc., " openly speciallyying permit communique ", clear and 56-75450).

Aforesaid method (1) route is oversize, and total yield is very low.Final step potassium nitrosodisulfonate

Make oxygenant, though can obtain higher yield, it costs an arm and a leg, and be difficult for preserving, therefore actual application value is little, method (2) is a kind of more satisfactory synthetic method, but wherein the methylation reaction time long, (be two in the bamboo, " openly specially permit communique ", clear and 55-94329), the final step yield is not high enough, separates purification difficult.

The objective of the invention is method (2) is improved, adopted new reagent and reaction conditions and post-treating method, shortened the reaction times, obtained high yield.

The present invention has improved in the aforesaid method (2) by 2,6-dimethoxy-4 '-methylphenol (VIII) preparation 3,4, the method for 5-trimethoxytoluene (IX).Use KOH and replace K ₂CO ₃Make acid binding agent, replace acetone to make solvent with toluene, add a spot of polyoxyethylene glycol and make phase-transfer catalyst (consumption is the 10-20% of compound VIII), can make the reaction times shorten to 1～2 hour in 30 hours by the backflow of reported in literature, and 3,4, the yield of 5-trimethoxytoluene is basic identical with relevant reported in literature.

The present invention has improved in the aforesaid method (2) by 3,4, and 5 one trimethoxytoluenes (IX) oxidation makes Q ₀Method, adopt (NH ₄) ₂S ₂O ₈-CH ₃COOH-H ₂SO ₄-H ₂O replaces (NH ₄) ₂S ₂O ₈-CH ₃OH-H ₂SO ₄-H ₂O makes oxygenant, Compound I X and blending oxidizing agent [(NH ₄) ₂S ₂O ₈: CH ₃COOH: H ₂SO ₄: H ₂O=1: 4～6.5: 1～2.5: 1.2] feed ratio be 1: 20～30,35～60 ℃ of down reactions 0.5～2 hour, reaction product is with saturated Fe2 (SO ₄) ₃The aqueous solution is handled.Its advantage is thick product content height, and the separate easily purification, and yield can reach 85%, and the correlation method of reporting than Japanese Patent has improved 30%.

Example below enforcement of the present invention is available illustrates:

The preparation of (1) 2,6-two bromo-4-methylphenols

In the 1000ml there-necked flask, add 162g (1.5mol) p-cresol and 200ml water, slowly drip the liquid bromine of 159ml (3.1mol), rate of addition rapidly disappears with the reddish-brown of bromine and is advisable.Dropwise, continue to stir 20 minutes, obtain white solid product after the cooling, after filtration, washing, drying, can obtain 402g white crystal product, fusing point is 43～46 ℃ (49 ℃ of literature values).

The preparation of (2) 2,6-dimethoxy-4 '-methylphenols

In the 1000ml there-necked flask, add 280ml methyl alcohol, carefully add 35g (1.5mol) sodium Metal 99.5.After treating that sodium dissolves fully, steam excessive methyl alcohol, obtain solid CH ₃ONa.In flask, add 240ml DMF then, 60g (0.226mol) 2,6-two bromo-4-methylphenols, 16.8g (0.088mol) CuI, backflow is after 2 hours down in 110 ℃, and cooling adds the 120ml concentrated hydrochloric acid more carefully, and making PH is 3-4, uses the ether extracting then.Extract (ether layer) can obtain 38.5g light brown viscous shape product 2 through washing, dry, precipitation, and 6-dimethoxy-4 '-methylphenol, content are 90%, and productive rate is 91%.

(3) 3, the preparation of 4,5 one trimethoxytoluenes

In the 250ml there-necked flask, add 34g (0.2mol) 2,6 one dimethoxy-4 's-methylphenol, 100ml toluene, 5g polyoxyethylene glycol-600 adds 15.8g (0.28mol) KOH powder, (the CH of 20ml again after mixing ₃) ₂SO ₄, refluxed 1 hour down at 90 ℃, add 10g (0.18mol) KOH powder and 10ml (CH again ₃) ₂SO ₄, to continue to reflux 0.5～1 hour, wash respectively for several times with dilute NaOH solution and water the cooling back, and toluene layer is precipitation after drying, can obtain the light brown oily product 3,4 of 39g, and 5-trimethoxytoluene, content are 86%, and productive rate is 92%.

(4) 2,3-dimethoxy-5-methyl isophthalic acid, the preparation of 4-benzoquinones

In the flask of 250ml, add 4.5g (25mmol) 3,4,5-trimethoxytoluene, 12.5g (55mmol) (NH ₄) ₂S ₂O ₈, 50～80ml Glacial acetic acid, the dense H of 5～15ml ₂SO ₄With 15ml water, stirred 0.5～2 hour down at 35～60 ℃, after having reacted, add a certain amount of water, and use the ether extracting.The ether layer is earlier with saturated Fe ₂(SO ₄) ₃The aqueous solution is handled, and then uses rare Na respectively ₂CO ₃Solution and water washing.The ether layer of the above-mentioned processing of process is precipitation after drying, obtains reddish-brown oily product.Crude product is further used the sherwood oil recrystallization, can obtain the red needle crystal product of 3.8g Q ₀, productive rate 85%, 58～59 ℃ of fusing points (58～59 ℃ of literature values).Product ¹HNMR conforms to literature value with spectroscopic datas such as UV.

Claims (5)

1. by 2,6-dimethoxy-4 '-methylphenol preparation 3,4, the 5-trimethoxytoluene is characterized in that making acid binding agent with KOH, makes solvent with toluene, and adds a certain amount of polyoxyethylene glycol and make phase-transfer catalyst, refluxes at a certain temperature 1-2 hour.

2. according to claim 1, the consumption that it is characterized in that polyoxyethylene glycol is 2, the 10-20% of 6-dimethoxy-4 '-methylphenol weight.

3. by 3,4, the 5-trimethoxytoluene prepares 2,3-dimethoxy-5-methyl isophthalic acid, and the 4-benzoquinones, it is levied the spy and is with (NH ₄) ₂S ₂O ₈-CH ₃COOH-H ₂SO ₄-H ₂O makes oxygenant, reacts 0.5-2 hour down at 35-60 ℃.

4. as described in the claim 3, it is characterized in that the ratio of oxygenant is:

(NH ₄) ₂S ₂O ₈∶CH ₃COOH∶H ₂SO ₄∶H ₂O＝1∶4～6.5∶1～2.5∶1.2

3,4,5-trimethoxytoluene: oxygenant=1: 20～30

5. as described in the claim 3, it is characterized in that the saturated Fe of reaction product ₂(SO ₄) ₃The aqueous solution handle.