CN102786398A

CN102786398A - Economic environment-friendly large-scale production technology for high-purity muscone

Info

Publication number: CN102786398A
Application number: CN 201210312548
Authority: CN
Inventors: 杨俊�; 邱培勇; 阎玺庆; 李斌; 梁长华; 袁会峰; 孙方杰
Original assignee: Xinxiang Medical University
Current assignee: Xinxiang Medical University
Priority date: 2012-08-30
Filing date: 2012-08-30
Publication date: 2012-11-21

Abstract

The invention discloses an economic environment-friendly large-scale production technology for high-purity muscone. The technology is characterized by comprising the steps of using cyclododecanone as raw material to react with methyl chloropropene in a nucleophilic substitution way; carrying out cyclization reaction to generate cyclic diolefine; carrying out selective reduction to obtain cyclenes; oxidizing to obtain the target product muscone; and finally purifying via molecular distilling so as to obtain high-purity muscone. The economic environment-friendly large-scale production technology has the advantages of low cost of production, and relatively simple production process; the product muscone has high purity; the production is environment-friendly, and less pollution is brought to the environment; the technical content of the synthesis technology for the muscone is completely suitable for large-scale production of the muscone. The target product high-purity muscone is suitable for being used in medical treatment, drugs, foods, spices, and cosmetics and the like.

Description

A kind of high purity muskone scale production process of economic environmental protection

Technical field

The present invention relates to a kind of muskone scale production process of economic environmental protection, belong to fine chemistry industry and pharmaceutical engineering field.

Background technology

In the Talmud when Moschus is documented in B.C. 5th century the earliest " tower wood moral through " (Talmud, Brachot 43), Moschus is mentioned as a kind of spices that is derived from animal.Natural musk purposes in medicine and perfume industry is very extensive, and its source is a kind of male musk deer deer (Moschus moschiferus L.) glandular secretion that moves in the Tibet region.Because the musk deer deer is deficient, extract very difficulty of Moschus through killing the musk deer deer, obtain one kilogram of Moschus and need sacrifice 30 to 50 musk deer deer, therefore the chemist pays special attention to the research of Moschus over 100 years.Walbaum in 1906 isolate the staple of natural musk---the macrocyclic lactone compounds; Nineteen twenty-six Ruzicka confirms that its molecular structure is 3-muscone (muskone); Nineteen fifty-one Stallberg-Stenhagen and Ark Kemi have synthesized muskone first; The new synthesising skill of muskone constantly occurs afterwards; Summarizing to get up its compound method mainly realizes through three approach:

α, the intramolecular cyclization of ω-bifunctional compound; Methylating of

exaltone;

cyclododecanone ring expansion.α, the intramolecular cyclization approach research of ω-bifunctional compound is very popular, problem still is not solved but synthesis step is long, productive rate is low etc.; The approach that methylates of exaltone is significant in theory, but exaltone is on the high side, and practical application still is restricted; The price of cyclododecanone is comparatively cheap in the cyclododecanone ring expansion approach, and the certain development prospect is being arranged aspect the suitability for industrialized production muskone.Because muskone as the heavy demand and the singularity of purity requirement of medicinal and spices purposes, is explored simply, the muskone synthesis technique of economy, environmental protection, is the key that synthetic musk ketone moves towards large-scale production.

Summary of the invention

The invention provides a kind of muskone scale production process of economic environmental protection; Main is that raw material and METHYL ALLYL CHLORIDE carry out nucleophilic substitution reaction with cyclododecanone cheap and easy to get, carries out ring-closure reaction and generates cyclic diolefine; Get cyclenes after the selective reduction; Reoxidize and generate the title product muskone, adopt the short-path distillation purifying at last, obtain highly purified muskone.

Shown in accompanying drawing, muskone production technique of the present invention, synthetic line may further comprise the steps:

1. cyclododecanone (C ₁₂H ₂₂O) and METHYL ALLYL CHLORIDE (C ₄H ₇Cl) at Tetrabutyl amonium bromide (Bu ₄NBr) and under sodium hydroxide (NaOH) catalysis, carry out nucleophilic substitution reaction and generate alkene butyl cyclododecanone (C ₁₆H ₂₈O);

2. alkene butyl cyclododecanone is at aluminium sesquioxide (Al ₂O ₃) and toluene (C ₇H ₈) under the catalysis, carry out ring-closure reaction and generate methyl bicycle 15 diene (C ₁₆H ₂₆);

3. methyl bicycle 15 diene are at ammonium formiate (HCOONH ₄) and palladium/carbon (Pd/C) catalysis under, selective reduction becomes methyl bicycle ten pentaene (C ₁₆H ₂₈);

4. methyl bicycle ten pentaenes are at sodium periodate (NaIO ₄), Tetrabutyl amonium bromide (Bu ₄NBr) and normal hexane (C ₆H ₁₄) in the environment, oxidation generates title product methyl ring 15 diketone (C1 ₆H ₂₈O ₂), i.e. muskone.

5. title product adopts the molecular distillation equipment purifying, obtains highly purified muskone.

The present invention has following characteristics:

1. technical strong:

(1) is reduced in the methyl bicycle ten pentaene reaction process at methyl bicycle 15 diene, adopts ammonium formiate (HCOONH ₄), palladium/carbon (Pd/C) catalytic hydrogen transfer method, the two keys on selective hydrogenation reduction methyl bicycle 15 diene;

(2) this muskone production process such as cyclododecanone and METHYL ALLYL CHLORIDE nucleophilic reaction become alkene butyl 12 reactive ketones and methyl bicycle ten pentaenes are oxidized to methyl ring 15 diketone; All in the profit mixed system, react; Do not need separated product, dispose waste liquid, environmental friendliness;

(3) this muskone production process is reacted requirement according to Atom economy, strict each step reaction of control, and prepared using is good, and yield is high.

2. environmental protection:

(1) becomes in the alkene butyl ten diketone reaction process, at cyclododecanone and METHYL ALLYL CHLORIDE nucleophilic reaction with Tetrabutyl amonium bromide (Bu ₄NBr) be phase-transfer catalyst, in the profit mixed system, react that environmental friendliness is convenient to liquid waste disposal;

(2) be oxidized to methyl ring 15 diketone at methyl bicycle ten pentaenes, promptly in the muskone reaction process, with the sodium periodate (NaIO of low toxicity ₄) as oxygenant, reduced the oxygenant such as the chromium trioxide (CrO of high poison ₃), titanium dioxide arsenic (SeO ₂) use that waits, reduced environmental pollution, the reaction process environmental protection;

(3) be oxidized to methyl ring 15 diketone at methyl bicycle ten pentaenes, promptly in the muskone reaction process, equally with Tetrabutyl amonium bromide (Bu ₄NBr) be phase-transfer catalyst, in the profit mixed system, react that environmental friendliness is convenient to liquid waste disposal;

(4) each reactions step of this muskone production process all is Atom economy reactions, and side reaction is few, and reaction is green.

3. economical:

(1) this muskone production technique starting raw material cyclododecanone of being, cheap being easy to get is fit to large-scale production;

(2) each reactions step of this muskone production process all is Atom economy reactions, and the production process waste is less.

4. mass-producing:

The production operation of this muskone is simple, and a production line yearly capacity surpasses 100 tons of muskones.

5. purity is high:

This muskone production technique gained muskone crude product adopts 2 ~ 8 grades of scraped film type molecular distillation methods to separate and purifies, and muskone purity surpasses 98.0%, and its technical scheme is following:

(1) adopts multistage scraped film type distillation plant to separate, comprise scraped film evaporator, molecular still and two-stage mixing distiller;

(2) spacing is 5 ~ 40cm between the generating surface of distillation plant and the condensing surface;

(3) vacuum pressure is 0.001 ~ 10 mbar;

(4) vaporization temperature is 20 ~ 200 ℃;

(5) cooling temperature-30 ~ 200 ℃;

(6) stir speed (S.S.) is 50 ~ 1000 rpm.

Advantage of the present invention:

1. low production cost;

2. production process is simple relatively;

3. product muskone purity is high;

4. production environmental protection, environmental pollution is less;

5. muskone synthesis technology content is high;

6. realized the large-scale production that muskone is produced;

7. title product high purity muskone is fit to purposes such as medical treatment, medicine, food, spices, makeup.

Description of drawings

The synthesis technique circuit of Fig. 1 muskone.(1) is cyclododecanone, C ₁₂H ₂₂O, molecular weight 182.30; (2) be METHYL ALLYL CHLORIDE, C ₄H ₇Cl, molecular weight 99.55; (3) be alkene butyl cyclododecanone, C ₁₆H ₂₈O, molecular weight 236.39; (4) be methyl bicycle 15 diene, C ₁₆H ₂₆, molecular weight 218.38; (5) be methyl bicycle ten pentaenes, C ₁₆H ₂₈, molecular weight 220.39; (6) be methyl ring 15 diketone, i.e. muskone, C1 ₆H ₂₈O ₂, molecular weight 252.39; Bu ₄NBr is a Tetrabutyl amonium bromide, molecular weight 322.37; NaOH is a sodium hydroxide, molecular weight 40.00; Toluene is a toluene, C ₇H ₈, molecular weight 92.14; Al ₂O ₃Be aluminium sesquioxide, molecular weight 101.96; HCOONH ₄Be ammonium formiate, molecular weight 63.06; Hexane is a normal hexane, C ₆H ₁₄, molecular weight 86.20; Pd/C is a palladium/carbon catalyst; NaIO ₄Be potassium periodate, molecular weight 213,89.

Claims

1. the muskone scale production process of an economic environmental protection; It is characterized in that with the cyclododecanone being that raw material and METHYL ALLYL CHLORIDE carry out nucleophilic substitution reaction, carry out ring-closure reaction and generate cyclic diolefine; Get cyclenes after the selective reduction; Reoxidize and generate the title product muskone, adopt the short-path distillation purifying at last, obtain highly purified muskone.

2. the said production technique of claim 1 is characterized in that synthetic line is following:

(1) cyclododecanone (C ₁₂H ₂₂O) and METHYL ALLYL CHLORIDE (C ₄H ₇Cl) at Tetrabutyl amonium bromide (Bu ₄NBr) and under sodium hydroxide (NaOH) catalysis, carry out nucleophilic substitution reaction and generate alkene butyl cyclododecanone (C ₁₆H ₂₈O);

(2) alkene butyl cyclododecanone is at aluminium sesquioxide (Al ₂O ₃) and toluene (C ₇H ₈) under the catalysis, carry out ring-closure reaction and generate methyl bicycle 15 diene (C ₁₆H ₂₆);

(3) methyl bicycle 15 diene are at ammonium formiate (HCOONH ₄) and palladium/carbon (Pd/C) catalysis under, selective reduction becomes methyl bicycle ten pentaene (C ₁₆H ₂₈);

(4) methyl bicycle ten pentaenes are at sodium periodate (NaIO ₄), Tetrabutyl amonium bromide (Bu ₄NBr) and normal hexane (C ₆H ₁₄) in the environment, oxidation generates title product methyl ring 15 diketone (C1 ₆H ₂₈O ₂), i.e. muskone;

(5) title product adopts the molecular distillation equipment purifying, obtains highly purified muskone.

3. claim 1 or 2 said production technique is characterized in that becoming in the alkene butyl ten diketone reaction process, with Tetrabutyl amonium bromide (Bu at cyclododecanone and METHYL ALLYL CHLORIDE nucleophilic reaction ₄NBr) be phase-transfer catalyst, in the profit mixed system, react that environmental friendliness is convenient to liquid waste disposal.

4. claim 1 or 2 said production technique is characterized in that being reduced in the methyl bicycle ten pentaene reaction process at methyl bicycle 15 diene, adopt ammonium formiate (HCOONH ₄), palladium/carbon (Pd/C) catalytic hydrogen transfer method, the two keys on selective hydrogenation reduction methyl bicycle 15 diene.

5. claim 1 or 2 said production technique is characterized in that being oxidized to methyl ring 15 diketone at methyl bicycle ten pentaenes, promptly in the muskone reaction process, with the sodium periodate (NaIO of low toxicity ₄) as oxygenant, reduced the oxygenant such as the chromium trioxide (CrO of high poison ₃), titanium dioxide arsenic (SeO ₂) use that waits, reduced environmental pollution, the reaction process environmental protection.

6. the said reactions step of claim 2 is characterized in that with Tetrabutyl amonium bromide (Bu ₄NBr) be phase-transfer catalyst, in the profit mixed system, react that environmental friendliness is convenient to liquid waste disposal.

7. claim 1 or 2 said production technique is characterized in that starting raw material is the cheap cyclododecanone that is easy to get, large-scale production economy.

8. claim 1 or 2 said production technique is characterized in that each reactions step all is Atom economy reactions, and side reaction is few.

9. claim 1 or 2 described large-scale productions is characterized in that simple to operately, and production line yearly capacity surpasses 100 tons of muskones.

10. claim 1 or 2 described title product muskones is characterized in that adopting short-path distillation to carry out purifying, and muskone purity surpasses 98.0%.