CN1038130C - Method for preparing tricyclic iso-chroman - Google Patents
Method for preparing tricyclic iso-chroman Download PDFInfo
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- CN1038130C CN1038130C CN92113052A CN92113052A CN1038130C CN 1038130 C CN1038130 C CN 1038130C CN 92113052 A CN92113052 A CN 92113052A CN 92113052 A CN92113052 A CN 92113052A CN 1038130 C CN1038130 C CN 1038130C
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Abstract
The present invention relates to a method for preparing a tricyclic isochroman compound, namely HHCB. The present invention does not separate intermediate hydroxyindane; substances which are complex with aluminum trichloride are directly added to a reaction mixture which can produce the hydroxyindane, and then, the ring-closing reaction of the hydroxyindane and formaldehyde is carried out. Accordingly, the method successfully realizes that the step starts from pentamethyl indane; tricyclic isochroman is once synthesized in the same reactor without separation; reaction steps are simplified; product yield and product quality are increased; the growth cycle reduces about 50%, and the production cost reduces about 40%.
Description
The present invention relates to tricyclic iso-chroman is the preparation method of Jiale muskiness, belongs to heterogeneous ring compound.The existing method for preparing Jiale muskiness all is that the pentamethyl-indane with formula (I) is a raw material, at anhydrous AlCl
3Following and the propylene oxide of catalysis
Carry out Friedel-crafts reaction, the indanol of production (II) makes (II) to carry out ring closure reaction with formaldehyde again under strong acid catalysis and generates Jiale muskiness (III), and used strong acid can be exsiccant HCl gas, tosic acid or phosphoric acid.This class methods shortcoming is to need to separate high boiling formula (II) the intermediate indanol of purifying, and needs to add in addition acid catalyst again and makes the compound of formula (II) and formaldehyde carry out ring closure reaction, and reactions steps is many, and the production cycle is long, and total recovery is low, the energy consumption height.Theimer[US 3532719 (1970)] Sprecker[US 4,178 311 (1979)] above method has been done improvement, be about to water or alcohol and be added in the reaction mixture of generation (II), make AlCl
3Partial hydrolysis or alcoholysis make it no longer to have the ability of catalysis Friedel-crafts reaction, but and the ring closure reaction of catalysis (II) and formaldehyde.But water or alcohol and AlCl
3Reaction too violent, emit a large amount of heat, local temperature is too high, side reaction increases, and produces a large amount of high boiling point tarry materialss, and easy caking, cause and stir difficulty, reaction not exclusively, yield descends.In addition, introducing water or alcohol can cause ring closure reaction to carry out not exclusively making to be mixed with a small amount of indanol in the product, and influencing quality product before ring closure reaction.
The inventive method is to add ester compound and AlCl in the reaction mixture after generating (II)
3Complexing reduces its activity, makes it no longer to have the ability of catalysis Friedel-crafts reaction and the ring closure reaction of only catalysis (II) and formaldehyde, has successfully realized from the pentamethyl-indane to tricyclic iso-chroman, without any separating step, once finishes reaction in same reactor.Because ester and ALCl
3Effect be a kind of complexing action, heat release hardly reacts very steady, complex compound easily in organic medium dissolving form homogeneous phase, and catalysis well (II) and formaldehyde generation ring closure reaction.Overcome water with the ester class well as passivator, alcohol is made the shortcoming of passivator, has improved the product yield, and has improved quality product and promptly improved the content of major ingredient in the product, and the synthetic route of an economical and convenient is provided for the industrial production Jiale muskiness.
The inventive method comprises:
1. make compound (I) and propylene oxide under Catalyzed by Anhydrous Aluminium Chloride, Friedel-crafts reaction takes place in organic solvent, generate compound (II), the compound of formula (I) and the mol ratio of propylene oxide are (1-5): 1, the mol ratio of aluminum trichloride (anhydrous) and propylene oxide is 1: 1, temperature of reaction-15--5 ℃, reaction times 1-3 hour
2. at-10--5 ℃, in the reaction mixture that contains (II), add a kind of C
1-C
2Carboxylic acid and C
1-C
3The ester that Fatty Alcohol(C12-C14 and C12-C18) forms, complexing AlCl
3, reducing its activity, the mol ratio of ester and aluminum trichloride (anhydrous) is (1-2): 1.
3. add compound and the formaldehyde generation ring closure reaction that formaldehyde makes formula (II) in above-mentioned reaction mixture, temperature of reaction is at 5-40 ℃, and the mol ratio of aldehyde and aluminum trichloride (anhydrous) is 1: (1.1-1.6).
Described organic solvent can be selected excessive formula (I) compound, C for use
1-C
2Chloroparaffin, chlorinated benzene or C
5-C
10Alkane or their mixture.Formaldehyde can be selected Paraformaldehyde 96 for use, trioxymethylene or formaldehyde and C
1-C
3The formaldehyde that forms of the alcohols glycol that contracts.The content of product Chinese style (III) compound is equal to or greater than 70%.
It is as shown in the table that the inventive method is better than the comparative data of currently known methods:
Reference ring closure reaction condition process characteristic total recovery boiling point US 3360530 (1967) Paraformaldehyde 96s+HCl must separate (II), and reaction divides 35-45% 129 °/0.8mmHg
℃ two steps of gas 25-120 carry out, 35% 117 °/1.2mmHg of long US 4315951 (1980) tosic acid of production cycle+the same
Virahol+poly
Formaldehyde 93-150 ℃ of the same 40% 150-55 of Chinese invention patent application Paraformaldehyde 96+phosphorus °/3mmHg prospectus publication number 80 ℃ of 1041362A of acid anhydrides (1990) US 3532719 (1967) water or alcohol moiety water must not separate (II), a 60-65.5% 89-139 °/0.9mmHg
Separate AlCl
3After add step reaction, with short production cycle, US 4178311 (1978) Paraformaldehyde 96s or first but the sticking silk fabric of reaction solution is easily tied 27-44% 127-36 °/2mmHg
The aldehyde glycol 10-piece that contracts, operation easier is big
50 ℃ of the inventive method ester complexing AlCl
3Must not separate (II), a 70-83% 145-55 °/2.5mmHg
The reaction of back+Paraformaldehyde 96 step, with short production cycle, * 70-76% (GC)
Or the contract content of the easy to operate * of glycol actual measurement formula (III) compound of formaldehyde
5-50 ℃ (GC method).
The inventive method and existing method shorten the production cycle 50% approximately, reduce production costs 40%, have improved product yield and quality product greatly.
The raw materials used pentamethyl-indane of the present invention major ingredient is the compound of formula (I), also contains formula (I ') and a small amount of other components, and the compounds content of formula (I) should be greater than 80%.
The inventive method synthetic three-ring different color is full of a mixture, and major ingredient is the compound of formula (III), also has the compound of a small amount of formula (III ') and formula (III ') and other compositions of trace.The content of formula (III) compound equals greater than 70%.
In order to be illustrated more clearly in the inventive method, enumerate the following example, but these there is not any restriction to scope of the present invention.
Embodiment: preparation 6-oxa--1,1,2,3,3,8-hexamethyl-2,3,5,6,7,8-six hydrogen-1H-benzo [f] indenes (being called for short the hexamethyl tricyclic iso-chroman, the trade(brand)name Jiale muskiness)
Example 1
Add chlorinated benzene 80ml in the 1000ml there-necked flask, pentamethyl-indane 150ml (137g, 0.73mole), aluminum trichloride (anhydrous) 95g (0.71mole), cooling is also stirred rapidly ,-15--10 ℃ dropping 80ml chlorobenzene and 54ml propylene oxide (46g, 0.80mole) mixture, dripped in 2-3 hour, holding temperature continues to stir 20-40 minute at-10--5 ℃.Drip the 102ml ethyl acetate at-5--0 ℃ then, after dripping in 20 minutes, add 45ml methylal (38.7g, 0.51mole), 15-30 ℃ stir 1.5-2 hour after, in frozen water cooling downhill reaction system impouring 300ml cold water stopped reaction, stir to leave standstill after 10 minutes and tell organic phase and wash once, more successively with the saturated Na of the saturated NaCl200ml of 200ml with the HCl aqueous solution of 200ml15%
2CO
3The NaCl aqueous solution that 200ml is saturated is respectively washed once, normal pressure steams ethyl acetate, steams the solvent chlorobenzene under the decompression, fractionates out unreacted raw material pentamethyl-indane 32.8g again under decompression, boiling point 78-82 °/2.5mmHg, Jiale muskiness 119.7g, boiling point 145-55 °/2.5mmHg, overall yield of reaction counts 83.7% with the actual consumption indane, the gas-chromatography of product (GC) content is 72.46% (see figure 1), and IR and NMR see Fig. 2 and Fig. 3.
Example 2
In the 1000ml there-necked flask, drop into pentamethyl-indane 222ml (200g, 1.06mole), aluminum trichloride (anhydrous) 100g (0.75mole), methylene dichloride 90ml is under the cooling and stirring, in-15--5 ℃ dropping 111ml pentamethyl-indane and 51ml propylene oxide (44g, 0.76mole) mixture, added the back in 2-3 hour and continue to stir 20 minutes ,-10--5 ℃ drips 108ml ethyl acetate (98.3g, 11mole), dripped in 20 minutes, and added the 47ml methylal, stirred 2 hours in 15-40 ℃, add 300ml water stopped reaction, aftertreatment fractionates out methylene dichloride and ethyl acetate with example 1 under the normal pressure, decompression steams pentamethyl-indane 186g, boiling point 80-7 °/2.5mmHg, Jiale muskiness 123.6g, boiling point 145-55 °/2.5mmHg, overall yield of reaction is counted 79% (content GC is 75.93%) with the actual consumption indane and is seen Fig. 4.
Example 3
Drop into pentamethyl-indane 206ml (187.5g in the 1000ml there-necked flask, 1.0mole), aluminum trichloride (anhydrous) 665g (0.50mole), under-15--5 ℃ stirring, drip 310ml pentamethyl-indane (282g, 1.50mole) and 44ml propylene oxide (37.8g, 0.50mole) mixture, dripped the back restir in 2-3 hour 20 minutes, in-5--0 ℃ dropping 82ml isopropyl acetate (0.74mole), after adding in 20 minutes, add the 30ml methylal (25.8g, 0.34mole), at 35-40 ℃ of stirring reaction after 2.5 hours, cooling adds 300ml water stopped reaction, aftertreatment is with example 1, and after normal pressure steamed isopropyl acetate, decompression steamed pentamethyl-indane 401.5g, boiling point 81-5 °/2.5mmHg, Jiale muskiness 76.3g, boiling point 145-55 °/2.5mmHg, overall yield of reaction is counted 81% (content GC is 69.96%) with the actual consumption indane.
Example 4
Drop into pentamethyl-indane 178ml (160g in the 1000ml there-necked flask, 0.85mole), aluminum trichloride (anhydrous) 80g (0.60mole), methylene dichloride 90ml, in-following (90ml that drips of 15--5 ℃ stirring, 81g, 0.43mole) (35g, the 0.61mole) mixture of propylene oxide stirred 20 minutes after adding in 2.5-3.0 hour again for pentamethyl-indane and 41ml,-10--0 ℃ drips 86.5ml ethyl acetate (78.6g, 0.88mole), after adding in 20 minutes, add 19.0ml, (0.63mole) Paraformaldehyde 96 of porphyrize, be warming up to 30 ℃ and stir after 5-8 hour, termination reaction in the impouring 300ml water under the cooling, aftertreatment is with example 1, elder generation's normal pressure steams after methylene dichloride and the ethyl acetate again, and decompression steams unreacted pentamethyl-indane, get 131g, boiling point 80-7 °/2.5mmHg, Jiale muskiness 103.6g, boiling point 145-55 °/2.5mmHg, overall yield of reaction counts 68.6% with the actual consumption indane.
Claims (5)
1 one kinds of methods that prepare tricyclic iso-chroman is characterized in that, described method comprises:
(1) in organic solvent, under Catalyzed by Anhydrous Aluminium Chloride, make propylene oxide and the reaction of pentamethyl-indane by following formula, the compound of production (II), temperature of reaction-15--5 ℃, propylene oxide and pentamethyl-indane mol ratio are 1: (1-5), the mol ratio of propylene oxide and aluminum trichloride (anhydrous) is 1: 1, reaction times 1-3 hour;
(2) after above-mentioned reaction is finished, dropwise carboxylate in this mixture, described carboxylicesters is meant C
1-C
2Carboxylic acid and C
1-C
3The ester that Fatty Alcohol(C12-C14 and C12-C18) forms keeps temperature-10-0 ℃, and the mol ratio of ester and aluminum trichloride (anhydrous) is (1.0-2.0): 1, in 10-30 minute, drip;
(3) drip off ester after, in reaction mixture, add formaldehyde, described formaldehyde is selected from the formaldehyde C that contracts
1-C
3Glycol, Paraformaldehyde 96 or trioxymethylene, the mol ratio of formaldehyde and aluminum chloride are 1: (1.1-1.6), and in 5-40 ℃ of compound and formaldehyde reaction that makes formula (II), the compound of production (III), reaction times 2-8 hour;
Above-mentioned reactions steps is all carried out in same reactor, need not to separate any intermediate, adds the water termination reaction at last, and described organic solvent is selected from pentamethyl-indane, C
1-C
3Alkyl chloride, chlorobenzene, C
5-C
10Alkane or their mixture, reaction product is handled according to a conventional method, and the content of the compound of product Chinese style (III) is equal to or greater than 70%.
2. according to the method for claim 1, it is characterized in that solvent used in the described method is, chlorobenzene, reaction conditions is:
(1) mol ratio of propylene oxide and pentamethyl-indane is 1: 1.2, and the mol ratio of aluminum chloride and propylene oxide is 1: 1.2, temperature of reaction is-and 15--10 ℃, reaction times 2-3 hour;
(2) in-5-0 ℃, drip ethyl acetate in above-mentioned reaction mixture, the mol ratio of ester and aluminum chloride is 1.5: 1;
(3) add methylal in last reaction mixture, the mol ratio of methylal and aluminum chloride is 1: 1.3, and temperature of reaction is 15-30 ℃, reacts 1.5-2 hour;
3. according to the method for claim 1, it is characterized in that solvent used in the described method is, the mixture of methylene dichloride and pentamethyl-indane, their volume ratio is 1: (2-3), reaction conditions is:
(1) temperature of reaction of pentamethyl-indane and propylene oxide is-15--5 ℃, and the mol ratio of propylene oxide and aluminum chloride is 1: 1, reaction times 2-3 hour;
(2) dripping ethyl acetate, temperature is-10-0 ℃, dripped in 20 minutes, the mol ratio of ethyl acetate and aluminum chloride is 1.47: 1;
(3) add methylal in last reaction mixture, the mol ratio of methylal and aluminum chloride is 1: 1.18, temperature of reaction 15-40 ℃, reacts 2 hours.
4. according to the method for claim 1, it is characterized in that solvent used in the described method is, the mixture of methylene dichloride and pentamethyl-indane, their volume ratio is 1: (2-3), reaction conditions is:
(1) temperature of reaction of pentamethyl-indane and propylene oxide is-15--5 ℃, and propylene oxide and aluminum chloride mol ratio are 1: 1, reaction times 2-3 hour;
(2) dripping ethyl acetate, temperature is-10-0 ℃, dripped in 20 minutes, the mol ratio of ethyl acetate and aluminum chloride is 1.47: 1;
(3) add Paraformaldehyde 96 in last reaction mixture, the mol ratio of formaldehyde and aluminum chloride is 1: 1, and 30 ℃ of temperature of reaction were reacted 5-8 hour;
5. according to the method for claim 1, it is characterized in that used solvent is the pentamethyl-indane in the described method, reaction conditions is:
(1) mol ratio of propylene oxide and pentamethyl-indane is 1: 4, and the mol ratio of propylene oxide and aluminum chloride is 1: 1, temperature of reaction is-and 15--5 ℃, reaction times 2-3 hour;
(2) in-5-0 ℃, drip isopropyl acetate in above-mentioned reaction mixture, isopropyl acetate and aluminum chloride mol ratio are 1.48: 1;
(3) add methylal in last reaction mixture, the mol ratio of methylal and aluminum chloride is 1: 1.47.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN92113052A CN1038130C (en) | 1992-11-21 | 1992-11-21 | Method for preparing tricyclic iso-chroman |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN92113052A CN1038130C (en) | 1992-11-21 | 1992-11-21 | Method for preparing tricyclic iso-chroman |
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| CN1072179A CN1072179A (en) | 1993-05-19 |
| CN1038130C true CN1038130C (en) | 1998-04-22 |
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|---|---|---|---|
| CN92113052A Expired - Lifetime CN1038130C (en) | 1992-11-21 | 1992-11-21 | Method for preparing tricyclic iso-chroman |
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| CN110563692A (en) * | 2019-08-15 | 2019-12-13 | 安徽金禾实业股份有限公司 | Method for preparing galaxolide musk by using superfine aluminum trichloride as catalyst |
| CN111718235B (en) * | 2020-07-21 | 2022-09-23 | 安徽金轩科技有限公司 | Method for recovering Jiale musk chlorobenzene solvent |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4162256A (en) * | 1978-04-19 | 1979-07-24 | International Flavors & Fragrances Inc. | Process for the production of compounds useful in perfumery |
| US4178311A (en) * | 1978-04-19 | 1979-12-11 | International Flavors & Fragrances Inc. | Process for the production of compounds useful in perfumery |
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1992
- 1992-11-21 CN CN92113052A patent/CN1038130C/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4162256A (en) * | 1978-04-19 | 1979-07-24 | International Flavors & Fragrances Inc. | Process for the production of compounds useful in perfumery |
| US4178311A (en) * | 1978-04-19 | 1979-12-11 | International Flavors & Fragrances Inc. | Process for the production of compounds useful in perfumery |
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|---|---|
| CN1072179A (en) | 1993-05-19 |
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Expiration termination date: 20121121 Granted publication date: 19980422 |