CN1229073A - Three-type high-purity synthetic borneols and economic making method for getting from crude product - Google Patents

Abstract

A low-cost process for preparing three kinds of high-purity synthetic borneol from the composite borneol containing borneol and isoborneol in market features that based on the chemical differentiation and physical frationation, the isoborneol is separated out of the composite borneol for other purposes and high-purity borneol is obtained. Based on the invented process, using dextro alpha pinene as raw material can obtain high-purity dextro bornol, using levo alpha pinene can obtain high-purity levo berneol, and using dextro and levo mixed pinene can obtain high-purity racemized borneol. Its advantage is no environmental pollution.

Description

Three kinds of high-purity borneolum syntheticums and the economic method for making that from crude product, gets thereof

Borneol originally is the crude substance that is present among the various plants, and pure and fresh banksia rose fragrance is arranged, and is applied to medicinal material and fragrance industry for a long time.Owing to resource is few, gathers processing and be difficult for, therefore with regard to very apparent preciousness.After the self energy synthetic, adapted to this growing demand.But current now firpene barkite choline is separated the prepared borneol of technology and is compared with natural product, and the ambassador people of quality discrepancy is not only discontented but also helpless.It has only accounted for cheap advantage, and all the other all are weak point.This just impels the scientific worker to go to explore better manufacture method, and can reach the purpose of the high-purity borneol of synthetic with several different methods.But this is learned success, and can't make cost drop to the receptible degree of user on manufacturing expense, and in face of that noble price, instead the user has solely natural product feelings and doted on.The said economic method for making of the present invention is meant that promptly the economy of method for making can reach that level that commercialization requires, and also is that cost drops to the price stage suitable with its use value significantly, thereby can be admitted by market.In order well to illustrate content of the present invention, just write as follows according to the requirement of patent law:

Before more than 100 year, scientist can make basic raw material with turps, and after this synthetic Borneolum Syntheticum is updated, and develops into today, although synthetic quality is unsatisfactory, has replaced the status of natural borneol basically.This is caused by two big reasons;

1, because borneol has significant status in Chinese medicine, the application quantity in the fragrance industry is also very big.Natural product are hard-earned, only produce domestic every year about one ton, do not apply without recourse to synthetics and use.2, natural product cost an arm and a leg, and general low value commodity can not used the raw material of this costliness, use synthetics instead and are still very wise move.

The present invention greatly improves the quality of borneolum syntheticum, even can account for item such as many height ratios with regard to optical direction, borneol composition and meet the particular requirement that application person proposes.If it is proper that the production of common borneolum syntheticum belongs to the woods chemical industry, that the present invention then can be arranged in the field of fine chemistry industry.

As far back as 19th century, scientist has three different kinds with regard to knowing natural borneol because of the difference on the rotary light performance.(1)

1, d-Bomeol (d-borneol) claims borneol again, is present in the dryobalanops aromatica Gaertner in Borneo, Nan Yang, and Ji'an Prefecture, China Jiangxi still extracts this crude substance in the several plant of locality at present.

2, left-handed borneol (l-borneol) claims the Chinese mugwort sheet again, is present in the wormwood in Guangxi, Guangdong.

3, racemization borneol (dl-borneol) is at natural camphor oil: existence is arranged in the Salvia Sclare L.oil.

From motherland's medicine viewpoint, borneol is better than the sheet that ends, the used borneol of traditional Chinese medicine before synthetic, the d-Bomeol that all is meant, and the isomer of borneol---isocamphol is very few at occurring in nature, in the Chinese medicine ancient books and records before 19th century reached, and the also record that does not substitute with it.

In nature, the borneol kind in the different plants is single, so its single pure product of being easy to get very much, though stock number is few, the pure material of three kinds of borneol still relatively is easy to get.Synthetic is just different, always is mixed with the isocamphol about 40% in the now general borneolum syntheticum, and isocamphol not only drug effect has a question, and its note also is inferior to borneol.

The scientific worker knows very well those shortcomings, has also once done the content that a large amount of work improves borneol in the sintetics, takes a blanking method, the formation of isocamphol in the containment chemical reaction.For example: the hydration method just can obtain high-purity borneol.Shanghai inorganic chemical industry institute produces borneolum syntheticum for oxalic acid as the esterification materials with Mono Chloro Acetic Acid.Also can obtain the good result that borneol accounts for finished product 90%.(2) but these novel methods all have the major defect that can not look down upon---operate hard to tacklely, row yielding is extremely low, and cost is high.Thereby make the constricted flow of finished product in business activity.Even the plum sheet to produce as a trial in Huangpu, Guangzhou chemical plant hydration method yet can fall and can't enlarge again because of cost height, price.Therefore high-purity borneol will become the mass-produced commodity of energy, just must develop the process recipes of very economical.

In general, the purity of modern chemistry synthetic drugs all is very high, nowadays contained 40% isocamphol in synthetic borneol, and it is a crude product at last just.The study of Confucian classics meaning that many allusions are arranged in the theory of the traditional Chinese medical science, but more be the empirical summary of long term medical, a lot of prescriptions all are the proved recipes that prolonged application all takes effect, therefore, can not substitute even some material Chemical Composition is identical, such as seeing according to traditional viewpoint, the zunsober of black can not replace red cinnabar to be used as medicine, modern medicine proves that again isoascorbic acid does not possess ascorbic anti-bad blood function, and this isocamphol just more can not go to have sent the purposes of borneol certainly.Traditional Chinese medicine is also in the constantly development along with the progress in epoch, containing how many effective ingredients in the medicine extremely payes attention to, in recent years many progress have been had, as from the medicinal material Chinese ephedra, extracting ephedrine hydrochloride, extract Myodigin from Folium Digitalis, extracting berberine hydrochloride etc. from the coptis all is to belong to the progress that removes crudely and store essence.Making not contain in the borneolum syntheticum or cut off to contain isocamphol less, also is a kind of effective work that improves the pharmacy level.

In field of perfumery, also be sought after high-purity borneol goods.When the perfumer prepares essence, except that a small amount of application natural essential oil is strengthened the natural flavor of furnishing product, more be the simple simple substance raw materials of needs, or need some combination products, and compositely proportional also has certain requirement.Now the compositely proportional of borneol is to be bordering on 6: 4 fixed value, and the blending worker can not be satisfied with to this.Though because the isocamphol of various opticities all has the camphoraceous refrigerant breath of class, the d-isocamphol also accompanies the zylonite smell, the l-isocamphol is also mixed musty (3).These thick turbid breaths make the people experience not good, are limited to 40% value so the isocamphol content that they require has more than, and face is also will be more still less.

The present invention does not resemble and studies the processing method that isocamphol seldom occurs in the chemical combination process emphatically the forefathers, does not painstakingly seek the raw catalyst of this effect yet.

Although the specific composition in the BTiG-95 catalyzer can make the borneol content in the work in-process reach 78% high levels, obvious decline has appearred in the total recovery of this moment.If must obtain the high-purity goods more than 90% thus, the number of times of recrystallization is inevitable a lot, and mother liquor occurs in a large number, and final yield rate is necessarily very low, so it is not also at the row of employing.

Main idea of the present invention is to separate in addition and use being mixed in isocamphol in the borneol, and the borneol of remainder just very easily has been refined into pure product.

Why to formulate so technical scheme? because two keys, a tetramethylene and a sec.-propyl are arranged in the molecular structure of firpene, this has just determined it that the polytropism of very high chemical activity and chemical transformation is arranged, it is carried out the result of various scientific practices, confirm that also the end reaction thing is multifarious, attempt merely is difficult to make one's wish fulfilled by the diversity that selectivity of catalyst overcomes reactant.Though borneol is very high to the ratio of isocamphol in the hydration method, it has produced a large amount of Terpineol 350s.This is a unexistent thing in boron, two kinds of catalyzed reactions of titanium.For the oxalic acid esterification, outside not only fenchol rolled up, the foreshot of compositions such as kautschin was doubled and redoubled again with Mono Chloro Acetic Acid, the low degree of halting to making prestige of the overall value of resultant.

So adopting this scheme is in the structure properties of having analyzed firpene with after having summed up multiple in the past high-purity borneol synthesis technique, weigh various pros and cons and concern and just formulate separately.

From an economic point of view, should be to only require that the overall value of gained resultant of chemical reaction is the highest, and then they have been separated just one by one.Just for this consideration economically, technically just focus on the maximum value that obtains the major-minor product population, and its isolation technique of research that stresses, so that they are separated one by one.Only this value and their the highest total value that just can embody each component is come.

The rerum natura voltinism of borneol and isocamphol is all very close, and simple use physical method or chemical process are difficult to the two is separated, and has the two only and reasonably unites to utilize one's abilities and prove effective.

Although borneol and isocamphol are very close aspect voltinism, but always because of there being textural difference slightly different, the two just has difference for the reaction of dewatering agent, isocamphol is easy to dehydration face in acidic solutions such as dilute sulphuric acid, oxalic acid, iron trichloride become embedding alkene, as long as the acid solution intensity of selecting is suitable, this reaction then can not take place in borneol.But to be applied to industrial production to this principle, also have one to prevent that the continuous change problem of isocamphol after becoming embedding alkene from will properly dispose.Polymerization can take place in embedding alkene in the pyritous acidic liquid, become flaxen resinous substance.Embedding alkene also is a kind of spices of great use, and this polymkeric substance there is no much use.Therefore, prevent and the fusion that reduces embedding alkene has been exactly very significant technical measures.

By many-sided exploration, and the various pros and cons that occur are analyzed, contrast, sum up, thereby determined technical process as shown in Figure 1.

In order to make for the purpose of colleague Geng Yi understands, just must do some explanation to the place that is easy among Fig. 1 misread: 101 dilute acid solns adopt sulfuric acid the most economical, concentration is advisable to be no more than 13%, too densely be unfavorable for preventing polymerization, 2% following person's reaction times is oversize, other acidic solutions also can adopt certainly, decide application concentration but also should take into account two sides.103 solvents must have to be stablized constantly in acid solution, does not produce chemical reaction with the rare and borneol of embedding again, and boiling point is in the middle of the boiling point of embedding alkene and borneol again, and these requirements make alternative organic solvent just few.Sym-trimethylbenzene and isooctyl alcohol effect in practical probation is better, recommends use in this head.

Though in principle, it is not definitely indispensable adding organic solvent, and from economic point of view and easy to operate, it but is very favourable adding organic solvent.Certainly, add the utilization ratio too much reduced volume of equipment, cross and operate at least and prevent that polymerization is unfavorable, recommending the weight ratio of isooctyl alcohol and thick borneol in this is 1: 2-2.5 (recommendation is not treated as boundary).

Below illustrated the process program of obtaining high-purity borneol substantially.Be the basis according to this, manually produce high-purity dextrorotation, left-handed, racemization borneol is just very easy.

The scientific worker knows for a long time: make starting raw material with turps, after esterification alkaline hydrolysis method had been synthesized borneol, the rotation direction of its opticity is special littlely not to be changed, but that the size of specific rotation will become is littler.Be raw materials used as being dextrorotation turps, what then obtain is exactly the mixture of d-Bomeol and dextrorotation isocamphol.Otherwise raw materials used has been exactly the mixture of left-handed borneol and left-handed isocamphol as what then obtain for left-handed turps.

At least to so far, the major ingredient in all turps---firpene all is active, and this firpene also is only the real object that utilizes.In practicality, the pinane that also also first necessity goes painstakingly to seek racemization is rare.

Domestic turps except that pinus khasys and pinus finlaysoniana is the dextrorotation, and remaining all is left-handed.The specific rotation of Pinus kesiya Royle ex Gord. Var. Langbianensis (A. Chev.) Gaussen oil is up to+52.85 °, and the composition of α firpene is up to 96%, so economic worth is very big.Should be preferred raw materials.

So far, utilize Pinus kesiya Royle ex Gord. Var. Langbianensis (A. Chev.) Gaussen oil, pinus finlaysoniana turps is by technical process of the present invention, and it is exactly fully feasible that separation makes high-purity borneol, and same reason can make high-purity Chinese mugwort sheet with the turps of Pinus massoniana Lamb slash pine.If 502 thick Chinese mugwort sheet and 502 thick borneol corresponding mixing before 601 operations, the just material as natural racemization borneol that so finally obtains.(can certainly give earlier mixing with left-handed and dextral turps, make the thick borneol of racemization then with it, obtain high-purity racemization borneol through separation and purification again).

Necessary make clear be: though the present invention can make borneolum syntheticum reach very purified degree, but do not reach the so good level of natural product.The specific rotation of high-purity borneol, high-purity Chinese mugwort sheet is all little more than 10 ° than natural product, uses as the Chinese medicine medicinal material, and curative effect will be weaker; High-purity racemization borneol is compared with natural racemization borneol, certainly cannot distinguish on the specific rotation, but in the natural racemization borneol except that borneol composition of 95～96%, what also have 4～5% but is the valuable material that has more tempting breath, this is just more valuable in blending, and high-purity racemization borneol can't possess the sort of special note.

Though three kinds of high-purity borneolum syntheticums all have its weak point, but be not very severe tight place requiring.Should be them fully passable as the surrogate of natural product.Just because of they are more cheap and easy to get than natural product, thus the coml special benefits of can extending out again, the promptly very easy particular requirement of satisfying the client.The America travelling trader once proposed to want to buy 90% borneol, 10% isocamphol and 80% borneol, 20% different two kinds of commodity forming through brain in the past, enter to satisfy customer requirement with natural borneol admixture isocamphol, but whoever can not do like this, calculate not come because be really economically, and utilize high-purity borneol of synthetic just can to do like this, because this still beneficial economically can getting.Certain this situation can't often run into, but the means of this client's of satisfying specific demand have been arranged, also just not anxious cannot having tackled.

After know-why of the present invention and scheme are illustrated, also have main points also must make clear, that is exactly what a problem of row yielding.Owing to change simple, added after the solvent, the generation trend of polymkeric substance is subjected to abundant choke suppress, also be easy to control in the operation, therefore row yielding can reach about 90% of theoretical value, if heat exchanger area is enough big, and can all dispose in the front and back of vacuum pump again, it is complete possible thing that yield rate reaches more than 90%.

New technology, product innovation also must be considered whether coincide social growth requirement and interests in consideration self benefit.Along with socioeconomic continuous development, people only can be more and more higher to the quality requirements of the consumer's goods, and are then just more severe tight for Medicines.

Traditional Chinese medical science is of long standing and well established, and before borneolum syntheticum occurred, the borneol in the Chinese medicine was just widely used, and even to this day, range of application is then more vast.Not only in the medicinal herbs most in use borneol is arranged in 95 editions Chinese Pharmacopoeias, in 44 kinds of one-tenth sides and single goods, also contain borneol, wherein be no lack of proved recipe and the ancient prescription that screens in life-time service arranged, perhaps wherein the dosage of used borneol all is meant at that time crude substance, infiltrates having disliked of making up the number as replacing with current borneolum syntheticum with regard to the unnecessary isocamphol of handlebar.The present invention does his usefulness in addition to isocamphol taking-up wherein, and pharmaceutical grade just can improve, thereby has acted in accordance with the worldwide trend that medicine purity will improve constantly in the pharmacopeia.

The current domestic producer that still has is producing a spot of natural Broneolum Syntheticum, and its outlet price per kilogram is up to 7.5 dollars more than.Production firm and use the price interest relations between the client to check and balance does not do a good job and will restrain mutually and become combined symptoms.The present invention handles the good way of this contradiction just, gives family planning and produces the cost of high-purity borneol and will drop to about the sixth of natural product, and do not have pollutant emission in the whole process of production, can be rated as good good friendly process.

Can also see from the flow process of Fig. 1 to draw that this technology is easy to realize, in the factory of current production borneolum syntheticum, after the thick borneol of work in-process, before the refining crystallization, increases a little easy facilities again, three kinds of high-purity borneol just can create.The content newly-increased at management aspect also only is that turps will split by opticity, and finished product will each separates by different grades, and this measure of avoiding confusion is not heavy yet.

The operating unit that fixed client is arranged also has a better shortcut to walk, and that is bought common borneolum syntheticum exactly and establishes workshop processing in addition, and like this, investment cost just can drop to bottom line, and short, adaptable and fast hope goes out just to be easy to realize.Reference:

(1) synthetic perfume and mono-isolate, P82～P90.Light industry press, nineteen sixty version.

(2) chemistry world, the 9th phase of nineteen eighty-three, P71.

(3) fine chemicals dictionary, P824, the Japanese fine chemicals dictionary editing council compiles, Chemical Industry Press's version in 1989.

Claims (4)

1, three kinds of high-purity borneolum syntheticums---d-borneol l-borneol dl-borneol.They can mix the racemization firpene of forming with d-firpene l-firpene and two kinds of rotation directions of corresponding rotation direction, obtain thick borneol earlier by existing esterification alkaline hydrolysis technology, then it is added to and goes reprocessing in the mixed solution of solvent and diluted acid, make isocamphol dehydration wherein be embedding alkene, then fractionation is refining, can obtain above-mentioned three kinds of high-purity borneolum syntheticums.

2, require according to right 1 that described reprocessing is special little to be: solvent and dewatering agent and close application, solvent be a kind of boiling point between embedding alkene and borneol boiling point, do not participate in the organic solvent that reacts again therebetween, dewatering agent then is the dilute acid soln of proper concn.Iso-campholic acid is separated dehydration should use rectification under vacuum technology for the fractionation separates after the embedding alkene.

3, according to the requirement of right 1: with the refining three kinds of high-purity borneolum syntheticums that get of isocamphol dehydration → rectifying separation → dissolving, its characteristic is: the dextrorotation specific rotation of high-purity synthetic d-borneol is less than natural product and hydration method product more than 10 °; The left-handed specific rotation of high-purity synthetic l-borneol is compared with hydration method product with natural product, also wants little more than 10 °; And high-purity synthesising racemation borneol is compared with natural product, will differ from a grade on the level of commenting perfume (or spice), product perfume.

4, according to the requirement of right 1: can mix with high-purity borneolum syntheticum and existing common borneolum syntheticum and to make the borneol ratio in the blending new variety more than 80%, its characteristic is that the shared composition of borneol exceeds in the existing common product borneol composition more than 10% in the product.

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