CN106397160A - Synthetic method for macrocyclic musk ketone - Google Patents
Synthetic method for macrocyclic musk ketone Download PDFInfo
- Publication number
- CN106397160A CN106397160A CN201610770424.5A CN201610770424A CN106397160A CN 106397160 A CN106397160 A CN 106397160A CN 201610770424 A CN201610770424 A CN 201610770424A CN 106397160 A CN106397160 A CN 106397160A
- Authority
- CN
- China
- Prior art keywords
- acid
- cyclopentadecanone
- olefin
- musk
- yield
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/41—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrogenolysis or reduction of carboxylic groups or functional derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/34—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with ozone; by hydrolysis of ozonides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/487—Separation; Purification; Stabilisation; Use of additives by treatment giving rise to chemical modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
Abstract
The invention provides a method for synthesizing high-grade perfume, i.e., high-value musk perfume cyclopentadecanone (macrocyclic musk ketone), from Malania oleifera oil. The Malania oleifera oil is used as a raw material and subjected to saponification, acidification, recrystallization, ozonization, oxidation, esterification, cyclization and reduction successively so as to prepare cyclopentadecanone. The method is high in yield, good in benefits and low in cost and overcomes the shortcomings of complex production process, low yield, high cost and no market advantage in the prior art. The Malania oleifera oil contains 40 to 60% of tetracos-15-enoic acid which is an ideal raw material for synthesis of the high-value musk perfume. Tetracos-15-enoic acid is a necessary nutriment for development of the brain, exerts critical effect on improvement of the activity of cranial nerves and prevention of encephalasthenia, has good curative effect on cardiovascular diseases and diseases caused by autoimmune deficiency, and can be used as a medicine and a health product.
Description
Technical field：
The invention belongs to technical field of chemical products is and in particular to a kind of medicine, health products, the synthesis of cosmetic additive agent
Method, more particularly, to a kind of method synthesizing macrocyclic musk ketone from Malania Oleifera Oil.
Background technology：
Moschus is a kind of valuable animal property spices, is thus referred to as the king of spices early in the Eastern Han Dynasty Moschus.Its diffusivity
Extremely strong with valence, there is special soft and the fragrance of gracefulness, good Titian effect and splendid fixation ability, it is to adjust
Join indispensable fixastive in high-grade essence, be widely used in essence and flavoring agent industry, tobacco industry, food industry, dailyization
The industries such as product industry.In the allotment of essence and flavoring agent, if add ten thousand/ Moschus, essence and perfuming can not only be made to produce
Product have gracefulness musk odor, and can also play fixation, set off by contrast, mellow and full with balance whole fragrance effect.
Moschus not only has important purposes on perfume industry, and pharmaceutically also critically important.In China's pharmacopeia, it
There is excitor nerve maincenter, respiratory center and heart, stimulate circulation, promote the effect of multiple glandular secretions, be treatment god
The important drugs of will stupor.Modern medicine study shows, the system such as Moschus Central nervous, breath cycle has spasmolysis of having one's ideas straightened out,
Cardiac stimulant etc. acts on, and has stronger antiinflammatory action.Moschus also has obvious work at treatment hepatopathy, cancer and the aspect such as antitumor
With.Because the curative effect of Moschus is rapid, it is the current clinically only Chinese medicine that can be used as first aid medicine.
Natural musk derives from and secretion is dried in the ripe hero body note capsule of animal in deer family woods musk deer, horse musk deer.Earliest musk deer
Ketone musk is that extract and separate obtains from the sachet of musk deer, catches and kills the pure muskone that up to ten thousand musk deers just can only obtain a kilogram.With thing
Matter levels, society increases year by year to the demand of muskone, the unrest of musk deer is caught and disorderly hunts, so that musk deer is greatly reduced, so that Moschus
The price of ketone more rapidly rises, and at present, its price has exceeded well over gold.This just promotes people to create it is carried out for a long time
The power of research and development, the musk ambrette active material prepared by artificial synthesis, close to natural musk, has identical
Or similar physicochemical properties, main pharmacological is essentially identical, and clinical efficacy is definite, safe and reliable, can be equal to use with natural musk.Cause
This, musk ambrette is to solve one of method of Moschus disparities between supply and demand.Musk ambrette is divided into nitro musk, polycyclic musk, big ring musk deer
Fragrant three major types.
Nitro musk is that the mankind develop and using earliest musk ambrette compound, so far the history in existing century.
Nitro musk has strong musk odor, and aroma strength is big, but fragrance is not very fine and smooth, graceful.This kind of compound is solid
Body, it is easy to allocate with other essential oils and spices, also has particularly preferred fixation ability, their price is than other kinds of in addition
Musk ambrette is cheap, and raw material is easy to get plentifully, produces stable, therefore using extremely wide.But nitro musk is under a cloud carcinogenicity,
Many countries forbid using it in cosmetics and the product that contacts with skin.
Polycyclic musk is the class musk ambrette that early 1950s come out.Compared with nitro musk, polycyclic musk
Fragrance is more graceful, stable chemical nature, is widely used in the composition of all kinds of daily chemical products.But, due to many
The synthesis of ring Moschus is difficult, and price is higher than nitro musk, thus how using in the product of higher gears.Nitro musk is because of its safety collar
Guarantor's problem and disabled and limit the use of, make polycyclic musk obtain very big development, almost occupy monopolization ground to the later stage eighties
Position.
Due to nitro musk, the toxic and side effect of polycyclic musk, biodegradable and enter human foods chain and in human body inner product
The safety and environmental protection problem such as tired, this two classes Moschus will gradually be eliminated.Macrocyclic musk is the main component of natural musk, performance in addition
Stable, nontoxic, therefore, the synthesis of macrocyclic musk is quickly become with the object of people's primary study, there is very big market potential.
The fragrance of macrocyclic musk is extremely graceful, and the musk ambrette being different from natural musk structure than those structures has higher
The aroma quality of level.Additionally, it is also a good fixastive, essence can be made to keep lasting fragrant breath.Macrocyclic musk
Without any side effects, do not find the safety and environmental protection problem as existing for nitro musk and polycyclic musk up to now, just yet
It is due to the macrocyclic musk compound advantage of itself, its development prospect is very optimistic.But, due to the production technology of macrocyclic musk
Complexity, yield is relatively low, relatively costly, does not also form the market advantage in the recent period, and it is mainly used in perfume and high-grade cosmetic at present
In the senior daily chemical essence such as product.
Malania oleifera also known as hedgehog hydnum fruit, mountain paulownia fruit etc., are that Olacaceae kalimeris wood belongs to unique Relict Plant, are Chinese the eastern regions of the Yunnan Province
South and the distinctive rareness species in the western karst in osmanthus ground mountain region, are Chinese Second Class Key Protected Plant, it is distributed in the wide of southeastern Yunnan
The Limestone Mountain Areas of the 500-1640m such as south, Funing and West Guangxi, are the important afforestation in karst seeds, are to pass again
The edible oil plant of system, has huge Ecosystem Service and high economic worth.
Malania Oleifera Oil contains 40%～60% tetracosa carbon -15- olefin(e) acid, is a kind of long-chain monounsaturated fatty acids, because
It is from shark brain earliest, separates and gain the name in bovine brain, tetracosa carbon -15- olefin(e) acid be brain development, maintain must seek
Foster thing, enlivening, preventing encephalasthenia from playing a very important role to raising cranial nerve；Cardiovascular and human autoimmune are lacked
Weary property disease also has goodish curative effect；It can be directly as medicine and health products application.The insatiable hunger of tetracosa carbon -15- olefin(e) acid
With key just on the 15th～16 carbon, it is synthesis high value Moschus class spices pentadacanolide, the desirable feedstock of cyclopentadecanone.
At present, there are no the report of the method for synthetic perfume cyclopentadecanone from Malania Oleifera Oil in prior art.
Content of the invention：
It is an object of the invention to overcoming the complex manufacturing of macrocyclic musk present in prior art, yield is relatively low,
Relatively costly, also do not form the scarce limit of the market advantage in the recent period, provide a kind of for fields such as medicine, health products, cosmetics
The synthetic method of spices cyclopentadecanone, the method contains 40%～60% tetracosa carbon -15- olefin(e) acid based on Malania Oleifera Oil, and
The unsaturated bond of tetracosa carbon -15- olefin(e) acid, just on the 15th～16 carbon, is in synthesis high value Moschus class spices ring 15
Ester, the mechanism of the desirable feedstock of cyclopentadecanone, there is provided extract the preferable method of cyclopentadecanone from Malania Oleifera Oil.
In order to realize the above-mentioned purpose of the present invention, the invention provides following technical scheme：
A kind of macrocyclic musk ketone is the synthetic method of cyclopentadecanone, with Malania Oleifera Oil as raw material, through saponification, is acidified and must mix
Aliphatic acid, fatty acid mixed recrystallizes to obtain tetracosa carbon 15 olefin(e) acid, by tetracosa carbon -15- olefin(e) acid in absolute ethyl alcohol, in drum
Bubbler leads to ozone to reaction end, ozonation products is moved into there-necked flask, heating stirring simultaneously adds hydrogen peroxide, and 1-2 is little for dropping
When, add distilled water suction filtration, be dried, obtain 1,15- pertadecane diacid；Dried 1,15- pertadecane diacid is dissolved in dichloro
Methane, adds methyl alcohol, and dropwise the dropping concentrated sulfuric acid, as catalyst, is heated to reflux 4-8 hour respectively at 90 DEG C, with petroleum ether extraction
Take, be evaporated petroleum ether and obtain pertadecane diacid dimethyl ester, pertadecane diacid dimethyl ester is through being cyclized to obtain Alpha-hydroxy cyclopentadecanone, α-hydroxyl
Base cyclopentadecanone is through reducing to obtain cyclopentadecanone.
Synthetic method as mentioned, wherein said Malania Oleifera Oil saponification, acidifying are to add NaOH in industrial alcohol to stir
Mix dissolving, dissolving adds completely afterwards equipped with the container of Malania Oleifera Oil, stirs saponification 4h, after reaction, use dilute sulphur in electric jacket
Acid carries out being acidified to pH=2, moves in separatory funnel, with hot wash for several times.
Synthetic method as mentioned, wherein said fatty acid mixed recrystallization is to be single molten with absolute ethyl alcohol or acetone
Agent, is recrystallized, vapor detection purity after esterification；With pyridine and absolute ethyl alcohol or with acetone or and petroleum ether, respectively
Alternate crystallization is carried out to fatty acid mixed.
Synthetic method as mentioned, wherein said pertadecane diacid dimethyl ester through be cyclized Alpha-hydroxy cyclopentadecanone be
Equipped with addition fresh metal sodium in the four-hole bottle of mechanical agitator, constant pressure funnel, spherical condensation tube and nitrogen protection device
The anhydrous dimethyl benzene newly steaming, N2Under protection, start and stir and be to slowly warm up to dimethylbenzene and closely boil, high-speed stirring under a nitrogen
Mix, sodium is broken into silvery white fine particles, above-mentioned system is down to room temperature 25-30 DEG C, in N2Under protection, by 15 carbon dicarboxylic acids
Dimethyl ester is dissolved in anhydrous dimethyl benzene, completion of dropping in 4h, 110 DEG C of reaction 2h, and reaction terminates, and is down to room temperature, under agitation,
Add appropriate glacial acetic acid, stop logical nitrogen, add suitable quantity of water, separate dimethylbenzene, the xylene extraction of aqueous phase equivalent amount
Twice, merge extract, wash with water, be dried, remove solvent, obtain hydroxyl cyclopentadecanone.
Synthetic method as mentioned, wherein said Alpha-hydroxy cyclopentadecanone through reduce cyclopentadecanone is equipped with stirring
Add Alpha-hydroxy cyclopentadecanone and ethanol in device, condenser pipe, dropping funel and thermometer four-hole bottle, add zinc powder, stir at 90 DEG C
Mix down, instill concentrated hydrochloric acid, cooling, add water, with benzene extraction, vacuum fractionation, remove benzene and water, dry cyclopentadecanone.
Compared with prior art, the excellent benefit of the present invention is：
The invention provides one kind synthesizes fine perfumery high value Moschus class spices cyclopentadecanone (big ring from Malania Oleifera Oil
Muskone) yield is high, profitable, low cost method, overcome macrocyclic musk complex manufacturing in prior art, yield
Relatively low, relatively costly, also do not form the scarce limit of the market advantage in the recent period.The present invention is a good fixation based on macrocyclic musk
Agent, without any side effects, there is not safety and environmental protection problem, and Malania Oleifera Oil contains 40%～60% tetracosa carbon -15- alkene
Acid, a kind of brain development, the required nutrients maintaining, to raising the enlivening of cranial nerve, to prevent encephalasthenia from having critically important
Effect；Also there is goodish curative effect to cardiovascular and human autoimmune's shortage property disease；It can be directly as medicine and health care
Product are applied.The unsaturated bond of tetracosa carbon -15- olefin(e) acid, just on the 15th～16 carbon, is synthesis high value Moschus class spices ring
Omega-pentadecanolide, the desirable feedstock of cyclopentadecanone.
Patent and document with regard to malania oleifera are as follows." one kind produces ring from Malania Oleifera Oil to invention disclosed patent in 2004
Adopt Malania Oleifera Oil to add reaction dissolvent to lead to ozone again in the method for 15 lactones ", then add reducing agent to ozonisation glyceride
Reaction generates the hydroxyl glyceride containing 15 carbon.But the shortcoming directly being ozonized with Malania Oleifera Oil is except containing in Malania Oleifera Oil
Have the present invention to synthesize outside the tetracosa carbon -15- olefin(e) acid that cyclopentadecanone needs also to contain 22 carbon -13- olefin(e) acids and Linolenic Acid -
The unwanted composition of the present invention such as olefin(e) acid, through peroxone oxidation, after oxidation, the dimethyl ester of synthesis can except pertadecane diacid dimethyl ester
The accessory substances such as hendecane dicarboxylic acid dimethyl ester can also be contained, carry out subsequent reactions be likely to result in reaction efficiency low the problems such as
Occur, therefore the route to directly be ozonized with Malania Oleifera Oil is carried out, need after esterification to increase pertadecane diacid dimethyl ester
The step purifying, increased the difficulty of operation.Therefore the present invention adopt Malania Oleifera Oil through saponification, acidifying after recrystallization purity up to
To 88%, once continue subsequent reactions it is possible to avoid other impurity in Malania Oleifera Oil to produce impact to experiment.
Brief description：
Fig. 1 is the synthetic route chart of cyclopentadecanone of the present invention (macrocyclic musk ketone).
Specific embodiment：
Below in conjunction with the accompanying drawings, further illustrate the essentiality content of the present invention with embodiments of the invention, but not with
This is limiting the present invention.
Embodiment 1：
1. the preparation of tetracosa carbon -15- olefin(e) acid, purifying.
The extraction of 1.1 Malania Oleifera Oils：
Malania oleifera is finely ground through mortar, with filter paper parcel, puts in apparatus,Soxhlet's, makees solvent refluxing with petroleum ether and extracts
6h, stores standby after the Malania Oleifera Oil solvent evaporated of extraction.
The preparation of 1.2 tetracosa carbon -15- olefin(e) acids, purifying.
1.2.1 Malania Oleifera Oil saponification, acidifying：
NaOH is added stirring and dissolving in industrial alcohol, dissolving adds equipped with the container of Malania Oleifera Oil, completely afterwards in electricity
Saponification 4h is stirred in hot jacket；After reaction, carry out being acidified to pH=2 with dilute sulfuric acid, move in separatory funnel, use hot wash number
Secondary, obtain fatty acid mixed standby.
1.2.2 tetracosa carbon -15- olefin(e) acid recrystallization：
With absolute ethyl alcohol, acetone, pyridine as single solvent, recrystallized, vapor detection purity after esterification.
1.2.3 tetracosa carbon -15- olefin(e) acid alternate crystallization：With absolute ethyl alcohol, acetone, pyridine, petroleum ether as solvent, carry out
Alternate crystallization, vapor detection purity after esterification.
1.3 result
1.3.1 fatty acid mixed yield：Malania Oleifera Oil gained fatty acid mixed data after saponification, acidifying is shown in Table 1.By table
1 data can obtain, and fatty acid mixed average yield is 75.235%.
Table 1 fatty acid mixed yield
1.3.2 the impact to tetracosa carbon -15- olefin(e) acid purity for the primary crystallization.
Experiment absolute ethyl alcohol, acetone, pyridine carry out primary crystallization to fatty acid mixed, and experiment in triplicate, is averaged
Value, the results are shown in Table 2.From the data of table 2, the impurities affect to tetracosa carbon -15- olefin(e) acid for the solvent selected by primary crystallization
Less, but with acetone for the tetracosa carbon -15- olefin(e) acid yield of solvent crystallization gained relative to two outer two little, so only
In the case of recrystallizing once, acetone as solvent should not be selected.
Table 2 once recrystallizes
1.3.3 alternate crystallization impact to tetracosa carbon -15- olefin(e) acid purity.
Respectively tetracosa carbon -15- the olefin(e) acid of primary crystallization gained is carried out using absolute ethyl alcohol, acetone, petroleum ether, pyridine
Crystallization, experiment in triplicate, is averaged, is obtained a result as table 3.From the data of table 3, an alternate crystallization is with respect to one
Secondary crystallization has in the purity of tetracosa carbon -15- olefin(e) acid and is obviously improved.Pyridine is replaced with absolute ethyl alcohol, acetone, petroleum ether
The yield of crystallization gained tetracosa carbon -15- olefin(e) acid, purity are of a relatively high, and purity has all reached more than 80%.
3 alternate crystallization of table
1.3.4 two alternate crystallization impact to tetracosa carbon -15- olefin(e) acid purity.
Experiment is using acetone-absolute ethyl alcohol, pyridine-absolute ethyl alcohol, pyridine-acetone, pyridine-petroleum ether respectively to mixing fat
Fat acid carries out secondary alternate crystallization, and experiment in triplicate, is averaged, obtained a result as table 4.From the data in table 4, it can be seen that secondary friendship
It is not apparent for the selected solvent of crystallization to tetracosa carbon -15- olefin(e) acid yield, impurities affect.With an alternate crystallization
The data obtained contrasts, and secondary alternate crystallization has still been lifted to tetracosa carbon -15- olefin(e) acid purity, but is lifted and inconspicuous.
4 two alternate crystallization of table
2. the preparation of pentadacanolide (macrocyclic musk lactone).
2.1 synthetic routes (as Fig. 1).
2.2 synthetic method：Tetracosa carbon -15- olefin(e) acid ozonization method.
2.2.1 the preparation of 15- hydroxypentadecanoic acid：
Tetracosa carbon -15- olefin(e) acid is dissolved in solvent, carries out ozonization under ice bath, be then slowly added dropwise KBH4
Solution reduction, after reaction terminates, with dilute HCl acidifying, filters, washs to neutrality, is vacuum dried to obtain 15- hydroxypentadecanoic acid.Point
Do not test the impact to 15- hydroxypentadecanoic acid yield of different solvents and ozonation time.
2.2.2 15- hydroxypentadecanoic acid methyl esters preparation：
By 15- hydroxypentadecanoic acid, methyl alcohol, the concentrated sulfuric acid in round-bottomed flask, flow back under 90 DEG C of water-baths 3h, and backflow terminates,
With ether extraction, wash to neutrality, vacuum distillation, be vacuum dried to obtain 15- hydroxypentadecanoic acid methyl esters.
2.2.3 the synthesis of pentadacanolide：
Take 15- hydroxypentadecanoic acid esters, be dissolved in hexamethylene, add catalyst, in uniform temperature back flow reaction one timing
Between.After end, through filtering, filtrate extracts through ether, distills water washing, vacuum distillation, is vacuum dried to obtain pentadacanolide.Respectively
Test different catalysts, different time, differential responses temperature, different ester group pairings become the impact of pentadacanolide.
2.3 result：
Using tetracosa carbon -15- olefin(e) acid ozonization method.
2.3.1 the preparation of 15- hydroxypentadecanoic acid：
2.3.1.1 the impact to synthesis 15- hydroxypentadecanoic acid for the solvent selected by ozonisation.
Experiment is ozonized as solvent using absolute ethyl alcohol, petroleum ether, absolute ethyl alcohol+petroleum ether, obtains 15- after carrying out reduction
Hydroxypentadecanoic acid, experiment in triplicate, is averaged, be the results are shown in Table 5, from the data in table 5, it can be seen that selecting different solvents to carry out
Ozonisation is on synthesis 15- hydroxypentadecanoic acid impact less.Consider, select mixed solvent more square in ozonisation
Just.
The ozonisation of table 5 different solvents, reduction gained 15- hydroxypentadecanoic acid
2.3.1.2 the impact to synthesis 15- hydroxypentadecanoic acid for the ozonation time.
Experiment ozonized as solvent using absolute ethyl alcohol+petroleum ether, ozonation time be respectively 15min, 30min,
60min, obtains 15- hydroxypentadecanoic acid after carrying out reduction, the results are shown in Table 6.
Table 6 ozonation time gained 15- hydroxypentadecanoic acid
From the data of table 6, ozonation time is that when 30min, 60min, 15- hydroxypentadecanoic acid average yield all reaches
To more than 88%, but ozonation time brings up to 60min and the yield of 15- hydroxypentadecanoic acid is not increased.
And the 15- hydroxypentadecanoic acid average yield that ozonation time is 15min only reaches 81%, illustrate that tetracosa carbon -15- olefin(e) acid is smelly
Oxidation is simultaneously incomplete, leads to its yield relatively low.So, consider, ozonation time is that 30min is the most suitable.
2.3.1.3 15- hydroxypentadecanoic acid methyl esters preparation：
The esterification under 90 DEG C of water-baths of 15- hydroxypentadecanoic acid obtains 15- hydroxypentadecanoic acid methyl esters, the results are shown in Table 7.By
The data of table 7 understands, the average yield of esterification process 15- hydroxypentadecanoic acid methyl esters is 88.34%.
Table 7 15- hydroxypentadecanoic acid esterification
Tetracosa carbon -15- olefin(e) acid ozonization method obtains 15- hydroxypentadecanoic acid methyl esters through six steps, and yield is
19.96%, gained 15- hydroxypentadecanoic acid methyl esters purity is higher, reaches 85.11%.
The synthesis of 2.4 pentadacanolides.
2.4.1 the impact that different catalysts synthesize to pentadacanolide.
Pentadacanolide, experiment weight are synthesized for catalyst 15- hydroxypentadecanoic acid methyl esters with the concentrated sulfuric acid and solid acid
Multiple three times, average, the results are shown in Table 8.As shown in Table 8, using solid acid catalyst, in the product finally giving not
Containing pentadacanolide.So all catalyst is made using the concentrated sulfuric acid in follow-up experiment.
Table 8 different catalysts synthesize pentadacanolide data
2.4.2 the impact that the reaction time synthesizes to pentadacanolide
With the concentrated sulfuric acid as catalyst, reaction 6h, 9h, 10h, 11h, 12h synthesis pentadacanolide, the results are shown in Table 9 respectively.By
Table 9 understands, the yield of pentadacanolide, purity all increase with the growth in reaction time.In conjunction with existing experiment condition, select
Determine the ring closure reaction time that 12h is 15- hydroxypentadecanoic acid methyl esters.
9 differential responses time of table gained pentadacanolide
2.4.3 the impact that 15- hydroxypentadecanoic acid esters difference ester group synthesizes to pentadacanolide
15- hydroxypentadecanoic acid first (second) ester cyclization under conditions of identical obtains pentadacanolide, and experiment repeats
Three times, average, the results are shown in Table 10. as shown in Table 10, in the case that reaction condition is identical, 15- hydroxypentadecanoic
It is better than 15- hydroxypentadecanoic acetoacetic ester that sour methyl esters synthesis pentadacanolide is intended in yield, purity.
The different ester group synthesis pentadacanolide of table 10
2.5 conclusion
Although tetracosa carbon -15- olefin(e) acid ozonization method reaction process is longer, it is that its purity is high, on reaction impact below
Very little, and whole experiment process is all relatively simple, smooth.In the range of the regular hour, the yield of pentadacanolide and pure
Degree increases with the growth in reaction time.Under identical experiment condition, 15- hydroxypentadecanoic acid methyl esters synthesizes ring 15
The yield of lactone, purity are higher than 15- hydroxypentadecanoic acetoacetic ester.
Embodiment 2：
The synthesis of cyclopentadecanone (macrocyclic musk ketone).
Experiment route (see Fig. 1)：Tetracosa carbon -15- olefin(e) acid ozonization method.
Synthetic method：
First prepare tetracosa carbon -15- olefin(e) acid：
1. the preparation of tetracosa carbon -15- olefin(e) acid, purifying.
The extraction of 1.1 Malania Oleifera Oils：
Malania oleifera is finely ground through mortar, with filter paper parcel, puts in apparatus,Soxhlet's, makees solvent refluxing with petroleum ether and extracts
6h, stores standby after the Malania Oleifera Oil solvent evaporated of extraction.
The preparation of 1.2 tetracosa carbon -15- olefin(e) acids, purifying.
1.2.1 Malania Oleifera Oil saponification, acidifying：
NaOH is added stirring and dissolving in industrial alcohol, dissolving adds equipped with the container of Malania Oleifera Oil, completely afterwards in electricity
Saponification 4h is stirred in hot jacket；After reaction, carry out being acidified to pH=2 with dilute sulfuric acid, move in separatory funnel, use hot wash number
Secondary, obtain fatty acid mixed standby.
1.2.2 tetracosa carbon -15- olefin(e) acid recrystallization：
With absolute ethyl alcohol, acetone, pyridine as single solvent, recrystallized, vapor detection purity after esterification.
1.2.3 tetracosa carbon -15- olefin(e) acid alternate crystallization：With absolute ethyl alcohol, acetone, pyridine petroleum ether as solvent, handed over
For crystallization, vapor detection purity after esterification.
1.3 result
1.3.1 fatty acid mixed yield：Malania Oleifera Oil gained fatty acid mixed data after saponification, acidifying is shown in Table 1.By table
1 data can obtain, and fatty acid mixed average yield is 75.235%.
Table 1 fatty acid mixed yield
1.3.2 the impact to tetracosa carbon -15- olefin(e) acid purity for the primary crystallization.
Experiment absolute ethyl alcohol, acetone, pyridine carry out primary crystallization to fatty acid mixed, and experiment in triplicate, is averaged
Value, the results are shown in Table 2.From the data of table 2, the impurities affect to tetracosa carbon -15- olefin(e) acid for the solvent selected by primary crystallization
Less, but with acetone for the tetracosa carbon -15- olefin(e) acid yield of solvent crystallization gained relative to two outer two little, so only
In the case of recrystallizing once, acetone as solvent should not be selected.
Table 2 once recrystallizes
1.3.3 alternate crystallization impact to tetracosa carbon -15- olefin(e) acid purity.
Respectively tetracosa carbon -15- the olefin(e) acid of primary crystallization gained is carried out using absolute ethyl alcohol, acetone, petroleum ether, pyridine
Crystallization, experiment in triplicate, is averaged, is obtained a result as table 3.From the data of table 3, an alternate crystallization is with respect to one
Secondary crystallization has in the purity of tetracosa carbon -15- olefin(e) acid and is obviously improved.Pyridine is replaced with absolute ethyl alcohol, acetone, petroleum ether
The yield of crystallization gained tetracosa carbon -15- olefin(e) acid, purity are of a relatively high, and purity has all reached more than 80%.
3 alternate crystallization of table
1.3.4 two alternate crystallization impact to tetracosa carbon -15- olefin(e) acid purity.
Experiment is using acetone-absolute ethyl alcohol, pyridine-absolute ethyl alcohol, pyridine-acetone, pyridine-petroleum ether respectively to mixing fat
Fat acid carries out secondary alternate crystallization, and experiment in triplicate, is averaged, obtained a result as table 4.From the data in table 4, it can be seen that secondary friendship
It is not apparent for the selected solvent of crystallization to tetracosa carbon -15- olefin(e) acid yield, impurities affect.With an alternate crystallization
The data obtained contrasts, and secondary alternate crystallization has still been lifted to tetracosa carbon -15- olefin(e) acid purity, but is lifted and inconspicuous.
4 two alternate crystallization of table
Prepared by 2.1,15- pertadecane diacid：
By tetracosa carbon -15- olefin(e) acid in a solvent, lead to ozone to reaction end in bubbler, ozonation products are moved into
There-necked flask, heating stirring the hydrogen peroxide adding, dropwise reaction certain time, add distilled water suction filtration, are dried, obtain 1,
15- pertadecane diacid.
3.1,15- prepared by pertadecane diacid dimethyl ester：
Dried 1,15- pertadecane diacid is dissolved in dichloromethane, adds methyl alcohol, dropwise the dropping concentrated sulfuric acid is as catalysis
Agent, is heated to reflux certain time at 90 DEG C respectively, with petroleum ether extraction, is evaporated petroleum ether and obtains pertadecane diacid dimethyl ester.
4. the preparation of Alpha-hydroxy cyclopentadecanone：
Four-hole bottle equipped with mechanical agitator, constant pressure funnel, spherical condensation tube and nitrogen protection device adds
Fresh metal sodium and the anhydrous dimethyl benzene newly steaming, N2Under protection, start and stir and be to slowly warm up to dimethylbenzene and closely boil, in nitrogen
High-speed stirred under atmosphere, sodium is broken into silvery white fine particles, above-mentioned system is suitably lowered the temperature, in N2Under protection, by 15 carbon two
First dimethyl phthalate is dissolved in anhydrous dimethyl benzene, completion of dropping in 4h, insulation reaction 2h, and reaction terminates.It is down to room temperature, in stirring
Under, add appropriate glacial acetic acid, stop logical nitrogen, add suitable quantity of water, separate dimethylbenzene, the dimethylbenzene extraction of aqueous phase equivalent amount
Take twice, merge extract, wash with water, be dried, remove solvent, obtain hydroxyl cyclopentadecanone.
5. the synthesis of cyclopentadecanone：
In equipped with agitator, condenser pipe, dropping funel and thermometer four-hole bottle add, add Alpha-hydroxy cyclopentadecanone and
Ethanol, adds a certain amount of zinc powder, under 90 DEG C of stirrings, instills appropriate concentrated hydrochloric acid, completion of dropping, cooling, adds water, extracted with benzene
Take, vacuum fractionation, remove benzene and water, drying to obtain cyclopentadecanone.
Each step product is all using its purity of gas chromatographic detection.
6. result.
Prepared by pertadecane diacid：
The ozonisation of tetracosa carbon -15- olefin(e) acid, oxidization condition as shown in table 11, can be obtained by table 11, tetracosa carbon -15- alkene
Acid ozonisation, the average yield obtaining pertadecane diacid after oxidation is 89.83%.
The ozonisation of table 1 tetracosa carbon -15- olefin(e) acid, oxidation
The impact to yield for the pertadecane diacid carboxylic acid methyl ester time：
(1) pertadecane diacid esterification 4h yield situation such as table 2.As shown in Table 2, the esterification time is 4h, 15 carbon two
The average yield of dimethyl phthalate is 80.72%.
The impact to yield for the table 2 esterification time
(2) as shown in Table 3, the esterification time is 6h to pertadecane diacid esterification 6h yield situation such as table 3., 15 carbon two
The average yield of dimethyl phthalate is 86.35%.
The impact to yield for the table 3 esterification time
(3) pertadecane diacid esterification 8h yield situation is as shown in table 4.As shown in Table 4, the esterification time is 8h, 15
The average yield of carbon acid dimethyl is 87.78%.
The impact to yield for the table 4 esterification time
Be can be seen that the increase in time of esterification efficiency and increased, esterification by table 2,3, the 4 different esterification time
Time is not obviously improved than esterification 6h yield for 8h, therefore the optimal esterification time is 6h, gas Chromatographic Determination 1,15-
Pertadecane diacid diformazan ester content is 73.61%.
It is raw material through saponification, acidifying, recrystallization etc. with Malania Oleifera Oil from aliphatic acid ozonization method is found through experiments
Tetracosa carbon -15- olefin(e) acid the purity that step obtains is higher, when carrying out following synthesis with the tetracosa carbon -15- of higher degree
Olefin(e) acid is raw material, and reaction is less by the impact of impurity, and the dimethyl ester impurity of generation is less, and Malania Oleifera Oil is after saponification, acidifying
Recrystallization purity can reach 88%, once continues subsequent reactions it is possible to avoid other impurity in Malania Oleifera Oil that experiment is produced
Impact, is easy to the carrying out of subsequent reactions.
7. the preparation of Alpha-hydroxy cyclopentadecanone.
It is shown in Table 5. with pertadecane diacid dimethyl ester for waste Alpha-hydroxy cyclopentadecanone yield situation as shown in Table 5, ten
The yield that five carbon acid dimethyl are converted into Alpha-hydroxy cyclopentadecanone is 83.11%, and gas Chromatographic Determination content can reach
35.79%.
The yield of table 5 hydroxyl cyclopentadecanone
The temperature of acyloin condensation selects.Under different temperatures, the situation of acyloin condensation is as shown in table 6.
The temperature of table 6 acyloin condensation
From the data in table 6, it can be seen that with the rising of reaction temperature, the content of hydroxyl cyclopentadecanone is also rising.But work as temperature
During more than 110 DEG C, reaction system can be changed into rufous, has illustrated that other accessory substances generate, therefore the reaction temperature adopting is 110
℃.It is only 35.79% with the pertadecane diacid dimethyl ester that content is 73.61% for the content of Material synthesis hydroxyl cyclopentadecanone,
The residual of some reactant or generate other accessory substances in reaction system, causes this knot as can be seen from the data
The reason fruit is probably that reactant covers on sodium sand surface, makes sodium sand lose the activity of catalytic reaction.
8. the synthesis of cyclopentadecanone
Alpha-hydroxy cyclopentadecanone synthesis cyclopentadecanone yield situation is as shown in table 7.As shown in Table 7, hydroxyl cyclopentadecanone is also
Originally it was cyclopentadecanone, average yield is 69.51%.
The yield of table 7 cyclopentadecanone
Conclusion
It is found through experiments, being best suitable for into cyclopentadecanone method is aliphatic acid ozonization method.During esterification, with
The esterification time increases, and yield gradually rises, but after reaction proceeds to 6h, with the increase in reaction time, the carrying of yield
Height is not too obvious, therefore the esterification time was 2-6h, less than 6 hours；Drawn by experiment and obtain hydroxyl ring in acyloin condensation
During 15 ketone, optimal reaction temperature is 110 DEG C.
Claims (5)
1. a kind of macrocyclic musk ketone is the synthetic method of cyclopentadecanone, with Malania Oleifera Oil as raw material, through saponification, is acidified and must mix fat
Fat acid, fatty acid mixed recrystallizes to obtain tetracosa carbon 15 olefin(e) acid, by tetracosa carbon -15- olefin(e) acid in absolute ethyl alcohol, in bubbling
Device leads to ozone to reaction end, ozonation products is moved into there-necked flask, heating stirring simultaneously adds hydrogen peroxide, drips 1-2 hour,
Add distilled water suction filtration, be dried, obtain 1,15- pertadecane diacid；Dried 1,15- pertadecane diacid is dissolved in dichloromethane
Alkane, adds methyl alcohol, and dropwise the dropping concentrated sulfuric acid, as catalyst, is heated to reflux 4-8 hour at 90 DEG C respectively, with petroleum ether extraction,
It is evaporated petroleum ether and obtains pertadecane diacid dimethyl ester, pertadecane diacid dimethyl ester is through being cyclized to obtain Alpha-hydroxy cyclopentadecanone, Alpha-hydroxy
Cyclopentadecanone is through reducing to obtain cyclopentadecanone.
2. synthetic method as claimed in claim is it is characterised in that described Malania Oleifera Oil saponification, acidifying are to add NaOH
Stirring and dissolving in industrial alcohol, dissolving adds completely afterwards equipped with the container of Malania Oleifera Oil, stirs saponification 4h, instead in electric jacket
Ying Hou, carries out being acidified to pH=2 with dilute sulfuric acid, moves in separatory funnel, with hot wash for several times.
3. synthetic method as claimed in claim 1 is it is characterised in that described fatty acid mixed recrystallization is with absolute ethyl alcohol
Or acetone is single solvent, recrystallized, vapor detection purity after esterification；With pyridine and absolute ethyl alcohol or with acetone or
With petroleum ether, respectively alternate crystallization is carried out to fatty acid mixed.
4. synthetic method as claimed in claim 1 is it is characterised in that described pertadecane diacid dimethyl ester is through being cyclized to obtain α-hydroxyl
Base cyclopentadecanone is in the four-hole bottle equipped with mechanical agitator, constant pressure funnel, spherical condensation tube and nitrogen protection device
Add fresh metal sodium and the anhydrous dimethyl benzene newly steaming, N2Under protection, start and stir and be to slowly warm up to dimethylbenzene and closely boil,
High-speed stirred under nitrogen, sodium is broken into silvery white fine particles, above-mentioned system is down to room temperature 25-30 DEG C, in N2Under protection, will
15 carbon dicarboxylic acid dimethyl esters are dissolved in anhydrous dimethyl benzene, completion of dropping in 4h, 110 DEG C of reaction 2h, and reaction terminates, and is down to room
Temperature, under agitation, adds appropriate glacial acetic acid, stops logical nitrogen, adds suitable quantity of water, separate dimethylbenzene, aqueous phase equivalent amount
Xylene extraction twice, merge extract, wash with water, be dried, remove solvent, obtain hydroxyl cyclopentadecanone.
5. synthetic method as claimed in claim 1 is it is characterised in that described Alpha-hydroxy cyclopentadecanone is through reducing to obtain ring 15
Ketone is to add Alpha-hydroxy cyclopentadecanone and ethanol in equipped with agitator, condenser pipe, dropping funel and thermometer four-hole bottle, adds
Zinc powder, under 90 DEG C of stirrings, instills concentrated hydrochloric acid, cooling, adds water, and with benzene extraction, vacuum fractionation, removes benzene and water, dry ring
15 ketone.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610770424.5A CN106397160A (en) | 2016-08-30 | 2016-08-30 | Synthetic method for macrocyclic musk ketone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610770424.5A CN106397160A (en) | 2016-08-30 | 2016-08-30 | Synthetic method for macrocyclic musk ketone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106397160A true CN106397160A (en) | 2017-02-15 |
Family
ID=58002158
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610770424.5A Pending CN106397160A (en) | 2016-08-30 | 2016-08-30 | Synthetic method for macrocyclic musk ketone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106397160A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107337592A (en) * | 2017-07-03 | 2017-11-10 | 辽宁科技学院 | Utilize the method for β methylglutaric acid mono-methyl musk ambrette ketone |
| CN107353199A (en) * | 2017-08-10 | 2017-11-17 | 王显权 | The method of Malania Oleifera Oil separating-purifying nervonic acid |
| CN107445813A (en) * | 2017-08-10 | 2017-12-08 | 王显权 | The method that Malania Oleifera Oil prepares cyclopentadecanone |
| CN107473946A (en) * | 2017-08-10 | 2017-12-15 | 王显权 | The method that Malania Oleifera Oil prepares muskone |
| CN107569411A (en) * | 2017-08-04 | 2018-01-12 | 杨宇明 | A kind of plant source Moschus cosmetics and preparation method thereof |
| CN114480513A (en) * | 2022-04-01 | 2022-05-13 | 北京林业大学 | Method for synthesizing muscone in vitro by gene editing yeast |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105732353A (en) * | 2016-03-17 | 2016-07-06 | 福建师范大学 | Preparation method of alpha-hydroxycyclopentadecanone |
-
2016
- 2016-08-30 CN CN201610770424.5A patent/CN106397160A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105732353A (en) * | 2016-03-17 | 2016-07-06 | 福建师范大学 | Preparation method of alpha-hydroxycyclopentadecanone |
Non-Patent Citations (2)
| Title |
|---|
| 卞金辉: "蒜头果油合成环十五酮的研究", 《万方数据知识服务平台》 * |
| 庞冬梅等: "麝香酮中间体——环十五酮的合成", 《吉林工学院学报》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107337592A (en) * | 2017-07-03 | 2017-11-10 | 辽宁科技学院 | Utilize the method for β methylglutaric acid mono-methyl musk ambrette ketone |
| CN107337592B (en) * | 2017-07-03 | 2020-11-13 | 辽宁科技学院 | Method for synthesizing muscone by using beta-methyl glutarate monomethyl ester |
| CN107569411A (en) * | 2017-08-04 | 2018-01-12 | 杨宇明 | A kind of plant source Moschus cosmetics and preparation method thereof |
| CN107353199A (en) * | 2017-08-10 | 2017-11-17 | 王显权 | The method of Malania Oleifera Oil separating-purifying nervonic acid |
| CN107445813A (en) * | 2017-08-10 | 2017-12-08 | 王显权 | The method that Malania Oleifera Oil prepares cyclopentadecanone |
| CN107473946A (en) * | 2017-08-10 | 2017-12-15 | 王显权 | The method that Malania Oleifera Oil prepares muskone |
| CN114480513A (en) * | 2022-04-01 | 2022-05-13 | 北京林业大学 | Method for synthesizing muscone in vitro by gene editing yeast |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106397160A (en) | Synthetic method for macrocyclic musk ketone | |
| CN106397384A (en) | Method for synthesis of macrocyclic musk lactone | |
| JPS5813541A (en) | Cyclodextrin clathrate compound of eicosapentaenoic acid or docosahexaenoic acid | |
| CA2574629A1 (en) | New selenohydroxy acids and their derivatives,applications in nutrition, cosmetics and pharmaceutics | |
| EP0165458A2 (en) | (+)-Ambrox, process for production thereof and use thereof | |
| CN106565662B (en) | Macrocyclic musk-pentadacanolide method is prepared using Malania Oleifera Oil | |
| JP2007124917A (en) | Method for producing rice oil richly containing oryzanol, and usage of the rice oil | |
| CN104673490B (en) | The method of refining of rice bran oil | |
| Yamashita et al. | Stereoselective synthesis and cytotoxicity of a cancer chemopreventive naphthoquinone from Tabebuia avellanedae | |
| CN102802600B (en) | As 2,4-disubstituted pyridines of perfuming component | |
| CN102603845B (en) | Method for synthesizing and separating phytosterol saturated fatty acid esters and phytosterol unsaturated fatty acid esters | |
| WO2015186614A1 (en) | Novel compound and fragrance composition containing same | |
| CN104151282A (en) | Method for preparing natural vitamin E and phytosterol with resin absorption method | |
| JP2009013106A (en) | Xanthone derivative having inhibitory action on inflammatory cytokine production, method for producing the same and food preparation, cosmetic and anti-inflammatory agent comprising the same | |
| JP2002535479A (en) | Method for obtaining an oil rich in hydroxyoctadecadienic fatty acid (HODE) or an ester thereof from a mixture containing linoleic acid or an ester thereof | |
| JPWO2003029391A1 (en) | Method for producing oil and fat composition containing oleanolic acid and / or maslinic acid | |
| JP2024068135A (en) | Method for producing cosmetic composition containing tea tree extract and cosmetic composition produced therefrom | |
| MX2012013823A (en) | Organic compounds. | |
| CN101643403A (en) | Method for extracting linolenic acid from purslane | |
| CN114568678B (en) | Preparation method of hydrogenated soybean oil enzymatic hydrolysate powder incense | |
| KR101843374B1 (en) | Method for refining deer oil, the refined deer oil and a cosmetic composition comprising the refined deer oil | |
| CN104693165A (en) | Method for producing long-chain diacid cyclic ethylene ester | |
| CN105534826A (en) | High-permeability environment-friendly antibacterial bath foam and preparation method thereof | |
| CN103608339B (en) | Macrolide | |
| JP2013184921A (en) | Expression modulator for clock gene |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170215 |