CN100590106C - Synthesis method of full antitype long chain terebanthenes primary alcohol - Google Patents
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Abstract
A synthetic method of the all trans long chain terpene primary alcohol is provided, which belongs to the technology field of the organic synthesis. The invention uses the cheap and easily gained geraniol, 2-allylic alcohol or the long chain terpene primary alcohol synthesized by the method as initial materials and uses the ethylenic chlorination reaction happened between the terpene primary alcohol acetate and the lime chlorite to form double bonds and the coupling reaction between the benzene sulphinate ester and the allyl chloride under alkali condition as the key steps, and gain the products through the hydrolysis reaction of the benzene removal sulphinate group and ester of the coupling product. The invention fully utilizes the complete framework of the primary alcohol and adds one ora plurality of isopentene units via coupling and synthesizes series of long chain terpene primary alcohol, which fully embodies the synthesis conception of the atomic economy; only a novel double bonds is formed in the reaction and other double bonds are the all trans double bonds in the raw materials, thereby ensures the trans configuration of the double bonds in the generated long chain terpeneprimary alcohol to the greatest extent. The invention has moderate reaction condition, simple synthetic route, simple operation, good reaction selectivity, high productive rate, easy separation and purification of the products and small environmental pollution.
Description
Technical field
The invention belongs to technical field of organic synthesis.
Background technology
Long-chain terpenes primary alconol is the long-chain alcohols with a plurality of isopentene units.The terpenes primary alconol mainly contains Geraniol, vernol and eggplant Buddhist nun alcohol etc. at occurring in nature.Long-chain terpenes primary alconol has crucial purposes on synthetic, at ubiquinone, vitamin K
2In series compound synthetic, all the different full antitype long chain terebanthenes primary alcohol of length available synthesizes side chain.Because ubiquinone, vitamin K
2Deng the good physiologically active of series compound, so the synthetic of them gets more and more people's extensive concerning always.Side chain synthetic aspect, though several different methods is arranged, reported method is not that step is long, overall yield is low, forms one or more pairs of keys exactly again and cause and have a large amount of cis-isomerides in the product when synthetic, cause product separation, purification difficult, be difficult to guarantee ubiquinone, vitamin K
2Two key alltranses Deng side chain in the series compound.Therefore,, how efficiently synthetic compactly full antitype long chain terebanthenes primary alcohol is for ubiquinone, vitamin K
2Has very important effect Deng series compound synthetic.
Mainly contain following several method commonly used about long-chain terpenes primary alconol synthetic:
(1) utilizes the α alkylation and the keto-acid of methyl aceto acetate to be decomposed to form ketone, by sodium carbide ketone is added and be shaped as the tertiary alcohol, form terminal double link, utilize bromination, esterification and alkaline ester hydrolysis to form primary alconol (Scheme 1) again through selective reduction.
(2) bromination product of terpenes primary alconol and methyl aceto acetate carry out carrying out the keto-acid decomposition behind the α alkylated reaction, and the ketone of generation forms alpha, beta-unsaturated esters with the diethyl malonate reaction again, forms primary alconol (Scheme 2) by the reduction to ester at last.
(3) the α methylene radical that utilizes highly basic to make to link to each other with diphenyl sulfide forms negative ion, again with chlorallylene generation linked reaction, again through reduce primary alconol (Scheme 3).
There is following deficiency in above-mentioned synthetic method: (1) step is tediously long.Just can connect an isopentene unit by multistep, isopentene unit of every increase, will increase new two keys that form newly, and in the new two keys that form, cis-configuration is occupied certain ratio, therefore, if increase a plurality of isopentene unit with this method, the then final long-chain terpenes primary alconol that forms will be the mixture of multiple cis-trans isomerism, and product is difficult to separate, and also can't guarantee the physiologically active when product has the side chain alltrans simultaneously.(2) part reagent costs an arm and a leg.As the highly basic NaH that uses, used reductive agent n-BuLi, Li and Dibal-H during reduction reaction.(3) severe reaction conditions.As be reflected at the low temperature reaction down of liquefied ammonia and-78 ℃.
Summary of the invention
The objective of the invention is to overcome the shortcoming of existing synthetic technology aspect, provide a kind of long-chain terpenes primary alconol succinctly, synthetic method efficiently.The present invention is the reaction conditions gentleness not only, and synthetic route is succinct, easy and simple to handle, and good reaction selectivity, the productive rate height, and product is easy to separation and purification, and is also very little to the pollution of environment.The more important thing is, (1) the present invention is with primary alconol cheap and easy to get, as Geraniol, 2-prenol is raw material, make full use of the complete skeleton of primary alconol, increase one or more isopentene unit by the link coupled method, utilize this synthetic method, can synthesize a series of long-chain terpenes primary alconols, this invention has demonstrated fully the synthetic conception of atom economy; (2) in reaction, owing to only formed new two keys when carrying out the alkene chlorination reaction with Losantin, and other pairs key is the two keys of alltrans in the raw material, and therefore this invention has farthest guaranteed the transconfiguration of pair keys in the long-chain terpenes primary alconol of generation.
The present invention sees Scheme. 4 about the synthetic method of long-chain terpenes primary alconol.
The present invention realizes by following synthesis step:
(1) acetylize of starting raw material:
With Geraniol or geranyl linalool (A) is starting raw material, make solvent with ethyl acetate, make catalyzer with pyridine, diacetyl oxide is made esterifying agent, about 8～the 10h of reaction under 50～60 ℃ of heating conditions, the mole proportioning of raw material and catalyzer is: starting raw material: aceticanhydride: pyridine=1: 1.05: 0.1.
(2) alkene chlorination reaction:
With (1) institute synthetic acetic ester (B) is raw material, with Ca (ClO)
2〉=65%, the Losantin of available chlorine 〉=30% is made the alkene chlorination reagent, in the mixed system of water-ethyl acetate, add Losantin after, under ice bath, drip Glacial acetic acid, the dropping time is 0.5～1 hour, dropwises the recession deicing and bathes, and reacts under room temperature 8.5～11 hours again.The mole proportioning of raw material and catalyzer is: acetic ester: Losantin: Glacial acetic acid=1: 0.75: 1.5.
(3) bromination reaction:
With 2-prenol or Geraniol or farnesol (C) is starting raw material, make catalyzer with pyridine, make solvent with sherwood oil, make bromizating agent with phosphorus tribromide, drip the mixed solution of the sherwood oil formation of phosphorus tribromide and 1 times of quality under ice bath, the dropping time is 0.5～1 hour, dropwises the recession deicing and bathes, reacted under room temperature 1～1.5 hour, the mole proportioning of raw material and catalyzer is: starting raw material: phosphorus tribromide: pyridine=1: 0.7: 0.1 again.
(4) the benzene sulfinic acid ester is synthetic: with (3) synthetic bromide (D) is raw material, and with N, dinethylformamide is a solvent, with anhydrous sodium benzene sulfinate (C
6H
5SO
2Na) be esterifying agent, at room temperature reacted 3～4 hours that after reaction is finished, add saturated aqueous common salt again and stirred 0.5～1 hour, the mole proportioning of raw material is: bromide: anhydrous sodium benzene sulfinate=1: 1.1.
(5) linked reaction: with (2), (4) synthetic alkene chlorizate (F) and-sulfinic acid ester (E) is raw material, makes alkali with potassium tert.-butoxide.The molar ratio of alkene chlorizate,-sulfinic acid ester and potassium tert.-butoxide is 1: 1: 1.1, thinks the tetrahydrofuran (THF) and the N of 3～5 times of alkene chlorizate quality, and 9: 1 mixed solutions of dinethylformamide volume ratio are made solvent.Earlier raw material-sulfinic acid ester, alkene chlorizate and stirring solvent are cooled to-20 ℃, N
2Protection is reacted about 3～4h after down adding potassium tert.-butoxide again, after reaction is finished with 5% H
3PO
4Acidifying, petroleum ether extraction, drying.
(6) the-sulfinic acid ester slough reaction: with (5) synthetic coupled product (G) is raw material, raw material 1mol is mixed under-20 ℃ of conditions with the anhydrous tetrahydro furan of dehydrated alcohol 8～10mol, 200～400mL, after adding sodium Metal 99.5 5～6mol, stirred 3～4 hours down at-20～0 ℃ in batches.
(7) hydrolysis reaction of ester: the synthetic product (H) with (6) is a raw material, adds 250～300mL volume ratio CH in the 1mol raw material
3OH: H
2O=1.5: 1 mixed solution and NaOH solid 1mol, reacted 6～8 hours down at 50～60 ℃, after reaction is finished, add suitable quantity of water behind the most of methyl alcohol of reclaim under reduced pressure, use petroleum ether extraction, the resistates behind the drying desolventizing obtains corresponding long chain terpenes primary alconol (I) with purification by silica gel column chromatography.
Described synthetic method, after the reaction of reactions steps (1), (4)～(7) during purification process, can be respectively with sherwood oil or ethyl acetate extraction, behind extraction back gained organic phase drying, the desolventizing, with silica gel (100～200 order) column chromatography purification, (V/V=80～5: 1) makes eluent with the petrol ether/ethyl acetate mixed solution.
The present invention adopts new synthetic thinking, make full use of the complete skeleton of raw material, form a new terminal double link by the alkene chlorination reaction, increase one or more isopentene unit by the committed step linked reaction again, thereby can synthesize the different full antitype long chain terebanthenes primary alcohol of a series of length, for full antitype long chain terebanthenes primary alcohol synthetic provides new efficient, a succinct synthetic route.Therefore, the present invention has the reaction conditions gentleness, and step is succinct, and is easy and simple to handle, the selectivity of reaction and transformation efficiency height, the easily separated purifying of product, the very little beneficial effect that waits of environmental pollution.
The present invention is described further by the following examples, present embodiment comprises and contains the synthetic of 3,4,6 and 7 unitary 4 full antitype long chain terebanthenes primary alcohols of isopentene, this invention can be synthesized a series of full antitype long chain terebanthenes primary alcohols, therefore is not subjected to the limitation of illustrated embodiment.
Embodiment
Be respectively tetrahydrofuran (THF), N at following examples Chinese and English THF, DMF and THF/DMF, dinethylformamide and tetrahydrofuran (THF) and N, the english abbreviation of dinethylformamide mixed solution, its English corresponding chemical name is unique.
Embodiment step 1.1B, 2B's is synthetic:
The general method of experiment:
Terpenes primary alconol 1A (2A) 1mol is placed the 1000mL reaction flask, adding quality is about 3～5 times ethyl acetate and makes the pyridine of solvent and about 1A (2A) 10%mol and make catalyzer, the acetic anhydride that stirs and slowly add 1.05mol under room temperature is made esterifying agent, treat acetic anhydride add finish after again in 50～60 ℃ of about 8～10h of reacting by heating, after the TLC detection reaction is finished, reaction mixture is poured in another container, to wherein adding a certain amount of NaHCO
3Saturated solution, regulate pH value about 6～7, tell the ethyl acetate phase, water is used an amount of ethyl acetate extraction secondary again, merges organic phase, with saturated common salt water washing organic phase once, anhydrous sodium sulfate drying gets light yellow oily liquid, again through silica gel column chromatography (eluent V/V: sherwood oil: ethyl ester ethyl ester=30～10: 1) can get purified esterification products 1B (2B) behind the desolventizing, productive rate 1B is 97.3%, and 2B is 94.5%.In actually operating, the liquid residue behind the desolventizing can be directly used in next step reaction without being further purified.
Meraneine (1B): C
12H
20O
2(M=196.29), light yellow oily liquid.
1H?NMR(CDCl
3，500MHz)δ5.37(m，1H)，5.22(m，1H)，4.70(d，2H)，2.03(s，3H)，1.98(m，2H)，1.95(m，2H)，1.68(s，9H).
13C?NMR(CDCl
3，75MHz)δ171.2(C)，135.9(C)，133.3(C)，123.7(CH)，123.2(CH)，61.2(CH
2)，40.4(CH
2)，27.9(CH
2)，25.1(CH
3)，21.2(CH
3)，19.9(CH
3)，17.0(CH
3).
3,7,11,15-tetramethyl--2E, 6E, 10E, 14E-cetene-1-acetic ester (2B): C
22H
36O
2(M=332.52), light yellow oily liquid.
1H?NMR(CDCl
3，500MHz)δ5.40(m，1H)，5.23～5.20(m，3H)，4.77(d，2H)，2.05(s，3H)，2.10～1.95(m，12H)，1.73～1.69(s，15H).
13C?NMR(CDCl
3，75MHz)δ170.7(C)，135.2(3C)，132.4(C)，123.8(CH)，123.5(CH)，122.1(2CH)，60.9(CH
2)，40.1(2CH
2)，39.1(CH
2)，26.0(3CH
2)，25.4(CH
3)，21.0(CH
3)，19.3(CH
3)，17.7(2CH
3)，17.0(CH
3).
Embodiment step 2.1D, 2D, 3D's is synthetic:
The general method of experiment:
Terpenes primary alconol 1C (2C, 3C) 1mol is placed the 1000mL reaction flask, adding quality is about 3～4 times sherwood oil and makes solvent, the pyridine that adds 1C (2C, 3C) quality 5% is made catalyzer, stir and slowly drip down the phosphorus tribromide of 0.7mol and the mixed solution of the sherwood oil formation of about 1 times of quality in ice bath, the dropping time is about 0.5～1h, dropwising the recession deicing bathes, under room temperature, react 1～1.5h again, after the TLC detection reaction is finished, reaction mixture is poured in another container, to wherein adding a certain amount of NaHCO
3Saturated solution, it is about 6～7 to regulate pH value, tells organic phase, water is used an amount of petroleum ether extraction secondary again, merges organic phase, with saturated common salt water washing organic phase once, anhydrous sodium sulfate drying, behind the desolventizing brown oily liquids.Because bromo-derivative takes place when carrying out silica gel column chromatography easily such as multiple side reactions such as cancellations, therefore react the bromo-derivative that is generated and to carry out purification by silica gel column chromatography, in actually operating, the liquid residue behind the desolventizing can be directly used in next step reaction without being further purified.Thick product yield 1D (2D, 3D) behind the desolventizing is about 97.5～98.1%.
Isopentene bromine (1D): C
5H
9Br (M=149.03), light yellow liquid.
Geranyl bromine (2D): C
10H
17Br (M=217.15), brown oily liquids.
3,7,11-trimethylammonium-2E, 6E, 10E-dodecylene-1-bromine (3D): C
15H
25Br (M=285.26), brown oily liquids.
Embodiment step 3.1E, 2E, 3E's is synthetic:
The general method of experiment:
Bromination product 1D (2D with the terpenes primary alconol, 3D) 1mol places the 1000mL reaction flask, add quality and be about 4～5 times N, dinethylformamide (DMF) is made solvent, under agitation add anhydrous sodium benzene sulfinate 1.1mol, about 3～the 4h of reaction under room temperature, after the TLC detection reaction is finished, in reaction mixture, add an amount of saturated aqueous common salt, under room temperature, stir 0.5～1h again, mixed solution ethyl acetate extraction three times, anhydrous sodium sulfate drying, get pale brown look mashed prod behind the desolventizing, again through silica gel column chromatography (eluent V/V: sherwood oil: ethyl ester ethyl ester=20～5: 1) can get purified product 1E, 2E, its productive rate of 3E is respectively: 85.1%, 83.3%, 84.71%.
2-isopentene-1-benzene sulfinic acid ester (1E): C
11H
14O
2S (M=210.29), pale brown look thick liquid.
1H?NMR(CDCl
3，500MHz)δ7.69(d，2H)，7.43(d，1H)，7.38(m，2H)，4.93(m，H)，3.61(d，2H)，1.74(m，3H)，1.44(m，3H).
13C?NMR(CDCl
3，75MHz)δ170.7(C)，135.2(3C)，132.4(C)，123.8(CH)，123.5(CH)，122.1(2CH)，60.9(CH
2)，40.1(2CH
2)，39.1(CH
2)，26.0(3CH
2)，25.4(CH
3)，21.0(CH
3)，19.3(CH
3)，17.7(2CH
3)，17.0(CH
3).
Benzene sulfinic acid geraniol ester (2E): C
16H
22O
2S (M=278.41), light yellow solid.
1H?NMR(CDCl
3，500MHz)δ7.70(d，1H)，7.64(d，2H)，7.52(m，2H)，5.33(m，H)，5.24(m，H)，3.91(d，2H)，1.94(m，4H)，1.74(m，9H).
13C?NMR(CDCl
3，75MHz)δ145.3(C)，134.3(C)，132.4(C)，127.8(2CH)，126.5(CH)，129.9(2CH)，125.2(CH)，123.1(CH)，63.7(CH
2)，40.5(CH
2)，29.6(CH
2)，23.4(CH
3)，19.4(CH
3)，17.0(CH
3).
3,7,11-trimethylammonium-2E, 6E, 10E-dodecylene-1-benzene sulfinic acid ester (3E): C
21H
30O
2S (M=346.53), light yellow solid.
1H?NMR(CDCl
3，500MHz)δ7.71(d，1CH)，7.61(d，2CH)，7.42(m，2CH)，5.26(m，1CH)，5.10(m，2CH)，4.15(d，CH
2)，1.98～2.08(m，4CH
2)，1.70(m，4CH
3).
13C?NMR(CDCl
3，75MHz)δ138.7(2C)，135.6(2C)，134.3(C)，132.4(CH)，131.4(CH)，130.3(CH)，129.9(C)，129.2(CH)，127.8(2CH)，126.5(2CH)，64.2(CH
2)，39.5(2CH
2)，26.6(2CH
2)，24.3(CH
3)，19.4(CH
3)，18.4(CH
3)，17.6(CH
3).
Embodiment step 4. alkene chlorination reaction is synthesized 1F, 2F:
The general method of experiment:
Terpenes primary alconol acetic ester 1B (2B) 1mol is placed the 1000mL reaction flask, add quality and be about 2 times ethyl acetate and make solvent, add Ca (ClO) again with isopyknic tap water of ethyl ester ethyl ester and 0.75mol
2, stir with mechanical stirrer, drip the extremely acid of ice of 1.5mol down in ice bath, the dropping time is about 0.5～1h, dropwises the recession deicing and bathes, and reacts 8～10h again under room temperature, after the TLC detection reaction is finished, reaction mixture is poured in another container, to wherein adding a certain amount of NaHCO
3Saturated solution, it is about 6～7 to regulate pH value, tells organic phase, water is used an amount of ethyl acetate extraction secondary again, merges organic phase, anhydrous sodium sulfate drying, behind the desolventizing yellow oily liquid.Because alkene chlorizate multiple side reactions such as easy as rolling off a log generation cancellation, isomery when carrying out silica gel column chromatography, therefore react the bromo-derivative that is generated and to carry out purification by silica gel column chromatography, in actually operating, the liquid residue behind the desolventizing can be directly used in next step reaction without being further purified.Thick product yield 1F (2F) behind the desolventizing is about 91.5～95.1%.
3,7-dimethyl-6-chloro-2E, 7 octadienes-1-acetic ester (1F): C
12H
19O
2Cl (M=230.73), yellow oily liquid.
3,7,11,15-tetramethyl--14-chloro-2E, 6E, 10E, 15-cetene-1-acetic ester (2F): C
22H
35O
2Cl (M=366.97), yellow oily liquid.
Embodiment step 5.1G, 2G, 3G, 4G's is synthetic:
The general method of experiment:
Compound 1E (2E, 3E) 1mol is placed the 1000mL reaction flask, add compound 1F (2F) 1mol and be about THF/DMF (9: the 1) mixed solution of 3～5 times of 1E quality, stir and be cooled to-20 ℃, N
2Protection adds down the potassium tert.-butoxide of 1.1mol in this mixed solution, the about 3～4h of reaction under same temperature, after reaction is finished with 5% H
3PO
4Petroleum ether extraction three times are used in acidifying, merge organic phase, wash organic phase with water, and anhydrous sodium sulfate drying gets yellow oily liquid behind the desolventizing, and (V/V=30～5: 1) makes eluent with petrol ether/ethyl acetate, through purification by silica gel column chromatography.Productive rate: 1G 85.3%, 2G 84.6%, and 3G 86.2%, 4G80.6%.
9-benzenesulfinyl-3,7,11-trimethylammonium-2E, 6E, 10E-dodecylene-1-acetic ester (1G): C
23H
32O
4S (M=404.56), light yellow solid.
1H?NMR(CDCl
3，500MHz)δ7.66(d，1H)，7.61(d，2H)，7.42(m，2H)，5.46(m，1H)，5.36(m，2H)，5.15(m，H)，4.10(d，2H)，1.98～2.21(m，2H)，1.90(m，4H)，1.85(s，3H)，1.70～1.79(m，15H).
13C?NMR(CDCl
3，75MHz)δ171.2(C)，134.3(2C)，133.4(C)，132.4(C)，131.6(2CH)，129.2(2CH)，129.0(CH)，125.1(CH)，122.3(CH)，65.5(CH)，59.3(CH
2)，42.0(CH
2)，39.1(2CH
2)，25.3(2CH
2)，23.1(CH
3)，19.4(CH
3)，17.6(CH
3)，17.0(CH
3).
9-benzenesulfinyl-3,7,11,15-tetramethyl--2E, 6E, 10E, 4E-cetene-1-acetic ester (2G): C
28H
40O
4S (M=472.68),, light yellow solid.
1H?NMR(CDCl
3，500MHz)δ7.69(d，1H)，7.64(d，2H)，7.42(m，2H)，5.40(m，1H)，5.33(m，2H)，5.13(m，2H)，4.23(s，2H)，2.01～2.22(m，2H)，1.98～2.12(m，8H)，1.90(s，3H)，1.70～1.79(m，15H).
13C?NMR(CDCl
3，75MHz)δ169.9(C)，135.1(3C)，134.2(C)，132.3(C)，130.9(2CH)，129.6(2CH)，128.6(CH)，122.7(2CH)，121.3(2CH)，65.4(CH)，59.6(CH
2)，44.2(CH
2)，38.1(2CH
2)，25.7(2CH
2)，24.1(CH3)，20.2(CH
3)，19.5(CH
3)，17.6(2CH
3)，17.1(CH
3).
17-benzenesulfinyl-3,7,11,15,19,23-hexamethyl-2E, 6E, 10E, 4E, 18E, 22E-tetracosene-1-acetic ester (3G): C
38H
56O
4S (M=608.91), light yellow solid.
1H?NMR(CDCl
3，500MHz)δ7.68(d，1H)，7.63(d，2H)，7.41(m，2H)，5.42(m，1H)，5.35(m，2H)，5.16(m，4H)，4.43(s，2H)，2.01～2.25(m，2H)，1.98～2.12(m，16H)，1.90(s，3H)，1.70～1.79(m，21H).
13C?NMR(CDCl
3，75MHz)δ169.7(C)，135(5C)，134.5(C)，132.1(C)，130.7(2CH)，129.3(2CH)，128.4(CH)，122.4(3CH)，121.6(3CH)，66.3(CH)，59.1(CH
2)，44.1(2CH
2)，39.7(2CH
2)，39.4(CH
2)，25.9(4CH
2)，24.6(CH
3)，20.1(CH
3)，19.2(CH
3)，17.7(4CH
3)，17.1(CH
3).
17-benzenesulfinyl-3,7,11,15,19,23,27-seven methyl-2E, 6E, 10E, 4E, 18E, 22E, 26E-two vaccenic acids-1-acetic ester (4G): C
43H
64O
4S (M=667.30), light yellow solid.
1H?NMR(CDCl
3，500MHz)δ7.70(d，1H)，7.61(d，2H)，7.43(m，2H)，5.51(m，1H)，5.45(m，H)，5.34(m，H)，5.18(m，5H)，4，21(s，2H)，2.01～2.23(m，2H)，1.98～2.12(m，20H)，2.03(s，3H)，1.70～1.79(m，24H).
13C?NMR(CDCl
3，75MHz)δ170.7(C)，135.6(6C)，134.5(C)，132.5(C)，130.7(2CH)，129.6(2CH)，129.5(CH)，123.5(2CH)，122.4(5CH)，66.1(CH)，59.6(CH
2)，44.8(CH
2)，40.4(CH
2)，39.5(2CH
2)，39.4(2CH
2)，26.9(5CH
2)，25.3(CH
3)，20.7(CH
3)，19.2(CH
3)，17.3(4CH
3)，16.9(2CH
3).
Embodiment step 6.1H, 2H, 3H, 4H's is synthetic:
The general method of experiment:
The dehydrated alcohol of compound 1G (2G, 3G, 4G) 1mol and 8～10mol, the anhydrous THF of 200～400mL are mixed under-20 ℃, the sodium Metal 99.5 that in batches adds about 5～6mol, add after sodium finishes, under-20～0 ℃, stir 3～4h again, use petroleum ether extraction three times after reaction is finished, merge organic phase, anhydrous sodium sulfate drying, get yellow liquid behind the desolventizing, (V/V=40～10: 1) makes eluent with petrol ether/ethyl acetate, through purification by silica gel column chromatography.Productive rate: 1H 83.3%, 2H 81.2%, and 3H 86.4%, and 4H 85.7%.
3,7,11-trimethylammonium-2E, 6E, 10E-dodecylene-1-acetic ester (1H): C
17H
28O
2(M=264.40), light yellow liquid.
1H?NMR(CDCl
3，500MHz)δ5.31(m，1H)，5.20(m，2H)，4.53(d，2H)，1.98～2.21(m，8H)，1.90(s，3H)，1.70～1.79(m，12H).
13C?NMR(CDCl
3，75MHz)δ170.2(C)，133.5(2C)，131.6(C)，122.2(CH)，121.6(CH)，120.0(CH)，59.3(CH
2)，39.4(2CH
2)，25.1(2CH
2)，24.3(CH
3)，20.1(CH
3)，19.1(CH
3)，17.5(CH
3)，17.2(CH
3).
3,7,11,15-tetramethyl--2E, 6E, 10E, 4E-cetene-1-acetic ester (2H): C
22H
36O
2(M=332.52), light yellow liquid.
1H?NMR(CDCl
3，500MHz)δ5.37(m，1H)，5.19(m，3H)，4.62(d，2H)，1.95～2.10(m，12H)，1.92(s，3H)，1.70～1.77(m，15H).
13C?NMR(CDCl
3，75MHz)δ169.7(C)，134.6(3C)，131.2(C)，122.4(2CH)，121.5(CH)，120.6(CH)，59.7(CH
2)，38.7(3CH
2)，25.8(3CH
2)，24.2(CH
3)，20.1(CH
3)，18.7(CH
3)，17.5(3CH
3).
3,7,11,15,19,23-hexamethyl-2E, 6E, 10E, 4E, 18E, 22E-tetracosene-1-acetic ester (3H): C
32H
52O
2(M=468.75), light yellow liquid.
1H?NMR(CDCl
3，500MHz)δ5.29(m，1H)，5.17(m，5CH)，4.32(d，2H)，1.95～2.14(m，20H)，1.81(s，3H)，1.70～1.77(m，21H).
13C?NMR(CDCl
3，75MHz)δ171.7(C)，139.6(C)，136.4(4C)，131.2(C)，125.5(CH)，124.1(4CH)，123.4(CH)，59.3(CH
2)，39.7(2CH
2)，34.4(3CH
2)，26.1(5CH
2)，24.3(CH
3)，20.4(CH
3)，18.6(CH
3)，16.9(5CH
3).
3,7,11,15,19,23,27-seven methyl-2E, 6E, 10E, 4E, 18E, 22E, 26E-two vaccenic acids-1-acetic ester (4H): C
37H
60O
2(M=536.87), light yellow liquid.
1H?NMR(CDCl
3，500MHz)δ5.28(m，1H)，5.19(m，6CH)，4.37(d，2H)，1.93～2.10(m，24H)，1.86(s，3H)，1.70～1.77(m，24H).
13C?NMR(CDCl
3，75MHz)δ171.5(C)，135.8(C)，135.3(5C)，131.7(C)，123.7(CH)，122.5(5CH)，121.9(CH)，59.1(CH
2)，39.4(2CH
2)，34.1(4CH
2)，26.2(6CH
2)，24.9(CH
3)，20.4(CH
3)，18.6(CH
3)，16.9(5CH
3)，16.3(CH
3).
Embodiment step 7.1I, 2I, 3I, 4I's is synthetic:
The general method of experiment:
With compound 1H (2H, 3H, 4H) 1mol and 250～300mL CH
3OH-H
2Mixed solution (the volume ratio V/V:CH of O
3OH: H
21) and NaOH solid (1mol) O=1.5:, reacted 6～8 hours down at 50～60 ℃, after reaction is finished, behind the most of methyl alcohol of reclaim under reduced pressure, add suitable quantity of water, with petroleum ether extraction three times, merge organic phase, anhydrous sodium sulfate drying gets yellow liquid behind the desolventizing, (V/V=80～30: 1) makes eluent with petrol ether/ethyl acetate, through purification by silica gel column chromatography.Productive rate: 1I 93.9%, 2I 93.3%, and 3I 94.3%, and 4I 95.1%.
(E, E, E)-3,7,11-trimethylammonium-2,6,10-dodecylene-1-alcohol (1I): C
15H
26O (M=222.37), yellow oily liquid.
1H?NMR(CDCl
3，500MHz)δ5.34(m，1H)，5.17(m，2H)，4.15(d，2H)，2.56(s，OH)，1.99～2.11(m，8)，1.67～1.70(m，12).
13C?NMR(CDCl
3，75MHz)δ133.5(2C)，130.1(C)，121.7(2CH)，120.2(CH)，59.5(CH
2)，38.5(2CH
2)，26.7(2CH
2)，24.6(CH3)，18.5(CH
3)，17.5(CH
3)，17.2(CH
3).
3,7,11,15-tetramethyl--2E, 6E, 10E, 4E-cetene-1-alcohol (2I): C
20H
34O (M=290.48), yellow oily liquid.
1H?NMR(CDCl
3，500MHz)δ5.39(m，1H)，5.10(m，3H)，4.08(d，2H)，2.55(s，OH)，1.97～2.14(m，12H)，1.59～1.74(m，15H).
13C?NMR(CDCl
3，75MHz)δ139.6(C)，136.1(C)，135.3(C)，131.4(C)125.1(CH)，124.9(CH)，124.8(CH)，124.5(CH)，59.4(CH
2)，40.1(CH
2)，34.6(CH
2)，26.9(4CH
2)，24.8(CH3)，17.9(CH
3)，16.5(CH
3)，16.3(2CH
3).
3,7,11,15,19,23-hexamethyl-2E, 6E, 10E, 4E, 18E, 22E-tetracosene-1-alcohol (3I): C
30H
50O (M=462.72), yellow oily liquid.
1H?NMR(CDCl
3，500MHz)δ5.38(m，1H)，5.12(m，5H)，4.10(d，2H)，2.57(s，OH)，1.96～2.14(m，20H)，1.54～1.72(m，21H).
13C?NMR(CDCl
3，75MHz)δ140.1(C)，136.2(C)，135.8(C)，135.4(C)，135.3(C)，131.4(C)，125.3(CH)，124.6(2CH)，124.4(2CH)，124.1(CH)，58.9(CH
2)，41.2(2CH
2)，34.7(3CH
2)，26.9(5CH
2)，24.7(CH3)，17.8(CH
3)，16.4(CH
3)，16.3(4CH
3).
3,7,11,15,19,23,27-seven methyl-2E, 6E, 10E, 4E, 18E, 22E, 26E-two vaccenic acids-1-alcohol (4I): C
35H
58O (M=494.83), yellow oily liquid.
1H?NMR(CDCl
3，500MHz)δ5.36(m，1H)，5.14(m，6H)，4.08(d，2H)，2.49(s，OH)，1.92～2.13(m，24H)，1.54～1.72(m，24H).
13C?NMR(CDCl
3，75MHz)δ138.2(C)，135.9(C)，135.7(2C)，135.5(C)，135.3(C)，131.2(C)，123.4(CH)，123.1(CH)，122.3(4CH)，122.0(CH)，59.1(CH
2)，40.1(2CH
2)，34.6(4CH
2)，26.7(6CH
2)，25.0(CH3)，17.9(CH
3)，16.4(CH
3)，16.1(5CH
3).
Claims (2)
1, the synthetic method of full antitype long chain terebanthenes primary alcohol, its steps in sequence is:
(1) acetylize of starting raw material:
With Geraniol or geranyl linalool is starting raw material, make solvent with ethyl acetate, make catalyzer with pyridine, diacetyl oxide is made esterifying agent, about 8～the 10h of reaction under 50～60 ℃ of heating conditions, the mole proportioning of raw material and catalyzer is: starting raw material: aceticanhydride: pyridine=1: 1.05: 0.1;
(2) alkene chlorination reaction:
With (1) institute synthetic acetic ester is raw material, with Ca (ClO)
2〉=65%, the Losantin of available chlorine 〉=30% is made the alkene chlorination reagent, after in the mixed system of water-ethyl acetate, adding Losantin, under ice bath, drip Glacial acetic acid, the dropping time is 0.5～1 hour, dropwise the recession deicing and bathe, reacted under room temperature 8～10 hours, the mole proportioning of raw material and catalyzer is: acetic ester: Losantin: Glacial acetic acid=1: 0.75: 1.5;
(3) bromination reaction:
With 2-prenol or Geraniol or farnesol is starting raw material, make catalyzer with pyridine, make solvent with sherwood oil, make bromizating agent with phosphorus tribromide, drip the mixed solution of the sherwood oil formation of phosphorus tribromide and 1 times of quality under ice bath, the dropping time is 0.5～1 hour, dropwises the recession deicing and bathes, reacted under room temperature 1～1.5 hour, the mole proportioning of raw material and catalyzer is: starting raw material: phosphorus tribromide: pyridine=1: 0.7: 0.1 again;
(4) the benzene sulfinic acid ester is synthetic:
With (3) synthetic bromide is raw material, and with N, dinethylformamide is a solvent, with anhydrous sodium benzene sulfinate (C
6H
5SO
2Na) be esterifying agent, at room temperature reacted 3～4 hours that after reaction is finished, add saturated aqueous common salt again and stirred 0.5～1 hour, the mole proportioning of raw material is: bromide: anhydrous sodium benzene sulfinate=1: 1.1;
(5) linked reaction:
With (2), (4) synthetic alkene chlorizate and-sulfinic acid ester is raw material, make alkali with potassium tert.-butoxide, the molar ratio of alkene chlorizate,-sulfinic acid ester and potassium tert.-butoxide is 1: 1: 1.1, tetrahydrofuran (THF) and N with 3～5 times of alkene chlorizate quality, the dinethylformamide mixeding liquid volume is made solvent than 9: 1 mixed solutions, earlier raw material-sulfinic acid ester, alkene chlorizate and stirring solvent are cooled to-20 ℃, N
2Protection is reacted about 3～4h after down adding potassium tert.-butoxide again, after reaction is finished with 5% H
3PO
4Acidifying, petroleum ether extraction, drying;
(6) the-sulfinic acid ester slough reaction:
With (5) synthetic coupled product is raw material, and raw material 1mol is mixed under-20 ℃ of conditions with the anhydrous tetrahydro furan of dehydrated alcohol 8～10mol, 200～400mL, add sodium Metal 99.5 5～6mol in batches after, stirred 3～4 hours down at-20～0 ℃;
(7) hydrolysis reaction of ester:
Synthetic product with (6) is a raw material, adds 250～300mL volume ratio CH in the 1mol raw material
3OH: H
2O=1.5: 1 mixed solution and NaOH solid 1mol, reacted 6～8 hours down at 50～60 ℃, after reaction is finished, the most of methyl alcohol of reclaim under reduced pressure.
2, the synthetic method of full antitype long chain terebanthenes primary alcohol according to claim 1, it is characterized in that when reactions steps (1), the reacted purification process in (4)～(7), with sherwood oil or ethyl acetate extraction, behind extraction back gained organic phase drying, the desolventizing, with silica gel 100～200 order column chromatography purifications, with the petrol ether/ethyl acetate mixeding liquid volume than (80～5): 1 makes eluent.
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Non-Patent Citations (6)
| Title |
|---|
| CARBON-CARBON BOND FORMATIONEMPLOYINGORGANOIRON REAGENTS. J. Celebuski et al.Tetrahedron,Vol.41 No.24. 1985 |
| CARBON-CARBON BOND FORMATIONEMPLOYINGORGANOIRON REAGENTS. J. Celebuski et al.Tetrahedron,Vol.41 No.24. 1985 * |
| THE REACTION OF HYPOCHLOROUS ACID WITHOLEFINS. A CONVENIENT SYNTHESIS OF ALLYLICCHLORIDES. Shridhar G. Hegde et al.Tetrahedron Letters,Vol.21 . 1980 |
| THE REACTION OF HYPOCHLOROUS ACID WITHOLEFINS. A CONVENIENT SYNTHESIS OF ALLYLICCHLORIDES. Shridhar G. Hegde et al.Tetrahedron Letters,Vol.21. 1980 * |
| 癸异戊二烯醇的合成研究. 王超杰等.精细化工，第17卷第9期. 2000 |
| 癸异戊二烯醇的合成研究. 王超杰等.精细化工，第17卷第9期. 2000 * |
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