CN1086187C - Method for preparing bicyclohexyl-18-crown-6 - Google Patents
Method for preparing bicyclohexyl-18-crown-6 Download PDFInfo
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- CN1086187C CN1086187C CN98125085A CN98125085A CN1086187C CN 1086187 C CN1086187 C CN 1086187C CN 98125085 A CN98125085 A CN 98125085A CN 98125085 A CN98125085 A CN 98125085A CN 1086187 C CN1086187 C CN 1086187C
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- 238000000034 method Methods 0.000 title claims abstract description 23
- 238000006243 chemical reaction Methods 0.000 claims abstract description 59
- ZNSMNVMLTJELDZ-UHFFFAOYSA-N Bis(2-chloroethyl)ether Chemical compound ClCCOCCCl ZNSMNVMLTJELDZ-UHFFFAOYSA-N 0.000 claims abstract description 25
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 17
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 claims abstract description 16
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 19
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 18
- 239000013078 crystal Substances 0.000 claims description 13
- 238000004821 distillation Methods 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 238000005984 hydrogenation reaction Methods 0.000 claims description 7
- 239000012046 mixed solvent Substances 0.000 claims description 7
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims description 6
- 238000013019 agitation Methods 0.000 claims description 5
- 239000011541 reaction mixture Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 3
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 abstract description 7
- 229910052707 ruthenium Inorganic materials 0.000 abstract description 7
- 238000000926 separation method Methods 0.000 abstract description 7
- 239000003054 catalyst Substances 0.000 abstract description 6
- 238000000746 purification Methods 0.000 abstract description 5
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- BBGKDYHZQOSNMU-UHFFFAOYSA-N dicyclohexano-18-crown-6 Chemical compound O1CCOCCOC2CCCCC2OCCOCCOC2CCCCC21 BBGKDYHZQOSNMU-UHFFFAOYSA-N 0.000 abstract 2
- 238000004519 manufacturing process Methods 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
- 239000000047 product Substances 0.000 description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 239000007788 liquid Substances 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 150000003983 crown ethers Chemical class 0.000 description 10
- 238000002329 infrared spectrum Methods 0.000 description 10
- 239000013067 intermediate product Substances 0.000 description 9
- 238000002425 crystallisation Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 238000001819 mass spectrum Methods 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 238000010792 warming Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 238000010189 synthetic method Methods 0.000 description 6
- -1 aromatic series crown ether Chemical class 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- YSSSPARMOAYJTE-UHFFFAOYSA-N dibenzo-18-crown-6 Chemical compound O1CCOCCOC2=CC=CC=C2OCCOCCOC2=CC=CC=C21 YSSSPARMOAYJTE-UHFFFAOYSA-N 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 238000000967 suction filtration Methods 0.000 description 4
- XKZQKPRCPNGNFR-UHFFFAOYSA-N 2-(3-hydroxyphenyl)phenol Chemical compound OC1=CC=CC(C=2C(=CC=CC=2)O)=C1 XKZQKPRCPNGNFR-UHFFFAOYSA-N 0.000 description 3
- 125000006414 CCl Chemical group ClC* 0.000 description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000001125 extrusion Methods 0.000 description 3
- 238000011010 flushing procedure Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000007614 solvation Methods 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 150000001263 acyl chlorides Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 230000000916 dilatatory effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012434 nucleophilic reagent Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 150000005206 1,2-dihydroxybenzenes Chemical class 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 229910018575 Al—Ti Inorganic materials 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- PDXRQENMIVHKPI-UHFFFAOYSA-N cyclohexane-1,1-diol Chemical compound OC1(O)CCCCC1 PDXRQENMIVHKPI-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a method for preparing dicyclohexyl-18-crown-6, which comprises the steps that firstly, diethylene glycol and thionyl chloride are synthesized into bis (2-chloroethyl) ether as intermediate bodies; secondly, the intermediate bodies and pyrocatechol generate back flow reaction in solvent and template agents to be synthesized into dibenzene-18-crown-6; finally, ruthenium is used as catalysts to synthesize dicyclohexyl-18-crown-6. The present invention has the advantages of convenient operation of the synthetic process, simple subsequent processes of separation and purification, low production cost, etc.
Description
The present invention relates to the preparation method of a kind of dicyclohexyl and 18 hats 6, belong to technical field of organic chemistry.
Crown ether is a class macrocyclic polyether compounds.Its synthetic method is to utilize some well-known type reaction to form ring substantially.Simple aliphatics or aromatic series crown ether generally are to borrow the method for the synthetic ether of Williamson to carry out cyclisation, and the synthetic of ester type or acid amide type crown ether then is the reaction of cyclisation when utilizing acyl chlorides and alcohol or amine generation acidylate.In addition, also has some other cyclization method.And along with carrying out rapidly of crown ether chemistry and applied research thereof, a large amount of macrocylc compound promptly are synthesized out, and kind is increasing, and synthetic method is development constantly also.
Crown ether synthetic basic raw material and intermediate have diphenol, multiethylene-glycol dihalide, multiethylene-glycol two p-toluenesulfonic esters etc.Diphenol and glycol under alkaline condition as nucleophilic reagent, and with dihalide or two p-toluenesulfonic esters phase reactions as alkylating agent.In addition, in ester type and acid amide type crown ether synthetic, then need acyl chlorides with how sweet acid as acylating agent, synthesizing of cave ether also needs with how sweet amine (diamines) as nucleophilic reagent.The existing commercial chemistry reagent that these raw materials and intermediate have is sold, and what have then needs self-control.
As crown ether synthetic basic raw material multiethylene-glycol dihalide, no matter be the method that is adopted when producing the commodity chemical reagent, still the synthetic method that in scientific research, adopted of chemists, all be the synthetic method that proposed 1967 time according to C.J.Pedersen (referring to C.J.Pedersen, J.Am.Chem.Soc., 1967,89,2495,7017), this method with corresponding multiethylene-glycol and thionyl chloride in benzene in the presence of the pyridine reaction make, the reactive chemistry formula is:
Wherein n is the integer more than or equal to 1.
This method also is applicable to glycol ether dichloride (promptly two (2-chloroethyl) ethers are called for short dichloroethyl ether), and productive rate is generally higher.Concrete grammar is to adopt benzene to make solvent, makes the absorption agent of acidic by-products with pyridine, carries out (on reaction mechanism, pyridine has in fact also participated in reaction process) to guarantee to be reflected under the alkaline environment, and the reactive chemistry formula is as follows:
This reaction is carried out very slowly, generally needed just can carry out in 15～16 hours relatively fully.After reacting completely, use hcl acidifying, tell organic phase, drying is filtered, and air distillation is steamed and desolventized benzene then, and underpressure distillation obtains target product again.
Because benzene and pyridine have the strong impulse smell, all be volatile strong carcinogen, so the operating environment toxicity of aforesaid method are very big.In addition, after reacting completely, the separation purification procedures unit of target product is more, has increased the complicacy of operation, also is not calculate on economy.
Aromatic series crown ether synthetic generally is to be raw material with dihydric phenol and multiethylene-glycol dichloride or two p-toluenesulfonic esters, and back flow reaction made under nitrogen was protected in caustic solution.In these reactions, common alkali metal hydroxides (MOH) generates phenates with the pyrocatechol reaction earlier, then with multiethylene-glycol dichloride generation nucleophilic substitution reaction.M in the reaction system
+The carrying out that plays a part template simultaneously and impel cyclization.With two (2-chloroethyl) ether, pyrocatechol and sodium hydroxide back flow reaction under the nitrogen protection in the propyl carbinol solvent, can generate dibenzo 18 hats 6, reaction is actually to be carried out in two steps, and reaction formula is as follows:
Therefore, the segmentation of multiethylene-glycol dichloride is added, can help the raising of dibenzo dilating ether productive rate.Because propyl carbinol is protonic solvent, the negatively charged ion of pyrocatechol salt there is solvation, so anionic reactive behavior is not high, so the long back flow reaction of this reaction needed, generally need are 20 hours.Propyl carbinol is changed into Pentyl alcohol, when under refluxing, reacting,, can shorten the reaction times because temperature of reaction is higher.As replacing propyl carbinol,, be reflected in 1～2 hour and can finish, but productive rate is lower than the result of Pedersen slightly at 120～130 ℃ with methyl-sulphoxide.This is because methyl-sulphoxide is strong polar aprotic solvent, and it is the negatively charged ion of solvation diphenol salt not basically, so two phenol salt anions is active high, reaction is fast, but Na
+Can solvation in methyl-sulphoxide, may therefore make as the effective concentration of the metal ion of template not high, thereby make the productive rate of crown ether be subjected to some influences.
Alicyclic crown ether is meant the crown ether of hexanaphthene and ether ring.They all have bigger solubleness in polarity, low polarity and non-polar organic solvent.Therefore, they have purposes widely than corresponding benzo-crown ether.This class crown ether can carry out catalytic hydrogenation or is that raw material is synthetic with the cyclohexanediol with benzo-crown ether, and the reactions steps of back one synthetic method is too many, and the meaning on not have to prepare is studied in order to make specific steric configuration isomer.
Pedersen reports that in its article the earliest (referring to J.Am.Chem.Soc., 1967,89,2495) synthesized 13 hexanaphthenes and crown ether.General synthesis method is that benzo-crown ether or dibenzo dilating ether are dissolved in dioxane or the propyl carbinol, up to 120 ℃ with under the 15MPa, carries out hydrogenation with the ruthenium catalyst that is loaded on the aluminum oxide, and the reaction times reaches 20 hours.USSR (Union of Soviet Socialist Republics) patent report after a while, in ethanol under 150～200 ℃ and the 10～20MPa, the catalytic hydrogenation of carrying out dibenzo 18 hats 6 with Raney nickel or Ni-Al-Cr (47: 50: 3, weight %) or Ni-Al-Ti (47: 50: 3, weight %) is preced with 6 method (referring to Egorov E.M. prepare dicyclohexyl and 18, Kobrin V.S., Lubenets E.G., Khmel ' nitskii A.G., U.S.S.R.Su, 1972,1027162).The reaction conditions of these synthetic methods is all relatively harsher.
The objective of the invention is to propose the preparation method of a kind of dicyclohexyl and 18 hats 6, make the building-up process of dicyclohexyl and 18 hats 6 simple to operate, and the later separation purification procedures is simplified.
The preparation method of dicyclohexyl of the present invention and 18 hats 6 comprises following each step:
1) two (2-chloroethyl) ethers of synthetic intermediate:
Adopt glycol ether and thionyl chloride direct reaction under agitation, reaction formula is as follows:
Usually the mol ratio of glycol ether and thionyl chloride is: 1: 2.1～3, and temperature of reaction is 90～130 ℃, reaction
Time is 60～150 minutes, and reaction is directly reduced pressure reaction mixture water circulating vacuum pump after finishing
108～110 ℃/10mmHg fraction is collected in distillation, is two (2-chloroethyl) ethers;
(2) synthetic intermediate dibenzo 18 hats 6:
Make solvent with propyl carbinol, Pentyl alcohol or methyl-sulphoxide, sodium hydroxide is made template, adopt the reaction under refluxing of two (2-chloroethyl) ethers and pyrocatechol to make dibenzo 18 hats 6, pyrocatechol with the mol ratio of two (2-chloroethyl) ethers is: 1: 1～1.5, when adopting propyl carbinol to be solvent, return time is 16～24 hours, temperature of reaction is 115 ℃, when adopting Pentyl alcohol to be solvent, return time is 8～12 hours, and temperature of reaction is 135 ℃, when adopting methyl-sulphoxide to be solvent, return time is 1～2 hour, and temperature of reaction is 125 ℃;
(3) synthetic dicyclohexyl and 18 hats 6:
Dibenzo 18 hats 6 usefulness rutheniums are carried out hydrogenation as catalyzer, add 0.5～2g catalyzer in dibenzo 18 hats 6 of 1mol question response, temperature of reaction is 30～100 ℃, and reaction pressure is 3～10MPa, 2～5 hours reaction times;
(4) with above-mentioned the 3rd step synthetic dicyclohexyl and 18 hats, 6 usefulness alcohol-water mixed solvents, make its dissolving, alcohol with the ratio of water is: 1: 0.5～4, and cryosel cementing crystalline substance obtains white prismatic crystal then, is target product dicyclohexyl of the present invention and 18 hats 6.
Prepare the method for intermediate double (2-chloroethyl) ether among the present invention, have lot of advantages.At first, reaction times shortens greatly: secondly, owing to do not use benzene and pyridine, thereby avoided operating under the very big environment of toxicity: the separation that reacts completely later is purified simple, target product can be directly from reaction mixture underpressure distillation obtain: in above synthetic agent, pyridine is the most expensive, owing to avoided use to pyridine and benzene, directly reduce the reagent cost of product, and because the reaction times shortens greatly, and the purification of product simplified control, adopt synthetic two (2-chloroethyl) ethers of method provided by the invention that cost is reduced significantly.
Among the preparation method of synthetic dicyclohexyl and 18 hats 6, hydrogenation adopts the Pichler ruthenium to make catalyzer among the present invention, and reaction formula is as follows:
Usually dibenzo 18 hats 6 of 1mol question response need to add 0.5～2g catalyzer, are preferably 0.8～1.5g.Under very gentle condition, reaction still is easy to carry out very much.Temperature of reaction is 30～100 ℃, is preferably 50～70 ℃.Reaction pressure is 3～10MPa, is preferably 5～8MPa.Reaction times shortens greatly, is generally 2～5 hours, is preferably 3～4 hours.
After reacting completely, because reaction system is clarifying liquid state, described catalyzer will be deposited at the bottom of the still, and the rate of recovery is up to 98%, not take out catalyzer after also can draining out supernatant liquor, and it is directly used in reaction next time.
It is one of main difficult point in its building-up process that the separation of dicyclohexyl and 18 hats, 6 sinteticses are purified, and general method is that at first underpressure distillation is steamed and desolventized after column chromatography, and elutant leaves standstill crystallization again after concentrated.But our practice shows that even like this, at room temperature they also are difficult to crystallization, can only obtain the heavy-gravity pasty substance usually.Its reason is that dicyclohexyl and 18 hats 6 that catalytic hydrogenation makes are steric isomer A (cis-syn-cis, 69～70 ℃ of mp) and isomer B (cis-anti-cis, 83～84 ℃ of mp) mixture, its fusing point is very low, about 30～50 ℃, nucleus is grown up slowly, is difficult to crystallization from thick liquid state under the room temperature, it is also not obvious to add the crystal seed effect, must be at low temperatures could crystallization through leaving standstill for a long time.The present invention dissolves it with a kind of alcohol-water mixed solvent after it being concentrated the reaction mixture air distillation under a little higher than room temperature, cryosel is bathed crystallization then, has obtained white prismatic crystal.This method is easy fast, and has avoided wasting time and energy and be not suitable for the column chromatography separation method of large-scale production.
Preferred methyl alcohol and the ethanol of using of alcohol in above-mentioned alcohol-water mixed solvent more preferably uses methyl alcohol, and the ratio of it and deionized water generally can elect 1: 0.5 as～and 6, be preferably 1: 0.5～2.
Adopt the method for the invention, can under gentle relatively reaction conditions, obtain dicyclohexyl and 18 hats 6, and, make reaction carry out very desirablely, also promoted the relative simplification of later separation Purification because employed ruthenium-containing catalyst activity is higher.
Embodiment 1
The preparation of two (2-chloroethyl) ethers of intermediate product
In the 500ml four-hole bottle that agitator, reflux exchanger, control temperature meter, constant pressure funnel are housed, put into glycol ether 190ml (2.0mol), thionyl chloride 294ml (4.1mol) under agitation, evolving gas absorbs with alkali lye.30min dropwises, and is warming up to 110 ℃ rapidly, and 100min is to there not being gas evolution in reaction.108～110 ℃/10mmHg fraction 232g (colourless liquid), productive rate 81.7% are collected in underpressure distillation.Product refractive index n
20 D=1.4563 (calculated values 1.4560): mass spectrum: 142 (theoretical values 142); Infrared spectra: discovery-OH peak not, at 752cm
-1There is the strong peak of C-Cl at the place; Ultimate analysis: C%33.6,33.7 (theoretical values 33.8), H%5.7,5.5 (theoretical values 5.6);
1HNMR meets the constitutional features of target product.
Embodiment 2
The preparation of two (2-chloroethyl) ethers of intermediate product
In with the device of embodiment 1, add glycol ether 190ml (2.0mol), under agitation thionyl chloride 294ml (4.1mol) in the 60min.Be warming up to 70 ℃ rapidly, reaction 20min is warming up to 100 ℃ again, and 60min is to there not being gas evolution in reaction.108～109 ℃/10mmHg fraction 218g (colourless liquid), productive rate 76.8% are collected in underpressure distillation.Product refractive index n
20 D=1.4561 (calculated values 1.4560); Mass spectrum: 142 (theoretical values 142); Infrared spectra: discovery-OH peak not, at 752cm
-1There is the strong peak of C-Cl at the place; Ultimate analysis: C%33.7 (theoretical value 33.8), H%5.6 (theoretical value 5.6);
1H NMR meets the constitutional features of target product.
Embodiment 3
The preparation of two (2-chloroethyl) ethers of intermediate product
In with the device of embodiment 1, add glycol ether 285ml (3.0mol), thionyl chloride 438ml (6.1mol) 70～75 ℃ time the under agitation, evolving gas absorbs with alkali lye.60min dropwises, and is warming up to 1 10 ℃ rapidly, and 90min is to there not being gas evolution in reaction.107～109 ℃/10mmHg fraction 339.5g (colourless liquid), productive rate 79.7% are collected in underpressure distillation.Product refractive index n
20 D=1.4562 (calculated values 1.4560); Mass spectrum: 142 (theoretical values 142); Infrared spectra: discovery-OH peak not, at 752cm
-1There is the strong peak of C-Cl at the place; Ultimate analysis: C%33.6 (theoretical value 33.8), H%5.7 (theoretical value 5.6);
1H NMR meets the constitutional features of target product.
Embodiment 4
The preparation of the preparation 1 of dicyclohexyl and 18 hats 6 (DCH18C6), two (2-chloroethyl) ethers of intermediate product
According to two (2-chloroethyl) ethers of embodiment 1 described method preparation.2, the preparation of intermediate product dibenzo 18 hats 6 (DB18C6)
In the 1L four-hole bottle that mechanical stirrer, reflux exchanger, control temperature meter, airway and dropping funnel are housed, add 66g (0.6mol) pyrocatechol and 400ml propyl carbinol.Stir, logical nitrogen adds the granular sodium hydroxide of 24.4g (0.61mol).Reflux (about 115 ℃) drips the solution that two (2-chloroethyl) ethers of 44.4g (0.31mol) and 30ml propyl carbinol are made in half an hour rapidly.Continue to reflux and stirred 1 hour.Be cooled to 90 ℃, add the granular sodium hydroxide of 24.4g (0.61mol) again, stirring and refluxing half an hour in half an hour, drip the solution that two (2-chloroethyl) ethers of 44.4g (0.31mol) and 30ml propyl carbinol are made into, continue reaction 16 hours.Use hcl acidifying, air distillation steams the about 200ml of propyl carbinol fast, drips deionized water in matrass, and its rate of addition makes that volume of mixture remains unchanged in the matrass.Continue distillation, redistillation is till 10 minutes after vapor temperature reaches 100 ℃.Be cooled to 30～40 ℃, with the soup compound of 100ml acetone diluted remainder, stir, suction filtration gets thick product.Crude product is mixed with 400ml water, stir suction filtration; Stir the back suction filtration with 200ml acetone again, use the 100ml washing with acetone, suction filtration, drying obtains 55.1g (productive rate 51%) white fiber shape crystal, 161～163 ℃ of its fusing points.Make solvent recrystallization with benzene, be further purified and obtain white fiber shape crystal.Product fusing point: 163～164 ℃ (164 ℃ of literature values); Mass spectrum: 360 (calculated values 360.1); Infrared spectra (KBr compressing tablet): 2860～2940cm
-1(CH
2Stretching vibration), 1320cm
-1, 1360cm
-1(CH
2Flexural vibration), 1060～1250cm
-1(C-O stretching vibration on the ether ring):
1H NMR: meet object construction; Ultimate analysis: C%66.5,66.5 (calculated values 66.67), H%6.7,6.8 (calculated values 6.67).3, the preparation of target product dicyclohexyl and 18 hats 6 (DCHl8C6)
In the 0.5L stainless steel autoclave, add 60g (0.167mol) dibenzo 18 hats 6,200ml propyl carbinol, 0.2g Pichler ruthenium catalyst.Behind system's usefulness nitrogen wash three times, feed hydrogen flushing three times, feed hydrogen again to 8MPa.Stir, be warming up to 90 ℃ of hydrogenations.System pressure no longer descends after about 3 hours, is cooled to room temperature, by the liquid discharge nozzle extrusion supernatant liquid of autoclave.Place rotatory evaporator to concentrate supernatant liquor, get the thick material of brown.It is dissolved in 40 ℃ of first alcohol and waters, and (1: 1, in mixed solvent v/v), cryosel was bathed crystallisation by cooling, gets the 40.3g white crystal, productive rate 65%.Product fusing point: 48～53 ℃ (30～56 ℃ of literature values); Mass spectrum: 372 (calculated values 372.41); Infrared spectra (KBr smear): compare with the infrared spectrum of DB18C6, find 3075cm
-1, 1450cm
-1, 1500cm
-1, 1580cm
-1, 735cm
-1, 770cm
-1Charateristic avsorption band Deng place's phenyl ring disappears, and 2860～2940cm
-1The CH of place
2The stretching vibration absorption peak strengthens;
1HNMR: meet object construction; Ultimate analysis: C%64.4,64.4 (calculated values 64.5), H%9.6,9.7 (calculated values 9.7).
Embodiment 5
The preparation of the preparation l of dicyclohexyl and 18 hats 6, two (2-chloroethyl) ethers of intermediate product
According to two (2-chloroethyl) ethers of embodiment 2 described method preparations.2, the preparation of intermediate product dibenzo 18 hats 6
With the reinforced and reaction of described method of the 2nd step among the embodiment 4, just solvent is changed to the 400ml Pentyl alcohol by the 400ml propyl carbinol, back flow reaction is 10 hours under about 135 ℃ temperature.Obtain 50g (46.3%) white crystal, 160～163 ℃ of fusing points.Make solvent recrystallization with benzene, be further purified and obtain white fiber shape crystal, the product fusing point is 162～163 ℃ (164 ℃ of literature values).3, the preparation of target product dicyclohexyl and 18 hats 6
In the 0.5L stainless steel autoclave, add 60g (0.167mol) dibenzo 18 hats 6,200ml propyl carbinol, 0.1g Pichler ruthenium catalyst.Behind system's usefulness nitrogen wash three times, feed hydrogen flushing three times, feed hydrogen again to 5MPa.Stir, be warming up to 50 ℃ of hydrogenations.System pressure no longer descends after about 5 hours, is cooled to room temperature, by the liquid discharge nozzle extrusion supernatant liquid of autoclave.Place rotatory evaporator to concentrate supernatant liquor, get the thick material of brown.It is dissolved in 40 ℃ of first alcohol and waters, and (1: 1, in mixed solvent v/v), cryosel was bathed crystallisation by cooling, gets the 44.6g white crystal, productive rate 71.9%.Product fusing point: 45～54 ℃ (30～56 ℃ of literature values); Mass spectrum: 372 (calculated values 372.41): infrared spectra (KBr smear): compare with the infrared spectrum of DB18C6, find 3075cm
-1, 1450cm
-1, 1500cm
-1, 1580cm
-1, 735cm
-1, 770cm
-1Charateristic avsorption band Deng place's phenyl ring disappears, and 2860～2940cm
-1The CH of place
2The stretching vibration absorption peak strengthens;
1HNMR: meet object construction; Ultimate analysis: C%64.4 (calculated value 64.5), H%9.6 (calculated value 9.7).
Embodiment 6
The preparation of the preparation 1 of dicyclohexyl and 18 hats 6, two (2-chloroethyl) ethers of intermediate product
According to two (2-chloroethyl) ethers of embodiment 3 described method preparations.2, the preparation of intermediate product dibenzo 18 hats 6
With the reinforced and reaction of described method of the 2nd step among the embodiment 4, just solvent is changed to the 400ml methyl-sulphoxide by the 400ml propyl carbinol, back flow reaction is 2 hours under 120～130 ℃ temperature.Obtain 37.8g (34.9%) white crystal, 161～163 ℃ of fusing points.Make solvent recrystallization with benzene, be further purified and obtain white fiber shape crystal, the product fusing point is 163～164 ℃ (164 ℃ of literature values).3, the preparation of target product dicyclohexyl and 18 hats 6
In the 0.5L stainless steel autoclave, add 60g (0.167mol) dibenzo 18 hats 6,200ml propyl carbinol, 0.3g Pichler ruthenium catalyst.Behind system's usefulness nitrogen wash three times, feed hydrogen flushing three times, feed hydrogen again to 8MPa.Stir, be warming up to 100 ℃ of hydrogenations.System pressure no longer descends after about 2 hours, is cooled to room temperature, by the liquid discharge nozzle extrusion supernatant liquid of autoclave.Place rotatory evaporator to concentrate supernatant liquor, get the thick material of brown.It is dissolved in 40 ℃ of first alcohol and waters, and (1: 1, in mixed solvent v/v), cryosel was bathed crystallisation by cooling, gets the 38.6g white crystal, productive rate 62.2%.Product fusing point: 43～53 ℃ (30～56 ℃ of literature values); Mass spectrum: 372 (calculated values 372.41); Infrared spectra (KBr smear): compare with the infrared spectrum of DB18C6, find 3075cm
-1, 1450cm
-1, 1500cm
-1, 1580cm
-1, 735cm
-1, 770cm
-1Charateristic avsorption band Deng place's phenyl ring disappears, and 2860～2940cm
-1The CH of place
2The stretching vibration absorption peak strengthens;
1HNMR: meet object construction; Ultimate analysis: C%64.4 (calculated value 64.5), H%9.7 (calculated value 9.7).
Claims (1)
1, the preparation method of a kind of dicyclohexyl and 18 hats 6 is characterized in that this method comprises following each step:
(1) two (2-chloroethyl) ethers of synthetic intermediate: adopt glycol ether and thionyl chloride direct reaction under agitation, reaction formula is as follows:
The mol ratio of glycol ether and thionyl chloride is: 1: 2.1～3, and temperature of reaction is 90～130 ℃, the reaction times is 60～150 minutes, after reaction finishes, directly, collect 108～110 ℃/10mmHg fraction, be two (2-chloroethyl) ethers the underpressure distillation of reaction mixture water circulating vacuum pump;
(2) synthetic intermediate dibenzo 18 hats 6:
Make solvent with propyl carbinol, Pentyl alcohol or methyl-sulphoxide, sodium hydroxide is made template, adopt the reaction under refluxing of two (2-chloroethyl) ethers and pyrocatechol to make dibenzo 18 hats 6, pyrocatechol with the mol ratio of two (2-chloroethyl) ethers is: 1: 1～1.5, when adopting propyl carbinol to be solvent, return time is 16～24 hours, temperature of reaction is 115 ℃, when adopting Pentyl alcohol to be solvent, return time is 8～12 hours, and temperature of reaction is 135 ℃, when adopting methyl-sulphoxide to be solvent, return time is 1～2 hour, and temperature of reaction is 125 ℃;
(3) synthetic dicyclohexyl and 18 hats 6:
Dibenzo 18 hats 6 usefulness rutheniums are carried out hydrogenation as catalyzer, add 0.5～2g catalyzer in dibenzo 18 hats 6 of 1mol question response, temperature of reaction is 30～100 ℃, and reaction pressure is 3～12MPa, 2～6 hours reaction times;
(4) with above-mentioned the 3rd step synthetic dicyclohexyl and 18 hats, 6 usefulness alcohol-water mixed solvents, make its dissolving, alcohol with the ratio of water is: 1: 0.5～4, and cryosel cementing crystalline substance obtains white prismatic crystal then, is dicyclohexyl and 18 hats 6.
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| CN98125085A CN1086187C (en) | 1998-12-04 | 1998-12-04 | Method for preparing bicyclohexyl-18-crown-6 |
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| CN98125085A CN1086187C (en) | 1998-12-04 | 1998-12-04 | Method for preparing bicyclohexyl-18-crown-6 |
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| CN1086187C true CN1086187C (en) | 2002-06-12 |
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| CN100395243C (en) * | 2005-07-15 | 2008-06-18 | 清华大学 | Improved systhesizing process for dicyclohexyl-18-crown-6 |
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| CN102040584B (en) * | 2010-12-16 | 2013-04-17 | 清华大学 | Synthesis method of dicyclohexyl-18-crown-6 |
| CN103012362A (en) * | 2012-12-27 | 2013-04-03 | 清华大学 | Preparation method of diamidodibenzo-18-crown ether-6 bonded silica gel stationary phase and intermediate thereof |
| CN104710402B (en) * | 2013-12-13 | 2017-01-18 | 中国科学院大连化学物理研究所 | Dicyclohexyl crown ether synthesis method |
| CN105356058B (en) * | 2015-11-26 | 2019-03-29 | 联想(北京)有限公司 | A kind of electronic equipment and antenna assembly |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN85102097A (en) * | 1985-04-01 | 1986-01-10 | 郑州大学 | Process for preparing benzo-crown ethers |
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| CN85102097A (en) * | 1985-04-01 | 1986-01-10 | 郑州大学 | Process for preparing benzo-crown ethers |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100395243C (en) * | 2005-07-15 | 2008-06-18 | 清华大学 | Improved systhesizing process for dicyclohexyl-18-crown-6 |
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