CN108840787B - Preparation method of junenol intermediate isopropyl cyclopentadiene - Google Patents
Preparation method of junenol intermediate isopropyl cyclopentadiene Download PDFInfo
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- CN108840787B CN108840787B CN201810637731.5A CN201810637731A CN108840787B CN 108840787 B CN108840787 B CN 108840787B CN 201810637731 A CN201810637731 A CN 201810637731A CN 108840787 B CN108840787 B CN 108840787B
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- isopropylcyclopentadiene
- cyclopentadiene
- dimethyl sulfoxide
- bromopropane
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- MWQKURVBJZAOSC-UHFFFAOYSA-N 1-propan-2-ylcyclopenta-1,3-diene Chemical compound CC(C)C1=CC=CC1 MWQKURVBJZAOSC-UHFFFAOYSA-N 0.000 title claims abstract description 36
- MSJJKJCIFIGTJY-LJISPDSOSA-N (1s,2s,4ar,8as)-4a-methyl-8-methylidene-2-propan-2-yl-1,2,3,4,5,6,7,8a-octahydronaphthalen-1-ol Chemical compound C1CCC(=C)[C@@H]2[C@@H](O)[C@H](C(C)C)CC[C@]21C MSJJKJCIFIGTJY-LJISPDSOSA-N 0.000 title description 3
- KTROAXMUYHQRSZ-UHFFFAOYSA-N Saussureamine E Natural products O=C1OC2C(C(=C)CCC3O)C3(C)CCC2C1CN1CCCC1C(O)=O KTROAXMUYHQRSZ-UHFFFAOYSA-N 0.000 title description 3
- MSJJKJCIFIGTJY-GBJTYRQASA-N beta-Verbesinol Natural products O[C@@H]1[C@H](C(C)C)CC[C@]2(C)[C@@H]1C(=C)CCC2 MSJJKJCIFIGTJY-GBJTYRQASA-N 0.000 title description 3
- 238000002360 preparation method Methods 0.000 title description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 57
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 claims abstract description 40
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 22
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 claims abstract description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 239000002002 slurry Substances 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims description 25
- 238000006317 isomerization reaction Methods 0.000 claims description 7
- CVIGYQZQDNHNTC-UHFFFAOYSA-N 5-propan-2-ylcyclopenta-1,3-diene Chemical compound CC(C)C1C=CC=C1 CVIGYQZQDNHNTC-UHFFFAOYSA-N 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- FUWUEFKEXZQKKA-UHFFFAOYSA-N beta-thujaplicin Chemical compound CC(C)C=1C=CC=C(O)C(=O)C=1 FUWUEFKEXZQKKA-UHFFFAOYSA-N 0.000 abstract description 12
- TUFYVOCKVJOUIR-UHFFFAOYSA-N alpha-Thujaplicin Natural products CC(C)C=1C=CC=CC(=O)C=1O TUFYVOCKVJOUIR-UHFFFAOYSA-N 0.000 abstract description 6
- 229930007845 β-thujaplicin Natural products 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 21
- 239000000243 solution Substances 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 11
- 239000000178 monomer Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 238000005406 washing Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- -1 cyclopentadiene anion Chemical class 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 238000005070 sampling Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 241000607479 Yersinia pestis Species 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- HECLRDQVFMWTQS-RGOKHQFPSA-N 1755-01-7 Chemical compound C1[C@H]2[C@@H]3CC=C[C@@H]3[C@@H]1C=C2 HECLRDQVFMWTQS-RGOKHQFPSA-N 0.000 description 1
- 241001117244 Chamaecyparis formosensis Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 244000000007 bacterial human pathogen Species 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 150000005826 halohydrocarbons Chemical class 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000077 insect repellent Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229930003658 monoterpene Natural products 0.000 description 1
- 150000002773 monoterpene derivatives Chemical class 0.000 description 1
- 235000002577 monoterpenes Nutrition 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000005871 repellent Substances 0.000 description 1
- 230000002940 repellent Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- MDYOLVRUBBJPFM-UHFFFAOYSA-N tropolone Chemical group OC1=CC=CC=CC1=O MDYOLVRUBBJPFM-UHFFFAOYSA-N 0.000 description 1
- 150000004788 tropolones Chemical class 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/26—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only halogen atoms as hetero-atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C5/00—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms
- C07C5/22—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms by isomerisation
- C07C5/23—Rearrangement of carbon-to-carbon unsaturated bonds
- C07C5/25—Migration of carbon-to-carbon double bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of medicine synthesis, and particularly relates to a method for preparing a hinokitiol intermediate 1-isopropylcyclopentadiene with high selectivity. Under the protection of nitrogen, dimethyl sulfoxide, 2-bromopropane and potassium hydroxide are added to form slurry, and then cyclopentadiene is added into the slurry to react to obtain isopropyl cyclopentadiene. The method can prepare the 1-position isopropylcyclopentadiene with high selectivity.
Description
Technical Field
The invention belongs to the technical field of medicine synthesis, and particularly relates to a method for preparing a hinokitiol intermediate 1-isopropylcyclopentadiene with high selectivity.
Background
Hinokitiol is a monoterpene natural compound with a tropolone skeleton, belongs to tropolone compounds, has good antibacterial property, moisture retention and pest repellent effect, is a high-safety plant component, can be used as an antibacterial and insect repellent agent, is a main component of Taiwan cypress essential oil, has wide biological activity and strong bactericidal capability, has the minimum inhibitory concentration of 10-100ppm to common bacteria, has fragrant smell and good effect, can kill bacteria and microbes in the air, prevents pests from invading human bodies and inhibits human pathogenic bacteria. The method is already used for producing products such as shower gel, cosmetics, medicines, agriculture and the like.
Through a search of the literature, patent JP5133901B (application 1970) discloses a method for preparing hinokitiol from isopropylcyclopentadiene, the specific route is as follows:
isopropyl cyclopentadiene as a key material for preparing hinokitiol, the prior literature reports the following route:
from the results of the present search, path 1 and path 2 appear in patent JP5133901B (applied in 1970); path 3 appears in WO99050215 (application 29/3 1999, 10/7/1999 International publication).
By analysis of the prior art, the preparation of isopropylcyclopentadiene via scheme 3 is the preferred method.
In general, 1-isopropylcyclopentadiene as a key intermediate for the synthesis of hinokitiol, prepared by scheme 3 involves three isomers with different substitution positions. They are cyclopentadiene substituted in the 1-position, 2-position and 5-position, respectively. The three structures are shown below:
under thermodynamic steady state equilibrium conditions, a mixture of predominantly a mixture of the 1-and 2-positions and a small amount of the 5-position isomer.
The synthesis of substituted cyclopentadiene monomers is mainly carried out by reacting cyclopentadiene monomer with electrophilic reagent such as halohydrocarbon in the presence of alkali to form cyclopentadiene anion, and first generating 5-position isomer, and then isomerizing to 1-position isomer and 2-position isomer. V.a.mironov et al indicate: isomerization of the 5-position isomer to the 1-position isomer proceeds even at lower temperatures, while isomerization of the 1-position isomer to the 2-position isomer requires higher temperatures. Mclean et al indicate that the above isomerization is effective in the absence of a strong base. In the presence of a strong base, the alkylcyclopentadiene anion generated by the 5-position isomer is very likely to be directly isomerized into an equilibrium mixture, and the selectivity of the 1-position isomer is reduced. CN1177789C states that the term "strong base" as used herein refers primarily to cyclopentadienylmetals.
Patent WO99050215 first reacts cyclopentadiene with potassium hydroxide to form potassium cyclopentadienyl, which is then further reacted to form isopropylcyclopentadiene, in two steps.
Patent JP2003055272A synthesizes isopropylcyclopentadiene by a one-step process, which comprises the steps of first forming a solution by coexistence of cyclopentadiene, 2-bromopropane and dimethyl sulfoxide, and then adding potassium hydroxide into the solution to form isopropylcyclopentadiene.
Although both methods produce 1-substituted isopropylcyclopentadiene with good selectivity, more than 6% of 2-substituted isopropylcyclopentadiene still remains.
Disclosure of Invention
The invention aims to find a better method for preparing the isopropyl cyclopentadiene of the junenol intermediate by improvement on the basis of the prior art.
The present inventors have found, through studies in comparative examples, that a partial proportion of 2-substituted isopropylcyclopentadiene (10%) is still present in the existing HPLC assay. The reason is presumed to be: after the potassium cyclopentadienyl dimethyl sulfoxide solution is prepared by the fractional step method (because the reaction is in a reversible equilibrium state, partial potassium hydroxide solid still exists), halogenated hydrocarbon is added, and meanwhile, the potassium hydroxide which is dissolved in the dimethyl sulfoxide and does not participate in the reaction still reacts with the isopropylcyclopentadiene, so that the alkylated cyclopentadiene anion is isomerized, and a certain amount of 2-bit isomer exists. Patent JP2003055272A is prepared by a homogeneous process, mainly by reaction with large amounts of 2-bromopropane immediately after the formation of potassium salt of cyclopentadiene, to form isopropylcyclopentadiene. The equilibrium of the reaction is continuously generated towards the direction of the isopropylcyclopentadiene. Meanwhile, due to the adoption of low-temperature reaction, the dissolving capacity of dimethyl sulfoxide to potassium hydroxide is limited, and once the dimethyl sulfoxide is dissolved, the dimethyl sulfoxide can participate in the reaction, so that large excess potassium hydroxide can not exist, and the generation of 2-position isomers can be controlled. However, the patent prefers to add potassium hydroxide in portions under the protection of inert gas, and the method still has the defects of excessive monomer, too fast reaction and increased 2-site generation speed.
Further, the comparative example in patent JP2003055272A discloses that cyclopentadiene, potassium hydroxide and dimethyl sulfoxide were first allowed to coexist to form a solution, and then by adding 2-bromopropane dropwise to the solution, the selectivity was 64.8%, and the selectivity was poor.
The inventor discovers that 2-position isomer appears after the 2-bromopropane is dripped from the beginning in a stepwise manner (the conventional HPLC), and the 2-position isomer is continuously increased even if the reaction liquid is liquid-liquid two-phase and must be stopped in time along with the extension of the reaction time by researching the stepwise method and the one-step method for preparing the isopropylcyclopentadiene. The isopropyl cyclopentadiene is synthesized by a one-step method, 2-position isomers (existing HPLC) can not appear at the beginning by adjusting the feeding sequence and a proper feeding proportion and adopting a mode of dripping cyclopentadiene monomers, and the 1-position isopropyl cyclopentadiene can obtain higher selectivity by timely tracking and stopping a liquid phase.
The purpose of the invention is realized by the following technical scheme:
the method for preparing the isopropylcyclopentadiene comprises the following steps of firstly adding dimethyl sulfoxide, 2-bromopropane and potassium hydroxide to form slurry under the protection of nitrogen, and then adding cyclopentadiene into the slurry to react to obtain the isopropylcyclopentadiene.
In the above aspect of the present invention, it is preferable that cyclopentadiene is added to the slurry at such a rate that the reaction temperature does not exceed a temperature range of 10 ℃.
The feeding mass ratio of the dimethyl sulfoxide to the 2-bromopropane is 1-2: 1, and the preferable feeding mass ratio is 1: 1.
The potassium hydroxide of the present invention is preferably bulk potassium hydroxide.
The method for preparing the isopropylcyclopentadiene further comprises an isomerization step: and a step of selectively isomerizing 5-isopropylcyclopentadiene in isopropylcyclopentadiene to 1-isopropylcyclopentadiene by heating.
The temperature of the isomerization step of the present invention is from 12 ℃ to 25 ℃, preferably the temperature of the isomerization step is in the range of from 12 ℃ to 18 ℃.
Drawings
FIG. 1: example 1 HPLC chromatogram was taken from a sample taken after incubation at 10 ℃ for 1 h.
FIG. 2: example 1 HPLC profile was taken after 2h incubation at 10 ℃ for 2 h.
FIG. 3: example HPLC chromatogram was taken from a sample taken 12h after reconstitution in a 118 ℃ reaction vessel.
FIG. 4: example HPLC chromatogram determined by sampling after 12h of work-up in the reaction vessel at 218 ℃.
FIG. 5: example HPLC chromatogram was taken from a sample taken after 12h of work-up in a 312 ℃ reaction vessel.
FIG. 6: comparative example 1 HPLC profile of samples taken after addition of bulk potassium hydroxide.
FIG. 7: comparative example HPLC chromatogram obtained by sampling and detecting 12 hours after the completion in the reaction vessel at 112 ℃.
FIG. 8: comparative example 2 HPLC chromatogram was taken after incubation at 10 ℃ for 1 hour.
FIG. 9: comparative example HPLC chromatogram obtained by sampling and detecting 12 hours after the completion in the reaction vessel at 212 ℃.
Detailed Description
The detailed description is only for the purpose of further explaining or illustrating the present invention and should not be construed as limiting the present invention in any way, and the present invention is described in further detail below with reference to examples.
The cyclopentadiene monomer is obtained by cracking dicyclopentadiene at the high temperature of 170-180 ℃, and other reagents and materials are commercially available.
Example 1, 20 ℃ A5L reactor was charged with 100.0g (94.0% by titration) of a potassium hydroxide cake solid, 500.8g of dimethyl sulfoxide, and 500.4g of 2-bromopropane, at which time the reactor internal temperature was lowered to 16 ℃ and the rotation speed was about 300 rpm. Under the protection of nitrogen, cooling to 0 ℃, and beginning to drop monomer cyclopentadiene 100.4g, wherein the internal temperature is not more than 10 ℃, and the dropping is completed within 2h and 10min, and the internal temperature is 1.5 ℃. After the reaction was incubated for 1h, sampling HPLC (batch No. 0457-. After 3h, it was added to an N-heptane solution which had been cooled to 5 ℃ beforehand, and this solution was then added dropwise to 80g of a 1N hydrochloric acid solution. 90mL of water was added to promote the extraction of the layers. The organic phase was washed once with 100g of saturated brine. After washing, the organic layer was placed in a 18 ℃ reaction vessel and stirred for 12h, and HPLC (batch number: 0457-. The 5-isomer was reduced to 0.18%, the 1-isopropylcyclopentadiene 93.71%, and the 2-isomer was almost invisible (existing HPLC).
Example 2, 20 ℃ A5L reactor was charged with 100.0g (94.0% by titration) of a bulk solid of potassium hydroxide, 501.5g of dimethyl sulfoxide and 500.0g of 2-bromopropane at about 300 rpm. Under the protection of nitrogen, the temperature is cooled to-0.87 ℃, 97.7g of monomer cyclopentadiene is added dropwise, the internal temperature is not more than 10 ℃, and the dropping is completed within 1h and 25min, wherein the internal temperature is 1.0 ℃. After the reaction is carried out for 3 hours under the condition of heat preservation, 1N hydrochloric acid solution and 195.7g of water are added dropwise to promote the layered extraction. 501.5g of n-heptane were added, and the organic phase was washed once with 102.7g of saturated brine. After washing with water, the organic layer was placed in a 18 ℃ reaction vessel and stirred for 12 hours, and HPLC (batch No. 0461) 1020-. The 5-isomer was reduced to 1.11%, the 1-isopropylcyclopentadiene 92.35% and the 2-isomer was barely found (current HPLC).
Example 3, 20 ℃ into a 5L reaction vessel were charged 500.0g of dimethyl sulfoxide and 500.0g of 2-bromopropane. Setting the rotation speed at 339rpm, cooling to-0.86 ℃ under the protection of nitrogen, adding 93.0g of potassium hydroxide blocky solid at one time, continuously cooling to-2.53 ℃, adding 100.0g of monomer cyclopentadiene at one time, cooling to-4.88 ℃, raising the temperature quickly after 30min, wherein the internal temperature is-2.00 ℃, and then increasing to 8.80 ℃ after 22 min. After the reaction was carried out for 3 hours and 20 minutes with heat preservation, 500g of n-heptane solution cooled in advance was added. 240mL of 1N hydrochloric acid solution was added dropwise to adjust the pH to neutral. Water 100mL x 2 washing 2 times, the organic phase using 150g saturated salt water washing 1 time. After washing, the organic layer was placed in a 12 ℃ reaction vessel and stirred for 12h, and HPLC (batch number: 0457-. The 5-isomer was reduced to 1.36%, the 1-isopropylcyclopentadiene 92.00% and the 2-isomer was almost invisible (existing HPLC).
Comparative example 1, under the protection of nitrogen, the rotation speed was 330rpm, the reaction vessel was set to 0 ℃, 60g of dimethyl sulfoxide and 30g of 2-bromopropane were added, the temperature was lowered to 8.5 ℃ by stirring, and 10g of cyclopentadiene monomer was added all at once. Controlling the temperature within 0-10 ℃, and adding 7.41g of blocky potassium hydroxide in batches within 4 h. After the addition, sampling HPLC (lot number: 0466-. The 5-position isomer is reduced to 0.12 percent, the 1-position isopropylcyclopentadiene is reduced to 76.74 percent, and the 2-position isopropylcyclopentadiene is reduced to 10.64 percent.
Comparative example 2, 470g of dimethyl sulfoxide and 61g of potassium hydroxide in bulk form were added to a 2L reaction vessel, and the mixture was stirred under nitrogen atmosphere to cool to 15 ℃ to begin dropping 100g of cyclopentadiene monomer, after dropping for 1 hour, the internal temperature was 18 ℃. Keeping the temperature to react for 2 hours to prepare the potassium cyclopentadienyl solution. 333g of n-heptane was added at the same temperature, and 147.6g of 2-bromopropane was added dropwise after the temperature was decreased to 10 ℃. After 2.5h of dropping, the reaction was carried out at an internal temperature of 8 ℃ for 1h and sample HPLC (batch No. 0457-1020-180207-1h) was added, and after 2.5h, 503g of N-heptane was added, and 1N hydrochloric acid was quenched for neutralization. The layers were separated and the organic layer was washed 2 times with 100mL of water. The mixture was washed 1 time with 100mL of saturated saline. After washing, the organic layer was placed in a 12 ℃ reaction vessel and stirred for 12h, and HPLC (batch number: 0457-. The 5-position isomer is reduced to 0.91 percent, 1-position isopropyl cyclopentadiene 76.06 percent and 2-position isopropyl cyclopentadiene 10.18 percent.
The liquid phase analysis data is summarized as follows:
the foregoing is only a preferred embodiment of the invention and is not intended to limit the scope of the invention, which is defined broadly in the claims appended hereto, and any other technical entity or method that is encompassed by the claims, either literally or under the doctrine of equivalents, is encompassed by the claims.
Claims (3)
1. A method for preparing 1-isopropylcyclopentadiene, the said method comprises the following steps, under the protection of nitrogen, add dimethyl sulfoxide, 2-bromopropane and blocky potassium hydroxide to form the slurry, then react and get isopropylcyclopentadiene by adding cyclopentadiene into said slurry with the speed that the reaction temperature does not exceed the temperature range of 10 duC, 5-isopropylcyclopentadiene in isopropylcyclopentadiene is isomerized into 1-isopropylcyclopentadiene selectively by heating, the temperature range of the isomerization step is 12 duC to 18 duC.
2. The method of claim 1, wherein the charged mass ratio of dimethyl sulfoxide to 2-bromopropane is 1-2: 1.
3. The process of claim 1, wherein the dimethyl sulfoxide and 2-bromopropane are fed in a mass ratio of 1: 1.
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|---|---|---|---|---|
| JP2001097916A (en) * | 1999-09-28 | 2001-04-10 | Asahi Kasei Corp | Method for producing hinokitiol |
| CN1291970A (en) * | 1998-03-30 | 2001-04-18 | 旭化成工业株式会社 | Process for producing hinokitiol |
| CN101602656A (en) * | 2009-07-20 | 2009-12-16 | 辽宁科技大学 | A kind of synthetic method of hinokitiol |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1291970A (en) * | 1998-03-30 | 2001-04-18 | 旭化成工业株式会社 | Process for producing hinokitiol |
| JP2001097916A (en) * | 1999-09-28 | 2001-04-10 | Asahi Kasei Corp | Method for producing hinokitiol |
| CN101602656A (en) * | 2009-07-20 | 2009-12-16 | 辽宁科技大学 | A kind of synthetic method of hinokitiol |
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| Title |
|---|
| Angular dependence of hydrogen magnetic resonance contact shifts in substituted nickelocenes. Molecular structure of bis(η5-isodicyclopentadienyl)nickel(II);Scroggins, William T.等，;《Inorganic Chemistry》;19760601;第1381-1390页 * |
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