CN113979864A - One-pot synthesis method of novel menthol carbonate cooling agent and application of novel menthol carbonate cooling agent in cigarettes - Google Patents
One-pot synthesis method of novel menthol carbonate cooling agent and application of novel menthol carbonate cooling agent in cigarettes Download PDFInfo
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- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 229940041616 menthol Drugs 0.000 title claims abstract description 40
- 239000002826 coolant Substances 0.000 title claims abstract description 37
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 title claims abstract description 35
- 238000000034 method Methods 0.000 title claims abstract description 22
- 235000019504 cigarettes Nutrition 0.000 title claims abstract description 16
- 238000005580 one pot reaction Methods 0.000 title claims abstract description 13
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 title claims abstract 18
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 241000208125 Nicotiana Species 0.000 claims abstract description 19
- 235000002637 Nicotiana tabacum Nutrition 0.000 claims abstract description 19
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 12
- 230000022244 formylation Effects 0.000 claims abstract description 10
- 238000006170 formylation reaction Methods 0.000 claims abstract description 10
- 239000000758 substrate Substances 0.000 claims abstract description 10
- 150000002191 fatty alcohols Chemical class 0.000 claims abstract description 9
- 230000000694 effects Effects 0.000 claims abstract description 8
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 7
- 230000000391 smoking effect Effects 0.000 claims abstract description 7
- 239000000654 additive Substances 0.000 claims abstract description 6
- 238000007043 one-pot condensation reaction Methods 0.000 claims abstract description 6
- 230000000996 additive effect Effects 0.000 claims abstract description 5
- 235000019505 tobacco product Nutrition 0.000 claims abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 3
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 238000001308 synthesis method Methods 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 5
- 239000003513 alkali Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 5
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- 239000007787 solid Substances 0.000 abstract description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 22
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 9
- -1 fatty alcohol compound Chemical class 0.000 description 8
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 238000003403 chloroformylation reaction Methods 0.000 description 3
- SYCXJIPGDBATKA-UHFFFAOYSA-N ethyl (5-methyl-2-propan-2-ylcyclohexyl) carbonate Chemical compound CCOC(=O)OC1CC(C)CCC1C(C)C SYCXJIPGDBATKA-UHFFFAOYSA-N 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 239000003205 fragrance Substances 0.000 description 3
- 238000006452 multicomponent reaction Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- XKXIQBVKMABYQJ-UHFFFAOYSA-M tert-butyl carbonate Chemical compound CC(C)(C)OC([O-])=O XKXIQBVKMABYQJ-UHFFFAOYSA-M 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 206010003497 Asphyxia Diseases 0.000 description 2
- 235000006679 Mentha X verticillata Nutrition 0.000 description 2
- 235000002899 Mentha suaveolens Nutrition 0.000 description 2
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 2
- 206010037423 Pulmonary oedema Diseases 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 208000005333 pulmonary edema Diseases 0.000 description 2
- 239000000779 smoke Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000002341 toxic gas Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- NFLGAXVYCFJBMK-RKDXNWHRSA-N (+)-isomenthone Natural products CC(C)[C@H]1CC[C@@H](C)CC1=O NFLGAXVYCFJBMK-RKDXNWHRSA-N 0.000 description 1
- BGUYVWYUIXKRDO-XYOKQWHBSA-N (6e)-2,6,10-trimethyldodeca-6,11-diene-2,3,10-triol Chemical compound CC(O)(C)C(O)CCC(/C)=C/CCC(C)(O)C=C BGUYVWYUIXKRDO-XYOKQWHBSA-N 0.000 description 1
- JFKCVAZSEWPOIX-GRYCIOLGSA-N 2-hydroxyethyl [(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] carbonate Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)OCCO JFKCVAZSEWPOIX-GRYCIOLGSA-N 0.000 description 1
- OSCILYIQKAVULO-UHFFFAOYSA-N 2-hydroxyethyl hydrogen carbonate;5-methyl-2-propan-2-ylcyclohexan-1-ol Chemical compound OCCOC(O)=O.CC(C)C1CCC(C)CC1O OSCILYIQKAVULO-UHFFFAOYSA-N 0.000 description 1
- FLYJSXDJKBHQAU-IBSWDFHHSA-N 2-hydroxypropyl [(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] carbonate Chemical compound CC(O)COC(=O)O[C@@H]1C[C@H](C)CC[C@H]1C(C)C FLYJSXDJKBHQAU-IBSWDFHHSA-N 0.000 description 1
- 238000006051 Asinger reaction Methods 0.000 description 1
- 238000005761 Biginelli synthesis reaction Methods 0.000 description 1
- 238000006150 Bucherer-Bergs reaction Methods 0.000 description 1
- 206010006784 Burning sensation Diseases 0.000 description 1
- 239000001338 FEMA 3805 Substances 0.000 description 1
- 238000006608 Hantzsch Dihydropyridine synthesis reaction Methods 0.000 description 1
- 238000006844 Kabachnik-Fields reaction Methods 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
- MXCRZZIYKYYFPP-UHFFFAOYSA-N Menthol propylene glycol carbonate Chemical compound OC(O)=O.CC(O)CO.CC(C)C1CCC(C)CC1O MXCRZZIYKYYFPP-UHFFFAOYSA-N 0.000 description 1
- NFLGAXVYCFJBMK-UHFFFAOYSA-N Menthone Chemical compound CC(C)C1CCC(C)CC1=O NFLGAXVYCFJBMK-UHFFFAOYSA-N 0.000 description 1
- ZBJCYZPANVLBRK-UHFFFAOYSA-N Menthone 1,2-glyceryl ketal Chemical compound CC(C)C1CCC(C)CC11OC(CO)CO1 ZBJCYZPANVLBRK-UHFFFAOYSA-N 0.000 description 1
- BLILOGGUTRWFNI-UHFFFAOYSA-N Monomenthyl succinate Chemical compound CC(C)C1CCC(C)CC1OC(=O)CCC(O)=O BLILOGGUTRWFNI-UHFFFAOYSA-N 0.000 description 1
- 238000006691 Passerini condensation reaction Methods 0.000 description 1
- 238000005990 Petasis reaction Methods 0.000 description 1
- 238000007059 Strecker synthesis reaction Methods 0.000 description 1
- 238000006058 Ugi-reaction Methods 0.000 description 1
- UJNOLBSYLSYIBM-WISYIIOYSA-N [(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] (2r)-2-hydroxypropanoate Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)[C@@H](C)O UJNOLBSYLSYIBM-WISYIIOYSA-N 0.000 description 1
- UJNOLBSYLSYIBM-SGUBAKSOSA-N [(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] 2-hydroxypropanoate Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)C(C)O UJNOLBSYLSYIBM-SGUBAKSOSA-N 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000035597 cooling sensation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- RBNPOMFGQQGHHO-UHFFFAOYSA-N glyceric acid Chemical compound OCC(O)C(O)=O RBNPOMFGQQGHHO-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229930007503 menthone Natural products 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 238000005648 named reaction Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 230000008786 sensory perception of smell Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- XKXIQBVKMABYQJ-UHFFFAOYSA-N tert-butyl hydrogen carbonate Chemical compound CC(C)(C)OC(O)=O XKXIQBVKMABYQJ-UHFFFAOYSA-N 0.000 description 1
- GLQWRXYOTXRDNH-UHFFFAOYSA-N thiophen-2-amine Chemical compound NC1=CC=CS1 GLQWRXYOTXRDNH-UHFFFAOYSA-N 0.000 description 1
- 238000010490 three component reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C68/00—Preparation of esters of carbonic or haloformic acids
-
- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- A24B3/00—Preparing tobacco in the factory
- A24B3/12—Steaming, curing, or flavouring tobacco
Abstract
The invention discloses a one-pot synthesis method of a novel menthol carbonate cooling agent and application thereof in cigarettes, wherein the method comprises the following steps of taking menthol and fatty alcohols as substrates and N, N' -carbonyldiimidazole as a formylation reagent in a reaction solvent for one-pot condensation reaction in an air environment, wherein the reaction general formula is as follows:
the invention adopts a one-pot synthesis method, in the air environment, the menthol and fatty alcohol are taken as substrates, N, N' -carbonyldiimidazole is taken as a formylation reagent, and the novel menthol carbonate cooling agent is prepared by one-pot condensation reaction in a reaction solvent, and the preparation process has mild reaction conditions and simple operation. In addition, the present inventionN, N '-carbonyldiimidazole is used as the formylating agent, and N' -carbonyldiimidazole is a white solid and is easy to transport and store. The novel menthol carbonate cooling agent prepared by the invention is added into tobacco products as a tobacco additive, and has the effects of improving the smoking comfort of cigarettes and clearing and benefiting throat.
Description
Technical Field
The invention belongs to the technical field of tobacco additives, and particularly relates to a one-pot synthesis method of a novel menthol carbonate cooling agent and application thereof in cigarettes.
Background
In daily life, a compound capable of generating a cooling sensation on the sense of smell, skin and oral cavity is generally called a cooling agent, and menthol is most known and most commonly used, but because the compound has strong mint fragrance and bitter taste when being used at a high concentration and also causes a burning sensation, so that the use of the compound in certain fields is influenced, fragrance chemists have searched for a substitute product or a derivative product of the menthol in the past decades, and a plurality of compounds which are considered safe are applied to industries such as food, tobacco, medicine, daily chemicals and the like, including various menthyl-containing derivatives and non-menthyl-containing derivatives, and the following are successful and commercialized: menthyl lactate (Frescolat ML FEMA #3748), menthol ethylene glycol carbonate (Frescolat MGC FEMA #3805), menthol propylene glycol carbonate (Frescolat MPC FEMA #3806) and menthone glycerol ketal (Frescolat MGA FEMA #3807), menthol glycerol ether of Japan high sand perfumery company (TK-10FEMA #3784), monomenthyl succinate of French VMF company (FEMA #3810), WS-3 of millennium Chemicals and Swiss Huaton company (FEMA #3455), WS-23 of millennium Chemicals and French Rodite company (FEMA #3804), etc. of Symrise, Germany.
The carbonate cooling agent is always one of the key directions of the chemical research of tobacco, and the preparation method commonly used at present is the traditional chemical synthesis method, but the traditional chemical synthesis process of the carbonate cooling agent needs a large amount of metal catalysts and ligands, high temperature and generates a large amount of waste. In addition, the chloroformylation reagent used in the prior preparation process is phosgene, and high concentration inhalation can cause pulmonary edema due to phosgene being a severe asphyxia toxic gas, which is not an ideal formylation reagent.
The present invention has been made to solve the above problems. The invention aims to provide a one-pot synthesis method of a novel menthol carbonate cooling agent, which can avoid the problems that a large amount of metal catalysts and ligands are needed, high temperature is high, a large amount of waste is generated and complex and toxic chloroformylation reagents are used in the traditional chemical synthesis process of the carbonate cooling agent.
Disclosure of Invention
The invention aims to provide a novel one-pot method for preparing carbonate cooling agents, aiming at the limitation of the traditional chemical synthesis method of the carbonate cooling agents. The method uses a one-pot reaction, and the carbonate cooling agent is obtained by the reaction of menthol, N' -carbonyldiimidazole and fatty alcohol in the air environment.
The invention adopts a one-pot synthesis method, in the air environment, the menthol and fatty alcohol are taken as substrates, N, N' -carbonyldiimidazole is taken as a formylation reagent, and the novel menthol carbonate cooling agent is prepared by one-pot condensation reaction in a reaction solvent, and the preparation process has mild reaction conditions and simple operation. In addition, the invention uses N, N '-carbonyl diimidazole as formylating agent, and the N' -carbonyl diimidazole is white solid and is easy to transport and store. The novel menthol carbonate cooling agent prepared by the invention is added into tobacco products as a tobacco additive, and has the effects of improving the smoking comfort of cigarettes and clearing and benefiting throat.
In order to achieve the purpose, the invention adopts the technical scheme that:
the invention provides a one-pot synthesis method of a novel menthol carbonate cooling agent, which comprises the following steps of carrying out one-pot condensation reaction in a reaction solvent by using menthol and fatty alcohol as substrates and N, N' -carbonyldiimidazole as a formylation reagent in an air environment, wherein the reaction general formula is as follows:
wherein the general formula of the fatty alcohol compound is ROH, and R is a substituent group such as alkyl.
Preferably, the aliphatic alcohol is one or more of methanol, ethanol or tert-butyl alcohol.
Preferably, the base of the present invention is Na2CO3NaOH, triethylamine or 1, 8-diazacyclo [5,4 ],0]one or more of undecene-7 are mixed for use.
Preferably, the solvent of the invention is one or a mixture of ethanol, acetonitrile, dimethyl sulfoxide and toluene.
Preferably, the molar ratio of the menthol to the N, N' -carbonyldiimidazole to the fatty alcohol to the base is (1-2) to (1-2): (1-2).
Preferably, the reaction temperature is between room temperature and 50 ℃, and the reaction time is 3-8 hours.
The second aspect of the invention provides an application of the novel menthol carbonate cooling agent prepared by the synthesis method of the first aspect of the invention in tobacco, and specifically, the novel menthol carbonate cooling agent is added into tobacco products as an additive for tobacco, so that the novel menthol carbonate cooling agent has the effects of improving the smoking comfort of cigarettes and clearing and benefiting throat.
Preferably, the novel menthol carbonate cooling agent is added into tobacco shreds according to the mass ratio of 0.0001-2%.
Compared with the traditional organic synthesis, the method has the unique advantages that:
1. the invention adopts a one-pot synthesis method, and in the air environment, menthol and fatty alcohol are taken as substrates, N, N' -carbonyldiimidazole is taken as a formylation reagent, and the novel menthol carbonate cooling agent is prepared by one-pot condensation reaction in a reaction solvent. Multi-component Reactions are Reactions in which three or more reaction materials are fed into a reactor and reacted under certain conditions to produce a single product, i.e., a "one-pot process". In the organic human name reaction, the multicomponent reaction is: asinger reaction, Biginelli reaction, Bucherer-Bergs reaction, Gewald aminothiophene synthesis,
-Blackburn-Bienaym-aminoimidazole Synthesis reaction, Hantzsch dihydropyridine Synthesis method, Kabachnik-Fields reaction, Liwanjun three-component reaction, Mannich reaction, Passerini reaction, Petasis reaction, Strecker amino acid Synthesis reaction, Ugi reaction, and the like. Some multi-component reactions have the advantages of simple and easily obtained raw materials, mild reaction conditions, simple operation, no need of separation of intermediates, high atom economy, high selectivity, small environmental pollution, easy realization of automation and the like, and are widely applied to the design and synthesis of new drugs, combinatorial chemistry and the synthesis of natural products.
2. The chloroformylation agent used in the prior preparation process is phosgene, and high concentration inhalation can cause pulmonary edema due to phosgene being a severe asphyxia toxic gas, and is not an ideal formylation agent. The invention uses N, N '-carbonyl diimidazole as formylation reagent, and the N' -carbonyl diimidazole is white solid, easy to transport and store and more ideal formylation reagent.
3. The invention can obtain a series of carbonate cooling agents with high yield under mild reaction conditions, and the carbonate cooling agents have wide application prospects in the synthesis of tobacco chemistry, natural products, medicines, pesticides and the like. The novel menthol carbonate cooling agent prepared by the invention is added into tobacco products as a tobacco additive, and has the effects of improving the smoking comfort of cigarettes and clearing and benefiting throat.
Drawings
FIG. 1 is a general reaction formula of the present invention, wherein the general formula of the fatty alcohol compound is ROH, and R is a substituent such as alkyl.
FIG. 2 shows the structural formula of ethyl (2-isopropyl-5-methylcyclohexyl) carbonate, a synthetic compound of the present invention.
FIG. 3 is a structural formula of the synthetic compound 2-isopropyl-5-methyl cyclohexyl methyl carbonate of the present invention.
FIG. 4 shows the structural formula of the synthesized compound of tert-butyl carbonate (2-isopropyl-5-methylcyclohexyl).
Detailed Description
The following specific embodiments:
the present invention will be described below with reference to specific examples, but the embodiments of the present invention are not limited thereto. The experimental methods not specified in the examples are generally commercially available according to the conventional conditions and the conditions described in the manual, or according to the general-purpose equipment, materials, reagents and the like used under the conditions recommended by the manufacturer, unless otherwise specified. The starting materials required in the following examples and comparative examples are all commercially available.
Example 1: (2-isopropyl-5-methylcyclohexyl) carbonic acid ethyl ester
A standard substrate of 46mg (1mmol) of ethanol and 156mg (1mmol) (-) -L-menthol was dissolved in 10mL of toluene, and the mixture was stirred and dissolved. To a 250mL round bottom flask were added 162mg (1mmol) of N, N' -carbonyldiimidazole and 304mg (2mmol) of 1, 8-diazacyclo [5,4,0] undecene-7 successively to effect a reaction at 50 ℃. The TLC detection reaction was carried out for about 5 hours, and the desired product, ethyl (2-isopropyl-5-methylcyclohexyl) carbonate, was obtained in 85% yield after extractive separation.
The product structure is as follows:
the nuclear magnetic spectrum of the obtained product is as follows:
1H NMR(400MHz,CDCl3):δ＝4.51(td,J＝4.4,11.4Hz,1H),4.23–4.17(m,2H),2.10–2.05(m,1H),1.99–1.92(m,1H),1.82–0.86(m,19H)ppm；13C NMR(100MHz,CDCl3):δ＝155.2,79.3,64.7,46.8,39.4,33.6,28.7,25.6,22.4,21.3,20.9,14.1ppm.
the obtained (2-isopropyl-5-methylcyclohexyl) ethyl carbonate is dissolved in food-grade ethanol, the solution is added into tobacco shreds according to the proportion of 0.01 percent of the mass of the tobacco shreds to prepare a heated cigarette, and the heated cigarette is compared with a control heated cigarette without the novel menthol carbonate cooling agent, so that the compound can improve the sweet and moist feeling of smoke, and clear and benefit the throat through smoke panel test.
Example 2: 2-isopropyl-5-methylcyclohexylcarbonate methyl ester
Substrate 32mg (1mmol) of methanol and 156mg (1mmol) (-) -L-menthol were used as standard substrates, and 10mL of toluene was added as a solvent, followed by dissolution with stirring. To a 250mL round bottom flask were added 162mg (1mmol) of N, N' -carbonyldiimidazole and 304mg (2mmol) of 1, 8-diazacyclo [5,4,0] undecene-7 successively to effect a reaction at 50 ℃. The TLC run was carried out for about 5 hours and the desired product was obtained in 78% yield after extractive separation.
The product structure is as follows:
the nuclear magnetic spectrum of the obtained product is as follows:
1H NMR(400MHz,CDCl3)δ4.51(td,J＝10.9,4.4Hz,1H),3.77(s,3H),2.13-2.04(m,1H),2.02-1.91(m,1H),1.74-1.63(m,2H),1.56-1.35(m,2H),1.14-0.99(m,2H),0.91(d,J＝6.9Hz,6H),0.85(m,1H),0.79(d,J＝7.0Hz,3H)ppm；13C NMR(101MHz,CDCl3)δ155.5,78.4,54.5,47.0,40.7,34.1,31.4,26.0,23.3,22.0,20.7,16.3ppm；HRMS(EI)Found:214.1571.Calcd for C12H22O3:214.1565.
the obtained 2-isopropyl-5-methyl cyclohexyl methyl carbonate is dissolved in food grade ethanol, added into tobacco shreds according to the proportion of 0.02 percent of the mass of the tobacco shreds to prepare a heated cigarette, and compared with a control heated cigarette without the 2-isopropyl-5-methyl cyclohexyl methyl carbonate, the compound can improve the comfort level, enrich the fragrance amount, clear the throat and benefit the throat through the test smoking.
Example 3: carbonic acid tert-butyl ester (2-isopropyl-5-methylcyclohexyl)
A standard substrate of 74mg (1mmol) of t-butanol and 156mg (1mmol) (-) -L-menthol was dissolved in 10mL of toluene, and the mixture was stirred and dissolved. To a 250mL round bottom flask were added 162mg (1mmol) of N, N' -carbonyldiimidazole and 304mg (2mmol) of 1, 8-diazacyclo [5,4,0] undecene-7 successively to effect a reaction at 50 ℃. The TLC run was about 5 hours and the desired product was obtained in 68% yield after extractive separation.
The product structure is as follows:
the nuclear magnetic spectrum of the obtained product is as follows:
1H NMR(400MHz,CDCl3)δ4.45(td,J＝10.8,4.0Hz,1H),2.02(m,1H),2.00-1.89(m,1H),1.65(m,2H),1.46-1.44(m,11H),1.04(m,2H),0.89-0.86(m,7H),0.77(d,J＝7.0Hz,3H)ppm；13C NMR(101MHz,CDCl3)δ154.7,81.4,77.7,47.0,40.7,34.1,31.4,27.8,26.0,23.3,22.0,20.6,16.1ppm；HRMS(EI)Found:256.2039.Calcd for C15H28O3:256.2042.
the obtained tert-butyl carbonate (2-isopropyl-5-methylcyclohexyl) is dissolved in food grade ethanol, the solution is added into tobacco shreds according to the proportion of 0.001% of the mass of the tobacco shreds to prepare a heated cigarette, and the compound can improve the comfort and has a cool feeling similar to mint through the test smoking compared with a control heated cigarette without the tert-butyl carbonate (2-isopropyl-5-methylcyclohexyl).
Claims (8)
1. A one-pot synthesis method of a novel menthol carbonate cooling agent is characterized in that in an air environment, menthol and fatty alcohol are used as substrates, N, N' -carbonyldiimidazole is used as a formylation reagent, and the reaction is carried out in a reaction solvent through one-pot condensation reaction, wherein the reaction general formula is as follows:
2. the method for synthesizing a novel menthol carbonate cooling agent according to claim 1, wherein the aliphatic alcohol is one or a mixture of methanol, ethanol and tert-butyl alcohol.
3. The method for synthesizing a novel menthol carbonate cooling agent according to claim 1, wherein the alkali is Na2CO3NaOH, triethylamine or 1, 8-diazacyclo [5,4,0]]One or more of undecene-7 are mixed.
4. The method for synthesizing the novel menthol carbonate cooling agent according to claim 1, wherein the reaction solvent is one or a mixture of ethanol, acetonitrile, dimethyl sulfoxide and toluene.
5. The method for synthesizing a novel menthol carbonate cooling agent according to claim 1, wherein the molar ratio of the reaction menthol to the N, N' -carbonyldiimidazole to the fatty alcohol to the base is (1-2): (1-2).
6. The method for synthesizing a novel menthol carbonate cooling agent according to claim 1, wherein the reaction temperature is from room temperature to 50 ℃ and the reaction time is from 3 to 8 hours.
7. The application of the novel menthol carbonate cooling agent prepared by the synthesis method of any one of claims 1 to 6 in tobacco is characterized in that the novel menthol carbonate cooling agent is added into tobacco products as a tobacco additive and has the effects of improving the smoking comfort of cigarettes and clearing and benefiting throat.
8. The use according to claim 1, characterized in that the novel menthol carbonate cooling agent is added to tobacco shreds in a mass proportion of 0.0001-2%.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1616406A (en) * | 2003-11-14 | 2005-05-18 | 上海香料研究所 | Method for synthesizing L-menthol glycol carbonic ester |
| CN102153475A (en) * | 2011-01-27 | 2011-08-17 | 台州市尔康药业有限公司 | Preparation method for mint derivatives |
| JP2012230356A (en) * | 2011-04-15 | 2012-11-22 | Sumitomo Chemical Co Ltd | Compound, resist composition and method for producing resist pattern |
| CN111517957A (en) * | 2019-01-16 | 2020-08-11 | 北京工商大学 | Perilla alcohol and menthol carbonate spice |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1616406A (en) * | 2003-11-14 | 2005-05-18 | 上海香料研究所 | Method for synthesizing L-menthol glycol carbonic ester |
| CN102153475A (en) * | 2011-01-27 | 2011-08-17 | 台州市尔康药业有限公司 | Preparation method for mint derivatives |
| JP2012230356A (en) * | 2011-04-15 | 2012-11-22 | Sumitomo Chemical Co Ltd | Compound, resist composition and method for producing resist pattern |
| CN111517957A (en) * | 2019-01-16 | 2020-08-11 | 北京工商大学 | Perilla alcohol and menthol carbonate spice |
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