CN114437047A - N-substituted furyl pyrrole compound and preparation method and application thereof - Google Patents
N-substituted furyl pyrrole compound and preparation method and application thereof Download PDFInfo
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- CN114437047A CN114437047A CN202011199667.0A CN202011199667A CN114437047A CN 114437047 A CN114437047 A CN 114437047A CN 202011199667 A CN202011199667 A CN 202011199667A CN 114437047 A CN114437047 A CN 114437047A
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- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title claims abstract description 35
- -1 furyl pyrrole compound Chemical class 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 235000019504 cigarettes Nutrition 0.000 claims abstract description 20
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000002994 raw material Substances 0.000 claims abstract description 10
- CBOJBBMQJBVCMW-BTVCFUMJSA-N (2r,3r,4s,5r)-2-amino-3,4,5,6-tetrahydroxyhexanal;hydrochloride Chemical compound Cl.O=C[C@H](N)[C@@H](O)[C@H](O)[C@H](O)CO CBOJBBMQJBVCMW-BTVCFUMJSA-N 0.000 claims abstract description 5
- 229960001911 glucosamine hydrochloride Drugs 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 15
- 239000013067 intermediate product Substances 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 10
- 241000208125 Nicotiana Species 0.000 claims description 9
- 235000002637 Nicotiana tabacum Nutrition 0.000 claims description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 claims description 7
- 239000002168 alkylating agent Substances 0.000 claims description 6
- 229940100198 alkylating agent Drugs 0.000 claims description 6
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 6
- 229960000583 acetic acid Drugs 0.000 claims description 5
- 239000012043 crude product Substances 0.000 claims description 5
- 239000012362 glacial acetic acid Substances 0.000 claims description 5
- 239000003208 petroleum Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000003480 eluent Substances 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims description 3
- 229940073608 benzyl chloride Drugs 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000007832 Na2SO4 Substances 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 239000005454 flavour additive Substances 0.000 claims description 2
- 235000013355 food flavoring agent Nutrition 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000012044 organic layer Substances 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 239000012071 phase Substances 0.000 claims description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 2
- 235000011152 sodium sulphate Nutrition 0.000 claims description 2
- 238000003828 vacuum filtration Methods 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000003750 conditioning effect Effects 0.000 claims 1
- 239000003205 fragrance Substances 0.000 abstract description 9
- 230000000391 smoking effect Effects 0.000 abstract description 4
- 238000005804 alkylation reaction Methods 0.000 abstract description 2
- ITAZJLXFCHDSNJ-UHFFFAOYSA-N 4-(1H-pyrrol-2-yl)butane-1,1,1,4-tetrol Chemical compound OC(CCC(O)(O)O)c1ccc[nH]1 ITAZJLXFCHDSNJ-UHFFFAOYSA-N 0.000 abstract 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 abstract 1
- 238000011160 research Methods 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000000779 smoke Substances 0.000 description 5
- 238000011161 development Methods 0.000 description 4
- 235000019634 flavors Nutrition 0.000 description 4
- 150000003233 pyrroles Chemical class 0.000 description 4
- 235000013599 spices Nutrition 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- JDFUJAMTCCQARF-UHFFFAOYSA-N tatb Chemical compound NC1=C([N+]([O-])=O)C(N)=C([N+]([O-])=O)C(N)=C1[N+]([O-])=O JDFUJAMTCCQARF-UHFFFAOYSA-N 0.000 description 3
- 230000002152 alkylating effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- SXFVCNMIMDCJQF-UHFFFAOYSA-N CCOC(C(C1)C(C)N(C(C)C)C1C=O)=O Chemical compound CCOC(C(C1)C(C)N(C(C)C)C1C=O)=O SXFVCNMIMDCJQF-UHFFFAOYSA-N 0.000 description 1
- CBOJBBMQJBVCMW-UHFFFAOYSA-N D-(+)-Galactosamine Chemical compound Cl.O=CC(N)C(O)C(O)C(O)CO CBOJBBMQJBVCMW-UHFFFAOYSA-N 0.000 description 1
- 238000006945 Knorr synthesis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
- A24B15/18—Treatment of tobacco products or tobacco substitutes
- A24B15/28—Treatment of tobacco products or tobacco substitutes by chemical substances
- A24B15/30—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances
- A24B15/36—Treatment of tobacco products or tobacco substitutes by chemical substances by organic substances containing a heterocyclic ring
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention provides an N-substituted furyl pyrrole compound and a preparation method and application thereof, wherein glucosamine hydrochloride and acetylacetone are taken as raw materials to be heated and refluxed to obtain 2-methyl-3-acetyl-5-1 '2' 3 '4' -tetrahydroxybutyl pyrrole, then intramolecular cyclization reaction is carried out on the tetrahydroxybutyl pyrrole, and alkylation reaction is carried out, the obtained N-substituted furyl pyrrole compound is applied to cigarette perfuming, the fragrance is not easy to volatilize, and the N-substituted furyl pyrrole compound can be cracked at high temperature to release various micromolecular pyrrole volatile fragrance components, so that the fragrance quality and the smoking quality of cigarettes are improved.
Description
Technical Field
The invention belongs to the technical field of cigarette additives, and particularly relates to an N-substituted furyl pyrrole compound and a preparation method and application thereof.
Background
In recent years, with the continuous promotion of health consciousness of people, the safety concern of cigarette consumers to cigarettes is increasingly strengthened, the development of the tobacco industry is undoubtedly a serious test, and the research, development, production and sale of low-tar cigarette products are the great trends of the development of the tobacco industry in China. More than 95% of cigarette products in China are flue-cured type cigarettes, and the sugar-base ratio of the cigarettes is higher, so the smoke is more acidic, the proportion of free nicotine is less, the physiological strength of the smoke is lower, the smoke is softer, the smoke is less vigorous than that of mixed type cigarettes with the same tar content, and the tar reduction difficulty is higher. Therefore, the research on the flavor compensation of the low-tar flue-cured tobacco type cigarette is more urgent, so that the flavor and fragrance technology called as the core technology is widely regarded by high attention of the industry. In recent years, although the technical research of the tobacco flavor and fragrance in China has a certain progress, the research mainly aims at imitation, products with independent intellectual property rights are lacked, and compared with the international advanced level, the research has a larger gap mainly represented by weak basic research, lack of systematic research on the fragrance and no stable core competitiveness.
Azoles have been widely noted and used for their outstanding aroma characteristics and extremely low threshold. It is an important five-membered nitrogen heterocyclic compound, and many natural or non-natural pyrrole derivatives have obvious biological activity and are widely applied to other fields of medicines, foods, spices, daily cosmetics, pesticides and the like. More than 50 pyrrole derivatives are found in the volatile components of food at present, mainly comprise pyrrole and alkyl, acyl substitutes, hydrogenation products and indole compounds thereof, and most of the pyrrole derivatives have the characteristics of scorched aroma, firm aroma and soil-like aroma. The aromatic substance can be well applied to the research of cigarette flavoring and has very important significance to the application of cigarette flavoring.
Although the aroma characteristics of the pyrrole spices are outstanding, due to the defects of low threshold value (generally one part per million), strong volatility, easy loss of aroma and the like, the application of the pyrrole spice compound in food flavoring is correspondingly limited, and people always try to find a novel pyrrole latent aroma compound which can be cracked at high temperature to release small-molecular pyrrole volatile aroma components to replace volatile pyrrole spices.
There are many methods for synthesizing pyrrole and its derivatives, and the conventional and classical synthetic routes of pyrrole are known, i.e., Knorr synthesis and paal. In terms of synthetic routes, the methods can be roughly classified into a condensation method, a ring conversion method, a ring reduction method, and an expansion method, and the condensation method is most widely and deeply studied. With the continuous deepening of the knowledge of pyrrole, the development of more pyrrole derivatives with better flavor enhancement effect is urgently needed.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a novel N-substituted furyl pyrrole compound and a preparation method thereof, which can be used as a latent fragrant compound to be applied to cigarettes and have better flavoring effect.
In order to solve the technical problems, the invention adopts the following technical scheme:
an N-substituted furanylpyrrole compound having the structure:
wherein R is selected from any one of ethyl, butyl and benzyl.
Another object of the present invention is to provide a process for preparing the above N-substituted furanylpyrrole compound, which comprises the steps of:
(1) under the alkaline condition, taking glucosamine hydrochloride and acetylacetone as raw materials, heating and refluxing in aqueous solution, tracking and detecting by TLC, stopping reaction when the raw material point disappears, cooling and crystallizing, and recrystallizing the precipitated solid by acetone to obtain an intermediate product A;
(2) dissolving the intermediate product A in anhydrous methanol, adding glacial acetic acid, carrying out stirring reflux reaction, tracking and detecting by TLC, stopping the reaction when the raw material point disappears, adding anhydrous sodium carbonate into the reaction system, stirring to remove excessive acid, carrying out vacuum filtration, carrying out reduced pressure distillation, and recrystallizing with acetone to obtain an intermediate product B;
(3) mixing the intermediate product B with anhydrous potassium carbonate, acetonitrile, tetrabutylammonium bromide and an alkylating agent in a container for reaction, tracking and detecting by TLC, stopping the reaction when the raw material point disappears, distilling the acetonitrile under reduced pressure, adding water into the residue to dissolve the potassium carbonate, separating an organic layer, extracting a water phase with ethyl acetate, combining organic phases, and drying the anhydrous Na2SO4 overnight; and distilling off ethyl acetate under reduced pressure, and separating and purifying the crude product by column chromatography to obtain a final product.
Preferably, the alkaline condition in step (1) adopts sodium bicarbonate as the regulator, and the molar ratio of glucosamine hydrochloride, acetylacetone and sodium bicarbonate is as follows: 1: (1-1.3): (1.3-1.6).
Preferably, the ratio of the intermediate product A in the step (2) to the anhydrous methanol and the glacial acetic acid is (0.2-0.3) mmol: 1 ml: (0.05-0.15) ml.
Preferably, the molar ratio of the intermediate product B, anhydrous potassium carbonate, tetrabutylammonium bromide and the alkylating reagent in the step (3) is 1: (2.5-3.5): (0.1-0.3): (2.5-3.5).
Preferably, the alkylating agent is still optionally selected from any of bromoethane, n-bromobutane, benzyl chloride.
Preferably, the eluent for column chromatography in step (3) is a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 5: 3.
The invention also aims to provide the application of the N-substituted furyl pyrrole compound or the compound obtained by the method in the field of cigarette flavoring, and when the N-substituted furyl pyrrole compound or the compound is used as a tobacco shred flavoring additive, the dosage is 0.01-0.03 percent of the mass of tobacco shreds.
Compared with the prior art, the invention has the beneficial effects that:
the N-substituted furyl pyrrole compound obtained by the application is applied to cigarette flavoring, the fragrance is not easy to volatilize, and various micromolecular pyrrole volatile fragrance components can be released by cracking at high temperature, so that the fragrance quality and the smoke quantity are improved, and the cigarette smoking quality is improved.
Drawings
FIG. 1 is a synthetic scheme of the present invention.
Detailed Description
The present invention will be further described with reference to the following examples.
Example 1
(1) Synthesis of intermediate A
D (+) -glucosamine hydrochloride (431.21mg,2mmol) was dissolved in 15mL water and acetylacetone (240mg,2.4mmol) and NaHCO were added3(252mg,3 mmol). Refluxing for about 8h, tracking and monitoring by TLC, and stopping the reaction when the raw material point disappears. Standing at low temperature for about 24h, separating out white, filtering, recrystallizing the filtrate with acetone to obtain 0.418g of white solid 2-methyl-3-acetyl-5-1 '2' 3 '4' -tetrahydroxybutyl pyrrole (intermediate product A), with yield of 86%;
of intermediate A1H NMR(D2O,400.1MHz):δ:6.45(s,1H,CH),4.70(s,1H,CH),3.65(m,2H,H-1′,H-4′a),3.58(d,J＝2.9Hz,1H,CH),3.47-3.57(dd,J＝6.5Hz,1H,CH),2.36(s,3H,CH3),2.32(s,3H,CH3)；13CNMR(100.6MHz,D2O):δ:199.9(C＝O),137.9(C),130.5(C),119.8(C),108.0(CH＝C),73.8(CH),71.2(CH),66.3(CH),62.4(CH2),27.5(CH3),13.1(CH3)；HRMS:Calcd for[M+H]+.244.1185,Found:[M+H]+ 244.1188。
(2) Synthesis of intermediate B
Intermediate A (365mg, 1.5mmol) was dissolved in 5mL of anhydrous methanol, 0.5mL of glacial acetic acid was added, the mixture was heated under reflux for about 8h with stirring, and the reaction was stopped when the starting material disappeared completely by TLC follow-up. Then, a small amount of anhydrous sodium carbonate was added to the reaction system, and stirring was continued for about 30 minutes to remove excess acid, followed by suction filtration, reduced pressure distillation, and recrystallization from acetone to give a white solid product, 274mg, with a yield of 81.2%.
The mp of the compound is 164.4-166.7 ℃; IR (KBr) 3326,2922,1624,1590,1463,1050 cm-1;1H NMR 2.28(s,3H,CH3),2.32(s,3H,CH3)；3.74-3.77(t,J1＝1.72MHz,J2＝8.6MHz,H,CH)；4.13-4.18(m,J＝4.32MHz,J＝6.04MHz,2H,CH2)；4.18-4.20(d,J＝4.68MHz,1H,CH)；4.26-4.29(m,J＝1.76MHz,1H,CH),4.57-4.59(d,J＝8.44MHz,1H,CH)；6.54(s,1H,CH)；13C NMR(100MHz,CDCL3),δ:13.1(CH3),27.5(CH3),70.8(CH2),72.5(CH),75.2(CH)；75.5(CH),109.9(CH),120.0(C),127.5(C),138.9(C),199.6(C＝O)；HRMS calcd For[M+H]+ 226.1040,found[M+H]+ 226.1037。
(3) synthesis of Compound 1
Tetrabutylammonium bromide (TBAB) is used as a phase transfer catalyst, acetonitrile is used as a solvent, and an alkylating reagent ethyl bromide reacts with a compound 7 under the action of anhydrous potassium carbonate; a25 mL round bottom flask was charged with 1.5mmol of 0.338g of Compound 7, 4.5mmol anhydrous potassium carbonate, 6mL acetonitrile, 0.1g TATB and an amount of alkylating agent (4.5mmol, C)2H5Br) was heated for 24h and monitored by TLC following the reaction. The crude product is purified by column chromatography using eluent [ V (petroleum ether): V (ethyl acetate)]An orange-yellow thick was obtained at 5:3 and was denoted as compound 1.
Compound (I)1HNMR(CDCL3,400MHz),δ:1.63(m,3H,CH3),2.21(d,2H,OH),2.46(s,3H,CH3),3.69(s,1H,CH),3.82-3.98(d,2H,CH2),4.01(s,1H,CH),6.16(s,1H,CH)；13CNMR(100MHz,CDCL3),δ:11.9(CH3),19.2(CH2),24.1(CH2),28.4(CH3),36.9(CH2),73.3(CH2),76.9(CH),79.9(CH),86.3(CH),103,2(CH＝C),124.7(C),132.7(C),133.5(C),199.8(C＝O)；HRMS calcd For[M+H]+ 254.1351,found[M+H]+254.1353。
Example 2
In a 25mL round bottom flask was added 1.5mmol 0.338g compound 7, 4.5mmol anhydrous potassium carbonate, 6mL acetonitrile, 0.1g tatb, n-bromobutane was used instead of bromoethane and the other procedure was the same as above, the crude product was purified by column chromatography eluting with [ V (petroleum ether): V (ethyl acetate) ] -5: 3 to give an orange-yellow thick mass, which was identified as compound 2.
Compound (I)1HNMR(CDCL3,400MHz),δ:1.01(m,3H,CH3),1.39(m,2H,CH2),1.81(m,2H,CH2),1.99(s,2H,OH),2.21(m,3H,CH3),2.60(s,3H,CH3),3.81(s,1H,CH),3.88-4.01(m,2H,CH2),4.05(s,2H,CH2),5.20(s,1H,CH),6.11(CH)；13CNMR(100MHz,CDCL3),δ:11.6(CH3),14.2(CH3),21.3(CH2),28.4(CH3),34.8(CH2),49.6(CH),73.7(CH2),78.1(CH),80.8(CH2),86.5(CH),102.9(CH),125.5(C),131.9(C),133.7(C),199.6(C＝O)；HRMS calcd For[M+H]+ 282.1655,found[M+H]+282.1657。
Example 3
In a 25mL round bottom flask was added 1.5mmol 0.338g compound 7, 4.5mmol anhydrous potassium carbonate, 6mL acetonitrile, 0.1g tatb, benzyl chloride was used instead of ethyl bromide, the other procedure was the same as above, the crude product was separated and purified by column chromatography, and eluent [ V (petroleum ether): V (ethyl acetate) ] -5: 3 gave an orange-yellow thick substance, which was identified as compound 3.
Compound (I)1HNMR(CDCL3,400MHz),δ:1.98(s,2H,OH),2.19(d,3H,CH3),2.60(s,3H,CH3),3.64(s,1H,CH),3.81-4.02(d,3H,CH),5.15(d,3H,CH),6.19(CH),7.05-7.10(m,3H,Ar-H),7.18(d,2H,Ar-H)；13CNMR(100MHz,CDCL3),δ:6.5(CH3),29.8(CH3),42.8(CH2),73.7(CH2),78.1(CH),79.8(CH),86.3(CH),103.1(CH＝C),125.3(C),126.0(Ar-C),128.9(Ar-C),129.3(Ar-C),132.5(C),133.8(C),136.6(Ar-C),199.9(C＝O)；HRMS calcd For[M+H]+316.1510,found[M+H]+316.1507。
Perfuming test
Uniformly adding the compounds 1-3 into single cut tobacco according to different amounts, rolling into cigarettes, and performing comprehensive evaluation and scoring by a smoking evaluation expert, wherein the smoking evaluation result is shown in the following table 2:
TABLE 2 cigarette flavoring results
Wherein:
the control 1 sample was intermediate a obtained in example 1.
Control 2 sample was the product of an alkylation reaction using n-propyl bromide instead of ethyl bromide based on the preparation described in example 1.
Control 3 sample was ethyl N-isopropyl-2-methyl-5-formyl-3-pyrrolidinecarboxylate prepared according to the method described in CN 1049616691A.
The protective scope of the present invention is not limited to the above-described embodiments, and it is apparent that various modifications and variations can be made to the present invention by those skilled in the art without departing from the scope and spirit of the present invention. It is intended that the present invention cover the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents.
Claims (8)
1. An N-substituted furanylpyrrole compound having the structure:
wherein R is selected from any one of ethyl, butyl and benzyl.
2. The process for preparing an N-substituted furanylpyrrole compound according to claim 1 comprising the steps of:
(1) under the alkaline condition, taking glucosamine hydrochloride and acetylacetone as raw materials, heating and refluxing in aqueous solution, tracking and detecting by TLC, stopping reaction when the raw material point disappears, cooling and crystallizing, and recrystallizing the precipitated solid by acetone to obtain an intermediate product A;
(2) dissolving the intermediate product A in anhydrous methanol, adding glacial acetic acid, carrying out stirring reflux reaction, tracking and detecting by TLC, stopping the reaction when the raw material point disappears, adding anhydrous sodium carbonate into the reaction system, stirring to remove excessive acid, carrying out vacuum filtration, carrying out reduced pressure distillation, and recrystallizing with acetone to obtain an intermediate product B;
(3) mixing the intermediate product B with anhydrous potassium carbonate, acetonitrile, tetrabutylammonium bromide and an alkylating agent in a container for reaction, tracking and detecting by TLC, stopping the reaction when the raw material point disappears, distilling the acetonitrile under reduced pressure, adding water into the residue to dissolve the potassium carbonate, separating an organic layer, extracting a water phase with ethyl acetate, combining organic phases, and drying the anhydrous Na2SO4 overnight; and distilling off ethyl acetate under reduced pressure, and separating and purifying the crude product by column chromatography to obtain a final product.
3. The process according to claim 2, wherein the alkaline conditions of step (1) are carried out using sodium bicarbonate as the conditioning agent, and the molar ratio between glucosamine hydrochloride, acetylacetone and sodium bicarbonate is: 1: (1-1.3): (1.3-1.6).
4. The preparation method of claim 2, wherein the ratio of the intermediate product A in the step (2) to the absolute methanol and the glacial acetic acid is (0.2-0.3) mmol: 1 ml: (0.05-0.15) ml.
5. The method according to claim 2, wherein the molar ratio of the intermediate product B, anhydrous potassium carbonate, tetrabutylammonium bromide and the alkylating agent in the step (3) is 1: (2.5-3.5): (0.1-0.3): (2.5-3.5).
6. The process of claim 2, wherein the alkylating agent is still optionally selected from any of ethyl bromide, n-bromobutane and benzyl chloride.
7. The method according to claim 2, wherein the eluent for column chromatography in step (3) is a mixture of petroleum ether and ethyl acetate in a volume ratio of 5: 3.
8. The application of the N-substituted furyl pyrrole compound of claim 1 or the compound prepared by the preparation method of any one of claims 2 to 7 in the field of cigarette flavoring is characterized in that the N-substituted furyl pyrrole compound or the compound is used as a tobacco shred flavoring additive, and the dosage of the N-substituted furyl pyrrole compound or the compound is 0.01 to 0.03 percent of the mass of tobacco shreds.
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| CN104961669A (en) * | 2015-03-18 | 2015-10-07 | 河南农业大学 | Preparation method for N-alkyl-2-methyl-5-formyl-3-pyrrole formate and application of N-alkyl2-methyl-5-formyl-3-pyrrole formate in cigarette flavoring |
| CN105777678A (en) * | 2016-03-30 | 2016-07-20 | 云南中烟工业有限责任公司 | 2-methyl ester based furan flavor enhancer compound, preparation method thereof and application thereof in cigarette moisture retention |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104961669A (en) * | 2015-03-18 | 2015-10-07 | 河南农业大学 | Preparation method for N-alkyl-2-methyl-5-formyl-3-pyrrole formate and application of N-alkyl2-methyl-5-formyl-3-pyrrole formate in cigarette flavoring |
| CN105777678A (en) * | 2016-03-30 | 2016-07-20 | 云南中烟工业有限责任公司 | 2-methyl ester based furan flavor enhancer compound, preparation method thereof and application thereof in cigarette moisture retention |
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