Multi-nitrogen heterocyclic precursor aromatic compound as well as synthesis method and application thereof

Abstract

The invention belongs to the field of organic synthesis, and particularly relates to a polynitrogen heterocyclic precursor-aroma compound and a synthesis method and application thereof, and the method comprises the following steps: taking resorcinol with different substituent groups as a raw material, and reacting with a nornicotine compound under the action of a catalyst and alkali to generate the polynitrogen heterocyclic precursor-aroma compound. According to the method, normal-pressure 50-80 DEG C low-temperature reaction is adopted, high-pressure equipment is not needed, the reaction condition is mild, and operation is The target product yield is greater than or equal to 75%, and the product purity is greater than 95% (HPLC); the cheap manganese / ruthenium catalyst is adopted to replace precious metal, the production cost is reduced, raw materials are simple and easy to obtain, and the method is suitable for industrial production; after the target compound is added into a cigarette product, the baking flavor of tobacco can be remarkably improved, and the sensory score is improved by 20-30% compared with that of commercially available spices.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a polynitrogen heterocyclic latent aroma compound and a synthesis method and application thereof. Background Art

[0002] Polynitrogen heterocyclic compounds (such as bispyrrolidine benzene derivatives) are important aroma precursors in tobacco. After combustion and cracking, they can release a large amount of nitrogen-containing heterocyclic aroma substances, which increase the nutty aroma, roasted sweet aroma and other aromas of cigarettes. However, their natural content is extremely low and the extraction cost is high. At present, there are no reports on the synthesis of polynitrogen heterocyclic compounds such as bispyrrolidine benzene derivatives and their application in tobacco flavoring. Therefore, through manganese / ruthenium catalyzed condensation reaction, polynitrogen heterocyclic latent aroma compounds can be efficiently synthesized in one step and added to cigarette products, which can further highlight the style characteristics of cigarette products and improve their sensory quality. Summary of the invention

[0003] The purpose of the present invention is to provide a polynitrogen heterocyclic latent aroma compound and a synthesis method and application thereof, so as to solve the problems existing in the above-mentioned background technology.

[0004] To achieve the above objectives, this application is implemented through the following technical solutions:

[0005] A polynitrogen heterocyclic latent aroma compound, the structural formula of which is as follows:

[0006] , where R 1 =H, or (o,m,p)-CH 3 , or (o,m,p)-OCH 3 Alkyl or alkoxy, R 2 =H, or (o,m,p)-CH 3 , or (o,m,p)-OCH 3 Alkyl or alkoxy.

[0007] A method for synthesizing a polynitrogen heterocyclic latent aroma compound comprises the following steps:

[0008] S1. Under nitrogen protection, adding a reaction solvent and a resorcinol derivative into a dry reactor;

[0009] S2, adding the nornicotine derivative to the reactor, stirring evenly, and then adding a catalyst and a base;

[0010] S3, heating the reaction for 5-10 hours, stopping the reaction, filtering, drying, concentrating under reduced pressure and then recrystallizing to obtain a polynitrogen heterocyclic latent aroma compound.

[0011] Furthermore, the resorcinol derivative is an alkyl- or alkoxy-substituted resorcinol.

[0012] Furthermore, the nornicotine derivative is an alkyl or alkoxy substituted nornicotine.

[0013] Furthermore, the reaction solvent is one of tetrahydrofuran, methanol, toluene, dimethyl sulfoxide, o-xylene or acetonitrile.

[0014] Furthermore, the catalyst is

[0015] One of them.

[0016] Furthermore, the base is one of potassium carbonate, potassium tert-butoxide, sodium carbonate, sodium tert-butoxide, lithium tert-butoxide, triethylamine or DBU.

[0017] Furthermore, the molar ratio of the meta-diphenol derivative, the nornicotine derivative, the metal catalyst, and the base is: 1:2.0-2.1:0.05-0.08:0.15-0.2.

[0018] An application is the application of any of the above-mentioned polynitrogen heterocyclic latent aroma compounds as a tobacco flavoring agent.

[0019] Furthermore, the added amount of the polynitrogen heterocyclic latent aroma compound is 0.01%-0.1% of the weight of the tobacco.

[0020] The beneficial effects of the present invention are:

[0021] This technical solution uses a manganese / ruthenium catalyzed condensation reaction to efficiently synthesize a new type of polynitrogen heterocyclic latent aroma compound in one step, uses cheap manganese / ruthenium catalysts to replace precious metals, reduces production costs, has a low reaction temperature, mild reaction conditions, simple operation, and a high yield, which is very beneficial to actual industrial production. The target compound is added to cigarette products, and the aroma-causing components are slowly released through combustion, and the sensory score is improved by more than 25% compared with vanillin. DETAILED DESCRIPTION

[0022] The technical solution of the present invention is described in detail below through examples. The following examples are merely exemplary and can only be used to explain and illustrate the technical solution of the present invention, but cannot be construed as limiting the technical solution of the present invention.

[0023] The polynitrogen heterocyclic latent aroma compound involved in this application has the following structural formula:

[0024] , where R 1 =H, or (o,m,p)-CH 3 , or (o,m,p)-OCH 3 Alkyl or alkoxy, R 2 =H, or (o,m,p)-CH 3 , or (o,m,p)-OCH3 Alkyl or alkoxy.

[0025] The synthetic route of the polynitrogen heterocyclic latent aroma compound of the present application is as follows:

[0026] , where R 1 =H, or (o,m,p)-CH 3 , or (o,m,p)-OCH 3 Alkyl or alkoxy, R 2 =H, or (o,m,p)-CH 3 , or (o,m,p)-OCH 3 Alkyl or alkoxy.

[0027] The catalyst involved in this application is:

[0028] One of them.

[0029] Example 1

[0030] Synthesis of 1,3-bis(2-(pyridin-3-yl)pyrrolidin-1-yl)benzene (R 1 =H,R 2 =pyridin-3-yl):

[0031] Raw materials and ratio: resorcinol (11 g, 0.1 mol), nornicotine (29.6 g, 0.2 mol), [RuCl2(p-cymene)] 2 (0.52 g, 0.0008 mol), potassium tert-butoxide (1.1 g, 0.01 mol), and methanol 200 mL.

[0032] Steps: Under nitrogen protection, react at 50°C for 6 hours, and obtain 27.8 g of white solid after recrystallization (yield 75%).

[0033] Characterization data: melting point: 185-187 ° C; HRMS (ESI+): m / z 586.2543 [M+H]⁺ (theoretical value 586.2548); ¹H NMR (400 MHz, CDCl 3 ): δ 8.67-6.28 (aromatic ring and pyridine hydrogen), 4.60-3.26 (pyrrolidine hydrogen).

[0034] Comparative Example 1

[0035] Materials and conditions: Same as Example 1, omitting [RuCl2(p-cymene)] 2 .

[0036] Results: The product yield was less than 10%, and HPLC showed that the proportion of unreacted raw materials was greater than 80%, proving the key role of the catalyst.

[0037] Example 2

[0038] Synthesis of 1,3-bis(2-(pyrimidin-2-yl)pyrrolidin-1-yl)-4-methoxybenzene (R 1 =OCH 3 , R 2 =pyrimidin-2-yl):

[0039] Raw materials and proportions: 4-methoxyresorcinol (13.8 g, 0.1 mol), pyrimidinylnornicotine (32.1 g, 0.2 mol), manganese triacetate (0.48 g, 0.0008 mol), potassium carbonate (1.38 g, 0.01 mol), and toluene 200 mL.

[0040] Steps: React at 70°C for 8 hours to obtain 30.2 g of product (yield 78%).

[0041] Characterization data: Melting point: 192-194°C; ¹³C NMR (100 MHz, CDCl 3 ): δ 156.9 (pyrimidine-C), 113.4 (methoxy-C), and the remaining peaks were consistent with the target structure.

[0042] Example 3

[0043] Halogenated substrate expansion (R 1 =Cl):

[0044] Raw materials and proportions: 4-chlororesorcinol (14.3 g, 0.1 mol), nornicotine (29.6 g, 0.2 mol), manganese acetylacetonate (0.55 g, 0.0008 mol), potassium tert-butoxide (1.1 g, 0.01 mol), and acetonitrile 200 mL.

[0045] Steps: React at 60°C for 7 hours to obtain 28.5 g of product (yield 73%).

[0046] Characterization data: Melting point: 178-180℃; HRMS (ESI+): m / z 620.2105 [M+H]⁺ (theoretical value 620.2109).

[0047] Example 4

[0048] Amplification experiment verifies industrial feasibility:

[0049] Raw materials and proportions (expanded 10 times based on Example 1): resorcinol (110 g, 1.0 mol), nornicotine (296 g, 2.0 mol), [RuCl2(p-cymene)] 2 (5.2 g, 0.008 mol), potassium tert-butoxide (11 g, 0.1 mol), methanol 2 L.

[0050] Steps: React at 50°C for 6 hours, and obtain 275 g of product (yield 74%) after industrial-grade centrifugation purification.

[0051] Key indicators: Product purity: 96.5% (HPLC); Unit production capacity: 1.8 kg / batch (24-hour continuous production).

[0052] Application Examples

[0053] Method: The product of Example 1 was added to shredded tobacco at a rate of 0.05%, and a blind test was conducted by a professional smoking evaluation panel of 10 persons. The evaluation results are shown in Table 1.

[0054] Table 1

[0055]

[0056] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solution of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solution to deviate from the spirit and scope of the technical solution of the present invention.

Claims

1. A polynitrogen heterocyclic latent aroma compound, characterized in that: Its structural formula is as follows: , wherein R1=H, or (o,m,p)-CH3, or (o,m,p)-OCH3 alkyl or alkoxy, R2=H, or (o,m,p)-CH3, or (o,m,p)-OCH3 alkyl or alkoxy.

2. A method for synthesizing a polynitrogen heterocyclic latent aroma compound, characterized in that: Use the following steps: S1. Under nitrogen protection, adding a reaction solvent and a resorcinol derivative into a dry reactor; S2, adding the nornicotine derivative to the reactor, stirring evenly, and then adding a catalyst and a base; S3, heating the reaction for 5-10 hours, stopping the reaction, filtering, drying, concentrating under reduced pressure and then recrystallizing to obtain a polynitrogen heterocyclic latent aroma compound.

3. The method for synthesizing the polynitrogen heterocyclic latent aroma compound according to claim 2, characterized in that: Resorcinol derivatives are resorcinol substituted with alkyl or alkoxy groups.

4. The method for synthesizing the polynitrogen heterocyclic latent aroma compound according to claim 2, characterized in that: The nornicotine derivative is an alkyl or alkoxy substituted nornicotine.

5. The method for synthesizing the polynitrogen heterocyclic latent aroma compound according to claim 2, characterized in that: The reaction solvent is one of tetrahydrofuran, methanol, toluene, dimethyl sulfoxide, o-xylene or acetonitrile.

6. The method for synthesizing the polynitrogen heterocyclic latent aroma compound according to claim 2, characterized in that: The catalyst is: One of them.

7. The method for synthesizing the polynitrogen heterocyclic latent aroma compound according to claim 2, characterized in that: The base is one of potassium carbonate, potassium tert-butoxide, sodium carbonate, sodium tert-butoxide, lithium tert-butoxide, triethylamine or DBU.

8. The method for synthesizing the polynitrogen heterocyclic latent aroma compound according to claim 2, characterized in that: The molar ratio of the meta-diphenol derivative, the nornicotine derivative, the metal catalyst and the base is 1:2.0-2.1:0.05-0.08:0.15-0.

2.

9. An application, characterized in that, Use of the polynitrogen heterocyclic latent aroma compound according to any one of claims 1 to 8 as a tobacco flavoring agent.

10. The use according to claim 9, characterized in that: The added amount of the polynitrogen heterocyclic latent aroma compound is 0.01%-0.1% of the weight of the tobacco.

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