Nitrogen-containing compound with medicinal herb fragrance, preparation method of nitrogen-containing compound and medicinal herb fragrance base

Abstract

The invention relates to the technical field of flavors and fragrances, in particular to a nitrogen-containing compound with medicinal herb fragrance, a preparation method of the nitrogen-containing compound and a medicinal herb fragrance base. The nitrogen-containing compound with the medicinal herb fragrance has the following structural formula: 1-(1H-indole-3-yl)-9H-pyrido [3, 4-b] indole, and the compound has the special medicinal herb spicy fragrance, has a little flower sweet fragrance, and is elegant in fragrance and long in fragrance holding time. The preparation method of the compound is simple in process, convenient to operate and control, high in production efficiency and suitable for industrial production. The herbal incense base prepared by the invention is added with the nitrogen-containing compound with herbal fragrance, and compared with the herbal incense base without the compound, the herbal incense base has more prominent herbal fragrance, characteristic herbal spicy fragrance is accompanied by fresh and sweet fragrance and has little flower fragrance, and the fragrance quality of the incense base is obviously improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of essence and flavor technology, and particularly relates to a nitrogen-containing compound with herbal fragrance, a preparation method thereof and a herbal fragrance base. BACKGROUND

[0002] Some traditional flavor compounds have certain herbal fragrance or floral fragrance, but there are deficiencies in the uniqueness and persistence of fragrance. For example, benzoic acid leaf alcohol ester (CAS No. 25152-85-6) has green, herbal, sweet, floral, spicy and fruity fragrance, but it is difficult to meet the needs of high-end daily chemical products in terms of fragrance retention time and other properties. In view of this, the present application researches a nitrogen-containing compound with herbal fragrance, and the developed compound has special herbal spicy fragrance and a little floral sweet fragrance. The chemical fragrance is elegant, and the fragrance retention time is long. The compound has important application value in the field of daily chemical flavoring, and has not been put forward by domestic and international essence and flavor companies. Therefore, the compound has important application value and broad market prospect in the field of flavoring. SUMMARY

[0003] In order to overcome the shortcomings and deficiencies in the prior art, the purpose of the present application is to provide a nitrogen-containing compound with herbal fragrance. The compound has special herbal spicy fragrance and a little floral sweet fragrance, the fragrance is elegant, the fragrance retention time is long, and the compound has important application value and market prospect in the field of flavoring.

[0004] Another purpose of the present application is to provide a preparation method of the nitrogen-containing compound with herbal fragrance. The preparation method is simple in process, easy to operate and control, high in production efficiency, and suitable for industrial production.

[0005] Still another purpose of the present application is to provide a herbal fragrance base. The herbal fragrance base is added with the nitrogen-containing compound with herbal fragrance. Compared with the herbal fragrance base without the compound, the herbal fragrance base has more prominent medicinal fragrance, characteristic herbal spicy fragrance accompanied by sweet fragrance, a little floral fragrance, and significantly improved fragrance quality.

[0006] The purpose of the present application is achieved by the following technical scheme: a nitrogen-containing compound with herbal fragrance has the following structural formula:

[0007]

[0008] The nitrogen-containing compound with herbal fragrance can be named as 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole.

[0009] The nitrogen-containing compound with herbal aroma of the present application is prepared by deprotonating aromatic ring through key Knochel-Hauser base, preparing zinc reagent through transmetalation, completing construction of key carbon-carbon bond under palladium catalysis, and finally preparing through trifluoroacetic acid catalyzed deprotection reaction, and has special herbal aroma and a little flower sweet aroma, and has important use in daily chemical perfumery field.

[0010] Another purpose of the present application is achieved by the following technical scheme: a preparation method of the nitrogen-containing compound with herbal aroma, comprising the following steps:

[0011] Step one: using compound and Boc2O as raw materials to prepare 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester, and the structure of the compound is shown in the following formula:

[0012]

[0013] The structure of 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester is shown in the following formula:

[0014]

[0015] Step two: using bromide and 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step one as raw materials to prepare 1-(1-(tert-butoxy carbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester, and the structure of the bromide is shown in the following formula:

[0016]

[0017] The structure of 1-(1-(tert-butoxy carbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester is shown in the following formula:

[0018]

[0019] Step three: using 1-(1-(tert-butoxy carbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step two as raw material, and after separation and purification, a nitrogen-containing compound with herbal aroma is obtained, and the nitrogen-containing compound with herbal aroma is 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole.

[0020] Further, in step one, the preparation method of 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester comprises the following steps:

[0021] A1, the compound is placed in a reaction vessel, DMAP and THF are added for dissolution, ice bath cooling to -1 -1℃, then slowly add Boc2O, maintain the reaction for 4-8 hours;

[0022] A2, after TLC detection of the complete disappearance of the raw material, the added ammonium chloride aqueous solution is used for quenching reaction, the organic phase is separated, and the water phase is extracted with ethyl acetate, the combined organic phase is dried and concentrated, and then column chromatography is used to separate the white solid product, i.e. 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester is obtained.

[0023] Further, in step A1, 15-25 g of the compound is placed in a reaction vessel, 1.2-1.6 g of DMAP and 150-170 mL of THF are added for dissolution, ice bath cooling to -1 -1℃, then slowly add 20-30 g of Boc2O, maintain the reaction for 4-8 hours.

[0024] Further, in step two, the preparation method of 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester includes the following steps:

[0025] B1, under the protection of argon, 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step one is dissolved in THF and placed in reaction bottle A, then slowly add TMPMgCl·LiCl THF / toluene solution, maintain stirring for 0.2-0.8 hours, then add zinc chloride THF solution, continue stirring for 0.2-0.8 hours, to obtain mixture one;

[0026] B2, in another reaction bottle B filled with argon protection, add bromide, catalyst XPhos Pd G3 and tetrahydrofuran, stir for 0.2-0.8 hours to obtain mixture two;

[0027] B3, mixture two prepared in reaction bottle B in step B2 is added to mixture one prepared in reaction bottle A in step B1, and the reaction is carried out at room temperature for 22-26 hours until the raw material is completely disappeared;

[0028] B4, after the reaction is completed, saturated ammonium chloride aqueous solution and saturated brine are added to the reaction system for quenching reaction, the organic phase is separated, then the water phase is extracted with ethyl acetate, the combined organic phase is dried and concentrated, and then column chromatography is used to separate the white solid, i.e. 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester is prepared.

[0029] Further, in step B1, 250-300 mg of 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step one is dissolved in 1-5 mL of THF and placed in reaction bottle A, then 1.2-1.8 mL of 0.5-1 mol / L TMPMgCl.LiCl THF / toluene solution is slowly added, stirring is maintained for 0.2-0.8 hours, then 0.2-1 mL of 1-2 mol / L zinc chloride THF solution is added, stirring is continued for 0.2-0.8 hours to obtain mixture one.

[0030] Further, in step B2, 250-350 mg of bromide, 45-55 mg of catalyst XPhos Pd G3 and 1-5 mL of tetrahydrofuran are added to another argon-protected reaction bottle B, stirring is carried out for 0.2-0.8 hours to obtain mixture two.

[0031] Further, in step three, the preparation method of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole includes the following steps:

[0032] C1, 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step two, dichloromethane and trifluoroacetic acid are sequentially added to the reactor, and stirring is carried out for 2-4 hours;

[0033] C2, after the reaction is completed, the reactant prepared in step C1 is diluted with dichloromethane, then saturated sodium bicarbonate solution is added for quenching reaction, after the organic phase is separated, the water phase is extracted with dichloromethane, the combined organic phase is dried and concentrated, then yellow solid is obtained by silica gel column chromatography, that is, 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole is prepared.

[0034] Further, in step C1, 900-1000 mg of 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step two, 10-30 mL of dichloromethane and 1-3 mL of trifluoroacetic acid are sequentially added to the reactor, and stirring is carried out for 2-4 hours.

[0035] Another object of the present application is achieved by the following technical solution: a medicinal herb fragrance base, comprising the following raw materials in parts by weight: 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole 45-55 parts, sandalwood oil 8-12 parts, linalyl acetate 12-18 parts, yohimbe extract 25-35 parts, decanal 20-30 parts, patchouli oil 2-8 parts, phenethyl alcohol 12-16 parts, eugenol 15-25 parts, isoamyl butyrate 2-6 parts, geraniol 55-65 parts, linalool oxide 20-30 parts, borneol 75-85 parts, vetiver oil 6-10 parts, ethyl heptanoate 15-25 parts, ionone 6-10 parts, and propylene glycol 600-700 parts.

[0036] The present application has the following advantages: the nitrogen-containing compound with medicinal herb fragrance prepared by the present application is 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole, the key Knochel-Hauser base of the compound is deprotonated on an aromatic ring, then a zinc reagent is prepared by transmetalation, a key carbon-carbon bond is constructed under palladium catalysis, and finally the compound is prepared by a trifluoroacetic acid catalyzed deprotection reaction, which has a special medicinal herb spicy fragrance, a little flower sweet fragrance, elegant fragrance, long fragrance retention time, important application value in the field of fragrance modulation, and market prospects. The preparation method of the compound is simple in process, easy to operate and control, high in production efficiency, and suitable for industrial production. The medicinal herb fragrance base prepared by the present application is added with the above-mentioned nitrogen-containing compound with medicinal herb fragrance, and compared with the medicinal herb fragrance base without the compound, the medicinal herb fragrance base has more outstanding medicinal herb fragrance, characteristic medicinal herb spicy fragrance accompanied by sweet fragrance, a little flower fragrance, and significantly improved fragrance quality of the fragrance base. BRIEF DESCRIPTION OF DRAWINGS

[0037] Figure 1 The hydrogen spectrum of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole prepared in Example 1.

[0038] Figure 2 The carbon spectrum of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole prepared in Example 1.

[0039] Figure 3 The gas chromatogram of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole prepared in Example 1. DETAILED DESCRIPTION

[0040] In order to facilitate the understanding of those skilled in the art, the present application is further described below in conjunction with examples and drawings, and the content mentioned in the embodiments is not a limitation on the present application.

[0041] In an embodiment of the present application, a nitrogen-containing compound with herbal fragrance has the following structural formula:

[0042]

[0043] The nitrogen-containing compound with herbal fragrance can be named as 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole.

[0044] In an embodiment of the present application, a preparation method of the nitrogen-containing compound with herbal fragrance comprises the following steps:

[0045] In step one, 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester is prepared from a compound and Boc2O, and the compound has the following structural formula:

[0046]

[0047] The 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester has the following structural formula:

[0048]

[0049] In step two, 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester is prepared from a bromide and the 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step one, and the bromide has the following structural formula:

[0050]

[0051] The 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester has the following structural formula:

[0052]

[0053] In step three, the 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step two is used as a raw material, and after separation and purification, the nitrogen-containing compound with herbal fragrance is obtained, and the nitrogen-containing compound with herbal fragrance is 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole.

[0054] Further, in step one, the preparation method of the 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester comprises the following steps:

[0055] A1, the compound is placed in a reaction vessel, DMAP and THF are added for dissolution, ice bath cooling to -1 -1℃, then slowly add Boc2O, maintain the reaction for 4-8 hours;

[0056] A2, after TLC detection of the complete disappearance of the raw material, the added ammonium chloride aqueous solution is used for quenching reaction, the organic phase is separated, and the water phase is extracted with ethyl acetate, the combined organic phase is dried and concentrated, and then column chromatography is used to separate the white solid product, i.e. 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester is obtained.

[0057] Further, in step A1, 15-25 g of the compound is placed in a reaction vessel, 1.2-1.6 g of DMAP and 150-170 mL of THF are added for dissolution, ice bath cooling to -1 -1℃, then 20-30 g of Boc2O is slowly added, and the reaction is maintained for 4-8 hours.

[0058] Further, in step two, the preparation method of 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester includes the following steps:

[0059] B1, under the protection of argon, 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step one is dissolved in THF and placed in reaction bottle A, then TMPMgCl·LiCl THF / toluene solution is slowly added, stirring is maintained for 0.2-0.8 hours, then zinc chloride THF solution is added, and stirring is continued for 0.2-0.8 hours to obtain mixture one;

[0060] B2, in another reaction bottle B filled with argon protection, bromide, catalyst XPhos Pd G3 and tetrahydrofuran are added, and stirring reaction is carried out for 0.2-0.8 hours to obtain mixture two;

[0061] B3, mixture two prepared in reaction bottle B in step B2 is added to mixture one prepared in reaction bottle A in step B1, and reaction is carried out at room temperature for 22-26 hours until the raw material is completely disappeared;

[0062] B4, after the reaction is completed, saturated ammonium chloride aqueous solution and saturated brine are added to the reaction system for quenching reaction, the organic phase is separated, then the water phase is extracted with ethyl acetate, the combined organic phase is dried and concentrated, and then column chromatography is used to separate the white solid, i.e. 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester is prepared.

[0063] Further, in step B1, 250-300 mg of 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step one is dissolved in 1-5 mL of THF and placed in reaction bottle A, then 1.2-1.8 mL of 0.5-1 mol / L TMPMgCl.LiCl THF / toluene solution is slowly added, stirring is maintained for 0.2-0.8 hours, then 0.2-1 mL of 1-2 mol / L zinc chloride THF solution is added, stirring is continued for 0.2-0.8 hours to obtain mixture one.

[0064] Further, in step B2, 250-350 mg of bromide, 45-55 mg of catalyst XPhos Pd G3 and 1-5 mL of tetrahydrofuran are added to another argon-protected reaction bottle B, stirring is carried out for 0.2-0.8 hours to obtain mixture two.

[0065] Further, in step three, the preparation method of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole includes the following steps:

[0066] C1, 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step two, dichloromethane and trifluoroacetic acid are sequentially added to the reactor, and stirring is carried out for 2-4 hours;

[0067] C2, after the reaction is completed, the reactant prepared in step C1 is diluted with dichloromethane, then saturated sodium bicarbonate solution is added for quenching reaction, after the organic phase is separated, the water phase is extracted with dichloromethane, the combined organic phase is dried and concentrated, then yellow solid is obtained by silica gel column chromatography, that is, 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole is prepared.

[0068] Further, in step C1, 900-1000 mg of 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step two, 10-30 mL of dichloromethane and 1-3 mL of trifluoroacetic acid are sequentially added to the reactor, and stirring is carried out for 2-4 hours.

[0069] In some embodiments of the present application, a medicinal herb fragrance base comprises the following raw materials by weight: 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole 45-55 parts, gurjun balsam 8-12 parts, sandalwood oil 8-12 parts, linalyl acetate 12-18 parts, patchouli extract 25-35 parts, decanal 20-30 parts, pachouli oil 2-8 parts, phenylethyl alcohol 12-16 parts, eugenol 15-25 parts, isoamyl butyrate 2-6 parts, geraniol 55-65 parts, linalool oxide 20-30 parts, borneol 75-85 parts, vetiver oil 6-10 parts, ethyl heptanoate 15-25 parts, ionone 6-10 parts, and propylene glycol 600-700 parts.

[0070] In a typical embodiment of the present application, a medicinal herb fragrance base comprises the following raw materials by weight: 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole 50 parts, sandalwood oil 10 parts, linalyl acetate 15 parts, patchouli extract 30 parts, decanal 25 parts, pachouli oil 5 parts, phenylethyl alcohol 14 parts, eugenol 20 parts, isoamyl butyrate 4 parts, geraniol 60 parts, linalool oxide 25 parts, borneol 80 parts, vetiver oil 8 parts, ethyl heptanoate 20 parts, ionone 8 parts, and propylene glycol 626 parts.

[0071] Example 1

[0072] The present embodiment provides a nitrogen-containing compound with medicinal herb fragrance, which has the following structural formula:

[0073]

[0074] The chemical name of the nitrogen-containing compound with medicinal herb fragrance is 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole.

[0075] The preparation method of the nitrogen-containing compound with medicinal herb fragrance comprises the following steps:

[0076] Step one: preparing 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester, and the chemical reaction formula of preparing 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester is as follows:

[0077]

[0078] A1, the compound (20 g, 120 mmol) is placed in a reaction container, DMAP (1.4 g, 11.9 mmol, 0.1 equiv) and THF (160 mL) are added for dissolution, and the ice bath is cooled to 0°C, then Boc2O (26 g, 119 mmol, 1.0 equiv) is slowly added, and the reaction is maintained for 6 hours; the structural formula of the compound is shown in formula 1;

[0079] A2, after TLC detection of the complete disappearance of the starting material, 10% ammonium chloride aqueous solution (160 mL) was added to quench the reaction, the organic phase was separated, and the aqueous phase was extracted with ethyl acetate (80 mL, x 3), and the combined organic phase was dried and concentrated, and then separated by column chromatography (DCM / MeOH = 20:1) to obtain 25.6 g of white solid product, i.e. 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester, with a yield of 80%, and the melting point of the white solid product was measured to be 128-132 °C; the structure of 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester is shown in formula 2, which has the following NMR spectral characteristics:

[0080] 1 H NMR (400 MHz, DMSO) δ 9.45 (s, 1H), 8.58 (d, J = 5.0 Hz, 1H), 8.33-8.27 (m, 2H), 8.19 (d, J = 4.9 Hz, 1H), 7.69 (t, J = 7.8 Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H), 1.75 (s, 9H).

[0081] 13 C NMR (101 MHz, DMSO) δ 150.3, 143.3, 138.7, 138.0, 134.6, 131.6, 130.4, 124.1, 123.7, 122.2, 116.5, 115.1, 85.4, 28.2.

[0082] Mass spectrometry data are as follows:

[0083] HRMS (ESI / [M+H] + ); high resolution electrospray ionization mass spectrometry theoretical calculation data for C 16 H 17 N2O2: 269.1285, actual measured value 269.1284 (HRMS (ESI / [M+H] + ) calculated for C 16 H 17 N2O2: 269.1285, found 269.1284.).

[0084] Step two: preparation of 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester, the chemical reaction formula for the preparation of 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester is as follows:

[0085]

[0086] B1, tert-butyl 9H-pyrido[3,4-b]indole-9-carboxylate (270 mg, 1 mmol) prepared in step one was dissolved in THF (3 mL) under argon protection and placed in reaction bottle A, then TMPMgCl.LiCl THF / toluene solution (0.74 M, 1.5 mL, 1.0 equiv) was slowly added, stirring was maintained for 0.5 h, then 1.9 mol / L zinc chloride THF solution (0.5 mL, 1 equiv) was added, stirring was continued for 0.5 h to obtain mixture one;

[0087] B2, another reaction bottle B was filled with bromide (300 mg, 1 mmol), catalyst XPhos Pd G3 (50 mg, 0.06 equiv) and tetrahydrofuran (3 mL) under argon protection, stirring was continued for 0.5 h to obtain mixture two; the structure of the bromide is shown in formula 4;

[0088] B3, mixture two prepared in reaction bottle B in step B2 was added to mixture one prepared in reaction bottle A in step B1, and the reaction was carried out at room temperature for 24 h until the raw material was completely consumed;

[0089] B4, after the reaction was completed, saturated aqueous ammonium chloride solution (10 mL) and saturated brine (10 mL) were added to quench the reaction, the organic phase was separated, then the aqueous phase was extracted with ethyl acetate (20 mL x 3), the combined organic phase was dried and concentrated, then separated by silica gel column chromatography (DCM / MeOH = 20:1) to obtain 340 mg of white solid compound, i.e. tert-butyl 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylate was prepared, the yield was 70%, the melting point of the white solid compound was measured to be 157-165 °C; the structure of tert-butyl 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylate is shown in formula 3, which has the following NMR spectral characteristics:

[0090] 1 H NMR (400 MHz, DMSO) δ 8.70 (d, J = 5.0 Hz, 1H), 8.37 (d, J = 7.8 Hz, 1H), 8.22-8.17 (m, 2H), 8.14 (d, J = 8.5 Hz, 1H), 7.97 (s, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.72 (t, J = 7.8 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 7.43 (t, J = 7.7 Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H), 1.67 (s, 9H), 1.09 (s, 9H).

[0091] 13 C NMR (101 MHz, DMSO) δ 148.6, 148.4, 142.5, 140.4, 139.4, 134.1, 133.2, 131.8, 129.6, 128.0, 124.3, 123.7, 123.1, 122.8, 122.7, 121.4, 120.9, 120.3, 114.3, 114.3, 112.5, 83.7, 27.1, 26.1.

[0092] Mass spectral data are as follows:

[0093] HRMS (ESI / [M+H] + ) high resolution electrospray ionization mass spectrum theoretical calculation data for C 29 H 30 N3O4: 484.2231, the actual measured value is 484.2231 (HRMS (ESI / [M+H] + ) calculated for C 29 H 30 N3O4: 484.2231, found 484.2231.).

[0094] Step three: preparation of the nitrogen-containing compound with herbal fragrance, which is 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole; the chemical reaction formula for preparing 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole is as follows:

[0095]

[0096] C1, 1-(1-(tert-butoxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester (970 mg, 2 mmol) prepared in step two, dichloromethane (20 mL) and trifluoroacetic acid (2 mL) were sequentially added in the reactor, and the reaction was stirred vigorously for 3 hours;

[0097] C2, after the reaction was completed, the reaction mixture prepared in step C1 was diluted with dichloromethane (50 mL), then quenched with saturated sodium bicarbonate solution (100 mL), after the organic phase was separated, the aqueous phase was extracted with dichloromethane (50 mL x 3), the combined organic phase was dried and concentrated, then separated by silica gel column chromatography (DCM / MeOH = 15:1) to obtain 0.5 g of yellow solid, i.e. 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole was prepared, the yield was 90%, the melting point of the yellow solid was measured to be 239-242°C; the structural formula of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole is shown in formula 5.

[0098] The 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole prepared in this example has the following NMR spectral characteristics:

[0099] 1 H NMR (400 MHz, DMSO) δ 11.70 (s, 1H), 11.28 (s, 1H), 8.56 (d, J = 7.9 Hz, 1H), 8.45 (d, J = 5.3 Hz, 1H), 8.30 (d, J = 2.8 Hz, 1H), 8.24 (d, J = 7.9 Hz, 1H), 7.96 (d, J = 5.1 Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.54 (dd, J = 13.2, 7.7 Hz, 2H), 7.23 (dt, J = 15.0, 7.6 Hz, 2H), 7.14 (t, J = 7.4 Hz, 1H).

[0100] 13 C NMR (101 MHz, DMSO) δ 141.2, 140.9, 138.5, 137.0, 132.5, 128.6, 128.1, 126.7, 126.4, 122.8, 122.5, 121.8, 121.7, 120.2, 119.9, 113.7, 112.9, 112.1, 112.0.

[0101] Mass spectrometry data are as follows:

[0102] HRMS (ESI / [M+H] + ) high resolution electrospray ionization mass spectrometry theoretical calculation data for C 19 H 14 N3: 284.1182, the actual measured value was 284.1179 (HRMS (ESI / [M+H] + ) calculated for C 19 H 14N3: 284.1182, found 284.1179.

[0103] Example 2

[0104] The 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole prepared in Example 1 was subjected to aroma rating, fragrance retention test and fragrance base aroma test, and the test results were as follows:

[0105] (1) Aroma evaluation: 12 perfumers with more than 5 years of work experience evaluated the aroma of the compound as follows: 12 perfumers unanimously believed that the compound had special herbal spicy aroma in addition to medicinal aroma, with a little floral sweet aroma.

[0106] (2) Fragrance retention test: 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole was configured into a propylene glycol solution with a mass fraction of 10%, 1 piece of smelling paper was taken, a little was dipped, the smelling paper was placed on the smelling frame, 3 perfumers smelled it every 2 hours, when more than or equal to 2 perfumers could not perceive the aroma of the smelling paper, the fragrance retention time was recorded.

[0107] The fragrance retention test showed that the medicinal aroma of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole had a fragrance retention time of 32 hours, and the special herbal spicy aroma and a little floral sweet aroma had a fragrance retention time of 42 hours.

[0108] (3) Fragrance base aroma test: the formula of herbal fragrance base is shown in the following table:

[0109]

[0110] A fragrance base and B fragrance base were configured according to the above table, the parts of each raw material in the table were weight parts, and B fragrance base was different from A fragrance base in that 50 parts of the target product 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole was added, 9 perfumers with more than 5 years of work experience evaluated the above fragrance bases and made the following evaluation: 9 perfumers unanimously believed that B fragrance base had more prominent medicinal aroma than A fragrance base, characteristic herbal spicy aroma was accompanied by sweet aroma, with a little floral aroma, and the quality of fragrance base aroma was significantly improved.

[0111] The above examples are the preferred implementation schemes of the present application, in addition to this, the present application can also be implemented in other ways, any obvious substitution within the concept of the present application is within the protection scope of the present application.

Claims

1. A nitrogen-containing compound with a herbal aroma, characterized in that: It has the following structural formula:

2. A method for preparing a nitrogen-containing compound with a herbal aroma as described in claim 1, characterized in that: Includes the following steps: Step 1: Using the compound and Boc2O as raw materials, prepare 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester. The structural formula of the compound is shown below: The structural formula of 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester is shown below: Step 2: Using the brominated product and the 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester obtained in Step 1 as raw materials, 1-(1-(tert-butoxycarbonyl)-1H-indole-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester was prepared. The structural formula of the brominated product is shown below: The structural formula of 1-(1-(tert-butyloxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indol-9-carboxylic acid tert-butyl ester is shown below: Step 3: Using 1-(1-(tert-butyloxycarbonyl)-1H-indole-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester obtained in Step 2 as the raw material, and after separation and purification, a nitrogen-containing compound with a herbal aroma is obtained. The nitrogen-containing compound with a herbal aroma is 1-(1H-indole-3-yl)-9H-pyrido[3,4-b]indole.

3. The method for preparing a nitrogen-containing compound with a herbal aroma according to claim 2, characterized in that: In step one, the preparation method of 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester includes the following steps: A1. Place the compound in a reaction vessel, add DMAP and THF to dissolve it, cool it in an ice bath to -1 to -1°C, and then slowly add Boc2O to maintain the reaction for 4 to 8 hours. A2. After the raw material was completely eliminated by TLC, ammonium chloride aqueous solution was added to quench the reaction, the organic phase was separated, and the aqueous phase was extracted with ethyl acetate. The combined organic phase was dried and concentrated, and then separated by column chromatography to obtain a white solid product, namely 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester.

4. The method for preparing a nitrogen-containing compound with a herbal aroma according to claim 3, characterized in that: In step A1, 15-25g of the compound is placed in a reaction vessel, and 1.2-1.6g of DMAP and 150-170mL of THF are added for dissolution. The mixture is cooled to -1 to 1°C in an ice bath, and then 20-30g of Boc2O is slowly added to maintain the reaction for 4-8 hours.

5. The method for preparing a nitrogen-containing compound with a herbal aroma according to claim 2, characterized in that: In step two, the preparation method of 1-(1-(tert-butoxycarbonyl)-1H-indole-2-yl)-9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester includes the following steps: B1. Under argon protection, the 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester obtained in step one is dissolved in THF and placed in reaction flask A. Then, a THF / toluene solution of TMPMgCl·LiCl is slowly added and stirred for 0.2-0.8 hours. Then, a THF solution of zinc chloride is added and stirred for another 0.2-0.8 hours to obtain mixture one. B2. In another reaction flask B filled with argon gas, add the brominated compound, the catalyst XPhos Pd G3 and tetrahydrofuran, and stir the reaction for 0.2-0.8 hours to obtain mixture two; B3. Add the mixture 2 obtained in reaction flask B in step B2 to the mixture 1 obtained in reaction flask A in step B1, and react at room temperature for 22-26 hours until all the raw materials are gone. B4. After the reaction is complete, saturated ammonium chloride aqueous solution and saturated brine are added to the reaction system to quench the reaction, the organic phase is separated, and then the aqueous phase is extracted with ethyl acetate. The combined organic phase is dried and concentrated, and then separated by silica gel column chromatography to obtain a white solid compound, namely 1-(1-(tert-butyloxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indol-9-carboxylic acid tert-butyl ester.

6. The method for preparing a nitrogen-containing compound with a herbal aroma according to claim 5, characterized in that: In step B1, under argon protection, 250-300 mg of 9H-pyrido[3,4-b]indole-9-carboxylic acid tert-butyl ester prepared in step one is dissolved in 1-5 mL of THF and placed in reaction flask A. Then, 1.2-1.8 mL of a 0.5-1 mol / L TMPMgCl·LiCl THF / toluene solution is slowly added. After stirring for 0.2-0.8 hours, 0.2-1 mL of a 1-2 mol / L zinc chloride THF solution is added, and stirring is continued for another 0.2-0.8 hours to obtain mixture one.

7. The method for preparing a nitrogen-containing compound with a herbal aroma according to claim 5, characterized in that: In step B2, 250-350 mg of bromide, 45-55 mg of catalyst XPhos PdG3 and 1-5 mL of tetrahydrofuran are added to another reaction flask B filled with argon gas and stirred for 0.2-0.8 hours to obtain mixture two.

8. The method for preparing a nitrogen-containing compound with a herbal aroma according to claim 2, characterized in that: In step three, the preparation method of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole includes the following steps: C1. Add 1-(1-(tert-butyloxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indol-9-carboxylic acid tert-butyl ester, dichloromethane and trifluoroacetic acid to the reactor in sequence, and stir vigorously for 2-4 hours. C2. After the reaction is complete, the reactants obtained in step C1 are diluted with dichloromethane, and then saturated sodium bicarbonate solution is added to quench the reaction. After separating the organic phase, the aqueous phase is extracted with dichloromethane. The combined organic phases are dried and concentrated, and then separated by silica gel column chromatography to obtain a yellow solid, which is the preparation of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole.

9. The method for preparing a nitrogen-containing compound with a herbal aroma according to claim 8, characterized in that: In step C1, 900-1000 mg of 1-(1-(tert-butyloxycarbonyl)-1H-indol-2-yl)-9H-pyrido[3,4-b]indol-9-carboxylic acid tert-butyl ester, 10-30 mL of dichloromethane, and 1-3 mL of trifluoroacetic acid are added sequentially to the reactor, and the mixture is stirred vigorously for 2-4 hours.

10. A herbal fragrance base, characterized in that: The raw materials include the following parts by weight: 45-55 parts of 1-(1H-indol-3-yl)-9H-pyrido[3,4-b]indole, 8-12 parts of vetiver oil, 12-18 parts of linalyl acetate, 25-35 parts of lysine extract, 20-30 parts of decanal, 2-8 parts of patchouli oil, 12-16 parts of phenylethanol, 15-25 parts of eugenol, 2-6 parts of isoamyl butyrate, 55-65 parts of geraniol, 20-30 parts of linalool oxide, 75-85 parts of borneol, 6-10 parts of vetiver oil, 15-25 parts of ethyl heptanoate, 6-10 parts of ethyl dihydroionone, and 600-700 parts of propylene glycol.

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