JPS6016942B2 - N-acyl-N-methyl-4-(3-pyridyl)-butylamines and their production method - Google Patents

Description

[Detailed description of the invention]

The present invention is a compound of the general formula [1] (wherein R is a propionyl group, a butyryl group, a valeryl group,
The present invention relates to N-acyl-N-methyl-4-(3-pyridyl)-butylamines (representing a cinnamoyl group or penzoyl group) (hereinafter referred to as N-acyl dihydromethanicotines) and a method for producing the same. The N-acyldihydromethanicotines according to the present invention are compounds useful as tobacco flavor improvers, and were synthesized for the first time by the present inventors. The N-acyl dihydromethanicotines of the present invention are derived from N-methyl-4-(3-pyridyl)-3-phthen-1-amine (hereinafter referred to as metanicotine), For nicotine, mix nicotine or nicotine sulfate with penzoyl chloride at 130 to 200 qo for 10 minutes.
It is easily obtained by reacting for 2 hours to obtain N-penzoylmetanicotine, and then performing a hydrolysis reaction with hydrochloric acid or the like [Ber. , 77B, 362 (1944
)]. In the production of N-acyldihydromethanicotines, metanicotine is converted into N-acyl-N-methyl-141(3-pyridyl)-13-buten-1-amines (hereinafter referred to as N-acylmetanicotine) by an N-acylation reaction. After that, the N-acylmetanicotines are converted into N-acylmetanicotines by a hydrogenation reaction.
- A method for producing acyl dihydromethanicotines, or
N-methyl-4-(
Any method can be arbitrarily selected in which the dihydromethanicotine is converted into 3-pyridyl)-butylamine (hereinafter referred to as dihydromethanicotine) and then subjected to an N-acylation reaction to form N-acyldihydromethanicotines. Also, among N-acyldihydromethanicotines, N-
Penzoyl dihydromethanicotine can also be produced by directly hydrogenating N-penzoylmetanicotine, which is an intermediate in producing metanicotine, which is its raw material. To explain the production method of the present invention in more detail, the N-acylation reaction of metanicotine or dihydrometanicotine is carried out in the presence of an alkali hydroxide such as sodium hydroxide or potassium hydroxide.

[0]RX [B] (However, in the formula, R has the same meaning as above, and X represents a halogen atom.) The acyl halide represented by "0"
By reacting at ~400C for 1 to 3 hours, N containing an acyl group corresponding to the acyl halide used in the reaction
-Acylmetanicotines or N-acyl dihydromethanicotines are produced. In addition, the hydrogenation reaction of metanicotine or N-acylmetanicotines can be carried out by a method generally used for hydrogenation of carbon-carbon unsaturated bonds, and usually involves catalytic hydrogenation in the presence of a transition metal catalyst. Addition is used. For example, metanicotine or N-acylmetanicotines are mixed in a solvent such as ethanol, n-propanol, isopropanol, or dioxane in the presence of a palladium metal catalyst, preferably palladium black, in a low, medium or By performing catalytic hydrogenation using high pressure hydrogen, dihydromethanicotine or N-acyldihydromethanicotines can be obtained. Isolation of reaction products from N-acylation reaction solution and hydrogenation reaction solution
During purification, in the case of a hydrogenation reaction, the catalyst is first separated in a furnace and then the reaction solvent is concentrated, or in the case of an N-acylation reaction, the reaction product is extracted with an organic solvent such as chloroform or carbon tetrachloride, and then the extraction solvent is concentrated. Further, if necessary, it is possible to use ordinary operating means for organic synthesis reactions, such as purification by distillation or column chromatography, or recrystallization. This will be explained below using reference examples and examples. Reference example 1N-benzoylmetanicotine nicotine 100
(0.617 mol) and 200 ml of penzoyl chloride (1.
43 mol) and heated at 190°C for 2 minutes. The reaction mixture is then cooled to room temperature, hydrochloric acid is added, and the resulting benzoic acid is heated in an oven for 8U. The furnace solution is made alkaline with sodium hydroxide and extracted with 200% chloroform. After extraction, the solvent was removed under reduced pressure, and the remaining light was distilled under reduced pressure to remove N.
-Penzoylmetanicotine 130mg (0.489mol)
I got it. Yield 79.2%. Boiling point 200~20〆○/1
Side Hg Nuclear magnetic resonance absorption (Mo-Ace's ne) 6 skin = 2.4-3.8 (m, 4 days, -ku CH2) 2'-) Kano N.C. -3-o (S.・ d3 SO> 6.4 (s, ga, -CH=CH-) 7.4 (s, ta, benzene ring) 7.1-8.7 (m, 4 days, pyridine ring) Infrared absorption ( K
Br) ShiC Ni. 1615 Arc-1 Reference Example 2 Metanicotine N-penzoylmetanicotine plaque. Add 600% of 20% hydrochloric acid to the mixture (0.219 mol) and heat under reflux for 10 hours while stirring. After the reaction, the mixture is cooled to room temperature and the precipitated benzoic acid is separated from the furnace.
After making the furnace solution alkaline with sodium hydroxide, extraction is performed with 300% chloroform. After extraction, the solvent was removed under reduced pressure, and the residue was distilled under reduced pressure to obtain metanicotine (0.0
．． 142 mol) was obtained. Yield 64.8%. Boiling point 88~
90 qo/1 skin Hg Example 1 N-propionyl dihydromethanicotine Metanicotine 25 mol (0.154 mol) was added to 370 ml of 10% aqueous sodium hydroxide solution, and the reaction temperature was increased to 20 ± 2
While keeping the temperature at °C and keeping the temperature well lit, propionyl chloride (0.465 mol) was gradually added dropwise over 30 minutes. After completion of the dropwise addition, heating was continued for 2 hours at room temperature to complete the reaction. After the reaction is complete, extract with 150% of chloroform.
After repeating the extraction, the extraction solvent was removed under reduced pressure, and the residue was distilled under reduced pressure to obtain 32 N-propionylmetanicotine (0.1
47 mol) was obtained. Yield 95.4%. Boiling point 1560/
1×10-3 rib Hg Nuclear magnetic resonance absorption (CDC13) Skin = 1.15 (t, lees-CO-CH2-CH3) 2.1
~3.7 (m, thin, -〃CH2)2-N'' 3-o (d, group, three days 3) 6.2~6.5 (m , spots, one CH=CH-)7.1-8
．． 7 (m, 4 days, pyridine ring) infrared absorption (Neat)
711 mol) was dissolved in 200 mol of ethanol, added with 500 mol of palladium black, and dissolved at room temperature using an atmospheric pressure reducing apparatus.
The hydrogenation reaction was carried out for an hour. After the catalyst was removed from the furnace, it was concentrated to obtain 15.0 mol (0.0682 mol) of N-propionyl dihydromethanicotine. Yield 9
5.9% (vs. N-propionylmetanicotine). Nuclear magnetic resonance absorption (CDC13) 6 skin = 1,15 (t, origin, -CO-CH2-CH3) 1
．． 5 to 3.6 (m, 1 cape, -ku CH2) 41N-C Lima also -) to Zozoso ・ 2.95 (d, QH, 7.1 to 8.6 (m, 4 days, pyridine ring) red External absorption (N
Example 2 N-cinnamoyl dihydromethanicotine Metanicotine 16.2 (0.10 mol) was dissolved in 200 mol of ethanol, 500 mol of palladium black was added, and the mixture was heated at normal pressure. A hydrogenation reaction was carried out at room temperature for 5 hours using a reduction device. After the catalyst was separated from the furnace, it was concentrated to obtain 15.4 moles (0.0939 mol) of dihydromethanicotine. Yield 93.9%. Nuclear magnetic resonance absorption (CDC13) 6 skin = 1.4 to 2.7 (m, navy blue, Yamatatsukoko "Misaki-WNH2-4 (S, So, and day 3) 7.1 to 8.7 (m, (4 days, pyridine ring) Next, 8.0 mol (0.0488 mol) of dihydromethanicotine was added to 100 mol of a 10% aqueous sodium hydroxide solution, and the reaction temperature was raised to 15 mol.
Cinnamoyl chloride 2
0.6 mol (0.124 mol) was added dropwise over 15 minutes. After completion of the dropwise addition, the mixture was concentrated at room temperature for 2 hours to complete the reaction, and then extracted twice with 100% of chloroform. The extraction solvent was distilled off under reduced pressure to obtain 13.5 moles (0.0459 mol) of N-cinnamoyldihydromethanicotine. Yield: 94.
1% (vs. dihydromethanicotine). Nuclear magnetic resonance absorption (C
DC13) 6 skin = 1.5-3.7 (m, thin, -ku CH2) "r-) -N" 3-1 (d, wide, to day 3) 6.6-8.5 (m , 11 days, pyridine ring and infrared absorption (KBr) C 0 1640 arc-1 Example 3 N-benzoyl dihydromethanicotine N-benzoyl metanicotine 19.0 minutes (0.0714
mol) in ethanol 250M, palladium black 5
9 of 00 was added, and a hydrogenation reaction was carried out at room temperature for 5.5 hours using an atmospheric pressure reduction apparatus. After the catalyst was removed from the furnace, it was concentrated to obtain 18.49 (6 moles of 0.0 gruel) of N-benzoyldihydromethanicotine. Yield: 96.
1%. Nuclear magnetic resonance absorption (CDC13) 6 pieces = 1.6-3
．． 5 (m, nail day, 7.0-8.6 (m, square, pyridine ring and benzene ring) Infrared absorption (Neat) ShiC Ni0 1630 skin-1 Example 4 N-butyryldihydromethanicotine halogen N-butyrylmetanicotine obtained by the N-acylation reaction of metanicotine in the same manner as in Example 1 except that butyryl chloride was used as the acyl chloride was treated in the same manner as in the hydrogenation reaction of Example 1. N-butyryl dihydromethanicotine was obtained at a rate of 90% (to metanicotine). Nuclear magnetic resonance absorption (CDC13) 7.1-8.6 (m, 4 days, pyridine ring) Infrared absorption (N
eat) C=0 1635 or -1 Example 5 N-valeryl dihydromethanicotine Example 5 except that dihydromethanicotine obtained by the hydrogenation reaction of Example 2 was used and valeryl chloride was used as the acyl halide. A reaction similar to the N-acylation reaction in 2 was conducted to obtain N-valeryldihydromethanicotine in a yield of 89% (based on dihydromethanicotine). Nuclear magnetic resonance absorption (CDC13) 7.0-8.6 (m, mountain, pyridine ring) Infrared absorption (Neat) Cni0 1635 arc-I

Claims (1)

[Claims] 1 General formula [I] ▲ Numerical formulas, chemical formulas, tables, etc.▼ (However, in the formula, R represents a propionyl group, a butyryl group, a valeryl group, a cinnamoyl group, or a benzoyl group)
N-acyl-N-methyl-4-(3-pyridyl)-butylamines represented by: 2 N-methyl-4-(3-pyridyl)-3-butene-
1-amine in the presence of alkali hydroxide, general formula [II]
RX [II] (wherein R represents a propionyl group, butyryl group, valeryl group, cinnamoyl group, or benzoyl group, and X represents a halogen atom) to form the general formula [III] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (However, R in the formula represents the same meaning as above) N-acyl-N-methyl-4-(3-pyridyl)-
General formula [I] which is characterized by hydrogenating 3-butene-1-amines ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (However, R in the formula represents the same meaning as above) A method for producing N-acyl-N-methyl-4-(3-pyridyl)-butylamines. 3 N-methyl-4-(3-pyridyl)-3-butene-
1-amine is hydrogenated to give N-methyl-4-(3-pyridyl)-butylamine, and this is converted into the general formula [II]RX [II] in the presence of an alkali hydroxide (wherein R is a propionyl group). , a butyryl group, a valeryl group, a cinnamoyl group, or a benzoyl group, and X represents a halogen atom. ▼ (However, R in the formula represents the same meaning as above) N-acyl-N-methyl-4-(3-pyridyl)-
A method for producing butylamines.