CN110818624B - Pyridine quaternary ammonium hydrazone compound, preparation method and application in antibacterial or slow release of spices - Google Patents

Abstract

The invention discloses a pyridine quaternary ammonium salt type hydrazone compound, which has the following structure:

For the definition of each substituent in the formula, see the description for details. The pyridine quaternary ammonium hydrazone compounds with long carbon chains in the invention have good water solubility, can be hydrolyzed in acidic aqueous solution to release aromatic aldehydes and ketones, and achieve the purpose of slowly releasing fragrances through dynamic balance. At the same time, the pyridine quaternary ammonium salt type hydrazide compound remaining in the solution system after hydrolysis still has good surface activity and antibacterial ability, and is a multifunctional surfactant, which has certain positive significance in practical applications.

Description

Pyridinium quaternary ammonium hydrazone compound and its preparation method and its application in antibacterial or fragrance slow-release application

technical field

The invention belongs to the technical field of synthesis of novel pyridine quaternary ammonium hydrazone compounds, and in particular relates to a pyridine quaternary ammonium hydrazone compound, its preparation method and its application in antibacterial or perfume slow-release.

Background technique

With the continuous development of society and the continuous advancement of science and technology, people's living standards are also constantly improving. After meeting the basic material needs of life, they begin to pursue a higher quality of life. Flavors and fragrances widely exist in daily life, such as food additives, daily chemical products, etc., flavors and fragrances are everywhere. In recent years, the continuous emergence of aromatic wallpapers, aromatic high-end seats, and aromatic textiles has confirmed that the people are no longer satisfied with traditional spices, and people desire more functional and longer-lasting fragrance products. At the same time, the function of essence is not limited to releasing fragrance to make people feel happy, but also plays many functions such as sterilization, antibacterial and disease treatment. Fragrance has such a wide range of use values, and its research is also a topic of great economic value and social significance. However, because the fragrance molecule itself has the characteristics of relatively high saturated vapor pressure, volatile and easily oxidized instability, it cannot maintain a lasting fragrance retention time. In order to solve this problem, various methods have also been proposed in recent years (review: Quellet, C, Schudel, M, Ringgenberg, R. Chimia 2001; 55:421-428), including microencapsulation method (review: Ciriminna, R, Pagliaro, M.Chem.Soc.Rev.2013; 42:9243-9250; He L, Hu J, Deng W.Polym.Chem.2018,9:4926-4946), organometallic framework material adsorption method (Liu Y, Wang Y, HuangJ, Zhou Z, Zhao D, Jiang L, Shen Y.AIChE J.2019;65:491-499) and chemical latent fragrance method (Herrmann A.Angew.Chem.Int.Ed.2007;46: 5836-5863) and so on; among them, the design and preparation of efficient chemical latent aroma body research has received extensive attention and research.

At present, there are many methods for fragrance slow release. The method of delaying fragrance release by using latent fragrance body is to use chemical means to combine volatile fragrance molecules with non-volatile precursors through covalent bonds, and selectively release fragrance under specific conditions. The chemical bond breaking that releases the fragrance active molecules occurs in a controlled and continuous manner. The conditions for breaking chemical bonds include light, oxidation, heating, hydrolysis, changing pH and enzyme catalysis, etc., which are widely found in nature and human daily life. As a common solvent, water is often used in various flavoring products, and the release of fragrance molecules by hydrolysis or changing the pH has been reported in many literatures. Hydrazone compounds are similar to Schiff bases, which can be hydrolyzed in acidic aqueous solution to release aldehydes and ketones fragrance molecules. At the same time, compared with Schiff bases, hydrazone compounds are more stable and will not undergo rapid hydrolysis. The pyridinium quaternary ammonium salt hydrazide compound reacts with aromatic aldehydes and ketones to obtain pyridinium quaternary ammonium salt hydrazone compounds, which can be hydrolyzed under acidic conditions to release aromatic aldehydes and ketone molecules. Most of the latent fragrance compounds left in the aqueous system after hydrolysis to release the fragrance molecules are useless. Therefore, a kind of latent fragrance compound with good water solubility and the same substances that remain in the solution system after releasing the fragrance has multiple functions becomes Technical issues that need to be resolved.

Contents of the invention

The first object of the present invention is to provide a kind of pyridine quaternary ammonium salt hydrazone compound.

The second object of the present invention is to provide a method for preparing the pyridine quaternary ammonium hydrazone compound.

The third object of the present invention is to provide an application of the pyridinium quaternary ammonium salt hydrazone compound in antibacterial or perfume sustained release.

In order to achieve the above object, the technical scheme adopted in the present invention is as follows:

The first aspect of the present invention provides a pyridine quaternary ammonium salt type hydrazone compound, which has the following structure:

R ₁ is selected from hydrogen, C ₁ -C ₂₀ alkyl;

R ₂ is selected from hydrogen, substituted or unsubstituted aryl, C ₁ -C ₂₀ alkenyl substituted aryl, substituted or unsubstituted cycloalkyl or heterocyclyl;

R ₃ is selected from hydrogen, C ₁ -C ₂₀ alkyl;

R ₄ is selected from hydrogen, C ₁ -C ₂₀ alkyl;

X is halogen (F, Cl, Br or I).

More preferably, in the pyridine quaternary ammonium salt type hydrazone compound,

R ₁ is selected from hydrogen, C ₅ -C ₁₈ alkyl;

R ₂ is selected from hydrogen, substituted or unsubstituted phenyl, substituted or unsubstituted benzoheterocycle, C ₁ -C ₂₀ alkenyl substituted phenyl, substituted or unsubstituted cyclohexene, substituted or unsubstituted Cycloalkyl;

R ₃ is selected from hydrogen, C ₅ -C ₁₈ alkyl;

R ₄ is selected from hydrogen, C ₅ -C ₁₈ alkyl;

X is Cl, Br.

More preferably, in the pyridine quaternary ammonium salt type hydrazone compound,

R ₁ is selected from hydrogen, C ₅ -C ₁₈ alkyl;

R ₂ is selected from hydrogen,

R ₃ is selected from hydrogen, methyl;

R ₄ is selected from hydrogen, methyl;

X is Br.

Most preferably, the pyridine quaternary ammonium hydrazone compound is one of the following structures:

A second aspect of the present invention provides a method for preparing the pyridine quaternary ammonium hydrazone compound, comprising the following steps:

Dissolve 3-hydroxypyridine in a solvent, add alkali, react at a temperature of 20-60°C for 0.1-48 hours, add haloalkane dropwise, the molar ratio of 3-hydroxypyridine, alkali, and bromoalkane is 1:(2～ 30): 1, the intermediate pyridine compound is obtained after the reaction is complete;

Dissolve the intermediate pyridine compound in the solvent, add ethyl haloacetate, the molar ratio of the intermediate pyridine compound to ethyl haloacetate is 1:(1.1~2), and react at a temperature of 20~60°C for 0.1 ~48h, to obtain the pyridinium quaternary ammonium salt compound;

Dissolve hydrazine hydrate in the solvent, dissolve the pyridinium quaternary ammonium compound in the solvent, and slowly add it to the solution of the above-mentioned hydrazine hydrate, the molar ratio of hydrazine hydrate to the pyridinium quaternary ammonium compound is (5～15):1, the temperature Reaction under the condition of 20-60°C for 0.1-48 hours to obtain pyridinium quaternary ammonium hydrazide compound;

The pyridine quaternary ammonium salt type hydrazide compound with a molar ratio of 1:(1.1-2) and aldehyde or ketone spices are dissolved in a solvent and reacted under reflux to obtain the pyridine quaternary ammonium salt type hydrazone compound.

Described solvent is dimethyl sulfoxide, ethyl acetate, ethanol.

Described alkali is potassium hydroxide, sodium hydroxide.

The haloalkane is bromododecane, bromooctane, bromodecane, bromotetradecane, bromohexadecane, bromoethane, bromopropane, bromobutane, bromopentane , bromohexane, bromoheptane, bromononane.

The ethyl haloacetate is ethyl bromoacetate.

The aldehyde or ketone fragrance is cinnamaldehyde, jasminaldehyde, β-ionone, rabbit ear oxalin, benzaldehyde, anisaldehyde, vanillin, citronellal, ionone, methyl ionone, carvone , Damascenone.

The third aspect of the present invention provides an application of the pyridinium quaternary ammonium salt type hydrazone compound in antibacterial or fragrance sustained release.

The fourth aspect of the present invention provides a use of the pyridinium quaternary ammonium hydrazone compound as an antibacterial agent or perfume slow-release agent.

Owing to adopting above-mentioned technical scheme, the present invention has following advantage and beneficial effect:

The pyridine quaternary ammonium salt hydrazone compounds with long carbon chains of the present invention have been subjected to a series of performance tests and characterizations, have good water solubility, can be hydrolyzed in acidic aqueous solution to release aromatic aldehydes and ketones, and can be achieved through dynamic equilibrium. To achieve the purpose of slow release of spices. At the same time, the pyridine quaternary ammonium salt type hydrazide compound remaining in the solution system after hydrolysis still has good surface activity and antibacterial ability, and is a multifunctional surfactant, which has certain positive significance in practical applications.

Description of drawings

Fig. 1 is a schematic diagram of the surface tension-concentration curve of pyridinium quaternary ammonium salt hydrazide compound.

Fig. 2 is a schematic diagram of time-peak area curves of pyridine quaternary ammonium hydrazone compound A and pure fragrance substances releasing aromatic substances.

Fig. 3 is a schematic diagram of time-peak area curves of pyridine quaternary ammonium hydrazone compound B and pure fragrance substances releasing aromatic substances.

Fig. 4 is a schematic diagram of time-peak area curves of pyridine quaternary ammonium hydrazone compound C and pure fragrance substances releasing aromatic substances.

Fig. 5 is a schematic diagram of time-peak area curves of pyridine quaternary ammonium hydrazone compound D and pure fragrance substances releasing aromatic substances.

Detailed ways

In order to illustrate the present invention more clearly, the present invention will be further described below in conjunction with preferred embodiments. Those skilled in the art should understand that the content specifically described below is illustrative rather than restrictive, and should not limit the protection scope of the present invention.

Example 1

The preparation method of pyridine quaternary ammonium hydrazone compound comprises the following steps:

(1) Put 10mmol of 3-hydroxypyridine in a flask and add 10mL of dimethyl sulfoxide to dissolve it. Add 2.7g KOH into the flask, stir for 30 minutes at 35°C, add 10mmol dodecane bromide dropwise, and react overnight. After the reaction, add saturated ammonium chloride aqueous solution to wash with water, extract with dichloromethane, and combine The extract was chromatographed with petroleum ether/ethyl acetate as an eluent to obtain a light yellow solid intermediate pyridine compound with a yield of 53%.

(2) Put 1 mmol of the above-mentioned intermediate pyridine compound in a flask, add 10 mL of ethyl acetate to dissolve, add 1.2 mmol of ethyl bromoacetate, and reflux for 24 hours at a temperature of 50 ° C. After the reaction is completed, solids precipitate out after cooling, and filter and recrystallized with n-hexane to obtain a white solid product pyridinium quaternary ammonium salt compound with a yield of 96%.

(3) Put 10mmol of hydrazine hydrate in a flask and add 15mL of absolute ethanol to dissolve it. 1 mmol of the above-mentioned pyridinium quaternary ammonium salt compound was dissolved in 10 mL of absolute ethanol, slowly added to the ethanol solution of the above-mentioned hydrazine hydrate, and reacted for four hours at a temperature of 50° C. After the reaction, part of the ethanol was distilled off under reduced pressure, cooled overnight in a refrigerator, and crystals were precipitated, filtered and washed with ice ethanol to obtain pyridine quaternary ammonium hydrazide compound, a white solid, with a yield of 63%.

(4) Add 0.8mmol of pyridinium quaternary ammonium hydrazide compound to the round bottom flask, add 1.2mmol of cinnamaldehyde, add 15mL of ethanol as solvent and reflux for 4h, cool to room temperature after the reaction, use dichloromethane/methanol as eluent , the light yellow target product (structure shown in formula A) was obtained after column chromatography, and the yield was 50%.

¹ H NMR (400MHz, CDCl ₃ ) δ12.40(s, 1H), 9.03(s, 1H), 8.82(d, J=5.4Hz, 1H), 8.19(d, J=8.7Hz, 1H), 7.82 (dd,J=13.9,8.3Hz,2H),7.34–7.29(m,2H),7.24(d,J=7.5Hz,3H),6.82(m,J=16.0,12.4Hz,2H),5.90( s,2H),4.12(t,J=6.3Hz,2H),1.75–1.68(m,2H),1.18(s,18H),0.80(t,J=6.8Hz,3H).

¹³ C NMR(101MHz,CDCl ₃ )δ159.29,157.07,151.59,140.81,137.39,134.58,131.27,131.21,128.28,127.81,127.01,126.27,123.45,76.39,76.07,75.75,70.36,60.55,30.89,28.63,28.61 ,28.56,28.47,28.33,28.27,27.67,24.73,21.67,13.12.

HRMS (ESI-TOF) m/z: [M-Br]+Calcd for C ₂₈ H ₄₀ N ₃ O ₂ 450.3115; Found 450.3120.

Example 2

The preparation method of pyridine quaternary ammonium hydrazone compound comprises the following steps:

Except that the cinnamaldehyde in step (4) of Example 1 was changed to jasmonal, all the other conditions were the same as in Example 1 to obtain the compound shown in formula B.

¹ H NMR (400MHz, CDCl ₃ ) δ12.28(s, 1H), 9.07(s, 1H), 8.83(s, 1H), 7.87(d, J=2.3Hz, 2H), 7.83(d, J= 6.2Hz, 1H), 6.67(d, J=7.8Hz, 1H), 6.60(d, J=1.4Hz, 1H), 6.56(m, J=7.9, 1.5Hz, 1H), 5.87(s, 2H) ,5.82(d,J=6.9Hz,2H),4.21(t,J=6.2Hz,3H),2.81(m,J=13.5,5.9Hz,2H),2.70–2.59(m,2H),2.44( m,J=13.6,8.7Hz,2H),1.80(m,J=14.6,6.6Hz,2H),1.23(s,18H),1.01–0.98(d,3H),0.85(t,J=6.8Hz ,3H).

¹³ C NMR(101MHz,CDCl ₃ )δ158.92,158.24,157.14,146.50,144.87,137.17,132.28,131.95,131.24,131.17,126.94,121.15,108.46,107.14,99.78,76.40,76.08,75.76,70.38,60.47,38.88 ,37.97,30.89,28.63,28.61,28.55,28.47,28.33,28.25,27.67,24.74,21.67,15.85,13.12.

HRMS (ESI-TOF) m/z: [M-Br]+Calcd for C ₃₀ H ₄₄ N ₃ O ₄ 510.3326; Found 510.3333.

Example 3

The preparation method of pyridine quaternary ammonium hydrazone compound comprises the following steps:

Except that the cinnamaldehyde in the step (4) of Example 1 was changed to β-ionone, the other conditions were the same as in Example 1 to obtain the compound shown in Formula C.

¹ H NMR (400MHz, CDCl ₃ )δ11.29(s,1H),9.29(s,1H),8.93(s,1H),7.89–7.80(d2H),6.62(d,J=16.5Hz,1H) ,6.23(d,J=16.5Hz,1H),6.13(s,2H),4.22(t,J=6.3Hz,2H),2.33(s,3H),1.97(t,J=6.1Hz,2H) ,1.85–1.76(m,3H),1.63(s,3H),1.60–1.54(m,2H),1.44–1.42(m,2H),1.23(s,18H),0.97(s,6H),0.84 (t,J=6.8Hz,3H).

¹³ C NMR(101MHz,CDCl ₃ )δ159.89,157.61,157.13,137.25,135.62,134.76,131.45,131.31,131.17,130.89,126.79,76.41,76.09,75.77,70.44,60.34,38.52,33.09,32.06,30.90,28.63 ,28.61,28.55,28.47,28.33,28.24,27.81,27.67,24.74,21.67,20.67,18.02.

HRMS (ESI-TOF) m/z: [M-Br]+Calcd for C ₃₂ H ₅₂ N ₃ O ₂ 510.4054; Found 510.4059.

Example 4

The preparation method of pyridine quaternary ammonium hydrazone compound comprises the following steps:

Except that the cinnamaldehyde in step (4) of Example 1 was changed to oxalin, all the other conditions were the same as in Example 1 to obtain the compound shown in formula D.

¹ H NMR (400MHz, CDCl ₃ )δ12.29(s,1H),9.10(s,1H),8.84(s,J=2.8Hz,1H),7.87(d,J=6.5Hz,2H),7.85 (d, J=0.9Hz, 1H), 7.11(d, J=8.0Hz, 2H), 7.04(d, J=8.1Hz, 2H), 5.85(d, J=6.7Hz, 2H), 4.22(t ,J=6.3Hz,2H),2.92–2.78(m,3H),2.74–2.65(m,1H),2.47(m,J=13.5,9.1Hz,1H),1.81(m,J=14.7,6.6 Hz, 2H), 1.24(s, 18H), 1.20(d, J=6.9Hz, 6H), 1.00(d, J=6.8Hz, 3H), 0.86(t, J=6.8Hz, 3H).

¹³ C NMR(101MHz,CDCl ₃ )δ158.87,158.54,157.16,145.67,137.11,135.45,131.25,131.14,128.10,126.91,125.40,76.40,76.08,75.76,70.40,60.46,38.70,37.78,32.65,30.89,28.63 ,28.61,28.55,28.47,28.33,28.24,27.66,24.74,23.00,21.67,15.85,13.12.

HRMS(ESI-TOF) m/z: [M-Br]+Calcd for C ₃₂ H ₅₀ N ₃ O ₂ 508.3898; Found 508.3904.

Example 5

The preparation method of pyridine quaternary ammonium hydrazone compound comprises the following steps:

Except changing the bromododecane in the embodiment 1 step (1) into bromooctane, and changing the cinnamaldehyde in the embodiment 1 step (4) into new jasmonal, all the other conditions are the same as in the embodiment 1 Same, the compound shown in formula E is obtained.

¹ H NMR (400MHz, CDCl ₃ ) δ12.32(s, 1H), 9.10(s, 1H), 8.83(s, 1H), 7.86(d, J=3.0Hz, 2H), 7.83(d, J= 6.2Hz, 1H), 6.67(d, J=7.8Hz, 1H), 6.60(d, J=1.4Hz, 1H), 6.56(dd, J=7.9, 1.5Hz, 1H), 5.87(s, 2H) ,5.82(d,J=7.3Hz,2H),4.21(t,J=6.2Hz,2H),2.81(m,J=13.6,5.8Hz,1H),2.65(m,J=10.6,4.2Hz, 1H), 2.43(m, J=13.6, 8.7Hz, 2H), 1.80(m, J=14.7, 6.6Hz, 2H), 1.25(s, J=1.8Hz, 10H), 0.99(d, J=6.8 Hz,3H),0.89–0.76(t,3H).

¹³ C NMR(101MHz,CDCl ₃ )δ158.88,158.24,157.16,146.50,144.87,137.09,131.94,131.24,131.17,126.94,121.14,108.45,107.14,99.77,76.40,76.08,75.77,70.40,60.45,38.88,37.96 ,30.72,28.68,28.17,28.11,27.65,24.72,21.61,15.85,13.08.

HRMS (ESI-TOF) m/z: [M-Br]+Calcd for C ₂₆ H ₃₆ N ₃ O ₄ 454.2700; Found 454.2707.

Example 6

The preparation method of pyridine quaternary ammonium hydrazone compound comprises the following steps:

Except that the bromododecane in the embodiment 1 step (1) is changed into bromodecane, and the cinnamaldehyde in the embodiment 1 step (4) is changed into new ocean jasmonal, all the other conditions are all the same as in the embodiment 1 Same, the compound shown in formula F is obtained.

¹ H NMR (400MHz, CDCl ₃ ) δ12.30(s, 1H), 9.09(s, 1H), 8.83(s, 1H), 7.86(d, J=3.1Hz, 2H), 7.83(d, J= 6.2Hz, 1H), 6.67(d, J=7.8Hz, 1H), 6.60(d, J=1.4Hz, 1H), 6.56(m, J=7.9, 1.5Hz, 1H), 5.87(s, 2H) ,5.83(d,J=7.3Hz,2H),4.22(t,J=6.2Hz,3H),2.82(m,J=13.6,5.9Hz,1H),2.64(m,J=13.9,7.3Hz, 1H), 2.44(m, J＝13.6, 8.7Hz, 1H), 1.87–1.75(m, 2H), 1.24(s, 14H), 1.00(d, J＝6.8Hz, 3H), 0.85(t, J =6.8Hz,3H).

¹³ C NMR(101MHz,CDCl ₃ )δ158.88,158.25,157.16,146.51,144.87,137.11,131.94,131.24,131.17,126.92,121.15,108.46,107.14,99.78,76.40,76.08,75.76,70.40,60.46,38.88,37.97 ,30.85,28.49,28.46,28.28,28.23,27.66,24.73,21.65,15.86,13.11.

HRMS (ESI-TOF) m/z: [M-Br]+Calcd for C ₂₈ H ₄₀ N ₃ O ₄ 482.3013; Found 482.3020.

Example 7

The preparation method of pyridine quaternary ammonium hydrazone compound comprises the following steps:

Except changing the bromododecane in the embodiment 1 step (1) into bromotetradecane, and changing the cinnamaldehyde in the embodiment 1 step (4) into new jasmonal, all the other conditions are the same as in the embodiment 1 In the same way, the compound shown in formula G is obtained.

¹ H NMR (400MHz, CDCl ₃ ) δ12.28(s, 1H), 9.08(s, 1H), 8.83(s, 1H), 7.86(d, J=3.1Hz, 2H), 7.83(d, J= 6.2Hz, 1H), 6.67(d, J=7.8Hz, 1H), 6.59(d, J=1.5Hz, 1H), 6.55(m, J=7.9, 1.6Hz, 1H), 5.87(s, 2H) ,5.83(d,J=7.2Hz,2H),4.21(t,J=6.2Hz,3H),2.81(m,J=13.5,5.9Hz,1H),2.64(m,J=19.3,6.4Hz, 1H), 2.43(m, J＝13.6, 8.7Hz, 1H), 1.87–1.67(m, 2H), 1.23(s, 22H), 0.99(d, J＝6.8Hz, 3H), 0.85(t, J =6.8Hz,3H).

¹³ C NMR(101MHz,CDCl ₃ )δ158.92,158.20,157.13,146.50,144.87,137.15,131.94,131.23,131.18,126.93,121.15,108.45,107.14,99.78,76.41,76.09,75.78,70.39,60.45,38.88,37.97 ,30.90,28.67,28.64,28.56,28.48,28.34,28.25,27.67,24.74,21.67,15.86,13.12.

HRMS (ESI-TOF) m/z: [M-Br]+Calcd for C ₃₂ H ₄₈ N ₃ O ₄ 538.3639; Found 538.3646.

Example 8

The preparation method of pyridine quaternary ammonium hydrazone compound comprises the following steps:

Except changing dodecane bromide in embodiment 1 step (1) into hexadecane bromide, cinnamaldehyde in embodiment 1 step (4) is changed into new ocean jasmonal, all the other conditions are all the same as embodiment 1 In the same way, the compound shown in formula H is obtained.

¹ H NMR (400MHz, CDCl ₃ ) δ12.29(s, 1H), 9.09(s, 1H), 8.83(s, 1H), 7.86(d, J=3.1Hz, 2H), 7.83(d, J= 6.2Hz, 1H), 6.67(d, J=7.8Hz, 1H), 6.60(d, J=1.4Hz, 1H), 6.56(dd, J=7.9, 1.5Hz, 1H), 5.88(s, 2H) ,5.83(d,J=7.4Hz,2H),4.22(t,J=6.2Hz,3H),2.82(m,J=13.5,5.9Hz,1H),2.65(m,J=12.9,6.4Hz, 1H), 2.44(m, J＝13.6, 8.7Hz, 1H), 1.87–1.76(m, 2H), 1.23(s, 26H), 1.00(d, J＝6.8Hz, 3H), 0.85(t, J =6.8Hz,3H).

¹³ C NMR(101MHz,CDCl ₃ )δ160.01,159.35,158.25,147.59,145.96,138.21,133.02,132.33,132.24,127.99,122.24,109.54,108.23,100.86,77.48,77.16,76.84,71.44,61.55,39.97,39.06 ,31.99,29.77,29.73,29.65,29.57,29.43,29.34,28.76,25.83,22.76,16.95,14.20.

HRMS (ESI-TOF) m/z: [M-Br]+Calcd for C ₃₄ H ₅₂ N ₃ O ₄ 566.3952; Found 566.3959.

Example 9

Test of surface tension of pyridinium quaternary ammonium hydrazide compound:

According to the method of (1), (2) and (3) in Example 1, the carbon chain lengths of 8 (structure as shown in formula 4a), 10 (structure as shown in formula 4b), 12 (structure as shown in formula 4c) were synthesized. Shown), 14 (structure shown in formula 4d), 16 (structure shown in formula 4e) pyridinium quaternary ammonium salt hydrazide compounds, these compounds have good solubility in water. During the surface tension test, 20 mL of water was taken as the benchmark, and the sample solution to be tested with a concentration of 0.005 mol/L was gradually added, and finally the logC of the added sample concentration was taken as the abscissa, and the surface tension value of water was plotted on the ordinate to obtain Schematic representation of the surface tension-concentration curve. The specific test results are shown in Figure 1.

The specific test results are shown in Figure 1, which is a schematic diagram of the surface tension-concentration curve of the pyridinium quaternary ammonium salt hydrazide compound. As can be seen from the figure, when the carbon chain length is 8-16, the surface tension of water decreases after adding the sample to be tested, indicating that the pyridine quaternary ammonium hydrazide compound can effectively reduce the surface tension of water. When the carbon chain length increased from 8 to 12, the effect of the compound on reducing the surface tension of water gradually increased, but when the carbon chain length continued to increase to 14 and 16, its surface activity weakened instead. When the carbon chain length is 12, it can reduce the surface tension of water to about 25.5mN/m, indicating that it is a very good surfactant. In the following, it is used as a substrate to react with various fragrance aldehydes and ketones to generate corresponding hydrazone compounds, and then its antibacterial and fragrance-releasing properties are tested.

Example 10

Bacteriostasis test of pyridinium quaternary ammonium hydrazone compounds and pyridinium quaternary ammonium hydrazide compounds:

The 8 pyridine quaternary ammonium salt hydrazone compounds prepared in Examples 1 to 8 and the pyridine quaternary ammonium salt hydrazide compound prepared in Example 9: the carbon chain length is 8 (structure shown in formula 4a), and the carbon chain length is 10 (structure shown in formula 4b), carbon chain length of 12 (structure shown in formula 4c), carbon chain length of 14 (structure shown in formula 4d), carbon chain length of 16 (structure shown in formula 4e) , respectively weighed 12.8 mg of the above compounds and placed them in a volumetric flask, diluted with water to a concentration of 1280 μg/mL, and filtered through a 0.45 μm organic phase filter head to ensure that no bacteria existed in the product aqueous solution. Subsequently, the above aqueous solutions were diluted to concentrations of: 640, 320, 160, 80, 40, 20, 10, 5, 2.5, 1.25 μg/mL. Pipette gun to pipette 10 μL of the above solutions of different concentrations into 96-well plates, and add 90 μL of bacterial culture medium with a concentration of 10 ⁵ cfu/mL to each well plate. After the addition, keep the 96-well plate at 37°C Place it in the box for 24 hours and observe the growth of bacteria to obtain the minimum concentration that inhibits the growth of bacteria, which is the MIC value. The lower the MIC value, the better the antibacterial performance of the compound, and the specific data results are shown in Table 1.

Table 1

As can be seen from Table 1, pyridinium quaternary ammonium hydrazone compounds or pyridinium quaternary ammonium hydrazide compounds have broad-spectrum antibacterial properties against Gram-positive bacteria and Gram-negative bacteria, and can be killed at a certain concentration. Inhibits the growth of bacterial cells. The prerequisite for pyridine quaternary ammonium hydrazone compounds to function is that the compound with a positively polarized head group undergoes electrostatic interaction with the negatively charged bacterial cell membrane on the surface, selectively adsorbs on the bacterial surface, and penetrates the bacterial cell plasma membrane. Sex changes, important enzymes and nutrients in bacteria flow out, and bacterial cells die to achieve the purpose of sterilization. Therefore, the longer the carbon chain length, the better the antibacterial performance, and when the carbon chain length increases to a certain extent, the adsorption force decreases, which directly affects the decisive conditions for the contact between pyridine quaternary ammonium hydrazone compounds and bacteria, thereby affecting the antibacterial effect. As can be seen from the data in Table 1, whether it is a pyridinium quaternary ammonium hydrazone compound or a pyridinium quaternary ammonium hydrazide compound, the antibacterial effect of the compound containing 12 or 14 carbons in the structure is higher than that containing 8, 10 or 16 carbons. Compounds of carbon are better. Also, since Gram-positive bacteria have only one cell wall that is not closely associated with the cell membrane, most compounds are more potent against Gram-positive bacteria than Gram-negative bacteria.

Observing the MIC values of the four pyridine quaternary ammonium salt hydrazone compounds containing the same long carbon chain but reacting with different aromatic aldehydes and ketones in Table 1, it can be found that the inhibitory effect of this series of compounds on bacterial cells Bacteria is not only related to long carbon chains. This is due to the active functional group of imine bond (-CONHN=CH-) contained in the pyridine quaternary ammonium hydrazone compound. The oxygen and nitrogen atoms contained in it can participate in the formation of hydrogen bonds in organisms and inhibit the occurrence of many biochemical processes. So it has good antibacterial activity.

Example 11

Detection of pyridine quaternary ammonium hydrazone compounds hydrolyzed to release aldehydes and ketones fragrance substances:

Using solid-phase microextraction-gas chromatography to detect the hydrolysis of pyridine quaternary ammonium hydrazone compounds in acidic aqueous solution, and the volatilization of equimolar amounts of pure fragrance molecules under the same experimental conditions, by comparing the peak area data of these two groups, It shows that the pyridine quaternary ammonium hydrazone compound has the function of controlling and delaying the release of fragrance substances.

The specific test method is: add 0.04mmol of pyridinium quaternary ammonium hydrazone compound into a sealed headspace bottle, add 0.5mL of absolute ethanol (using the miscibility of water and ethanol to better dissolve the sample) and 0.5mL of lemon acid-sodium citrate buffer, then place the headspace vial in an oil bath and heat at 60 °C. After heating for 10 minutes, the extraction fiber was inserted into the upper space of the headspace bottle and extracted for 10 minutes. Quickly insert the needle into the rear sampling port of the GC, and the fragrance components adsorbed on the fiber are desorbed at high temperature, and enter the gas phase smoothly for analysis. The desorption time was 5 minutes, and the gas chromatograph was started for data acquisition at the same time. For reference, pure fragrance molecules are treated in the same way.

Solid phase microextraction operating conditions: Aldehyde/ketone fragrance release performance was assessed by solid phase microextraction (SPME) consisting of a SPME holder and a needle with fibers. The fibers were coated with a carboxy/polydimethylsiloxane (CAR/PDMS) adsorption coating and had a diameter of 75 μm. Before use, the SPME needle with the extraction fiber was inserted into the rear inlet of the GC, and pretreated at 250 °C for 30 minutes, and the flow rate of the carrier gas (helium) was kept at 1.0 mL/min.

Figures 2 to 5 show the headspace release properties of various pyridinium quaternary ammonium salt hydrazone compounds, taking time as the abscissa, and releasing the peak area of the aroma substance as the ordinate to obtain a time-peak area curve, and Fig. 2 is a pyridinium quaternary ammonium Salt hydrazone compounds A and pure fragrance substances release the time-peak area curve schematic diagram of aromatic substances. A schematic diagram of the time-peak area curve of the release of aromatic substances by the quaternary ammonium salt hydrazone compound C and pure fragrance substances.

As can be seen from the figure, the release amount of all pure fragrance substances is greater than the hydrolysis release amount of pyridine quaternary ammonium salt hydrazone compounds. This is due to the fact that under the condition of acidic aqueous solution, the imine bond of the pyridine quaternary ammonium hydrazone compound is broken and hydrolyzed to form hydrazide and aromatic aldehyde and ketone. As the reaction progresses, the hydrolysis gradually tends to a dynamic equilibrium, and the aromatic gas phase components that volatilize into the upper space of the headspace bottle under heating conditions gradually become stable, while the pure fragrance substances show a Tendency for rapid, high-volume release over time.

By comparing several pictures, it can be found that different aromatic aldehyde and ketone molecules have different release rates and release amounts. Among them, the release amount of compound C and its corresponding β-ionone is the largest, because the boiling point of β-ionone is only 126°C, which is lower than the other three aromatic aldehydes. In addition, the release profiles of four pyridinium quaternary ammonium hydrazone compounds with different chemical structures were also significantly different. The ratio of the release amount of pure samples of cinnamaldehyde and β-ionone to the amount of aromatic substances released by the hydrolysis of the pyridine quaternary ammonium salt hydrazone compounds formed respectively is greater than that of Xinyang jasmonal and rabbit ear oxalin (A: 18 times, C: 17 times compared to B: 8 times, D: 6 times), which is attributed to the existence of the conjugated structure in compounds A and C, which makes the chemical structure more stable. It can be concluded that the pyridine quaternary ammonium hydrazone compounds have the effect of controlling and delaying the release of aroma, and the different structures of the compounds and the different boiling points of the aromatic substances can lead to different aroma release behaviors.

The pyridinium quaternary ammonium hydrazone compounds synthesized in the present application can hydrolyze and release aldehydes, ketones and fragrance substances in aqueous solution, and the pyridinium quaternary ammonium hydrazide compounds remaining in the solution system after hydrolysis also have good surface activity and antibacterial ability. If it is applied to some weakly acidic washing products, it can not only reduce the surface tension of water, but also sterilize and inhibit the bacteria of clothes, and at the same time make the fragrance in washing products last longer, so it has a certain market application prospect .

The above description is only a preferred embodiment of the present invention, and does not limit the present invention in any form. Although the present invention has been disclosed as above with preferred embodiments, it is not intended to limit the present invention. Anyone familiar with the technology of this patent Without departing from the scope of the technical solution of the present invention, personnel can use the technical content of the above prompts to make some changes or modify them into equivalent embodiments with equivalent changes. In essence, any simple modifications, equivalent changes and modifications made to the above embodiments still fall within the scope of the solutions of the present invention.

Claims (3)

1. a pyridine quaternary ammonium salt type hydrazone compound, is characterized in that, described pyridine quaternary ammonium salt type hydrazone compound is a kind of in the following structure:

2. a preparation method of the described pyridine quaternary ammonium salt type hydrazone compound of claim 1, is characterized in that, comprises the following steps: Dissolve 3-hydroxypyridine in the solvent, add base, react at a temperature of 20-60°C for 0.1-48 hours, add haloalkane dropwise, the molar ratio of 3-hydroxypyridine, base, and haloalkane is 1:(2-30) : 1, obtain intermediate pyridine compound after reaction is complete; Dissolve the intermediate pyridine compound in the solvent, add ethyl haloacetate, the molar ratio of the intermediate pyridine compound to ethyl haloacetate is 1:(1.1~2), and react at a temperature of 20~60°C for 0.1 ~48h, to obtain the pyridinium quaternary ammonium salt compound; Dissolve hydrazine hydrate in the solvent, dissolve the pyridinium quaternary ammonium compound in the solvent, and slowly add it to the solution of the above-mentioned hydrazine hydrate, the molar ratio of hydrazine hydrate to the pyridinium quaternary ammonium compound is (5～15):1, the temperature Reaction under the condition of 20-60°C for 0.1-48 hours to obtain pyridinium quaternary ammonium hydrazide compound; dissolving the pyridinium quaternary ammonium salt type hydrazide compound and aldehyde or ketone spices in a molar ratio of 1:(1.1～2) in a solvent, and reacting under reflux to obtain the pyridinium quaternary ammonium salt type hydrazone compound; Wherein, the solvent is dimethyl sulfoxide, ethyl acetate or ethanol; the alkali is potassium hydroxide or sodium hydroxide; the halogenated alkyl is bromododecane or bromotetradecane; the halogenated Ethyl acetate is ethyl bromoacetate; the aldehyde or ketone fragrance is cinnamaldehyde, jasmonal, β-ionone or rabbit ear oxalin. 3. the application of a pyridinium quaternary ammonium salt type hydrazone compound according to claim 1 in the preparation of antibacterial agent or perfume slow-release agent.

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