CN107879950B

CN107879950B - N' -long-chain alkyl-N, N-diethyl acetamidine and preparation method and application thereof

Info

Publication number: CN107879950B
Application number: CN201710952052.2A
Authority: CN
Inventors: 侯庆锋; 郭东红; 赵玉军; 徐艳; 王帆; 罗健辉
Original assignee: Petrochina Co Ltd
Current assignee: Petrochina Co Ltd
Priority date: 2017-10-13
Filing date: 2017-10-13
Publication date: 2020-05-08
Anticipated expiration: 2037-10-13
Also published as: CN107879950A

Abstract

The invention provides N' -long-chain alkyl-N, N-diethyl acetamidine and a preparation method and application thereof. The preparation method comprises the following steps: dissolving N-long-chain alkyl acetimidate methyl ester and diethylamine in an organic solvent, wherein the molar ratio of the N-long-chain alkyl acetimidate methyl ester to the diethylamine is 1:1-1:100, and the weight percentage of the organic solvent accounts for 0-99% of the total weight of the N-long-chain alkyl acetimidate methyl ester, the diethylamine and the organic solvent; heating to 20-100 ℃, and reacting for 0.1-100 h under normal pressure; reducing the pressure to 0.01-0.08 MPa, reacting for 0.1-24 h at the temperature of 20-120 ℃, and stopping the reaction to obtain the N' -long-chain alkyl-N, N-diethyl acetamidine. The invention also provides the N' -long-chain alkyl-N, N-diethyl acetamidine prepared by the preparation method and application thereof. The preparation method of the N' -long-chain alkyl-N, N-diethyl acetamidine is simple in synthesis and environment-friendly.

Description

N' -long-chain alkyl-N, N-diethyl acetamidine and preparation method and application thereof

Technical Field

The invention relates to an amidine compound and a preparation method thereof, in particular to N' -long-chain alkyl-N, N-diethyl acetamidine and a preparation method thereof, and belongs to the technical field of organic material synthesis.

Background

Amidines are important organic synthetic intermediates which are widely used as anti-inflammatory agents, herbicides, anthelmintics, acaricides, diuretics, drugs for treating diabetes and cardiovascular and cerebrovascular diseases and anticancer drugs (Qinhang, Yangjing, Wehui, etc.. aryl, arylmethyl and piperazinylamines are designed and synthesized and have double inhibitory activities on 5-HT and NE reuptake [ J]The Proc of chemical schools higher 2009,30(5): 938-. In recent years, the compound is found to be novel CO₂/N₂The interface activity of the responsive surfactant can be bidirectionally regulated according to environmental changes, and is widely researched in the fields of emulsion polymerization, nano materials, environmental protection and the like (Y.Liu, P.G.Jeshop, M.Cunningham M, C.A.Eckert, C.L.Liotta, science.2006,313, 958-960).

At present, the synthetic methods of amidine compounds mainly comprise:

(1) direct process

The direct method adopts the condensation reaction of carbonyl amine, and is a classical method for forming carbon-nitrogen double bonds. For example, aldehyde and ketone react with primary amine, hydroxylamine and hydrazine to produce Schiff base, oxime and hydrazone, respectively. Such reactions have long been used for purification and identification of ketones and aldehydes, and for protection of carboxamides (Wanlin. research on synthesis and application of amidino-containing switch-type surfactants [ D ] university of university, 2008.).

(2) An indirect method:

the indirect method adopts amide acetal reaction, under the protection of nitrogen, N-dimethyl amide dimethyl acetal and primary long-chain aliphatic amine are used as raw materials to synthesize the long-chain alkyl amidine compound (Dojie, Dougui. Xiaohui. the amide acetal method is used to synthesize the mono (di) long-chain alkyl amidine compound [ J ]. the synthetic chemistry, 2010,18(5): 636-638.).

(3) Acid chloride process

Yamada et al, using an amide to react with dimethylcarbamoyl chloride to form an amidine under the following reaction conditions: the feeding ratio of the amide to the dimethylcarbamoyl chloride is 1: toluene as solvent, at 110 ℃ for 16 hours (Yamada T, Lukac P J, MathewGeorge A, et al. reversible, from-Temperature Ionic liquids. Amidinium Carbomate derivatives from amides and Aliphatic Primary amides with Carbon Dioxide [ J ]. Chemistry of Materials,2007,19(5): 967-969.).

However, the above synthetic methods have some disadvantages in application: the amine carbonyl condensation reaction method needs to consume a large amount of phosphorus trichloride as a catalyst and a dehydrating agent to promote the reaction, and the phosphorus trichloride is a highly toxic product and can cause pollution to the environment and damage to human bodies, so that the development and application of the phosphorus trichloride are limited; in the acyl chloride method, the reaction of amide and acyl chloride is a complex process, N-disubstituted amidine is easy to generate, and the operation is complicated; in the indirect amide acetal reaction, the synthesis process of the N, N-dimethyl amide dimethyl acetal is complex, the comprehensive yield is low, and the generated reaction product amidine has single type.

Moreover, when the above synthesis method is applied to the synthesis of N '-long-chain alkyl-N, N-substituent amidine, the method is mainly limited to the target product of connecting a single-bond nitrogen atom with a methyl group, and a production method for connecting other groups (such as an ethyl group) such as N' -long-chain alkyl-N, N-diethylacetamidine to the single-bond nitrogen atom has not been reported so far.

Disclosure of Invention

In order to solve the technical problems, the invention aims to provide a preparation method of N' -long-chain alkyl-N, N-diethyl acetamidine, which has a simple synthesis method and is environment-friendly.

In order to achieve the above technical object, the present invention provides a method for preparing N' -long-chain alkyl-N, N-diethylacetamidine (long-chain alkyl is an alkyl having 7 or more carbons), comprising the steps of:

dissolving N-long-chain alkyl acetimidate methyl ester and diethylamine in an organic solvent at the temperature of 5-40 ℃, wherein the molar ratio of the N-long-chain alkyl acetimidate methyl ester to the diethylamine is 1:1-1:100, and the weight percentage of the organic solvent accounts for 0-99% of the total weight of the N-long-chain alkyl acetimidate methyl ester, the diethylamine and the organic solvent (the organic solvent can be not added);

heating to 20-100 ℃, and reacting for 0.1-100 h under normal pressure;

reducing the pressure to 0.01-0.08 MPa, reacting for 0.1-24 h at the temperature of 20-120 ℃, and stopping the reaction to obtain the N' -long-chain alkyl-N, N-diethyl acetamidine.

In the above production method, preferably, the organic solvent used is an organic amine solution and/or an aprotic solvent.

In the above preparation method, preferably, the organic solvent used is one or a combination of several of triethylamine, tripropylamine, 1, 4-dioxane and acetonitrile.

In the above production method, it is preferable that the molar ratio of the methyl N-long-chain alkyl acetimidate to the diethylamine is 1:1 to 1: 80; more preferably, the molar ratio is 1: 20.

In the above production method, preferably, the absolute pressure of the atmospheric reaction is 0.08MPa to 0.15 MPa; more preferably, the absolute pressure is 0.1 MPa.

The invention also provides N' -long-chain alkyl-N, N-diethyl acetamidine, which is prepared by the preparation method.

Among the above-mentioned N '-long-chain alkyl-N, N-diethylacetamidins, preferably, the N' -long-chain alkyl-N, N-diethylacetamidins has the following structural formula:

wherein R is C_nH_2n+1Wherein n is an integer greater than 7.

The N' -long-chain alkyl-N, N-diethylacetamidine can be used as CO₂/N₂Response switch type surfactants are used in oil extraction.

The N' -long-chain alkyl-N, N-diethyl acetamidine can also be used for synthesizing anti-inflammatory drugs, herbicides, anthelmintics, acaricides, diuretics, hypoglycemic drugs or anticancer drugs, or for synthesizing drugs for treating cardiovascular and cerebrovascular diseases.

The preparation method of the N' -long-chain alkyl-N, N-diethyl acetamidine takes diethylamine and N-long-chain alkyl acetimidate methyl ester as raw materials, the reaction is carried out in an organic solvent, methanol is volatilized through decompression reaction, and the reaction is continued to synthesize a target product under the condition of continuously removing the product methanol; and in the reaction process, carrying out a normal pressure reaction and then carrying out a reduced pressure reaction, and removing volatile substances and an organic solvent during the reaction until the organic solvent is completely removed to obtain the N' -long-chain alkyl-N, N-diethyl acetamidine.

The preparation method of the N '-long-chain alkyl-N, N-diethyl acetamidine takes the N-long-chain alkyl acetimidate methyl ester and diethylamine as raw materials, the reaction selectivity of the target product is 100 percent, no other by-product is generated, and the yield of the N' -long-chain alkyl-N, N-diethyl acetamidine can reach more than 60 percent at most.

The preparation method of the N '-long-chain alkyl-N, N-diethyl acetamidine has simple process and is environment-friendly, and provides a novel alternative technology for the production of the N' -long-chain alkyl-N, N-diethyl acetamidine.

Drawings

FIG. 1 is a mass spectrum (acetonitrile dilution) of the reaction product of example 1.

FIG. 2 is a 1H NMR (CDCl3,500M) spectrum of the reaction product of example 1.

FIG. 3 is a 13C NMR (CDCl3,125M) spectrum of the reaction product of example 1.

FIG. 4 is an IR spectrum of the reaction product of example 1.

FIG. 5 is a mass spectrum (acetonitrile dilution) of the reaction product of example 3.

FIG. 6 is a 1H NMR (CDCl3,500M) spectrum of the reaction product of example 3.

FIG. 7 is a 13C NMR (CDCl3,125M) spectrum of the reaction product of example 3.

FIG. 8 is an IR spectrum of the reaction product of example 3.

Fig. 9 is a conductivity cycling curve for example 7.

Detailed Description

The technical solutions of the present invention will be described in detail below in order to clearly understand the technical features, objects, and advantages of the present invention, but the present invention is not limited to the practical scope of the present invention.

Example 1

This example provides a N' -hexadecyl-N, N-diethylacetamidine, prepared as follows:

weighing 2.97g of methyl N-hexadecylethylidene acid into a four-neck flask with a condensing tube, a vacuum device and a thermometer at 25 ℃, adding 14.63 of diethylamine, then adding 20mL of triethylamine and 30mL of 1, 4-dioxane, heating to 85 ℃ in a constant-temperature oil bath, and reacting for 36h under 0.1 MPa;

then decompressing to 0.08MPa, reacting for 30min at 60 ℃ to obtain a light yellow liquid product, namely N '-hexadecyl-N, N-diethyl acetamidine, wherein the yield of the N' -hexadecyl-N, N-diethyl acetamidine is 60%.

The mass spectrum (diluted acetonitrile) of the product synthesized in this example is shown in fig. 1, wherein M/z-339.3757 is the molecular weight of the target product N' -hexadecyl-N, N-diethylacetamidine [ M + H + ] and the theoretical calculation value is 339.3733.

The 1H NMR (CDCl3,500M) spectrum of the product synthesized in this example is shown in FIG. 2, wherein the chemical shifts of the hydrogens of N' -hexadecyl-N, N-diethylacetamidine are contained: 0.88 (t; 3H; CH3C15H 30); 1.08 (t; 6H; N (CH)₂CH₃)₂)；1.26(m；26H；CH₃C₁₃H₂₆CH₂CH₂N)；1.47(m；2H；CH₃C₁₃H₂₆CH₂CH₂N)；1.87(s；3H；CH₃-C)；3.17(t；2H；C₁₅H₃₁CH₂N)；3.31(q；4H；N(CH₂CH₃)₂) (the chemical shift values corresponding to the positions of the obtained product hydrogen are labeled as the chemical formula in FIG. 2).

Of the product synthesized in this example¹³C NMR(CDC_l3125M) spectrum shown in fig. 3, wherein the chemical shift peak of the target product N' -hexadecyl-N, N-diethylacetamidine is contained: 13.67 (CH)₃-C)；14.04(C₁₅H₃₀CH₃)；14.34(N(CH₂CH₃)₂) (ii) a 22.65-29.68 (multiplet, C)₁₅H₃₀CH₃)；31.90(NCH₂CH₂)；49.29(N(CH₂CH₃)₂)；49.73(C₁₅H₃₁CH₂N)；156.57(C＝N)。

The infrared spectrum of the product synthesized in this example is shown in FIG. 4, wherein the wavelength is 1620.76cm^-1The peak is the absorption peak of-N-C ═ N- (amidine compound) bond, and the peak is the characteristic peak of N' -hexadecyl-N, N-diethylacetamidine.

Example 2

weighing 2.97g of N-hexadecyl ethylidene amino methyl ester into a four-neck flask with a condensing tube, a vacuum device and a thermometer at 25 ℃, adding 7.26 of diethylamine, then adding 30mL of triethylamine and 20mL of 1, 4-dioxane, heating to 70 ℃ in a constant-temperature oil bath, and reacting for 42h under 0.1 MPa;

then reducing the pressure to 0.03MPa, and reacting for 10h at 60 ℃ to obtain a light yellow liquid product, namely N '-hexadecyl-N, N-diethyl acetamidine, wherein the yield of the N' -hexadecyl-N, N-diethyl acetamidine is 58%.

Example 3

This example provides a method for synthesizing N' -octadecyl-N, N-diethylacetamidine, which includes the following steps:

weighing 3.25g of N-octadecyl ethylidene amino acid methyl ester into a four-neck flask with a condensing tube, a vacuum device and a thermometer at 35 ℃, adding 14.63 of diethylamine, then adding 20mL of triethylamine and 30mL of 1, 4-dioxane, heating to 85 ℃ in a constant-temperature oil bath, and reacting for 36h under 0.1 MPa;

then, the pressure is reduced to 0.05MPa, and the reaction is carried out for 2h at the temperature of 60 ℃ to obtain a light yellow liquid product, namely N '-octadecyl-N, N-diethyl acetamidine, wherein the yield of the N' -octadecyl-N, N-diethyl acetamidine is 54%.

The mass spectrum (diluted acetonitrile) of the product synthesized in this example is shown in fig. 5, where M/z-367.4065 is the molecular weight of the target product N' -octadecyl-N, N-diethylacetamidine [ M + H + ], and the theoretical calculation value is 367.4046.

1H NMR (CDC) of the product synthesized in this example_l3500M) spectrum shown in FIG. 6, wherein the chemical shift of hydrogen containing N' -octadecyl-N, N-diethylacetamidine: 0.88 (t; 3H; CH)₃C₁₇H₃₄)；1.10(t；6H；N(CH₂CH₃)₂)；1.26(m；30H；CH₃C₁₅H₃₀CH₂CH₂N)；1.48(m；2H；CH₃C₁₅H₃₀CH₂CH₂N)；1.88(s；3H；CH₃-C)；3.16(t；2H；C₁₇H₃₅CH₂N)；3.32(q；4H；N(CH₂CH₃)₂) (the chemical shift values corresponding to the positions of the obtained product hydrogen are labeled by the chemical formula in FIG. 6).

Of the product synthesized in this example¹³C NMR(CDC_l3125M) spectrum is shown in fig. 7, wherein the chemical shift peak of the target product, N' -octadecyl-N, N-diethylacetamidine, is contained: 13.67 (CH)₃-C)；14.03(C₁₇H₃₄CH₃)；14.34(N(CH₂CH₃)₂) (ii) a 22.64-29.67 (multiplet, C)₁₇H₃₄CH₃)；31.81(NCH2CH2)；49.28(N(CH₂CH₃)₂)；49.77(C₁₇H₃₅CH₂N)；156.55(C＝N)。

The infrared spectrum of the product synthesized in this example is shown in FIG. 8, wherein the wavelength is 1621.46cm^-1The peak is the absorption peak of-N-C ═ N- (amidine compound) bond, and the peak is the characteristic peak of N' -octadecyl-N, N-diethylacetamidine.

Example 4

This example provides a N' -octadecyl-N, N-diethylacetamidine, prepared by the following steps:

weighing 3.25g of N-octadecyl ethylidene amino acid methyl ester into a four-neck flask with a condensing tube, a vacuum device and a thermometer at 30 ℃, adding 21.95g of diethylamine, then adding 20mL of triethylamine and 25mL of 1, 4-dioxane, heating to 80 ℃ in a constant-temperature oil bath, and reacting for 34h under 0.1 MPa;

then reducing the pressure to 0.03MPa, reacting for 10h at 55 ℃ to obtain a light yellow liquid product, namely N '-octadecyl-N, N-diethyl acetamidine, wherein the yield of the N' -octadecyl-N, N-diethyl acetamidine is 52%.

Example 5

This example provides a N' -dodecyl-N, N-diethylacetamidine, prepared as follows:

weighing 2.41g of N-dodecyl methyl acetimidate into a four-neck flask with a condenser tube, a vacuum device and a thermometer at 10 ℃, adding 29.3g of diethylamine, heating to 50 ℃ in a constant-temperature oil bath, and reacting for 48h under 0.1 MPa;

then reducing the pressure to 0.03MPa, reacting for 2h at 55 ℃ to obtain a light yellow liquid product, namely N '-dodecyl-N, N-diethyl acetamidine, wherein the yield of the N' -dodecyl-N, N-diethyl acetamidine is 56%.

Example 6

This example provides a N' -tetradecyl-N, N-diethylacetamidine, prepared by the following steps:

weighing 2.69g of N-tetradecyl ethylidene amino acid methyl ester into a four-neck flask with a condenser tube, a vacuum device and a thermometer at the temperature of 15 ℃, firstly adding 25.6g of diethylamine, then adding 10mL of triethylamine and 30mL of 1, 4-dioxane, heating to 80 ℃ in a constant-temperature oil bath, and reacting for 36h under the pressure of 0.1 MPa;

then, the pressure is reduced to 0.06MPa, and the reaction is carried out for 4h at 60 ℃ to obtain a light yellow liquid product, namely N '-tetradecyl-N, N-diethylacetamidine, wherein the yield of the N' -tetradecyl-N, N-diethylacetamidine is 57%.

Example 7

This example uses N' -hexadecyl-N, N-diethylacetamidine synthesized in example 1 as an example, by switching the CO introduction₂And N₂Gas, measuring the change in conductivity, demonstrating CO of N' -long chain alkyl-N, N-diethylacetamidine₂/N₂And (4) switching on and off.

Pouring 45mL of dimethyl sulfoxide and 5mL of water into a brown flask by using a measuring cylinder, heating the flask to 65 ℃ in a constant-temperature oil bath, and adding 0.15g of the N' -hexadecyl-N, N-diethylacetamidine synthesized in example 1 into the solution; opening a conductivity meter switch, setting automatic recording data, and recording once every 10 s; the mass flow meter was turned on and CO was introduced at a flow rate of 400mL/min₂Until the conductivity curve is flat, the conductivity curve is not changed;

stopping the introduction of CO₂N was introduced at a flow rate of 800mL/min₂Until the conductivity value approaches the initial CO cut-in₂A previous conductivity value;

sequentially and circularly introducing CO according to the steps₂And N₂Four cycles were achieved and the experiment was stopped to obtain an N' -hexadecyl-N, N-diethylacetamidine on-off cycle curve as shown in FIG. 9. When CO is introduced₂Then, the conductivity of the solution rapidly rises to a peak value, and the conductivity of the peak value is kept stable; in the introduction of N₂During the process, the conductivity value gradually decreases and returns to the initial value. This demonstrates that the N' -hexadecyl-N, N-diethylacetamidinetomidine synthesized in this example has excellent CO₂/N₂Switching performance. And the repeatability of four cycles indicates that the surfactant has better stability.

Example 8

In this example, using N '-octadecyl-N, N-diethylacetamidine synthesized in example 3 as an example, a dodecane-water oil-water system containing N' -octadecyl-N, N-diethylacetamidine was passed through a respective CO-trap₂And N₂It is proved that N' -long-chain alkyl-N, N-diethyl acetamidine is introduced into CO₂And N₂Has emulsification-demulsification performance under the condition of (1).

2.5mL of water and 2.5mL of dodecane were added to a stoppered tube, and 0.022g of the N' -octadecyl-N, N-diethylacetamidine of example 3 was weighed out;

introducing CO at room temperature at a gas flow rate of 20mL/min₂5min, observing the emulsification state;

after standing for 12 hours, observing the demulsification condition;

introducing N at 40 deg.C with a gas flow of 40ml/min₂And (5) observing the emulsion breaking condition of the emulsion.

The emulsion breaking performance of the N' -octadecyl-N, N-diethylacetamidine synthesized in the example was tested. It was found that CO was not introduced₂The oil-water system is in a two-phase insoluble state; when CO is introduced₂After 5min of gas, uniformly mixing oil and water phases to form uniform emulsion; after the emulsion is stood for 12 hours at room temperature, 90 percent of an emulsion layer still exists; finally introducing N at 40 DEG C₂And (5) gas for 1h, emulsion breaking and layering. Illustrating the introduction of CO into the N' -octadecyl-N, N-diethylacetamidine synthesized in this example₂And N₂Has emulsification-demulsification performance under the condition of (1).

The above examples illustrate that, in the method for preparing N ' -alkyl-N, N-diethylacetamidine, the yield of N ' -long-chain alkyl-N, N-diethylacetamidine can reach more than 50%, the method is simple to operate, the volatile product is easy to recover, the method is environment-friendly, and the prepared N ' -alkyl-N, N-diethylacetamidine has better CO content₂/N₂Sensitive switching property and emulsion breaking property, and can be applied to the oil exploitation industry.

Claims

1. A preparation method of N' -long-chain alkyl-N, N-diethyl acetamidine is characterized by comprising the following steps:

dissolving N-long-chain alkyl acetimidate methyl ester and diethylamine in an organic solvent at the temperature of 5-40 ℃, wherein the molar ratio of the N-long-chain alkyl acetimidate methyl ester to the diethylamine is 1:1-1:100, and the weight percentage of the organic solvent accounts for 0-99% of the total weight of the N-long-chain alkyl acetimidate methyl ester, the diethylamine and the organic solvent;

heating to 20-100 ℃, and reacting for 0.1-100 h under normal pressure;

reducing the pressure to 0.01-0.08 MPa, reacting for 0.1-24 h at the temperature of 20-120 ℃, and stopping the reaction to obtain N' -long-chain alkyl-N, N-diethyl acetamidine;

the N' -long-chain alkyl-N, N-diethyl acetamidine has the following structural formula:

wherein R is C_nH_2n+1Wherein n is an integer greater than 7.

2. The method according to claim 1, wherein the organic solvent is an organic amine solution and/or an aprotic solvent.

3. The preparation method according to claim 1 or 2, wherein the organic solvent is one or a combination of triethylamine, tripropylamine, 4-dioxane and acetonitrile.

4. The method according to claim 1, wherein the molar ratio of the methyl N-long-chain alkyl acetimidate to the diethylamine is 1:1 to 1: 80.

5. The method according to claim 1 or 4, wherein the molar ratio of the methyl N-long-chain alkyl acetimidate to the diethylamine is 1: 20.

6. The method according to claim 1, wherein the absolute pressure of the atmospheric reaction is 0.08MPa to 0.15 MPa.

7. The production method according to claim 6, wherein the absolute pressure is 0.1 MPa.