CN102993056A - Preparation method of chlorhexidine compound - Google Patents

Preparation method of chlorhexidine compound Download PDF

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CN102993056A
CN102993056A CN2012105116734A CN201210511673A CN102993056A CN 102993056 A CN102993056 A CN 102993056A CN 2012105116734 A CN2012105116734 A CN 2012105116734A CN 201210511673 A CN201210511673 A CN 201210511673A CN 102993056 A CN102993056 A CN 102993056A
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chlorhexidine
hexamethylene
preparation method
solvent
reaction
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CN2012105116734A
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刘国华
耿来红
张鹏云
刘茵
霍利春
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甘肃省化工研究院
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Abstract

The invention discloses a preparation method of chlorhexidine compound and belongs to the field of organic chemical synthesis. The preparation method comprises the following steps: carrying out a heating reflux reaction on hexamethylene-dicyanoguanidine and chloroaniline hydrochloride as raw materials and glycol ether or normal butanol as a solvent to directly obtain a target compound in a single step. The preparation method is simple in process, mild in reaction condition, short in reaction time, rapid and efficient; as the glycol ether or normal butanol is used as the solvent, the influence of the toxic or side effect of the solvent on a human body is reduced, meanwhile the environmental pollution is reduced; and as a catalyst is not used in the synthesis process, an aftertreatment process is simplified, the synthetic comprehensive cost is effectively reduced, the yield of a final product can reach as high as 84.7%, the purity of the final product can reach as high as 97%, thus the preparation method has a better industrial application prospect.

Description

一种双氯苯双胍己烷化合物的制备方法 A method of preparing the compounds of chlorhexidine

技术领域 FIELD

[0001] 本发明属于有机合成化学领域,涉及一种抗菌剂一双氯苯双胍己烷化合物的制备方法。 [0001] The present invention belongs to the field of organic synthetic chemistry, a process for preparing a compound hexane pair of an antimicrobial agent chlorhexidine.

背景技术 Background technique

[0002] 双氯苯双胍己烷,又名盐酸氯己定,具有相当强的广谱抑菌、杀菌作用,是一种较好的杀菌消毒剂,对革兰氏阳性和阴性菌的抗菌作用,比新洁尔灭等消毒药强,即使在有血清、血液等存在时仍有效。 [0002] chlorhexidine, chlorhexidine hydrochloride, also known as having a very strong broad-spectrum antimicrobial, bactericidal effect, is a good disinfectant, antibacterial activity against Gram-positive and negative bacteria strong disinfectants such as benzalkonium bromide ratio is still effective even in the presence of serum and blood. 它广泛应用于口腔消炎、抑制牙斑形成、治疗座疮和手术过程中的腹腔、肠道粘膜消毒等领域。 It is widely used oral anti-inflammatory, inhibiting formation of dental plaque, the treatment of abdominal seat, intestinal mucosa and disinfection art sores and surgical procedures.

[0003] 双氯苯双胍己烷的分子式为=C22H3tlC12Nltl • 2HC1 ;化学结构式为: [0003] Formula chlorhexidine is = C22H3tlC12Nltl • 2HC1; chemical structural formula:

Figure CN102993056AD00031

目前,双氯苯双胍己烷的合成,一般是通过对氯苯胺盐酸盐与双氰胺钠在乙醇中反应生成中间体,再与己二胺盐酸盐在硝基苯中加热反应制备而得。 Currently, the synthesis of chlorhexidine, generally by dicyandiamide-chloroaniline hydrochloride to form intermediate sodium in ethanol was prepared by reacting the reaction was heated with hexamethylenediamine hydrochloride and nitrobenzene too. 这种方法存在着溶剂硝基苯的价格比较昂贵,而且污染高,毒副作用大,总产率低,且副反应不易控制等一切问题,因而影响了双氯苯双胍己烷的工业化应用。 In this way there is nitrobenzene solvent expensive, and high pollution, toxic side effects, the total yield is low, and the side reaction is difficult to control all the other problems, thereby affecting the industrial application of the chlorhexidine.

发明内容 SUMMARY

[0004] 本发明的目的是针对现有技术中存在的问题,提供一种高效率、高产率、低成本合成双氯苯双胍己烧的方法。 [0004] The object of the present invention is directed to the problems in the prior art, to provide a highly efficient, high yield, low cost synthetic chlorhexidine already burning method.

[0005] 本发明制备双氯苯双胍己烷化合物的方法,是在有机溶剂中,己撑-二氰基胍与对氯苯胺盐酸盐以1:1. 8〜1:2. 4的摩尔比,于135〜175°C下,冷凝回流反应2〜7h ;反应液静置,抽滤,加水洗漆,得到白色固体;再用乙醇洗涤纯化,得到纯品双氯苯双胍己烷化合物。 [0005] The method of preparing the compounds of chlorhexidine of the present invention, in an organic solvent, hexamethylene - bis-cyanoguanidine and p-chloroaniline hydrochloride 1: 24 mol: 1 8~1. ratio, at 135~175 ° C, the reaction reflux condenser 2~7h; the reaction was allowed to stand, filtered off with suction, washed with water add paint to give a white solid; purification washed with ethanol to give chlorhexidine pure compound.

[0006] 所述有机溶剂为乙二醇乙醚或正丁醇。 The [0006] organic solvent is a glycol ether or n-butanol.

[0007] 所述己撑二氰基胍的结构式为: [0007] The hexamethylene cyanoguanidine of the formula:

Figure CN102993056AD00032

所述己撑-二氰基胍的制备方法:己二胺盐酸盐与双氰胺钠在正丁醇中以1.0:1. 6〜1. 0:2. 4的摩尔比,于10(n40°C下回流反应2h〜7h ;减压蒸除溶剂,洗涤,抽滤,真 The hexamethylene - Preparation of two cyanoguanidine: hexamethylenediamine hydrochloride in n-butanol with sodium dicyandiamide to 1.0: 1 molar ratio, in 10 (24: 1 6~1 0... the reaction was refluxed under 2h~7h n40 ° C; the solvent was distilled off under reduced pressure, washing, filtration, true

空干燥,即得。 Air drying, ie.

[0008] 本发明制备的产物经红外谱图、核磁谱图、质谱等检测,确定为化合物双氯苯双胍己烧。 [0008] The product prepared in the present invention by IR spectrum, NMR spectrum, mass spectrometry detection, the compound identified as chlorhexidine have burned.

[0009] 本发明与现有技术相比具有以下优点: [0009] The present invention and the prior art has the following advantages:

1、本发明以己撑-二氰基胍与对氯苯胺盐酸盐为原料,经一步反应,直接得到目标化合物,其工艺简单,反应条件温和,反应时间短,快速、高效; 1, the present invention is to hexamethylene - dicyano-p-chloroaniline and guanidine hydrochloride as the raw material, the reaction step, to give the title compound directly, the process is simple, mild reaction conditions and short reaction times, quick, and efficient;

2、本发明以乙二醇乙醚或正丁醇为溶剂,降低了溶剂的毒副作用对人体的影响,同时也降低了对环境的污染; 2, the present invention is ethylene glycol ethyl ether or n-butanol as the solvent, the solvent to reduce the influence of toxicity on the human body, but also reduces environmental pollution;

3、本发明合成中不使用催化剂,简化了后处理工艺,有效降低了合成的综合成本; 3, the present invention is not used in the synthesis of the catalyst, simplified post-treatment process, effectively reducing the overall cost of the synthesis;

4、本发明最终产物的收率高(可达84. 7%),纯度高(最终产物的纯度可达97%),具有较好的工业应用前景。 4, high yield of the final product of the present invention (up to 84.7%), high purity (purity of the final product up to 97%), it has good prospects for industrial applications.

具体实施方式 Detailed ways

[0010] 下面通过具体实施例对本发明双氯苯双胍己烷的制备及结构表征作进一步的说明。 [0010] The following specific embodiments of the preparation and structure of chlorhexidine of the present invention is characterized further described.

[0011] 实施例1 [0011] Example 1

(1)己撑-二氰基胍的制备 (1) hexamethylene - Preparation of two cyanoguanidine

称取己二胺盐酸盐(9. 45g,0. 05mol),双氰胺钠(8. 90g,0.1mol ),加入到250ml三口烧瓶中,加入200ml正丁醇,加热至130°C,磁力搅拌下回流2h ;将反应液减压蒸馏除去正丁醇,然后加水搅拌洗涤3次,抽滤得白色固体;白色固体在0. 06MPa、60°C下真空干燥,得纯品1,6-双氰基胍基己烷化合物。 Weigh hexamethylenediamine hydrochloride (9. 45g, 0. 05mol), sodium dicyandiamide (8. 90g, 0.1mol), was added to a 250ml three-necked flask, 200ml of n-butanol was added and heated to 130 ° C, 2H refluxed with magnetic stirring; the reaction of n-butanol was distilled off under reduced pressure, water was added and then washed three times with stirring, suction filtered to give a white solid; white solid 0. 06MPa, and dried under vacuum at 60 ° C, to give pure 1,6 - bis cyano compound guanidino hexane. 称重计算收率为96%。 Weigh 96% yield calculated.

[0012]产物的表征数据:IR (neat) v : 3447,3146,2942,2867,2179,1660,1620,1541,1477, 1432, 1378, [0012] Characterization data of the product: IR (neat) v: 3447,3146,2942,2867,2179,1660,1620,1541,1477, 1432, 1378,

1327, 1124,942 cm' Anal, calcd for C10H18N8. C 47.98,H 7. 25, N 44.77. foundC 48.01,H 7. 23, N44. 76. 1H NMR (400 MHz, DMSO) S :1. 23-1. 40 (m, 8H, -CH2-),2.99-3. 37 (m, 4H, -CH2-N), 6. 56-7. 26 ( NH, 6H). ESI +_MS( 35 eV, m/Z) :251[M+H]+。 . 1327, 1124,942 cm 'Anal, calcd for C10H18N8 C 47.98, H 7. 25, N 44.77 foundC 48.01, H 7. 23, N44 76. 1H NMR (400 MHz, DMSO) S:... 1 23- 1. 40 (m, 8H, -CH2 -)..., 2.99-3 37 (m, 4H, -CH2-N), 6. 56-7 26 (NH, 6H) ESI + _MS (35 eV, m / Z): 251 [M + H] +.

[0013] 其结构式为: [0013] Its structural formula is:

Figure CN102993056AD00041

(2)双氯苯双胍己烷的制备 Chlorhexidine preparation (2)

称取己撑-二氰基胍(7. 5g,0. 03mol),对氯苯胺盐酸盐(11. 8g,0. 072mol),加入到250ml三口烧瓶中,加入溶剂乙二醇乙醚;磁力搅拌,135°C下冷凝回流反应3h,得反应液;静置,抽滤得到白色固体,取出固体加水洗涤,抽滤得粗产品;纯化,得到纯品双氯苯双胍己烷化合物。 Weigh hexamethylene - bis cyanoguanidine (7. 5g, 0 03mol.), P-chloroaniline hydrochloride (11. 8g, 0 072mol.), Was added to a 250ml three-necked flask, ethylene glycol ethyl ether solvent was added; magnetic stirring, reflux condenser reaction at 135 ° C 3h, to obtain a reaction solution; allowed to stand to give a white solid by suction filtration, washed with water, add solid was removed by suction filtration to obtain a crude product; give chlorhexidine pure compound. 称重计算产率为84. 7%。 Weighing yield of 84.7%.

[0014]产物的表征数据 IR (neat) v :3311, 3198,2939,2855,1636,1603,1581,1533,1415,1240, 1158, 1093, [0014] The product characterization data IR (neat) v: 3311, 3198,2939,2855,1636,1603,1581,1533,1415,1240, 1158, 1093,

824,725CHT1. Anal, calcd for C22H30 N10Cl2 • 2HC1. C 52. 28,H 5. 98,N 27. 71,Cl 14. 03. found C 52. 26,H 6. 00,N 27. 74,Cl 14. 00. 1H NMR (600 MHz, DMSO) S :1. 08-1. 47 (m, 8H,-CH2-), 3. 07-3. 47 (m, 4H, -CH2-N), 6. 80-7. 40 (m, 8H, Ar-H),7. 71-9. 96 (NH). ESI +_MS( 35 eV, m/Z): 824,725CHT1. Anal, calcd for C22H30 N10Cl2 • 2HC1. C 52. 28, H 5. 98, N 27. 71, Cl 14. 03. found C 52. 26, H 6. 00, N 27. 74, Cl 14. 00. 1H NMR (600 MHz, DMSO) S:... 1 08-1 47 (m, 8H, -CH2-), 3. 07-3 47 (m, 4H, -CH2-N), 6 ..... 80-7 40 (m, 8H, Ar-H), 7 71-9 96 (NH) ESI + _MS (35 eV, m / Z):

253. 5 [M-CH2CH2CH2NHC=NHNHC=NHNHArCl+H] + 0 253. 5 [M-CH2CH2CH2NHC = NHNHC = NHNHArCl + H] + 0

[0015] 产物的结构式为: Structural formula [0015] product was:

Figure CN102993056AD00051

实施例2 Example 2

(I)己撑-二氰基胍的制备:同实施例1。 (I) hexamethylene - Preparation of two cyanoguanidine: same as in Example 1.

[0016] (2)双氯苯双胍己烷的制备: [0016] (2) Preparation of chlorhexidine:

称取己撑-二氰基胍(2. 5g,0. Olmol),对氯苯胺盐酸盐(3. 9g,0. 024mol),加入到IOOml三口烧瓶中,加入溶剂乙二醇乙醚;磁力搅拌,135°C下冷凝回流反应3h,得反应液;静置,抽滤得到白色固体;取出固体加水洗涤,抽滤得粗产品;纯化,得到纯品双氯苯双胍己烷化合物。 Weigh hexamethylene - bis cyanoguanidine, chloroaniline hydrochloride (3. 9g, 0 024mol.), Was added to a three-necked flask IOOml, ethylene glycol ethyl ether solvent was added (2. 5g, 0 Olmol.); Magnetic stirring, reflux condenser reaction at 135 ° C 3h, to obtain a reaction solution; left, suction filtration to give a white solid; was added. the solid was washed with water and filtration to obtain a crude product; give chlorhexidine pure compound. 称重计算产率为78. 1%。 Weighing yield of 78.1%.

[0017] 产物的表征同实施例1。 Characterization [0017] The product described in Example 1.

[0018] 实施例3 [0018] Example 3

(I)己撑-二氰基胍的制备:同实施例1。 (I) hexamethylene - Preparation of two cyanoguanidine: same as in Example 1.

[0019] (2)双氯苯双胍己烷的制备: [0019] (2) Preparation of chlorhexidine:

称取己撑-二氰基胍(2. 5g,0. Olmol),对氯苯胺盐酸盐(2. 8g,0. 016mol),加入到100ml三口烧瓶中,加入溶剂乙二醇乙醚,磁力搅拌,135°C下冷凝回流反应3h,得反应液;静置,抽滤得到白色固体;取出固体加水洗涤后,抽滤得粗产品;纯化,得到纯品双氯苯双胍己烷化合物。 Weigh hexamethylene - (. 2. 5g, 0 Olmol) two cyanoguanidine, chloroaniline hydrochloride (. 2. 8g, 0 016mol), was added to a 100ml three-necked flask, ethylene glycol ethyl ether solvent was added, magnetic stirring, reflux condenser reaction at 135 ° C 3h, to obtain a reaction solution; left, suction filtration to give a white solid; was added after removing the solid washed with water and filtration to obtain a crude product; give chlorhexidine pure compound. 称重计算产率为74. 8%。 Weighing yield of 74.8%.

[0020] 产物的表征同实施例1。 Characterization [0020] The product described in Example 1.

[0021] 实施例4 [0021] Example 4

(I)己撑-二氰基胍的制备:同实施例1。 (I) hexamethylene - Preparation of two cyanoguanidine: same as in Example 1.

[0022] (2)双氯苯双胍己烷的制备: [0022] (2) Preparation of chlorhexidine:

称取己撑-二氰基胍(7. 5g,0. 0311101),对氯苯胺盐酸盐(11. 8g,0. 072mol),加入到250ml三口烧瓶中,加入溶剂乙二醇乙醚,磁力搅拌,145°C下冷凝回流反应3h,得反应液;静置,抽滤得到白色固体,取出固体加水洗涤,抽滤得粗产品;纯化,得到纯品双氯苯双胍己烷化合物。 Weigh hexamethylene - bis-cyanoguanidine (. 7. 5g, 0 0311101), p-chloroaniline hydrochloride (. 11. 8g, 0 072mol), was added to a 250ml three-necked flask, ethylene glycol ethyl ether solvent was added, magnetic stirring, reflux condenser reaction at 145 ° C 3h, to obtain a reaction solution; allowed to stand to give a white solid by suction filtration, washed with water, add solid was removed by suction filtration to obtain a crude product; give chlorhexidine pure compound. 称重计算产率为84. 1%。 Weighing yield of 84.1%.

[0023] 产物的表征同实施例1。 Characterization [0023] The product described in Example 1.

[0024] 实施例5 [0024] Example 5

(I)己撑-二氰基胍的制备:同实施例1。 (I) hexamethylene - Preparation of two cyanoguanidine: same as in Example 1.

[0025] (2)双氯苯双胍己烷的制备: [0025] (2) Preparation of chlorhexidine:

称取己撑-二氰基胍(7. 5g,0. 0311101),对氯苯胺盐酸盐(11. 8g,0. 072mol),加入到250ml三口烧瓶中,加入溶剂乙二醇乙醚,磁力搅拌,165 °C下冷凝回流反应3h,得反应液;静置,抽滤得到白色固体;取出固体加水洗涤,抽滤得粗产品;纯化,得到纯品双氯苯双胍己烷化合物。 Weigh hexamethylene - bis-cyanoguanidine (. 7. 5g, 0 0311101), p-chloroaniline hydrochloride (. 11. 8g, 0 072mol), was added to a 250ml three-necked flask, ethylene glycol ethyl ether solvent was added, magnetic stirring, reflux condenser reaction at 165 ° C 3h, to obtain a reaction solution; left, suction filtration to give a white solid; was added. the solid was washed with water and filtration to obtain a crude product; give chlorhexidine pure compound. 称重计算产率为81. 3%。 Weighing yield of 81.3%.

[0026] 产物的表征同实施例1。 Characterization [0026] The product described in Example 1.

[0027] 实施例6 [0027] Example 6

(I)己撑-二氰基胍的制备:同实施例1。 (I) hexamethylene - Preparation of two cyanoguanidine: same as in Example 1.

[0028] (2)双氯苯双胍己烷的制备: [0028] (2) Preparation of chlorhexidine:

称取己撑-二氰基胍(7. 5g,0. 03mol),对氯苯胺盐酸盐(11. 8g,0. 072mol),加入到250ml三口烧瓶中,加入溶剂乙二醇乙醚,磁力搅拌,175 °C下冷凝回流反应3h,得反应液; 静置,抽滤得到白色固体;取出固体加水洗涤,抽滤得粗产品;纯化,得到纯品双氯苯双胍己烷化合物。 Weigh hexamethylene - bis-cyanoguanidine (. 7. 5g, 0 03mol), p-chloroaniline hydrochloride (. 11. 8g, 0 072mol), was added to a 250ml three-necked flask, ethylene glycol ethyl ether solvent was added, magnetic stirring, reflux condenser reaction at 175 ° C 3h, to obtain a reaction solution; left, suction filtration to give a white solid; was added. the solid was washed with water and filtration to obtain a crude product; give chlorhexidine pure compound. 称重计算产率为82. 4%。 Weighing yield of 82.4%.

[0029] 产物的表征同实施例1。 Characterization [0029] The product described in Example 1.

[0030] 实施例7 [0030] Example 7

(I)己撑-二氰基胍的制备:同实施例1。 (I) hexamethylene - Preparation of two cyanoguanidine: same as in Example 1.

[0031] (2)双氯苯双胍己烷的制备: [0031] (2) Preparation of chlorhexidine:

称取己撑-二氰基胍(2. 5g,0. Olmol ),对氯苯胺盐酸盐(3. 9g,0. 024mol),加入到IOOml三口烧瓶中,加入溶剂乙二醇乙醚,磁力搅拌,135°C下冷凝回流反应2h,得反应液;静置,抽滤得到白色固体;取出固体加水洗涤,抽滤得粗产品;纯化,得到纯品双氯苯双胍己烷化合物。 Weigh hexamethylene - (. 2. 5g, 0 Olmol) two cyanoguanidine, chloroaniline hydrochloride (. 3. 9g, 0 024mol), was added to a three-necked flask IOOml, ethylene glycol ethyl ether solvent was added, magnetic stirring, reflux condenser reaction at 135 ° C 2h, a reaction solution; left, suction filtration to give a white solid; was added. the solid was washed with water and filtration to obtain a crude product; give chlorhexidine pure compound. 称重计算产率为72. 7%。 Weighing yield of 72.7%.

[0032] 产物的表征同实施例1。 Characterization [0032] The product described in Example 1.

[0033] 实施例8 [0033] Example 8

Cl)己撑-二氰基胍的制备:同实施例1。 Cl) hexamethylene - Preparation of two cyanoguanidine: same as in Example 1.

[0034] (2)双氯苯双胍己烷的制备: [0034] (2) Preparation of chlorhexidine:

称取取己撑-二氰基胍(2. 5g,0. Olmol ),对氯苯胺盐酸盐(3. 9g,0. 024mol),加入到IOOml三口烧瓶中,加入溶剂乙二醇乙醚,磁力搅拌,135°C下冷凝回流反应5h,得反应液;静置,抽滤得到白色固体;取出固体加水洗涤,抽滤得粗产品;纯化,得到纯品双氯苯双胍己烷化合物。 Weigh take hexamethylene - (. 2. 5g, 0 Olmol) two cyanoguanidine, chloroaniline hydrochloride (. 3. 9g, 0 024mol), was added to a three-necked flask IOOml, ethylene glycol ethyl ether solvent was added, magnetic stirring, reflux condenser for 5h at 135 ° C, to obtain a reaction solution; left, suction filtration to give a white solid; was added. the solid was washed with water and filtration to obtain a crude product; give chlorhexidine pure compound. 称重计算产率为74. 4%。 Weighing yield of 74.4%.

[0035] 产物的表征同实施例1。 Characterization [0035] The product described in Example 1.

[0036] 实施例9 [0036] Example 9

(I)己撑-二氰基胍的制备:同实施例1。 (I) hexamethylene - Preparation of two cyanoguanidine: same as in Example 1.

[0037] (2)双氯苯双胍己烷的制备: [0037] (2) Preparation of chlorhexidine:

称取己撑-二氰基胍(2. 5g,0. Olmol ),对氯苯胺盐酸盐(3. 9g,0. 024mol),加入到IOOml三口烧瓶中,加入溶剂正丁醇,磁力搅拌,110°C下冷凝回流反应3h,得反应液;静置,抽滤得到白色固体;取出固体加50ml水洗涤,抽滤得粗产品;纯化,得到纯品双氯苯双胍己烷化合物。 Weigh hexamethylene - bis-cyanoguanidine (. 2. 5g, 0 Olmol), p-chloroaniline hydrochloride (3. 9g, 0 024mol.), Was added to a three-necked flask IOOml, a solvent of n-butanol was added, with magnetic stirring , 110 ° C for reflux condensation reaction 3h, to obtain a reaction solution; allowed to stand to give a white solid was suction filtered; the solid was washed with 50ml of water extraction, filtration to obtain a crude product; give chlorhexidine pure compound. 称重计算产率为84. 2%。 Weighing yield of 84.2%.

[0038] 产物的表征同实施例1。 Characterization [0038] The product described in Example 1.

Claims (4)

1. 一种双氯苯双胍己烷化合物的制备方法,是在有机溶剂中,己撑二氰基胍与对氯苯胺盐酸盐以1:1.8〜1:2.4的摩尔比,于1351:〜175°C下,冷凝回流反应疒7h ;反应液静置,抽滤,加水洗涤,得到白色固体;纯化,得到纯品双氯苯双胍己烷化合物。 Preparation of Compound 1. A method of hexane chlorhexidine, in an organic solvent, and hexamethylene cyanoguanidine chloroaniline hydrochloride 1: 1.8~1: 2.4 molar ratio, at 1351: ~ at 175 ° C, the reaction reflux condenser epileptic 7H; the reaction was allowed to stand, filtered by suction, washed with water, was added to give a white solid; give chlorhexidine pure compound.
2.如权利要求1所述双氯苯双胍己烷化合物的制备方法,其特征在于:所述有机溶剂为乙二醇乙醚或正丁醇。 A process as defined in claim 1, chlorhexidine compound as claimed in claim wherein: said organic solvent is a glycol ether or n-butanol.
3.如权利要求1所述双氯苯双胍己烷化合物的制备方法,其特征在于:所述己撑-二氰基胍的结构式为: 3. The method as in claim 1, chlorhexidine compound as claimed in claim, wherein: said hexamethylene - bis-cyanoguanidine of the formula:
Figure CN102993056AC00021
4.如权利要求3所述双氯苯双胍己烷化合物的制备方法,其特征在于:所述己撑-二氰基胍的制备方法:己二胺盐酸盐与双氰胺钠在正丁醇中以1. 0:1. 6^1.0:2. 4的摩尔比,于10(Tl4(rC下回流反应2tT7h;减压蒸除溶剂,洗涤,抽滤,真空干燥,即得。 4. The method as in claim 3, chlorhexidine compound as claimed in claim, wherein: said hexamethylene - Preparation of two cyanoguanidine: hexamethylenediamine hydrochloride with sodium in n-dicyandiamide . alcohol to 1.0: 1.0 ^ 16: 4 molar ratio, at 10 ((rC Tl4 under reflux 2tT7h; solvent was distilled off under reduced pressure, washing, filtration, and dried in vacuo to obtain.
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