WO2021120896A1 - 一种降冰片烷二甲胺的制备方法 - Google Patents

一种降冰片烷二甲胺的制备方法 Download PDF

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WO2021120896A1
WO2021120896A1 PCT/CN2020/125793 CN2020125793W WO2021120896A1 WO 2021120896 A1 WO2021120896 A1 WO 2021120896A1 CN 2020125793 W CN2020125793 W CN 2020125793W WO 2021120896 A1 WO2021120896 A1 WO 2021120896A1
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acid
preparation
formula
solvent
reaction
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翟宏斌
任永平
梁万根
张超
崔卫华
费潇瑶
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山东益丰生化环保股份有限公司
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/82—Purification; Separation; Stabilisation; Use of additives
    • C07C209/84—Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
    • C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms

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  • the invention relates to the technical field of organic compound synthesis, and more specifically, to a method for preparing norbornane dimethylamine.
  • Norbornane dimethylamine also known as norbornane dimethylamine, is often used as a curing agent for epoxy resins. It can be cured quickly even at low temperatures, and the cured product strength, flexibility, heat deformation resistance, and impact resistance , Weather resistance, chemical resistance and yellowing resistance are all excellent performance.
  • the preparation method of norbornane dimethylamine in the prior art includes:
  • the patent with publication number CN101443308A discloses a method for producing dicyanonorbornane and a zero-valent nickel coordination compound catalyst, which uses norbornane dinitrile as a raw material to produce norbornane dimethylamine; but norbornane Dinitrile is synthesized from cyanonorbornene and hydrogen cyanide as raw materials.
  • the patent with publication number CN104781228A discloses a method for producing aldehyde compounds, using formyl cyano norbornane as a raw material to produce norbornane dimethylamine; but formyl cyano norbornane is based on cyano Raw materials such as bornene, rhodium catalyst, carbon monoxide and hydrogen are synthesized under high pressure.
  • method (1) uses hydrogen cyanide in the process of manufacturing norbornane dimethylamine. Because hydrogen cyanide is highly toxic and its boiling point is low, the explosion limit in the air is 5.6%-12.8 %, it is extremely prone to dangerous existence; and method (2) in the process of manufacturing norbornane dimethylamine uses expensive rhodium catalyst, and also need to be used with other ligands, the method is more complicated. In addition, the post-processing of the above two methods is relatively complicated, and there are problems of low yield and complicated operation.
  • the object of the present invention is to provide a method for preparing norbornane dimethylamine, which can avoid the use of hydrogen cyanide, rhodium catalyst and other ligands, is simple, easy to operate, and has a high product yield.
  • the present invention provides a method for preparing norbornane dimethylamine, which comprises the following steps:
  • step b) Mixing the structure compound represented by formula (II) obtained in step a) with hydrogen, a catalyst, and a second solvent, and performing a second reaction to obtain a second reaction mixture; and then filtering the above-mentioned second reaction mixture a second time , The obtained filtrate is purified for the second time to obtain norbornane dimethylamine.
  • the acid in step a) is selected from one or more of hydrobromic acid, oxalic acid, hypochlorous acid, p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, nitric acid, acetic acid and trifluoroacetic acid.
  • the first solvent in step a) is selected from one or more of acrylonitrile, acetonitrile, propionitrile, acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, cyclohexanone and ether.
  • the molar ratio of the compound of formula (I) to urotropine is 1: (0.25-1).
  • the mass ratio of the compound of the formula (I), the acid and the first solvent in step a) is 1: (1-10): (5-20).
  • the temperature of the first reaction in step a) is 30°C-100°C, and the time is 4h-17h.
  • the catalyst in step b) is selected from one or more of palladium carbon, nickel formate, platinum black, platinum carbon, nickel-alumina, ultrafine nickel, Raney nickel, Raney cobalt and Raney copper Kind.
  • the second solvent in step b) is selected from one or more of methanol, toluene, o-xylene, meta-xylene and p-xylene.
  • the mass ratio of the structure compound represented by formula (II), the catalyst and the second solvent in step b) is 1: (0.01-0.35): (20-50).
  • the temperature of the second reaction in step b) is 60° C. to 140° C.
  • the pressure is 0.5 MPa to 2 MPa
  • the time is 3 h to 10 h.
  • the present invention provides a method for preparing norbornane dimethylamine, which comprises the following steps: a) Mixing a compound of the structure represented by formula (I) with urotropine, acid, and a first solvent to perform the first reaction , Obtain the first reaction mixture; and then sequentially neutralize the first reaction mixture and filter for the first time, and the obtained filtrate is purified for the first time to obtain the structure compound represented by formula (II); b) obtain step a) The structure compound represented by the formula (II) is mixed with hydrogen, a catalyst, and a second solvent to perform a second reaction to obtain a second reaction mixture; then the second reaction mixture is filtered a second time, and the obtained filtrate is subjected to a second reaction.
  • norbornane dimethylamine is obtained.
  • the preparation method provided by the present invention can avoid the use of hydrogen cyanide, rhodium catalyst and other ligands, the method is simple, easy to operate, and the product yield is higher, and has broad application prospects.
  • Figure 1 is a hydrogen spectrum of norbornane dimethylamine provided in Example 1 of the present invention.
  • Example 2 is a high-resolution mass spectrum of norbornane dimethylamine provided in Example 1 of the present invention.
  • the present invention provides a method for preparing norbornane dimethylamine, which comprises the following steps:
  • step b) Mixing the structure compound represented by formula (II) obtained in step a) with hydrogen, a catalyst, and a second solvent, and performing a second reaction to obtain a second reaction mixture; and then filtering the above-mentioned second reaction mixture a second time , The obtained filtrate is purified for the second time to obtain norbornane dimethylamine.
  • the compound of the structure represented by formula (I) is mixed with urotropine, acid, and the first solvent, and the first reaction is performed to obtain the first reaction mixture.
  • the compound of the structure represented by formula (I) is norbornadiene.
  • the present invention has no special restrictions on the sources of the norbornadiene and urotropine, and commercially available products well known to those skilled in the art can be used.
  • the molar ratio of the compound represented by the formula (I) to urotropine is preferably 1: (0.25 to 1), more preferably 1: (0.35 to 0.6).
  • the acid is preferably selected from one or more of hydrobromic acid, oxalic acid, hypochlorous acid, p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, nitric acid, acetic acid and trifluoroacetic acid, more preferably sulfuric acid, Acetic acid or trifluoroacetic acid.
  • the present invention has no special restrictions on the source of the acid, and the above-mentioned commercial products of hydrobromic acid, oxalic acid, hypochlorous acid, p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, nitric acid, acetic acid and trifluoroacetic acid are used. That's it.
  • the mass ratio of the compound represented by the formula (I) and the acid is preferably 1:(1-10), more preferably 1:(3-6).
  • the first solvent is an inert organic solvent, preferably one selected from the group consisting of acrylonitrile, acetonitrile, propionitrile, acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, cyclohexanone and diethyl ether Or more, more preferably acetone, acetonitrile or ether.
  • the present invention has no particular limitation on the source of the first solvent, and the above-mentioned acrylonitrile, acetonitrile, propionitrile, acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, cyclohexanone and diethyl ether, which are well known to those skilled in the art, are used.
  • the commercially available products can be.
  • the mass ratio of the compound represented by the formula (I) and the first solvent is preferably 1:(5-20), more preferably 1:(10-15).
  • the present invention has no special restrictions on the mixing device, and a single-necked flask well known to those skilled in the art can be used.
  • the temperature of the first reaction is preferably 30°C to 100°C, more preferably 30°C to 70°C, which is achieved by means of an oil bath well known to those skilled in the art;
  • the time is preferably 4h to 17h, more preferably 5h to 15h.
  • the first reaction mixture is sequentially neutralized and filtered for the first time, and the obtained filtrate is purified for the first time to obtain the structural compound represented by formula (II).
  • the neutralization process is preferably carried out with saturated sodium carbonate solution or saturated sodium bicarbonate solution, and the system can be adjusted to neutral.
  • the present invention has no special restrictions on the process of the first filtration, and the purpose is to obtain a filtrate containing the structure compound represented by formula (II).
  • the first purification process is preferably specifically:
  • the present invention mixes the obtained structure compound represented by the formula (II) with hydrogen, a catalyst, and a second solvent, and performs a second reaction to obtain a second reaction mixture.
  • the present invention has no special restrictions on the source of the hydrogen, and commercial products or self-made products well known to those skilled in the art can be used.
  • the catalyst is preferably selected from one or more of palladium carbon, nickel formate, platinum black, platinum carbon, nickel-alumina, ultrafine nickel, Raney nickel, Raney cobalt and Raney copper , More preferably palladium carbon or Raney nickel.
  • the present invention has no special restrictions on the source of the catalyst.
  • the above-mentioned palladium carbon, nickel formate, platinum black, platinum carbon, nickel-alumina, ultrafine nickel, Raney nickel, Raney cobalt, and Raney are well known to those skilled in the art. Commercial products of Nepalese copper can be used.
  • the mass ratio of the structure compound represented by the formula (II) to the catalyst is preferably 1: (0.01 to 0.35), more preferably 1: (0.05 to 0.15).
  • the second solvent is an inert organic solvent, preferably one or more selected from methanol, toluene, o-xylene, meta-xylene and p-xylene, more preferably toluene or methanol.
  • the present invention does not have any special restrictions on the source of the second solvent, and the commercially available products of methanol, toluene, o-xylene, m-xylene and p-xylene that are well known to those skilled in the art can be used.
  • the mass ratio of the structure compound represented by formula (II) and the second solvent is preferably 1: (20-50), more preferably 1: (25-35).
  • the mixing device preferably adopts an autoclave well known to those skilled in the art; the amount of hydrogen is preferably the amount of hydrogen required to pressurize the autoclave to the reaction pressure of the second reaction.
  • the temperature of the second reaction is preferably 60°C to 140°C, more preferably 95°C to 130°C;
  • the pressure of the second reaction is preferably 0.5 MPa to 2 MPa, more preferably 0.7 MPa ⁇ 1.7MPa;
  • the time for the second reaction is preferably 3h-10h, more preferably 5h-10h.
  • the second reaction mixture is filtered for a second time, and the obtained filtrate is purified for the second time to obtain norbornane dimethylamine.
  • the purpose of the second filtration is to remove the solid compounds in the second reaction mixture.
  • the present invention has no special limitation on this, and it is only necessary to adopt a filtration technical solution well known to those skilled in the art.
  • the second purification process uses the technical solution of rotary evaporation well known to those skilled in the art, and the purpose is to remove the solvent to obtain the pure norbornane dimethylamine.
  • the preparation method provided by the present invention avoids the use of hydrogen cyanide. Because hydrogen cyanide is highly toxic and has a low boiling point, the explosion limit in the air is 5.6% to 12.8%, which is extremely dangerous; thereby greatly reducing the risk of the present invention.
  • the preparation method is dangerous; it also avoids the use of expensive rhodium catalysts and other ligands. Combining the above two points, the preparation method provided by the present invention is simple, easy to operate, easy to obtain, low cost, and high product yield. Application prospects.
  • the present invention provides a method for preparing norbornane dimethylamine, which comprises the following steps: a) Mixing a compound of the structure represented by formula (I) with urotropine, acid, and a first solvent to perform the first reaction , Obtain the first reaction mixture; and then sequentially neutralize the first reaction mixture and filter for the first time, and the obtained filtrate is purified for the first time to obtain the structure compound represented by formula (II); b) obtain step a) The structure compound represented by the formula (II) is mixed with hydrogen, a catalyst, and a second solvent to perform a second reaction to obtain a second reaction mixture; then the second reaction mixture is filtered a second time, and the obtained filtrate is subjected to a second reaction.
  • norbornane dimethylamine is obtained.
  • the preparation method provided by the present invention can avoid the use of hydrogen cyanide, rhodium catalyst and other ligands, the method is simple, easy to operate, and the product yield is higher, and has broad application prospects.
  • step (2) Weigh 15.02g of norbornene dimethylamine obtained in step (1) in a 500mL autoclave, add 1.05g Raney nickel and 376.25g methanol to it in sequence, and then pressurize with hydrogen to 0.9MPa and react During the process, the pressure was maintained, and the temperature was raised to 100° C. to react for 6 hours. After the reaction was completed, the system was filtered, and the filtrate was rotary evaporated to obtain 14.65 g of norbornane dimethylamine.
  • step (2) Weigh 15.02g of the norbornene dimethylamine obtained in step (1) into a 1000mL autoclave, add 1.05g Raney nickel and 450.6g methanol to it in sequence, then pressurize with hydrogen to 1.7MPa and react During the process, the pressure was maintained and the temperature was raised to 130° C. to react for 10 hours. After the reaction was completed, the system was filtered, and the filtrate was rotary evaporated to obtain 14.03 g of norbornane dimethylamine.
  • the preparation method provided by the present invention can avoid the use of hydrogen cyanide, rhodium catalyst and other ligands.
  • the method is simple, easy to operate, and less dangerous.
  • the raw materials are easily available and The cost is low and the product yield is high.

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Abstract

提供了一种降冰片烷二甲胺的制备方法，包括以下步骤：a)将式(I)所示结构的化合物与乌洛托品、酸、第一溶剂混合，进行第一次反应，得到第一反应混合物；再将上述第一反应混合物依次进行中和、第一次过滤，得到的滤液进行第一次提纯，得到式(II)所示结构化合物；b)将步骤a)得到的式(II)所示结构化合物与氢气、催化剂、第二溶剂混合，进行第二次反应，得到第二反应混合物；再将上述第二反应混合物进行第二次过滤，得到的滤液进行第二次提纯，得到降冰片烷二甲胺。与现有技术相比，该制备方法能够避免使用氰化氢、铑催化剂及其他配体，方法简单、易操作，产品收率较高，具有广阔的应用前景。

Description

一种降冰片烷二甲胺的制备方法
本申请要求于2019年12月18日提交中国专利局、申请号为201911308027.6、发明名称为“一种降冰片烷二甲胺的制备方法”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
技术领域
本发明涉及有机化合物合成技术领域，更具体地说，是涉及一种降冰片烷二甲胺的制备方法。
背景技术
降冰片烷二甲胺又称降莰烷二甲胺，常用作环氧树脂固化剂，具有即使在低温下也可快速固化，且固化后的产品强度、挠度、耐热变形性、耐撞击性、耐候性、耐药品性及耐黄变性均很优良的优良性能。
目前，现有技术中降冰片烷二甲胺的制备方法包括：
(1)公开号为CN101443308A的专利，其公开了二氰基降冰片烷的制造方法及零价镍配位化合物催化剂，以降冰片烷二腈为原料制造降冰片烷二甲胺；但降冰片烷二腈是以氰基降冰片烯及氰化氢为原料进行合成得到。
(2)公开号为CN104781228A的专利，其公开了醛化合物的制造方法，以甲酰基氰基降冰片烷为原料制造降冰片烷二甲胺；但甲酰基氰基降冰片烷是以氰基降冰片烯、铑催化剂、一氧化碳、氢气等原料在高压下进行合成得到。
上述制备方案中，方法(1)在制造降冰片烷二甲胺的过程中使用氰化氢，由于氰化氢为剧毒，且其沸点较低，在空气中的爆炸极限为5.6％～12.8％，极易发生危险存；而方法(2)在制造降冰片烷二甲胺的过程中使用了昂贵的铑催化剂，并且还需配合其他配体使用，方法较繁杂。此外上述两种方法的后处理均比较复杂，存在收率低、操作繁杂的问题。
发明内容
有鉴于此，本发明的目的在于提供一种降冰片烷二甲胺的制备方法，能够避免使用氰化氢、铑催化剂及其他配体，方法简单、易操作，产品收率较高。
本发明提供了一种降冰片烷二甲胺的制备方法，包括以下步骤：
a)将式(I)所示结构的化合物与乌洛托品、酸、第一溶剂混合，进行第一次反应，得到第一反应混合物；再将上述第一反应混合物依次进行中和、第一次过滤，得到的滤液进行第一次提纯，得到式(II)所示结构化合物；
Figure PCTCN2020125793-appb-000001
Figure PCTCN2020125793-appb-000002
b)将步骤a)得到的式(II)所示结构化合物与氢气、催化剂、第二溶剂混合，进行第二次反应，得到第二反应混合物；再将上述第二反应混合物进行第二次过滤，得到的滤液进行第二次提纯，得到降冰片烷二甲胺。
优选的，步骤a)中所述酸选自氢溴酸、草酸、次氯酸、对甲苯磺酸、盐酸、硫酸、硝酸、乙酸和三氟乙酸中的一种或多种。
优选的，步骤a)中所述第一溶剂选自丙烯腈、乙腈、丙腈、丙酮、甲乙酮、甲基异丁基酮、环己酮、环己酮和乙醚中的一种或多种。
优选的，步骤a)中所述式(I)所示结构的化合物和乌洛托品的摩尔比为1：(0.25～1)。
优选的，步骤a)中所述式(I)所示结构的化合物、酸和第一溶剂的质量比为1：(1～10)：(5～20)。
优选的，步骤a)中所述第一次反应的温度为30℃～100℃，时间为4h～17h。
优选的，步骤b)中所述催化剂选自钯碳、甲酸镍、铂黑、铂碳、镍-氧化铝、超细镍、雷尼镍、雷尼钴和雷尼铜中的一种或多种。
优选的，步骤b)中所述第二溶剂选自甲醇、甲苯、邻二甲苯、间二甲苯和对二甲苯中的一种或多种。
优选的，步骤b)中所述式(II)所示结构化合物、催化剂和第二溶剂的质量比为1：(0.01～0.35)：(20～50)。
优选的，步骤b)中所述第二次反应的温度为60℃～140℃，压力为0.5MPa～2MPa，时间为3h～10h。
本发明提供了一种降冰片烷二甲胺的制备方法，包括以下步骤：a)将式(I)所示结构的化合物与乌洛托品、酸、第一溶剂混合，进行第一次反应，得到第一反应混合物；再将上述第一反应混合物依次进行中和、第一次过滤，得到的滤液进行第一次提纯，得到式(II)所示结构化合物；b)将步骤a)得到的式(II)所示结构化合物与氢气、催化剂、第二溶剂混合，进行第二次反应，得到第二反应混合物；再将上述第二反应混合物进行第二次过滤，得到的滤液进行第二次提纯，得到降冰片烷二甲胺。与现有技术相比，本发明提供的制备方法能够避免使用氰化氢、铑催化剂及其他配体，方法简单、易操作，产品收率较高，具有广阔的应用前景。
附图说明
图1为本发明实施例1提供的降冰片烷二甲胺的氢谱；
图2为本发明实施例1提供的降冰片烷二甲胺的高分辨质谱图。
具体实施方式
下面将结合本发明实施例，对本发明的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
本发明提供了一种降冰片烷二甲胺的制备方法，包括以下步骤：
a)将式(I)所示结构的化合物与乌洛托品、酸、第一溶剂混合，进行第一次反应，得到第一反应混合物；再将上述第一反应混合物依次进行中和、第一次过滤，得到的滤液进行第一次提纯，得到式(II)所示结构化合物；
Figure PCTCN2020125793-appb-000003
Figure PCTCN2020125793-appb-000004
b)将步骤a)得到的式(II)所示结构化合物与氢气、催化剂、第二溶剂 混合，进行第二次反应，得到第二反应混合物；再将上述第二反应混合物进行第二次过滤，得到的滤液进行第二次提纯，得到降冰片烷二甲胺。
本发明首先将式(I)所示结构的化合物与乌洛托品、酸、第一溶剂混合，进行第一次反应，得到第一反应混合物。在本发明中，所述式(I)所示结构的化合物为降冰片二烯。本发明对所述降冰片二烯及乌洛托品的来源没有特殊限制，采用本领域技术人员熟知的市售商品即可。在本发明中，所述式(I)所示结构的化合物和乌洛托品的摩尔比优选为1：(0.25～1)，更优选为1：(0.35～0.6)。
在本发明中，所述酸优选选自氢溴酸、草酸、次氯酸、对甲苯磺酸、盐酸、硫酸、硝酸、乙酸和三氟乙酸中的一种或多种，更优选为硫酸、乙酸或三氟乙酸。本发明对所述酸的来源没有特殊限制，采用本领域技术人员熟知的上述氢溴酸、草酸、次氯酸、对甲苯磺酸、盐酸、硫酸、硝酸、乙酸和三氟乙酸的市售商品即可。在本发明中，所述式(I)所示结构的化合物和酸的质量比优选为1：(1～10)，更优选为1：(3～6)。
在本发明中，所述第一溶剂为惰性有机溶剂，优选选自丙烯腈、乙腈、丙腈、丙酮、甲乙酮、甲基异丁基酮、环己酮、环己酮和乙醚中的一种或多种，更优选为丙酮、乙腈或乙醚。本发明对所述第一溶剂的来源没有特殊限制，采用本领域技术人员熟知的上述丙烯腈、乙腈、丙腈、丙酮、甲乙酮、甲基异丁基酮、环己酮、环己酮和乙醚的市售商品即可。在本发明中，所述式(I)所示结构的化合物和第一溶剂的质量比优选为1：(5～20)，更优选为1：(10～15)。
本发明对所述混合的装置没有特殊限制，采用本领域技术人员熟知的单口烧瓶即可。
在本发明中，所述第一次反应的温度优选为30℃～100℃，更优选为30℃～70℃，通过本领域技术人员熟知的油浴的方式实现；所述第一次反应的时间优选为4h～17h，更优选为5h～15h。
得到所述第一反应混合物后，本发明将上述第一反应混合物依次进行中和、第一次过滤，得到的滤液进行第一次提纯，得到式(II)所示结构化合物。在本发明中，所述中和的过程优选采用饱和的碳酸钠溶液或饱和碳酸氢钠溶液进行，将体系调至中性即可。
本发明对所述第一次过滤的过程没有特殊限制，目的是得到含有式(II)所示结构化合物的滤液。
在本发明中，所述第一次提纯的过程优选具体为：
在分液漏斗中对滤液进行分层得到有机相，再对有机相进行旋蒸，得到式(II)所示结构化合物。
得到所述式(II)所示结构化合物后，本发明将得到的式(II)所示结构化合物与氢气、催化剂、第二溶剂混合，进行第二次反应，得到第二反应混合物。本发明对所述氢气的来源没有特殊限制，采用本领域技术人员熟知的市售商品或自制品均可。
在本发明中，所述催化剂优选选自钯碳、甲酸镍、铂黑、铂碳、镍-氧化铝、超细镍、雷尼镍、雷尼钴和雷尼铜中的一种或多种，更优选为钯碳或雷尼镍。本发明对所述催化剂的来源没有特殊限制，采用本领域技术人员熟知的上述钯碳、甲酸镍、铂黑、铂碳、镍-氧化铝、超细镍、雷尼镍、雷尼钴和雷尼铜的市售商品即可。在本发明中，所述式(II)所示结构化合物和催化剂的质量比优选为1：(0.01～0.35)，更优选为1：(0.05～0.15)。
在本发明中，所述第二溶剂为惰性有机溶剂，优选选自甲醇、甲苯、邻二甲苯、间二甲苯和对二甲苯中的一种或多种，更优选为甲苯或甲醇。本发明对所述第二溶剂的来源没有特殊限制，采用本领域技术人员熟知的上述甲醇、甲苯、邻二甲苯、间二甲苯和对二甲苯的市售商品即可。在本发明中，所述式(II)所示结构化合物和第二溶剂的质量比优选为1：(20～50)，更优选为1：(25～35)。
在本发明中，所述混合的装置优选采用本领域技术人员熟知的高压釜；所述氢气的用量优选为使上述高压釜充压至第二反应的反应压力下的氢气量。
在本发明中，所述第二次反应的温度优选为60℃～140℃，更优选为95℃～130℃；所述第二次反应的压力优选为0.5MPa～2MPa，更优选为0.7MPa～1.7MPa；所述第二次反应的时间优选为3h～10h，更优选为5h～10h。
得到所述第二反应混合物后，本发明将上述第二反应混合物进行第二次过滤，得到的滤液进行第二次提纯，得到降冰片烷二甲胺。在本发明中，所述第二次过滤的目的是除去第二反应混合物中的固体化合物，本发明对此没有特殊限制，采用本领域技术人员熟知的过滤的技术方案即可。
在本发明中，所述第二次提纯的过程采用本领域技术人员熟知的旋蒸的技术方案即可，目的是除去溶剂得到降冰片烷二甲胺纯品。
本发明提供的制备方法避免使用氰化氢，由于氰化氢为剧毒，且其沸点较低，在空气中的爆炸极限为5.6％～12.8％，极易发生危险；从而大大降低本发明的制备方法的危险性；同时还避免使用昂贵的铑催化剂及其他配体，综合以上两点，本发明提供的制备方法简单、易操作，原料易得且成本低，产品收率较高，具有广阔的应用前景。
本发明提供了一种降冰片烷二甲胺的制备方法，包括以下步骤：a)将式(I)所示结构的化合物与乌洛托品、酸、第一溶剂混合，进行第一次反应，得到第一反应混合物；再将上述第一反应混合物依次进行中和、第一次过滤，得到的滤液进行第一次提纯，得到式(II)所示结构化合物；b)将步骤a)得到的式(II)所示结构化合物与氢气、催化剂、第二溶剂混合，进行第二次反应，得到第二反应混合物；再将上述第二反应混合物进行第二次过滤，得到的滤液进行第二次提纯，得到降冰片烷二甲胺。与现有技术相比，本发明提供的制备方法能够避免使用氰化氢、铑催化剂及其他配体，方法简单、易操作，产品收率较高，具有广阔的应用前景。
为了进一步说明本发明，下面通过以下实施例进行详细说明。本发明以下实施例所用的原料均为市售商品；其中，所用的降冰片二烯具有式(I)所示结构；
Figure PCTCN2020125793-appb-000005
实施例1
(1)称取9.21g降冰片二烯于500mL单口烧瓶中，依次加入9.81g乌洛托品、64.47g硫酸、138.15g丙酮，在油浴T＝70℃下反应15h，反应完成后用饱和的碳酸钠溶液将体系调至中性，再进行过滤，得到含有式(II)所示结构化合物的滤液；
Figure PCTCN2020125793-appb-000006
然后在分液漏斗中对滤液进行分层得到有机相，再对有机相进行旋蒸得到13.82g降冰片烯二甲胺；对以上步骤进行重复从而获得更多目标产物，共得到27.63g降冰片烯二甲胺。
(2)称取15.02g步骤(1)得到的降冰片烯二甲胺于500mL高压釜中，向其中依次加入1.05g钯碳、376.25g甲苯，然后用氢气充压至0.7MPa并在反应过程中保持此压力，升温至95℃反应5h，反应完成后对体系进行过滤，将滤液旋蒸，得到13.88g降冰片烷二甲胺，具有式(III)所示结构：
Figure PCTCN2020125793-appb-000007
对本发明实施例1提供的制备方法制备得到的降冰片烷二甲胺的结构进行鉴定，结果参见图1～2所示；其中，图1为本发明实施例1提供的降冰片烷二甲胺的氢谱，图2为本发明实施例1提供的降冰片烷二甲胺的高分辨质谱图。
实施例2
(1)称取9.21g降冰片二烯于250mL单口烧瓶中，依次加入5.61g乌洛托品、36.84g乙酸、92.1g乙腈，在油浴T＝50℃下反应10h，反应完成后用饱和的碳酸钠溶液将体系调至中性，再进行过滤，得到含有式(II)所示结构化合物的滤液；
Figure PCTCN2020125793-appb-000008
然后在分液漏斗中对滤液进行分层得到有机相，再对有机相进行旋蒸得到14.27g降冰片烯二甲胺；对以上步骤进行重复从而获得更多目标产物，共得到28.55g降冰片烯二甲胺。
(2)称取15.02g步骤(1)得到的降冰片烯二甲胺于500mL高压釜中，向其中依次加入1.05g雷尼镍、376.25g甲醇，然后用氢气充压至0.9MPa并在反应过程中保持此压力，升温至100℃反应6h，反应完成后对体系进行过滤，将滤液旋蒸，得到14.65g降冰片烷二甲胺。
实施例3
(1)称取9.21g降冰片二烯于250mL单口烧瓶中，依次加入3.51g乌洛托品、27.63g三氟乙酸、110.52g乙醚，在油浴T＝30℃下反应5h，反应完成后用饱和的碳酸钠溶液将体系调至中性，再进行过滤，得到含有式(II)所示结构化合物的滤液；
Figure PCTCN2020125793-appb-000009
然后在分液漏斗中对滤液进行分层得到有机相，再对有机相进行旋蒸得到13.22g降冰片烯二甲胺；对以上步骤进行重复从而获得更多目标产物，共得到26.42g降冰片烯二甲胺。
(2)称取15.02g步骤(1)得到的降冰片烯二甲胺于1000mL高压釜中，向其中依次加入1.05g雷尼镍、450.6g甲醇，然后用氢气充压至1.7MPa并在反应过程中保持此压力，升温至130℃反应10h，反应完成后对体系进行过滤，将滤液旋蒸，得到14.03g降冰片烷二甲胺。
对比例1
向装有搅拌机、温度计、氮导入口、冷凝器的50mL玻璃制圆底烧瓶中，装入1.07g(4.5mmol)氯化镍六水合物和0.60g(9.2mmol)锌、8.90g(28.7mmol)采用公知方法精制的含有0.2重量％三苯基磷酸酯的三苯基亚磷酸酯、26.5g(22.2mmol)氰基降冰片烯，确实地进行气相部的氮置换，得到四(三苯基亚磷酸酯)镍催化剂。
然后，向装有搅拌机、温度计、氮导入口、氰化氢导入口、冷凝器的1L玻璃制平底可分离型烧瓶中装入307.0g(2.58mol)氰基降冰片烯、90.0g甲苯和上述得到的催化剂合成液，在室温下充分进行气相部的氮置换后，升温至60℃。
然后，经3.5小时供给69.13g(2.66mol)液体氰化氢，进行氰化氢化反应，得到480.7g粗二氰基降冰片烷；以氮气500ml/min的流速向480.7g所得的粗二氰基降冰片烷中鼓泡1小时，使其脱气后，过滤不溶物；向此滤液中加入1.9g 40％硫酸，在60℃下加热3小时，进行催化剂的酸分解，进而加入5.5g 25％氢氧化钠，在40℃下加热2小时，中和后，加入449.0g甲苯，萃取二氰基降冰片烷，得到二氰基降冰片烷甲苯溶液后，蒸馏除去甲苯，得到447.6g 85％的二氰基降 冰片烷。
然后，向500mL高压釜中装入287.8g上述得到的二氰基降冰片烷和32.6g 25％氨水及7.9g催化剂雷尼钴，在氢气压力3.5MPa、120℃下进行催化加氢反应430分钟；冷却至室温，过滤除去催化剂雷尼钴后，向滤液中添加0.5g 32wt％苛性钠，在2.6KPa、75℃下蒸馏除去二氰基降冰片烷中所含的氨、甲苯；然后，在0.1MPa、烧瓶内部温度150℃～160℃的条件下蒸馏，得到204g降冰片烷二甲胺。
通过对以上实施例和对比例进行比较可以看出，本发明提供的制备方法能够避免使用氰化氢、铑催化剂及其他配体，方法简单、易操作、危险性不大，同时原料易得且成本低，产品收率较高。
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。

Claims (10)

  1. 一种降冰片烷二甲胺的制备方法，包括以下步骤：
    a)将式(I)所示结构的化合物与乌洛托品、酸、第一溶剂混合，进行第一次反应，得到第一反应混合物；再将上述第一反应混合物依次进行中和、第一次过滤，得到的滤液进行第一次提纯，得到式(II)所示结构化合物；
    Figure PCTCN2020125793-appb-100001
    b)将步骤a)得到的式(II)所示结构化合物与氢气、催化剂、第二溶剂混合，进行第二次反应，得到第二反应混合物；再将上述第二反应混合物进行第二次过滤，得到的滤液进行第二次提纯，得到降冰片烷二甲胺。
  2. 根据权利要求1所述的制备方法，其特征在于，步骤a)中所述酸选自氢溴酸、草酸、次氯酸、对甲苯磺酸、盐酸、硫酸、硝酸、乙酸和三氟乙酸中的一种或多种。
  3. 根据权利要求1所述的制备方法，其特征在于，步骤a)中所述第一溶剂选自丙烯腈、乙腈、丙腈、丙酮、甲乙酮、甲基异丁基酮、环己酮、环己酮和乙醚中的一种或多种。
  4. 根据权利要求1所述的制备方法，其特征在于，步骤a)中所述式(I)所示结构的化合物和乌洛托品的摩尔比为1：(0.25～1)。
  5. 根据权利要求1所述的制备方法，其特征在于，步骤a)中所述式(I)所示结构的化合物、酸和第一溶剂的质量比为1：(1～10)：(5～20)。
  6. 根据权利要求1所述的制备方法，其特征在于，步骤a)中所述第一次反应的温度为30℃～100℃，时间为4h～17h。
  7. 根据权利要求1所述的制备方法，其特征在于，步骤b)中所述催化剂选自钯碳、甲酸镍、铂黑、铂碳、镍-氧化铝、超细镍、雷尼镍、雷尼钴和雷尼铜中的一种或多种。
  8. 根据权利要求1所述的制备方法，其特征在于，步骤b)中所述第二溶剂选自甲醇、甲苯、邻二甲苯、间二甲苯和对二甲苯中的一种或多种。
  9. 根据权利要求1所述的制备方法，其特征在于，步骤b)中所述式(II)所示结构化合物、催化剂和第二溶剂的质量比为1：(0.01～0.35)：(20～50)。
  10. 根据权利要求1所述的制备方法，其特征在于，步骤b)中所述第二次反应的温度为60℃～140℃，压力为0.5MPa～2MPa，时间为3h～10h。
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