CN104016913A - Method for preparing amide compound - Google Patents
Method for preparing amide compound Download PDFInfo
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- CN104016913A CN104016913A CN201410227369.6A CN201410227369A CN104016913A CN 104016913 A CN104016913 A CN 104016913A CN 201410227369 A CN201410227369 A CN 201410227369A CN 104016913 A CN104016913 A CN 104016913A
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- -1 amide compound Chemical class 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title claims abstract description 17
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 12
- 239000012046 mixed solvent Substances 0.000 claims abstract description 9
- 239000003586 protic polar solvent Substances 0.000 claims abstract description 6
- 239000012429 reaction media Substances 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 238000010898 silica gel chromatography Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 2
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 2
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 claims 1
- 235000015320 potassium carbonate Nutrition 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 10
- 230000007062 hydrolysis Effects 0.000 abstract description 7
- 238000002360 preparation method Methods 0.000 abstract description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 abstract description 4
- 239000000010 aprotic solvent Substances 0.000 abstract description 4
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 abstract description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 abstract description 2
- 238000005859 coupling reaction Methods 0.000 abstract description 2
- 238000010438 heat treatment Methods 0.000 abstract description 2
- 150000002894 organic compounds Chemical class 0.000 abstract description 2
- 239000007800 oxidant agent Substances 0.000 abstract description 2
- 239000004327 boric acid Substances 0.000 abstract 1
- 230000003197 catalytic effect Effects 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 4
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 2
- XHYGUDGTUJPSNX-UHFFFAOYSA-N 6-bromopyridine-3-carbonitrile Chemical compound BrC1=CC=C(C#N)C=N1 XHYGUDGTUJPSNX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- QQLRSCZSKQTFGY-UHFFFAOYSA-N (2,4-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C=C1F QQLRSCZSKQTFGY-UHFFFAOYSA-N 0.000 description 1
- VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 description 1
- XRNBLQCAFWFFPM-UHFFFAOYSA-N 4-iodobenzamide Chemical compound NC(=O)C1=CC=C(I)C=C1 XRNBLQCAFWFFPM-UHFFFAOYSA-N 0.000 description 1
- XOKDXPVXJWTSRM-UHFFFAOYSA-N 4-iodobenzonitrile Chemical compound IC1=CC=C(C#N)C=C1 XOKDXPVXJWTSRM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- CANPFCFJURGKAX-JTQLQIEISA-N iolopride Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C(I)=CC=C1OC CANPFCFJURGKAX-JTQLQIEISA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/06—Preparation of carboxylic acid amides from nitriles by transformation of cyano groups into carboxamide groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
本发明属于有机化合物制备领域，具体涉及一种制备酰胺化合物的方法。具体为在加热条件下，以质子性溶剂和非质子性溶剂的混合溶剂作为反应介质，空气氛围和碱性催化条件下，通过氰基化合物选择性水解，高效制备相应的酰胺化合物；同时还可以进一步利用碳碳偶联反应，通过选用同时含用氰基与卤素基团的化合物与硼酸化合物反应，可以一步法制备得到偶联后的酰胺化合物。该方法避免了传统的双氧水等有毒有害氧化剂的使用，是制备酰胺化合物的一种简便高效、绿色环保的合成方法。The invention belongs to the field of organic compound preparation, and in particular relates to a method for preparing amide compounds. Specifically, under heating conditions, the mixed solvent of protic solvent and aprotic solvent is used as the reaction medium, and the corresponding amide compound is efficiently prepared by selective hydrolysis of the cyano compound under air atmosphere and basic catalytic conditions; at the same time, it can also Further utilizing the carbon-carbon coupling reaction, the coupled amide compound can be prepared in one step by selecting a compound containing both a cyano group and a halogen group to react with a boric acid compound. The method avoids the use of traditional hydrogen peroxide and other toxic and harmful oxidants, and is a simple, efficient, green and environment-friendly synthesis method for preparing amide compounds.
Description
技术领域 technical field
本发明属于有机化合物制备领域，具体涉及一种制备酰胺化合物的方法。 The invention belongs to the field of organic compound preparation, and in particular relates to a method for preparing amide compounds.
背景技术 Background technique
酰胺化合物是一类重要的化工原材料，在生物、医学、制药等领域有着广泛的应用。现有技术中制备酰胺化合物的方式有两种：一种是通过羧基与氨基的缩合反应来制备得到酰胺，但该反应通常需要对原料进行活化处理，反应条件通常比较苛刻。 Amide compounds are an important class of chemical raw materials, which are widely used in the fields of biology, medicine, and pharmacy. There are two ways to prepare amide compounds in the prior art: one is to prepare amides through the condensation reaction of carboxyl and amino groups, but this reaction usually requires activation of raw materials, and the reaction conditions are usually relatively harsh.
另外则是通过氰基水解方式制备酰胺化合物，主要分为在酸性条件或者碱性条件下水解氰基。在碱性条件下，利用过氧化氢氧化的方法可在室温下短时间内水解腈为酰胺；但该方法通常不容易控制反应的进度，而使氰基完全水解成羧酸。 In addition, amide compounds are prepared by hydrolysis of cyano group, which is mainly divided into hydrolysis of cyano group under acidic or alkaline conditions. Under alkaline conditions, the hydrogen peroxide oxidation method can hydrolyze nitriles to amides in a short period of time at room temperature; but this method is usually not easy to control the progress of the reaction, and the cyano group is completely hydrolyzed into carboxylic acids.
因此寻找新的高效、可控制备酰胺化合物的合成方法具有十分重要的意义。 Therefore, it is of great significance to find new efficient and controllable synthetic methods for the preparation of amides.
发明内容 Contents of the invention
本发明的目的是提供一种酰胺化合物的制备方法。 The purpose of this invention is to provide a kind of preparation method of amide compound.
为达到上述发明目的，本发明采用的技术方案是：一种制备酰胺化合物的方法，包括如下步骤：空气氛围中，以氰基化合物为原料，以质子性溶剂以及非质子性溶剂的混合溶剂为反应介质，在碱存在下，于40-150℃下通过氰基水解反应制备得到酰胺化合物； In order to achieve the above-mentioned purpose of the invention, the technical solution adopted in the present invention is: a method for preparing amide compounds, comprising the following steps: in air atmosphere, using cyano compounds as raw materials, using a mixed solvent of protic solvent and aprotic solvent as In the reaction medium, in the presence of a base, an amide compound is prepared by hydrolysis of a cyano group at 40-150°C;
所述氰基化合物的结构式为以下结构式中的一种： The structural formula of the cyano compound is one of the following structural formulas:
式中，R1、R2、R3、R4独立的选自H、F、Cl、Br、I、CH3、OMe、CH2CH3中的一种；n为0-4； In the formula, R 1 , R 2 , R 3 , and R 4 are independently selected from one of H, F, Cl, Br, I, CH 3 , OMe, CH 2 CH 3 ; n is 0-4;
所述酰胺化合物的结构式为以下结构式中的一种： The structural formula of the amide compound is one of the following structural formulas:
式中，R1、R2、R3、R4独立的选自H、F、Cl、Br、I、CH3、OMe、CH2CH3中的一种；n为0-4。 In the formula, R 1 , R 2 , R 3 , and R 4 are independently selected from one of H, F, Cl, Br, I, CH 3 , OMe, CH 2 CH 3 ; n is 0-4.
上述技术方案中，所述非质子性溶剂为甲苯、二甲苯、四氢呋喃、丙酮、N，N-二甲基甲酰胺、N，N-二甲基亚砜中的一种或一种以上混合物；所述质子性溶剂是水、乙醇、乙二醇乙醚、乙二醇甲醚中的一种或一种以上混合物。 In the above technical scheme, the aprotic solvent is one or more mixtures of toluene, xylene, tetrahydrofuran, acetone, N,N-dimethylformamide, N,N-dimethylsulfoxide; The protic solvent is one or more mixtures of water, ethanol, ethylene glycol ether, and ethylene glycol methyl ether.
上述技术方案中，所述碱为碳酸钠、碳酸钾、叔丁醇钠、叔丁醇钾、甲醇钠、甲醇钾、氢氧化钠、氢氧化钾、浓氨水、吡啶或者1,8-二氮杂二环十一碳-7-烯。 In the above technical scheme, the alkali is sodium carbonate, potassium carbonate, sodium tert-butoxide, potassium tert-butoxide, sodium methoxide, potassium methoxide, sodium hydroxide, potassium hydroxide, concentrated ammonia, pyridine or 1,8-diazepine Heterobicycloundec-7-ene.
上述技术方案中，所述氰基水解反应的时间为0.5-48 h。 In the above technical scheme, the time for the hydrolysis reaction of the cyano group is 0.5-48 h.
优选的技术方案中，所述氰基水解反应的温度为回流温度。 In a preferred technical solution, the temperature of the cyano hydrolysis reaction is the reflux temperature.
上述技术方案中，所述氰基化合物与碱的摩尔比为1∶10-100。 In the above technical solution, the molar ratio of the cyano compound to the base is 1:10-100.
上述技术方案还包括提纯步骤，具体为反应结束后，旋干溶剂，然后利用硅胶柱层析进行纯化分离后得到产物酰胺化合物。 The above technical scheme also includes a purification step, specifically, after the reaction is completed, the solvent is spin-dried, and then purified and separated by silica gel column chromatography to obtain the product amide compound.
上述技术方案中，浓氨水的质量浓度为22-25%；1,8-二氮杂二环十一碳-7-烯又称DBU，其结构式为： In the above technical scheme, the mass concentration of concentrated ammonia water is 22-25%; 1,8-diazabicycloundec-7-ene is also called DBU, and its structural formula is:
。 .
本发明中质子溶剂和非质子溶剂的混合可以提高反应的效率；加热克服了反应的活化能，有利于反应的顺利进行。 The mixing of the protic solvent and the aprotic solvent in the present invention can improve the efficiency of the reaction; the heating overcomes the activation energy of the reaction, which is beneficial to the smooth progress of the reaction.
以2-氰基吡啶制备2-酰胺吡啶为例，本发明可用以下反应式表示： Taking 2-cyanopyridine to prepare 2-amidopyridine as an example, the present invention can be represented by the following reaction formula:
由于上述技术方案运用，本发明与现有技术相比具有下列优点: Owing to above-mentioned technical scheme uses, the present invention has following advantage compared with prior art:
1．本发明公开的新的制备酰胺化合物的方法避免了现有技术中氧化剂的使用，从而有效抑制了氰基的过度水解，避免了酰胺进一步水解为羧酸的现象，极大提高了酰胺化合物的反应产率，甚至超过90%； 1. The new method for preparing amide compounds disclosed in the present invention avoids the use of oxidizing agents in the prior art, thereby effectively inhibiting the excessive hydrolysis of cyano groups, avoiding the further hydrolysis of amides into carboxylic acids, and greatly improving the reaction of amide compounds Yield, even more than 90%;
2．本发明公开的氰基水解制备酰胺化合物的方法可与其它反应，比如碳碳偶联反应同时进行，制备更多酰胺化合物，对于酰胺化合物的工业化生成具有重要的市场价值和经济效益； 2. The method for preparing amide compounds by hydrolysis of cyano groups disclosed in the present invention can be carried out simultaneously with other reactions, such as carbon-carbon coupling reactions, to prepare more amide compounds, which has important market value and economic benefits for the industrial production of amide compounds;
3. 本发明公开的制备酰胺化合物的合成路线短，只需一步；制备过程简单可控，效率高，环保，易于产业化。 3. The synthesis route for the preparation of amide compounds disclosed in the present invention is short and only needs one step; the preparation process is simple and controllable, with high efficiency, environmental protection and easy industrialization.
具体实施方式 Detailed ways
下面结合实施例对本发明作进一步描述： The present invention will be further described below in conjunction with embodiment:
实施例1Example 1
将2-氰基吡啶 (10 mmol, 1.04 g)，NaOH (0.1 mmol, 4 mg)溶于甲苯/水（V:V=3：1）的混合溶剂中，回流反应6小时后，停止反应，静置室温后，将溶剂旋干后，利用硅胶柱层析进行纯化分离后得到白色固体2-酰胺吡啶 0.95 g (产率：78%)；Ms(M/Z):122.0 (M+)。 Dissolve 2-cyanopyridine (10 mmol, 1.04 g) and NaOH (0.1 mmol, 4 mg) in a mixed solvent of toluene/water (V:V=3:1), and stop the reaction after reflux for 6 hours. After standing at room temperature, the solvent was spin-dried, purified and separated by silica gel column chromatography to obtain 0.95 g (yield: 78%) of white solid 2-amidopyridine; Ms (M/Z): 122.0 (M + ).
实施例2Example 2
将2-氰基吡啶 (10 mmol, 1.04 g)，K2CO3 (0.5 mmol, 69 mg)溶于甲苯/水/乙醇（V:V:V=6:2:1）的混合溶剂中，回流反应12小时后，停止反应，静置室温后，将溶剂旋干后，利用硅胶柱层析进行纯化分离后得到白色固体2-酰胺吡啶 1.04 g (产率：85%)；Ms(M/Z):122.0 (M+)。 Dissolve 2-cyanopyridine (10 mmol, 1.04 g), K 2 CO 3 (0.5 mmol, 69 mg) in a mixed solvent of toluene/water/ethanol (V:V:V=6:2:1), After 12 hours of reflux reaction, the reaction was stopped, and after standing at room temperature, the solvent was spin-dried, and purified and separated by silica gel column chromatography to obtain 1.04 g (yield: 85%) of white solid 2-amidopyridine; Ms (M/ Z): 122.0 (M + ).
实施例3Example 3
将2-溴-5-氰基吡啶 (10 mmol, 1.83g)，叔丁醇钠 (0.1 mmol, 9.6 mg) 溶于二甲苯/乙醇（V:V=3:1）的混合溶剂中，回流反应4小时后，停止反应，静置室温后，将溶剂旋干后，利用硅胶柱层析进行纯化分离后得到白色固体2-溴-5-酰胺吡啶 1.84 g (产率：92%)；Ms(M/Z):201.0 (M+)。 Dissolve 2-bromo-5-cyanopyridine (10 mmol, 1.83g), sodium tert-butoxide (0.1 mmol, 9.6 mg) in a mixed solvent of xylene/ethanol (V:V=3:1), and reflux After reacting for 4 hours, the reaction was stopped, and after standing at room temperature, the solvent was spin-dried, purified and separated by silica gel column chromatography to obtain 1.84 g of white solid 2-bromo-5-amidopyridine (yield: 92%); Ms (M/Z):201.0 (M + ).
上述2-溴-5-酰胺吡啶的结构式为： The structural formula of above-mentioned 2-bromo-5-amide pyridine is:
。 .
实施例4Example 4
将苯乙腈 (10 mmol, 1.17g)，浓氨水 (2 mL，质量浓度为23%) 溶于丙酮/水（V:V=3:1）的混合溶剂中，回流反应12小时后，停止反应，静置室温后，将溶剂旋干后，利用硅胶柱层析进行纯化分离后得到白色固体苯乙酰胺 1.2 g (产率：89%)；Ms(M/Z):135.1 (M+)。 Dissolve phenylacetonitrile (10 mmol, 1.17g) and concentrated ammonia water (2 mL, mass concentration: 23%) in a mixed solvent of acetone/water (V:V=3:1), reflux for 12 hours, and then stop the reaction , after standing at room temperature, the solvent was spin-dried, purified and separated by silica gel column chromatography to obtain 1.2 g of white solid phenylacetamide (yield: 89%); Ms (M/Z): 135.1 (M + ).
实施例5Example 5
将对碘苯氰 (10 mmol, 2.28g)，Na2CO3 (0.5mmol, 57 mg) 溶于四氢呋喃/水（V:V=3:1）的混合溶剂中，回流反应6小时后，停止反应，静置室温后，将溶剂旋干后，利用硅胶柱层析进行纯化分离后得到白色固体对碘苯酰胺2.2 g (产率：89%)；Ms(M/Z):247.0 (M+)。 Dissolve p-iodobenzonitrile (10 mmol, 2.28g), Na 2 CO 3 (0.5mmol, 57 mg) in a mixed solvent of tetrahydrofuran/water (V:V=3:1), reflux for 6 hours, stop Reaction, after standing at room temperature, the solvent was spin-dried, purified and separated by silica gel column chromatography to obtain 2.2 g of white solid p-iodobenzamide (yield: 89%); Ms (M/Z): 247.0 (M + ).
上述对碘苯酰胺的结构式为： The structural formula of above-mentioned iodobenzamide is:
。 .
实施例6Example 6
将2-溴-5-氰基吡啶 (10 mmol, 1.83g)，2,4-二氟苯硼酸(10 mmol,1.58g), Na2CO3 (0.5mmol, 57 mg) ，四三苯基磷钯（0.1 mmol，115mg）溶于甲苯/乙醇/水（V:V:V=5:2:1）的混合溶剂中，回流反应24小时后，停止反应，静置室温后，利用二氯甲烷进行水洗后，收集有机相，然后利用硅胶柱层析进行纯化分离后得到白色固体 2-(2’,4’-二氟苯基)-5’-酰胺吡啶2.1 g (产率：89%)；Ms(M/Z):234.1 (M+)；1H NMR (DMSO-d 6 , 400 MHz), δppm:9.15 (s, 1 H), 8.33 (dd, J=8 Hz, 2 Hz,1H), 8.22(s, 1H), 8.06 (m, 1H), 7.88(m, 1H), 7.66 (s, 1H), 7.44 (m, 1H), 7.27 (m, 1H)。 2-Bromo-5-cyanopyridine (10 mmol, 1.83g), 2,4-difluorophenylboronic acid (10 mmol, 1.58g), Na 2 CO 3 (0.5mmol, 57 mg), tetratriphenyl Phosphopalladium (0.1 mmol, 115 mg) was dissolved in a mixed solvent of toluene/ethanol/water (V:V:V=5:2:1). After 24 hours of reflux reaction, the reaction was stopped. After standing at room temperature, dichloro After methane was washed with water, the organic phase was collected, and then purified and separated by silica gel column chromatography to obtain 2.1 g of white solid 2-(2',4'-difluorophenyl)-5'-amidopyridine (yield: 89% ); Ms(M/Z):234.1 (M + ); 1 H NMR (DMSO- d 6 , 400 MHz), δppm: 9.15 (s, 1 H), 8.33 (dd, J=8 Hz, 2 Hz, 1H), 8.22(s, 1H), 8.06 (m, 1H), 7.88(m, 1H), 7.66 (s, 1H), 7.44 (m, 1H), 7.27 (m, 1H).
上述2-(2’,4’-二氟苯基)-5’-酰胺吡啶的结构式为： The structural formula of the above-mentioned 2-(2',4'-difluorophenyl)-5'-amidopyridine is:
。 .
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| CN103342654A (en) * | 2013-07-02 | 2013-10-09 | 扬州大学 | Novel method for hydrolyzing nitrile group to acylamino |
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| JPS56128761A (en) * | 1980-03-12 | 1981-10-08 | Dai Ichi Seiyaku Co Ltd | Preparation of pyridoxine |
| CN102603563A (en) * | 2012-01-16 | 2012-07-25 | 山东康乔生物科技有限公司 | Preparation method of metominostrobin |
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