CN108840806B - 一种苯甲酰胺类化合物的制备方法 - Google Patents
一种苯甲酰胺类化合物的制备方法 Download PDFInfo
- Publication number
- CN108840806B CN108840806B CN201810653261.1A CN201810653261A CN108840806B CN 108840806 B CN108840806 B CN 108840806B CN 201810653261 A CN201810653261 A CN 201810653261A CN 108840806 B CN108840806 B CN 108840806B
- Authority
- CN
- China
- Prior art keywords
- formula
- preparation
- solvent
- reaction
- benzamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- -1 benzamide compound Chemical class 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 title claims abstract description 9
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 8
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 229910052802 copper Inorganic materials 0.000 claims abstract description 7
- 239000010949 copper Substances 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 7
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 5
- 239000003480 eluent Substances 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 150000003936 benzamides Chemical class 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical group ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical group Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 3
- 229940117389 dichlorobenzene Drugs 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 239000012044 organic layer Substances 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- ACRWYXSKEHUQDB-UHFFFAOYSA-N 3-phenylpropionitrile Chemical compound N#CCCC1=CC=CC=C1 ACRWYXSKEHUQDB-UHFFFAOYSA-N 0.000 claims description 2
- 238000005481 NMR spectroscopy Methods 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- 229940045803 cuprous chloride Drugs 0.000 claims description 2
- 238000001514 detection method Methods 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims 1
- 238000013461 design Methods 0.000 abstract description 2
- 238000009509 drug development Methods 0.000 abstract description 2
- 238000007877 drug screening Methods 0.000 abstract description 2
- 239000002547 new drug Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000012295 chemical reaction liquid Substances 0.000 abstract 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000006549 C4-C10 aryl group Chemical group 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000005749 Copper compound Substances 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001880 copper compounds Chemical class 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B43/00—Formation or introduction of functional groups containing nitrogen
- C07B43/06—Formation or introduction of functional groups containing nitrogen of amide groups
-
- 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Abstract
本发明提供一种苯甲酰胺类化合物的制备方法,将氨基化合物与苯乙氰混合加入溶剂中,在铜催化剂作用下,在80~120℃温度下搅拌反应15‑30小时,反应结束后,反应液后处理制得苯甲酰胺类化合物。本发明提供的制备方法,设计合理,该工艺反应条件温和,原料易得,操作方便,有着广泛的工业应用前景。为新药筛选及开发奠定了基础,具有较好的实用价值。
Description
技术领域
本发明属于制药领域,涉及一种苯甲酰胺类化合物的制备方法。
背景技术
酰胺类化合物不仅是重要的有机合成中间体,也广泛应用于医药、农药及材料的合成中。因此研究开发该类化合物的制备方法具有一定的应用价值。
发明内容
本发明提供一种苯甲酰胺类化合物的制备方法,所述的苯甲酰胺类化合物的结构通式如式(II)所示,通过以下技术方案实现:
式(II)中R为C4~C10芳基;优选为苯基或芳杂环;其中芳杂环优选为吡啶或嘧啶。
具体制备方法如下:
将式(I)所示的氨基化合物与苯乙氰混合加入溶剂中,在铜催化剂作用下,在80~120℃温度下搅拌反应15~30小时,反应结束后,反应液后处理制得式(II)所示的苯甲酰胺类化合物。
式(I)所示的氨基化合物与苯乙氰、金属铜催化剂的量比为1:1.0~10.0:0.1~0.4。
式(I)结构式为:
R-NH2 (1)
其中R的定义同通式(II)相同。
所述的溶剂为芳烃类;优选为取代苯类,优选为二氯苯或氯苯。所述溶剂的体积用量通常以氨基化合物的质量计为2~10mL/mmol。
所述金属铜催化剂为一价铜化合物;优选为溴化亚铜或氯化亚铜。
本发明所述制备方法中,所述后处理可采用如下方法:反应结束后,加水,用二氯甲烷萃取萃取,合并有机层,用无水硫酸钠干燥,过滤,浓缩滤液,柱层析(石油醚:乙酸乙酯=10:1,V:V),收集洗脱液,减压蒸馏,残渣干燥后经核磁共振检测确定为目标化合物(II)。
本发明开发了一种苯甲酰胺类化合物的制备方法,设计合理,该工艺反应条件温和,原料易得,操作方便,有着广泛的工业应用前景。为新药筛选及开发奠定了基础,具有较好的实用价值。
具体实施方式
下面将通过实施例对本发明作进一步的说明,但本发明的保护范围不限于此。
实施例1化合物(II-1)的制备:
将苯胺(118.8mg,1.28mmol),苯乙腈(748.5mg,6.39mmol),CuCl(24.2mg,0.24mmol)在氯苯(2.0mL)中混合,在120℃条件下反应,反应15h,反应结束后,加水50mL,用二氯甲烷萃取(20mL×3),合并有机层,用无水硫酸钠干燥,过滤,浓缩,柱层析(洗脱剂为石油醚:乙酸乙酯=10:1,V:V),收集Rf值0.3~0.35的洗脱液(TLC监测,展开剂同洗脱剂),减压蒸馏除去溶剂,干燥得目标化合物(II-1)150.1mg,收率60%。1H NMR(500MHz,CDCl3):δ7.91(s,1H),7.89-7.87(m,2H),7.67-7.65(m,2H),7.58-7.55(m,1H),7.51-7.48(m,2H),7.40-7.37(m,2H),7.19-7.16(m,1H)。
实施例2:
将氯化亚铜改为溴化亚铜(79mg,0.5mmol),苯乙腈改为(1.5g,12.8mmol),时间改为30h,其他操作同实施例1,得量137.6mg,收率55%。
实施例3:
将氯苯改为二氯苯(13mL),苯乙腈改为(150mg,1.28mmol),温度改为80℃,其他操作同实施例1,得量50mg,收率20%。
实施例4:
将苯胺改为2-氨基吡啶(119.4mg,1.27mmol),其他操作同实施例1,目标化合物(II-2)186.8mg,收率75%。1H NMR(500MHz,CDCl3):δ9.03(s,1H),8.43-8.41(m,1H),8.22-8.20(m,1H),7.95-7.94(m,2H),7.78-7.75(m,1H),7.59-7.55(m,1H),7.51-7.48(m,2H),7.07-7.04(m,1H)。
实施例5:
将苯胺改为2-氨基嘧啶(120.5mg,1.27mmol),CuCl改为(12.8mg,0.13mmol),其他操作同实施例1,目标化合物(II-3)68.1mg,收率28%。1H NMR(500MHz,CDCl3):δ8.87(s,1H),8.66(d,J=4.9Hz,2H),7.96-7.94(m,2H),7.61-7.57(m,1H),7.53-7.50(m,2H),7.07(t,J=4.9Hz,1H)。
Claims (2)
2.根据权利要求1所述的一种苯甲酰胺类化合物的制备方法,其特征在于,所述后处理采用如下方法:反应结束后,加水,用二氯甲烷萃取,合并有机层,用无水硫酸钠干燥,过滤,浓缩滤液,柱层析,其中石油醚:乙酸乙酯的体积比为10:1,收集洗脱液,减压蒸馏,残渣干燥后经核磁共振检测确定为目标化合物(II)。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810653261.1A CN108840806B (zh) | 2018-06-22 | 2018-06-22 | 一种苯甲酰胺类化合物的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810653261.1A CN108840806B (zh) | 2018-06-22 | 2018-06-22 | 一种苯甲酰胺类化合物的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN108840806A CN108840806A (zh) | 2018-11-20 |
CN108840806B true CN108840806B (zh) | 2020-11-06 |
Family
ID=64203096
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810653261.1A Expired - Fee Related CN108840806B (zh) | 2018-06-22 | 2018-06-22 | 一种苯甲酰胺类化合物的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN108840806B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112920079A (zh) * | 2021-01-29 | 2021-06-08 | 广西田园生化股份有限公司 | 一种酰胺化合物的制备方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104710259A (zh) * | 2015-03-16 | 2015-06-17 | 浙江工业大学 | 一种酰胺类化合物的合成方法 |
-
2018
- 2018-06-22 CN CN201810653261.1A patent/CN108840806B/zh not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104710259A (zh) * | 2015-03-16 | 2015-06-17 | 浙江工业大学 | 一种酰胺类化合物的合成方法 |
Non-Patent Citations (3)
Title |
---|
An efficient protocol for the preparation of amides by copper-catalyzed reactions between nitriles and amines in water;XiaoyaLi等;《Tetrahedron Letters》;20131231;第54卷(第18期);第2212-2216页 * |
Copper catalyzed N-arylation between aryl halides and nitriles in water: an efficient tandem synthesis of benzanilides;Jichao Wang等;《Tetrahedron》;20131231;第69卷;第10463-10469页 * |
Ruthenium-catalyzed oxidative decyanative cross-coupling of acetonitriles with amines in air: a general access to primary to tertiary amides under mild conditions;Yuguang Wang等;《Catalysis Science & Technology》;20171231;第7卷(第17期);第3747-757页 * |
Also Published As
Publication number | Publication date |
---|---|
CN108840806A (zh) | 2018-11-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI580675B (zh) | Preparation of 4- [5- (pyridin-4-yl) -1H-1,2,4-triazol-3-yl] pyridine-2-carbonitrile and intermediates | |
CN111646922B (zh) | 一种2-(4-溴-2-氰基-6-氟苯基)乙酸的合成方法 | |
CN104447686B (zh) | 多取代2-吡咯吡啶衍生物及其制备方法 | |
CN105001031B (zh) | 含单酚功能化咪唑啉阳离子的离子型铁(iii)配合物及其制备方法与应用 | |
CN108794414B (zh) | 芳酰胺基取代的均三嗪类化合物及制备和应用 | |
CN108840806B (zh) | 一种苯甲酰胺类化合物的制备方法 | |
CN105985258B (zh) | 一种苯甲酰胺化合物的制备方法及其中间体 | |
CN113416150A (zh) | 一种洛铂中间体的新合成方法 | |
KR102443292B1 (ko) | 1-[5-(2-플루오로페닐)-1-(피리딘-3-일술포닐)-1h-피롤-3-일]-n-메틸메탄아민모노푸마르산염의 제조법 | |
CN107522742B (zh) | 一种Brigatinib关键中间体的均相“一锅法”制备方法 | |
CN108503501B (zh) | 一种合成2-氟代-n-取代芳基甲酰胺类化合物的方法 | |
CN105272987A (zh) | 一种3-氰基-n-错位卟啉化合物的制备方法 | |
CN108840829A (zh) | 一种4-芳基-1,3,5-三嗪-2-酮类化合物的制备方法 | |
CN110028448B (zh) | 一种3-羟基-2,3-二氢异喹啉-1,4-二酮化合物的制备方法 | |
CN106242989B (zh) | 一种草酰苯胺类衍生物的合成方法 | |
CN107163036A (zh) | 一种含噻唑环5,6‑二取代吡啶‑2‑酮化合物及其制备方法 | |
KR100574350B1 (ko) | 2-아미노피리딘 유도체의 제조방법 | |
CN107915694A (zh) | 1‑[2‑(2,4‑二甲基苯基巯基)苯基]哌嗪盐酸盐及其制备方法 | |
CN107573263B (zh) | 一种ω-取代缩二脲类化合物的合成方法 | |
CN105198806A (zh) | 一种利用芳香胺、二酮合成喹啉衍生物的方法 | |
CN105153048A (zh) | 一种2,4-喹唑啉二酮类化合物的制备方法 | |
CN110683943B (zh) | 一种氟代1,3-烯炔类化合物及其制备方法 | |
CN117510403A (zh) | 一种3-乙基-吡啶-2-甲脒盐酸盐的合成方法 | |
CN115772115B (zh) | 一种芳基吡啶溴代衍生物的合成方法 | |
CN102093258A (zh) | 芳香型二脒化合物及其合成方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20201106 |