CN102816042A - A kind of method of synthesizing β-amide carbonyl compound - Google Patents
A kind of method of synthesizing β-amide carbonyl compound Download PDFInfo
- Publication number
- CN102816042A CN102816042A CN201210320524XA CN201210320524A CN102816042A CN 102816042 A CN102816042 A CN 102816042A CN 201210320524X A CN201210320524X A CN 201210320524XA CN 201210320524 A CN201210320524 A CN 201210320524A CN 102816042 A CN102816042 A CN 102816042A
- Authority
- CN
- China
- Prior art keywords
- synthesizing
- reaction
- carbonyl compound
- amide carbonyl
- acetonitrile
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 24
- 230000002194 synthesizing effect Effects 0.000 title claims abstract 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 57
- 239000003054 catalyst Substances 0.000 claims abstract description 17
- 125000003118 aryl group Chemical group 0.000 claims abstract description 6
- 238000004440 column chromatography Methods 0.000 claims abstract description 6
- 125000001424 substituent group Chemical group 0.000 claims abstract description 6
- 238000001953 recrystallisation Methods 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims abstract 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 99
- 150000001875 compounds Chemical class 0.000 claims description 35
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- 150000003934 aromatic aldehydes Chemical class 0.000 claims description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- -1 nitrile compound Chemical class 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 6
- 239000003208 petroleum Substances 0.000 claims description 6
- 239000000376 reactant Substances 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 239000012074 organic phase Substances 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 239000012429 reaction media Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 2
- 229940095564 anhydrous calcium sulfate Drugs 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 239000002274 desiccant Substances 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 239000012065 filter cake Substances 0.000 claims description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 2
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 2
- 238000002390 rotary evaporation Methods 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
- 150000001263 acyl chlorides Chemical class 0.000 claims 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical group C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims 1
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 1
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 claims 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 150000008282 halocarbons Chemical class 0.000 claims 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 239000008096 xylene Substances 0.000 claims 1
- 239000000758 substrate Substances 0.000 abstract description 8
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 abstract description 5
- 239000012346 acetyl chloride Substances 0.000 abstract description 5
- 238000000746 purification Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 231100000252 nontoxic Toxicity 0.000 abstract 1
- 230000003000 nontoxic effect Effects 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 65
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical class CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 62
- 238000005481 NMR spectroscopy Methods 0.000 description 34
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 32
- 239000000047 product Substances 0.000 description 30
- 239000011734 sodium Substances 0.000 description 26
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 16
- 230000003595 spectral effect Effects 0.000 description 15
- NTPLXRHDUXRPNE-UHFFFAOYSA-N 4-methoxyacetophenone Chemical compound COC1=CC=C(C(C)=O)C=C1 NTPLXRHDUXRPNE-UHFFFAOYSA-N 0.000 description 14
- 238000001228 spectrum Methods 0.000 description 10
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 7
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical class CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 7
- WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 6
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 6
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 6
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 5
- YQYGPGKTNQNXMH-UHFFFAOYSA-N 4-nitroacetophenone Chemical compound CC(=O)C1=CC=C([N+]([O-])=O)C=C1 YQYGPGKTNQNXMH-UHFFFAOYSA-N 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- ARKIFHPFTHVKDT-UHFFFAOYSA-N 1-(3-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC=CC([N+]([O-])=O)=C1 ARKIFHPFTHVKDT-UHFFFAOYSA-N 0.000 description 4
- YSFBEAASFUWWHU-UHFFFAOYSA-N 2,4-dichlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C(Cl)=C1 YSFBEAASFUWWHU-UHFFFAOYSA-N 0.000 description 4
- SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 3
- OACPOWYLLGHGCR-UHFFFAOYSA-N 2-chloro-6-fluorobenzaldehyde Chemical compound FC1=CC=CC(Cl)=C1C=O OACPOWYLLGHGCR-UHFFFAOYSA-N 0.000 description 3
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 0 CC(NC(CC(c1ccccc1)=O)c(c(*)ccc1)c1F)=O Chemical compound CC(NC(CC(c1ccccc1)=O)c(c(*)ccc1)c1F)=O 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000001805 chlorine compounds Chemical class 0.000 description 3
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical class CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- KUCOHFSKRZZVRO-UHFFFAOYSA-N terephthalaldehyde Chemical compound O=CC1=CC=C(C=O)C=C1 KUCOHFSKRZZVRO-UHFFFAOYSA-N 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- LQZKMASBFQOGJR-UHFFFAOYSA-N 2-[[2-amino-4-hydroxy-4-(4-hydroxyphenyl)-3-methylbutanoyl]amino]-2-[5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]acetic acid Chemical compound C=1C=C(O)C=CC=1C(O)C(C)C(N)C(=O)NC(C(O)=O)C(C(C1O)O)OC1N1C=CC(=O)NC1=O LQZKMASBFQOGJR-UHFFFAOYSA-N 0.000 description 2
- 150000003935 benzaldehydes Chemical class 0.000 description 2
- 150000001576 beta-amino acids Chemical class 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- IEJPPSMHUUQABK-UHFFFAOYSA-N 2,4-diphenyl-4h-1,3-oxazol-5-one Chemical compound O=C1OC(C=2C=CC=CC=2)=NC1C1=CC=CC=C1 IEJPPSMHUUQABK-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- OCMCJRIPIDJTJJ-UHFFFAOYSA-N CC(NC(CC(c1ccc(C(CC(c2ccccc2)=O)NC(C)=O)cc1)=O)c1ccccc1)=N Chemical compound CC(NC(CC(c1ccc(C(CC(c2ccccc2)=O)NC(C)=O)cc1)=O)c1ccccc1)=N OCMCJRIPIDJTJJ-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 238000006021 Dakin-West synthesis reaction Methods 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- QSDSSSQWVNLFIG-UHFFFAOYSA-N Neosporin Natural products CC(O)CC1=C(OC)C(=O)C2=CC(O)=C3OCOC4=C(O)C=C5C6=C4C3=C2C1=C6C(CC(C)O)=C(OC)C5=O QSDSSSQWVNLFIG-UHFFFAOYSA-N 0.000 description 1
- 229930184499 Nikkomycin Natural products 0.000 description 1
- OYYBZOZCMOFKEF-UHFFFAOYSA-N Nikkomycin Bx Natural products C=1C=C(O)C=CC=1C(O)C(C)C(N)C(=O)NC(C(O)=O)C(C(C1O)O)OC1N1C=C(C=O)NC1=O OYYBZOZCMOFKEF-UHFFFAOYSA-N 0.000 description 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 150000008062 acetophenones Chemical class 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000007697 cis-trans-isomerization reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 108010046161 drug combination polymyxin B neomycin sulfate bacitracin zinc Proteins 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- AGPADOSSJFUOHL-UHFFFAOYSA-N n-(3-oxo-1,3-diphenylpropyl)acetamide Chemical compound C=1C=CC=CC=1C(NC(=O)C)CC(=O)C1=CC=CC=C1 AGPADOSSJFUOHL-UHFFFAOYSA-N 0.000 description 1
- WWJFFVUVFNBJTN-UHFFFAOYSA-N neopolyoxin C Natural products C=1C=C(O)C=NC=1C(O)C(C)C(N)C(=O)NC(C(O)=O)C(C(C1O)O)OC1N1C=CC(=O)NC1=O WWJFFVUVFNBJTN-UHFFFAOYSA-N 0.000 description 1
- 229940049337 neosporin Drugs 0.000 description 1
- 108010021771 nikkomycin B Proteins 0.000 description 1
- WWJFFVUVFNBJTN-VHDFTHOZSA-N nikkomycin Z Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)[C@H](NC(=O)[C@@H](N)[C@H](C)[C@H](O)C=2N=CC(O)=CC=2)C(O)=O)C=CC(=O)NC1=O WWJFFVUVFNBJTN-VHDFTHOZSA-N 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
（一）技术领域 (1) Technical field
本发明涉及一种经由芳醛，羰基化合物和腈类化合物反应制备β-酰胺羰基化合物（β-acetamide carbonyl compounds）的合成方法。The invention relates to a synthesis method for preparing β-acetamide carbonyl compounds (β-acetamide carbonyl compounds) through the reaction of aromatic aldehydes, carbonyl compounds and nitrile compounds.
（二）背景技术 (2) Background technology
近年来β-酰胺酮因其结构广泛存在于很多的具有生理活性和药理活性的天然药物结构中而广泛引起了化学家和医学家们的关注。β-酰胺羰基化合物能很简便的转化成1,3-二氨基醇，或者β-氨基酸等化合物。1,3-二氨基醇和β-氨基酸等化合物都是合成一些核苷肽类型抗生素的核心结构，例如尼可霉素和新多氧菌素。β-芳基异苏氨酸的前体可以和一分子的氨基酸组合成相应的二肽异构体，它也可以以β-酰胺羰基化合物为前体来合成。机制抑制性蛋白酶近年来也引起了化学家和医学家们的关注，例如研究如何改进具有肽类结构且对humanimmunodeficiency virus type1(HIV 1)疾病有抑制作用的抑制性蛋白酶，使其对acquiredimmunodeficiency syndrome(AIDS)疾病有治疗作用，已经成为研究治疗AIDS抑制型蛋白酶的一个新方向。β-酰胺羰基化合物对于合成机制抑制性蛋白酶也有很大的用处。In recent years, β-amide ketones have attracted the attention of chemists and medical scientists because their structures widely exist in many natural drug structures with physiological and pharmacological activities. β-amide carbonyl compounds can be easily converted into 1,3-diaminoalcohols, or β-amino acids and other compounds. Compounds such as 1,3-diaminoalcohol and β-amino acid are the core structures for the synthesis of some nucleoside peptide antibiotics, such as nikkomycin and neosporin. The precursor of β-aryl isotreonine can be combined with a molecule of amino acid to form the corresponding dipeptide isomer, and it can also be synthesized using β-amide carbonyl compound as a precursor. Mechanism-inhibitory proteases have also attracted the attention of chemists and medical scientists in recent years, for example, how to improve the inhibitory proteases with peptide structure and inhibitory effect on humanimmunodeficiency virus type 1 (HIV 1) disease, so that they can inhibit acquiredimmunedeficiency syndrome ( AIDS) disease has a therapeutic effect, and has become a new direction for research on the treatment of AIDS-inhibited proteases. β-Amide carbonyl compounds are also of great use for synthetic machinery inhibitory proteases.
Nikkomycin BNikkomycin B
β-酰胺羰基化合物最早在1928年由Dakin和West用Dakin-West反应合成，该反应是α-氨基酸和醋酸酐在碱的存在下经过吖内酯中间体缩合而得。（Dakin,H.D.;West,R.J. Biol.Chem.1928,78,45.）Iqbal实验组在1994年用一锅法缩合也合成出了此类化合物。（Bhatia.,B.;Reddy，M.M.;Iqbal,J.J. Chem.Soc.Chem.Comm.1994,6,713.）The β-amide carbonyl compound was first synthesized by Dakin and West in 1928 by the Dakin-West reaction, which is obtained by condensation of α-amino acid and acetic anhydride through an azlactone intermediate in the presence of a base. (Dakin, H.D.; West, R.J. Biol. Chem. 1928, 78, 45.) Iqbal's experimental group also synthesized this type of compound by one-pot condensation in 1994. (Bhatia., B.; Reddy, M.M.; Iqbal, J.J. Chem. Soc. Chem. Comm. 1994, 6, 713.)
近年来该类化合物的合成有了较大的发展，主要的合成方法如下：In recent years, the synthesis of this type of compound has made great progress, and the main synthesis methods are as follows:
（1）印度的Paramasivan实验小组以苯甲醛或取代的苯甲醛，苯乙酮或其他的羰基化合物为反应底物，腈类化合物为反应底物和溶剂，以Ce(SO4)2为催化剂在加热回流的条件下合成了此类化合物，但是此方法所使用的催化剂价格较为昂贵，反应的温度较高。(Nagarajan,P.S.;Paramasivan,T.P.Arkivoc,2009,x,265.)(1) The Paramasivan experimental group in India used benzaldehyde or substituted benzaldehyde, acetophenone or other carbonyl compounds as the reaction substrate, nitrile compounds as the reaction substrate and solvent, and Ce(SO 4 ) 2 as the catalyst in the This type of compound is synthesized under the condition of heating and reflux, but the catalyst used in this method is more expensive and the reaction temperature is higher. (Nagarajan, PS; Paramasivan, T Arkivoc, 2009, x, 265.)
（2）2011年，印度的Bahulayan小组用金属有机化合物Metalopthalocyanines做催化剂，在酰氯的存在下合成出了此类化合物，但是此方法使用的催化剂毒性较大。（Shinu,V.S.;Pramitha,P.;Bahulayan,D.Tetrahedron Lett.2011,52,3110.）(2) In 2011, the Bahulayan group in India used metal organic compounds Metalopthalocyanines as catalysts to synthesize such compounds in the presence of acid chlorides, but the catalysts used in this method are highly toxic. (Shinu, V.S.; Pramitha, P.; Bahulayan, D. Tetrahedron Lett. 2011, 52, 3110.)
（3）Momeni等人用Zn(HSO4)2和Co(HSO4)2作催化剂在室温的条件下合称出了此类化合物，但是此方法只涉及到CH3CN作反应物和溶剂，而没有涉及到其他的腈类化合物作溶剂，反应底物结构受限较大。（Momeni,A.R.;Sadeghi,M.;Hadizadeh,M.Turk.J.Chem.2009,33,751.）(3) Momeni et al. used Zn(HSO 4 ) 2 and Co(HSO 4 ) 2 as catalysts to weigh such compounds at room temperature, but this method only involves CH 3 CN as a reactant and solvent. Without involving other nitrile compounds as solvents, the structure of the reaction substrate is relatively limited. (Momeni, AR; Sadeghi, M.; Hadizadeh, M. Turk. J. Chem. 2009, 33, 751.)
（4）2007，Khan等人报道了用FeCl3催化此类反应，得到了比较好的结果，但是此类方法涉及到的有-NO2取代基的苯甲醛不能得到相应的预期产物，而得到的是脑温格尔反应的产物。（Khan,A.T.;Parvin,T.;Choudhury，L.H.Tetrahedron,2007,63,5593。）(4) In 2007, Khan et al. reported using FeCl 3 to catalyze this type of reaction and obtained relatively good results, but the benzaldehyde with -NO2 substituent involved in this type of method could not obtain the corresponding expected product, and the obtained It is a product of the Wenger reaction in the brain. (Khan, AT; Parvin, T.; Choudhury, LH Tetrahedron, 2007, 63, 5593.)
（5）2011年，Gholivand用BPO作催化剂，也合成出了此类化合物。(5) In 2011, Gholivand also synthesized such compounds using BPO as a catalyst.
综上所述，已知的β-酰胺羰基化合物的合成方法中，或温度较高、或催化剂价格昂贵，难于制备、或方法适用的底物的范围较窄。这些不足对这类化合物的合成尤其是工业化生产带来了诸多不便。To sum up, in the known synthetic methods of β-amide carbonyl compounds, either the temperature is high, or the catalyst is expensive, it is difficult to prepare, or the range of substrates applicable to the method is relatively narrow. These deficiencies have brought a lot of inconvenience to the synthesis of this type of compound, especially the industrialized production.
(三)发明内容(3) Contents of the invention
为克服上述现有技术所存在的问题，本发明提供了一种β-酰胺羰基化合物的新方法，本发明原料易得，工艺简单，催化剂便宜易得，反应条件温和；反应应用范围广，可用多种不同底物合成多种β-酰胺羰基化合物。In order to overcome the existing problems in the above-mentioned prior art, the present invention provides a new method for β-amide carbonyl compounds. The raw materials of the present invention are easy to obtain, the process is simple, the catalyst is cheap and easy to obtain, and the reaction conditions are mild; the reaction has a wide range of applications and can be used A variety of β-amide carbonyl compounds were synthesized from a variety of different substrates.
本发明的技术方案是：室温下，芳醛、羰基化合物和腈类化合物反应，在乙酰氯的存在下，用TiCl4作催化剂和成一系列的相应的β-酰胺羰基化合物，反应通式为：The technical scheme of the present invention is: under room temperature, aromatic aldehyde, carbonyl compound and nitrile compounds react, and in the presence of acetyl chloride, use TiCl as catalyst and form a series of corresponding β-amide carbonyl compounds, and the general reaction formula is:
其中R1为芳醛上的取代基，可以为H，F，Cl，Br，NO2，烷基，或者烷氧基，也可以是2，4-二氯，2-Cl-6-F等双取代基；该取代基的数量和位置不限。R2，R3可以为H，烷基，芳基或烷氧基，或者R1、R2与所连接的碳原子一起形成6元的环烷基。R4可以为甲基，苯乙基或者苯甲基等。所使用的催化剂为TiCl4。芳醛，苯乙酮，腈类化合物，乙酰氯以及催化剂的加入顺序可以任意互换。Where R 1 is a substituent on an aromatic aldehyde, which can be H, F, Cl, Br, NO 2 , alkyl, or alkoxy, or 2,4-dichloro, 2-Cl-6-F, etc. Disubstituents; the number and position of the substituents are not limited. R 2 and R 3 can be H, alkyl, aryl or alkoxy, or R 1 and R 2 together with the connected carbon atoms form a 6-membered cycloalkyl group. R 4 can be methyl, phenethyl or benzyl, etc. The catalyst used was TiCl 4 . The order of adding aromatic aldehyde, acetophenone, nitrile compound, acetyl chloride and catalyst can be interchanged arbitrarily.
制备过程为：The preparation process is:
（一）加料(1) Feeding
在反应容器内加入摩尔比为1:1的芳醛与羰基化合物的混合物，加入用量为芳醛1~3倍的酰氯，加入用量为芳醛1~500倍的腈类溶剂作为反应介质。芳醛为，但不仅为苯甲醛、取代的苯甲醛，酰氯为，但并不仅为乙酰氯；羰基化合物为，但不限于苯乙酮、取代的苯乙酮、苯丙酮、乙酰乙酸乙酯、乙酰丙酮、丙二酸二乙酯、环己酮等反应物中的一种；腈类溶剂为，但不限于乙腈、苯乙腈、苯甲腈等溶剂中的一种。然后加入量为苯甲醛1-1.2倍的催化剂。此方法较优的是，但不限于：芳醛、羰基化合物、腈类化合物、酰氯以及催化剂的加入顺序可以任意互换。Add a mixture of aromatic aldehyde and carbonyl compound at a molar ratio of 1:1 into the reaction vessel, add acid chloride in an amount 1 to 3 times that of aromatic aldehyde, and add a nitrile solvent in an amount 1 to 500 times that of aromatic aldehyde as a reaction medium. Aromatic aldehydes are, but not only benzaldehyde, substituted benzaldehydes, acid chlorides are, but not exclusively acetyl chloride; carbonyl compounds are, but are not limited to, acetophenone, substituted acetophenones, propiophenone, ethyl acetoacetate, A kind of in the reactants such as acetylacetone, diethyl malonate, cyclohexanone; Nitrile solvent is, but not limited to a kind of in the solvents such as acetonitrile, phenylacetonitrile, benzonitrile. Then add the catalyst that is 1-1.2 times of benzaldehyde. This method is preferably, but not limited to: the order of adding aromatic aldehydes, carbonyl compounds, nitrile compounds, acid chlorides and catalysts can be interchanged arbitrarily.
（二）反应(2) Response
在常规的搅拌装置中，使反应物在室温的反应温度下搅拌反应1-3小时，以薄层色谱（TLC）监测反应进程。薄层色谱的展开剂为乙酸乙酯、石油醚、环己烷、正己烷、甲醇、氯仿、丙酮、四氢呋喃，或者其中的两者或三者的混合液。In a conventional stirring device, the reactant is stirred at room temperature for 1-3 hours, and the progress of the reaction is monitored by thin layer chromatography (TLC). The developer of thin-layer chromatography is ethyl acetate, petroleum ether, cyclohexane, n-hexane, methanol, chloroform, acetone, tetrahydrofuran, or a mixture of two or three of them.
（三）反应液后处理(3) Reaction liquid post-treatment
将反应结束后的反应液分散于反应液1-20倍体积以下的分散介质中，分散介质为，但不限于水、乙醇、甲醇、石油醚，或者其中两者的混合液中。用乙酸乙酯，或者是二氯甲烷、氯仿、乙醚中的一种有机溶剂萃取2-5次，合并有机相。将滤饼用甲醇，或者乙醇、丙酮、四氢呋喃、乙酸乙酯、乙腈中的一种有机溶剂抽提，抽提后的有机相与以上萃取得到的有机相混合。然后将混合后的液体用、但不限于无水硫酸钠、无水硫酸钙、无水硫酸镁、无水氯化钙干燥剂中的一种干燥后，旋转蒸出溶剂，得到固体或者油状混合物。Disperse the reaction solution after the reaction in a dispersion medium of 1-20 times the volume of the reaction solution. The dispersion medium is, but not limited to, water, ethanol, methanol, petroleum ether, or a mixture of the two. Extract with ethyl acetate, or an organic solvent among dichloromethane, chloroform, and ether for 2-5 times, and combine the organic phases. The filter cake is extracted with methanol, or an organic solvent among ethanol, acetone, tetrahydrofuran, ethyl acetate, and acetonitrile, and the extracted organic phase is mixed with the organic phase obtained by the above extraction. Then the mixed liquid is dried with, but not limited to, one of anhydrous sodium sulfate, anhydrous calcium sulfate, anhydrous magnesium sulfate, and anhydrous calcium chloride desiccant, and the solvent is evaporated by rotary evaporation to obtain a solid or oily mixture .
（四）产物纯化(4) Product purification
对于步骤三的粗产物进行重结晶或者柱层析纯化，得到产率为1-99%的纯目标化合物。重结晶溶剂可以是，但不限于水、甲醇、乙醇、异丙醇、丙酮、乙腈、四氢呋喃、二氧六环、乙酸乙酯、二氯甲烷、苯、甲苯。柱层析时采用硅胶柱或者氧化铝柱，展开剂为，但不限于乙酸乙酯/石油醚（1:1~1:3，体积比）、甲醇/氯仿（1:5~1:50，体积比）、二氯甲烷、丙酮。Recrystallization or column chromatography purification is performed on the crude product in step 3 to obtain the pure target compound with a yield of 1-99%. The recrystallization solvent can be, but not limited to, water, methanol, ethanol, isopropanol, acetone, acetonitrile, tetrahydrofuran, dioxane, ethyl acetate, dichloromethane, benzene, toluene. Silica gel column or alumina column is used for column chromatography, and the developing solvent is, but not limited to, ethyl acetate/petroleum ether (1:1~1:3, volume ratio), methanol/chloroform (1:5~1:50, volume ratio), dichloromethane, acetone.
本发明优点在于：原料易得，工艺简单，催化剂便宜易得，反应时间短，反应条件温和。应用范围广泛，可用多种不同的底物一步合成各种β-酰胺羰基化合物。The invention has the advantages of easy to obtain raw materials, simple process, cheap and easy to obtain catalyst, short reaction time and mild reaction conditions. It has a wide range of applications and can be used to synthesize various β-amide carbonyl compounds in one step from a variety of different substrates.
（四）具体实施方式： (4) Specific implementation methods:
实例例1Example 1
于25ml的圆底烧瓶中加入5ml已干燥的乙腈，搅拌下加入2mmol苯甲醛，加入2mmol苯乙酮，再加入1.5ml乙酰氯和2mmol TiCl4，将混合液搅拌反应3h，反应完成后，将反应液倒入25ml的冰水混合物中，析出油与固体的混合物，用柱层析分离产物，乙酸乙酯：石油醚(1:1,v:v)，得到N-(3-氧代-1,3-二苯基丙基)乙酰胺（1），收率90%，Mp103-104℃。苯甲醛与苯乙酮，乙腈的反应式为：Add 5ml of dried acetonitrile into a 25ml round bottom flask, add 2mmol of benzaldehyde and 2mmol of acetophenone while stirring, then add 1.5ml of acetyl chloride and 2mmol of TiCl 4 , and stir the mixture for 3 hours. After the reaction is completed, put The reaction solution was poured into 25ml of ice-water mixture, a mixture of oil and solid was precipitated, and the product was separated by column chromatography, ethyl acetate:petroleum ether (1:1, v:v), to obtain N-(3-oxo- 1,3-diphenylpropyl)acetamide (1), yield 90%, Mp103-104℃. Benzaldehyde and acetophenone, the reaction formula of acetonitrile is:
产物（1）的波谱数据为：1H NMR(400MHz,CDCl3)δ:2.00(3H,s,COCH3),3.42(1H,dd,J 6.0,16.8Hz,CH2),3.71(1H,dd,J 4.8,17.2Hz,CH2),5.49-5.54(1H,m,CH),6.60(1H,d,J 8.4Hz,NH),7.27-7.30(5H,m,Ph),7.44(2H,t,J 8.0Hz,Ph),7.56(1H,t,J 7.2Hz,Ph),7.88(2H,d,J8.4Hz,Ph);IR(film)νmax 3275,3082,2926,1693,1646,1552,1443,1355,1195,990,752cm-1;MS(ESI):m/z(relative intensity)290.0([M+Na]+,100).The spectrum data of the product (1) is: 1 H NMR (400MHz, CDCl 3 ) δ: 2.00(3H,s,COCH 3 ),3.42(1H,dd,J 6.0,16.8Hz,CH 2 ),3.71(1H, dd,J 4.8,17.2Hz,CH 2 ),5.49-5.54(1H,m,CH),6.60(1H,d,J 8.4Hz,NH),7.27-7.30(5H,m,Ph),7.44(2H ,t,J 8.0Hz,Ph),7.56(1H,t,J 7.2Hz,Ph),7.88(2H,d,J8.4Hz,Ph);IR(film)ν max 3275,3082,2926,1693, 1646,1552,1443,1355,1195,990,752cm -1 ; MS(ESI):m/z(relative intensity)290.0([M+Na] + ,100).
实施例2Example 2
用对氯苯甲醛代替苯甲醛，其它同实施例1。得目标化合物（2），收率96%，Mp143-145℃。对氯苯甲醛与苯乙酮，乙腈的反应式为：Replace benzaldehyde with p-chlorobenzaldehyde, and others are with embodiment 1. The target compound (2) was obtained with a yield of 96%, Mp143-145°C. p-Chlorobenzaldehyde and acetophenone, the reaction formula of acetonitrile is:
产物（2）的波谱数据为：1H NMR(400MHz,CDCl3)δ:2.04(3H,s,COCH3),3.42(1H,dd,J 6.4,17.2Hz,CH2),3.74(1H,dd,J 4.8,17.2Hz,CH2),5.52–5.59(1H,m,CH),6.77(1H,d,J 8.0Hz,NH),7.26–7.27(4H,m,Ph),7.46(2H,t,J 7.6Hz,Ph),7.59(1H,t,J 7.2Hz,Ph),7.85(2H,d,J7.6Hz,Ph);IR(film)νmax 3289,3084,2926,1686,1651,1551,1372,1199,987,757cm-1;MS(ESI):m/z(relative intensity)224.1([M+Na]+,100).The spectral data of the product (2) is: 1 H NMR (400MHz, CDCl 3 ) δ: 2.04(3H,s,COCH 3 ),3.42(1H,dd,J 6.4,17.2Hz,CH 2 ),3.74(1H, dd,J 4.8,17.2Hz,CH 2 ),5.52–5.59(1H,m,CH),6.77(1H,d,J 8.0Hz,NH),7.26–7.27(4H,m,Ph),7.46(2H ,t,J 7.6Hz,Ph),7.59(1H,t,J 7.2Hz,Ph),7.85(2H,d,J7.6Hz,Ph);IR(film)ν max 3289,3084,2926,1686, 1651,1551,1372,1199,987,757cm -1 ; MS(ESI):m/z(relative intensity)224.1([M+Na] + ,100).
实施例3Example 3
用对氟苯甲醛代替苯甲醛，其它同实施例1，得目标化合物（3），收率93%，Mp108-111℃。对氟苯甲醛与苯乙酮，乙腈的反应式为：P-fluorobenzaldehyde was used instead of benzaldehyde, and the others were the same as in Example 1 to obtain the target compound (3), with a yield of 93%, Mp 108-111°C. p-Fluorobenzaldehyde and acetophenone, the reaction formula of acetonitrile is:
产物（3）的波谱数据为：1H NMR(400MHz,CDCl3)δ:2.04(3H,s,COCH3),3.43(1H,dd,J 6.0,16.8Hz,CH2),3.75(1H,dd,J 5.2,17.2Hz,CH2),5.52–5.58(1H,m,CH),6.77(1H,d,J 5.6Hz,NH),6.97-7.01(2H,m,Ph),7.30-7.33(2H,m,Ph),7.47(2H,t,J 7.6Hz,Ph),7.59(1H,t,J 7.2Hz,Ph),7.91(2H,d,J 8.0Hz,Ph);IR(film)νmax 3286,3082,2956,2844,1687,1648,1550,1508,1371,1226,990,751cm-1;MS(ESI):m/z(relative intensity)308.0([M+Na]+,100).The spectral data of the product (3) is: 1 H NMR (400MHz, CDCl 3 ) δ: 2.04(3H,s,COCH 3 ),3.43(1H,dd,J 6.0,16.8Hz,CH 2 ),3.75(1H, dd,J 5.2,17.2Hz,CH 2 ),5.52–5.58(1H,m,CH),6.77(1H,d,J 5.6Hz,NH),6.97-7.01(2H,m,Ph),7.30-7.33 (2H,m,Ph),7.47(2H,t,J 7.6Hz,Ph),7.59(1H,t,J 7.2Hz,Ph),7.91(2H,d,J 8.0Hz,Ph);IR(film )ν max 3286,3082,2956,2844,1687,1648,1550,1508,1371,1226,990,751cm -1 ; MS(ESI):m/z(relative intensity)308.0([M+Na] + ,100 ).
实施例4Example 4
用3-硝基苯甲醛代替苯甲醛，其它同实施例1，得目标化合物（4），收率92%，Mp139-142℃。对氟苯甲醛与苯乙酮，乙腈的反应式为：3-nitrobenzaldehyde was used instead of benzaldehyde, and the others were the same as in Example 1 to obtain the target compound (4), with a yield of 92%, Mp 139-142°C. p-Fluorobenzaldehyde and acetophenone, the reaction formula of acetonitrile is:
产物(4)的波谱数据为：1H NMR(400MHz,CDCl3)δ:2.07(3H,s,COCH3),3.51(1H,dd,J 5.6,17.6Hz,CH2),3.61(1H,dd,J 5.6,17.6Hz,CH2),5.65-5.67(1H,m,CH),6.99(1H,d,J 8.0Hz,NH),7.44-7.70(5H,m,Ph),7.88-7.90(2H,m,Ph),8.22(1H,t,J 1.6Hz,Ph),8.29(2H,d,J 5.6Hz,Ph);IR(film)νmax 3297,3066,2962,2824,1690,1644,1525,1347,1226,990,751,683cm-1;MS(ESI):m/z(relative intensity)335.0([M+Na]+,100).The spectral data of the product (4) are: 1 H NMR (400MHz, CDCl 3 )δ: 2.07(3H,s,COCH 3 ),3.51(1H,dd,J 5.6,17.6Hz,CH 2 ),3.61(1H, dd,J 5.6,17.6Hz,CH 2 ),5.65-5.67(1H,m,CH),6.99(1H,d,J 8.0Hz,NH),7.44-7.70(5H,m,Ph),7.88-7.90 (2H,m,Ph),8.22(1H,t,J 1.6Hz,Ph),8.29(2H,d,J 5.6Hz,Ph);IR(film)ν max 3297,3066,2962,2824,1690, 1644,1525,1347,1226,990,751,683cm -1 ; MS(ESI):m/z(relative intensity)335.0([M+Na] + ,100).
实施例5Example 5
用2-氯-6-氟苯甲醛代替苯甲醛，其它同实施例1，得目标化合物（5），收率85%，Mp92-93℃。2-氯-6-氟苯甲醛与苯乙酮，乙腈的反应式为：2-Chloro-6-fluorobenzaldehyde was used instead of benzaldehyde, and the others were the same as in Example 1 to obtain the target compound (5) with a yield of 85%, Mp 92-93°C. The reaction formula of 2-chloro-6-fluorobenzaldehyde and acetophenone, acetonitrile is:
产物(5)的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:1.78(3H,s,COCH3),3.40(1H,dd,J5.2,17.2Hz,CH2),3.83(1H,dd,J 8.8,17.2Hz,CH2),5.85–5.90(1H,m,CH),7.17(1H,d,J8.0Hz,NH),7.25-7.34(2H,m,Ph),7.53–7.65(3H,m,Ph),7.96(2H,t,J 8Hz,Ph),8.36(1H,d,J6.8Hz,Ph);IR(film)νmax 3262,3062,2929,1685,1650,1555,1450,1359,1304,1224,990,754,687cm-1;MS(ESI):m/z(relative intensity)342.1([M+Na]+,100).The spectral data of the product (5) is: 1 H NMR (400MHz, DMSO-d 6 ) δ: 1.78 (3H, s, COCH 3 ), 3.40 (1H, dd, J5.2, 17.2Hz, CH 2 ), 3.83 (1H,dd,J 8.8,17.2Hz,CH 2 ),5.85–5.90(1H,m,CH),7.17(1H,d,J8.0Hz,NH),7.25-7.34(2H,m,Ph), 7.53–7.65(3H,m,Ph),7.96(2H,t,J 8Hz,Ph),8.36(1H,d,J6.8Hz,Ph);IR(film)ν max 3262,3062,2929,1685, 1650,1555,1450,1359,1304,1224,990,754,687cm -1 ; MS(ESI):m/z(relative intensity)342.1([M+Na] + ,100).
实施例6Example 6
用2,4-二氯苯甲醛代替苯甲醛，其它同实施例1，得目标化合物（6），收率90%，Mp185-187℃。2,4-二氯苯甲醛与苯乙酮，乙腈的反应式为：2,4-dichlorobenzaldehyde was used instead of benzaldehyde, and the rest was the same as in Example 1 to obtain the target compound (6) with a yield of 90%, Mp185-187°C. The reaction formula of 2,4-dichlorobenzaldehyde with acetophenone and acetonitrile is:
产物(6)的波谱数据为：1H NMR(400MHz,CDCl3)δ:2.04(3H,s,COCH3),3.43(1H,dd,J 5.2,16.8Hz,CH2),3.75(1H,dd,J5.6,16.8Hz,CH2),5.74–5.77(1H,m,CH),7.19(1H,d,J2.0Hz,NH),7.43-7.46(5H,m,Ph),7.57(1H,t,J 7.2Hz,Ph),7.87-7.89(2H,m,Ph);IR(film)νmax 3283,3082,2970,1689,1652,1549,1471,1353,1298,1232,1000,755,687cm-1;MS(ESI):m/z(relative intensity)358.0([M+Na]+,100).The spectral data of the product (6) is: 1 H NMR (400MHz, CDCl 3 ) δ: 2.04(3H,s,COCH 3 ),3.43(1H,dd,J 5.2,16.8Hz,CH 2 ),3.75(1H, dd,J5.6,16.8Hz,CH 2 ),5.74–5.77(1H,m,CH),7.19(1H,d,J2.0Hz,NH),7.43-7.46(5H,m,Ph),7.57( 1H,t,J 7.2Hz,Ph),7.87-7.89(2H,m,Ph);IR(film)ν max 3283,3082,2970,1689,1652,1549,1471,1353,1298,1232,1000, 755,687cm -1 ; MS(ESI):m/z(relative intensity)358.0([M+Na] + ,100).
实施例7Example 7
用对甲基苯甲醛代替苯甲醛，其它同实施例1，得目标化合物（7），收率89%，Mp87-90℃。对甲基苯甲醛与苯乙酮，乙腈的反应式为：P-tolualdehyde was used instead of benzaldehyde, and the others were the same as in Example 1 to obtain the target compound (7), with a yield of 89%, Mp 87-90°C. p-Tolualdehyde and acetophenone, the reaction formula of acetonitrile is:
产物(7)的波谱数据为：1H NMR(400MHz,CDCl3)δ:2.02(3H,s,COCH3),2.30(3H,s,CH3),3.44(1H,dd,J 6.4,16.8Hz,CH2),3.76(1H,dd,J 4.8,16.8Hz,CH2),5.51–5.55(1H,m,CH),6.62(1H,d,J8.0Hz,NH),7.11-7.23(4H,m,Ph),7.45(2H,t,J7.6Hz,Ph),7.57(1H,t,J5.6Hz,Ph),7.92(2H,t,J 7.2Hz,Ph).IR(film)νmax 3288,3084,2950,1686,1653,1553,1447,1365,1296,987,756,688cm-1;MS(ESI):m/z(relative intensity)304.1([M+Na]+,100).The spectral data of the product (7) are: 1 H NMR (400MHz, CDCl 3 ) δ: 2.02(3H,s,COCH 3 ),2.30(3H,s,CH 3 ),3.44(1H,dd,J 6.4,16.8 Hz,CH 2 ),3.76(1H,dd,J 4.8,16.8Hz,CH 2 ),5.51–5.55(1H,m,CH),6.62(1H,d,J8.0Hz,NH),7.11-7.23( 4H,m,Ph),7.45(2H,t,J7.6Hz,Ph),7.57(1H,t,J5.6Hz,Ph),7.92(2H,t,J7.2Hz,Ph).IR(film) ν max 3288,3084,2950,1686,1653,1553,1447,1365,1296,987,756,688cm -1 ; MS(ESI):m/z(relative intensity)304.1([M+Na] + ,100).
实施例8Example 8
用3-甲氧基苯甲醛代替苯甲醛，其它同实施例1。得目标化合物（8），收率91%，Mp125-127℃。3-甲氧基苯甲醛与苯乙酮，乙腈的反应式为：Replace benzaldehyde with 3-methoxybenzaldehyde, and others are with embodiment 1. The target compound (8) was obtained with a yield of 91%, Mp125-127°C. 3-methoxybenzaldehyde and acetophenone, the reaction formula of acetonitrile is:
产物（8）的波普数据为：1H NMR(400MHz,CDCl3)δ:2.03(3H,s,COCH3),3.43(1H,dd,J 6.0,16.8Hz,CH2),3.73(1H,dd,J 6.0,17.2Hz,CH2),3.77(3H,s,OCH3),5.53–5.55(1H,m,CH),6.66(1H,d,J 8.0Hz,NH),6.76-6.92(4H,m,Ph),7.45(2H,t,J 7.6Hz,Ph),7.57(1H,t,J 7.2Hz,Ph),7.90(2H,t,J 5.6Hz,Ph).IR(film)νmax 3258,3079,2950,1689,1642,1558,1450,1291,1149,1223,1049,990,751,703,693cm-1;MS(ESI):m/z(relative intensity)320.2([M+Na]+,100).The Popper data of the product (8) is: 1 H NMR (400MHz, CDCl 3 ) δ: 2.03 (3H, s, COCH 3 ), 3.43 (1H, dd, J 6.0, 16.8Hz, CH 2 ), 3.73 (1H ,dd,J 6.0,17.2Hz,CH 2 ),3.77(3H,s,OCH 3 ),5.53–5.55(1H,m,CH),6.66(1H,d,J 8.0Hz,NH),6.76-6.92 (4H,m,Ph),7.45(2H,t,J 7.6Hz,Ph),7.57(1H,t,J 7.2Hz,Ph),7.90(2H,t,J 5.6Hz,Ph).IR(film )ν max 3258,3079,2950,1689,1642,1558,1450,1291,1149,1223,1049,990,751,703,693cm -1 ; MS(ESI):m/z(relative intensity)320.2([M+Na] + ,100).
实施例9Example 9
用4-甲氧基苯甲醛代替苯甲醛，其它同实施例1，得到目标化合物（9），收率88%，Mp 113-115℃。4-甲氧基苯甲醛与苯乙酮，乙腈的反应式为：4-methoxybenzaldehyde was used instead of benzaldehyde, and the others were the same as in Example 1 to obtain the target compound (9) with a yield of 88% and Mp 113-115°C. 4-methoxybenzaldehyde and acetophenone, the reaction formula of acetonitrile is:
产物（9）的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:1.77(3H,s,COCH3),3.37(1H,dd,J 6.0,16.8Hz,CH2),3.50(1H,dd,J 8.0,16.8Hz,CH2),3.72(3H,s,OCH3),5.29-5.34(1H,m,CH),6.86(2H,d,J 8.4Hz,CH),7.26(2H,d,J 8.4,Ph),7.52(2H,t,J 7.6Hz,Ph),7.64(1H,t,J7.6Hz,Ph),7.94(2H,d,J 8.4Hz,Ph),8.25(1H,d,J 8.0Hz,NH).IR(film)νmax 3304,2833,1649,1625,1240,1031,987,756cm-1;MS(ESI):m/z(relative intensity)320.2([M+Na]+,100).The spectrum data of the product (9) is: 1 H NMR (400MHz, DMSO-d 6 ) δ: 1.77(3H,s,COCH 3 ),3.37(1H,dd,J 6.0,16.8Hz,CH 2 ),3.50( 1H,dd,J 8.0,16.8Hz,CH 2 ),3.72(3H,s,OCH 3 ),5.29-5.34(1H,m,CH),6.86(2H,d,J 8.4Hz,CH),7.26( 2H,d,J 8.4,Ph),7.52(2H,t,J 7.6Hz,Ph),7.64(1H,t,J7.6Hz,Ph),7.94(2H,d,J 8.4Hz,Ph),8.25 (1H,d,J 8.0Hz,NH).IR(film)ν max 3304,2833,1649,1625,1240,1031,987,756cm -1 ; MS(ESI):m/z(relative intensity)320.2([ M+Na] + ,100).
实施例10Example 10
用4-甲氧基苯甲醛代替苯甲醛，3-硝基苯乙酮代替苯乙酮，其它同实施例1，得到目标化合物（10），收率87%，Mp 186-189℃。4-甲氧基苯甲醛与3-硝基苯乙酮，乙腈的反应式为：4-methoxybenzaldehyde was used instead of benzaldehyde, 3-nitroacetophenone was used instead of acetophenone, and the rest were the same as in Example 1 to obtain the target compound (10) with a yield of 87% and Mp 186-189°C. 4-methoxybenzaldehyde and 3-nitroacetophenone, the reaction formula of acetonitrile is:
产物（10）的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:1.77(3H,s,COCH3),3.49(1H,dd,J 6.0,17.2Hz,CH2),3.61(1H,dd,J 8.8,16.8Hz,CH2),3.72(3H,s,OCH3),5.28-5.34(1H,m,CH),6.87(2H,d,J 8.4Hz,Ph),7.28(2H,d,J 8.4Hz,Ph),7.83(1H,t,J 7.6Hz,Ph),8.27(1H,d,J 8.0Hz,Ph),8.38(1H,d,J 7.2Hz,Ph),8.47(1H,d,J 7.2Hz,Ph),8.62(1H,s,NH).IR(film)νmax 3315,3095,1693,1646,1348,1032,734cm-1;MS(ESI):m/z(relative intensity)365.1([M+Na]+,100).The spectrum data of the product (10) is: 1 H NMR (400MHz, DMSO-d 6 ) δ: 1.77(3H,s,COCH 3 ),3.49(1H,dd,J 6.0,17.2Hz,CH 2 ),3.61( 1H,dd,J 8.8,16.8Hz,CH 2 ),3.72(3H,s,OCH 3 ),5.28-5.34(1H,m,CH),6.87(2H,d,J 8.4Hz,Ph),7.28( 2H,d,J 8.4Hz,Ph),7.83(1H,t,J 7.6Hz,Ph),8.27(1H,d,J 8.0Hz,Ph),8.38(1H,d,J 7.2Hz,Ph), 8.47(1H,d,J 7.2Hz,Ph),8.62(1H,s,NH).IR(film)ν max 3315,3095,1693,1646,1348,1032,734cm -1 ; MS(ESI):m /z(relative intensity)365.1([M+Na] + ,100).
实施例11Example 11
用对氯苯甲醛代替苯甲醛，4-硝基苯乙酮代替苯乙酮，其它同实施例1，得到目标化合物（11），收率91%，Mp 144-146℃。对氯苯甲醛与4-硝基苯乙酮，乙腈的反应式为：P-chlorobenzaldehyde was used instead of benzaldehyde, 4-nitroacetophenone was used instead of acetophenone, and the others were the same as in Example 1 to obtain the target compound (11) with a yield of 91% and Mp 144-146°C. p-Chlorobenzaldehyde and 4-nitroacetophenone, the reaction formula of acetonitrile is:
产物（11）的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:1.79(3H,s,COCH3),3.49(1H,dd,J 5.2,17.2Hz,CH2),3.62(1H,dd,J 8.8,17.6Hz,CH2),5.32-5.34(1H,m,CH),7.38,(4H,s,Ph),8.18(2H,d,J 8.8Hz,Ph),8.33(2H,d,J 8.8Hz,Ph),8.36(1H,s,NH);13C NMR(100MHz,DMSO-d6)δ:22.6,44.9,48.2,123.8,128.6,129.5,127.4,141.0,141.9,150.0,168.5,186.3.IR(film)νmax 3277,1690,1668,1516,1343,1189,747,690cm-1;MS(ESI):m/z(relative intensity)369.1([M+Na]+,100).The spectrum data of the product (11) is: 1 H NMR (400MHz, DMSO-d 6 )δ: 1.79(3H,s,COCH 3 ),3.49(1H,dd,J 5.2,17.2Hz,CH 2 ),3.62( 1H,dd,J 8.8,17.6Hz,CH 2 ),5.32-5.34(1H,m,CH),7.38,(4H,s,Ph),8.18(2H,d,J 8.8Hz,Ph),8.33( 2H,d,J 8.8Hz,Ph),8.36(1H,s,NH); 13 C NMR(100MHz,DMSO-d 6 )δ:22.6,44.9,48.2,123.8,128.6,129.5,127.4,141.0,141.9 ,150.0,168.5,186.3.IR(film)ν max 3277,1690,1668,1516,1343,1189,747,690cm -1 ; MS(ESI):m/z(relative intensity)369.1([M+Na] + ,100).
实施例12Example 12
用2,4-二氯苯甲醛代替苯甲醛，4-硝基苯乙酮代替苯乙酮，其它同实施例1，得到目标化合物（12），收率93%，Mp 198-200℃。2,4-二氯苯甲醛与4-硝基苯乙酮，乙腈的反应式为：2,4-dichlorobenzaldehyde was used instead of benzaldehyde, 4-nitroacetophenone was used instead of acetophenone, and the rest were the same as in Example 1 to obtain the target compound (12) with a yield of 93%, Mp 198-200°C. The reaction formula of 2,4-dichlorobenzaldehyde and 4-nitroacetophenone, acetonitrile is:
产物（12）的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:1.80(3H,s,COCH3),3.40(1H,dd,J4.0,17.6Hz,CH2),3.58(1H,dd,J9.6,17.6Hz,CH2),5.61-5.65(1H,m,CH),7.44-7.51(2H,m,Ph),7.60(1H,d,J2.0Hz,Ph),8.20(2H,d,J 7.2Hz,Ph),8.34(2H,d,J 8.8Hz,Ph),8.42(1H,d,J 8.0Hz,NH);13C NMR(100MHz,DMSO-d6)δ:22.5,43.5,45.8,123.9,127.6,128.8,129.2,129.6,132.3,139.4,140.8,150.0,168.6,195.8.IR(film)νmax 3296,3077,1695,1654,1532,1228,1101,744,686cm-1;MS(ESI):m/z(relative intensity)403.1([M+Na]+,100).The spectral data of the product (12) is: 1 H NMR (400MHz, DMSO-d 6 ) δ: 1.80 (3H, s, COCH 3 ), 3.40 (1H, dd, J4.0, 17.6Hz, CH 2 ), 3.58 (1H,dd,J9.6,17.6Hz,CH 2 ),5.61-5.65(1H,m,CH),7.44-7.51(2H,m,Ph),7.60(1H,d,J2.0Hz,Ph) ,8.20(2H,d,J 7.2Hz,Ph),8.34(2H,d,J 8.8Hz,Ph),8.42(1H,d,J 8.0Hz,NH); 13 C NMR(100MHz,DMSO-d 6 )δ:22.5,43.5,45.8,123.9,127.6,128.8,129.2,129.6,132.3,139.4,140.8,150.0,168.6,195.8.IR(film)ν max 3296,3077,1695,1654,1532,12128,110 ,744,686cm -1 ; MS(ESI):m/z(relative intensity)403.1([M+Na] + ,100).
实施例13Example 13
用4-甲氧基苯乙酮代替苯乙酮，其它同实施例1，得目标化合物（13），收率90%，Mp127-128℃。苯甲醛与4-甲氧基苯乙酮，乙腈的反应式为：4-methoxyacetophenone was used instead of acetophenone, and the others were the same as in Example 1 to obtain the target compound (13) with a yield of 90%, Mp 127-128°C. Benzaldehyde and 4-methoxyacetophenone, the reaction formula of acetonitrile is:
产物（13）的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:1.79(3H,s,COCH3),3.20(1H,dd,J 5.6,16.4Hz,CH2),3.46(1H,dd,J 8.4,16.8Hz,CH2),5.32-5.38(1H,m,CH),7.03,(2H,d,J12.8Hz,Ph),7.21(1H,t,J6.8Hz,Ph),7.28-7.34(4H,m,Ph),,7.93(2H,d,J 8.8Hz,Ph),8.29(1H,d,J8.0Hz,NH);13C NMR(100MHz,DMSO-d6)δ:22.6,40.1,44.2,55.5,113.9,126.6,126.8,128.2,129.5,130.3,143.1,163.1,168.2,195.4.IR(film)νmax 3296,3077,1695,1654,1532,1228,1101,744,686cm-1;MS(ESI):m/z(relative intensity)320.2([M+Na]+,100).The spectrum data of the product (13) is: 1 H NMR (400MHz, DMSO-d 6 )δ: 1.79(3H,s,COCH 3 ),3.20(1H,dd,J 5.6,16.4Hz,CH 2 ),3.46( 1H,dd,J 8.4,16.8Hz,CH 2 ),5.32-5.38(1H,m,CH),7.03,(2H,d,J12.8Hz,Ph),7.21(1H,t,J6.8Hz,Ph ),7.28-7.34(4H,m,Ph),,7.93(2H,d,J 8.8Hz,Ph),8.29(1H,d,J8.0Hz,NH); 13 C NMR(100MHz,DMSO-d 6 )δ:22.6,40.1,44.2,55.5,113.9,126.6,126.8,128.2,129.5,130.3,143.1,163.1,168.2,195.4.IR(film)ν max 3296,3077,1695,1654,1532,1228,110 ,744,686cm -1 ; MS(ESI):m/z(relative intensity)320.2([M+Na] + ,100).
实施例14Example 14
用3-硝基苯甲醛代替苯甲醛，3-硝基苯乙酮代替苯乙酮，其它同实施例1，得目标化合物（14），收率86%，Mp 204-205℃。3-硝基苯甲醛与3-硝基苯乙酮，乙腈的反应式为：3-nitrobenzaldehyde was used instead of benzaldehyde, 3-nitroacetophenone was used instead of acetophenone, and the others were the same as in Example 1 to obtain the target compound (14) with a yield of 86%, Mp 204-205°C. 3-nitrobenzaldehyde and 3-nitroacetophenone, the reaction formula of acetonitrile is:
产物（14）的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:1.82(3H,s,COCH3),3.62(1H,dd,J 5.2,18.0Hz,CH2),3.77(1H,dd,J 8.4,17.2Hz,CH2),5.45-5.50(1H,m,CH),7.64,(2H,t,J8.0Hz,Ph),7.85(1H,t,J6.4Hz,Ph),8.11(1H,d,J 8.4Hz,Ph),8.25(1H,d,J 1.6Hz,Ph),8.39(1H,d J 7.2Hz,Ph),8.46-8.52(2H,m,Ph),8.66(1H,d,J 8.0Hz,NH);13C NMR(100MHz,DMSO-d6)δ:22.6,44.3,48.3,121.4,121.9,122.4,127.5,129.8,130.6,133.7,134.2,137.6,145.3,147.8,148.0,195.3.IR(film)νmax 3296,3077,1695,1654,1532,1228,1101,744,686cm-1;MS(ESI):m/z(relative intensity)380.1([M+Na]+,100).The spectrum data of the product (14) is: 1 H NMR (400MHz, DMSO-d 6 ) δ: 1.82(3H,s,COCH 3 ),3.62(1H,dd,J 5.2,18.0Hz,CH 2 ),3.77( 1H,dd,J 8.4,17.2Hz,CH 2 ),5.45-5.50(1H,m,CH),7.64,(2H,t,J8.0Hz,Ph),7.85(1H,t,J6.4Hz,Ph ),8.11(1H,d,J 8.4Hz,Ph),8.25(1H,d,J 1.6Hz,Ph),8.39(1H,d J 7.2Hz,Ph),8.46-8.52(2H,m,Ph) ,8.66(1H,d,J 8.0Hz,NH); 13 C NMR(100MHz,DMSO-d 6 )δ:22.6,44.3,48.3,121.4,121.9,122.4,127.5,129.8,130.6,133.7,134.2,137.6 ,145.3,147.8,148.0,195.3.IR(film)ν max 3296,3077,1695,1654,1532,1228,1101,744,686cm -1 ; MS(ESI):m/z(relative intensity)380.1([M +Na] + ,100).
实施例15Example 15
用3-溴苯甲醛代替苯甲醛，4-甲氧基苯乙酮代替苯乙酮，其它同实施例1，得目标化合物（15），收率82%，Mp 155-157℃。3-溴苯甲醛与4-甲氧基苯乙酮，乙腈的反应式为：3-Bromobenzaldehyde was used instead of benzaldehyde, 4-methoxyacetophenone was used instead of acetophenone, and the rest were the same as in Example 1 to obtain the target compound (15) with a yield of 82%, Mp 155-157°C. 3-bromobenzaldehyde and 4-methoxyacetophenone, the reaction formula of acetonitrile is:
产物（15）的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:1.80(3H,s,COCH3),3.34(1H,dd,J 6.0,16.4Hz,CH2),3.49(1H,dd,J 8.0,16.4Hz,CH2),5.30-5.35(2H,m,CH),7.02,(1H,d,J7.6Hz,Ph),7.28(1H,t,J 6.8Hz,Ph),7.35(1H,d,J 7.2Hz Ph),7.52(1H,s,Ph),7.94(2H,d,J7.2Hz,Ph),8.34(1H,d,J 7.6Hz,NH);13C NMR(100MHz,DMSO-d6)δ:22.6,43.9,48.6,55.5,113.9,125.9,129.4,129.6,130.4,146.1,163.2,168.4,195.1.IR(film)νmax 3296,3077,1695,1654,1532,1228,1101,744,686cm-1;MS(ESI):m/z(relative intensity)398.1([M+Na]+,100).The spectrum data of the product (15) is: 1 H NMR (400MHz, DMSO-d 6 ) δ: 1.80(3H,s,COCH 3 ),3.34(1H,dd,J 6.0,16.4Hz,CH 2 ),3.49( 1H,dd,J 8.0,16.4Hz,CH 2 ),5.30-5.35(2H,m,CH),7.02,(1H,d,J7.6Hz,Ph),7.28(1H,t,J 6.8Hz,Ph ),7.35(1H,d,J 7.2Hz Ph),7.52(1H,s,Ph),7.94(2H,d,J7.2Hz,Ph),8.34(1H,d,J 7.6Hz,NH); 13 C NMR(100MHz,DMSO-d 6 )δ:22.6,43.9,48.6,55.5,113.9,125.9,129.4,129.6,130.4,146.1,163.2,168.4,195.1.IR(film)ν max 3296,3077,1695, 1654,1532,1228,1101,744,686cm -1 ; MS(ESI):m/z(relative intensity)398.1([M+Na] + ,100).
实施例16Example 16
用4-甲氧基苯甲醛代替苯甲醛，4-甲氧基苯乙酮代替苯乙酮，其它同实施例1，得目标化合物（16），收率87%，Mp 134-136℃。4-甲氧基苯甲醛与4-甲氧基苯乙酮，乙腈的反应式为：4-methoxybenzaldehyde was used instead of benzaldehyde, 4-methoxyacetophenone was used instead of acetophenone, and the rest were the same as in Example 1 to obtain the target compound (16) with a yield of 87% and Mp 134-136°C. 4-methoxybenzaldehyde and 4-methoxyacetophenone, the reaction formula of acetonitrile is:
产物（16）的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:1.77(3H,s,COCH3),3.29(1H,dd,J 6.4,16.4Hz,CH2),3.46(1H,dd,J 7.6,16.4Hz,CH2),5.27-5.33(1H,m,CH),6.85,(2H,d,J8.8Hz,Ph),7.02,(2H,d,J 8.8Hz,Ph),7.24,(2H,d,J 8.8Hz,Ph),7.92,(2H,d,J 8.8Hz,Ph),8.24(1H,d,J 8.0Hz,NH).IR(film)νmax 3296,3077,1695,1654,1532,1228,1101,744,686cm-1;MS(ESI):m/z(relative intensity)350.2([M+Na]+,100).The spectrum data of the product (16) is: 1 H NMR (400MHz, DMSO-d 6 )δ: 1.77(3H,s,COCH 3 ),3.29(1H,dd,J 6.4,16.4Hz,CH 2 ),3.46( 1H,dd,J 7.6,16.4Hz,CH 2 ),5.27-5.33(1H,m,CH),6.85,(2H,d,J8.8Hz,Ph),7.02,(2H,d,J 8.8Hz, Ph),7.24,(2H,d,J 8.8Hz,Ph),7.92,(2H,d,J 8.8Hz,Ph),8.24(1H,d,J 8.0Hz,NH).IR(film)ν max 3296,3077,1695,1654,1532,1228,1101,744,686cm -1 ; MS(ESI):m/z(relative intensity)350.2([M+Na] + ,100).
实施例17Example 17
用3-溴苯甲醛代替苯甲醛，4-硝基苯乙酮代替苯乙酮，其它同实施例1，得目标化合物（17），收率80%，Mp 155-157℃。3-溴苯甲醛与4-甲氧基苯乙酮，乙腈的反应式为：3-bromobenzaldehyde was used instead of benzaldehyde, 4-nitroacetophenone was used instead of acetophenone, and the others were the same as in Example 1 to obtain the target compound (17) with a yield of 80% and Mp 155-157°C. 3-bromobenzaldehyde and 4-methoxyacetophenone, the reaction formula of acetonitrile is:
产物（17）的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:1.81(3H,s,COCH3),3.52(1H,dd,J 5.2,18.4Hz,CH2),3.64(1H,dd,J 8.8,17.2Hz,CH2),5.31-5.36(1H,m,CH),7.30-7.46(3H,m,Ph),7.58,(1H,s,Ph),8.21,(2H,d,J8.4Hz,Ph),8.34,(2H,d,J8.8Hz,Ph),8.24(1H,d,J4.0Hz,NH).IR(film)νmax 3296,3077,1695,1654,1532,1228,1101,744,686cm-1;MS(ESI):m/z(relative intensity)415.0([M+Na]+,100).The spectrum data of the product (17) is: 1 H NMR (400MHz, DMSO-d 6 ) δ: 1.81(3H,s,COCH 3 ),3.52(1H,dd,J 5.2,18.4Hz,CH 2 ),3.64( 1H,dd,J 8.8,17.2Hz,CH 2 ),5.31-5.36(1H,m,CH),7.30-7.46(3H,m,Ph),7.58,(1H,s,Ph),8.21,(2H ,d,J8.4Hz,Ph),8.34,(2H,d,J8.8Hz,Ph),8.24(1H,d,J4.0Hz,NH).IR(film)ν max 3296,3077,1695,1654 ,1532,1228,1101,744,686cm -1 ; MS(ESI):m/z(relative intensity)415.0([M+Na] + ,100).
实施例18Example 18
用苯乙腈代替乙腈，其它同实施例1，得目标化合物（18），收率81%，Mp 98-100℃。苯甲醛与苯乙酮，苯乙腈的反应式为：Phenylacetonitrile was used instead of acetonitrile, and the others were the same as in Example 1 to obtain the target compound (18) with a yield of 81%, Mp 98-100°C. Benzaldehyde and acetophenone, the reaction formula of phenylacetonitrile is:
产物（18）的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:3.43(1H,dd,J20.4,36.4Hz,CH2),3.58(1H,dd,J 8.8,17.2Hz,CH2),3.77(2H,s,CH2),5.37-5.43(1H,m,CH),7.20-7.66(3H,m,Ph),7.59(1H,d,J8.0Hz,NH),13C NMR(100MHz,DMSO-d6)δ：42.3,44.6,49.1,126.2,126.5,126.8,128.0,128.1,128.2,128.7,128.9,129.5,133.2,136.3,136.6,142.8,169.2,197.1.IR(film)νmax 3277,3058,3027,1681,1645,1543,1449,1361,1218,1150,982,733,689cm-1;MS(ESI):m/z(relative intensity)366.2([M+Na]+,100).The spectral data of the product (18) is: 1 H NMR (400MHz, DMSO-d 6 ) δ: 3.43 (1H, dd, J20.4, 36.4Hz, CH 2 ), 3.58 (1H, dd, J 8.8, 17.2Hz ,CH 2 ),3.77(2H,s,CH 2 ),5.37-5.43(1H,m,CH),7.20-7.66(3H,m,Ph),7.59(1H,d,J8.0Hz,NH), 13 C NMR (100MHz, DMSO-d 6 )δ: 42.3, 44.6, 49.1, 126.2, 126.5, 126.8, 128.0, 128.1, 128.2, 128.7, 128.9, 129.5, 133.2, 136.3, 136.6, 142.8, 169.2IR, 197.1. (film)ν max 3277,3058,3027,1681,1645,1543,1449,1361,1218,1150,982,733,689cm -1 ; MS(ESI):m/z(relative intensity)366.2([M+Na] + ,100).
实施例19Example 19
用对氯苯甲醛代替苯甲醛，苯丙酮代替苯乙酮，其它同实施例1，得目标化合物（19），收率94%，Mp 181-183℃。顺反异构比例由核磁共振氢谱中次甲基H原子基于耦合常数的比例看出，顺式：反式为15:85。对氯苯甲醛与苯丙酮，乙腈的反应式为：P-chlorobenzaldehyde was used instead of benzaldehyde, propiophenone was used instead of acetophenone, and the rest were the same as in Example 1 to obtain the target compound (19) with a yield of 94% and Mp 181-183°C. The ratio of cis-trans isomerism can be seen from the ratio of methine H atoms based on the coupling constant in the proton nuclear magnetic resonance spectrum, cis:trans is 15:85. p-Chlorobenzaldehyde and propiophenone, the reaction formula of acetonitrile is:
产物（19）的波谱数据为：1H NMR(400MHz,CDCl3)δ:1.19(3H,d,J6.8Hz,CH3),1.97(3H,s,COCH3),4.01(1H,t,J 7.2Hz,CH),5.39(1H,t,J 8.0Hz,CH),6.11(1H,d,J 7.6Hz,NH),7.25(4H,d,J 5.2Hz,Ph),7.45(2H,t,J 7.6Hz,Ph),7.54-7.58(1H,m,Ph),7.87(2H,d,J 8Hz,Ph).IR(film)νmax 3267,3064,2979,1682,1651,1554,1491,1372,1290,1089,988,959,781,691cm-1;MS(EI):m/z(relative intensity)338.0([M+Na]+,100).The spectral data of the product (19) are: 1 H NMR (400MHz, CDCl 3 )δ: 1.19(3H,d,J6.8Hz,CH 3 ),1.97(3H,s,COCH 3 ),4.01(1H,t, J 7.2Hz, CH), 5.39 (1H, t, J 8.0Hz, CH), 6.11 (1H, d, J 7.6Hz, NH), 7.25 (4H, d, J 5.2Hz, Ph), 7.45 (2H, t,J 7.6Hz,Ph),7.54-7.58(1H,m,Ph),7.87(2H,d,J 8Hz,Ph).IR(film)ν max 3267,3064,2979,1682,1651,1554, 1491,1372,1290,1089,988,959,781,691cm -1 ; MS(EI):m/z(relative intensity)338.0([M+Na] + ,100).
实施例20Example 20
用3-甲氧基甲醛代替苯甲醛，苯丙酮代替苯乙酮，其它同实施例1，得目标化合物（20），收率87%，Mp 163-165℃。顺反异构比例由核磁共振氢谱中次甲基H原子基于耦合常数的比例看出，顺式：反式为10:90。3-甲氧基苯甲醛与苯丙酮，乙腈的反应式为：3-methoxyformaldehyde was used instead of benzaldehyde, propiophenone was used instead of acetophenone, and the rest were the same as in Example 1 to obtain the target compound (20) with a yield of 87% and Mp 163-165°C. The cis-trans isomerization ratio can be seen from the ratio of methine H atoms based on the coupling constant in the H NMR spectrum. The cis-form: trans-form is 10:90. The reaction formula of 3-methoxybenzaldehyde with propiophenone and acetonitrile is :
产物（20）的波谱数据为：1H NMR(400MHz,CDCl3)δ:1.21(3H,d,J 6.8Hz,CH3),1.98(3H,s,COCH3),3.76(3H,s,OCH3),4.04(1H,t,J 7.2Hz,CH),5.44(1H,t,J 8.0Hz,CH),6.03(1H,d,J 7.6Hz,NH),6.75-6.96(4H,m,Ph),7.45(2H,t,J 7.6Hz,Ph),7.56(1H,t,J 7.6Hz,Ph),7.89-7.91(2H,m,Ph).IR(film)νmax 3319,3058,2991,1676,1646,1536,1454,1373,1266,1051,970,781,706cm-1;MS(EI):m/z(relative intensity)334.0([M+Na]+,100).The spectral data of the product (20) are: 1 H NMR (400MHz, CDCl 3 )δ: 1.21(3H,d,J 6.8Hz,CH 3 ),1.98(3H,s,COCH 3 ),3.76(3H,s, OCH 3 ),4.04(1H,t,J 7.2Hz,CH),5.44(1H,t,J 8.0Hz,CH),6.03(1H,d,J 7.6Hz,NH),6.75-6.96(4H,m ,Ph),7.45(2H,t,J 7.6Hz,Ph),7.56(1H,t,J 7.6Hz,Ph),7.89-7.91(2H,m,Ph).IR(film)ν max 3319,3058 ,2991,1676,1646,1536,1454,1373,1266,1051,970,781,706cm -1 ; MS(EI):m/z(relative intensity)334.0([M+Na] + ,100).
实施例21Example 21
用苯丙酮代替苯乙酮，其它同实施例1，得目标化合物（21），收率94%，Mp 166-168℃。顺反异构比例由核磁共振氢谱中次甲基H原子基于耦合常数的比例看出，顺式：反式为20:80。苯甲醛与苯丙酮，乙腈的反应式为：Propiophenone was used instead of acetophenone, and the others were the same as in Example 1 to obtain the target compound (21) with a yield of 94% and Mp 166-168°C. The ratio of cis-trans isomerism can be seen from the ratio of methine H atoms based on the coupling constant in the H NMR spectrum, and the cis-trans form is 20:80. Benzaldehyde and propiophenone, the reaction formula of acetonitrile is:
产物（21）的波谱数据为：1H NMR(400MHz,CDCl3)δ:1.13(3H,d,J 6.8Hz,CH3),1.85(3H,s,COCH3),4.00-4.14(1H,m,CH),5.26(1H,t,J 11.6Hz,CH),7.12(1H,t,J 6.8Hz,Ph),7.22(2H,t,J 8.0Hz,Ph),7.29(2H,d,J7.6Hz,Ph),7.47(2H,t,J 8.0Hz,Ph),7.58(1H,t,J6.8Hz,Ph),7.80(2H,t,J7.6Hz,Ph),8.30(1H,d,J9.2Hz,NH).IR(film)νmax 3297,3061,2980,1683,1651,1544,1448,1370,1208,1140,970,707,615cm-1.MS(ESI):m/z(relative intensity)304.2([M+Na]+,100).The spectral data of the product (21) is: 1 H NMR (400MHz, CDCl 3 )δ: 1.13(3H,d,J 6.8Hz,CH 3 ),1.85(3H,s,COCH 3 ),4.00-4.14(1H, m,CH),5.26(1H,t,J 11.6Hz,CH),7.12(1H,t,J 6.8Hz,Ph),7.22(2H,t,J 8.0Hz,Ph),7.29(2H,d, J7.6Hz,Ph),7.47(2H,t,J 8.0Hz,Ph),7.58(1H,t,J6.8Hz,Ph),7.80(2H,t,J7.6Hz,Ph),8.30(1H, d,J9.2Hz,NH).IR(film)ν max 3297,3061,2980,1683,1651,1544,1448,1370,1208,1140,970,707,615cm -1 .MS(ESI):m/z(relative intensity)304.2([M+Na] + ,100).
实施例22Example 22
用4-甲氧基苯甲醛代替苯甲醛，丙二酸二乙酯代替苯乙酮，其它同实施例1，得目标化合物（22），收率88%，Mp 112-114℃。4-甲氧基苯甲醛与丙二酸二乙酯，乙腈的反应式为：4-methoxybenzaldehyde was used instead of benzaldehyde, diethyl malonate was used instead of acetophenone, and the rest were the same as in Example 1 to obtain the target compound (22) with a yield of 88%, Mp 112-114°C. 4-methoxybenzaldehyde and diethyl malonate, the reaction formula of acetonitrile is:
产物（22）的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:0.94(3H,t,J 6.8Hz,CH3),1.54(3H,t,J 7.2Hz,CH3),1.76(3H,s,CH3),2.25(3H,s,COCH3),3.89(4H,m,2CH2),4.42(1H,t,J7.2Hz,CH),5.40(1H,t,J 10.0Hz,CH),7.09-7.20(4H,m,Ph),8.38(1H,d,J 9.2Hz,NH).IR(film)νmax 3258,3066,2990,1758,1642,1556,1445,1368,1295,1148,1034,816,727,516cm-1;MS(ESI):m/z(relative intensity)344.2([M+Na]+,100).The spectral data of the product (22) are: 1 H NMR (400MHz, DMSO-d 6 ) δ: 0.94(3H,t,J 6.8Hz,CH 3 ),1.54(3H,t,J 7.2Hz,CH 3 ), 1.76(3H,s,CH 3 ),2.25(3H,s,COCH 3 ),3.89(4H,m,2CH 2 ),4.42(1H,t,J7.2Hz,CH),5.40(1H,t,J 10.0Hz,CH),7.09-7.20(4H,m,Ph),8.38(1H,d,J 9.2Hz,NH).IR(film)ν max 3258,3066,2990,1758,1642,1556,1445, 1368,1295,1148,1034,816,727,516cm -1 ; MS(ESI):m/z(relative intensity)344.2([M+Na] + ,100).
实施例23Example 23
用3-硝基苯甲醛代替苯甲醛，乙酰丙酮代替苯乙酮，其它同实施例1，得目标化合物（23），收率83%，Mp 159-161℃。3-硝基苯甲醛与乙酰丙酮，乙腈的反应式为：3-nitrobenzaldehyde was used instead of benzaldehyde, acetylacetone was used instead of acetophenone, and the rest were the same as in Example 1 to obtain the target compound (23) with a yield of 83% and Mp 159-161°C. 3-nitrobenzaldehyde and acetylacetone, the reaction formula of acetonitrile is:
产物（23）的波谱数据为：1H NMR(400MHz,CDCl3)δ:1.79(3H,s,COCH3),1.79(3H,s,COCH3),2.03(3H,s,COCH3),2.23(3H,s,CH3),4.64(1H,dd,J 6.4,10.4Hz,CH),5.61(1H,t,J10.4Hz,CH),7.59-7.78(2H,m,CH),8.10-8.23(2H,m,Ph),7.11-7.23(4H,m,Ph),8.55(1H,d,J 8.8Hz,Ph).IR(film)νmax 3283,2930,1723,1699,1530,1350,1277,1208,739,596cm-1;MS(ESI):m/z(relative intensity)315.2([M+Na]+,100).The spectral data of the product (23) are: 1 H NMR (400MHz, CDCl 3 ) δ: 1.79(3H,s,COCH 3 ),1.79(3H,s,COCH 3 ),2.03(3H,s,COCH 3 ), 2.23(3H,s,CH 3 ),4.64(1H,dd,J 6.4,10.4Hz,CH),5.61(1H,t,J10.4Hz,CH),7.59-7.78(2H,m,CH),8.10 -8.23(2H,m,Ph),7.11-7.23(4H,m,Ph),8.55(1H,d,J 8.8Hz,Ph).IR(film)ν max 3283,2930,1723,1699,1530, 1350,1277,1208,739,596cm -1 ; MS(ESI):m/z(relative intensity)315.2([M+Na] + ,100).
实施例24Example 24
用乙酰乙酸乙酯代替苯乙酮，其它同实施例1，得目标化合物（24），收率80%，Mp131-133℃。顺反异构比例由核磁共振氢谱中次甲基H原子基于耦合常数的比例看出，顺式：反式为25:75。苯甲醛与乙酰乙酸乙酯，乙腈的反应式为：Ethyl acetoacetate was used instead of acetophenone, and the others were the same as in Example 1 to obtain the target compound (24). The yield was 80%, and the Mp was 131-133°C. The ratio of cis-trans isomerism can be seen from the ratio of methine H atoms based on the coupling constant in the H NMR spectrum, cis:trans is 25:75. Benzaldehyde and ethyl acetoacetate, the reaction formula of acetonitrile is:
产物（24）的波谱数据为：1H NMR(400MHz,CDCl3)δ:2.02(3H,s,COCH3),2.30(3H,s,CH3),3.44(1H,dd,J 6.4,16.8Hz,CH2),3.76(1H,dd,J 4.8,16.8Hz,CH2),5.51–5.55(1H,m,CH),6.62(1H,d,J8.0Hz,NH),7.11-7.23(4H,m,Ph),7.45(2H,t,J7.6Hz,Ph),7.57(1H,t,J5.6Hz,Ph),7.92(2H,t,J 7.2Hz,Ph),13C NMR(100MHz,DMSO-d6)δ:13.5,13.9,22.6,28.9,29.6,51.1,51.7,61.0,64.0,64.7,127.3,128.2,140.2,166.4,167.0,168.3,200.8.IR(film)νmax 3288,3084,2950,1686,1653,1553,1447,1365,1296,987,756,688cm-1;MS(ESI):m/z(relativeintensity)304.1([M+Na]+,100).The spectral data of the product (24) are: 1 H NMR (400MHz, CDCl 3 ) δ: 2.02(3H,s,COCH 3 ),2.30(3H,s,CH 3 ),3.44(1H,dd,J 6.4,16.8 Hz,CH 2 ),3.76(1H,dd,J 4.8,16.8Hz,CH 2 ),5.51–5.55(1H,m,CH),6.62(1H,d,J8.0Hz,NH),7.11-7.23( 4H,m,Ph),7.45(2H,t,J7.6Hz,Ph),7.57(1H,t,J5.6Hz,Ph),7.92(2H,t,J7.2Hz,Ph), 13 C NMR( 100MHz,DMSO-d 6 )δ:13.5,13.9,22.6,28.9,29.6,51.1,51.7,61.0,64.0,64.7,127.3,128.2,140.2,166.4,167.0,168.3,200.8.IR(film)ν max 3288 ,3084,2950,1686,1653,1553,1447,1365,1296,987,756,688cm -1 ; MS(ESI):m/z(relativeintensity)304.1([M+Na] + ,100).
实施例25Example 25
用环己酮代替苯乙酮，其它同实施例1，得目标化合物（25），收率82%，Mp 172-174℃。顺反异构比例由核磁共振氢谱中次甲基H原子基于耦合常数的比例看出，顺式：反式为30:70。苯甲醛与环己酮，乙腈的反应式为：Cyclohexanone was used instead of acetophenone, and the others were the same as in Example 1 to obtain the target compound (25) with a yield of 82% and Mp 172-174°C. The ratio of cis-trans isomerism can be seen from the ratio of methine H atoms based on the coupling constant in the proton nuclear magnetic resonance spectrum, and the cis-trans form is 30:70. The reaction formula of benzaldehyde and cyclohexanone, acetonitrile is:
产物（25）的波谱数据为：1H NMR(400MHz,CDCl3)δ:1.16-1.22(1H,m,CH2),1.49-1.74(4H,m,CH2),1.77(3H,s,COCH3),1.80-1.82(1H,m,CH2),2.73-2.97(1H,m,CH),5.17(1H,t,J 8.8Hz,CH),7.20-7.25(1H,m,Ph),7.29(4H,d,J4.4Hz,Ph),8.19(1H,d,J8.4Hz,NH);13C NMR(100MHz,DMSO-d6)δ:28.3,28.5,33.2,36.1,57.5,60.7,115.1,133.0,133.7,147.1,173.8,216.3.IR(film)νmax 3326,2924,2826,1703,1650,1547,1375,1310,1239,1131,1071,717,699,592cm-1;MS(ESI):m/z(relative intensity)268.1([M+Na]+,100).The spectral data of the product (25) are: 1 H NMR (400MHz, CDCl 3 )δ: 1.16-1.22(1H,m,CH 2 ),1.49-1.74(4H,m,CH 2 ),1.77(3H,s, COCH 3 ),1.80-1.82(1H,m,CH 2 ),2.73-2.97(1H,m,CH),5.17(1H,t,J 8.8Hz,CH),7.20-7.25(1H,m,Ph) ,7.29(4H,d,J4.4Hz,Ph),8.19(1H,d,J8.4Hz,NH); 13 C NMR(100MHz,DMSO-d 6 )δ:28.3,28.5,33.2,36.1,57.5, MS ( ESI ):m/z(relative intensity)268.1([M+Na] + ,100).
实施例26Example 26
用对苯二甲醛代替苯甲醛，其它同实施例1，得目标化合物（26），收率90%，Mp251-253℃。对苯二甲醛与苯乙酮，乙腈的反应式为：Terephthalaldehyde was used instead of benzaldehyde, and the others were the same as in Example 1 to obtain the target compound (26), with a yield of 90%, Mp 251-253°C. Terephthalaldehyde and acetophenone, the reaction formula of acetonitrile is:
产物（26）的波谱数据为：1H NMR(400MHz,DMSO-d6)δ:1.77(6H,s,COCH3),3.37(2H,dd,J4.8,16.8Hz,CH2),3.52(2H,dd,J8,16.4Hz,CH2),5.35(2H,d,J6Hz,NH),7.29(4H,s,Ph),7.52(4H,s,Ph),7.63(2H,s,Ph),7.95(4H,d,J 7.6Hz,Ph),8.28(2H,d,J 7.6Hz,Ph);IR(film)νmax 3296,3081,2902,1688,1651,1548,1447,1298,991,755,688cm-1;MS(ESI):m/z(relativeintensity)479.2([M+Na]+,100).The spectrum data of the product (26) is: 1 H NMR (400MHz, DMSO-d 6 ) δ: 1.77(6H,s,COCH 3 ),3.37(2H,dd,J4.8,16.8Hz,CH 2 ),3.52 (2H,dd,J8,16.4Hz,CH 2 ),5.35(2H,d,J6Hz,NH),7.29(4H,s,Ph),7.52(4H,s,Ph),7.63(2H,s,Ph ),7.95(4H,d,J 7.6Hz,Ph),8.28(2H,d,J 7.6Hz,Ph);IR(film)ν max 3296,3081,2902,1688,1651,1548,1447,1298, 991,755,688cm -1 ; MS(ESI):m/z(relative intensity)479.2([M+Na] + ,100).
Claims (11)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210320524XA CN102816042A (en) | 2012-08-31 | 2012-08-31 | A kind of method of synthesizing β-amide carbonyl compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210320524XA CN102816042A (en) | 2012-08-31 | 2012-08-31 | A kind of method of synthesizing β-amide carbonyl compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102816042A true CN102816042A (en) | 2012-12-12 |
Family
ID=47300545
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210320524XA Pending CN102816042A (en) | 2012-08-31 | 2012-08-31 | A kind of method of synthesizing β-amide carbonyl compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102816042A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103086818A (en) * | 2013-01-15 | 2013-05-08 | 上海药明康德新药开发有限公司 | Method for synthesizing alpha-oxyamide with 2-hydroxy propylene cyanide |
| CN104496837A (en) * | 2014-11-24 | 2015-04-08 | 苏州乔纳森新材料科技有限公司 | Method used for synthesizing beta-ketoamide compounds |
| CN109232291A (en) * | 2017-07-11 | 2019-01-18 | 中国科学院福建物质结构研究所 | A kind of beta amino acids derivative, its synthetic method and the application in drug |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1381755A (en) * | 1971-11-10 | 1975-01-29 | Calgon Corp | Substituted n-alkylamino-acrylamides |
| CN102134176A (en) * | 2011-01-18 | 2011-07-27 | 北京理工大学 | A new method for preparing aromatic amines from halogenated aromatic hydrocarbons |
-
2012
- 2012-08-31 CN CN201210320524XA patent/CN102816042A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1381755A (en) * | 1971-11-10 | 1975-01-29 | Calgon Corp | Substituted n-alkylamino-acrylamides |
| CN102134176A (en) * | 2011-01-18 | 2011-07-27 | 北京理工大学 | A new method for preparing aromatic amines from halogenated aromatic hydrocarbons |
Non-Patent Citations (3)
| Title |
|---|
| FARAHNAZ K. BEHBAHANI等: "CuSO4 5H2O: A NOVEL, GREEN, REUSABLE, AND ENVIRONMENTALLY FRIENDLY CATALYST FOR THE ONE-POT, FOUR-COMPONENT SYNTHESIS OF b-ACETAMIDO CARBONYL COMPOUNDS", 《SYNTHETIC COMMUNICATIONS1》 * |
| NAGARAJAN PANNEER SELVAM等: "Cerium(IV) sulfate catalyzed simple and convenient synthesis of β-acetamidocarbonyl compounds", 《ARKIVOC》 * |
| 杨德利等: "室温下TiCl4 催化简便合成β-氨基酮化合物", 《中国化学会第28届学术年会第6分会场摘要集》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103086818A (en) * | 2013-01-15 | 2013-05-08 | 上海药明康德新药开发有限公司 | Method for synthesizing alpha-oxyamide with 2-hydroxy propylene cyanide |
| CN103086818B (en) * | 2013-01-15 | 2016-08-10 | 武汉药明康德新药开发有限公司 | Method by 2-hydroxyl the third dicyan synthesis Alpha-hydroxy amide |
| CN104496837A (en) * | 2014-11-24 | 2015-04-08 | 苏州乔纳森新材料科技有限公司 | Method used for synthesizing beta-ketoamide compounds |
| CN109232291A (en) * | 2017-07-11 | 2019-01-18 | 中国科学院福建物质结构研究所 | A kind of beta amino acids derivative, its synthetic method and the application in drug |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101190899B (en) | A method for synthesizing 1,2-dihydroquinazolin-4(3H)-ketones | |
| CN103755541B (en) | One class chalcone derivative and its production and use | |
| CN103304393B (en) | A kind of synthetic method of benzil analog derivative | |
| CN102816042A (en) | A kind of method of synthesizing β-amide carbonyl compound | |
| CN104326892A (en) | Synthetic method of indanone by gold-catalysis | |
| CN114634482A (en) | Diazo difluoromethylation reagent and synthesis method and application thereof | |
| CN106187825B (en) | A kind of N, N diamides base substitute hydazone derivative and synthetic method | |
| CN105820174A (en) | Polysubstituted thienoindole derivative and preparation method thereof | |
| CN104327126B (en) | Pyrimidyl ruthenium copper heteronuclear compounds, and preparation method and application thereof | |
| CN109896944B (en) | A kind of method for synthesizing 1,4-naphthoquinocyclopropane compounds | |
| HUP0100146A2 (en) | 3-(1-hydroxy-pentylidene)-5-nitro-3h-benzofuran-2-one, process for its preparation and use thereof | |
| CN109535037B (en) | A kind of N,N'-disubstituted urea compound and its synthetic method | |
| CN108191736B (en) | 2, 3-disubstituted indole derivatives and preparation method thereof | |
| Ghashang et al. | An efficient and environmentally friendly procedure for the synthesis of some novel 8-benzylidene-4-phenyl-3, 4, 5, 6, 7, 8-hexahydro-1H-quinazolin-2-ones/thiones using tetrabutylammonium hexatungstate as a reusable heterogeneous catalyst under solvent-free conditions | |
| CN102382051A (en) | Method for preparing isoquinoline ketone and derivatives thereof | |
| CN101245040B (en) | Process for producing 4-ethynyl benzene sulfonamide (I) | |
| CN106554254A (en) | A kind of synthetic method of 2,3 ', 4,5 ' tetrahydroxy bibenzyl of natural product | |
| CN106045836A (en) | Method for synthesizing aromatic hydrocarbon or heterocyclic trifluoromethylketone under catalytic action of copper | |
| CN105237460B (en) | 2-acyl group replaces the one-step method for synthesizing of 1-isoindolinone compounds | |
| CN112745275B (en) | Synthetic method of 1,3, 4-oxadiazole heterocyclic compound | |
| CN104710305B (en) | A kind of synthetic method of 2-(2-hydroxy phenyl)-2-fluoroacetic acid ester | |
| CN114436919B (en) | A kind of α-difluorothiomethyl ketone (alcohol) derivative and its synthesis method | |
| CN104844429B (en) | A kind of method of gold catalysis pinacol rearrangement | |
| CN115043799B (en) | Preparation method of 5, 6-dihydrobenzofuranone derivative | |
| CN107954960A (en) | A kind of synthetic method of 1,3- dihydroisobenzofurans class compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20121212 |