CN101774940A - Para-N-(4-hydroxyl-3-methoxy benzyl)-8-methyl-5-nonene amide and method for preparing same - Google Patents
Para-N-(4-hydroxyl-3-methoxy benzyl)-8-methyl-5-nonene amide and method for preparing same Download PDFInfo
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- CN101774940A CN101774940A CN201010040082A CN201010040082A CN101774940A CN 101774940 A CN101774940 A CN 101774940A CN 201010040082 A CN201010040082 A CN 201010040082A CN 201010040082 A CN201010040082 A CN 201010040082A CN 101774940 A CN101774940 A CN 101774940A
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- Prior art keywords
- methyl
- acid
- hydroxyl
- nonene
- methoxy
- Prior art date
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Links
- 238000000034 method Methods 0.000 title claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 30
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims abstract description 30
- -1 isopentyl aldehyde Chemical class 0.000 claims abstract description 19
- 150000001412 amines Chemical class 0.000 claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 229940005605 valeric acid Drugs 0.000 claims abstract description 15
- RWBSUACWLXYFPL-UHFFFAOYSA-N 6-[bromo(triphenyl)-$l^{5}-phosphanyl]hexanoic acid Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(CCCCCC(=O)O)C1=CC=CC=C1 RWBSUACWLXYFPL-UHFFFAOYSA-N 0.000 claims abstract description 12
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims abstract description 12
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000007788 liquid Substances 0.000 claims abstract description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims abstract description 6
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 claims abstract description 6
- 235000012141 vanillin Nutrition 0.000 claims abstract description 6
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000003513 alkali Substances 0.000 claims abstract description 5
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 107
- 238000004821 distillation Methods 0.000 claims description 41
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 32
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 28
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 21
- 239000007864 aqueous solution Substances 0.000 claims description 21
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 17
- 238000000605 extraction Methods 0.000 claims description 17
- 235000009499 Vanilla fragrans Nutrition 0.000 claims description 16
- 244000263375 Vanilla tahitensis Species 0.000 claims description 16
- 235000012036 Vanilla tahitensis Nutrition 0.000 claims description 16
- 238000010992 reflux Methods 0.000 claims description 15
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- YGHRJJRRZDOVPD-UHFFFAOYSA-N 3-methylbutanal Chemical compound CC(C)CC=O YGHRJJRRZDOVPD-UHFFFAOYSA-N 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 5
- ALQSHHUCVQOPAS-UHFFFAOYSA-N Pentane-1,5-diol Chemical compound OCCCCCO ALQSHHUCVQOPAS-UHFFFAOYSA-N 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- UOHBMRODJBFDPN-UHFFFAOYSA-N C(C)(C)(C)O.[Li] Chemical compound C(C)(C)(C)O.[Li] UOHBMRODJBFDPN-UHFFFAOYSA-N 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- 239000003810 Jones reagent Substances 0.000 claims description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 claims description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 claims description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims description 2
- 239000012670 alkaline solution Substances 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 229940071870 hydroiodic acid Drugs 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 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
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 230000002829 reductive effect Effects 0.000 claims description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 2
- 239000012279 sodium borohydride Substances 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 238000000638 solvent extraction Methods 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 125000001033 ether group Chemical group 0.000 claims 1
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical class COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 abstract description 25
- 238000005893 bromination reaction Methods 0.000 abstract 1
- 230000003472 neutralizing effect Effects 0.000 abstract 1
- 230000003647 oxidation Effects 0.000 abstract 1
- 238000007254 oxidation reaction Methods 0.000 abstract 1
- UWJJYHHHVWZFEP-UHFFFAOYSA-N pentane-1,1-diol Chemical compound CCCCC(O)O UWJJYHHHVWZFEP-UHFFFAOYSA-N 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 239000000047 product Substances 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- 238000001035 drying Methods 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- AKDLSISGGARWFP-UHFFFAOYSA-N Homodihydrocapsaicin Chemical compound COC1=CC(CNC(=O)CCCCCCCC(C)C)=CC=C1O AKDLSISGGARWFP-UHFFFAOYSA-N 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000013078 crystal Substances 0.000 description 9
- 230000006837 decompression Effects 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- 244000124209 Crocus sativus Species 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- VQEONGKQWIFHMN-UHFFFAOYSA-N Nordihydrocapsaicin Chemical compound COC1=CC(CNC(=O)CCCCCC(C)C)=CC=C1O VQEONGKQWIFHMN-UHFFFAOYSA-N 0.000 description 6
- 238000013019 agitation Methods 0.000 description 6
- 239000008367 deionised water Substances 0.000 description 6
- 229910021641 deionized water Inorganic materials 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 235000002566 Capsicum Nutrition 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 240000008574 Capsicum frutescens Species 0.000 description 4
- 239000001390 capsicum minimum Substances 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- XJQPQKLURWNAAH-UHFFFAOYSA-N dihydrocapsaicin Chemical compound COC1=CC(CNC(=O)CCCCCCC(C)C)=CC=C1O XJQPQKLURWNAAH-UHFFFAOYSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical group NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 229960002504 capsaicin Drugs 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 229960000935 dehydrated alcohol Drugs 0.000 description 3
- RBCYRZPENADQGZ-UHFFFAOYSA-N dihydrocapsaicin Natural products COC1=CC(COC(=O)CCCCCCC(C)C)=CC=C1O RBCYRZPENADQGZ-UHFFFAOYSA-N 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000003810 ethyl acetate extraction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- GRRIMVWABNHKBX-UHFFFAOYSA-N (3-methoxyphenyl)methanamine Chemical compound COC1=CC=CC(CN)=C1 GRRIMVWABNHKBX-UHFFFAOYSA-N 0.000 description 1
- SRJYAIHGVHXPNT-UHFFFAOYSA-N 2-methoxy-4-[(9-methyldecylamino)methyl]phenol Chemical compound COC1=CC(CNCCCCCCCCC(C)C)=CC=C1O SRJYAIHGVHXPNT-UHFFFAOYSA-N 0.000 description 1
- KDEDMKWIDSIATQ-UHFFFAOYSA-N 4-[(decylamino)methyl]-2-methoxyphenol Chemical compound CCCCCCCCCCNCC1=CC=C(O)C(OC)=C1 KDEDMKWIDSIATQ-UHFFFAOYSA-N 0.000 description 1
- YVFBKRXXJPQLTK-UHFFFAOYSA-N CCC(C)CCCCCCCNCC1=CC(=C(C=C1)O)OC Chemical compound CCC(C)CCCCCCCNCC1=CC(=C(C=C1)O)OC YVFBKRXXJPQLTK-UHFFFAOYSA-N 0.000 description 1
- JYZDUDMWJFJCON-UHFFFAOYSA-N Caprylic acid vanillylamide Natural products CCCCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 JYZDUDMWJFJCON-UHFFFAOYSA-N 0.000 description 1
- 241000208293 Capsicum Species 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- KGWDUNBJIMUFAP-KVVVOXFISA-N Ethanolamine Oleate Chemical compound NCCO.CCCCCCCC\C=C/CCCCCCCC(O)=O KGWDUNBJIMUFAP-KVVVOXFISA-N 0.000 description 1
- 208000001034 Frostbite Diseases 0.000 description 1
- 241000256602 Isoptera Species 0.000 description 1
- LNEUSMKJJRXQGJ-UHFFFAOYSA-N N-[(4-hydroxy-3-methoxyphenyl)methyl]-7-methyldecanamide Chemical compound CCCC(C)CCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 LNEUSMKJJRXQGJ-UHFFFAOYSA-N 0.000 description 1
- 239000006002 Pepper Substances 0.000 description 1
- 235000016761 Piper aduncum Nutrition 0.000 description 1
- 235000017804 Piper guineense Nutrition 0.000 description 1
- 244000203593 Piper nigrum Species 0.000 description 1
- 235000008184 Piper nigrum Nutrition 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003373 anti-fouling effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001139 anti-pruritic effect Effects 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
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- 230000003628 erosive effect Effects 0.000 description 1
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- 235000019634 flavors Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical class COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- QLHTWDQJPOTDMV-UHFFFAOYSA-N n-[(4-hydroxy-3-methoxyphenyl)methyl]decanamide Chemical compound CCCCCCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 QLHTWDQJPOTDMV-UHFFFAOYSA-N 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 125000001402 nonanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- RGOVYLWUIBMPGK-UHFFFAOYSA-N nonivamide Chemical compound CCCCCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 RGOVYLWUIBMPGK-UHFFFAOYSA-N 0.000 description 1
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- 230000020477 pH reduction Effects 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
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- 238000000926 separation method Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides para-N-(4-hydroxyl-3-methoxy benzyl)-8-methyl-5-nonene amide, which has a structural formula represented by a formula(1). The preparation method comprises the following steps of: performing mono-bromination of pentanediol to obtain 5-bromine amyl alcohol; performing oxidation of the 5-bromine amyl alcohol to obtain 5-bromine valeric acid; performing a reaction of the 5-bromine valeric acid and triphenyl phosphorus to prepare (5-carboxyl amyl)triphenyl phosphorus bromide; performing a reaction of the (5-carboxyl amyl)triphenyl phosphorus bromide and isopentyl aldehyde to obtain para-8-methyl-5-nonenoic acid, and performing a reaction of the para-8-methyl-5-nonenoic acid and an acylating agent to obtain para-8-methyl-5-nonene acyl chloride; performing a reaction of vanillin and ammonium formate to obtain vanillic amine, acidifying the vanillic amine, neutralizing the vanillic amine by using alkali liquid, and performing a reaction of the treated vanillic amine and the para-8-methyl-5-nonene acyl chloride to obtain the finished product. The method has the advantages of simple process, low cost and mild reaction conditions; and the prepared capsaicin derivative of the para-N-(4-hydroxyl-3-methoxy benzyl)-8-methyl-5-nonene amid provides a new development space for a research on the capsaicin-type matters.
Description
Technical field
The present invention relates to capsicine material and preparation method thereof, especially suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides and preparation method thereof.
Background technology
The fruit of capsicum plant (Capsicum) is one of maximum seasonings of whole world consumption.Contain at least 12 kinds of capsicine materials that can produce pungent in these pepper fruits, be respectively capsicine (N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-6-nonene acid amides), Dihydrocapsaicin (N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-pelargonamide), capsicine (N-(4-hydroxyl-3-methoxy-benzyl)-7-methyl-5-octene acid amides) falls, Nordihydrocapsaicin (N-(4-hydroxyl-3-methoxy-benzyl)-7-methyl-decoylamide), homocpsaicin (I) (N-(4-hydroxyl-3-methoxy-benzyl)-9-methyl-7-decene acid amides), Homodihydrocapsaicin I (I) (N-(4-hydroxyl-3-methoxy-benzyl)-9-methyl-decyl amide), homocpsaicin (II) (N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-6-decene acid amides), Homodihydrocapsaicin I (II) (N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-decyl amide), capsicine (N-(4-hydroxyl-3-methoxy-benzyl)-6-methyl-4-heptene acid amides) falls, the blue amine (N-(4-hydroxyl-3-methoxy-benzyl)-pelargonamide) of nonanoyl pod, decoyl vanillylamide (N-(4-hydroxyl-3-methoxy-benzyl)-decoylamide), the blue amine (N-(4-hydroxyl-3-methoxy-benzyl)-decyl amide) of caprinoyl pod.
In the natural capsicum bases material, capsicine (46%～69%), Dihydrocapsaicin (21%～40%), Nordihydrocapsaicin (～7%), Homodihydrocapsaicin I (I) (～1%), homocpsaicin (I) (～1%), all the other capsicine materials are trace.Wherein the peppery degree of capsicine is maximum, up to 16,000, and 000 Scoville Heat Unit (SHU); Secondly being Dihydrocapsaicin, is 15,000,000SHU; Nordihydrocapsaicin, Homodihydrocapsaicin I (I), the peppery degree of homocpsaicin (I) are respectively 9,100,000SHU, 8,600,000SHU, 8,6000,000SHU.
Except natural capsicine material, also have a lot of capsicine analogues also to have peppery degree.Organoleptic analysis result to capsicine material and capsicine analogue shows that peppery degree depends on its molecular characterization to a great extent:
The hydroxyl that will contain ortho position or contraposition in the i alkylamide molecule in the benzylamine part phenyl ring, the neighbour position of contraposition hydroxyl hydroxyl is more effective.If hydroxyl is replaced by other group, will cause this compound to lose peppery degree, if just can not produce peppery degree as benzylamine or 3-methoxybenzylamine;
The derivative of ii vanilla amine is the pepperyyest, but the derivative of o-hydroxyanisole and thanomin also has peppery degree;
Iii is when the place-exchange of amino and carbonyl, and peppery degree can not disappear, and increases to some extent on the contrary;
Iv has only aliphatic side chain can produce peppery degree, and straight chain or ring-shaped fat side chain can.
VC
9-C
11The peppery degree of straight chain amide compound is the highest, and oversize or too short peppery degree all can obviously reduce when aliphatic lateral chain.Such as being longer than twelve carbon atom or being shorter than 6 carbon atoms, just do not have tangible peppery having spent when alkyl group side chain.
The capsicine material has multiple pharmacological effect because of its sharp flavor, as analgesia, anti-inflammatory, treatment frostbite, antipruritic, sterilization, wind-damp dispelling etc.; Be mainly used in refractory diseases such as neural painful, the serious psoriatic of treatment diabetic clinically; In agriculture production, be used as the environment-friendly biological pesticide; In anti-fouling ship paint, be used as driving agent, prevent that marine life from adhering to; Add in the sheath of electric wire, cable, optical cable, can prevent the food erosion injury of mouse, termite; Can also be as making tear bomb and alert with defensive weapon etc.
At present, it is less to utilize chemical synthesis process to prepare the research of capsicine and class material thereof, and domestic rarely have report, also few abroad.Harumi Kaga etc. has reported the synthetic method [Harumi Kaga, Masakatsu Miura, Kazuhiko Orito.A Facile Procedure for Synthesis of Capsaicin.J.Org.Chem.1989,54,3477-3478] of capsicine; Peter M.Gannett etc. has reported synthetic [the Peter M.Gannett of capsicine material, Donald L. Nagel, Pam J.Reilly, Terence Lawson, Jody Sharpe, Bela Toth.The Capsaicinoids:Their Separation, Synthesis and Mutagenicity.J.Org.Chem.1988,53:1064-1071]; Yang Yan etc. reported capsaicine and capsicum ester synthetic method [Yang Yan, gold immortality, Dong Zhenxiu etc. capsaicine and capsicum ester synthetic. SCI .2007,28 (7): 1310～1312].But the synthetic report that N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides is not all arranged in the above-mentioned document.
Summary of the invention
The purpose of this invention is to provide a kind of capsaicin derivatives suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides and preparation method thereof.
Of the present invention suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides, its structural formula is as the formula (1)
Formula (1)
The preparation method of suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides may further comprise the steps:
(1) with 1,5-pentanediol and Hydrogen bromide are according to mol ratio 1: 1-1: 5 in the presence of minute aqua, carries out single bromo-reaction in reflux temperature, obtains 5-bromine amylalcohol;
(2) 5-bromine amylalcohol is dissolved in the acetone, drips Jones reagent and carry out oxidizing reaction, generate 5-bromine valeric acid;
(3) with 5-bromine valeric acid and triphenyl phosphorus according to mol ratio 1.5: 1-1: 1.5 are dissolved in the benzene, in the reflux temperature reaction, obtain (5-carboxyl pentyl) tri-phenyl-phosphorus bromide;
(4) under the alkaline effect, (5-carboxyl pentyl) tri-phenyl-phosphorus bromide and isovaleric aldehyde under normal temperature according to mol ratio 1.5: 1-1: 1.5 at N, reacts in the dinethylformamide, generates suitable-8-methyl-5-nonenoic acid;
(5) suitable-8-methyl-5-nonenoic acid and excessive acylating reagent in reflux temperature reaction down, obtains suitable-8-methyl-5-nonene acyl chlorides;
(6) Vanillin and ammonium formiate are according to mol ratio 1: 1-1: 5, in 150-200 ℃ down reaction obtain vanilla amine, vanilla amine obtains the vanilla amine salt through acidifying;
(7) use in the alkali lye vanilla amine salt and back and suitable-8-methyl-5-nonene acyl chloride reaction, obtain suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-thick product of 5-nonene acid amides.
Further feature of the present invention is that suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-thick product of 5-nonene acid amides is carried out purifying, step is as follows: earlier thick product is extracted with alkali lye, extraction liquid diluted acid acidifying, use organic solvent extraction again, organic solvent is removed in underpressure distillation, carry out recrystallization with ether/normal hexane then, the volume ratio of ether/normal hexane is 1: 1～1: 10.
The used organic solvent of purifying can be ether, propyl carbinol, ethyl acetate, toluene, dimethylbenzene, chloroform or methylene dichloride.
Among the present invention, aqua can be one or more mixtures in normal heptane, normal hexane, hexanaphthene, benzene,toluene,xylene and the sherwood oil in said minute.
Among the present invention, said highly basic can be n-Butyl Lithium, phenyl lithium, sodium amide, sodium cyanide, potassium tert.-butoxide, sodium tert-butoxide or trimethyl carbinol lithium.
Among the present invention, the acid of acidifying vanilla amine can be the aqueous solution of hydrochloric acid, Hydrogen bromide, hydroiodic acid HI, sulfuric acid, sulfurous acid, nitric acid, nitrous acid, phosphoric acid, metaphosphoric acid, formic acid, acetate or propionic acid.
Among the present invention, in and the used alkaline solution of vanilla amine salt can be aqueous sodium hydroxide solution, potassium hydroxide aqueous solution, aqueous sodium carbonate or sodium bicarbonate aqueous solution.
Among the present invention, said acylating reagent can be SOCl
2
Among the present invention, used 1, the 5-pentanediol can be commercially available, also can be by glutaraldehyde through the reduction gained, and used reductive agent is POTASSIUM BOROHYDRIDE or sodium borohydride.
The invention discloses a kind of new capsaicin derivatives suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides, its preparation technology is easy, and cost is low, and raw material is easy to get, the reaction conditions gentleness is for the research of capsicine material provides new development space.
Embodiment
Further specify the present invention below in conjunction with embodiment.
Embodiment 1
(1) with 4.0g NaBH
4Be made into the 50mL aqueous solution, and add small amount of N aOH.In ice-water bath, this solution slowly is added drop-wise in the glutaraldehyde solution of 100g 25%, reacts 4h after dropwising again.Drip the rare HCl of 1M then, to pH=3～4.In product, drip the 2M NaOH aqueous solution, transfer product pH=8～9; Underpressure distillation dewaters, and adds proper amount of acetone and anhydrous Na then
2SO
4Dry; Filter; The filtrate decompression distillation removes acetone; Underpressure distillation collects 1 again, 5-pentanediol product, and productive rate can reach 91%.
Claim 5.2g 1,5-pentanediol, 13.1g 40% Hydrogen bromide, 300mL normal heptane and add an amount of vitriol oil in there-necked flask, react 8h under reflux state.With separating funnel separate the normal heptane phase, and with deionized water wash normal heptane phase, to water pH=7.Normal heptane is used anhydrous sodium sulfate drying mutually then, filters, and underpressure distillation removes normal heptane, promptly gets 5-bromine amylalcohol, productive rate 40.1%.
(2) in 2.5g 5-bromine amylalcohol, add 30mL acetone, slowly drip Jones (Jones) reagent then, be safran to reaction solution solution, and safran is not taken off (can see that green matter generates) in the 10min.Filter, underpressure distillation removes acetone; Add less water, use extracted with diethyl ether 4 times; Extraction liquid merges, with NaOH aqueous solution extraction organic phase; Water is regulated pH=1～2 with rare HCl, makes the acidifying of 5-bromine natrium valericum, generates 5-bromine valeric acid, uses extracted with diethyl ether again 4 times; Extraction liquid merges, and uses the deionized water wash organic phase, to washing lotion pH=7, adds anhydrous sodium sulfate drying; Filter; Filtrate decompression distillation obtains the 5-bromine valeric acid product behind the purifying, productive rate 30%.
(3) claim 2.0g 5-bromine valeric acid, add 3.0g triphenyl phosphorus and 50mL benzene, reflux state is reaction 24h down.Underpressure distillation removes benzene, adds 20mL methylene dichloride stirring and dissolving then, slowly adds ether again, gets white solid.Filter, vacuum-drying gets (5-carboxyl pentyl) tri-phenyl-phosphorus bromide, productive rate 91%.
(4) take by weighing the 2.1g potassium metal and join in the excessive trimethyl carbinol, nitrogen protection, 70 ℃ of down reactions, to potassium metal by the melt metal bead to completely dissolve (crystal of bottle wall adularescent is separated out), adding 20mL N, dinethylformamide (DMF).N
2Protection slowly drips following mixture down: (5-carboxyl pentyl) tri-phenyl-phosphorus bromide 4.5g, isovaleric aldehyde 1.2g, 20mL DMF.Dropwise the back at stirring at room reaction 12h, suspended substance is poured in the 80mL frozen water, suction filtration, filtrate is used the dilute hydrochloric acid acidifying, uses extracted with diethyl ether then four times.Extraction liquid merges, with saturated strong brine washing, anhydrous sodium sulfate drying.Filter, underpressure distillation desolventizes, and obtains suitable-8-methyl-5-nonenoic acid, productive rate 55%.
(5) to 5.2g suitable-add the 12.3g sulfur oxychloride in 8-methyl-5-alkene n-nonanoic acid, nitrogen protection, magnetic agitation, reflux state be reaction 1h down.Unnecessary sulfur oxychloride is removed in underpressure distillation then, and adds the 35mL anhydrous diethyl ether, obtains the diethyl ether solution of 8-methyl-4-alkene pelargonyl chloride.
(6) in the 150mL there-necked flask, add the 60.0g ammonium formiate, oil bath heating under argon shield, the magnetic agitation.After ammonium formiate dissolves fully, add the 45.8g Vanillin, and react 3h down at 170 ℃, unnecessary ammonium formiate is removed in underpressure distillation then.Then in reaction system, add the 36mL concentrated hydrochloric acid, back flow reaction 1h, unnecessary hydrochloric acid is gone out in underpressure distillation then.Add the 100mL dehydrated alcohol again, have a large amount of crystal to separate out, filter, and become white with absolute ethanol washing to crystal.Filter cake obtains product 4-hydroxyl-3 methoxyl groups-benzylamine hydrochloride 50 ℃ of oven dry down.
(7) 7.4g vanilla amine hydrochlorate is dissolved in the saturated NaHCO of 6.5g
3In the aqueous solution, treat that it dissolves fully after, slowly add the diethyl ether solution of 8-methyl-4-alkene pelargonyl chloride, at 30 ℃ of reaction 1h down, add ether 26mL therebetween then.Then the mixing solutions that obtains is poured in the separating funnel and left standstill, remove water layer, organic phase is used the hydrochloric acid of 35mL 1mol/L, saturated NaHCO successively
3Solution washing.The diethyl ether solution anhydrous sodium sulfate drying that obtains filters then.Filtrate is removed ether through underpressure distillation, obtains the crude product of structural formula suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides as the formula (1), productive rate 56%.
Formula (1)
Get an amount of 5.0g suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-thick product of 5-nonene acid amides is dissolved in the ether, uses the 0.5%NaOH aqueous solution extraction then.The dilute hydrochloric acid acidification is used in water intaking mutually, uses extracted with diethyl ether again.Aqueous phase discarded, the organic phase anhydrous sodium sulfate drying adds proper amount of active carbon absorption impurity wherein, filters, and the ether of the overwhelming majority is removed in the filtrate decompression distillation.Use ether/normal hexane (1/3) recrystallization purifying then.
Embodiment 2
(1) 8.0g KBH4 is made into the 100mL aqueous solution, and adds small amount of N aOH.In ice-water bath, this solution slowly is added drop-wise in the glutaraldehyde solution of 150g 25%, reacts 5h after dropwising again.Drip the rare HCl of 1M then, to pH=3～4.In product, drip the 2M NaOH aqueous solution, transfer product pH=8～9; Underpressure distillation dewaters, and adds proper amount of acetone and anhydrous Na then
2SO
4Dry; Filter; The filtrate decompression distillation removes acetone; Underpressure distillation collects 1 again, 5-pentanediol product, and productive rate reaches 88%.
Claim 10.4g 1,5-pentanediol, 30.5g 40% Hydrogen bromide, 500mL normal heptane and add an amount of vitriol oil in there-necked flask, react 8h under reflux state.With separating funnel separate the normal heptane phase, and with deionized water wash normal heptane phase, to water pH=7.Normal heptane is used anhydrous sodium sulfate drying mutually then, filters, and underpressure distillation removes normal heptane, promptly gets 5-bromine amylalcohol, productive rate 44.3%.
(2) in 5.5g 5-bromine amylalcohol, add 50mL acetone, slowly drip Jones (Jones) reagent then, be safran to reaction solution solution, and safran is not taken off (can see that green matter generates) in the 10min.Filter, underpressure distillation removes acetone; Add less water, use CH
2Cl
2Extract 4 times; Extraction liquid merges, with NaOH aqueous solution extraction organic phase; Water is regulated pH=1～2 with rare HCl, makes the acidifying of 5-bromine natrium valericum, generates 5-bromine valeric acid, uses CH again
2Cl
2Extract 4 times; Extraction liquid merges, and uses the deionized water wash organic phase, to washing lotion pH=7, adds anhydrous sodium sulfate drying; Filter; Filtrate decompression distillation obtains the 5-bromine valeric acid product behind the purifying, productive rate 32%.
(3) claim 4.0g 5-bromine valeric acid, add 9.0g triphenyl phosphorus and 50mL benzene, reflux state is reaction 24h down.Underpressure distillation removes benzene, adds 20mL methylene dichloride stirring and dissolving then, slowly adds ether again, gets white solid.Filter, vacuum-drying gets (5-carboxyl pentyl) tri-phenyl-phosphorus bromide, productive rate 93%.
(4) take by weighing the 2.3g potassium metal and join in the excessive trimethyl carbinol, nitrogen protection, 70 ℃ of down reactions, to potassium metal by the melt metal bead to completely dissolve (crystal of bottle wall adularescent is separated out), adding 20mL N, dinethylformamide (DMF).N
2Protection slowly drips following mixture down: (5-carboxyl pentyl) tri-phenyl-phosphorus bromide 6.8g, isovaleric aldehyde 1.2g, 20mL DMF.Dropwise the back at stirring at room reaction 12h, suspended substance is poured in the 80mL frozen water, suction filtration, filtrate is used the dilute hydrochloric acid acidifying, uses extracted with diethyl ether then four times.Extraction liquid merges, with saturated strong brine washing, anhydrous sodium sulfate drying.Filter, underpressure distillation desolventizes, and obtains suitable-8-methyl-5-nonenoic acid, productive rate 38%.
(5) to 6.4g suitable-add the 20.1g sulfur oxychloride in 8-methyl-5-alkene n-nonanoic acid, nitrogen protection, magnetic agitation, reflux state be reaction 1h down.Unnecessary sulfur oxychloride is removed in underpressure distillation then, and adds the 35mL anhydrous diethyl ether, obtains the diethyl ether solution of 8-methyl-4-alkene pelargonyl chloride.
(6) in the 150mL there-necked flask, add the 94.6g ammonium formiate, oil bath heating under argon shield, the magnetic agitation.After ammonium formiate dissolves fully, add the 46.0g Vanillin, and react 3h down at 175 ℃, unnecessary ammonium formiate is removed in underpressure distillation then.Then in reaction system, add the 36mL concentrated hydrochloric acid, back flow reaction 1h, unnecessary hydrochloric acid is gone out in underpressure distillation then.Add the 100mL dehydrated alcohol again, have a large amount of crystal to separate out, filter, and become white with absolute ethanol washing to crystal.Filter cake obtains product 4-hydroxyl-3 methoxyl groups-benzylamine hydrochloride 50 ℃ of oven dry down.
(7) 9.3g vanilla amine hydrochlorate is dissolved in the 100mL 1M NaOH aqueous solution, treat that it dissolves fully after, slowly add the diethyl ether solution of 8-methyl-4-alkene pelargonyl chloride, at 30 ℃ of reaction 1h down, add ether 26mL therebetween then.Then the mixing solutions that obtains is poured in the separating funnel and left standstill, remove water layer, organic phase is used hydrochloric acid, the 1M NaOH solution washing of 35mL 1M successively.The diethyl ether solution anhydrous sodium sulfate drying that obtains filters then.Filtrate is removed ether through underpressure distillation, obtains the crude product of structural formula suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides as the formula (1), productive rate 52%.
Get an amount of 8.0g suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-thick product of 5-nonene acid amides is dissolved in the ether, uses the 0.5%KOH aqueous solution extraction then.1M H is used in water intaking mutually
2SO
4Acidification is used extracted with diethyl ether again.Aqueous phase discarded, the organic phase anhydrous sodium sulfate drying adds proper amount of active carbon absorption impurity wherein, filters, and the ether of the overwhelming majority is removed in the filtrate decompression distillation.Use ether/normal hexane (1/10) recrystallization purifying then.
Embodiment 3
(1) with 5.8g KBH
4Be made into the 70mL aqueous solution, and add a small amount of KOH.In ice-water bath, this solution slowly is added drop-wise in the glutaraldehyde solution of 100g 25%, reacts 5h after dropwising again.Drip the rare HCl of 2M then, to pH=3～4.In product, drip the 2M NaOH aqueous solution, transfer product pH=8～9; Underpressure distillation dewaters, and adds proper amount of acetone and anhydrous Na then
2SO
4Dry; Filter; The filtrate decompression distillation removes acetone; Underpressure distillation collects 1 again, 5-pentanediol product, and productive rate reaches 89%.
Claim 15.5g 1,5-pentanediol, 30.5g 40% Hydrogen bromide, 800mL normal heptane and add an amount of vitriol oil in there-necked flask, react 8h under reflux state, remove the water that generates by water-and-oil separator simultaneously.With separating funnel separate the normal heptane phase, and with deionized water wash normal heptane phase, to water pH=7.Normal heptane is used anhydrous sodium sulfate drying mutually then, filters, and underpressure distillation removes normal heptane, promptly gets 5-bromine amylalcohol, productive rate 54.3%.
(2) in 7.5g 5-bromine amylalcohol, add 50mL acetone, slowly drip Jones (Jones) reagent then, be safran to reaction solution solution, and safran is not taken off (can see that green matter generates) in the 10min.Filter, underpressure distillation removes acetone; Add less water, use ethyl acetate extraction 4 times; Extraction liquid merges, with KOH aqueous solution extraction organic phase; Water is regulated pH=1～2 with rare HCl, makes the acidifying of 5-bromine natrium valericum, generates 5-bromine valeric acid, uses ethyl acetate extraction again 4 times; Extraction liquid merges, and uses the deionized water wash organic phase, to washing lotion pH=7, adds anhydrous sodium sulfate drying; Filter; Filtrate decompression distillation obtains the 5-bromine valeric acid product behind the purifying, productive rate 32%.
(3) claim 6.0g 5-bromine valeric acid, add 6.0g triphenyl phosphorus and 50mL benzene, reflux state is reaction 24h down.Underpressure distillation removes benzene, adds 20mL methylene dichloride stirring and dissolving then, slowly adds ether again, gets white solid.Filter, vacuum-drying gets (5-carboxyl pentyl) tri-phenyl-phosphorus bromide, productive rate 53%.
(4) take by weighing the 2.7g potassium metal and join in the excessive trimethyl carbinol, nitrogen protection, 70 ℃ of down reactions, to potassium metal by the melt metal bead to completely dissolve (crystal of bottle wall adularescent is separated out), adding 20mL N, dinethylformamide (DMF).N
2Protection slowly drips following mixture down: (5-carboxyl pentyl) tri-phenyl-phosphorus bromide 4.6g, isovaleric aldehyde 1.8g, 20mL DMF.Dropwise the back at stirring at room reaction 12h, suspended substance is poured in the 80mL frozen water, suction filtration, filtrate is used the dilute hydrochloric acid acidifying, uses extracted with diethyl ether then four times.Extraction liquid merges, with saturated strong brine washing, anhydrous sodium sulfate drying.Filter, underpressure distillation desolventizes, and obtains suitable-8-methyl-5-nonenoic acid, productive rate 58%.
(5) to 7.6g suitable-add the 20.3g sulfur oxychloride in 8-methyl-5-alkene n-nonanoic acid, nitrogen protection, magnetic agitation, reflux state be reaction 1h down.Unnecessary sulfur oxychloride is removed in underpressure distillation then, and adds the 35mL anhydrous diethyl ether, obtains the diethyl ether solution of 8-methyl-4-alkene pelargonyl chloride.
(6) in the 150mL there-necked flask, add the 18.9g ammonium formiate, oil bath heating under argon shield, the magnetic agitation.After ammonium formiate dissolves fully, add the 45.8g Vanillin, and react 3h down at 180 ℃, unnecessary ammonium formiate is removed in underpressure distillation then.Then in reaction system, add the 36mL concentrated hydrochloric acid, back flow reaction 1h, unnecessary hydrochloric acid is gone out in underpressure distillation then.Add the 100mL dehydrated alcohol again, have a large amount of crystal to separate out, filter, and become white with absolute ethanol washing to crystal.Filter cake obtains product 4-hydroxyl-3 methoxyl groups-benzylamine hydrochloride 50 ℃ of oven dry down.
(7) 10.8g vanilla amine hydrochlorate is dissolved in 100mL 0.5M Na
2CO
3In the aqueous solution, treat that it dissolves fully after, slowly add the diethyl ether solution of 8-methyl-4-alkene pelargonyl chloride, at 30 ℃ of reaction 1h down, add ether 36mL therebetween then.Then the mixing solutions that obtains is poured in the separating funnel and left standstill, remove water layer, organic phase is used hydrochloric acid, the 1M KOH solution washing of 35mL 1M successively.The diethyl ether solution anhydrous sodium sulfate drying that obtains filters then.Filtrate is removed ether through underpressure distillation, obtains the crude product of structural formula suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides as the formula (1), productive rate 42%.
Get an amount of 9.0g suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-thick product of 5-nonene acid amides is dissolved in the ether, uses the 0.5%KOH aqueous solution extraction then.1M H is used in water intaking mutually
2SO
4Acidification is used extracted with diethyl ether again.Aqueous phase discarded, the organic phase anhydrous sodium sulfate drying adds proper amount of active carbon absorption impurity wherein, filters, and the ether of the overwhelming majority is removed in the filtrate decompression distillation.Use ether/normal hexane (1/1) recrystallization purifying then.
Claims (10)
1. suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides, its structural formula as the formula (1)
Formula (1)
2. prepare claim 1 described suitable-method of N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides, it is characterized in that may further comprise the steps:
(1) with 1,5-pentanediol and Hydrogen bromide are according to mol ratio 1: 1-1: 5 in the presence of minute aqua, carries out single bromo-reaction in reflux temperature, obtains 5-bromine amylalcohol;
(2) 5-bromine amylalcohol is dissolved in the acetone, drips Jones reagent and carry out oxidizing reaction, generate 5-bromine valeric acid;
(3) with 5-bromine valeric acid and triphenyl phosphorus according to mol ratio 1.5: 1-1: 1.5 are dissolved in the benzene, in the reflux temperature reaction, obtain (5-carboxyl pentyl) tri-phenyl-phosphorus bromide;
(4) under the alkaline effect, (5-carboxyl pentyl) tri-phenyl-phosphorus bromide and isovaleric aldehyde under normal temperature according to mol ratio 1.5: 1-1: 1.5 at N, reacts in the dinethylformamide, generates suitable-8-methyl-5-nonenoic acid;
(5) suitable-8-methyl-5-nonenoic acid and excessive acylating reagent in reflux temperature reaction down, obtains suitable-8-methyl-5-nonene acyl chlorides;
(6) Vanillin and ammonium formiate are according to mol ratio 1: 1-1: 5, in 150-200 ℃ down reaction obtain vanilla amine, vanilla amine obtains the vanilla amine salt through acidifying;
(7) use in the alkali lye vanilla amine salt and back and suitable-8-methyl-5-nonene acyl chloride reaction, obtain suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-thick product of 5-nonene acid amides.
3. according to claim 1 suitable-preparation method of N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides, it is characterized in that suitable-N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-thick product of 5-nonene acid amides is carried out purifying, step is as follows: earlier thick product is extracted with alkali lye, extraction liquid diluted acid acidifying, use organic solvent extraction again, organic solvent is removed in underpressure distillation, carries out recrystallization with ether/normal hexane then, and the volume ratio of ether/normal hexane is 1: 1～1: 10.
4. according to claim 3 suitable-preparation method of N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides, it is characterized in that used organic solvent is ether, propyl carbinol, ethyl acetate, toluene, dimethylbenzene, chloroform or methylene dichloride.
5. according to claim 1 suitable-preparation method of N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides, it is characterized in that the branch aqua is one or more mixtures in normal heptane, normal hexane, hexanaphthene, benzene,toluene,xylene and the sherwood oil.
6. according to claim 1 suitable-preparation method of N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides, it is characterized in that highly basic is n-Butyl Lithium, phenyl lithium, sodium amide, sodium cyanide, potassium tert.-butoxide, sodium tert-butoxide or trimethyl carbinol lithium.
7. according to claim 1 suitable-preparation method of N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides, the acid that it is characterized in that acidifying vanilla amine is the aqueous solution of hydrochloric acid, Hydrogen bromide, hydroiodic acid HI, sulfuric acid, sulfurous acid, nitric acid, nitrous acid, phosphoric acid, metaphosphoric acid, formic acid, acetate or propionic acid.
8. according to claim 1 suitable-preparation method of N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides, in it is characterized in that and the used alkaline solution of vanilla amine salt be aqueous sodium hydroxide solution, potassium hydroxide aqueous solution, aqueous sodium carbonate or sodium bicarbonate aqueous solution.
9. according to claim 1 suitable-preparation method of N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides, it is characterized in that acylating reagent is SOCl
2
10. according to claim 1 suitable-preparation method of N-(4-hydroxyl-3-methoxy-benzyl)-8-methyl-5-nonene acid amides, it is characterized in that describedly 1, through the reduction gained, used reductive agent is POTASSIUM BOROHYDRIDE or sodium borohydride to the 5-pentanediol by glutaraldehyde.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010040082A CN101774940A (en) | 2010-01-19 | 2010-01-19 | Para-N-(4-hydroxyl-3-methoxy benzyl)-8-methyl-5-nonene amide and method for preparing same |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102174061A (en) * | 2011-03-08 | 2011-09-07 | 上海统麦生物科技有限公司 | Novel method for synthesizing 4-carboxybutyl triphenyl phosphonium bromide |
| CN113943207A (en) * | 2021-11-23 | 2022-01-18 | 中国成达工程有限公司 | Process for synthesizing butanediol by hydrogenation of succinaldehyde |
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2010
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102174061A (en) * | 2011-03-08 | 2011-09-07 | 上海统麦生物科技有限公司 | Novel method for synthesizing 4-carboxybutyl triphenyl phosphonium bromide |
| CN113943207A (en) * | 2021-11-23 | 2022-01-18 | 中国成达工程有限公司 | Process for synthesizing butanediol by hydrogenation of succinaldehyde |
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