CN114621121B - Preparation methods and products of camphorsulfonyl hydrazide compounds and their applications - Google Patents
Preparation methods and products of camphorsulfonyl hydrazide compounds and their applications Download PDFInfo
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- CN114621121B CN114621121B CN202210264700.6A CN202210264700A CN114621121B CN 114621121 B CN114621121 B CN 114621121B CN 202210264700 A CN202210264700 A CN 202210264700A CN 114621121 B CN114621121 B CN 114621121B
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- camphorsulfonyl
- hydrazide compounds
- chloride
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- hydrazide
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 84
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 241000209140 Triticum Species 0.000 claims abstract description 15
- 235000021307 Triticum Nutrition 0.000 claims abstract description 14
- 241000233866 Fungi Species 0.000 claims abstract description 12
- 241000196324 Embryophyta Species 0.000 claims abstract description 11
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 claims abstract description 7
- 235000009025 Carya illinoensis Nutrition 0.000 claims abstract description 7
- 241000223218 Fusarium Species 0.000 claims abstract description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 84
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical class CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 56
- BGABKEVTHIJBIW-XVKPBYJWSA-N [(1s,4r)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonyl chloride Chemical compound C1C[C@]2(CS(Cl)(=O)=O)C(=O)C[C@H]1C2(C)C BGABKEVTHIJBIW-XVKPBYJWSA-N 0.000 claims description 34
- 238000006243 chemical reaction Methods 0.000 claims description 31
- 239000007787 solid Substances 0.000 claims description 22
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- JOVOSQBPPZZESK-UHFFFAOYSA-N phenylhydrazine hydrochloride Chemical class Cl.NNC1=CC=CC=C1 JOVOSQBPPZZESK-UHFFFAOYSA-N 0.000 claims description 8
- 229940038531 phenylhydrazine hydrochloride Drugs 0.000 claims description 8
- 241000233616 Phytophthora capsici Species 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 239000012141 concentrate Substances 0.000 claims description 6
- FYSSYOCJFZSKNW-UHFFFAOYSA-N hydron;naphthalen-1-ylhydrazine;chloride Chemical compound [Cl-].C1=CC=C2C(N[NH3+])=CC=CC2=C1 FYSSYOCJFZSKNW-UHFFFAOYSA-N 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 4
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 2
- 241001453450 Carya illinoinensis Species 0.000 claims 1
- 244000068645 Carya illinoensis Species 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 4
- 235000002566 Capsicum Nutrition 0.000 abstract description 3
- 239000006002 Pepper Substances 0.000 abstract description 3
- 241000233614 Phytophthora Species 0.000 abstract description 3
- 235000016761 Piper aduncum Nutrition 0.000 abstract description 3
- 235000017804 Piper guineense Nutrition 0.000 abstract description 3
- 244000203593 Piper nigrum Species 0.000 abstract description 3
- 235000008184 Piper nigrum Nutrition 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 130
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 239000002994 raw material Substances 0.000 description 23
- 238000004440 column chromatography Methods 0.000 description 21
- 239000012043 crude product Substances 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 12
- 241000723346 Cinnamomum camphora Species 0.000 description 10
- 229930008380 camphor Natural products 0.000 description 9
- 229960000846 camphor Drugs 0.000 description 8
- 238000000967 suction filtration Methods 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 206010039509 Scab Diseases 0.000 description 6
- 238000010586 diagram Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
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- 239000000047 product Substances 0.000 description 5
- 244000061456 Solanum tuberosum Species 0.000 description 4
- 235000002595 Solanum tuberosum Nutrition 0.000 description 4
- -1 cooled to 0°C Chemical compound 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
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- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 235000012015 potatoes Nutrition 0.000 description 3
- 229940085790 synthetic camphor Drugs 0.000 description 3
- QELCWIMDZKOJBU-UHFFFAOYSA-N (2-chloro-4-fluorophenyl)hydrazine;hydrochloride Chemical compound [Cl-].[NH3+]NC1=CC=C(F)C=C1Cl QELCWIMDZKOJBU-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000001293 FEMA 3089 Substances 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001674251 Serpula lacrymans Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 241000589652 Xanthomonas oryzae Species 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- DSSYKIVIOFKYAU-UHFFFAOYSA-N camphor Chemical group C1CC2(C)C(=O)CC1C2(C)C DSSYKIVIOFKYAU-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000000855 fungicidal effect Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- VFZYLSYYMHFPSY-UHFFFAOYSA-N (2-fluoroanilino)azanium;chloride Chemical compound Cl.NNC1=CC=CC=C1F VFZYLSYYMHFPSY-UHFFFAOYSA-N 0.000 description 1
- CRRIAWUJYMLJOE-UHFFFAOYSA-N (3-chlorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=CC(Cl)=C1 CRRIAWUJYMLJOE-UHFFFAOYSA-N 0.000 description 1
- SKVGLOFWEJFQKU-UHFFFAOYSA-N (3-fluorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=CC(F)=C1 SKVGLOFWEJFQKU-UHFFFAOYSA-N 0.000 description 1
- RGGOWBBBHWTTRE-UHFFFAOYSA-N (4-bromophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(Br)C=C1 RGGOWBBBHWTTRE-UHFFFAOYSA-N 0.000 description 1
- YQVZREHUWCCHHX-UHFFFAOYSA-N (4-chlorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(Cl)C=C1 YQVZREHUWCCHHX-UHFFFAOYSA-N 0.000 description 1
- FEKUXLUOKFSMRO-UHFFFAOYSA-N (4-fluorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(F)C=C1 FEKUXLUOKFSMRO-UHFFFAOYSA-N 0.000 description 1
- PBGQZFXOUDOZCB-UHFFFAOYSA-N (4-iodophenyl)hydrazine;hydrochloride Chemical compound [Cl-].[NH3+]NC1=CC=C(I)C=C1 PBGQZFXOUDOZCB-UHFFFAOYSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 description 1
- 239000001686 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one Substances 0.000 description 1
- IYDMICQAKLQHLA-UHFFFAOYSA-N 1-phenylnaphthalene Chemical group C1=CC=CC=C1C1=CC=CC2=CC=CC=C12 IYDMICQAKLQHLA-UHFFFAOYSA-N 0.000 description 1
- ADODRSVGNHNKAT-UHFFFAOYSA-N 2-Chlorophenylhydrazine hydrochloride Chemical compound Cl.NNC1=CC=CC=C1Cl ADODRSVGNHNKAT-UHFFFAOYSA-N 0.000 description 1
- DGOAXBPOVUPPEB-UHFFFAOYSA-N 3-(difluoromethyl)-N-methoxy-1-methyl-N-[1-(2,4,6-trichlorophenyl)propan-2-yl]pyrazole-4-carboxamide Chemical compound C=1N(C)N=C(C(F)F)C=1C(=O)N(OC)C(C)CC1=C(Cl)C=C(Cl)C=C1Cl DGOAXBPOVUPPEB-UHFFFAOYSA-N 0.000 description 1
- UXDLLFIRCVPPQP-UHFFFAOYSA-N 4-hydrazinylbenzonitrile;hydrochloride Chemical compound [Cl-].[NH3+]NC1=CC=C(C#N)C=C1 UXDLLFIRCVPPQP-UHFFFAOYSA-N 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 241000123650 Botrytis cinerea Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000035240 Disease Resistance Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000005782 Fluopicolide Substances 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 240000007049 Juglans regia Species 0.000 description 1
- 235000009496 Juglans regia Nutrition 0.000 description 1
- 241000218195 Lauraceae Species 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 241000233622 Phytophthora infestans Species 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 241000221696 Sclerotinia sclerotiorum Species 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- OPIOKSFIERNABH-UHFFFAOYSA-N [3,5-bis(trifluoromethyl)anilino]azanium;chloride Chemical compound Cl.NNC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 OPIOKSFIERNABH-UHFFFAOYSA-N 0.000 description 1
- KQXZVSQCMVKMBK-UHFFFAOYSA-N [4-(trifluoromethoxy)phenyl]hydrazine;hydrochloride Chemical compound Cl.NNC1=CC=C(OC(F)(F)F)C=C1 KQXZVSQCMVKMBK-UHFFFAOYSA-N 0.000 description 1
- WCAGNYIHAYOPSE-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical compound [Cl-].[NH3+]NC1=CC=C(C(F)(F)F)C=C1 WCAGNYIHAYOPSE-UHFFFAOYSA-N 0.000 description 1
- 230000009418 agronomic effect Effects 0.000 description 1
- ZWWXDCOPVYATOQ-UHFFFAOYSA-N amino-(4-nitrophenyl)azanium;chloride Chemical compound [Cl-].N[NH2+]C1=CC=C([N+]([O-])=O)C=C1 ZWWXDCOPVYATOQ-UHFFFAOYSA-N 0.000 description 1
- BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 244000000005 bacterial plant pathogen Species 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001604 bicyclic monoterpene derivatives Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960000411 camphor oil Drugs 0.000 description 1
- 239000010624 camphor oil Substances 0.000 description 1
- 239000002361 compost Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- GBOYJIHYACSLGN-UHFFFAOYSA-N fluopicolide Chemical compound ClC1=CC(C(F)(F)F)=CN=C1CNC(=O)C1=C(Cl)C=CC=C1Cl GBOYJIHYACSLGN-UHFFFAOYSA-N 0.000 description 1
- 244000053095 fungal pathogen Species 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- ADTJGIMHXSBSPS-UHFFFAOYSA-N hydron;(2,4,6-trichlorophenyl)hydrazine;chloride Chemical compound Cl.NNC1=C(Cl)C=C(Cl)C=C1Cl ADTJGIMHXSBSPS-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000000077 insect repellent Substances 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- HCOVEUUIZWEZBK-UHFFFAOYSA-N n-(2,2-diethoxyethyl)formamide Chemical compound CCOC(OCC)CNC=O HCOVEUUIZWEZBK-UHFFFAOYSA-N 0.000 description 1
- 239000000618 nitrogen fertilizer Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000017260 vegetative to reproductive phase transition of meristem Effects 0.000 description 1
- 235000020234 walnut Nutrition 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/48—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups having nitrogen atoms of sulfonamide groups further bound to another hetero atom
- C07C311/49—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups having nitrogen atoms of sulfonamide groups further bound to another hetero atom to nitrogen atoms
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N41/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom
- A01N41/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom containing a sulfur-to-oxygen double bond
- A01N41/04—Sulfonic acids; Derivatives thereof
- A01N41/06—Sulfonic acid amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/38—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
- C07D213/77—Hydrazine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dentistry (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Agronomy & Crop Science (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了樟脑磺酰肼类化合物的制备方法和产品及其应用，所述樟脑磺酰肼类化合物结构式如下所示：所述樟脑磺酰肼类化合物在防治农业或林业的植物真菌的应用，活性结果表明：本发明所提供的化合物对小麦赤霉病菌，辣椒疫霉病菌和山核桃干腐病菌有较好的防治效果。
The present invention discloses a preparation method and product of a camphorsulfonylhydrazide compound and application thereof. The camphorsulfonylhydrazide compound has a structural formula as shown below: The camphorsulfonylhydrazide compounds are used in preventing and controlling plant fungi in agriculture or forestry. The activity results show that the compounds provided by the present invention have good control effects on wheat fusarium, pepper phytophthora and pecan dry rot.
Description
技术领域Technical field
本发明属于农药合成技术领域，具体涉及到樟脑磺酰肼类化合物的制备方法和产品及其应用。The invention belongs to the technical field of pesticide synthesis, and specifically relates to preparation methods and products of camphorsulfonyl hydrazide compounds and their applications.
背景技术Background technique
小麦赤霉病是危害小麦生长的主要病害。小麦赤霉病可引起引起苗枯、穗腐、茎基腐、秆腐和穗腐，从幼苗到抽穗都可受害，需要及时防治。Wheat fusarium head blight is a major disease that harms wheat growth. Wheat fusarium head blight can cause seedling blight, ear rot, stem base rot, stalk rot and ear rot, and can harm the entire wheat plant from seedling to heading, so timely prevention and control is required.
小麦赤霉病防治方法：Methods for preventing and controlling wheat scab:
(1)选用抗(耐)病品种：目前虽未找到免疫品种，但有一些农艺性状良好的耐病品种，如苏麦3号、苏麦2号等。春小麦有定丰3号、宁春24号。各地可因地制宜地选用。(1) Select disease-resistant (tolerant) varieties: Although no immune varieties have been found yet, there are some disease-resistant varieties with good agronomic properties, such as Sumai No. 3, Sumai No. 2, etc. Spring wheat includes Dingfeng 3 and Ningchun 24. Each place can choose according to local conditions.
(2)农业防治：合理排灌，湿地要开沟排水。收获后要深耕灭茬，减少菌源。适时播种，避开扬花期遇雨。提倡施用酵素菌沤制的堆肥，采用配方施肥技术，合时施肥，忌偏施氮肥，提高植株抗病力。(2) Agricultural prevention and control: Reasonable drainage and irrigation, and ditches should be dug in wetlands for drainage. After harvesting, it is necessary to plow deeply to eliminate stubble and reduce the source of bacteria. Sow seeds at the right time to avoid rain during the flowering period. It is recommended to use compost made by enzyme bacteria, adopt formula fertilization technology, apply fertilizer at the right time, and avoid excessive application of nitrogen fertilizer to improve plant disease resistance.
在另一方面，近年来，萜类化合物在医用或者农用领域的研究备受广泛关注，作为林产重要资源的樟脑，是一种具有双环单萜结构的非木质林产品，天然存在于樟科植物中，是我国的可再生天然优势生物质资源，其IUPAC名称为1,7,7-三甲基二环[2.2.1]庚烷-2-酮，化学式为C10H16O。室温下为白色或透明的蜡状固体，可用于驱虫。樟脑提炼自樟树干中，树龄越老的的樟树所富含樟脑比例越多。提炼方法为将树干切成小块用水蒸馏，樟脑油受热后随着水蒸汽上升，在接触到预先放置在上方的陶缸冷却后便可形成樟脑。在中药成方制剂中主要利用其具有清凉、芳香及温散止痛的功效。常入橡胶膏剂、酊剂、膏药、油剂、软膏剂。因此，樟脑在医药中间体、环境友好型防虫蛀剂、香料、熏香、工业原料等领域内得到了广泛的应用。On the other hand, in recent years, research on terpenoids in the medical or agricultural fields has attracted widespread attention. As an important forest resource, camphor is a non-wood forest product with a bicyclic monoterpene structure that naturally exists in Lauraceae plants. , is China's renewable natural dominant biomass resource, its IUPAC name is 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one, and its chemical formula is C 10 H 16 O. It is a white or transparent waxy solid at room temperature and can be used to repel insects. Camphor is extracted from the trunk of the camphor tree. The older the camphor tree, the more camphor it contains. The extraction method is to cut the tree trunk into small pieces and distill it with water. After the camphor oil is heated, the water vapor rises. After contacting the pottery jar placed above and cooling, camphor can be formed. It is mainly used in traditional Chinese medicine preparations for its cooling, aromatic, warming and analgesic effects. Often used in rubber pastes, tinctures, plasters, oils, and ointments. Therefore, camphor has been widely used in the fields of pharmaceutical intermediates, environmentally friendly insect repellents, spices, incense, industrial raw materials and other fields.
天然来源的樟脑由于资源匮乏及保护等原因已经远不能满足日益扩大的樟脑市场需求，因此，以松节油为原料生产的合成樟脑应运而生。由于松节油资源丰富，合成樟脑与天然樟脑在化学性质及应用性能等方面没有本质区别，合成樟脑完全可以替代天然樟脑使用。Camphor from natural sources can no longer meet the growing market demand for camphor due to resource scarcity and protection reasons. Therefore, synthetic camphor produced from turpentine oil has emerged. Due to the abundance of turpentine oil resources, there is no essential difference between synthetic camphor and natural camphor in terms of chemical properties and application performance. Synthetic camphor can completely replace natural camphor.
本发明所提供的樟脑磺酰肼类化合物的制备方法与杀菌方面的应用尚未报道。The preparation method and bactericidal application of the camphorsulfonyl hydrazide compounds provided by the present invention have not been reported yet.
发明内容Summary of the invention
本部分的目的在于概述本发明的实施例的一些方面以及简要介绍一些较佳实施例。在本部分以及本申请的说明书摘要和发明名称中可能会做些简化或省略以避免使本部分、说明书摘要和发明名称的目的模糊，而这种简化或省略不能用于限制本发明的范围。The purpose of this section is to outline some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section, the abstract and the title of the invention to avoid obscuring the purpose of this section, the abstract and the title of the invention, and such simplifications or omissions cannot be used to limit the scope of the invention.
鉴于上述和/或现有技术中存在的问题，提出了本发明。In view of the above and/or problems existing in the prior art, the present invention is proposed.
因此，本发明的目的是，克服现有技术中的不足，提供樟脑磺酰肼类化合物。Therefore, the object of the present invention is to overcome the deficiencies in the prior art and provide camphorsulfonyl hydrazide compounds.
为解决上述技术问题，本发明提供了如下技术方案：樟脑磺酰肼类化合物，所述樟脑磺酰肼类化合物结构式如下所示：In order to solve the above technical problems, the present invention provides the following technical solution: camphorsulfonyl hydrazide compounds, the structural formula of the camphorsulfonyl hydrazide compounds is as follows:
其中， in,
本发明的再一个目的是，克服现有技术中的不足，提供樟脑磺酰肼类化合物的制备方法。Another object of the present invention is to overcome the deficiencies in the prior art and provide a preparation method for camphorsulfonyl hydrazide compounds.
为解决上述技术问题，本发明提供了如下技术方案：樟脑磺酰肼类化合物的制备方法，包括，L-10-樟脑磺酸与氯化亚砜反应合成L-10-樟脑磺酰氯中间体；In order to solve the above technical problems, the present invention provides the following technical solution: a method for preparing camphorsulfonyl hydrazide compounds, including reacting L-10-camphorsulfonic acid with thionyl chloride to synthesize an L-10-camphorsulfonyl chloride intermediate;
L-10-樟脑磺酰氯中间体与取代苯肼盐酸盐、三乙胺和4-二甲氨基吡啶反应，合成樟脑磺酰肼类化合物I-1～I-18；The L-10-camphorsulfonyl chloride intermediate reacts with substituted phenylhydrazine hydrochloride, triethylamine and 4-dimethylaminopyridine to synthesize camphorsulfonyl hydrazide compounds I-1 to I-18;
L-10-樟脑磺酰氯中间体与1-萘肼盐酸盐、三乙胺和4-二甲氨基吡啶反应合成樟脑磺酰肼类化合物I-19。L-10-camphorsulfonyl chloride intermediate was reacted with 1-naphthylhydrazine hydrochloride, triethylamine and 4-dimethylaminopyridine to synthesize camphorsulfonyl hydrazide compound I-19.
作为本发明所述樟脑磺酰肼类化合物的制备方法的一种优选方案，其中：L-10-樟脑磺酰氯中间体，其制备方法，包括，As a preferred embodiment of the preparation method of camphorsulfonyl hydrazide compounds of the present invention, wherein: L-10-camphorsulfonyl chloride intermediate, its preparation method includes,
单口瓶中加入L-10-樟脑磺酸3.0mmol并加入氯化亚砜3.3mmol溶解，升温至回流温度反应5h，冷却，浓缩除去大部分溶剂和HCl，得白色固体L-10-樟脑磺酰氯。Add 3.0 mmol of L-10-camphorsulfonic acid to the single-neck bottle and add 3.3 mmol of thionyl chloride to dissolve, raise the temperature to the reflux temperature and react for 5 hours, cool and concentrate to remove most of the solvent and HCl to obtain white solid L-10-camphorsulfonyl chloride. .
作为本发明所述樟脑磺酰肼类化合物的制备方法的一种优选方案，其中：中间体L-10-樟脑磺酰氯与取代苯肼盐酸盐的投料摩尔比为1.1:1。As a preferred embodiment of the preparation method of camphorsulfonyl hydrazide compounds of the present invention, the molar ratio of the intermediate L-10-camphorsulfonyl chloride to substituted phenylhydrazine hydrochloride is 1.1:1.
作为本发明所述樟脑磺酰肼类化合物的制备方法的一种优选方案，其中：取代苯肼盐酸盐与三乙胺投料摩尔比为1:1.1。As a preferred embodiment of the preparation method of camphorsulfonyl hydrazide compounds of the present invention, the molar ratio of substituted phenylhydrazine hydrochloride to triethylamine is 1:1.1.
作为本发明所述樟脑磺酰肼类化合物的制备方法的一种优选方案，其中：L-10-樟脑磺酰氯中间体与4-二甲氨基吡啶的摩尔比为1.1:0.1。As a preferred embodiment of the preparation method of camphorsulfonyl hydrazide compounds of the present invention, the molar ratio of L-10-camphorsulfonyl chloride intermediate to 4-dimethylaminopyridine is 1.1:0.1.
作为本发明所述樟脑磺酰肼类化合物的制备方法的一种优选方案，其中：合成樟脑磺酰肼类化合物I-1～I-18，其中，合成反应温度为25℃，反应时间为5-10h；反应合成樟脑磺酰肼类化合物I-19，其反应温度为25℃，反应时间为5-10h。As a preferred embodiment of the preparation method of camphorsulfonyl hydrazide compounds of the present invention, camphorsulfonyl hydrazide compounds I-1 to I-18 are synthesized, wherein the synthesis reaction temperature is 25°C and the reaction time is 5 -10h; react to synthesize camphorsulfonyl hydrazide compound I-19, the reaction temperature is 25°C, and the reaction time is 5-10h.
作为本发明所述樟脑磺酰肼类化合物的制备方法的一种优选方案，其中：中间体L-10-樟脑磺酰氯与1-萘肼盐酸盐的投料摩尔比为1.1:1。As a preferred embodiment of the preparation method of camphorsulfonyl hydrazide compounds of the present invention, the molar ratio of the intermediate L-10-camphorsulfonyl chloride and 1-naphthylhydrazine hydrochloride is 1.1:1.
本发明的另一个目的是，克服现有技术中的不足，提供樟脑磺酰肼类化合物在防治农业或林业的植物真菌的应用，所述植物真菌包括小麦赤霉病菌，辣椒疫霉病菌和山核桃干腐病菌。Another object of the present invention is to overcome the deficiencies in the prior art and provide the application of camphorsulfonyl hydrazide compounds in preventing and controlling plant fungi in agriculture or forestry. The plant fungi include Fusarium tritici, Phytophthora capsici and Phytophthora capsici. Walnut dry rot fungus.
本发明有益效果：Beneficial effects of the present invention:
(1)本发明所述樟脑磺酰肼类化合物，分子结构新颖，均为新化合物；化学结构特征鲜明，结构式中含有磺酰肼，其中取代苯(萘)基基团与樟脑磺酸通过磺酰肼键相连接；所述的化合物的制备方法简便，原料易得，反应条件易控，尤其在合成樟脑磺酰肼类化合物这步反应中，产物经柱层析即可得到。(1) The camphorsulfonyl hydrazide compounds of the present invention have novel molecular structures and are all new compounds; the chemical structure has distinct characteristics, and the structural formula contains sulfonyl hydrazide, in which the substituted phenyl (naphthalene) group and camphorsulfonic acid pass through the sulfonate. The compounds are connected by hydrazide bonds; the preparation method of the compound is simple, the raw materials are easily available, and the reaction conditions are easy to control. Especially in the reaction step of synthesizing camphorsulfonyl hydrazide compounds, the product can be obtained by column chromatography.
(2)本发明所述的化合物是一种在农业或林业领域的防治植物真菌的药剂，这种药剂对于小麦赤霉病菌，辣椒疫霉病菌和山核桃干腐病菌和有较好的防治效果。(2) The compound of the present invention is an agent for preventing and treating plant fungi in the field of agriculture or forestry. This agent has a good control effect on wheat scab, Phytophthora capsici and pecan dry rot. .
附图说明BRIEF DESCRIPTION OF THE DRAWINGS
为了更清楚地说明本发明实施例的技术方案，下面将对实施例描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动性的前提下，还可以根据这些附图获得其它的附图。其中：In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present invention. Those of ordinary skill in the art can also obtain other drawings based on these drawings without exerting any creative effort. in:
图1为本发明实施例中樟脑磺酰肼类化合物I-1～I-18制备方法示意图。Figure 1 is a schematic diagram of the preparation method of camphorsulfonyl hydrazide compounds I-1 to I-18 in the embodiment of the present invention.
图2为本发明实施例中樟脑磺酰肼类化合物I-19制备方法示意图。Figure 2 is a schematic diagram of the preparation method of camphorsulfonyl hydrazide compound I-19 in the embodiment of the present invention.
图3为本发明实施例中化合物I-11对小麦赤霉病菌的离体实验(平板)示意图(从左至右浓度依次为0.781mg/L,0.195mg/L,0.049mg/L,0.012mg/L和0.003mg/L)。Figure 3 is a schematic diagram of the in vitro experiment (plate) of compound I-11 against wheat scab fungus in the embodiment of the present invention (the concentration from left to right is 0.781mg/L, 0.195mg/L, 0.049mg/L, 0.012mg /L and 0.003mg/L).
具体实施方式Detailed ways
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合说明书实施例对本发明的具体实施方式做详细的说明。In order to make the above-mentioned objects, features and advantages of the present invention more obvious and understandable, the specific implementation modes of the present invention will be described in detail below in conjunction with the examples in the description.
在下面的描述中阐述了很多具体细节以便于充分理解本发明，但是本发明还可以采用其他不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似推广，因此本发明不受下面公开的具体实施例的限制。Many specific details are set forth in the following description to fully understand the present invention. However, the present invention can also be implemented in other ways different from those described here. Those skilled in the art can do so without departing from the connotation of the present invention. Similar generalizations are made, and therefore the present invention is not limited to the specific embodiments disclosed below.
其次，此处所称的“一个实施例”或“实施例”是指可包含于本发明至少一个实现方式中的特定特征、结构或特性。在本说明书中不同地方出现的“在一个实施例中”并非均指同一个实施例，也不是单独的或选择性的与其他实施例互相排斥的实施例。Second, reference herein to "one embodiment" or "an embodiment" refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. "In one embodiment" appearing in different places in this specification does not all refer to the same embodiment, nor is it a separate or selective embodiment that is mutually exclusive with other embodiments.
将取代苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应5-10h。Dissolve substituted phenylhydrazine hydrochloride (1.0 mmol), 4-dimethylaminopyridine (0.1 mmol), and triethylamine (1.1 mmol) in anhydrous dichloromethane, cool to 0°C, add L-10-camphorsulfonyl chloride (1.1 mol) in batches, and heat to 25°C for reaction for 5-10 hours.
TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-1～I-18。樟脑磺酰肼类化合物I-1～I-18制备方法示意图，见图1。TLC monitored the complete reaction of the raw materials. The organic layer was washed three times with water (8ml*3) and saturated brine three times (8mL*3). It was dried, filtered, and concentrated to remove methylene chloride. The crude product was subjected to column chromatography (CH2Cl2: MeOH=20:1) to obtain target compounds I-1 to I-18. The schematic diagram of the preparation method of camphorsulfonyl hydrazide compounds I-1 to I-18 is shown in Figure 1.
本发明中L-10-樟脑磺酸，4-二甲氨基吡啶和三乙胺，取代苯肼盐酸盐均购自上海毕得科技有限公司；氯化亚砜购自天津光复精细化工厂；其他原料，均为普通市售产品。In the present invention, L-10-camphorsulfonic acid, 4-dimethylaminopyridine and triethylamine, and substituted phenylhydrazine hydrochloride are all purchased from Shanghai Bide Technology Co., Ltd.; sulfoxide chloride is purchased from Tianjin Guangfu Fine Chemical Factory; Other raw materials are all common commercially available products.
实施例1Example 1
2-氯苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应5h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-1.白色固体，m.p.150–151℃,收率：60％.1H NMR(600MHz,CDCl3)δ7.38(dd,J＝8.2,1.3Hz,1H),7.25(d,J＝1.2Hz,1H),7.21(t,J＝8.4Hz,2H),6.85–6.82(m,1H),6.45(s,1H),3.79(d,J＝15.5Hz,1H),2.90(d,J＝15.5Hz,1H),2.49–2.44(m,1H),2.35–2.30(m,1H),2.18(t,J＝4.5Hz,1H),2.10–2.04(m,1H),1.99(J＝18.8Hz,1H),1.89–1.84(m,1H),1.52–1.47(m,1H),1.03(s,3H),0.94(s,3H).13C NMR(150MHz,CDCl3)δ218.84,143.07,129.08,127.88,121.35,118.57,115.14,59.06,49.46,46.65,43.07,42.68,27.13,26.12,19.85,19.35.Dissolve 2-chlorophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) in anhydrous dichloromethane, cool to 0°C, and add L- in batches 10-camphorsulfonyl chloride (1.1mol), raise to 25°C and react for 5 hours. TLC monitors that the raw material reaction is complete. Wash the organic layer with water 3 times (8ml*3), wash with saturated brine 3 times (8mL*3), and dry. Suction filtration, concentration to remove methylene chloride, and the crude product was subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain target compound I-1. White solid, mp 150–151°C, yield: 60%. 1 H NMR (600MHz, CDCl 3 )δ7.38(dd,J＝8.2,1.3Hz,1H),7.25(d,J＝1.2Hz,1H),7.21(t,J＝8.4Hz,2H),6.85–6.82( m,1H),6.45(s,1H),3.79(d,J＝15.5Hz,1H),2.90(d,J＝15.5Hz,1H),2.49–2.44(m,1H),2.35–2.30(m ,1H),2.18(t,J＝4.5Hz,1H),2.10–2.04(m,1H),1.99(J＝18.8Hz,1H),1.89–1.84(m,1H),1.52–1.47(m, 1H), 1.03 (s, 3H), 0.94 (s, 3H). 13 C NMR (150MHz, CDCL 3 ) Δ218.84,143.07,127.88,121.35, 118.57.14,59.06.46.65,43.07,42.68 ,, 27.13,26.12,19.85,19.35.
实施例2Example 2
4-氰基苯肼盐酸盐(1.0mmol),4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应5.5h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-2.棕色固体，m.p.97–99.5℃,收率65％.1H NMR(600MHz,CDCl3)δ7.52(d,J＝8.2Hz,2H),7.06(d,J＝8.4Hz,2H),6.50(s,1H),3.68(d,J＝15.4Hz,1H),2.90(d,J＝15.4Hz,1H),2.48–2.44(m,1H),2.36–2.31(m,1H),2.20(t,J＝4.4Hz,1H),2.11–2.06(m,1H),2.00(d,J＝18.9Hz,1H),1.84–1.80(m,2H),1.53–1.49(m,1H),1.04(s,3H),0.93(s,3H).13C NMR(150MHz,CDCl3)δ219.30,150.67,133.59,119.57,113.36,103.28,59.03,49.57,46.89,43.06,42.59,27.07,25.92,19.85,19.29.4-Cyanophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane, cooled to 0°C, and added L in batches -10-camphorsulfonyl chloride (1.1mol), raised to 25°C and reacted for 5.5h. TLC monitored the complete reaction of the raw materials. Wash the organic layer with water 3 times (8ml*3) and saturated brine 3 times (8mL*3). Dry, filter, and concentrate to remove dichloromethane. The crude product is subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain target compound I-2. Brown solid, mp97-99.5°C, yield 65%. 1 H NMR (600MHz, CDCl 3 ) δ7.52(d,J＝8.2Hz,2H),7.06(d,J＝8.4Hz,2H),6.50(s,1H),3.68(d,J＝15.4Hz,1H ),2.90(d,J＝15.4Hz,1H),2.48–2.44(m,1H),2.36–2.31(m,1H),2.20(t,J＝4.4Hz,1H),2.11–2.06(m, 1H), 2.00 (d, J＝18.9Hz, 1H), 1.84–1.80 (m, 2H), 1.53–1.49 (m, 1H), 1.04 (s, 3H), 0.93 (s, 3H). 13 C NMR (150MHz, CDCl 3 )δ219.30,150.67,133.59,119.57,113.36,103.28,59.03,49.57,46.89,43.06,42.59,27.07,25.92,19.85,19.29.
实施例3Example 3
4-三氟甲基苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应6h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-3.浅黄色固体，m.p.143–144℃,收率67％.1H NMR(600MHz,CDCl3)δ7.49(d,J＝8.5Hz,2H),7.09(d,J＝8.5Hz,2H),6.90(s,1H),6.44(s,1H),3.70(d,J＝15.5Hz,1H),2.90(d,J＝15.5Hz,1H),2.51–2.41(m,1H),2.37–2.29(m,1H),2.19(t,J＝4.5Hz,1H),2.11–2.05(m,1H),1.99(d,J＝18.8Hz,1H),1.86–1.81(m,1H),1.52–1.48(m,1H),1.03(s,3H),0.93(s,3H).13C NMR(150MHz,CDCl3)δ218.94,149.85(d,J＝5.3Hz),126.47(t,J＝4.8Hz),124.49(q,J＝269.7Hz),122.85(q,J＝31.8Hz),121.64,113.09,59.01,49.42,46.81,43.02,42.60,27.04,25.96,19.79,19.29.4-Trifluoromethylphenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane, cooled to 0°C, and batched Add L-10-camphorsulfonyl chloride (1.1mol), raise to 25°C and react for 6 hours. TLC monitors the complete reaction of the raw materials. Wash the organic layer with water 3 times (8ml*3) and saturated brine 3 times (8ml*3). , dried, suction filtered, concentrated to remove methylene chloride, and the crude product was subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain the target compound I-3. A light yellow solid, mp 143-144°C, yield 67%. 1 H NMR (600MHz, CDCl 3 ) δ7.49 (d, J = 8.5 Hz, 2H), 7.09 (d, J = 8.5 Hz, 2H), 6.90 (s, 1H), 6.44 (s, 1H), 3.70 (d,J＝15.5Hz,1H),2.90(d,J＝15.5Hz,1H),2.51–2.41(m,1H),2.37–2.29(m,1H),2.19(t,J＝4.5Hz, 1H),2.11–2.05(m,1H),1.99(d,J＝18.8Hz,1H),1.86–1.81(m,1H),1.52–1.48(m,1H),1.03(s,3H),0.93 (s, 3H). 13 C NMR (150MHz, CDCl 3 ) δ 218.94, 149.85 (d, J = 5.3Hz), 126.47 (t, J = 4.8Hz), 124.49 (q, J = 269.7Hz), 122.85 (q ,J＝31.8Hz),121.64,113.09,59.01,49.42,46.81,43.02,42.60,27.04,25.96,19.79,19.29.
实施例4Example 4
4-硝基苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应8h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-4.浅黄色固体，m.p.140.7–141℃,收率30.1％.1H NMR(600MHz,CDCl3)δ8.13(d,J＝9.2Hz,2H),7.55–7.29(m,1H),7.05(d,J＝9.2Hz,2H),6.62(s,1H),3.68(d,J＝15.5Hz,1H),2.92(d,J＝15.5Hz,1H),2.48–2.44(m,1H),2.36–2.31(m,1H),2.20(t,J＝4.5Hz,1H),2.11–2.05(m,1H),2.00(d,J＝18.9Hz,1H),1.84–1.79(m,1H),1.53–1.48(m,1H),1.03(s,3H),0.93(s,3H).13C NMR(150MHz,CDCl3)δ219.53,152.50,141.13,125.79,112.39,59.01,49.63,46.84,43.04,42.53,27.04,25.82,19.81,19.26.4-Nitrophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane, cooled to 0°C, and added L in batches -10-camphorsulfonyl chloride (1.1mol), raise to 25℃ and react for 8 hours. TLC monitors that the raw material reaction is complete. Wash the organic layer with water 3 times (8ml*3), wash with saturated brine 3 times (8mL*3), and dry , suction filtration, concentration to remove methylene chloride, and the crude product was subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain the target compound I-4. A light yellow solid, mp 140.7-141°C, yield 30.1%. 1 H NMR (600MHz, CDCl 3 ) δ8.13(d,J＝9.2Hz,2H),7.55–7.29(m,1H),7.05(d,J＝9.2Hz,2H),6.62(s,1H) ,3.68(d,J＝15.5Hz,1H),2.92(d,J＝15.5Hz,1H),2.48–2.44(m,1H),2.36–2.31(m,1H),2.20(t,J＝4.5 Hz,1H),2.11–2.05(m,1H),2.00(d,J＝18.9Hz,1H),1.84–1.79(m,1H),1.53–1.48(m,1H),1.03(s,3H) ,0.93(s,3H). 13 C NMR (150MHz, CDCl 3 ) δ219.53,152.50,141.13,125.79,112.39,59.01,49.63,46.84,43.04,42.53,27.04,25.82,19.81,19.26.
实施例5Example 5
4-氯苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应9h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-5.浅黄色固体，m.p.131–133℃,收率33％.1H NMR(600MHz,CDCl3)δ7.21(d,J＝8.8Hz,2H),6.98(d,J＝8.8Hz,2H),6.40(s,1H),3.70(d,J＝15.5Hz,1H),2.88(d,J＝15.5Hz,1H),2.46–2.42(m,1H),2.34–2.29(m,1H),2.18(t,J＝4.4Hz,1H),2.10–2.04(m,1H),1.98(d,J＝18.8Hz,1H),1.87–1.83(m,1H),1.67(s,1H),1.51–1.47(m,1H),1.03(s,3H),0.92(s,3H).13C NMR(150MHz,CDCl3)δ218.66,145.67,129.01,125.95,115.17,58.99,49.37,46.90,43.02,42.60,27.05,26.03,19.85,19.33.Dissolve 4-chlorophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) in anhydrous dichloromethane, cool to 0°C, and add L- in batches 10-camphorsulfonyl chloride (1.1 mol), raised to 25°C and reacted for 9 hours. TLC monitored that the raw material reaction was complete. The organic layer was washed 3 times with water (8ml*3), washed with saturated brine 3 times (8mL*3), and dried. Suction filtration, concentration to remove methylene chloride, and the crude product was subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain target compound I-5. Light yellow solid, mp 131–133°C, yield 33%. 1 H NMR (600MHz, CDCl 3 ) δ7.21(d,J＝8.8Hz,2H),6.98(d,J＝8.8Hz,2H),6.40(s,1H),3.70(d,J＝15.5Hz,1H) ,2.88(d,J＝15.5Hz,1H),2.46–2.42(m,1H),2.34–2.29(m,1H),2.18(t,J＝4.4Hz,1H),2.10–2.04(m,1H ),1.98(d,J＝18.8Hz,1H),1.87–1.83(m,1H),1.67(s,1H),1.51–1.47(m,1H),1.03(s,3H),0.92(s, 3H). 13 C NMR (150MHz, CDCl 3 ) δ218.66,145.67,129.01,125.95,115.17,58.99,49.37,46.90,43.02,42.60,27.05,26.03,19.85,19.33.
实施例6Example 6
3-氯苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应8h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-6.浅黄色固体，m.p.136.5–139.5℃，收率79.2％.1H NMR(600MHz,CDCl3)δ7.16(t,J＝8.0Hz,1H),7.06(t,J＝2.1Hz,1H),6.91–6.87(m,2H),6.43(s,1H),3.69(d,J＝15.5Hz,1H),2.89(d,J＝15.5Hz,1H),2.46–2.41(m,1H),2.34–2.28(m,1H),2.18(t,J＝4.5Hz,1H),2.10–2.04(m,1H),1.98(d,J＝18.8Hz,1H),1.87–1.82(m,1H),1.51–1.47(m,1H),1.02(s,3H),0.92(s,3H).13C NMR(150MHz,CDCl3)δ218.74,148.29,134.95,130.16,121.16,113.91,111.96,59.00,49.39,46.89,43.01,42.60,27.05,26.01,19.81,19.30.Dissolve 3-chlorophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) in anhydrous dichloromethane, cool to 0°C, and add L- in batches 10-camphorsulfonyl chloride (1.1 mol), raised to 25°C and reacted for 8 hours. TLC monitored the complete reaction of the raw materials. The organic layer was washed 3 times with water (8ml*3), washed with saturated brine 3 times (8mL*3), and dried. Suction filtration, concentration to remove methylene chloride, and the crude product was subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain the target compound I-6. A light yellow solid, mp 136.5-139.5°C, yield 79.2%. 1 H NMR (600MHz, CDCl 3 ) δ7.16 (t, J = 8.0 Hz, 1H), 7.06 (t, J = 2.1 Hz, 1H), 6.91–6.87 (m, 2H), 6.43 (s, 1H), 3.69(d,J＝15.5Hz,1H),2.89(d,J＝15.5Hz,1H),2.46–2.41(m,1H),2.34–2.28(m,1H),2.18(t,J＝4.5Hz ,1H),2.10–2.04(m,1H),1.98(d,J＝18.8Hz,1H),1.87–1.82(m,1H),1.51–1.47(m,1H),1.02(s,3H), 0.92 (s, 3H). 13 C NMR (150MHz, CDCl 3 ) δ218.74,148.29,134.95,130.16,121.16,113.91,111.96,59.00,49.39,46.89,43.01,42.60,27.05,26.01,19. 81,19.30.
实施例7Example 7
4-氟苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应10h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-7.浅黄色固体，m.p.91–93℃.收率51％.1HNMR(600MHz,CDCl3)δ7.07–6.83(m,4H),6.43(s,1H),3.70(d,J＝15.4Hz,1H),2.87(d,J＝15.5Hz,1H),2.46–2.41(m,1H),2.33–2.28(m,1H),2.18(t,J＝4.5Hz,1H),2.10–2.04(m,1H),1.97(d,J＝18.8Hz,1H),1.88–1.84(m,1H),1.51–1.47(m,1H),1.02(s,3H),0.92(s,3H).13C NMR(150MHz,CDCl3)δ218.58,158.03(d,J＝237.5Hz),143.13(d,J＝2.3Hz),115.66(d,J＝22.6Hz),115.41(d,J＝7.8Hz),115.41(d,J＝7.8Hz),59.04,49.37,46.85,43.05,42.64,27.08,26.13,19.85,19.35.4-Fluorophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane, cooled to 0°C, and L- was added in batches 10-camphorsulfonyl chloride (1.1mol), raise to 25°C and react for 10 hours. TLC monitors that the raw material reaction is complete. Wash the organic layer with water 3 times (8ml*3), wash with saturated brine 3 times (8ml*3), and dry. Suction filtration, concentration to remove methylene chloride, and the crude product was subjected to column chromatography (CH 2 Cl 2 :MeOH=20:1) to obtain target compound I-7. Light yellow solid, mp91-93°C. Yield 51%. 1 HNMR ( 600MHz, CDCl 3 )δ7.07–6.83(m,4H),6.43(s,1H),3.70(d,J＝15.4Hz,1H),2.87(d,J＝15.5Hz,1H),2.46–2.41 (m,1H),2.33–2.28(m,1H),2.18(t,J＝4.5Hz,1H),2.10–2.04(m,1H),1.97(d,J＝18.8Hz,1H),1.88– 1.84(m,1H),1.51–1.47(m,1H),1.02(s,3H),0.92(s,3H). 13 C NMR(150MHz, CDCl 3 )δ218.58,158.03(d,J＝237.5Hz) ,143.13(d,J＝2.3Hz),115.66(d,J＝22.6Hz),115.41(d,J＝7.8Hz),115.41(d,J＝7.8Hz),59.04,49.37,46.85,43.05,42.64 ,27.08,26.13,19.85,19.35.
实施例8Example 8
2,4,6-三氯苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应9.5h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-8.白色固体，m.p.128.9–129.5℃.收率90.5％.1H NMR(600MHz,CDCl3)δ7.30(s,2H),7.19(s,1H),6.67(s,1H),3.62(d,J＝15.3Hz,1H),2.83(d,J＝15.4Hz,1H),2.45–2.33(m,2H),2.16(t,J＝4.5Hz,1H),2.08–2.03(m,1H),1.98(d,J＝18.7Hz,1H),1.82–1.77(m,1H),1.50–1.46(m,1H),1.01(s,3H),0.86(s,3H).13C NMR(150MHz,CDCl3)δ217.13,138.93,128.99,128.73,127.55,58.58,48.87,48.03,42.73,42.55,26.97,25.00,19.66,19.38.2,4,6-Trichlorophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane, and the temperature was cooled to 0°C. Add L-10-camphorsulfonyl chloride (1.1mol) in batches, raise to 25°C and react for 9.5h. TLC monitors the complete reaction of the raw materials. Wash the organic layer with water 3 times (8ml*3) and saturated brine 3 times (8mL *3), dried, suction filtered, concentrated to remove methylene chloride, and the crude product was subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain the target compound I-8. White solid, mp 128.9–129.5°C. Collected The rate is 90.5%. 1 H NMR (600MHz, CDCl 3 ) δ7.30 (s, 2H), 7.19 (s, 1H), 6.67 (s, 1H), 3.62 (d, J = 15.3Hz, 1H), 2.83 ( d,J＝15.4Hz,1H),2.45–2.33(m,2H),2.16(t,J＝4.5Hz,1H),2.08–2.03(m,1H),1.98(d,J＝18.7Hz,1H ),1.82–1.77(m,1H),1.50–1.46(m,1H),1.01(s,3H),0.86(s,3H). 13 C NMR (150MHz, CDCl 3 )δ217.13,138.93,128.99,128.73 ,127.55,58.58,48.87,48.03,42.73,42.55,26.97,25.00,19.66,19.38.
实施例9Example 9
4-三氟甲氧基苯肼盐酸盐(1.0mmol),4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应6.5h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-9.米黄色固体，m.p.95–97℃收率30％.1H NMR(600MHz,CDCl3)δ7.11(d,J＝8.7Hz,2H),7.04(d,J＝9.0Hz,2H),6.45(s,1H),3.71(d,J＝15.5Hz,1H),2.88(d,J＝15.5Hz,1H),2.46–2.42(m,1H),2.33–2.29(m,1H),2.18(t,J＝4.4Hz,1H),2.10–2.06(m,1H),1.98(d,J＝18.8Hz,1H),1.88–1.83(m,1H),1.51–1.47(m,1H),1.02(s,3H),0.92(s,3H).13C NMR(150MHz,CDCl3)δ218.91,145.73,143.21(d,J＝1.5Hz),122.22,118.8(q,J＝254.6Hz),114.57,59.01,49.45,46.68,43.03,42.57,27.05,26.04,19.81,19.29.4-Trifluoromethoxyphenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane, cooled to 0°C, and separated. Add L-10-camphorsulfonyl chloride (1.1 mol) in batches, raise to 25°C and react for 6.5 hours. TLC monitors the complete reaction of the raw materials. Wash the organic layer with water 3 times (8ml*3) and saturated brine 3 times (8mL* 3), dry, suction filtrate, concentrate to remove methylene chloride, and the crude product is subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain target compound I-9. Beige solid, mp95-97°C, yield 30% . 1 H NMR (600MHz, CDCl 3 ) δ7.11 (d, J = 8.7Hz, 2H), 7.04 (d, J = 9.0Hz, 2H), 6.45 (s, 1H), 3.71 (d, J = 15.5 Hz,1H),2.88(d,J＝15.5Hz,1H),2.46–2.42(m,1H),2.33–2.29(m,1H),2.18(t,J＝4.4Hz,1H),2.10–2.06 (m,1H),1.98(d,J＝18.8Hz,1H),1.88–1.83(m,1H),1.51–1.47(m,1H),1.02(s,3H),0.92(s,3H). 13 C NMR (150MHz, CDCl 3 ) δ218.91, 145.73, 143.21 (d, J = 1.5Hz), 122.22, 118.8 (q, J = 254.6Hz), 114.57, 59.01, 49.45, 46.68, 43.03, 42.57, 27.05, 26.04 ,19.81,19.29.
实施例10Example 10
4-溴苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应7.5h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-10.米黄色固体，m.p.109–111.5℃，收率20.5％.1H NMR(600MHz,CDCl3)δ7.34(d,J＝8.8Hz,2H),6.93(d,J＝8.8Hz,2H),6.40(s,1H),3.70(d,J＝15.5Hz,1H),2.88(d,J＝15.5Hz,1H),2.46–2.42(m,1H),2.34–2.29(m,1H),2.18(t,J＝4.5Hz,1H),2.10–2.05(m,1H),1.98(d,J＝18.8Hz,1H),1.87–1.82(m,1H),1.51–1.47(m,1H),1.03(s,3H),0.92(s,3H).13C NMR(150MHz,CDCl3)δ218.65,146.20,131.91,115.55,113.20,58.99,49.37,46.79,43.01,42.61,27.05,26.00,19.82,19.33.4-Bromophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane, cooled to 0℃, L-10-camphorsulfonyl chloride (1.1mol) was added in batches, and the temperature was raised to 25℃ for reaction for 7.5h. TLC monitored the complete reaction of the raw materials. The organic layer was washed with water 3 times (8ml*3), saturated brine 3 times (8mL*3), dried, filtered, concentrated to remove dichloromethane, and the crude product was purified by column chromatography (CH 2 Cl 2 :MeOH＝20:1) to obtain the target compound I-10. Beige solid, mp109–111.5℃, yield 20.5％. 1 H NMR (600MHz,CDCl 3 )δ7.34(d,J＝8.8Hz,2H),6.93(d,J＝8.8Hz,2H),6.40(s,1H),3.70(d,J＝15.5Hz,1H),2.88(d,J＝15.5Hz,1H),2.46–2.42(m,1H),2.34–2.29(m,1H),2.18(t,J＝4.5Hz,1H),2.10–2.05(m,1H),1.98(d,J＝18.8Hz,1H),1.87–1.82(m,1H),1.51–1.47(m,1H),1.03(s,3H),0.92(s,3H). 13 C NMR(150MHz,CDCl 3 )δ218.65,146.20,131.91,115.55,113.20,58.99,49.37,46.79,43.01,42.61,27.05,26.00,19.82,19.33.
实施例11Example 11
2-氯-4-氟苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应5.5h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-11.米黄色固体，m.p.133.1–135℃,收率79％.1H NMR(600MHz,CDCl3)δ7.35(dd,J＝9.1,5.3Hz,1H),7.11(s,1H),7.03(dd,J＝8.1,2.8Hz,1H),6.97–6.94(m,1H),6.45(s,1H),3.79(d,J＝15.5Hz,1H),2.89(d,J＝15.5Hz,1H),2.49–2.45(m,1H),2.34–2.29(m,1H),2.19(t,J＝4.5Hz,1H),2.10–2.05(m,1H),1.99(d,J＝18.8Hz,1H),1.88–1.84(m,1H),1.52–1.48(m,1H),1.04(s,3H),0.94(s,3H).13C NMR(150MHz,CDCl3)δ219.13,156.76(d,J＝240.5Hz),139.70,118.58(d,J＝10.5Hz),116.16(d,J＝3.9Hz),116.05(d,J＝13.8Hz),114.76(d,J＝21.9Hz),59.02,49.5,46.41,43.05,42.59,27.08,26.06,19.80,19.29.2-Chloro-4-fluorophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane, cooled to 0℃, L-10-camphorsulfonyl chloride (1.1mol) was added in batches, and the temperature was raised to 25℃ for reaction for 5.5h. TLC monitored the complete reaction of the raw materials. The organic layer was washed with water 3 times (8ml*3), saturated brine 3 times (8mL*3), dried, filtered, concentrated to remove dichloromethane, and the crude product was purified by column chromatography (CH 2 Cl 2 :MeOH＝20:1) to obtain the target compound I-11. Beige solid, mp133.1–135℃, yield 79％. 1 H NMR (600MHz,CDCl 3 )δ7.35(dd,J＝9.1,5.3Hz,1H),7.11(s,1H),7.03(dd,J＝8.1,2.8Hz,1H),6.97–6.94(m,1H),6.45(s,1H),3.79(d,J＝15.5Hz,1H),2.89(d,J＝15.5Hz,1H),2.49–2.45(m,1H),2.34–2.29(m,1H),2.19(t,J＝4.5Hz,1H),2.10–2.05(m,1H),1.99(d,J＝18.8Hz,1H),1.88–1.84(m,1H),1.52–1.48(m,1H),1.04(s,3H),0.94(s,3H). 13 C NMR (150 MHz, CDCl 3 ) δ 219.13, 156.76 (d, J = 240.5 Hz), 139.70, 118.58 (d, J = 10.5 Hz), 116.16 (d, J = 3.9 Hz), 116.05 (d, J = 13.8 Hz), 114.76 (d, J = 21.9 Hz), 59.02, 49.5, 46.41, 43.05, 42.59, 27.08, 26.06, 19.80, 19.29.
实施例12Example 12
3,5-二三氟甲基苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应6.5h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-12.白色固体，m.p.136.5–137.5℃,收率29.0％.1H NMR(600MHz,CDCl3)δ7.45(s,2H),7.38(s,1H),7.18(s,1H),6.48(s,1H),3.71(d,J＝15.6Hz,1H),2.92(d,J＝15.6Hz,1H),2.49–2.45(m,1H),2.37–2.31(m,1H),2.22(t,J＝4.5Hz,1H),2.13–2.07(m,1H),2.01(d,J＝18.9Hz,1H),1.86–1.81(m,1H),1.54–1.50(m,1H),1.04(s,3H),0.95(s,3H).13C NMR(150MHz,CDCl3)δ219.62,148.32,132.4(q,J＝33.0Hz),123.3(q,J＝271.1Hz),120.53,114.17(q,J＝3.8Hz),113.24(d,J＝3.0Hz),59.05,49.65,46.70,43.04,42.54,27.01,25.96,19.75,19.20.3,5-Ditrifluoromethylphenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane and cooled to 0°C. , add L-10-camphorsulfonyl chloride (1.1mol) in batches, raise to 25°C and react for 6.5h. TLC monitors the complete reaction of the raw materials. Wash the organic layer with water 3 times (8ml*3) and saturated brine 3 times ( 8mL*3), dried, suction filtered, concentrated to remove methylene chloride, and the crude product was subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain the target compound I-12. White solid, mp136.5–137.5°C, Yield 29.0%. 1 H NMR (600MHz, CDCl 3 ) δ7.45 (s, 2H), 7.38 (s, 1H), 7.18 (s, 1H), 6.48 (s, 1H), 3.71 (d, J＝ 15.6Hz,1H),2.92(d,J＝15.6Hz,1H),2.49–2.45(m,1H),2.37–2.31(m,1H),2.22(t,J＝4.5Hz,1H),2.13– 2.07(m,1H),2.01(d,J＝18.9Hz,1H),1.86–1.81(m,1H),1.54–1.50(m,1H),1.04(s,3H),0.95(s,3H) . 13 C NMR (150MHz, CDCl 3 ) δ219.62, 148.32, 132.4 (q, J = 33.0Hz), 123.3 (q, J = 271.1Hz), 120.53, 114.17 (q, J = 3.8Hz), 113.24 (d, J＝3.0Hz),59.05,49.65,46.70,43.04,42.54,27.01,25.96,19.75,19.20.
实施例13Example 13
2,4-二氯苯肼盐酸盐(1.0mmol),4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应6h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-13.米黄色固体，m.p.125–126.5℃,收率76.1％.1H NMR(600MHz,CDCl3)δ7.32(d,J＝8.8Hz,1H),7.25(s,2H),7.18(dd,J＝8.8,2.2Hz,1H),6.44(s,1H),3.77(d,J＝15.5Hz,1H),2.89(d,J＝15.5Hz,1H),2.49–2.45(m,1H),2.35–2.30(m,1H),2.19(t,J＝4.4Hz,1H),2.11–2.01(m,1H),1.99(d,J＝18.9Hz,1H),1.87–1.82(m,1H),1.52–1.48(m,1H),1.04(s,3H),0.94(s,3H).13C NMR(150MHz,CDCl3)δ219.14,141.96,128.61,127.94,125.42,118.78,115.94,77.00,59.03,49.52,46.54,43.05,42.62,27.09,26.04,19.81,19.29.2,4-Dichlorophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane, cooled to 0°C, and batched Add L-10-camphorsulfonyl chloride (1.1mol), raise to 25°C and react for 6 hours. TLC monitors the complete reaction of the raw materials. Wash the organic layer with water 3 times (8ml*3) and saturated brine 3 times (8ml*3). , dried, suction filtered, concentrated to remove methylene chloride, and the crude product was subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain target compound I-13. Beige solid, mp 125-126.5°C, yield 76.1%. 1 H NMR (600MHz, CDCl 3 ) δ7.32 (d, J = 8.8 Hz, 1H), 7.25 (s, 2H), 7.18 (dd, J = 8.8, 2.2 Hz, 1H), 6.44 (s, 1H) ,3.77(d,J＝15.5Hz,1H),2.89(d,J＝15.5Hz,1H),2.49–2.45(m,1H),2.35–2.30(m,1H),2.19(t,J＝4.4 Hz,1H),2.11–2.01(m,1H),1.99(d,J＝18.9Hz,1H),1.87–1.82(m,1H),1.52–1.48(m,1H),1.04(s,3H) ,0.94(s,3H). 13 C NMR (150MHz, CDCl 3 )δ219.14,141.96,128.61,127.94,125.42,118.78,115.94,77.00,59.03,49.52,46.54,43.05,42.62,27.09,26 .04,19.81,19.29 .
实施例14Example 14
4-碘苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应5h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-14.浅黄色固体，m.p.101–103℃.收率70％.1H NMR(600MHz,CDCl3)δ7.52(d,J＝8.6Hz,2H),6.82(d,J＝8.7Hz,2H),6.38(s,1H),3.69(d,J＝15.4Hz,1H),2.87(d,J＝15.4Hz,1H),2.46–2.42(m,1H),2.34–2.29(m,1H),2.18(t,J＝4.4Hz,1H),2.09–2.07(m,1H),1.98(d,J＝18.8Hz,1H),1.86–1.82(m,1H),1.51–1.47m,1H),1.03(s,3H),0.92(s,3H).13C NMR(150MHz,CDCl3)δ218.73,146.84,137.83,115.98,83.04,59.02,49.41,46.86,43.04,42.62,27.08,26.05,19.85,19.33.Dissolve 4-iodophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) in anhydrous dichloromethane, cool to 0°C, and add L- in batches 10-camphorsulfonyl chloride (1.1mol), raise to 25°C and react for 5 hours. TLC monitors that the raw material reaction is complete. Wash the organic layer with water 3 times (8ml*3), wash with saturated brine 3 times (8mL*3), and dry. Suction filtration, concentration to remove methylene chloride, and the crude product was subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain target compound I-14. Light yellow solid, mp 101–103°C. Yield 70%. 1 H NMR (600MHz, CDCl 3 ) δ7.52(d,J＝8.6Hz,2H),6.82(d,J＝8.7Hz,2H),6.38(s,1H),3.69(d,J＝15.4Hz,1H) ,2.87(d,J＝15.4Hz,1H),2.46–2.42(m,1H),2.34–2.29(m,1H),2.18(t,J＝4.4Hz,1H),2.09–2.07(m,1H ),1.98(d,J＝18.8Hz,1H),1.86–1.82(m,1H),1.51–1.47m,1H),1.03(s,3H),0.92(s,3H). 13 C NMR(150MHz , CDCl 3 )δ218.73,146.84,137.83,115.98,83.04,59.02,49.41,46.86,43.04,42.62,27.08,26.05,19.85,19.33.
实施例15Example 15
2,,4-二氟苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应5.5h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-15.黄色固体，m.p.103–105℃,收率65％.1H NMR(600MHz,CDCl3)δ7.36–7.32(m,1H),6.84–6.78(m,2H),6.45(s,1H),3.76(d,J＝15.5Hz,1H),2.89(d,J＝15.5Hz,1H),2.48–2.44(m,1H),2.33–2.27(m,1H),2.19(t,J＝4.5Hz,1H),2.10–2.06(m,1H),1.98(d,J＝18.8Hz,1H),1.90–1.85(m,1H),1.52–1.48(m,1H),1.03(s,3H),0.94(s,3H).13C NMR(150MHz,CDCl3)δ218.89,156.86(d,J＝239.4,10.7Hz),150.31(d,J＝241.5,12.0Hz),131.61(dd,J＝10.5,3.1Hz),116.94(dd,J＝8.9,3.3Hz),111.22(dd,J＝21.9,3.6Hz),103.54(d,J＝22.1Hz),103.36(d,J＝22.2Hz),103.28,59.06,49.45,46.58,43.03,42.64,27.07,26.18,19.84,19.31.2,,4-Difluorophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane, cooled to 0°C, and separated. Add L-10-camphorsulfonyl chloride (1.1 mol) in batches, raise to 25°C and react for 5.5 hours. TLC monitors the complete reaction of the raw materials. Wash the organic layer with water 3 times (8ml*3) and saturated brine 3 times (8mL* 3), dry, suction filtrate, and concentrate to remove methylene chloride. The crude product is subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain target compound I-15. Yellow solid, mp 103-105°C, yield 65% . 1 H NMR (600MHz, CDCl 3 ) δ7.36–7.32(m,1H),6.84–6.78(m,2H),6.45(s,1H),3.76(d,J＝15.5Hz,1H),2.89 (d,J＝15.5Hz,1H),2.48–2.44(m,1H),2.33–2.27(m,1H),2.19(t,J＝4.5Hz,1H),2.10–2.06(m,1H), 1.98(d,J＝18.8Hz,1H),1.90–1.85(m,1H),1.52–1.48(m,1H),1.03(s,3H),0.94(s,3H). 13 C NMR(150MHz, CDCl 3 )δ218.89,156.86(d,J＝239.4,10.7Hz),150.31(d,J＝241.5,12.0Hz),131.61(dd,J＝10.5,3.1Hz),116.94(dd,J＝8.9,3.3 Hz),111.22(dd,J＝21.9,3.6Hz),103.54(d,J＝22.1Hz),103.36(d,J＝22.2Hz),103.28,59.06,49.45,46.58,43.03,42.64,27.07,26.18 ,19.84,19.31.
实施例16Example 16
2-吡啶肼盐酸盐(1.0mmol),4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应6h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-16.黄色固体，m.p.163–165℃,收率69％.1H NMR(600MHz,CDCl3)δ8.11(d,J＝5.9Hz,1H),7.63–7.56(m,1H),7.49(s,1H),7.10(d,J＝8.4Hz,1H),6.81(dd,J＝6.8,4.8Hz,1H),3.80(d,J＝15.5Hz,1H),2.91(d,J＝15.5Hz,1H),2.43–2.39(m,1H),2.26–2.22(m,1H),2.14(t,J＝4.5Hz,1H),2.07–2.01(m,1H),1.97–1.93(m,2H),1.49–1.44(m,1H),1.01(s,3H),0.86(s,3H).13C NMR(150MHz,CDCl3)δ217.72,158.61,146.90,138.57,116.52,108.38,59.17,49.21,47.08,42.98,42.74,27.05,26.45,19.74,19.35.Dissolve 2-pyridine hydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) in anhydrous dichloromethane, cool to 0°C, and add L-10 in batches -Camphorsulfonyl chloride (1.1mol), raise to 25°C and react for 6 hours. TLC monitors that the raw material reaction is complete. Wash the organic layer with water 3 times (8ml*3), wash with saturated brine 3 times (8mL*3), dry and pump Filter, concentrate to remove methylene chloride, and the crude product is subjected to column chromatography (CH 2 Cl 2 :MeOH=20:1) to obtain the target compound I-16. Yellow solid, mp 163-165°C, yield 69%. 1 H NMR (600MHz , CDCl 3 )δ8.11(d,J＝5.9Hz,1H),7.63–7.56(m,1H),7.49(s,1H),7.10(d,J＝8.4Hz,1H),6.81(dd, J＝6.8,4.8Hz,1H),3.80(d,J＝15.5Hz,1H),2.91(d,J＝15.5Hz,1H),2.43–2.39(m,1H),2.26–2.22(m,1H ),2.14(t,J＝4.5Hz,1H),2.07–2.01(m,1H),1.97–1.93(m,2H),1.49–1.44(m,1H),1.01(s,3H),0.86( s,3H). 13 C NMR (150MHz, CDCl 3 ) δ217.72,158.61,146.90,138.57,116.52,108.38,59.17,49.21,47.08,42.98,42.74,27.05,26.45,19.74,19.35.
实施例17Example 17
3-氟苯肼盐酸盐(1.0mmol),4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应6.5h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-17.黄色固体，m.p.139–139.5℃,收率59％.1H NMR(600MHz,CDCl3)δ7.17(td,J＝8.1,6.4Hz,1H),6.84–6.73(m,2H),6.59(td,J＝8.4,2.3Hz,1H),6.49(s,1H),3.69(d,J＝15.4Hz,1H),2.89(d,J＝15.4Hz,1H),2.46–2.41(m,1H),2.33–2.28(m,1H),2.17(t,J＝4.5Hz,1H),2.09–2.03(m,1H),1.97(d,J＝18.8Hz,1H),1.86–1.81(m,1H),1.50–1.46(m,1H),1.02(s,3H),0.91(s,3H).13C NMR(150MHz,CDCl3)δ218.66,163.71(d,J＝243.0Hz),148.96(d,J＝10.2Hz),130.35(d,J＝9.6Hz),109.27(d,J＝2.6Hz),107.76(d,J＝21.4Hz),101.25(d,J＝26.0Hz),77.00,59.00,49.38,46.91,43.01,42.61,27.05,26.02,19.81,19.31.3-Fluorophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane, cooled to 0°C, and L- was added in batches 10-camphorsulfonyl chloride (1.1 mol), raise to 25°C and react for 6.5 hours. TLC monitors that the raw material reaction is complete. Wash the organic layer with water 3 times (8ml*3), wash with saturated brine 3 times (8ml*3), and dry , suction filtration, concentration to remove methylene chloride, and the crude product was subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain target compound I-17. Yellow solid, mp 139–139.5°C, yield 59%. 1 H NMR (600MHz, CDCl 3 ) δ7.17(td,J＝8.1,6.4Hz,1H),6.84–6.73(m,2H),6.59(td,J＝8.4,2.3Hz,1H),6.49(s,1H ),3.69(d,J＝15.4Hz,1H),2.89(d,J＝15.4Hz,1H),2.46–2.41(m,1H),2.33–2.28(m,1H),2.17(t,J＝ 4.5Hz,1H),2.09–2.03(m,1H),1.97(d,J＝18.8Hz,1H),1.86–1.81(m,1H),1.50–1.46(m,1H),1.02(s,3H ), 0.91 (s, 3H). 13 C NMR (150MHz, CDCl 3 ) δ218.66, 163.71 (d, J = 243.0Hz), 148.96 (d, J = 10.2Hz), 130.35 (d, J = 9.6Hz), 109.27(d,J＝2.6Hz),107.76(d,J＝21.4Hz),101.25(d,J＝26.0Hz),77.00,59.00,49.38,46.91,43.01,42.61,27.05,26.02,19.81,19.31.
实施例18Example 18
2-氟苯肼盐酸盐(1.0mmol),4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应6.5h，TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-18.黄色固体，m.p.137.9–138.5℃,收率60％.1H NMR(600MHz,CDCl3)δ7.37(td,J＝8.4,1.6Hz,1H),7.08(t,J＝7.8Hz,1H),7.02–6.99(m,1H),6.86–6.83(m,2H),6.44(s,1H),3.76(d,J＝15.5Hz,1H),2.90(d,J＝15.5Hz,1H),2.48–2.43(m,1H),2.34–2.29(m,1H),2.18(t,J＝4.5Hz,1H),2.10–2.05(m,1H),1.98(d,J＝18.8Hz,1H),1.90–1.85(m,1H),1.51–1.47(m,1H),1.03(s,3H),0.94(s,3H).13C NMR(150MHz,CDCl3)δ218.59,150.83(d,J＝238.4Hz),135.15(d,J＝10.0Hz),124.67(d,J＝3.5Hz),121.03(d,J＝7.0Hz),116.02(d,J＝2.1Hz),114.80(d,J＝17.9Hz),59.03,49.36,46.70,42.99,42.64,27.06,26.11,19.83,19.33.2-Fluorophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) were dissolved in anhydrous dichloromethane, cooled to 0°C, and L- was added in batches 10-camphorsulfonyl chloride (1.1 mol), raise to 25°C and react for 6.5 hours. TLC monitors that the raw material reaction is complete. Wash the organic layer with water 3 times (8ml*3), wash with saturated brine 3 times (8ml*3), and dry , suction filtration, concentration to remove methylene chloride, and the crude product was subjected to column chromatography (CH 2 Cl 2 : MeOH = 20:1) to obtain the target compound I-18. Yellow solid, mp 137.9-138.5°C, yield 60%. 1 H NMR (600MHz, CDCl 3 ) δ7.37(td,J＝8.4,1.6Hz,1H),7.08(t,J＝7.8Hz,1H),7.02–6.99(m,1H),6.86–6.83(m ,2H),6.44(s,1H),3.76(d,J＝15.5Hz,1H),2.90(d,J＝15.5Hz,1H),2.48–2.43(m,1H),2.34–2.29(m, 1H),2.18(t,J＝4.5Hz,1H),2.10–2.05(m,1H),1.98(d,J＝18.8Hz,1H),1.90–1.85(m,1H),1.51–1.47(m , 1H), 1.03 (s, 3H), 0.94 (s, 3H). 13 C NMR (150MHz, CDCl 3 ) δ 218.59, 150.83 (d, J = 238.4Hz), 135.15 (d, J = 10.0Hz), 124.67 (d,J＝3.5Hz),121.03(d,J＝7.0Hz),116.02(d,J＝2.1Hz),114.80(d,J＝17.9Hz),59.03,49.36,46.70,42.99,42.64,27.06 ,26.11,19.83,19.33.
实施例19Embodiment 19
樟脑磺酰肼类化合物I-19方法示意图见图2，具体制备工艺为：The schematic diagram of the method of camphorsulfonyl hydrazide compound I-19 is shown in Figure 2. The specific preparation process is:
将1-萘肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于无水二氯甲烷中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应6h。TLC监测原料反应完全，有机层以水洗涤3次(8ml*3)，饱和食盐水洗涤3次(8mL*3)，干燥，抽滤，浓缩除去二氯甲烷，粗品经柱层析(CH2Cl2:MeOH＝20:1)得目标化合物I-19.棕色固体，m.p.133.8–135.1℃,收率65％.Dissolve 1-naphthylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) in anhydrous dichloromethane, cool to 0°C, and add L- in batches 10-camphorsulfonyl chloride (1.1 mol), raised to 25°C and reacted for 6 hours. TLC monitored the complete reaction of the raw materials. The organic layer was washed three times with water (8ml*3) and saturated brine three times (8mL*3). It was dried, filtered, and concentrated to remove methylene chloride. The crude product was subjected to column chromatography (CH2Cl2: MeOH=20:1) to obtain the target compound I-19. Brown solid, m.p. 133.8-135.1°C, yield 65%.
1H NMR(600MHz,CDCl3)δ7.91(d,J＝8.8Hz,1H),7.84–7.82(m,1H),7.50–7.37(m,5H),6.33(s,1H),3.83(d,J＝15.5Hz,1H),2.93(d,J＝15.5Hz,1H),2.51–2.38(m,2H),2.19(t,J＝4.4Hz,1H),2.10–1.99(m,1H),2.01(d,J＝18.8Hz,1H),1.88–1.83(m,1H),1.52–1.48(m,1H),1.03(s,3H),0.93(s,3H).13C NMR(150MHz,CDCl3)δ218.74,141.75,134.06,128.60,126.24,125.86,125.40,122.66,121.19,119.81,108.61,58.97,49.34,46.98,43.03,42.57,27.05,25.75,19.78,19.33. 1 H NMR (600MHz, CDCl 3 ) δ7.91 (d, J = 8.8Hz, 1H), 7.84–7.82 (m, 1H), 7.50–7.37 (m, 5H), 6.33 (s, 1H), 3.83 ( d,J＝15.5Hz,1H),2.93(d,J＝15.5Hz,1H),2.51–2.38(m,2H),2.19(t,J＝4.4Hz,1H),2.10–1.99(m,1H ), 2.01(d,J＝18.8Hz,1H),1.88–1.83(m,1H),1.52–1.48(m,1H),1.03(s,3H),0.93(s,3H). 13 C NMR( 150MHz, CDCl 3 )δ218.74,141.75,134.06,128.60,126.24,125.86,125.40,122.66,121.19,119.81,108.61,58.97,49.34,46.98,43.03,42.57,27.05 ,25.75,19.78,19.33.
实施例20Embodiment 20
将2-氯-4-氟苯肼盐酸盐(1.0mmol)，4-二甲氨基吡啶(0.1mmol)，三乙胺(1.1mmol)溶解于中，降温至0℃，分批加入L-10-樟脑磺酰氯(1.1mol)，升至25℃反应5.5h。反应经后处理，得化合物I-11，并统计收率。Dissolve 2-chloro-4-fluorophenylhydrazine hydrochloride (1.0mmol), 4-dimethylaminopyridine (0.1mmol), and triethylamine (1.1mmol) in water, cool to 0°C, and add L- in batches 10-camphorsulfonyl chloride (1.1 mol), raised to 25°C and reacted for 5.5 hours. After post-treatment of the reaction, compound I-11 was obtained, and the yield was calculated.
探讨了三种溶剂对酰肼化反应的收率因素，其中以二氯甲烷做溶剂，反应收率最高(79％)；以三氯甲烷做溶剂，收率次之；四氢呋喃做溶剂，收率最低(50％)。故该酰肼化反应使用二氯甲烷作为溶剂最佳。The yield factors of three solvents for the hydrazidation reaction were discussed. Among them, dichloromethane was used as the solvent, and the reaction yield was the highest (79%); chloroform was used as the solvent, and the yield was second; and tetrahydrofuran was used as the solvent, and the yield was the highest (79%). lowest (50%). Therefore, dichloromethane is the best solvent for this hydrazidation reaction.
实施例21Example 21
杀菌活性(离体)实验Bactericidal activity (in vitro) test
本实验中所用的植物真菌为实验室4℃保存的菌种，为番茄灰霉病菌、小麦赤霉病菌、马铃薯晚疫病菌、辣椒疫霉病菌、山核桃干腐病菌、油菜菌核病菌、苹果轮纹病菌和水稻纹枯病菌。采用的培养基为马铃薯琼脂葡萄糖培养基(简称PDA)。PDA培养基配方:马铃薯(去皮)200g，葡萄糖20g，琼脂15g，蒸馏水1000mL，配制方法：将马铃薯洗净去皮，称200g切成小块，加水煮烂(煮沸20-30分钟，能被玻璃棒戳破即可)，用八层纱布过滤于烧杯中，根据实验需要加15–20g琼脂，加入20g葡萄糖，搅拌均匀，充分溶解后稍冷却，补足水至1000mL，分装后121℃灭菌15分钟，冷却后备用。The plant fungi used in this experiment were strains stored at 4°C in the laboratory, including Botrytis cinerea on tomatoes, Fusarium head blight on wheat, Phytophthora infestans on potatoes, Phytophthora capsici, dry rot on pecans, Sclerotinia sclerotiorum on rape, and Apple Xanthomonas oryzae and Xanthomonas oryzae. The medium used was potato agar-dextrose medium (PDA). PDA medium formula: 200g potatoes (peeled), 20g glucose, 15g agar, 1000mL distilled water. Preparation method: wash and peel the potatoes, weigh 200g and cut into small pieces, add water and boil (boil for 20-30 minutes, it can be The glass rod can be pierced), filter it into a beaker with eight layers of gauze, add 15-20g agar according to the experimental needs, add 20g glucose, stir evenly, fully dissolve and then cool slightly, add water to 1000mL, aliquot and sterilize at 121°C Bacteria for 15 minutes, cool and set aside.
实验方法：采用生长速率法。Experimental method: Growth rate method was used.
(1)先将8种植物真菌在PDA平板上25℃培养3-6d左右待用；(1) First culture 8 kinds of plant fungi on a PDA plate at 25°C for about 3-6 days and set aside for use;
(2)将PDA培养基加热溶化，冷却至45–50℃，加入250μL的10g/L浓度的待测化合物制成含50mg/L药液的培养基，并分别倒入培养皿中冷却，氟唑菌酰羟胺(pydiflumetofen)作为阳性对照；(2) Heat and dissolve the PDA culture medium, cool it to 45-50°C, add 250 μL of the compound to be tested at a concentration of 10 g/L to make a culture medium containing 50 mg/L drug solution, and pour it into a petri dish to cool. Pydiflumetofen was used as a positive control;
(3)以无菌操作，用打孔器在培养6d的各菌株菌丝边缘(生长状况尽量一致)打取圆形菌饼(直径0.50cm)，再用接种针挑至含药平板中央，然后将培养皿倒置于培养箱(28℃)中培养；(3) Using aseptic operation, use a hole punch to punch out a round fungus cake (0.50cm in diameter) from the edge of the mycelium of each strain that has been cultured for 6 days (the growth status should be as consistent as possible), and then use an inoculation needle to pick it up to the center of the drug-containing plate. Then place the Petri dish upside down in an incubator (28°C) for cultivation;
(4)于处理后不同时间观察测定菌丝的生长情况，并采用十字交叉法测得直径并处理数据，计算抑制率；(4) Observe and measure the growth of mycelium at different times after treatment, measure the diameter using the cross method and process the data to calculate the inhibition rate;
(5)抑制率(％)＝(对照菌丝直径-处理菌丝直径)/(对照菌丝直径-0.5)×100；(5) Inhibition rate (%) = (control mycelial diameter - treated mycelial diameter) / (control mycelial diameter - 0.5) × 100;
(6)每个处理重复3次。(6) Each treatment was repeated three times.
表1樟脑磺酰肼类化合物对八种农业致病真菌的抑制活性试验结果Table 1 Results of the inhibitory activity test of camphorsulfonylhydrazide compounds against eight agricultural pathogenic fungi
a注:试验中每个处理设三次重复，表中数据为三次重复的平均值。Note: Each treatment was repeated three times in the experiment, and the data in the table are the average values of the three repetitions.
表2部分化合物的EC50值Table 2 EC 50 values of some compounds
实验组I-1～I-19以及对照药剂氟唑菌酰羟胺的杀菌活性测定结果见表1和表2。由表1和表2的结果可见，50mg/L浓度时，化合物I-1～I-19对8种植物真菌显示出不同程度的杀菌活性，部分化合物对辣椒疫霉病菌，小麦赤霉病菌和山核桃干腐病菌有较好的抑制活性；其中，化合物I-6,I-8,I-13在50mg/L浓度下对辣椒疫霉病菌的抑制率达98％；The results of the fungicidal activity determination of the experimental groups I-1 to I-19 and the control agent fluopicolide are shown in Tables 1 and 2. It can be seen from the results in Tables 1 and 2 that at a concentration of 50 mg/L, compounds I-1 to I-19 showed different degrees of fungicidal activity against 8 plant fungi, and some compounds had good inhibitory activity against pepper phytophthora, wheat fusarium and pecan dry rot; among them, compounds I-6, I-8, and I-13 had an inhibition rate of 98% against pepper phytophthora at a concentration of 50 mg/L;
此外，多个化合物对山核桃干腐病菌抑制率达90％以上，与阳性对照氟唑菌酰羟胺相当；对于小麦赤霉病菌，个别化合物如I-1,I-6,I-11,I-13,I-15和I-17对此病菌的抑制率达90％，与阳性对照氟唑菌酰羟胺相当。In addition, multiple compounds inhibited pecan dry rot fungus by more than 90%, which was equivalent to the positive control triflufenac; for wheat scab, individual compounds such as I-1, I-6, I-11, I The inhibition rate of -13, I-15 and I-17 against this pathogen reached 90%, which was equivalent to the positive control triflufenac.
鉴于目标化合物对几种植物病菌具有较好的抑制活性，测试了普筛抑制率较高的化合物的EC50值。部分化合物的EC50列于表2，可以看出，化合物I-1,I-11和I-13对小麦赤霉病菌的EC50值均小于1.0mg/L，化合物I-11的EC50值为0.407mg/L，接近阳性对照氟唑菌酰羟胺(0.296mg/L)。此外，部分化合物对辣椒疫霉病菌的EC50值介于0.9-1.5mg/L之间，接近阳性对照。该系列化合物对几种真菌均有较好的抑制活性，具有开发抗真菌剂的潜力。In view of the fact that the target compound has good inhibitory activity against several plant pathogenic bacteria, the EC 50 value of the compound with a higher general screening inhibition rate was tested. The EC 50 values of some compounds are listed in Table 2. It can be seen that the EC 50 values of compounds I-1, I-11 and I-13 against wheat scab are all less than 1.0 mg/L. The EC 50 value of compound I-11 is It is 0.407mg/L, which is close to the positive control triflufenac (0.296mg/L). In addition, the EC 50 values of some compounds against Phytophthora capsici ranged from 0.9 to 1.5 mg/L, which was close to the positive control. This series of compounds has good inhibitory activity against several fungi and has the potential to develop antifungal agents.
本发明所述含有磺酰肼基的樟脑类化合物，结构区别明显，化学结构特征鲜明，对于防治小麦赤霉病菌、辣椒疫霉病菌和山核桃干腐病菌显示出较好的效果。可用于防治农业或林业植物真菌病害。所述化合物的制备方法简便，收率较高，产物性质稳定。The camphor compound containing a sulfonyl hydrazide group of the present invention has obvious structural differences and distinct chemical structural characteristics, and shows good effects on preventing and treating wheat scab, Phytophthora capsici and pecan dry rot. Can be used to control plant fungal diseases in agriculture or forestry. The preparation method of the compound is simple, the yield is high, and the product properties are stable.
应说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的精神和范围，其均应涵盖在本发明的权利要求范围当中。It should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solution of the present invention can be carried out. Modifications or equivalent substitutions without departing from the spirit and scope of the technical solution of the present invention shall be included in the scope of the claims of the present invention.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH111469A (en) * | 1997-04-14 | 1999-01-06 | Sumitomo Chem Co Ltd | Camphor-based disulfone derivatives, intermediates, production methods and applications |
| JP2002179659A (en) * | 2000-08-23 | 2002-06-26 | Sumika Fine Chemicals Co Ltd | Method for producing camphorsultam |
| CN109232468A (en) * | 2018-11-06 | 2019-01-18 | 南京林业大学 | A kind of camphorsulfonic acid thiosemicarbazones thiazole compound, preparation method and its application |
| CN110003133A (en) * | 2019-03-05 | 2019-07-12 | 上海工程技术大学 | A kind of chiral camphor sulfohydrazide bifunctional catalyst and the preparation method and application thereof |
| WO2020169682A1 (en) * | 2019-02-19 | 2020-08-27 | Yncrea Hauts De France | Hydrazide derivatives and their specific use as antibacterial agents by controlling acinetobacter baumannii bacterium |
| CN111848463A (en) * | 2020-07-08 | 2020-10-30 | 南京林业大学 | Camphor sulfonamide oxime ether compound and its preparation method and application |
-
2022
- 2022-03-17 CN CN202210264700.6A patent/CN114621121B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH111469A (en) * | 1997-04-14 | 1999-01-06 | Sumitomo Chem Co Ltd | Camphor-based disulfone derivatives, intermediates, production methods and applications |
| JP2002179659A (en) * | 2000-08-23 | 2002-06-26 | Sumika Fine Chemicals Co Ltd | Method for producing camphorsultam |
| CN109232468A (en) * | 2018-11-06 | 2019-01-18 | 南京林业大学 | A kind of camphorsulfonic acid thiosemicarbazones thiazole compound, preparation method and its application |
| WO2020169682A1 (en) * | 2019-02-19 | 2020-08-27 | Yncrea Hauts De France | Hydrazide derivatives and their specific use as antibacterial agents by controlling acinetobacter baumannii bacterium |
| CN110003133A (en) * | 2019-03-05 | 2019-07-12 | 上海工程技术大学 | A kind of chiral camphor sulfohydrazide bifunctional catalyst and the preparation method and application thereof |
| CN111848463A (en) * | 2020-07-08 | 2020-10-30 | 南京林业大学 | Camphor sulfonamide oxime ether compound and its preparation method and application |
Non-Patent Citations (2)
| Title |
|---|
| Novel Camphor Sulfonohydrazide and Sulfonamide Derivatives as Potential Succinate Dehydrogenase Inhibitors against Phytopathogenic Fungi/Oomycetes;Yang, Zihui;Journal of Agricultural and Food Chemistry;20221223;第71卷(第1期);第174-185页 * |
| 樟脑酸基双酰肼化合物的合成及其抑菌活性;马献力 等;精细化工;20151231;第32卷(第12期);第1426-1430页 * |
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