CN105693569A - Synthesis method of 3-[4-(methyl sulfonyl)-2-chlorobenzoyl]bicyclo[3.2.1]-2.4-octanedione - Google Patents
Synthesis method of 3-[4-(methyl sulfonyl)-2-chlorobenzoyl]bicyclo[3.2.1]-2.4-octanedione Download PDFInfo
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Abstract
3-[4-(methyl sulfonyl)-2-chlorobenzoyl]bicyclo[3.2.1]-octane-2.4-diketone is an intermediate body for synthesizing rice field herbicide. The invention discloses a method for synthesizing 3-[4-(methyl sulfonyl)-2-chlorobenzoyl]bicycle[3.2.1]-octane-2.4- diketone. The method includes the following steps that norbornene serves as raw materials, 3-cholorine-bicyclo[3.2.1]-3-octene-2-alcohol is generated through addition and ring expansion reaction of dichlorocarbene and hydrothermal reaction; then allyl alcohol is oxidized so that alpha, beta-unsaturated ketone can be prepared; alpha, beta-unsaturated ketone reacts with sodium hydroxide under the action of a catalyst, and bicyclo[3.2.1]-octane-2.4-diketone is obtained, finally, an acylation reaction happens, and a target product is obtained. Raw materials and reagents in use are low in price and easy to obtain, the synthesis method is simple and easy to implement, and reaction conditions are mild.
Description
Technical field
The present invention relates to the synthetic method of a kind of 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2,4-acetyl caproyl, belong to chemical industry and chemical medicine。
Background technology
2-substituted benzoyl-1; hydroresorcinol compound has certain activity of weeding (US5006158; CN85109770); the aryl dicyclo diketone of 3-(sulfenyl)-2-benzoyl hexamethylene-2-ketone and replacement can as weeding active compound (US4762551, EP0338992)。But, Oryza sativa L. is had significantly high phytotoxicity by these compounds, and they are difficult to use as herbicides for use in paddy。Compared with there is activity of weeding with above-mentioned cyclohexadione compounds; annual and the perennial weeds being grown in rice terrace is suffered from a relatively high activity of weeding by the benzoyl cyclic enone 1 replaced; and rice plant is shown very low phytotoxicity (CN1105023A); soil has good mobility and water solublity (CN1105023A; JP10109972A; AU672058B2, JP07082240A)。
A:RS-,RSO2-, RO-；B:X, NO2,R,RSO2-；D:X, RSO2-.
CN1105023A discloses 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] dicyclo [3.2.1]-octane-2; 4-diketone is the intermediate of synthesis herbicides for use in paddy 1; and dicyclo [3.2.1] octane-2; 4-diketone is again synthesis 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] dicyclo [3.2.1]-octane-2; the important intermediate (WO0194339A1, WO0166522A1) of 4-diketone。Synthesize dicyclo [3.2.1] octane-2,4-diketone at present and have following method: make initiation material synthesis dicyclo [3.2.1] octane-2,4-diketone (JP10265441 (A), JP10265415) with norborneol alkanone；With cycle pentadiene dimer for raw material, it is obtained by reacting dicyclo [3.2.1] octane-2,4-diketone (CN1450044A) through 6 steps；Also have with bicyclo-[3.2.1]-2-octene for Material synthesis dicyclo [3.2.1] octane-2,4-diketone (WO2005105717)；Also have document with cyclopentadiene, 1,2,3,3-tetrachloro cyclopropylene and ethylene glycol for raw material, (TetrahedronLett., 2013,54 (6): 557-561) is synthesized through 6 steps；With 1,1,2,2,3-five chlorcyclopropane and cyclopentadiene are raw material, through series reaction, first obtain dicyclo [3.2.1]-6-octene-2,4-diketone, then catalytic hydrogenation synthesis compound dicyclo [3.2.1] octane-2,4-diketone (WO2005123667)。These methods or cost of material is higher, otherwise synthesis step is many, and therefore these methods seem uneconomical。The present invention is with norborene cheap and easy to get for raw material; through simple 4 step reactions; first synthesize dicyclo [3.2.1] octane-2; 4-diketone; then with 4-(methyl sulphonyl)-2-chlorobenzoyl chloride generation acylation reaction; 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] dicyclo [3.2.1]-octane-2,4-diketone are synthesized。
Summary of the invention
It is an object of the invention to provide a kind of 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2; the synthetic method of 4-acetyl caproyl; the method low in raw material price; synthesis step is few; and reaction condition is gentle; yield is high, and environmental pollution is few, is suitable to industrialized production。
The technical solution adopted for the present invention to solve the technical problems is:
The synthetic method of a kind of 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2,4-acetyl caproyl, comprises the following steps:
1) with norborene for initial main material, norborene in the presence of a base, and haloform reaction, obtain 3,4-dichloro dicyclo [3.2.1]-2-octenes (formula III)；
2) the allyl chloride hydrolysis of 3,4-dichloro dicyclo [3.2.1]-2-octenes, obtains 3-chlorine dicyclo [3.2.1]-3-octen-2-ol (formula IV)；
3) 1-propenol-3 of 3-chlorine dicyclo [3.2.1]-3-octen-2-ol is aoxidized under oxidant effect, obtain 3-chlorine dicyclo [3.2.1]-3-octene-2-ketone (formula V)；
4) by 3-chlorine dicyclo [3.2.1]-3-octene-2-ketone under the effect of catalyst and alkali reaction, dicyclo [3.2.1]-2,4-diketone (formula VI) is obtained；
5) dicyclo [3.2.1]-2,4-diketone and 4-(methyl sulphonyl)-2-chlorobenzoyl chloride are reacted, obtain target product 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2,4-acetyl caproyl；
Wherein, step 1) the following reaction mechanism of middle experience: dichlorocarbene and norborene generation additive reaction, the three-membered ring intermediate 1 ' formed takes off chloride ion, obtain carbonium ion 2 ', then three-membered ring open loop, rearrangement reaction occurring, forms more stable carbonium ion 3 ', last carbonium ion 3 ' and chloride binding obtain compound ii。
Compound V changes into compound VI and experiences reaction mechanism possible as follows: first cyano group anion and α, alpha, beta-unsaturated ketone V occurs 1,4 additive reaction, generate intermediate 1', intermediate 1' belongs to allylic nitrile compounds, with sodium hydroxide generation nucleophilic substitution, obtain negative oxygen ion intermediate 2', accepting a proton in methanol, form the intermediate 3' of vinyl alcohol-type, tautomeric transformations becomes intermediate 4', under the effect of alkali, occurring E2 to eliminate reaction, form the intermediate 5' of vinyl alcohol-type, tautomeric transformations becomes keto-acid product VI。
VI belongs to 1,3-cyclohexadione compounds, and methylene, by the joint effect of two carbonyls, has stronger acidity, there is tautomerism。
The absworption peak of the existing keto-acid of proton nmr spectra, also has the absworption peak of enol form。From the area ratio of proton nmr spectra absworption peak, at CDCl3Middle keto-acid accounts for 93%, and enol form accounts for 7%。If VI exists with keto-acid, carbon spectrum only 5 peaks, if only existed with enol form, carbon spectrum only 8 peaks, and the result carbon spectrum measured has 13 peaks, carbon spectrum also illustrates that VI is the dynamic equilibrium of keto-acid and enol form。
Step 5): the preferred aluminum trichloride (anhydrous) of synthesis of compounds I makes catalyst, 1,2-methylene chloride as solvent。The keto-acid of compound VI is converted first into enol form; then the alcoholic extract hydroxyl group in 4-mesyl-2-chlorobenzoyl chloride and enol form is under Catalyzed by Anhydrous Aluminium Chloride; there is acylation reaction; obtain carboxylate; the last reaction occurring like Fries rearrangement under Catalyzed by Anhydrous Aluminium Chloride, the enol obtained becomes compounds I by tautomeric transformations。
If compounds I exists with ketone form structure, then the absworption peak chemical shift of the methine being connected with three carbonyls is estimated at 4.5-5.0ppm。Owing to there is no absworption peak herein, illustrate that compounds I is at CDCl3Solvent does not have ketone form structure, and is entirely enol-type structure。Carbon spectrum absworption peak is 16, also demonstrates that target product is to exist with enol-type structure。Three methylene being connected with end of the bridge chiral carbon atom are all non-equivalence protons, and chemical shift is different, and these three methylene all occurs with the form of multiplet。
Specifically, described step 1) be: with norborene for initial main material, norborene is under alkali existence, quaternary ammonium salt phase-transfer catalysis, with haloform reaction, reaction temperature is 0-100 DEG C, obtains 3,4-dichloro dicyclo [3.2.1]-2-octene, the mol ratio of described norborene and chloroform is 1:1-4, and the mol ratio of described norborene and quaternary ammonium salt is 100:0.1-1, and the mol ratio of described norborene and alkali is 1:1-4。
As preferably, described step 1) in alkali be alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal alcoholates or alkali metal ammonia compound。
As preferably, described step 1) in alkali be NaOH, KOH or Feldalat NM, quaternary ammonium salt is benzyltrimethylammonium chloride, benzyltriethylammoinium chloride or tri-n-octyl methyl ammonium chloride。
Specifically, described step 2) in the allyl chloride of 3,4-dichloro dicyclo [3.2.1]-2-octenes be hydrolyzed in the presence of a base, described alkali is alkali metal hydroxide or alkaline earth metal hydroxide, the mol ratio of described 3,4-dichloro dicyclo [3.2.1]-2-octenes and alkali is 1:1-4。
As preferably, described step 3) in oxidant be metal-oxide, dimethyl sulfoxide, oxygen, Jones reagent or salt。
As preferably, described step 4) in catalyst be potassium cyanide or Cyanogran., the mol ratio of described 3-chlorine dicyclo [3.2.1]-3-octene-2-ketone and catalyst is 100:1-10。
As preferably, described step 4) in alkali be alkali metal hydroxide or alkaline earth metal hydroxide, the mol ratio of described 3-chlorine dicyclo [3.2.1]-3-octene-2-ketone and alkali is 1:1-5。
Specifically; described step 5) it is by dicyclo [3.2.1]-2; 4-diketone and 4-(methyl sulphonyl)-2-chlorobenzoyl chloride react under lewis acid and solvent existent condition; obtain target product 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2; 4-acetyl caproyl; described lewis acid is aluminum chloride, ferric chloride, zinc dichloride or boron trifluoride, and described solvent is 1,2-dichloroethanes, chloroform or dichloromethane。
As preferably, described step 5) in the mol ratio of dicyclo [3.2.1]-2,4-diketone and 4-(methyl sulphonyl)-2-chlorobenzoyl chloride be 1:1-3, dicyclo [3.2.1]-2,4-diketone and lewis acidic mol ratio are 1:1-5。
The invention has the beneficial effects as follows: a kind of 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2 provided by the invention; the synthetic method of 4-acetyl caproyl; the method low in raw material price; synthesis step is few; and reaction condition is gentle; yield is high, and environmental pollution is few, is suitable to industrialized production。
Detailed description of the invention
Embodiment 1
The synthesis of 1.3,4-dichloro dicyclo [3.2.1]-2-octene
Norborene 80.0g (0.848mol) is dissolved in 406.8g (3.408mol) chloroform and 8mL ethanol, add 1.6g (0.0084mol) benzyltrimethylammonium chloride again, it is heated to 50 DEG C, 50% sodium hydrate aqueous solution 272g (3.4mol) is dripped under electric stirring, after adding, mixture is at 50 DEG C of stirring reactions 3 hours, thin layer detection reaction process (developing solvent: petroleum ether)。Mixture is poured in 300g frozen water, extraction into ethyl acetate (400mL × 2)。Organic layer 300mL water washing 1 time, anhydrous sodium sulfate dries, and is concentrated into dry。Obtain oil product 122g, productivity 81.2%。It is not further purified and is made directly next step reaction。1H-NMR(400MHz,CDCl3, δ/ppm): 6.14 (d, J=7.2Hz, 1H ,=CH), 4.22 (d, J=2.8Hz, 1H, CHCl), 2.74～2.62 (m, 2H, CH2), 2.07～1.95 (m, 2H, CH2), 1.73～1.69 (m, 2H, CH2), 1.45～1.32 (m, 2H, CH2)。
The synthesis of 2.3-chlorine dicyclo [3.2.1]-3-octen-2-ol
Sodium hydroxide 105.2g (2.63mol) is dissolved in 1080mL water, add 3,4-dichloro dicyclo [3.2.1]-2-octene 116.4g (0.657mol) and benzyltrimethylammonium chloride 154mg, heated overnight at reflux, thin layer detection reaction process (developing solvent: dichloromethane)。Being cooled to room temperature, mixture is with dichloromethane extraction (450mL × 2), and with 300mL water washing once, anhydrous sodium sulfate dries organic layer, and solvent is removed in distillation, obtains orange oily product liquid 96.92g, productivity 93%。1H-NMR(400MHz,CDCl3, δ/ppm): 6.12 (d, J=7.0Hz, 1H ,=CH), 3.76 (d, J=3.2Hz, 1H, CHOH), 2.66～2.45 (m, 2H, 2CH), 2.26 (s, 1H, OH), 2.58～2.00 (m, 4H, 2CH2), 1.40～1.24 (m, 2H, CH2)。
The synthesis of 3.3-chlorine dicyclo [3.2.1]-3-octene-2-ketone
Method one (manganese dioxide method): 3-chlorine dicyclo [3.2.1]-3-octen-2-ol 93.6g (0.594mol) is dissolved in 1800mL chloroform, adds activated manganese dioxide 664.2g (7.65mol), is stirred at room temperature 4 days。Then add 180g (2.07mol) manganese dioxide again, be stirred at reflux 8 hours, thin layer detection reaction process (developing solvent: petrol ether/ethyl acetate=5/1)。Sucking filtration, again with 300mL chloroform once, filtrate rotation is evaporated off solvent to filter cake, obtains product 72g, productivity 77.4%。Fusing point 35-36 DEG C。1H-NMR(400MHz,CDCl3, δ/ppm): 7.37 (d, J=7.2Hz, 1H ,=CH), 3.19 (t, J=6.0Hz, 1H, CH), 3.02 (d, J=6.0Hz, 1H, CH), 2.10～1.61 (m, 6H, 3CH2)。
Method two (dimethylsulfoxide oxidation method): at-60 DEG C, the 25mL dichloromethane solution of 6.4g (0.08mol) dimethyl sulfoxide is added drop-wise in the 125mL dichloromethane solution of thionyl chloride 8.25g (0.07mol)。After 10min, add the 50mL dichloromethane solution of 10g (0.063mol) 3-chlorine dicyclo [3.2.1]-3-octen-2-ol, after adding, mixture is stirred at this temperature 15min。Then at-60 DEG C, add 32g (0.315mol) triethylamine, mixture is slowly warming to room temperature。Adding 100mL water, stirring is lower regulates pH=1 with 2N hydrochloric acid, separates organic layer, and with 100mL water washing once, organic over anhydrous dried over sodium sulfate, filtrate rotation is evaporated off solvent, obtains product 8.99g, productivity 91.2%。M.p.35.2-36.1 DEG C。Nuclear magnetic data is identical with method one。
4. the synthesis of dicyclo [3.2.1]-2,4-diketone
3-chlorine dicyclo [3.2.1]-3-octene-2-ketone 61g (0.39mol) is dissolved in 500mL methanol, add potassium cyanide 1.25g (0.02mol, the sodium hydroxide solution 109g (1.365mol) of 5mol%) He 50%, it is heated to reflux 3 hours, thin layer detection reaction process (developing solvent: petrol ether/ethyl acetate=3/2)。Concentrating under reduced pressure removes solvent, and the dilute hydrochloric acid adding 5%, until pH=3～4, is extracted with ethyl acetate (500mL × 2)。Organic over anhydrous dried over sodium sulfate, concentrating under reduced pressure obtains brown solid crude product, re-crystallizing in ethyl acetate, obtains pure products 45.5g, productivity 84.4%。Fusing point 128-129.5 DEG C。The area percentage (purity) that HPLC measures is 97.96%。1H-NMR(400MHz,CDCl3, δ/ppm): diketone formula: 3.32 (d, J=19.6Hz, 1H, COCH2CO), 3.17 (d, J=19.6Hz, 1H, COCH2CO), 3.04 (s, 2H, 2CH), 2.22～2.13 (m, 2H, CH2), 2.09～1.86 (m, 4H, 2CH2). keto-enol formula (analytic signal): 5.12 (s, 1H ,=CH), 2.87 (s, 2H, 2CH), 1.75～1.73 (m, 4H, 2CH2), 1.59～1.56 (m, 2H, CH2)；13C-NMR(100MHz,CDCl3,δ/ppm):203.4,200.8,197.4,99.9,51.4,49.6,45.6,39.5,38.7,31.9,31.3,27.9,26.1。
The synthesis of 5.4-(methyl sulphonyl)-2-chlorobenzoyl chloride
Four-necked bottle adds compound 4-(methyl sulphonyl)-2-chlorobenzoic acid 100g (0.426mol), adds 500mL toluene (room temperature can not be entirely molten), adds the dimethylformamide 2mL of catalytic amount under stirring。Installing gas absorbing device, be cooled to 0 DEG C, slowly dropping thionyl chloride 100g (0.84mol), dropping needs 3h, maintains the temperature at less than 5 DEG C in dropping process。After dripping, it is slowly warmed up 50 DEG C (mixture is clarified gradually, eventually forms settled solution), reacts 24h, thin layer detection reaction process (developing solvent: ethyl acetate)。Rotation is evaporated off solvent and excessive thionyl chloride, obtains residue 105g, productivity 97%, it does not have be further purified, and is directly used in next step reaction。
The synthesis of 6.3-[2-chloro-4-(methyl sulphonyl) benzoyl] bicyclo-[3.2.1]-2,4-acetyl caproyl
220mL1; 2-dichloroethanes adds aluminum trichloride (anhydrous) powder 30.8g (0.23mol) and stirs 30 minutes (1; after 2-dichloroethanes and aluminum trichloride (anhydrous) mixing; solution yellowing); it is subsequently adding 4-(methyl sulphonyl)-2-chlorobenzoyl chloride 19.23g (0.076mol) (yellow mercury oxide occurs), continues stirring 30 minutes。It is subsequently adding dicyclo [3.2.1]-2,4-diketone 10.5g (0.076mol), reacting by heating device, (after adding dicyclo [3.2.1]-2,4-diketone, precipitation is dissolved gradually to make internal temperature rise to 58 DEG C, become settled solution, in soy sauce color)。Continue stirring 3 hours, thin layer detection reaction process (developing solvent: ethyl acetate)。After reaction terminates, being cooled to room temperature, and continuation is with after frozen water cooling, stirring is lower instills 6N hydrochloric acid 178mL。Separating organic layer, water layer extracts with 1,2-dichloroethanes 110mL。After merging organic layer, concentrating under reduced pressure removes solvent, is subsequently adding methanol 120mL post-heating and dissolves (in bottle temperature 62 DEG C), then 6N hydrochloric acid 22mL was instilled in 15 minutes。Stir 1 hour at 62 DEG C, stirred overnight at room temperature。The goal object sucking filtration precipitated out, solids with methanol/water=25:1 recrystallization obtains product 24g product, yield 89%。The area percentage (purity) that HPLC measures is 98.42%。1H-NMR(400MHz,CDCl3, δ/ppm): 7.96 (s, 1H, Ar-H), 7.90 (d, J=8Hz, 1H, Ar-H), 7.39 (d, J=8Hz, 1H, Ar-H), 3.18 (t, 1H, J=5.0Hz, CH), 3.09 (s, 3H, CH3), 2.92 (t, J=5.6Hz, 1H, CH), 2.27～2.05 (m, 4H, 2CH2), 1.80～1.76 (m, 2H, CH2)；13C-NMR(100MHz,CDCl3,δ/ppm):204.8,193.0,187.8,145.3,140.5,133.8,131.1,130.2,125.0,116.6,49.5,47.7,43.9,30.4,27.5,21.4.
Each embodiment is substantially the same manner as Example 1, is different in that table 1。
With the desirable embodiment of the present invention for enlightenment, by above-mentioned description, relevant staff in the scope not necessarily departing from this invention technological thought, can carry out various change and amendment completely。The technical scope of this invention is not limited to the content in description, it is necessary to determine its technical scope according to right。
Claims (10)
1. the synthetic method of 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2, a 4-acetyl caproyl, comprises the following steps:
1) with norborene for initial main material, norborene in the presence of a base, and haloform reaction, obtain 3,4-dichloro dicyclo [3.2.1]-2-octenes (formula III)；
2) the allyl chloride hydrolysis of 3,4-dichloro dicyclo [3.2.1]-2-octenes, obtains 3-chlorine dicyclo [3.2.1]-3-octen-2-ol (formula IV)；
3) 1-propenol-3 of 3-chlorine dicyclo [3.2.1]-3-octen-2-ol is aoxidized under oxidant effect, obtain 3-chlorine dicyclo [3.2.1]-3-octene-2-ketone (formula V)；
4) by 3-chlorine dicyclo [3.2.1]-3-octene-2-ketone under the effect of catalyst and alkali reaction, dicyclo [3.2.1]-2,4-diketone (formula VI) is obtained；
5) dicyclo [3.2.1]-2,4-diketone and 4-(methyl sulphonyl)-2-chlorobenzoyl chloride are reacted, obtain target product 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2,4-acetyl caproyl；
2. 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2 as claimed in claim 1, the synthetic method of 4-acetyl caproyl, it is characterized in that: described step 1) be: with norborene for initial main material, norborene exists at alkali, under quaternary ammonium salt phase-transfer catalysis, with haloform reaction, reaction temperature is 0-100 DEG C, obtain 3, 4-dichloro dicyclo [3.2.1]-2-octene, the mol ratio of described norborene and chloroform is 1:1-4, the mol ratio of described norborene and quaternary ammonium salt is 100:0.1-1, the mol ratio of described norborene and alkali is 1:1-4。
3. 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2 as claimed in claim 1 or 2; the synthetic method of 4-acetyl caproyl, it is characterised in that: described step 1) in alkali be alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal alcoholates or alkali metal ammonia compound。
4. 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2 as claimed in claim 3; the synthetic method of 4-acetyl caproyl; it is characterized in that: described step 1) in alkali be NaOH, KOH or Feldalat NM, quaternary ammonium salt is benzyltrimethylammonium chloride, benzyltriethylammoinium chloride or tri-n-octyl methyl ammonium chloride。
5. 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2 as claimed in claim 1; the synthetic method of 4-acetyl caproyl; it is characterized in that: described step 2) in 3; the allyl chloride of 4-dichloro dicyclo [3.2.1]-2-octene is hydrolyzed in the presence of a base; described alkali is alkali metal hydroxide or alkaline earth metal hydroxide; the mol ratio of described 3,4-dichloro dicyclo [3.2.1]-2-octenes and alkali is 1:1-4。
6. 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2 as claimed in claim 1; the synthetic method of 4-acetyl caproyl, it is characterised in that: described step 3) in oxidant be metal-oxide, dimethyl sulfoxide, oxygen, Jones reagent or salt。
7. 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2 as claimed in claim 1; the synthetic method of 4-acetyl caproyl; it is characterized in that: described step 4) in catalyst be potassium cyanide or Cyanogran., the mol ratio of described 3-chlorine dicyclo [3.2.1]-3-octene-2-ketone and catalyst is 100:1-10。
8. 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2 as claimed in claim 1; the synthetic method of 4-acetyl caproyl; it is characterized in that: described step 4) in alkali be alkali metal hydroxide or alkaline earth metal hydroxide, the mol ratio of described 3-chlorine dicyclo [3.2.1]-3-octene-2-ketone and alkali is 1:1-5。
9. 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2 as claimed in claim 1, the synthetic method of 4-acetyl caproyl, it is characterized in that: described step 5) for by dicyclo [3.2.1]-2, 4-diketone and 4-(methyl sulphonyl)-2-chlorobenzoyl chloride react under lewis acid and solvent existent condition, obtain target product 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2, 4-acetyl caproyl, described lewis acid is aluminum chloride, ferric chloride, zinc dichloride or boron trifluoride, described solvent is 1, 2-dichloroethanes, chloroform or dichloromethane。
10. 3-[4-(methyl sulphonyl)-2-chlorobenzene formacyl] bicyclo-[3.2.1]-2 as claimed in claim 9; the synthetic method of 4-acetyl caproyl; it is characterized in that: described step 5) in dicyclo [3.2.1]-2; the mol ratio of 4-diketone and 4-(methyl sulphonyl)-2-chlorobenzoyl chloride is 1:1-3; dicyclo [3.2.1]-2,4-diketone and lewis acidic mol ratio are 1:1-5。
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