CN104230875A - One-step method for preparing alpha-halogenated acetophenone glycol ketal compound - Google Patents
One-step method for preparing alpha-halogenated acetophenone glycol ketal compound Download PDFInfo
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- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
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Abstract
The invention discloses a one-step method for preparing an alpha-halogenated acetophenone glycol ketal compound by acetophenone. The method is characterized in that acetophenone, halogenated reagents and glycol are simultaneously subjected to alpha-halogenating reaction and condensation reaction with the glycol by one step to obtain the alpha-halogenated acetophenone glycol ketal compound. According to the one-step method for preparing the alpha-halogenated acetophenone glycol ketal compound, two steps of original reactions are simplified to one step, other catalysts and dehydrating agents are not required, reaction conditions are gentle, the yield is high, costs are saved, the operation is convenient, and the post-processing is simple.
Description
Technical field
The invention belongs to organic compound preparation technical field, be specifically related to a kind of method that single stage method prepares alpha-halo acetophenone ethylene ketal compounds.
Background technology
Alpha-halogen (chlorine or bromine) product of various acetophenone compounds is important organic synthesis intermediate, is widely used in the organic synthesis of the fine chemicals such as doctor agricultural chemicals, dyestuff and spices.But due to the carbonyl that contains in this quasi-molecule and alpha-position two reactive sites thereof, further carbonyl is often protected by reaction.In actual applications, maximum is that carbonyl compound and glycol effect cheap and easy to get are formed ketal.As: in the synthesis of efficient germicide penta ring azoles, difenoconazole, Wocosin 50TK and difenoconazole, alpha-halo acetophenone glycol ketal compounds is all key intermediate (Sun Jialong, modern synthetic technology, Chemical Industry Press, 2011,478-502).
Contracting ketone fragrance is that recent two decades develops novel fragrance rapidly, and it has the fragrance being more better than its parent compound, and fragrance temperature is each, lasting is lasting, therefore extensively by favor (Ding Desheng, Gong Juanfang, practical synthetic perfume, Science and Technology of Shanghai press, 1991).Also just because of this, the method for the simpler alpha-halo acetophenone of synthesis efficiently glycol ketal compounds has extremely important using value.
The method that the synthesis of alpha-halo acetophenone contracting glycol compound is commonly used the most is as follows, generally needs experience two step, i.e. the first step carbonyl alpha-halogen, conventional chlorine, bromine etc. are as halogenating agent, also NCS, NBS can be used, (Zou Xinzhuo etc., the CN1699322 such as preparing halogenated hydantoin; CN101121661; CN1733677A); Second step and glycol carry out condensation, and this reaction often uses protonic acid, metal-salt (Yuan Xianyou, Zhang Min, Wang little Yong, chemical reagent, 2006,28 (9), 541), solid super-strong acid, molecular sieve (Gao Shan, Liang Xuezheng, Yang Jianguo, fine chemistry industry, 2006,23 (5), 469) and exchange resin etc. as catalyzer, and to carry out under water entrainer (as: cyclohexane, benzene, toluene etc.) exists.
Above-mentioned traditional method prepares this compounds, and complex steps, condition are harsh and yield is also unsatisfactory.Therefore, needs of production develops the acquisition alcohol of easy, high yield and the novel method of acetophenone compounds halo condensation.At present, the method for one-step synthesis method alpha-halo acetophenone dimethyl acetal compounds has been reported: use AlCl
3simple substance chlorine is produced as chlorine source with Sodium Persulfate effect original position, chloroacetophenone compounds and original acid A ester exist under, alpha-chloro acetophenone dimethyl acetal compounds (Zhou Zhong-shi can be prepared in one pot, Li Li, He Xue-hua, J.Chem.Res., 2013,10,633), the method is very effective to the acetophenone compounds containing strong electron-withdrawing substituent; Zhou Bin and Zou Xinzhuo etc. report and use preparing halogenated hydantoin to be halogenating agent, single stage method is reacted by acetophenone compounds and methyl alcohol and has been prepared corresponding alpha-halo acetophenone dimethyl ketal (CN101624321A), yield can reach 80 ~ 94%, but the method use aminated compounds as catalyzer, and using relatively large molecular sieve as dewatering agent, post-processing difficulty is larger.
Therefore, produce actual needs develop further easy and simple to handle, reaction conditions is gentle, yield is high, low for equipment requirements, by methyl phenyl ketone and halogenating agent and glycol one-step synthesis method alpha-halo acetophenone contracting glycol compound novel method.
Summary of the invention
For the deficiencies in the prior art, the object of the present invention is to provide a kind of single stage method to prepare the method for alpha-halo acetophenone contracting glycol compound by methyl phenyl ketone, this preparation method can carry out under mild conditions, simple and safe operation, raw material is easy to get simultaneously, and production cost is low.
For solving the problems of the technologies described above, the technical solution used in the present invention is:
A kind of single stage method prepares the method for alpha-halo acetophenone contracting glycol compound by methyl phenyl ketone, feature be with methyl phenyl ketone, halogenating agent and glycol one step carry out simultaneously alpha-position halogenating reaction and and the condensation reaction of glycol, obtain alpha-halo acetophenone contracting glycol compound, its synthetic route is:
Described acetophenone compounds specifically refers to following compound:
Wherein R
1, R
2, R
3, R
4, R
5identical or different, be selected from H ,-OCH respectively
3,-CH
3,-C
2h
5,-F ,-Cl ,-Br ,-I ,-CF
3,-CN ,-NO
2or
1 kind in substituting group.
Described halogenating agent is chlorine, N-chlorosuccinimide (NCS), 1,3-bis-chloro-5,5-dimethyl hydantion (DCDMH), bromine, N-bromo-succinimide (NBS), 1,3-bis-bromo-5, one in 5-dimethyl hydantion (DBDMH), the consumption of halogenating agent is 0.5 ~ 2.0 times of acetophenone compounds, 0.8 ~ 1.5 times of preferably acetophenone compounds; Preferred 0.95-1.12 doubly again.
Described glycol is one in ethylene glycol, 1,2-PD, 1,3-PD, 1,2-butyleneglycol, 1,2-pentanediol, 1,2-hexylene glycol, and the consumption of glycol is 1.2 ~ 10 times of acetophenone compounds, and optimum is 2.0 ~ 6.0 times; Preferred 3.4-4.2 doubly again.
Concrete reactions steps is:
A, take acetophenone compounds, halogenating agent, glycol by proportional quantity, add in reaction vessel and mix;
B, react at 0-90 DEG C react 1 ~ 12 hour; Preferable reaction temperature is 20 ~ 50 DEG C;
C, add extraction into ethyl acetate, reclaim glycol that is insoluble and ethyl, ethyl acetate washed with water washs, anhydrous sodium sulfate drying, filters, revolves and steam to obtain alpha-halo acetophenone glycol ketal compounds.
Advantage of the present invention is:
1, use acetophenone compounds just directly to obtain corresponding alpha-halo acetophenone glycol ketal compounds to halogenating agent, glycol single step reaction, original two-step reaction is reduced to a step and carries out;
2, do not use other catalyzer and dewatering agent, and reaction conditions is gentle, yield is high, and this has not only saved cost, and easy to operate, and aftertreatment is simple, therefore, has good application prospect.
Embodiment
Be below specific embodiments more of the present invention, but the present invention is not only confined to following examples.
Embodiment 1 is that halogenating agent prepares alpha-chloro acetophenone ethylene ketal with chlorine
Methyl phenyl ketone 10mmol, chlorine 12mmol, ethylene glycol 12mmol, 20 DEG C, stopped reaction after stirring 1h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro acetophenone ethylene ketal, productive rate 82%.
1H?NMR(CDCl
3,300MHz)δ3.75(2H,s),3.90-3.92(2H,m),4.15-4.19(2H,m),7.25-7.39(3H,m),7.51-7.53(2H,m)。
Embodiment 2 with two chlordantoins for halogenating agent prepares alpha-chloro acetophenone ethylene ketal
Methyl phenyl ketone 10mmol, two chlordantoin 5mmol, ethylene glycol 12mmol, 30 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro acetophenone ethylene ketal, productive rate 84%.
Embodiment 3 with two chlordantoins for halogenating agent prepares alpha-chloro acetophenone ethylene ketal
Methyl phenyl ketone 10mmol, two chlordantoin 8mmol, ethylene glycol 20mmol, 30 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro acetophenone ethylene ketal, productive rate 95%.
Embodiment 4 is that halogenating agent prepares alpha-chloro acetophenone ethylene ketal with NCS
Methyl phenyl ketone 10mmol, NCS 20mmol, ethylene glycol 60mmol, 30 DEG C, stopped reaction after stirring 2h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro acetophenone ethylene ketal, productive rate 85%.
1H?NMR(CDCl
3,300MHz)δ3.75(2H,s),3.90-3.92(2H,m),4.15-4.19(2H,m),7.25-7.39(3H,m),7.51-7.53(2H,m)。
Embodiment 5 is that halogenating agent prepares alpha-chloro acetophenone 1,2-PD ketal with chlorine
Methyl phenyl ketone 10mmol, chlorine 12mmol, 1,2-PD 60mmol, 30 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive 1,2-PD, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro acetophenone 1,2-PD ketal, productive rate 88%.
1H?NMR(CDCl
3,300MHz)δ1.21(3H,dd),3.75(2H,dd),3.80-3.90(2H,m),4.15-4.19(1H,m),7.24-7.40(3H,m),7.50-7.53(2H,m)。
Embodiment 6 is that halogenating agent prepares alpha-brominated acetophenone ethylene glycol ketal with bromine
Methyl phenyl ketone 10mmol, bromine 12mmol, ethylene glycol 80mmol, 30 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated acetophenone ethylene glycol ketal, productive rate 97%.
1H?NMR(CDCl
3,300MHz)δ3.66(2H,s),3.88-3.92(2H,m),4.17-4.20(2H,m),7.32-7.38(3H,m),7.51-7.53(2H,m)。
Embodiment 7 is that halogenating agent prepares alpha-brominated acetophenone ethylene glycol ketal with C5H6Br2N2O2
Methyl phenyl ketone 10mmol, C5H6Br2N2O2 12mmol, ethylene glycol 100mmol, 20 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated acetophenone ethylene glycol ketal, productive rate 81%.
Embodiment 8 is that halogenating agent prepares alpha-brominated acetophenone ethylene glycol ketal with NBS
Methyl phenyl ketone 10mmol, NBS 16mmol, ethylene glycol 60mmol, 50 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro acetophenone ethylene ketal, productive rate 89%.
Embodiment 9 is that halogenating agent prepares alpha-brominated methyl phenyl ketone 1,2-PD ketal with bromine
Methyl phenyl ketone 10mmol, bromine 12mmol, 1,2-PD 70mmol, 30 DEG C, stopped reaction after stirring 2h, adds ethyl acetate 10mL, and extraction, reclaim excessive 1,2-PD, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated methyl phenyl ketone 1,2-PD ketal, productive rate 90%.
1H?NMR(CDCl
3,300MHz)δ1.23(3H,dd),3.89(2H,dd),3.85-3.95(1H,m),4.00-4.20(2H,m),7.20-7.39(3H,m),7.45-7.55(2H,m)。
Embodiment 10 with two chlordantoins for halogenating agent prepares alpha-chloro-4-bromoacetophenone ethylene ketal
4-bromoacetophenone 10mmol, two chlordantoin 5mmol, ethylene glycol 30mmol, 30 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro acetophenone ethylene ketal, productive rate 92%.
1H?NMR(CDCl
3,300MHz)δ3.74(2H,s),3.90-3.92(2H,m),4.15-4.19(2H,m),7.10(2H,d),7.40(2H,d)。
Embodiment 11 is that halogenating agent prepares alpha-brominated-4-bromoacetophenone ethylene ketal with C5H6Br2N2O2
4-bromoacetophenone 10mmol, C5H6Br2N2O2 5mmol, ethylene glycol 30mmol, 30 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated acetophenone ethylene glycol ketal, productive rate 85%.
1H?NMR(CDCl
3,300MHz)δ3.88(2H,s),3.90-3.98(2H,m),4.10-4.20(2H,m),7.08(2H,d),7.36(2H,d)。
Embodiment 12 is that halogenating agent prepares alpha-chloro-4-chloro-acetophenone ethylene ketal with chlorine
4-chloro-acetophenone 10mmol, chlorine 12mmol, ethylene glycol 45mmol, 20 DEG C, stopped reaction after stirring 2h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro-4-chloro-acetophenone ethylene ketal, productive rate 92%.
1H?NMR(CDCl
3,300MHz)δ3.70(2H,s),3.88-3.90(2H,m),4.15-4.18(2H,m),7.33(2H,d),7.45(2H,d)。
Embodiment 13 is that halogenating agent prepares alpha-brominated-4-chloro-acetophenone ethylene ketal with bromine
4-bromoacetophenone 10mmol, bromine 12mmol, ethylene glycol 45mmol, 30 DEG C, stopped reaction after stirring 3h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro acetophenone ethylene ketal, productive rate 93%.
1H?NMR(CDCl
3,300MHz)δ3.85(2H,s),3.90-4.00(2H,m),4.15-4.25(2H,m),7.64(2H,d),7.86(2H,d)。
Embodiment 14 is that halogenating agent prepares alpha-chloro-4-methyl acetophenone ethylene ketal with NCS
4-methyl acetophenone 10mmol, NCS 12mmol, ethylene glycol 12mmol, 40 DEG C, stopped reaction after stirring 2h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro 4-methyl acetophenone ethylene ketal, productive rate 89%.
1H?NMR(CDCl
3,300MHz)δ2.41(3H,s),3.76(2H,s),3.87-3.91(2H,m),4.10-4.20(2H,m),7.21(2H,d),7.83(2H,d)。
Embodiment 15 is that halogenating agent prepares alpha-brominated-4-methyl acetophenone ethylene ketal with NBS
4-methyl acetophenone 10mmol, NBS 15mmol, ethylene glycol 12mmol, 50 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated 4-methyl acetophenone ethylene ketal, productive rate 92%.
1H?NMR(CDCl
3,300MHz)δ2.38(3H,s),3.85(2H,s),3.90-4.00(2H,m),4.15-4.25(2H,m),7.26(2H,d),7.88(2H,d)。
Embodiment 16 with two chlordantoins for halogenating agent prepares alpha-chloro-4-methoxyacetophenone ethylene ketal
4-methoxyacetophenone 10mmol, two chlordantoin 12mmol, ethylene glycol 12mmol, 40 DEG C, stopped reaction after stirring 2h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro 4-methoxyacetophenone ethylene ketal, productive rate 80%.
1H?NMR(CDCl
3,300MHz)δ2.41(3H,s),3.76(2H,s),3.87-3.91(2H,m),4.10-4.20(2H,m),7.21(2H,d),7.83(2H,d)。
Embodiment 17 is that halogenating agent prepares alpha-brominated-4-methoxyacetophenone ethylene ketal with C5H6Br2N2O2
4-methoxyacetophenone 10mmol, C5H6Br2N2O2 5mmol, ethylene glycol 12mmol, 40 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated 4-methoxyacetophenone ethylene ketal, productive rate 85%.
1H?NMR(CDCl
3,300MHz)δ3.81(3H,s),3.85(2H,s),3.90-4.00(2H,m),4.15-4.25(2H,m),7.26(2H,d),7.88(2H,d)。
Embodiment 18 with two chlordantoins for halogenating agent prepares alpha-chloro-3-nitro-acetophenone ethylene ketal
3-nitro-acetophenone 10mmol, two chlordantoin 12mmol, ethylene glycol 12mmol, 50 DEG C, stopped reaction after stirring 2h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro-3-nitro-acetophenone ethylene ketal, productive rate 75%.
1H?NMR(CDCl
3,300MHz)δ3.73(2H,s),3.92-3.94(2H,m),4.19-4.22(2H,m),7.55(1H,t),7.86(1H,d),8.20(1H,d),8.39(1H,s)。
Embodiment 19 is that halogenating agent prepares alpha-brominated-4-nitro-acetophenone ethylene ketal with C5H6Br2N2O2
4-nitro-acetophenone 10mmol, C5H6Br2N2O2 5mmol, ethylene glycol 12mmol, 50 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated-4-nitro-acetophenone ethylene ketal, productive rate 80%.
1H?NMR(CDCl
3,300MHz)δ?3.62(2H,s),3.89-3.92(2H,m),4.20-4.23(2H,m),7.70(2H,d),8.21(2H,d)。
Embodiment 20 is that halogenating agent prepares alpha-brominated-3-nitro-acetophenone ethylene ketal with C5H6Br2N2O2
3-nitro-acetophenone 10mmol, C5H6Br2N2O2 6mmol, ethylene glycol 12mmol, 50 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated-3-nitro-acetophenone ethylene ketal, productive rate 89%.
1H?NMR(CDCl
3,300MHz)δ3.63(2H,s),3.90-3.93(2H,m),4.20-4.24(2H,m),7.55(1H,t),7.86(1H,d),8.20(1H,d),8.39(1H,s)。
Embodiment 21 is that halogenating agent prepares alpha-brominated-3-bromoacetophenone ethylene ketal with C5H6Br2N2O2
3-bromoacetophenone 10mmol, C5H6Br2N2O2 6mmol, ethylene glycol 12mmol, 30 DEG C, stopped reaction after stirring 8h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated-3-bromoacetophenone ethylene ketal, productive rate 92%.
1H?NMR(CDCl
3,300MHz)δ3.63(2H,s),3.89-3.91(2H,m),4.17-4.20(2H,m),7.23-7.28(1H,m),7.45-7.48(2H,m),7.68(1H,s)。
Embodiment 22 is that halogenating agent prepares alpha-chloro-3,4-dichloroacetophenone ethylene ketal with NCS
3,4-dichloroacetophenone 10mmol, NCS 5mmol, ethylene glycol 12mmol, 30 DEG C, stopped reaction after stirring 6h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro 3,4-dichloroacetophenone ethylene ketal, productive rate 87%.
1H?NMR(CDCl
3,300MHz)δ3.78(2H,s),3.92-3.95(2H,m),4.17-4.21(2H,m),7.01(1H,m),7.51-7.53(2H,m)。
Embodiment 23 is that halogenating agent prepares alpha-brominated-2,4 dichloro benzene ethyl ketone ethylene ketal with bromine
2,4 dichloro benzene ethyl ketone 10mmol, bromine 13mmol, ethylene glycol 43mmol, 25 DEG C, stopped reaction after stirring 2h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated 2,4 dichloro benzene ethyl ketone ethylene ketal, productive rate 89%.
1H?NMR(CDCl
3,300MHz)δ3.89(2H,s),3.93-3.95(2H,m),4.10-4.15(2H,m),7.07(1H,d),7.08(1H,d),7.21(1H,s)。
Embodiment 24 is that halogenating agent prepares alpha-brominated-2,4 dichloro benzene ethyl ketone 1,2-PD ketal with bromine
2,4 dichloro benzene ethyl ketone 10mmol, bromine 13mmol, 1,2-PD 50mmol, 50 DEG C, stopped reaction after stirring 2h, adds ethyl acetate 10mL, and extraction, reclaim excessive 1,2-PD, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam alpha-brominated-2,4 dichloro benzene ethyl ketone 1,2-PD ketal, productive rate 92%.
1H?NMR(CDCl
3,300MHz)δ1.21(3H,dd),3.77-3.90(2H,m),3.93-3.95(2H,m),4.05-4.10(1H,m),?7.05(1H,d),7.09(1H,d),7.23(1H,s)。
Embodiment 25 is that halogenating agent prepares alpha-brominated-2,4 dichloro benzene ethyl ketone 1,2-butyleneglycol ketal with C5H6Br2N2O2
2,4 dichloro benzene ethyl ketone 10mmol, bromine 13mmol, 1,2-butyleneglycol 60mmol, 50 DEG C, stopped reaction after stirring 4h, adds ethyl acetate 10mL, and extraction, reclaim 1,2-excessive butyleneglycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam alpha-brominated-2,4 dichloro benzene ethyl ketone 1,2-butyleneglycol ketal, productive rate 88%.
1H?NMR(CDCl
3,300MHz)δ0.96(3H,m),1.46(2H,m),3.75-3.92(2H,m),3.92-3.96(2H,m),4.06-4.11(1H,m),7.07(1H,d),7.11(1H,d),7.23(1H,s)。
Embodiment 26 is that halogenating agent prepares alpha-brominated-2,4 dichloro benzene ethyl ketone 1,2-pentanediol ketal with bromine
Methyl phenyl ketone 10mmol, bromine 13mmol, 1,2-pentanediol 20mmol, 50 DEG C, stopped reaction after stirring 1h, adds ethyl acetate 10mL, and extraction, reclaim 1,2-excessive pentanediol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro acetophenone methyl phenyl ketone 1,2-pentanediol ketal, productive rate 89%.
1H?NMR(CDCl
3,300MHz)δ0.95(3H,m),1.33-1.46(4H,m),3.76-3.91(2H,m),3.93-3.96(2H,m),4.05-4.10(1H,m),7.06(1H,d),7.13(1H,d),7.19(1H,s)。
Embodiment 27 is that halogenating agent prepares alpha-brominated-4-(4 '-chlorophenoxy)-2-chloro-acetophenone 1,2-PD ketal with C5H6Br2N2O2
2-(4 '-chlorophenoxy)-4-chloro-acetophenone 10mmol, C5H6Br2N2O2 13mmol, 1,2-PD 43mmol, 30 DEG C, stopped reaction after stirring 5h, adds ethyl acetate 10mL, extraction, reclaim excessive 1,2-PD, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated methyl phenyl ketone methyl phenyl ketone 1,2-PD ketal, productive rate 89%.
cis:
1H?NMR(CDCl
3,300MHz)δ1.16-1.18(3H,m),3.29-3.33(1H,m),3.76-3.82(1H,m),3.85-3.89(1H,m),4.20-4.23(1H,m),4.30-4.36(1H,m),6.76-6.78(1H,m),6.87-6.91(3H,m),7.23(2H,d),7.61-7.63(1H,m).
trans:
1H?NMR(CDCl
3,300MHz)δ1.31(3H,d),3.60-3.62(1H,m),3.86(1H,d),3.94-3.98(2H,m),4.07-4.09(1H,m),6.76-6.78(1H,m),6.87-6.91(3H,m),7.23(2H,d),7.55(1H,d).
Embodiment 28 with two chlordantoins for halogenating agent prepares alpha-chloro-4-(4 '-chlorophenoxy)-2-chloro-acetophenone 1,2-PD ketal
2-(4 '-chlorophenoxy)-4-chloro-acetophenone 10mmol, two chlordantoin 16mmol, 1,2-PD 44mmol, 30 DEG C, stopped reaction after stirring 5h, adds ethyl acetate 10mL, extraction, reclaim excessive 1,2-PD, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro acetophenone methyl phenyl ketone 1,2-PD ketal, productive rate 92%.
cis:
1H?NMR(CDCl
3,300MHz)δ1.17-1.19(3H,m),3.30-3.33(1H,m),3.75-3.85(1H,m),3.87-3.90(1H,m),4.21-4.23(1H,m),4.30-4.35(1H,m),6.75-6.78(1H,m),6.87-6.92(3H,m),7.21(2H,d),7.60-7.64(1H,m).
trans:
1H?NMR(CDCl
3,300MHz)δ1.33(3H,d),3.61-3.64(1H,m),3.85(1H,d),3.96-4.00(2H,m),4.07-4.10(1H,m),6.76-6.79(1H,m),6.87-6.93(3H,m),7.24(2H,d),7.54(1H,d).
Embodiment 29 is that halogenating agent prepares alpha-brominated-4-(4 '-chlorophenoxy)-2-chloro-acetophenone 1,2-PD ketal with bromine
2-(4 '-chlorophenoxy)-4-chloro-acetophenone 10mmol, bromine 12mmol, 1,2-PD 50mmol, 20 DEG C, stopped reaction after stirring 1h, adds ethyl acetate 10mL, extraction, reclaim excessive 1,2-PD, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated methyl phenyl ketone methyl phenyl ketone 1,2-PD ketal, productive rate 85%.
cis:
1H?NMR(CDCl
3,300MHz)δ1.16-1.18(3H,m),3.29-3.33(1H,m),3.76-3.82(1H,m),3.85-3.89(1H,m),4.20-4.23(1H,m),4.30-4.36(1H,m),6.76-6.78(1H,m),6.87-6.91(3H,m),7.23(2H,d),7.61-7.63(1H,m).
trans:
1H?NMR(CDCl
3,300MHz)δ1.31(3H,d),3.60-3.62(1H,m),3.86(1H,d),3.94-3.98(2H,m),4.07-4.09(1H,m),6.76-6.78(1H,m),6.87-6.91(3H,m),7.23(2H,d),7.55(1H,d).
Embodiment 30 is that halogenating agent prepares alpha-chloro acetophenone ethylene ketal with chlorine
Methyl phenyl ketone 10mmol, chlorine 11.2mmol, ethylene glycol 12mmol, 20 DEG C, stopped reaction after stirring 1h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro acetophenone ethylene ketal, productive rate 92%.
Embodiment 31 is that halogenating agent prepares alpha-chloro acetophenone ethylene ketal with chlorine
Methyl phenyl ketone 10mmol, chlorine 11.2mmol, ethylene glycol 34mmol, 20 DEG C, stopped reaction after stirring 1h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-chloro acetophenone ethylene ketal, productive rate 95%.
Embodiment 32 is that halogenating agent prepares alpha-brominated-2,4 dichloro benzene ethyl ketone ethylene ketal with bromine
2,4 dichloro benzene ethyl ketone 10mmol, bromine 13mmol, ethylene glycol 42mmol, 25 DEG C, stopped reaction after stirring 2h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated 2,4 dichloro benzene ethyl ketone ethylene ketal, productive rate 92%.
Embodiment 33 is that halogenating agent prepares alpha-brominated-2,4 dichloro benzene ethyl ketone ethylene ketal with bromine
2,4 dichloro benzene ethyl ketone 10mmol, bromine 11.2mmol, ethylene glycol 42mmol, 25 DEG C, stopped reaction after stirring 2h, adds ethyl acetate 10mL, and extraction, reclaim excessive ethylene glycol, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated 2,4 dichloro benzene ethyl ketone ethylene ketal, productive rate 96%.
Embodiment 34 is that halogenating agent prepares alpha-brominated-4-(4 '-chlorophenoxy)-2-chloro-acetophenone 1,2-PD ketal with bromine
2-(4 '-chlorophenoxy)-4-chloro-acetophenone 10mmol, bromine 9.5mmol, 1,2-PD 50mmol, 20 DEG C, stopped reaction after stirring 1h, adds ethyl acetate 10mL, extraction, reclaim excessive 1,2-PD, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated methyl phenyl ketone methyl phenyl ketone 1,2-PD ketal, productive rate 90%.
Embodiment 35 is that halogenating agent prepares alpha-brominated-4-(4 '-chlorophenoxy)-2-chloro-acetophenone 1,2-PD ketal with bromine
2-(4 '-chlorophenoxy)-4-chloro-acetophenone 10mmol, bromine 9.5mmol, 1,2-PD 42mmol, 20 DEG C, stopped reaction after stirring 1h, adds ethyl acetate 10mL, extraction, reclaim excessive 1,2-PD, ethyl acetate layer water 30mL washes three times, anhydrous sodium sulfate drying.Filter, revolve and steam to obtain alpha-brominated methyl phenyl ketone methyl phenyl ketone 1,2-PD ketal, productive rate 93%.
At use acetophenone compounds and the halogenating agent of the present invention's discovery, glycol single step reaction just directly obtains on the basis of corresponding alpha-halo acetophenone glycol ketal compounds, we find that the consumption of raw material also has considerable influence to final product yield, by embodiment 1 and 30, 31, embodiment 23 and 32, 33, embodiment 29 and 34, 35, halogenating agent, acetophenone compounds, the productive rate of mole dosage between glycol three on the product finally obtained has larger impact, when the mole dosage of halogenating agent be the 0.95-1.12 of acetophenone compounds mole dosage doubly, when the mole dosage of glycol is the 3.4-4.2 times of acetophenone compounds mole dosage, now product yield is obviously better than other amount ratios.
The foregoing is only better embodiment of the present invention, not in order to limit the present invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (7)
1. a single stage method prepares the method for alpha-halo acetophenone glycol ketal compounds, it is characterized in that the method mix in glycol using acetophenone compounds as reactant with halogenating agent after a step carry out alpha-halogen reaction and with glycol condensation reaction, obtain alpha-halo acetophenone glycol ketal compounds.
2. method according to claim 1, described acetophenone compounds specifically refers to following compound:
Wherein R
1, R
2, R
3, R
4, R
5identical or different, be selected from H ,-OCH respectively
3,-CH
3,-C
2h
5,-F ,-Cl ,-Br ,-I ,-CF
3,-CN ,-NO
2or
one in substituting group.
3. method according to claim 1, described halogenating agent is chlorine, N-chlorosuccinimide (NCS), 1,3-bis-chloro-5,5-dimethyl hydantion (DCDMH), bromine, N-bromo-succinimide (NBS) or 1, one in bromo-5, the 5-dimethyl hydantion (DBDMH) of 3-bis-.
4. method according to claim 1, it is waited to levy and is that the mole dosage of halogenating agent is 0.5-2.0 times of acetophenone compounds mole dosage, preferably 0.8 ~ 1.5 times, more preferably 0.95-1.12 times.
5. preparation method according to claim 1, described glycol is the one in ethylene glycol, 1,2-PD, 1,3-PD, 1,2-butyleneglycol, 1,2-pentanediol or 1,2-hexylene glycol.
6. method according to claim 1, is characterized in that the mole dosage of glycol is 1.2-10 times of acetophenone compounds mole dosage, preferably 2.0 ~ 6.0 times, more preferably 3.4-4.2 times.
7. method according to claim 1, concrete reactions steps is:
A, take acetophenone compounds, halogenating agent, glycol by proportional quantity, add in reaction vessel and mix;
B, react and react 6-24 hour at 0-90 DEG C; Preferable reaction temperature is 20 ~ 50 DEG C;
C, add extraction into ethyl acetate, reclaim glycol that is insoluble and ethyl, ethyl acetate washed with water washs, anhydrous sodium sulfate drying, filters, revolves and steam to obtain alpha-halo acetophenone glycol ketal compounds.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104844648A (en) * | 2015-04-02 | 2015-08-19 | 中国人民解放军63975部队 | Synthetic method of phosphorothioate compound |
| CN116041309A (en) * | 2023-01-17 | 2023-05-02 | 浙江宇龙生物科技股份有限公司 | Continuous extraction synthesis method of substituted ketal |
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| US3944568A (en) * | 1973-12-20 | 1976-03-16 | Lever Brothers Company | Process for the preparation of selectively halogenated ketals |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104844648A (en) * | 2015-04-02 | 2015-08-19 | 中国人民解放军63975部队 | Synthetic method of phosphorothioate compound |
| CN116041309A (en) * | 2023-01-17 | 2023-05-02 | 浙江宇龙生物科技股份有限公司 | Continuous extraction synthesis method of substituted ketal |
| CN116041309B (en) * | 2023-01-17 | 2023-11-14 | 浙江宇龙生物科技股份有限公司 | Continuous extraction synthesis method of substituted ketal |
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