CN106518663B - A kind of preparation method of alpha-acyloxy ketone compound - Google Patents

A kind of preparation method of alpha-acyloxy ketone compound Download PDF

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CN106518663B
CN106518663B CN201610946542.7A CN201610946542A CN106518663B CN 106518663 B CN106518663 B CN 106518663B CN 201610946542 A CN201610946542 A CN 201610946542A CN 106518663 B CN106518663 B CN 106518663B
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王桦
魏伟
朱明慧
崔环环
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Qufu Normal University
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Abstract

The invention discloses a kind of preparation methods of alpha-acyloxy ketone compound.With alcohol and carboxylic acid raw material simple and easy to get in NBS(N- bromo-succinimide) and 11 carbon -7- alkene of DBU(1,8- diazabicylo) mediate under " one kettle way " reaction prepare alpha-acyloxy ketone.This method have the advantage that: reaction condition is mild, raw material is simple and easy to get, and substrate wide adaptation range does not need to avoid metallic pollution using the reaction condition of the harshness such as any metallic catalyst, per-compound, low or high temperature and anhydrous and oxygen-free；This law the advantages that there are also stable process conditions, easy to operate and safe, easy purification of products.

Description

A kind of preparation method of alpha-acyloxy ketone compound
Technical field
The invention belongs to synthetic organic chemical arts, are related to a kind of preparation method of alpha-acyloxy ketone compound, specifically It is related to a kind of direct method that synthesis alpha-acyloxy ketone compound is reacted using alcohol and carboxylic acid that NBS/DBU is mediated.
Background technique
Alpha-acyloxy ketone (α-acyloxyketones) compound is ground in chemical research, chemical industry, functional material and drug There is extremely significant meaning in the practical applications such as hair.Alpha-acyloxy ketone compound structure fragment is widely present in natural products In, often as the key structure skeleton of physiological activity molecule and drug molecule.Alpha-acyloxy ketone is risen in organic synthesis body Important bracket effect.Studies have shown that the substance containing the structure fragment has numerous biological activities, such as antibacterial, anti-inflammatory, resist Tuberculosis, anticonvulsion, antitumor etc..
Traditional synthetic method is generally ketone compound and toxic heavy metal Pb (OAc) 4, Tl (OAc)3, Hg(OAc)2Directly It is reversed to answer ((a) J. D. Cocker, H. B. Henbest, G. H. Phillipps, G. P. Slater and D. A. Thomas, J. Chem. Soc.,1965, 6; (b) M. E. Kuehne and T. C. Giacobbe, J. Org. Chem., 1968, 33, 3359; (c) D. J. Rawilson and G. Sosnovsky, Synthesis, 1973, 567; (d) J. C. Lee, Y. S. Jin and J.-H. Choi, Chem. Commun., 2001, 956), or for carboxylate and α-halogenatedketone compound reaction (P. A. Levine and A. Walti,Org. Synth. Coll.,1943, 2, 5).Such method uses toxic heavy metal, big to environmental hazard.With the development of Green Chemistry, people Seek a kind of more efficient method to prepare the alpha-acyloxy ketone compound with important synthesis meaning.In recent years, with high price Iodine compound improves esterification rate as oxidant and obtains research and development as catalyst, peroxide, and details are as follows:
2005, M Ochiai group reports was with benzene iodide (PhI) and metachloroperbenzoic acid (m- CPBA) Catalyst and oxidant are coupled ketone and acetic acid oxidation catalysed cross and generate α-acyl-oxygen carbonyls, which can also select H2O2As oxidant, Ac2O is as acetyl oxidation reagent (M. Ochiai, Y. Takeuchi, T. Katayama, T. Sueda and K. Miyamoto, J. Am. Chem. Soc. 2005, 127, 12244) and (reaction equation is as follows).
2011, M. Uyanik was reported using ketone and carboxylic acid as raw material and is carried out synthetic reaction, used H2O2/Bu4NI or TBHP/ Bu4NI obtains similar α-acyl-oxygen carbonyls (M. Uyanik, D. as oxidant and catalyst Suzuki, T. Yasui and K. Ishihara, Angew. Chem., Int. Ed. 2011, 50, 5331) and (reaction Formula is as follows).
2014, it was raw material in Bu that S. Gu chemical group, which is reported again using ketone and benzyl alcohol,4NI and peroxide TBHP Under conditions of directly carry out catalysis oxidation cross-coupling reaction (reaction equation is as follows), which only obtains medium yield (S. Guo, J.-T. Yu, Q. Dai, H. Yang and J. Cheng, Chem. Commun., 2014, 50, 6240).
2014, it was raw material in Bu that A.Sudalai group, which reports using ketone and toluene derivative,4NI and peroxide Catalysis oxidation cross-coupling reaction synthesis α-acyl-oxygen ketone compound (reaction equation is as follows), the reaction are directly carried out under conditions of TBHP Only obtain medium and preferable yield (R. N. Reddi, P. K. Prasad and A. Sudalai,Org. Lett. 2014,16,5674).
2014, it was raw material in Bu4NI and peroxide TBHP that Wang group, which reports using ketone and styrene derivative, Under conditions of, using benzene plus nitrile as solvent, carries out catalysis oxidation cross-coupling reaction and generate alpha-acyloxy ketone (reaction equation is as follows) (F. Zhu and Z-X. Wang, Tetrahedron 2014,70,9819).
2015, it was raw material under conditions of iodine and peroxide TBHP that Pan group, which reports using alkene and carboxylic acid, Using triethylamine as alkali, DMSO is solvent, carries out oxidation acyloxylation reaction response and obtains alpha-acyloxy ketone (B. Mondal, S. C. Sahoo and S. C. Pan, Eur. J. Org. Chem.2015,3135) (reaction equation is as follows).
In addition, 2015, Wang group, which also reported, is directly catalyzed propiophenone and acetophenone using 20mol% mantoquita in α- C(sp3) replace on H and generate α-acyl-oxygen carbonyls reaction, which is being catalyst using CuI, and oxygen is as reaction oxygen Agent achieves low to medium yield on the upper side, the higher reaction temperature (120 of reaction needsoC) (J. Du, X. Zhang,X. Sun and L. Wang, Chem. Commun., 2015, 51, 1043) and (reaction equation is as follows).
The above research work sufficiently shows the importance of alpha-acyloxy ketone compounds, their synthesis is by chemistry The great attention of family.But above-mentioned synthetic method still either uses risk using some toxic metallic catalysts Big peroxide is oxidant, it is made to limit their extensive uses in organic synthesis and field of medicinal chemistry, institute With, study a kind of simple, safe and efficient synthetic method be very there is an urgent need to.
Summary of the invention
Technical problem to be solved by the present invention lies in researching and designing synthesizes alpha-acyloxy using raw material simple and easy to get The method of ketone compound, this method pass through " one kettle way " two-step reaction, alpha-acyloxy assimilation are effectively obtained under shirtsleeve operation Object is closed, is realized by nonmetal catalyzed and approach without using peroxide, reaction is mild, convenient, economical.
Technical solution of the present invention is as follows:
A kind of preparation method of alpha-acyloxy ketone compound, comprising: be with carboxylic acid shown in pure and mild formula (II) shown in formula (I) Beginning raw material, under conditions of mono- bromo-succinimide of N (NBS) and diazabicylo (DBU) mediate, reaction synthesis formula (III) Shown alpha-acyloxy ketone compound, reaction equation are as follows:
Wherein, R1For aryl, aralkyl, alkyl, naphthenic base, halogen, ester group, alkoxy or itrile group；R2For aryl, aralkyl Base, alkyl, naphthenic base or hydrogen atom；R3For aryl, aralkyl, alkyl, naphthenic base, alkynyl or alkenyl.
Further, the aryl includes monokaryon aryl group and multicore aryl group, as phenyl, naphthalene, green onion base or Phenanthryl etc., monokaryon aryl and multicore aryl can be to be replaced on one or more positions；When for the monokaryon aryl of substitution, Alkoxy, halogen, cyano, acetyl group, nitro, alkoxy carbonyl group or the ester group of the alkyl of the preferred C1-C7 of substituent group, C1-C7；
Further, the aryl includes the heteroaryl containing nitrogen, oxygen or sulphur atom, and the heteroaryl includes replacing The heteroaryl that base replaces, alkoxy, halogen, cyano, acetyl group, the nitre of the alkyl of the preferred C1-C7 of the substituent group, C1-C7 Base, alkoxy carbonyl group or ester group；
Further, the heteroaryl be monokaryon heteroaryl when, preferably pyridyl group, furyl, pyrrole radicals, imidazole radicals, Thiazolyl or methylthiophene base；The heteroaryl be multicore heteroaryl when, preferably xenyl, naphthalene, pyrrole radicals, thienyl, Benzofuranyl, indyl, quinolyl, imidazole radicals, pyrazolyl or pyridyl group；
Further, the aralkyl represents aromatic yl elementary alkyl, and the aryl is as defined above, the lower alkyl Base is the alkyl of C1-C7；The aralkyl is unsubstituted aralkyl or substituted aralkyl, the unsubstituted preferred benzyl of aralkyl Base, the preferred methoxy-benzyl of substituted aralkyl, methylbenzyl, Fluoro-benz rLl, chlorobenzyl, nitrobenzyl, phenethyl or pyrrole Pyridine methyl；
Further, the alkyl, is the linear or branched alkyl group of C1-C20, the preferred alkyl of C1-C6, as ethyl, Propyl, isopropyl, butyl, n-pentyl, isopentyl, hexyl, heptyl or octyl；
Further, the naphthenic base is the naphthenic base of C3-C10, such as cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl Or adamantane；
Further, the halogen, preferably fluorine, chlorine, bromine, iodine；The ester, preferably methyl formate or Ethyl formate； The alkoxy, preferably methoxyl group, ethyoxyl or propoxyl group；The alkynyl, preferably propine, butine, phenyl-allylene or hexin； The alkenyl, preferably propylene, butylene, styrene or butylene.
In preparation method of the present invention, the molar ratio of raw alcohol and carboxylic acid is 1:1~8, preferably 1:1~5.
In above-mentioned preparation method, the dosage of the NBS and DBU preferably 2 equivalents.
In above-mentioned preparation method, the reaction, temperature is 0~100 DEG C, preferably 40~60 DEG C.
In above-mentioned preparation method, the reaction can react in oxygen, nitrogen or air, preferably anti-in air It answers.
Preferably, the preparation method of alpha-acyloxy ketone compound of the present invention, specific steps include: at room temperature, successively by alcohol, Carboxylic acid, NBS and organic solvent mixing, in 40~60 DEG C of stirring 1h, are then added DBU, the reaction was continued 2h obtains alpha-acyloxy ketone Compound.
The organic solvent be non-protonic solvent, including Isosorbide-5-Nitrae-dioxane, tetrahydrofuran, acetonitrile, ethyl acetate, Dimethyl sulfoxide, methylene chloride, chloroform, 1,2- dichloroethanes, 1,2- dimethoxy-ethane, toluene, benzene or N, N- dimethyl formyl Amine, preferably Isosorbide-5-Nitrae-dioxane.
The present invention provides the preparation methods of alpha-acyloxy ketone compound, and compared with the method reported in the past, this method is former Expect that cheap and easily-available, reaction condition is mild, Atom economy is high, substrate wide adaptation range, yield are high, need using any metal The reaction condition of catalyst and per-compound oxidant etc.；There are also short preparation period, stable process conditions, operation letters for this method Just the advantages of safety, easy purification of products, large-scale production can be carried out.
Specific embodiment
The present invention is further illustrated below by specific embodiment, it should be understood that the preparation side of the embodiment of the present invention Method is only used for illustrating the present invention, rather than limiting the invention；Under the premise of present inventive concept, prepared by the present invention The simple modifications of method belong to the present invention claims protection scope.
Embodiment 1:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), benzoic acid are sequentially added in 50 mL round-bottomed flasks (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (yellow solid 0.251g, yield 99%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.12 (d, J= 7.1 Hz, 2H), 8.03 (d, J = 7.1 Hz, 2H), 7.63-7.58 (m, 2H), 7.53-7.45 (m, 4H), 6.24 (q, J= 7.0 Hz, 3H), 1.70 (d, J= 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.7, 166.0, 134.5, 133.6, 133.3, 129.9, 129.5, 128.8, 128.5, 128.4, 71.9, 17.2; HRMS calc. for C16H14O3Na (M+Na)+, 277.0841; found, 277.0846.
Embodiment 2:
At room temperature, 4- methyl-1-phenylpropanol (0.15 g, 1 mmol), benzene first are sequentially added in 50 mL round-bottomed flasks Sour (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is small in 60 DEG C of stirrings 1 When, DBU (0.304 g, 2 mmol) then are added, the reaction was continued 4 hours (TLC detection reaction).Then, stop reaction, It is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) Obtain corresponding product alpha-acyloxy ketone compound (white solid 0.239g, yield 89%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.11 (d, J= 7.0 Hz, 2H), 7.93 (d, J = 8.2 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.47 (t, J= 7.9 Hz, 2H), 7.31 (d, J= 8.0 Hz,2H), 6.22 (q, J= 7.0 Hz, 1H), 2.44 (s, 3H), 1.69 (d, J= 7.0 Hz, 3H);13C NMR (CDCl3, 100 MHz, ppm): δ196.2, 166.0, 144.5, 133.2, 132.0, 129.9, 129.6, 129.5, 128.7, 128.4, 71.8, 21.7, 17.3; HRMS calc. for C17H16O3Na (M+Na)+, 291.0997; found, 291.0999.
Embodiment 3:
At room temperature, 1- benzyl carbinol (0.122 g, 1 mmol), benzoic acid are sequentially added in 50 mL round-bottomed flasks (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 4 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (white solid 0.211g, yield 88%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.17 (d, J = 7.1 Hz, 2H), 8.00 (d, J = 7.1 Hz, 2H), 7.66-7.61 (m, 2H), 7.56-7.48 (m, 4H), 5.61 (s, 2H); 13C NMR (CDCl3, 100 MHz, ppm): δ192.3, 166.0, 134.4, 133.9, 133.3, 130.0, 128.9, 128.5, 127.9, 66.5; HRMS calc. for C15H12O3Na (M+Na)+, 263.0684; found, 263.0685.
Embodiment 4:
At room temperature, 4- methoxyl group -1- benzyl carbinol (0.152 g, 1 mmol) is sequentially added in 50 mL round-bottomed flasks, Benzoic acid (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred at 60 DEG C It mixes 1 hour, DBU (0.304 g, 2 mmol) then is added, the reaction was continued 4 hours (TLC detection reaction).Then, stop Reaction is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicon Rubber column gel column) obtain corresponding product alpha-acyloxy ketone compound (white solid 0.230g, yield 85%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.17 (d, J = 7.1 Hz, 2H), 7.98 (d, J= 6.9 Hz, 2H), 7.62 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.00 (d, J= 6.9 Hz, 2H), 5.57 (s, 2H), 3.91 (s, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ 190.6, 166.1, 164.1, 133.3, 130.2, 130.0, 129.6, 128.4, 127.4, 114.1, 66.2, 55.5; HRMS calc. for C16H14O4Na (M+Na)+, 293.0790; found, 293.0791.
Embodiment 5:
At room temperature, the fluoro- 1- benzyl carbinol of 4- (0.14 g, 1 mmol), benzoic acid are sequentially added in 50 mL round-bottomed flasks (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 4 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (white solid 0.178g, yield 69%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.16 (d, J= 7.1 Hz,2H), 8.06-8.02 (m, 2H), 7.63 (t, J= 7.5 Hz, 1H), 7.50 (t, J= 7.9 Hz,2H), 7.21 (t, J= 8.6 Hz, 2H), 5.57 (s, 2H); 13C NMR (CDCl3, 100 MHz, ppm): δ190.7, 166.2 (d, J= 254.5 Hz), 166.1, 133.4, 130.8 (d, J= 2.9 Hz), 130.6 (d, J= 9.4 Hz), 130.0, 129.3, 128.5, 116.1 (d, J= 21.9 Hz), 66.3; HRMS calc. for C15H11O3FNa (M+Na)+, 281.0590; found, 281.0593.
Embodiment 6:
At room temperature, 4- chlorine 1- benzyl carbinol (0.156 g, 1 mmol), benzoic acid are sequentially added in 50 mL round-bottomed flasks (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 4 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (white solid 0.233g, yield 85%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.16 (d, J = 7.1 Hz, 2H), 7.94 (d, J= 8.6 Hz, 2H), 7.63 (t, J= 7.4 Hz, 1H), 7.52-7.48 (m, 3H), 5.56 (s, 2H); 13C NMR (CDCl3, 100 MHz, ppm): δ191.1, 166.0 140.4, 133.4, 132.7, 130.0, 129.3, 129.2, 128.5, 66.3; HRMS calc. for C15H11O3ClNa (M+Na)+, 297.0294; found, 297.0291.
Embodiment 7:
At room temperature, the bromo- 1- benzyl carbinol of 4- (0.2 g, 1 mmol), benzoic acid are sequentially added in 50 mL round-bottomed flasks (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 4 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (white solid 0.210g, yield 66%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.17-8.15 (m, 2H), 7.86 (d, J = 8.6 Hz, 2H), 7.68 (d, J= 8.6 Hz,2H), 7.63 (t, J= 7.4 Hz, 1H), 7.50 (t, J= 7.9 Hz, 2H), 5.55 (s, 2H); 13C NMR (CDCl3, 100 MHz, ppm): δ191.3, 166.0, 133.4, 133.1, 132.3, 130.0, 129.3, 129.3, 129.2, 128.5, 66.3; HRMS calc. for C15H11O3BrNa (M+ Na)+, 340.9789; found, 340.9791.
Embodiment 8:
At room temperature, 3- Trifluoromethyl-1-benzyl carbinol (0.19 g, 1 mmol) is sequentially added in 50 mL round-bottomed flasks, Benzoic acid (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred at 60 DEG C It mixes 1 hour, DBU (0.304 g, 2 mmol) then is added, the reaction was continued 4 hours (TLC detection reaction).Then, stop Reaction is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicon Rubber column gel column) obtain corresponding product alpha-acyloxy ketone compound (white solid 0.170, yield 55%)
1H NMR (CDCl3, 400 MHz, ppm): δ8.26 (s, 1H), 8.19-8.14 (m, 3H), 7.91 (d, J = 7.8 Hz, 1H), 7.69 (t, J = 7.8 Hz, 1H), 7.66-7.62 (m, 1H), 7.51 (t, J = 7.9 Hz, 2H), 5.60 (s, 2H); 13C NMR (CDCl3, 100 MHz, ppm): δ191.2, 166.0, 134.9, 133.5, 131.6 (d, J = 33.0 Hz), 131.0, 130.3 (q, J= 3.4 Hz,Hz), 130.0, 129.6, 129.2, 128.5, 128.4, 124.8 (d, J= 4.1 Hz), 66.4;HRMS calc. for C16H11O3F3Na (M+Na)+, 331.0558; found, 331.0561.
Embodiment 9:
At room temperature, 1- fenipentol (0.164 g, 1 mmol), benzoic acid are sequentially added in 50 mL round-bottomed flasks (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 4 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (yellow liquid 0.260g, yield 92%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.13 (d, J= 7.1 Hz, 2H), 8.03 (J= 7.2 Hz, 2H), 7.62-7.59 (m, 2H), 7.54-7.46 (m, 4H), 6.14 (dd, J 1 = 5.4 Hz, J 2 = 7.9 Hz, 1H), 2.04-1.99 (m, 2H), 1.66-1.59 (m, 2H), 1.03 (t, J= 7.4 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.5, 166.2, 134.9, 133.5, 133.2, 129.9, 129.6, 128.8, 128.5, 128.4, 75.6, 33.5, 19.0, 13.8; HRMS calc. for C18H18O3Na (M+Na)+, 305.1154; found, 305.1155.
Embodiment 10:
At room temperature, 1- benzene hexanol (0.178 g, 1 mmol), benzoic acid are sequentially added in 50 mL round-bottomed flasks (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (yellow liquid 0.270g, yield 91%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.13 (d, J= 7.1 Hz, 2H), 8.03 (d, J= 7.1 Hz, 2H), 7.64-7.59 (m, 2H), 7.54-7.47 (m, 4H), 6.12 (t, J= 6.2 Hz, 1H), 2.06-2.01 (m, 2H), 1.59-1.53(m, 2H), 1.46-1.39 (m, 2H), 0.95 (t, J= 7.3 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.5, 166.2, 135.0, 133.5, 133.2, 129.9, 129.6, 128.8, 128.5, 128.4, 75.8, 31.2, 27.7, 22.4, 13.8; HRMS calc. for C19H20O3Na (M+Na)+, 319.1310; found, 319.1311.
Embodiment 11:
At room temperature, 1- naphthalene ethyl alcohol (0.172 g, 1 mmol), benzoic acid are sequentially added in 50 mL round-bottomed flasks (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 4 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (white liquid 0.203g, yield 70%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.71 (d, J = 8.6 Hz, 1H), 8.18 (t, J= 7.1 Hz,2H), 8.07 (d, J = 8.3 Hz, 1H), 7.98 (dd, J 1 = 0.9 Hz, J 2 = 7.2 Hz, 1H), 7.92 (d, J = 7.6 Hz, 1H), 7.65-7.61 (m, 2H), 7.59-7.56 (m, 2H), 7.50 (t, J = 7.8 Hz, 1H), 5.59 (s, 2H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.0, 166.1, 134.0, 133.5, 133.4, 132.5, 130.3, 130.2, 130.0, 129.5, 128.5, 128.4, 127.5, 126.8, 125.7, 124.3, 67.9; HRMS calc. for C19H14O3Na (M+Na)+, 313.0841; found, 313.0844.
Embodiment 12:
At room temperature, 2,3- dihydro -1- indanol (0.134 g, 1 mmol), benzene are sequentially added in 50 mL round-bottomed flasks Formic acid (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).1 is stirred at 60 DEG C Hour, DBU (0.304 g, 2 mmol) then are added, the reaction was continued 4 hours (TLC detection reaction).Then, stop anti- It answers, is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silica gel Column) obtain corresponding product alpha-acyloxy ketone compound (yellow liquid 0.222g, yield 88%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.12 (d, J = 7.1 Hz, 2H), 7.87 (d, J = 7.7 Hz, 1H), 7.70 (dt, J 1 = 1.1 Hz, J 2 = 7.6 Hz, 1H), 7.63-7.59 (m, 1H), 7.52- 7.46 (m, 4H), 5.67 (dd, J 1 = 4.8 Hz, J 2 = 8.0 Hz, 1H), 3.80 (dd, J 1 = 8.0 Hz,J 2 = 17.0 Hz, 1H), 3.23 (dd, J 1 = 4.8 Hz, J 2 = 17.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz, ppm): δ200.4, 166.1, 150.4, 135.9, 134.7, 133.4, 130.0, 129.4, 128.4, 128.2, 126.7, 124.6, 74.5, 33.6; HRMS calc. for C16H12O3Na (M+Na)+, 275.0684; found, 275.0685.
Embodiment 13:
At room temperature, 1 is sequentially added in 50 mL round-bottomed flasks, and -1 alcohol of 2,3,4- tetrahydros-naphthalene (0.148 g, 1 Mmol), benzoic acid (0.183g, 1.5 mmol), NBS(0.356g, 2 mmol) and Isosorbide-5-Nitrae-dioxane (2 mL).60 DEG C stirring 1 hour, DBU (0.304 g, 2 mmol) then are added, the reaction was continued 2 hours (TLC detection reaction).Then, Stop reaction, is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, flash column Analysis (silicagel column) obtains corresponding product alpha-acyloxy ketone compound (yellow liquid 0.245g, yield 92%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.19-8.16 (m, 2H), 8.09 (dd, J 1 = 1.1 Hz, J 2 = 7.8 Hz, 1H), 7.64-7.59 (m, 1H), 7.56 (dt, J 1 = 1.4 Hz, J 2 = 7.5 Hz, 1H), 7.49 (t, J= 7.8 Hz,2H), 7.38 (t, J= 7.6 Hz, 1H), 7.32 (d, J= 7.7 Hz, 1H), 5.83 (dd, J 1 = 5.2 Hz, J 2 = 13.2 Hz, 1H), 3.36-3.28 (m, 1H), 3.21-3.15 (m, 1H), 2.60-2.54 (m, 1H), 2.52-2.41 (m, 1H); 13C NMR (CDCl3, 100 MHz, ppm): δ192.8, 165.8, 143.1, 133.9, 133.2, 131.7, 129.9, 129.8, 128.7, 128.4, 127.9, 127.0, 75.0, 29.3, 28.0; HRMS calc. for C17H14O3Na (M+Na)+, 289.0841; found, 289.0845.
Embodiment 14:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), 4- methylbenzene are sequentially added in 50 mL round-bottomed flasks Formic acid (0.204g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).1 is stirred at 60 DEG C Hour, DBU (0.304 g, 2 mmol) then are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop anti- It answers, is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silica gel Column) obtain corresponding product alpha-acyloxy ketone compound (yellow solid 0.241g, yield 90%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.04-7.99 (m, 4H), 7.61 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 6.21 (q, J= 7.0 Hz, 1H), 2.44 (s, 3H), 1.69 (d, J = 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ 196.9, 166.1, 144.1, 134.5, 133.6, 129.9, 129.1, 128.8, 128.6, 126.7, 71.7, 21.7, 17.2; HRMS calc. for C17H16O3Na (M+Na)+, 291.0997; found, 291.0993.
Embodiment 15:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), 4- methoxybenzene are sequentially added in 50 mL round-bottomed flasks Formic acid (0.228g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).1 is stirred at 60 DEG C Hour, DBU (0.304 g, 2 mmol) then are added, the reaction was continued 4 hours (TLC detection reaction).Then, stop anti- It answers, is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silica gel Column) obtain corresponding product alpha-acyloxy ketone compound (yellow solid 0.259g, yield 91%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.08-8.01 (m, 4H), 7.61 (t, J= 7.4 Hz, 1H), 7.51 (t, J= 7.8 Hz, 2H), 6.94 (d, J= 9.0 Hz,2H), 6.20 (q, J = 7.0 Hz, 1H), 3.89 (s, 3H), 1.68 (d, J= 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ 197.0, 165.7, 163.7, 134.6, 133.5, 132.0, 128.8, 128.6, 121.9, 113.7, 71.6, 55.5, 17.2; HRMS calc. for C17H16O4Na (M+Na)+, 307.0946; found, 307.0944.
Embodiment 16:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), 3- methylbenzene first are sequentially added in 50 mL round-bottomed flasks Sour (0.204g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is small in 60 DEG C of stirrings 1 When, DBU (0.304 g, 2 mmol) then are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop reaction, It is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) Obtain corresponding product alpha-acyloxy ketone compound (yellow liquid 0.250g, yield 93%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.03 (d, J= 7.8 Hz, 2H), 7.92 (d, J = 9.0 Hz, 2H), 7.62 (t, J = 7.2 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 7.41 (d, J= 7.6 Hz, 1H), 7.36 (t, J= 7.5 Hz, 1H), 6.23 (q, J= 7.0 Hz,1H), 2.43 (s, 3H), 1.70 (d, J= 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.8, 166.2, 138.2, 134.5, 134.1, 133.6, 130.4, 129.4, 128.8, 128.6, 128.3, 127.1, 71.8, 21.3, 17.2; HRMS calc. for C17H16O3Na (M+Na)+, 291.0997; found, 291.0991.
Embodiment 17:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), 4- chlorobenzoic acid are sequentially added in 50 mL round-bottomed flasks (0.234g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (yellow solid 0.266g, yield 92%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.07-8.01 (m, 4H), 7.63 (t, J = 7.4 Hz, 1H), 7.52 (t, J= 7.8 Hz,2H), 7.45 (d, J= 8.6 Hz,2H), 6.22 (q, J= 7.0 Hz,1H), 1.70 (d, J= 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.5, 165.1, 139.8, 134.3, 133.7, 131.3, 128.9, 128.8, 128.5, 128.0, 72.1, 17.2; HRMS calc. for C16H13O3ClNa (M+Na)+, 311.0451; found, 311.0453.
Embodiment 18:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), 4- bromobenzene first are sequentially added in 50 mL round-bottomed flasks Sour (0.3g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 4 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (white solid 0.300g, yield 90%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.02-7.97 (m, 4H), 7.64-7.60 (m, 3H), 7.52 (t, J = 7.9 Hz, 2H), 6.22 (q, J= 7.0 Hz,1H), 1.69 (d, J = 7.0 Hz, 3H);13C NMR (CDCl3, 100 MHz, ppm): δ196.5, 165.3, 134.3, 133.7, 131.8, 131.4, 128.9, 128.5, 128.4, 72.1, 17.3; HRMS calc. for C16H13O3BrNa (M+Na)+, 354.9946; found, 354.9949.
Embodiment 19:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), 4- nitrobenzoyl are sequentially added in 50 mL round-bottomed flasks Sour (0.251g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is small in 60 DEG C of stirrings 1 When, DBU (0.304 g, 2 mmol) then are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop reaction, It is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) Obtain corresponding product alpha-acyloxy ketone compound (yellow solid 0.275g, yield 92%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.35-8.29 (m, 4H), 8.01 (t, J = 7.2 Hz, 2H), 7.66 (t, J= 7.4 Hz, 1H), 7.54 (t, J= 7.9 Hz, 2H), 6.28 (q, J= 7.0 Hz, 1H), 1.74 (d, J= 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.0, 164.2, 150.8, 135.0, 134.2, 133.9, 131.0, 129.0, 128.5, 123.6, 72.8, 17.3; HRMS calc. for C16H13NO5Na (M+Na)+, 322.0691, found, 322.0693.
Embodiment 20:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), 4- trifluoromethyl are sequentially added in 50 mL round-bottomed flasks Benzoic acid (0.285g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred at 60 DEG C 1 hour, DBU (0.304 g, 2 mmol) then are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop anti- It answers, is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silica gel Column) obtain corresponding product alpha-acyloxy ketone compound (yellow solid 0.232g, yield 72%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.24 (d, J = 8.0 Hz, 2H), 8.01 (d, J = 7.2 Hz, 2H), 7.74 (d, J = 8.2 Hz, 2H), 7.64 (t, J = 7.3 Hz, 1H), 7.53 (t, J= 7.8 Hz, 2H), 6.26 (q, J= 7.0 Hz, 1H), 1.72 (d, J= 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.3, 164.8, 134.7(d, J = 32.5 Hz), 134.3, 133.8, 132.8, 130.3, 128.9, 128.5, 125.5 (q, J= 3.7 Hz), 123.6 (d, J = 271.1 Hz), 72.4, 17.3; HRMS calc. for C17H13O3F3Na (M+Na)+, 345.0714; found, 345.0717.
Embodiment 21:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), 2- chlorobenzene first are sequentially added in 50 mL round-bottomed flasks Sour (0.234g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is small in 60 DEG C of stirrings 1 When, DBU (0.304 g, 2 mmol) then are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop reaction, It is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) Obtain corresponding product alpha-acyloxy ketone compound (yellow liquid 0.269g, yield 93%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.02 (t, J= 7.4 Hz, 2H), 7.98 (d, J = 7.1 Hz, 1H), 7.64 (t, J = 7.3 Hz, 1H), 7.53 (t, J = 7.9 Hz, 2H), 7.50-7.44 (m, 2H), 7.38-7.34 (m, 1H), 6.27 (q, J= 7.0 Hz, 1H), 1.69 (d, J = 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.4, 164.9, 134.1, 133.6, 132.8, 131.8, 131.1, 129.4, 128.8, 128.5, 126.6, 72.3, 17.1;HRMS calc. for C16H13O3ClNa (M+ Na)+, 311.0451; found, 311.0553.
Embodiment 22:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), the bromo- 5- first of 2- are sequentially added in 50 mL round-bottomed flasks Yl benzoic acid (0.321g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred at 60 DEG C It mixes 1 hour, DBU (0.304 g, 2 mmol) then is added, the reaction was continued 2 hours (TLC detection reaction).Then, stop Reaction is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicon Rubber column gel column) obtain corresponding product alpha-acyloxy ketone compound (yellow liquid 0.306g, yield 88%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.03 (d, J = 7.7 Hz, 2H), 7.76 (d, J= 1.9 Hz,1H), 7.63 (t, J= 7.2 Hz, 1H), 7.56-7.51 (m, 3H), 7.18 (dd, J 1 = 2.2 Hz,J 2 = 8.2 Hz, 1H), 6.27 (q, J= 7.0 Hz, 1H), 2.37 (s, 3H), 1.69 (d, J = 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.5, 165.6, 137.4, 134.4, 134.1, 133.8, 133.7, 132.3, 131.0, 128.8, 128.6, 118.5, 72.3, 20.8, 17.2; HRMS calc. for C17H15O3BrNa (M+Na)+, 369.0102; found, 369.0104.
Embodiment 23:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), 2- bromobenzoic acid are sequentially added in 50 mL round-bottomed flasks (0.3 g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 4 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (yellow liquid 0.280g, yield 84%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.01 (d, J = 7.2 Hz, 2H), 7.97 (dd, J 1 = 2.0 Hz, J 2 = 7.6 Hz, 1H), 7.69 (dd, J 1 = 1.2 Hz, J 2 = 7.6 Hz, 1H), 7.63 (t, J = 7.4 Hz, 1H), 7.52 (t, J= 7.8 Hz, 2H), 7.43-7.37 (m, 2H), 6.27 (q, J= 7.0 Hz, 1H), 1.69 (d, J = 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.4, 165.4, 134.4, 134.4, 133.7, 132.8, 131.8, 131.4, 128.8, 128.5, 127.2, 121.9, 72.4, 17.1; HRMS calc. for C16H13O3BrNa (M+Na)+, 354.9946; found, 354.9949.
Embodiment 24:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), 2- iodo-benzoic acid are sequentially added in 50 mL round-bottomed flasks (0.372g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (yellow liquid 0.296g, yield 78%).
1H NMR (CDCl3, 400 MHz, ppm): δ8.02 (d, J = 7.2 Hz, 3H), 7.99 (dd, J 1 = 1.7 Hz, J 2 = 7.8 Hz, 1H), 7.66-7.61 (m, 1H), 7.53 (t, J= 7.8 Hz, 2H), 7.45 (dt, J 1 = 1.1 Hz, J 2 = 7.6 Hz, 1H), 7.20 (dt, J 1 = 1.7 Hz, J 2 = 7.7 Hz, 1H), 6.28 (q, J= 7.0 Hz, 1H), 1.70 (d, J= 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.4, 165.8, 141.4, 134.3, 134.2, 133.7, 133.0, 131.6, 128.9, 128.6, 128.0, 94.3, 72.5, 17.2; HRMS calc. for C16H13O3INa (M+Na)+, 402.9807; found, 402.9809 .
Embodiment 25:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), 2- phenyl benzene first are sequentially added in 50 mL round-bottomed flasks Sour (0.297g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is small in 60 DEG C of stirrings 1 When, DBU (0.304 g, 2 mmol) then are added, the reaction was continued 4 hours (TLC detection reaction).Then, stop reaction, It is concentrated under reduced pressure, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) Obtain corresponding product alpha-acyloxy ketone compound (yellow liquid 0.271g, yield 82%).
1H NMR (CDCl3, 400 MHz, ppm): δ7.97-7.92 (m, 3H), 7.57 (t, J = 8.5 Hz, 2H), 7.50-7.45 (m, 3H), 7.41-7.6-35 (m, 6H), 5.96 (q, J= 7.0 Hz, 1H), 1.32 (d, J= 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.5, 167.6, 143.0, 141.4, 134.4, 133.5, 131.6, 130.8, 130.4, 130.0, 128.7, 128.6, 128.5, 128.0, 127.2, 127.2, 72.0, 16.8; HRMS calc. for C22H18O3Na (M+Na)+, 353.1154; found, 353.1151.
Embodiment 26:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), benzenpropanoic acid are sequentially added in 50 mL round-bottomed flasks (0.225g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (yellow liquid 0.262g, yield 93%).
1H NMR (CDCl3, 400 MHz, ppm): δ7.96 (d, J= 7.2 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.9 Hz, 2H), 7.31 (t, J= 7.6 Hz, 2H), 7.24-7.22 (m, 3H), 6.00 (q, J= 7.0 Hz, 1H), 3.00 (t, J= 7.9 Hz,2H), 2.80-2.75 (m, 2H), 1.54 (d, J= 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.9, 172.3, 140.4, 134.4, 133.6, 128.8, 128.5, 128.5, 128.3, 126.3, 71.4, 35.5, 30.8, 17.1; HRMS calc. for C18H18O3Na (M+Na)+, 305.1154; found, 305.1157.
Embodiment 27:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), acetic acid are sequentially added in 50 mL round-bottomed flasks (0.09g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (yellow liquid 0.161g, yield 84%).
1H NMR (CDCl3, 400 MHz, ppm): δ7.97 (d, J = 7.2 Hz, 2H), 7.62 (t, J= 7.5 Hz, 1H), 7.51 (t, J= 7.8 Hz, 2H), 5.99 (q, J= 7.0 Hz, 1H), 2.17 (s, 3H), 1.56 (d, J = 7.1 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ196.9, 170.4, 134.5, 133.5, 128.8, 128.5, 71.4, 20.7, 17.1; HRMS calc. for C11H12O3Na (M+Na)+, 215.0684; found, 215.0682.
Embodiment 28:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), propionic acid are sequentially added in 50 mL round-bottomed flasks (0.111g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (yellow liquid 0.175g, yield 85%).
1H NMR (CDCl3, 400 MHz, ppm): δ7.97 (d, J = 7.7 Hz, 2H), 7.61 (t, J = 7.3 Hz, 1H), 7.50 (t, J = 7.8 Hz, 2H), 6.00 (q, J= 7.0 Hz,1H), 2.47-2.43 (m, 2H), 1.55 (d, J= 7.0 Hz, 3H), 1.18 (t, J= 7.0 Hz,3H); 13C NMR (CDCl3, 100 MHz, ppm): δ197.1, 173.9, 134.6, 133.5, 128.7, 128.4, 71.2, 27.3, 17.1, 8.9; HRMS calc. for C12H14O3Na (M+Na)+, 229.0841; found, 229.0845.
Embodiment 29:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), 2- tetrolic acid are sequentially added in 50 mL round-bottomed flasks (0.126g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (yellow liquid 0.194g, yield 90%).
1H NMR (CDCl3, 400 MHz, ppm): δ7.96 (d, J= 8.1 Hz, 2H), 7.63 (t, J= 7.4 Hz, 1H), 7.51 (t, J= 7.9 Hz, 2H), 6.05 (q, J= 7.0 Hz,1H), 2.03 (s, 3H), 1.60 (d, J= 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz, ppm): δ195.7, 152.8, 134.1, 133.7, 128.8, 128.5, 87.1, 72.7, 71.9, 17.1, 3.9; HRMS calc. for C13H12O3Na (M+ Na)+, 239.0684; found, 239.0687.
Embodiment 30:
At room temperature, 1- phenylpropanol (0.136 g, 1 mmol), crotonic acid are sequentially added in 50 mL round-bottomed flasks (0.129g, 1.5 mmol), NBS(0.356g, 2 mmol) and 1,4- dioxane (2 mL).It is stirred 1 hour at 60 DEG C, Then DBU (0.304 g, 2 mmol) are added, the reaction was continued 2 hours (TLC detection reaction).Then, stop reaction, decompression Concentration, obtains crude product.It is finally rinsed with the mixtures of eluents of petroleum ether and ethyl acetate, rapid column chromatography (silicagel column) obtains Corresponding product alpha-acyloxy ketone compound (yellow solid 0.109g, yield 50%).
1H NMR (CDCl3, 500 MHz, ppm): δ7.98 (d, J= 7.2 Hz, 2H), 7.61 (t, J= 7.4 Hz, 1H), 7.50 (t, J= 7.9 Hz, 2H), 7.11-7.04 (m,1H), 6.05(q, J= 7.0 Hz, 1H), 5.96 (dq, J 1 = 1.6 Hz, J 2 = 15.6 Hz, 1H), 1.91 (dd, J 1 = 1.7 Hz, J 2 = 7.0 Hz, 3H), 1.58 (d, J= 7.0 Hz, 3H); 13C NMR (CDCl3, 125 MHz, ppm): δ197.0, 165.7, 146.1, 134.5, 133.5, 128.8, 128.5, 121.9, 71.1, 18.1, 17.1; HRMS calc. for C13H14O3Na (M+Na)+, 241.0841; found, 241.0845。

Claims (15)

1. a kind of preparation method of alpha-acyloxy ketone compound characterized by comprising with carboxylic shown in pure and mild Formula II shown in Formulas I Acid is starting material, under conditions of mono- bromo-succinimide of N (NBS) and diazabicylo (DBU) mediate, reacts synthesis formula Alpha-acyloxy ketone compound shown in III, reaction equation are as follows: Wherein, R1For aryl, aralkyl, alkyl, naphthenic base, halogen, ester group, alkoxy or cyano；R2For aryl, aralkyl, alkyl, Naphthenic base or hydrogen atom；R3For aryl, aralkyl, alkyl, naphthenic base, alkynyl or alkenyl.
2. preparation method according to claim 1, it is characterised in that: the aryl includes monokaryon aryl group and multicore Aryl group.
3. preparation method according to claim 2, it is characterised in that: the aryl is phenyl, naphthalene or phenanthryl.
4. preparation method according to claim 1, it is characterised in that: the alkyl is the linear chain or branched chain alkane of C1-C20 Base；The naphthenic base is the naphthenic base of C3-C10；The halogen is fluorine, chlorine, bromine or iodine；The ester be methyl formate or Ethyl formate；The alkoxy is methoxyl group, ethyoxyl or propoxyl group；The alkynyl is propine, butine or hexin；It is described Alkenyl be propylene or butylene.
5. the preparation method according to claim 4, it is characterised in that: the linear or branched alkyl group of the C1-C20 is The alkyl of C1-C6；The naphthenic base of the C3-C10 is cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl or adamantane.
6. preparation method according to claim 5, it is characterised in that: the alkyl of the C1-C6 is ethyl, propyl, different Propyl, butyl, n-pentyl, isopentyl, hexyl.
7. preparation method according to claim 1, it is characterised in that: the molar ratio of raw alcohol and carboxylic acid is 1:1~8.
8. preparation method according to claim 7, it is characterised in that: the molar ratio of raw alcohol and carboxylic acid is 1:1~5.
9. preparation method according to claim 1, it is characterised in that: the dosage of the NBS and DBU are 2 equivalents.
10. preparation method according to claim 1, it is characterised in that: the reaction, temperature are 0~100 DEG C；It is described Reaction, can be reacted in oxygen, nitrogen or air.
11. preparation method according to claim 10, it is characterised in that: the reaction, temperature are 40~60 DEG C；It is described Reaction, react in air.
12. preparation method according to claim 1, it is characterised in that: specific steps include: at room temperature, successively by alcohol, carboxylic Acid, NBS and organic solvent mixing, in 40~60 DEG C of stirring 1h, are then added DBU, and the reaction was continued 2h obtains alpha-acyloxy assimilation and closes Object.
13. preparation method according to claim 12, it is characterised in that: the organic solvent is non-protonic solvent.
14. preparation method according to claim 13, it is characterised in that: the non-protonic solvent is Isosorbide-5-Nitrae-dioxy six Ring, tetrahydrofuran, acetonitrile, ethyl acetate, dimethyl sulfoxide, methylene chloride, chloroform, 1,2- dichloroethanes, 1,2- dimethoxy second Alkane, toluene, benzene or N,N-dimethylformamide.
15. preparation method according to claim 14, it is characterised in that: the non-protonic solvent is Isosorbide-5-Nitrae-dioxy six Ring.
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* Cited by examiner, † Cited by third party
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102964232A (en) * 2011-08-30 2013-03-13 北京大学深圳研究生院 Preparation method of ketone compound and its derivatives

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
An approach for the enantioselective synthesis of biologically active furanones from a MoritaeBayliseHillman adduct;Giovanni W. Amarante et al.;《Tetrahedron》;20100703;第66卷;第6749—6753页
Bu4NI-catalyzed a-acyloxylation reaction of ethers and ketones with aldehydes and tert-butyl hydroperoxide;Feng Zhu et al.;《Tetrahedron》;20141112;第70卷;第9819—9827页
The Bu4NI-catalyzed alfa-acyloxylation of ketones with benzylic alcohols;Songjin Guo et al.;《Chemical Communications》;20140318;第50卷;第6240—6242页

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