CN105294495A - Preparation method of cyanomethyl ester - Google Patents
Preparation method of cyanomethyl ester Download PDFInfo
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- CN105294495A CN105294495A CN201510602853.7A CN201510602853A CN105294495A CN 105294495 A CN105294495 A CN 105294495A CN 201510602853 A CN201510602853 A CN 201510602853A CN 105294495 A CN105294495 A CN 105294495A
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Abstract
The invention discloses a preparation method of cyanomethyl ester. In the presence of an oxidizing agent, a carboxylic acid compound and cyanoacetic acid are used as reactants, iodide is used as a catalyst, and sodium acetate is used as alkali, so as to prepare the cyanomethyl ester in a mixed solvent through nucleophilic substitution. According to the method, the reactivity of the catalyst is high, reaction conditions are mild, the application range of substrates is wide, the postprocessing is convenient, the yield of target products is high, a preparation process is simple, green and environmentally friendly, and the sources of used raw material are wide.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to a kind of method preparing cyanomethyl ester.
Background technology
Cyanomethyl ester is prepared in the cyaniding of carboxylic acid very important application in Synthetic Organic Chemistry because cyanomethyl ester is common medicines structure unit, biology, medicine, agricultural chemicals, food, etc. in have and apply quite widely.Cyanomethyl ester can be converted into much useful functional compounds, the nitrogen heterocyclic alkene of such as alpha hydroxy acid, beta-alkamine, alpha-hydroxy esters, α-sulphonyl nitrile, alpha-aminonitriles, α-fluoridize nitrile, 3-amino-2-alkenoic acid and various replacement.
Under the effect of triethylamine, chloromethyl cyanide and carboxylic acid cpd a step can build cyanomethyl ester compound (HelmutM.Hugel, K.VijavaBhashai by nucleophilic substitution reaction, RobertW.Longmore, SyntheticCommunication, 1992,22,693-697); But this system produces the halogen materialization of equivalent, has very serious environmental pollution.Under the effect of electron reduction agent, utilize benzoyl nitrile can build cyanomethyl ester compound (MitsuhiroOkimoto, ToshiakiItoh, ToshiroChiba, J.Org.Chem., 1996,61,4835-4837); This system can not solely generate cyanomethylation compound, and the by product often with 1,2-diketone occurs, the Atom economy of reaction is not high.Under the condition of Lewis base, benzoyl nitrile and pimelinketone can build cyanalcohol compounds (WenZhang, MinShi, Org.Biomol.Chem., 2006,4,1671-1674); This system can only build the cyanalcohol compounds containing ring-type, and the universality of system is not high.
Therefore find that a kind of raw material sources are simple, reactive behavior is higher, cost is low, safety, environmental protection, substrate applicability preparation method that is strong, good operability be necessary effectively to synthesize cyanomethyl ester.
Summary of the invention
The object of this invention is to provide a kind of method preparing cyanomethyl ester, the method cost be low, preparation process is simple and easy, environmental protection.
To achieve the above object of the invention, the technical solution used in the present invention is:
A kind of method preparing cyanomethyl ester, comprise the following steps: under the existence of organic oxidizing agent, with carboxylic acid cpd and cyanoacetic acid for reactant, with elemental iodine or iodide for catalyzer, be alkali with sodium compound, in mixed solvent, prepare product cyanomethyl ester by nucleophilic substitution reaction;
Wherein, described carboxylic acid cpd is selected from the one in following chemical structural formula:
,
,
,
,
,
,
,
,
; Wherein, R
1be selected from hydrogen, methyl, bromine, iodine, benzoyl or methoxyl group; R
2be selected from fluorine, chlorine, methyl, cyano group, ester group or trifluoromethyl; R
3be selected from fluorine, chlorine, bromine, cyano group, nitro or the tertiary butyl;
Described mixed solvent is the mixed solution of water and organic solvent.
In technique scheme, described alkali is sodium-acetate (NaOAc); Iodide are selected from the one in tetrabutylammonium iodide, N-N-iodosuccinimide, iodine bromide IBr.
In technique scheme, described mixed solvent is the mixed solution of water, tetrahydrofuran (THF), and the volume ratio of the two is 1: 1.
In technique scheme, described oxygenant is peroxy tert-butyl alcohol.
In technique scheme, according to mol ratio, carboxylic acid cpd: cyanoacetic acid=1: 1 ~ 3, is preferably 1: 2.
In technique scheme, according to mol ratio, catalyzer: oxygenant: alkali: carboxylic acid cpd=0.10 ~ 0.20: 1 ~ 3: 1 ~ 3: 1; Preferably, catalyzer: oxygenant: alkali: carboxylic acid cpd=0.15: 2.2: 2: 1.
In technique scheme, reaction process comprises in air atmosphere, carboxylic acid cpd, cyanoacetic acid, iodide, oxygenant and solvent is mixed, stir 2 ~ 14 hours at 70 ~ 100 DEG C, termination reaction, reaction solution extracts, silica gel adsorption, obtains cyanomethyl ester finally by rapid column chromatography.
In technique scheme, the preferred reaction times is 12 hours, and temperature of reaction is 80 DEG C.
In technique scheme, the consumption of described catalyzer is 10% ~ 20% of the mole number of reactant, be preferably 15%, the consumption of catalyzer crosses that I haven't seen you for ages makes reaction efficiently carry out, but the consumption of catalyzer is crossed conference and increased reaction cost and the aftertreatment affecting reaction system.
In technique scheme, described termination reaction, extraction, silica gel adsorption, obtain the operations such as cyanomethyl ester finally by rapid column chromatography and all belong to prior art, wherein used extraction agent, eluent are also prior aries, those skilled in the art can select suitable reagent according to the character of final product, in preferred technical scheme, termination reaction adopts saturated sodium sulfite cancellation, and extraction agent is ethyl acetate, and eluent is ethyl acetate/petroleum ether system.
Because technique scheme is used, the present invention compared with prior art has following advantages:
1. the present invention first with carboxylic acid cpd and cyanoacetic acid for reactant, in atmosphere, prepare cyanomethyl ester, wide application range of substrates, the reaction times is shorter, yield is high; And reactive behavior is good, not having poisonous and hazardous by product to produce, is that a kind of cost is low, raw material availability is high, the preparation method of environmental protection.
2. the present invention uses iodide to carry out substitution reaction as catalyst carboxylic acid cpd and cyanoacetic acid to prepare cyanomethyl ester, compared with the catalyzer such as metal of the prior art, react safer, more green, more economical; And catalyst levels is not high, product yield is high, achieves beyond thought technique effect.
3. the method preparing cyanomethyl ester disclosed by the invention avoids the complex operations of anhydrous and oxygen-free, and reaction conditions is gentle, and aftertreatment is more simple, is conducive to the purifying of product; The cheaper starting materials such as reactant, catalyzer used is easy to get, and non-pollutant discharge, meets requirement and the direction of contemporary green chemistry, is suitable for industrial production.
Embodiment
Below in conjunction with embodiment, the invention will be further described:
Embodiment one
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 78%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment two
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 90 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 77%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment three
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 100 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 74%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment four
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NH
4hCO
3(4mmol, 316mg), TBHP(0.6mL), water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 80%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment five
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), KF(4mmol, 232mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 75%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment six
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaHCO
3(4mmol, 336mg), TBHP(0.6mL), water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 65%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment seven
TBAI(0.2mmol, 74mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 65%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment eight
TBAI(0.4mmol, 148mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 84%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment nine
I is loaded successively in reaction flask
2(0.3mmol, 76.5mg), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 60%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment ten
NIS(0.3mmol, 67.5mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 55%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment 11
BrI(0.3mmol, 62.3mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 60%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment 12
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 2 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 60%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment 13
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 4 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 70%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment 14
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 14 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 78%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment 15
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.27mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 55%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment 16
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1a(2mmol, 247mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.82mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3a, yield is 70%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.04(m,2H),7.65–7.61(m,1H),7.50–7.46(m,2H),4.96(s,2H);
13CNMR(100MHz,CDCl
3)δ164.9,134.1,129.9,128.6,127.8,114.4,48.8;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
7NO
2+H
+:162,Found:162(M+H
+);IR(neat,cm
-1):υ2957,2918,2240,1729,1494,1252。
Embodiment 17
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1b(2mmol, 281mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3b, yield is 82%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.10–8.06(m,2H),7.18–7.13(m,2H),4.97(s,2H);
13CNMR(100MHz,CDCl
3)δ166.3(d,
J=254.5Hz),163.9,132.6(d,
J=9.6Hz),124.1(d,
J=3.0Hz),115.9(d,
J=22.9Hz),114.4,48.9;HRMS(ESI-TOF):Anal.Calcd.ForC
9H
6FNO
2+Na
+:202.0275,Found:202.0269(M+Na
+);IR(neat,cm
-1):υ2960,2925,2256,1731,1600,1507。
Embodiment 18
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1c(2mmol, 312mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3c, yield is 92%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.00–7.97(m,2H),7.47–7.43(m,2H),4.97(s,2H);
13CNMR(100MHz,CDCl
3)δ164.0,140.7,131.3,129.0,126.2,114.3,48.9;HRMS(ESI-TOF):Anal.Calcd.ForC
9H
6 35ClNO
2+Na
+:217.9979,C
9H
6 37ClNO
2+Na
+:219.9950,Found:217.9979(M+Na
+),219.9942(M+Na
+);IR(neat,cm
-1):υ2969,2923,2248,1728,1488,1289。
Embodiment 19
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1d(2mmol, 401mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3d, yield is 88%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ7.92–7.89(m,2H),7.63–7.60(m,2H),4.97(s,2H);
13CNMR(100MHz,CDCl
3)δ164.2,132.0,131.3,129.4,126.7,114.2,48.9;HRMS(ESI-TOF):Anal.Calcd.ForC
9H
6 79BrNO
2+Na
+:261.9474,C
9H
6 81BrNO
2+Na
+:263.9454,Found:261.9463(M+Na
+),263.9450(M+Na
+);IR(neat,cm
-1):υ2966,2921,2248,1727,1587,1261。
Embodiment 20
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1e(2mmol, 294mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3e, yield is 60%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.19–8.17(m,2H),7.82–7.80(m,2H),5.02(s,2H);
13CNMR(100MHz,CDCl
3)δ163.4,132.4,131.6,130.4,117.5,113.9,99.9,49.3;HRMS(ESI-TOF):Anal.Calcd.ForC
10H
6N
2O
2+Na
+:209.0321,Found:209.0313(M+Na
+);IR(neat,cm
-1):υ2922,2851,2263,2231,1731,1261,1107。
Embodiment 21
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1f(2mmol, 334mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3f, yield is 60%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.36–8.33(m,2H),8.28–8.24(m,2H),5.04(s,2H);
13CNMR(100MHz,CDCl
3)δ163.2,151.1,133.1,131.2,123.8,113.8,49.4;HRMS(ESI-TOF):Anal.Calcd.ForC
9H
6N
2O
4+Na
+:229.0220,Found:229.0215(M+Na
+);IR(neat,cm
-1):υ2954,2923,2265,1731,1347,1262。
Embodiment 22
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1g(2mmol, 356mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3g, yield is 99%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.00–7.97(m,2H),7.50–7.48(m,2H),4.95(s,2H),1.34(s,9H);
13CNMR(100MHz,CDCl
3)δ164.9,157.9,129.9,125.6,124.9,114.6,48.6,35.1,30.9;HRMS(ESI-TOF):Anal.Calcd.ForC
13H
15NO
2+Na
+:240.0995,Found:240.0995(M+Na
+);IR(neat,cm
-1):υ2964,2907,2258,1730,1608,1264。
Embodiment 23
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1h(2mmol, 281mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3h, yield is 88%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ7.87–7.84(m,1H),7.74–7.71(m,1H),7.50–7.45(m,1H),7.36–7.31(m,1H),4.98(s,2H);
13CNMR(100MHz,CDCl
3)δ163.8(d,
J=3.1Hz),162.4(d,
J=246.6Hz),130.4(d,
J=7.8Hz),129.9(d,
J=7.6Hz),125.7(d,
J=3.2Hz),121.2(d,
J=21.1Hz),116.8(d,
J=23.3Hz),114.2,49.0;HRMS(ESI-TOF):Anal.Calcd.ForC
9H
6FNO
2+Na
+:202.0275,Found:202.0276(M+Na
+);IR(neat,cm
-1):υ2918,2849,2238,1725,1443,1266。
Embodiment 24
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1i(2mmol, 312mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3i, yield is 90%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.02–7.93(m,2H),7.61–7.59(m,1H),7.45–7.41(m,1H),4.98(s,2H);
13CNMR(100MHz,CDCl
3)δ163.7,134.8,134.1,130.0,129.9,129.5,128.0,114.2,49.0;HRMS(ESI-TOF):Anal.Calcd.ForC
9H
6 35ClNO
2+Na
+:217.9979,C
9H
6 37ClNO
2+Na
+:219.9950,Found:217.9978(M+Na
+),219.9953(M+Na
+);IR(neat,cm
-1):υ2968,2921,2254,1732,1422,1252。
Embodiment 25
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1j(2mmol, 272mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3j, yield is 93%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ7.86–7.83(m,2H),7.43–7.41(m,1H),7.37–7.33(m,1H),4.94(s,2H),2.40(s,3H);
13CNMR(100MHz,CDCl
3)δ165.0,138.5,134.8,130.3,128.5,127.7,127.0,114.5,48.7,21.1;HRMS(ESI-TOF):Anal.Calcd.ForC
10H
9NO
2+Na
+:198.0525,Found:198.0532(M+Na
+);IR(neat,cm
-1):υ2924,2866,2267,1729,1271,1187。
Embodiment 26
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1k(2mmol, 294mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3k, yield is 70%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.35–8.29(m,2H),7.94–7.92(m,1H),7.68–7.65(m,1H),5.02(s,2H);
13CNMR(100MHz,CDCl
3)δ163.1,137.0,133.9,133.5,129.8,129.2,117.4,113.9,113.4,49.3;HRMS(ESI-TOF):Anal.Calcd.ForC
10H
6N
2O
2+Na
+:209.0321,Found:209.0314(M+Na
+);IR(neat,cm
-1):υ2979,2948,2232,2194,1739,1272,1186。
Embodiment 27
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1l(2mmol, 380mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3l, yield is 90%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.32–8.25(m,2H),7.91–7.89(m,1H),7.67–7.63(m,1H),5.02(s,2H);
13CNMR(100MHz,CDCl
3)δ163.7,133.1,131.9,131.6,131.2,130.9,130.7,130.61,130.57,130.54,129.5,128.7,127.4,126.92,126.88,126.85,126.81,124.7,122.0,119.3,114.1,49.2;HRMS(ESI-TOF):Anal.Calcd.ForC
10H
6F
3NO
2+Na
+:252.0243,Found:252.0242(M+Na
+);IR(neat,cm
-1):υ3015,2962,2259,1737,1618,1332。
Embodiment 28
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1m(2mmol, 496mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3m, yield is 92%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.05–8.03(m,1H),7.89–7.87(m,1H),7.47–7.43(m,1H),7.24–7.20(m,1H),4.98(s,2H);
13CNMR(100MHz,CDCl
3)δ164.3,141.8,133.7,132.1,131.5,128.1,114.1,94.6,49.1;HRMS(ESI-TOF):Anal.Calcd.ForC
9H
6INO
2+Na
+:309.9335,Found:309.9337(M+Na
+);IR(neat,cm
-1):υ2959,2921,2248,1731,1618,1426。
Embodiment 29
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1n(2mmol, 401mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3n, yield is 95%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ7.89–7.85(m,1H),7.72–7.68(m,1H),7.43–7.38(m,2H),4.98(s,2H);
13CNMR(100MHz,CDCl
3)δ164.0,134.7,133.7,131.8,129.2,127.3,122.3,114.1,49.0;MS(ESI-quadrupole):Anal.Calcd.ForC
9H
6 79BrNO
2+H
+:240,C
9H
6 81BrNO
2+H
+:242,Found:240(M+H
+),242(M+H
+);IR(neat,cm
-1):υ3011,2966,2248,1727,1624,1468。
Embodiment 30
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1o(2mmol, 272mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3o, yield is 92%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ7.97–7.95(m,1H),7.48–7.45(m,1H),7.29–7.26(m,2H),4.92(s,2H),2.62(s,3H);
13CNMR(100MHz,CDCl
3)δ165.3,141.4,133.2,132.0,131.0,126.8,125.9,114.6,48.4,21.8;HRMS(ESI-TOF):Anal.Calcd.ForC
10H
9NO
2+Na
+:198.0525,Found:198.0530(M+Na
+);IR(neat,cm
-1):υ2969,2931,2252,1731,1237,1069。
Embodiment 31
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1p(2mmol, 304mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3p, yield is 70%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ7.88–7.85(m,1H),7.57–7.52(m,1H),7.02–6.99(m,2H),4.93(s,2H),3.92(s,3H);
13CNMR(100MHz,CDCl
3)δ164.0,159.9,135.0,132.2,120.2,117.0,114.6,112.1,55.9,48.4;MS(ESI-quadrupole):Anal.Calcd.ForC
10H
9NO
3+H
+:192,Found:192(M+H
+);IR(neat,cm
-1):υ2963,2920,2250,1731,1467,1437。
Embodiment 32
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1q(2mmol, 300mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3q, yield is 98%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ7.25–7.21(m,1H),7.06–7.04(m,2H),4.92(s,2H),2.33(s,6H);
13CNMR(100MHz,CDCl
3)δ168.0,135.6,131.0,130.2,127.7,114.2,48.3,19.7;HRMS(ESI-TOF):Anal.Calcd.ForC
11H
11NO
2+Na
+:212.0682,Found:212.0677(M+Na
+);IR(neat,cm
-1):υ2924,2852,2263,1736,1260,1247。
Embodiment 33
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1r(2mmol, 296mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3r, yield is 88%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ7.78(d,
J=16.0Hz,1H),7.54–7.50(m,2H),7.45–7.37(m,3H),6.44(d,
J=16.0Hz,1H),4.84(s,2H);
13CNMR(100MHz,CDCl
3)δ165.0,147.6,133.6,131.0,128.9,128.3,115.2,114.5,48.3;MS(ESI-quadrupole):Anal.Calcd.ForC
11H
9NO
2+H
+:188,Found:188(M+H
+);IR(neat,cm
-1):υ2948,2854,2260,1718,1638,1574。
Embodiment 34
TBAI(0.3mmol, 148mg is loaded successively in reaction flask), compound
1s(2mmol, 360mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3s, yield 92%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.69–8.68(m,1H),8.30–8.23(m,2H),7.61–7.57(m,1H),5.02(s,2H),3.97(s,3H);
13CNMR(100MHz,CDCl
3)δ165.7,164.1,134.8,134.0,130.9,130.8,128.9,128.3,114.2,52.4,49.0;HRMS(ESI-TOF):Anal.Calcd.ForC
11H
9NO
4+Na
+:242.0424,Found:242.0434(M+Na
+);IR(neat,cm
-1):υ2950,2921,2250,1737,1718,1172,1105。
Embodiment 35
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1t(2mmol, 256mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3t, yield is 88%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ7.89–7.88(m,1H),7.68–7.67(m,1H),7.16–7.14(m,1H),4.94(s,2H);
13CNMR(100MHz,CDCl
3)δ160.3,135.1,134.3,130.7,128.1,114.3,48.7;MS(ESI-quadrupole):Anal.Calcd.ForC
7H
5NO
2S+H
+:168,Found:168(M+H
+);IR(neat,cm
-1):υ2968,2923,2250,1712,1424,1275。
Embodiment 36
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1u(2mmol, 300mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.60mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3u, yield is 75%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ7.31–7.28(m,2H),7.23–7.18(m,3H),4.67(s,2H),2.97(t,
J=7.7Hz,2H）,2.72(t,
J=7.7Hz,2H);
13CNMR(100MHz,CDCl
3)δ171.1,139.5,128.6,128.2,126.5,114.3,48.2,35.0,30.4;HRMS(ESI-TOF):Anal.Calcd.ForC
11H
11NO
2+Na
+:212.0682,Found:212.0684(M+Na
+);IR(neat,cm
-1):υ2955,2933,2257,1750,1454,1425。
Embodiment 37
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1v(2mmol, 352mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3v, yield is 80%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.19–8.17(m,1H),7.50–7.49(m,2H),7.39–7.35(m,1H),5.08(s,2H),4.20(s,3H);
13CNMR(100MHz,CDCl
3)δ160.6,141.0,132.3,127.2,123.79,123.77,121.6,114.4,109.7,48.5,36.6;HRMS(ESI-TOF):Anal.Calcd.ForC
11H
9N
3O
2+Na
+:238.0587,Found:238.0589(M+Na
+);IR(neat,cm
-1):υ2922,2852,2249,1713,1361,1271。
Embodiment 38
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1w(2mmol, 392mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3w, yield is 82%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ7.90–7.84(m,2H),7.81–7.79(m,1H),7.56–7.47(m,2H),7.44–7.37(m,2H),4.62(s,2H),4.12(s,2H);
13CNMR(100MHz,CDCl
3)δ169.9,133.8131.8,128.84,128.81,128.6,128.2,126.7,125.9,125.4,123.3,114.2,48.6,38.1;HRMS(ESI-TOF):Anal.Calcd.ForC
16H
11NO
3+Na
+:248.0682,Found:248.0678(M+Na
+);IR(neat,cm
-1):υ2918,2851,2254,1747,1414,1153。
Embodiment 39
TBAI(0.3mmol, 111mg is loaded successively in reaction flask), compound
1x(2mmol, 452mg), compound
2(4mmol, 341mg), NaOAc(4mmol, 164mg), TBHP(0.6mL) and, water (4.0mL), tetrahydrofuran (THF) (4.0mL).Then, after this system heats about 12 hours under 80 DEG C of conditions in atmosphere, use saturated sodium bisulfite solution cancellation, be extracted with ethyl acetate (40mL × 3), silica gel adsorption, by simple column chromatography product
3x, yield is 92%.The main test data of obtained product is as follows, and known by analyzing, actual synthetic product is consistent with theoretical analysis.
1HNMR(400MHz,CDCl
3)δ8.07–8.05(m,1H),7.76–7.68(m,3H),7.63–7.55(m,2H),7.46–7.43(m,3H),4.67(s,2H);
13CNMR(100MHz,CDCl
3)δ196.2,164.3,142.0,136.5,133.4,133.3,130.4,129.8,129.3,128.6,128.1,126.9,113.7,48.8;HRMS(ESI-TOF):Anal.Calcd.ForC
16H
11NO
3+H
+:266.0812,Found:266.0812(M+H
+);IR(neat,cm
-1):υ2918,2850,2254,1721,1673,1486。
Claims (10)
1. the preparation method of a cyanomethyl ester, it is characterized in that: under the existence of organic oxidizing agent, with carboxylic acid cpd and cyanoacetic acid for reactant, with elemental iodine or iodide for catalyzer, be alkali with sodium compound, in mixed solvent, prepare product cyanomethyl ester by nucleophilic substitution reaction;
Wherein, described carboxylic acid cpd is selected from the one in following chemical structural formula:
,
,
,
,
,
,
,
,
; Wherein, R
1be selected from hydrogen, methyl, bromine, iodine, benzoyl or methoxyl group; R
2be selected from fluorine, chlorine, methyl, cyano group, ester group or trifluoromethyl; R
3be selected from fluorine, chlorine, bromine, cyano group, nitro or the tertiary butyl;
Described mixed solvent is the mixed solution of water and organic solvent.
2. the preparation method of cyanomethyl ester according to claim 1, is characterized in that: described alkali is sodium-acetate; Described oxygenant is peroxy tert-butyl alcohol.
3. the preparation method of cyanomethyl ester according to claim 1, is characterized in that: described iodide are selected from the one in tetrabutylammonium iodide, N-N-iodosuccinimide, iodine bromide IBr.
4. the preparation method of cyanomethyl ester according to claim 1, is characterized in that: described mixed solvent is volume ratio is the water of 1: 1 and the mixed solution of tetrahydrofuran (THF).
5. the preparation method of cyanomethyl ester according to claim 1, is characterized in that: described nucleophilic substitution reaction carries out in atmosphere.
6. the preparation method of cyanomethyl ester according to claim 1, is characterized in that: according to a mole meter, carboxylic acid cpd: cyanoacetic acid=1: 1 ~ 3; Described catalyzer is 10 ~ 20% of carboxylic acid cpd; Described oxygenant is 1 ~ 3 times of carboxylic acid cpd; Described alkali is 1 ~ 3 times of carboxylic acid cpd.
7. the preparation method of cyanomethyl ester according to claim 6, is characterized in that, according to a mole meter, and carboxylic acid cpd: cyanoacetic acid=1: 2; Described catalyzer is 15% of carboxylic acid cpd; Described oxygenant is 2.2 times of carboxylic acid cpd; Described alkali is 2 times of carboxylic acid cpd.
8. the preparation method of cyanomethyl ester according to claim 1, it is characterized in that, described nucleophilic substitution reaction temperature is 70 ~ 100 DEG C; Time is 2 ~ 14 hours.
9. the preparation method of cyanomethyl ester according to claim 8, it is characterized in that, described nucleophilic substitution reaction temperature is 80 DEG C; Time is 12 hours.
10. the preparation method of cyanomethyl ester according to claim 1, is characterized in that, after reaction terminates, termination reaction, through silica gel adsorption after reaction solution extraction, obtains cyanomethyl ester finally by rapid column chromatography.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060069077A1 (en) * | 2002-07-15 | 2006-03-30 | Rice Kenneth D | Receptor-type kinase modulators and methods of use |
| WO2008131119A2 (en) * | 2007-04-17 | 2008-10-30 | Acropolis Pharmaceuticals, Inc. | Composition and method for cancer treatment and prevention |
| WO2013149362A1 (en) * | 2012-04-06 | 2013-10-10 | Glaxosmithkline Llc | 1-(dihydronaphthalenyl)pyridones as melanin-concentrating hormone receptor 1 antagonists |
| CN104693035A (en) * | 2015-02-12 | 2015-06-10 | 中国农业大学 | Salicylic acid trans-(beta)-farnesene analogues and application thereof |
-
2015
- 2015-09-21 CN CN201510602853.7A patent/CN105294495A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060069077A1 (en) * | 2002-07-15 | 2006-03-30 | Rice Kenneth D | Receptor-type kinase modulators and methods of use |
| WO2008131119A2 (en) * | 2007-04-17 | 2008-10-30 | Acropolis Pharmaceuticals, Inc. | Composition and method for cancer treatment and prevention |
| WO2013149362A1 (en) * | 2012-04-06 | 2013-10-10 | Glaxosmithkline Llc | 1-(dihydronaphthalenyl)pyridones as melanin-concentrating hormone receptor 1 antagonists |
| CN104693035A (en) * | 2015-02-12 | 2015-06-10 | 中国农业大学 | Salicylic acid trans-(beta)-farnesene analogues and application thereof |
Non-Patent Citations (5)
| Title |
|---|
| JIE ZHANG等: "A New Strategy for the Construction of α-Amino Acid Esters via Decarboxylation", 《ORGANIC LETTERS》 * |
| JIE ZHANG等: "Transition-metal-free decarboxylation of dimethyl malonate: an efficient construction of α-amino acid esters using TBAI/TBHP", 《ORG.BIOMOL.CHEM.》 * |
| LILI CHEN等: "Binding interaction of quercetin-3-β-galactoside and its synthetic derivatives with SARS-CoV 3CLpro: Structure–activity relationship studies reveal salient pharmacophore features", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
| QIAO REN等: "Highly Efficient Assembly of 3-Hydroxy Oxindole Scaffold via a Catalytic Decarboxylative [1,2]-Addition Strategy", 《ACS CATAL.》 * |
| V. PRATAP REDDY GAJULAPALLI等: "Organocatalytic asymmetric decarboxylative cyanomethylation of isatins using L-proline derived bifunctional thiourea", 《ORG. BIOMOL. CHEM.》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112694398A (en) * | 2018-07-31 | 2021-04-23 | 苏州大学 | Application of diazo compound and alpha-Br ketone compound as raw materials in preparation of oxalate |
| CN112694398B (en) * | 2018-07-31 | 2022-04-26 | 苏州大学 | Application of diazo compound and alpha-Br ketone compound as raw materials in preparation of oxalate |
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