CN102584509A - Preparation method of amide - Google Patents
Preparation method of amide Download PDFInfo
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- CN102584509A CN102584509A CN2012100159220A CN201210015922A CN102584509A CN 102584509 A CN102584509 A CN 102584509A CN 2012100159220 A CN2012100159220 A CN 2012100159220A CN 201210015922 A CN201210015922 A CN 201210015922A CN 102584509 A CN102584509 A CN 102584509A
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- 0 *c1ccc(C=O)cc1 Chemical compound *c1ccc(C=O)cc1 0.000 description 2
- CVVVRVRQWUMYNX-UHFFFAOYSA-N C=CCN(CC=C)C=O Chemical compound C=CCN(CC=C)C=O CVVVRVRQWUMYNX-UHFFFAOYSA-N 0.000 description 1
- CPSNYKXHMCDALW-UHFFFAOYSA-N CN(C)C(c(cc1)ccc1C#N)=O Chemical compound CN(C)C(c(cc1)ccc1C#N)=O CPSNYKXHMCDALW-UHFFFAOYSA-N 0.000 description 1
- WZWIQYMTQZCSKI-UHFFFAOYSA-N N#Cc1ccc(C=O)cc1 Chemical compound N#Cc1ccc(C=O)cc1 WZWIQYMTQZCSKI-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention discloses a preparation method of amide. With an aldehyde derivative and a formamide derivative as a reaction substrate, iodide as catalyst and tert-butanol hydrogen peroxide as an oxidizing agent, the amide is prepared through decarbonylation double free radical cross-coupling reaction, wherein in the chemical structural formula of the aldehyde derivative, R1 is selected from a naphthyl, a heterlcyclic ring, an alkylene or a mono-substituted aryl; and the iodide is one selected from sodium iodide, potassium iodide, cuprous iodide, lithium iodate, an iodine elementary substance, tetrabutyl ammonium iodide, tetraheptylammonium iodide, tetramethylammonium iodide and benzyltrimethylammonium iodide. According to the invention, because the amide is prepared by using the iodide as the catalyst and using the double free radical cross-coupling method, the use of the traditional metal catalyst with expensive price and larger toxicity as well as a complicated experiment method is avoided so that the reaction is simpler, more convenient, easier, safer, greener and more economic; moreover, the preparation method of the amide disclosed by the invention has the advantages of quite moderate reaction condition, simpler post-treatment and potential industrial application value.
Description
Technical field
The present invention relates to a kind of method for preparing acid amides.
Background technology
Acid amides is one type of very important structural unit, extensively is present among natural product that physiologically active is arranged, the drug molecule, and is also visible often in synthetic intermediate.
At present, the method for preparing acid amides has catalyst levels bigger, and price is comparatively expensive, and toxicity is bigger, severe reaction conditions, the shortcoming that selectivity is low, the substrate use range is narrow.For example:
(1) people such as J.M.J.Williams has reported that use carboxylic acid and verivate and amine linked reaction thereof prepare acid amides, (referring to: C.L.Allen, J.M.J.Williams, Chem.Soc.Rev 2011,40, and 3405);
(2) thus people such as H.Alper have reported the ammonia carboxylation reaction through halogenated aryl hydrocarbon can optionally synthesize one type of acid amides, (referring to Y.-S.Lin, H.Alper, Angew.Chem.2001,113,801; Angew.Chem.Int.Ed.2001,40,779);
(3) people such as S.Murahashi has reported that the transition metal-catalyzed oxidation alcohol and the linked reaction of ammonia directly make the reaction of acid amides, (referring to: T.Naota, S.Murahashi, Synlett 1991,693);
(4) people such as S.B.Kent has reported and has utilized thiocarboxylic acid or sulfur ester to come effectively to make up amido linkage as acylting agent, (referring to: P.E.Dawson, T.W.Muir, I.Clark-Lewis, S.B.Kent, Science 1994,266, and 776);
(5) patent No. is the method that 01807450.2 Chinese invention patent discloses a kind of 6-of preparation aminocaproamide; Comprise 5-cyanovaleramide and hydrogen are reacted in the presence of metal catalyst; Said metal catalyst is selected from metal catalyst, sponge metal catalyst, homogeneous catalyst and reductive MOX, oxyhydroxide or the carbonate catalyst of carrierization; If wherein catalyzer is the carrier metal catalyst that contains cobalt or nickel; And if the calcining of carrier process, then before using nickel or cobalt, calcine, wherein be reflected under the situation that does not have diox and carry out;
(6) patent No. a kind of method that under mild condition, prepares acid amides that has been 03803556.1 Chinese disclosure of the Invention, shown in the following chemical formula of its reaction process:
Work as R
9When being methyl, ethyl or aryl, under the situation that has Lewis acid, aprotic organic solvent and alkali, reaction can be carried out under 20～80 ℃; Perhaps work as R
9When being hydrogen, under the situation that has THIONYL CHLORIDE 97, aprotic organic solvent and alkali, reaction can be carried out under 20～70 ℃;
(7) other methods that make up acid amides also have: and the hydrolysis of itrile group (referring to: T.Ghaffar, A.W.Parkins, Tetrahedron Lett.1995,36; 8657), the rearrangement of oxime (referring to: N.A.Owston, A.J.Parker, J.M.J.Williams, Org.Lett.2007; 9,3599), the acylations of amine is (referring to J.W.W.Chang, P.W.H.Chan; Angew.Chem.2008,120,1154; Angew.Chem.Iht.Ed.2008,47,1138), improved Staudinger reaction (referring to: E.Saxon; C.R.Bertozzi, Science 2000,287; 2007), the acylations of alkene and alkynes is (referring to M.Beller, B.Cornils, C.D.Frohning; C.W.Kohlpaintner, J.Mol.Catal.A:Chem.1995,104; B.E.Ali, J.Tijani, Appl.Organomet.Chem.2003,17; 921), the amidation of cyanic acid (referring to: S.-I.Murahashi, T.Naota, E.Saito, J.Am.Chem.Soc.1986; 108,7846) and transition metal-catalyzed C-C bond cleavage method such as separate (referring to Y.Kuninobu, T.Uesugi, A.Kawata; K.Takai, Angew.Chem.2011,123,10590; Angew.Chem.Iht.Ed.2011,50,10406).
Although the method for synthesizing amide is numerous; But in these methods some the catalyzer that uses relatively expensive (like Ru, Rh, Pd, Ni, Cu), some catalystsystem is more loaded down with trivial details, some reactant preparation trouble; Price is more expensive; The use range of substrate is narrow simultaneously, and bigger limitation is arranged, and has limited its large-scale application.
Therefore, need to seek a kind of relative low price, toxicity is lower, and catalyst system easy and simple to handle replaces above catalystsystem to prepare the method for acid amides.
Summary of the invention
Goal of the invention of the present invention provides a kind of method for preparing acid amides, guarantees to be reflected at when reacting under the gentle condition, reduces the use expensive or catalyzer that toxicity is high, makes the more environmental protection of preparation process, and is more economical.
For reaching the foregoing invention purpose; The technical scheme that the present invention adopts is: a kind of method for preparing acid amides; With aldehyde derivatives and carboxamides derivatives is reaction substrate, is catalyzer with iodide, and trimethyl carbinol hydrogen peroxide is that oxygenant prepares acid amides through decarbonylation diradical cross-coupling reaction;
Wherein, the chemical structural formula of said aldehyde derivatives is:
In the formula, R
1Be selected from: naphthyl, heterocycle, alkylene or single substituted aryl
Wherein, R
2Be selected from: the ester group of hydrogen, methyl, methoxyl group, phenoxy, styryl, phenylacetylene base, methylthio group, cyanic acid, C1～C6, nitro, carboxamido-group, halogen, trifluoromethyl, the amino of Methyl benzenesulfonyl base protection, the hydroxyl of tertbutyloxycarbonyl protection;
Preferably, heterocycle is selected from: thienyl, furyl, thiazolyl, pyridyl; Alkene is selected from: allyl group, styryl, phenylacetylene base etc.;
The chemical structural formula of said carboxamides derivatives is:
Wherein, R
3, R
4Be selected from: the saturated chain type alkyl of C1～C4, benzyl, allyl group, the saturated five-ring of C4～C5, six-ring, heterocycle;
Preferably, heterocycle is selected from: morpholine, pyrazoles, piperazine;
Said iodide are selected from: Soiodin NaI, potassiumiodide KI, cuprous iodide CuI, lithium iodide LiI, elemental iodine I
2, tetrabutylammonium iodide, four n-heptyl ammonium iodides, Tetramethylammonium iodide, a kind of in the benzyltrimethylammonium iodide.
In the technique scheme, the said temperature of reaction for preparing the method for acid amides is 60～100 ℃, preferred 90 ℃; Reaction times is 2～24 hours, preferred 24 hours.
In the technique scheme, catalyst consumption be the reaction substrate aldehyde derivatives amount of substance 5～40%, catalyst levels increases or reduces the productive rate influence little; Preferred 20%.
In the technique scheme, the consumption of methane amide is 10～20 equivalents of reaction substrate aldehyde derivatives amount of substance, promptly 2～20 of the amount of substance of reaction substrate aldehyde derivatives times; Be preferably 15 equivalents.
In the technique scheme, used solvent is: vinyl trichloride, toluene, acetonitrile, 1,2-ethylene dichloride or 1.
In the technique scheme, oxygenant is peroxy tert-butyl alcohol TBHP, and the consumption of oxygenant is 1～10 equivalent, is preferably 5～6 equivalents, most preferably is 5.8 equivalents.
Further in the technical scheme; After accomplishing, reaction reacts with the saturated sodium sulfite cancellation earlier; With ETHYLE ACETATE or dichloromethane extraction, recycle silicon glue adsorbs vacuum and revolves dried solvent then, carries out simple column chromatography with the mixed solvent of ETHYLE ACETATE and sherwood oil then and just can get final product.
In the technique scheme, said catalyzer, reactant are all market-oriented commodity, can directly buy to obtain.
Because the technique scheme utilization, the present invention compared with prior art has advantage:
1. because the present invention adopts iodide to prepare acid amides as catalyst; Expensive catalysts and the dangerous acid amides halogenide that is difficult to preserve have traditionally been avoided using; Make reaction safer more green more economical; And reaction conditions is gentle, and aftertreatment is simpler, carries out simple column chromatography after reaction is accomplished and just can get final product.
2. raw materials used aldehyde according to the invention and methane amide, catalyzer are all the commercially produced product of wide material sources; Be simple and easy to; Greatly improve the utilising efficiency of atom as starting raw material compared to traditional method with aldehyde and methane amide, met the requirement and the direction of contemporary Green Chemistry development.
3. this catalystsystem can both be obtained good and even outstanding productive rate to general aldehyde and methane amide etc., and functional group is compatible high, and with respect to traditional method, the use range of substrate is comparatively extensive.
4. the present invention adopts radical link coupled mode directly to make acid amides first, utilizes the methane amide decarbonylation to obtain amino radical first.
Embodiment
Below in conjunction with embodiment the present invention is further described:
Embodiment one:
Bu successively packs in the reaction flask
4NI (20mol%), and compound 1a (2mmol, 312mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), acetonitrile 8mL.This system heating after about 24 hours under 100 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3a, yield is 79%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 7.88-7.64 (m, 3H), 7.48-7.26 (m, 4H), 3.16 (s, 3H), 2.71 (s, 3H).
13CNMR (75MHz, CDCl
3): 170.8,134.6,133.3,129.3,128.9,128.3,126.9,126.2,125.1,124.7,123.8,38.8,34.8.MS:Anal.Calcd.For C
13H
12NO:199, Found:199 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1621. compound is the purpose product.
Embodiment two:
Bu successively packs in the reaction flask
4NI (20mol%), and compound 1a (2mmol, 312mg), TBHP (2mmol), N, dinethylformamide (2.4mL), toluene 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3a, yield is 85%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 7.88-7.64 (m, 3H), 7.48-7.26 (m, 4H), 3.16 (s, 3H), 2.71 (s, 3H).
13CNMR (75MHz, CDCl
3): 170.8,134.6,133.3,129.3,128.9,128.3,126.9,126.2,125.1,124.7,123.8,38.8,34.8.MS:Anal.Calcd.For C
13H
12NO:199, Found:199 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1621. compound is the purpose product.
Embodiment three:
Bu successively packs in the reaction flask
4NI (20mol%), and compound 1a (2mmol, 312mg), TBHP (2mmol), N, dinethylformamide (2.4mL), acetonitrile 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3a, yield is 59%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 7.88-7.64 (m, 3H), 7.48-7.26 (m, 4H), 3.16 (s, 3H), 2.71 (s, 3H).
13CNMR (75MHz, CDCl
3): 170.8,134.6,133.3,129.3,128.9,128.3,126.9,126.2,125.1,124.7,123.8,38.8,34.8.MS:Anal.Calcd.For C
13H
12NO:199, Found:199 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1621. compound is the purpose product.
Embodiment four:
Bu successively packs in the reaction flask
4NI (20mol%), and compound 1a (2mmol, 312mg), TBHP (4mmol), N, dinethylformamide (2.4mL), 1,2-ethylene dichloride 8mL.This system heating after about 24 hours under 70 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3a, yield is 80%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 7.88-7.64 (m, 3H), 7.48-7.26 (m, 4H), 3.16 (s, 3H), 2.71 (s, 3H).
13CNMR (75MHz, CDCl
3): 170.8,134.6,133.3,129.3,128.9,128.3,126.9,126.2,125.1,124.7,123.8,38.8,34.8.MS:Anal.Calcd.For C
13H
12NO:199, Found:199 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1621. compound is the purpose product.
Embodiment five:
Me successively packs in the reaction flask
4NI (20mol%), and compound 1a (2mmol, 312mg), TBHP (6mmol), N, dinethylformamide (2.4mL), 1 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3a, yield is 75%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 7.88-7.64 (m, 3H), 7.48-7.26 (m, 4H), 3.16 (s, 3H), 2.71 (s, 3H).
13CNMR (75MHz, CDCl
3): 170.8,134.6,133.3,129.3,128.9,128.3,126.9,126.2,125.1,124.7,123.8,38.8,34.8.MS:Anal.Calcd.For C
13H
12NO:199, Found:199 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1621. compound is the purpose product.
Embodiment six:
The KI (20mol%) that packs into successively in the reaction flask, and compound 1b (2mmol, 240mg), TBHP (11mmol), N, dinethylformamide (2.4mL), 1 8mL.This system heating after about 24 hours under 80 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3b, yield is 63%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 7.23 (d, J=7.3Hz, 2H), 7.10 (d, J=7.3Hz, 2H), 2.95 (s, 6H), 2.28 (s, 3H);
13CNMR (CDCl
3, 75MHz): δ 172.6,139.4, and 133.1,128.7,126.9,39.3,35.1,21.2; MS:Anal.Calcd.ForC
10H
13NO:163, Found:163 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1622. compound is the purpose product.
Embodiment seven:
The KI (20mol%) that packs into successively in the reaction flask, and compound 1c (2mmol, 262mg), TBHP (20mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 60 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3c, yield is 57%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.72 (d, J=8.2Hz, 2H), 7.53 (d, J=8.2Hz, 2H), 3.13 (s, 3H), 2.96 (s, 3H);
13CNMR (100MHz, CDCl
3): δ 169.3,140.5, and 132.1,127.5,118.0,113.0,39.1,35.1; MS:Anal.Calcd.For C
10H
10N
2O:174, Found:174 (M
+); IR (KBr, cm
-1): v1630.Above digital proof gained compound is the purpose product.
Embodiment eight:
I successively packs in the reaction flask
2(20mol%), and compound 1d (2mmol, 302mg), TBHP (18mmol), N, dinethylformamide (0.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 70 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3d, yield is 47%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 8.28 (d, J=8.4Hz, 2H), 7.60 (d, J=8.4Hz, 2H), 3.15 (s, 3H), 2.98 (s, 3H);
13CNMR (CDCl
3, 75MHz): δ 169.1,148.0,142.4,127.9,123.6,39.2,35.2.; MS:Anal.Calcd.For C
9H
10N
2O
3: 194, Found:194 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1638. compound is the purpose product.
Embodiment nine:
The NaI (20mol%) that packs into successively in the reaction flask, and compound 1e (2mmol, 248mg), TBHP (11.6mmol), N, dinethylformamide (0.8mL), vinyl trichloride 8mL.This system heating after about 12 hours under 100 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3e, yield is 79%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.53-7.30 (m, 2H), 7.17-6.96 (m, 2H), 3.09 (s, 3H), 2.98 (s, 3H);
13CNMR (100MHz, CDCl
3): δ 170.3,164.1, and 161.6,132.02,131.99,129.07,128.99,115.1,114.9,39.3,35.1; MS:Anal.Calcd.For C
9H
10FNO:167, Found:167 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1631. compound is the purpose product.
Embodiment ten:
The LiI (10mol%) that packs into successively in the reaction flask, and compound 1f (2mmol, 280mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), 1 8mL.This system heating after about 12 hours under 100 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3f, yield is 82%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.37-7.35 (m, 4H), 3.09 (s, 3H), 2.96 (s, 3H).
13CNMR (101MHz, CDCl
3) δ 170.1,135.2,134.4,128.33,128.28,39.2,35.1; MS:Anal.Calcd.For C
9H
11 35ClNO:184, C
9H
11 37ClNO:186, Found:184 ((M+1)
+,
35Cl), 186 ((M+1)
+,
37Cl); IR (KBr, cm
-1): the above digital proof gained of v1639. compound is the purpose product.
Embodiment 11:
Bu successively packs in the reaction flask
4NI (20mol%), and compound 1g (2mmol, 366mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 16 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3g, yield is 76%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.53 (d, J=8.3Hz, 2H), 7.30 (d, J=8.3Hz, 2H), 3.09 (s, 3H), 2.96 (s, 3H);
13CNMR (CDCl
3, 100MHz): δ 170.3,134.9, and 131.4,131.4,128.6,123.6,39.3,35.2; MS:Anal.Calcd.ForC
9H
10 79BrNO:228, C
9H
10 81BrNO:230, Found:228 (M+1
+,
79Br); 230 (M+1
+,
81Br) IR (KBr, cm
-1): the above digital proof gained of v1626. compound is the purpose product.
Embodiment 12:
Pack into successively in the reaction flask (
nC
7H
15)
4NI (40mol%), and compound 1h (2mmol, 348mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 2 hours under 60 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3h, yield is 74%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.66 (d, J=8.0Hz, 2H), 7.52 (d, J=8.0Hz, 2H), 3.11 (s, 3H), 2.94 (s, 3H);
13CNMR (100MHz, CDCl
3): δ 169.9,139.8, and 131.3,130.97,127.2,125.3,125.24,125.20,125.16,124.9,122.2,39.1,35.0; MS:Anal.Calcd.For C
10H
10F
3NO:217, Found:217 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1639. compound is the purpose product.
Embodiment 13:
Bu successively packs in the reaction flask
4NI (30mol%), and compound 1i (2mmol, 304mg), TBHP (11.6mmol), N, dinethylformamide (3.0mL), vinyl trichloride 8mL.This system heating after about 20 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3i, yield is 84%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.24 (d, J=8.4Hz, 2H), 7.13 (d, J=8.4Hz, 2H), 2.97 (s, 3H), 2.88 (s, 3H), 2.37 (s, 3H).
13CNMR (75MHz, CDCl
3): δ 170.9,140.6,132.2,127.5,125.3,39.4,35.1,15.0.MS:Anal.Calcd.For C
10H
14NOS:196, Found:196 (M+1)
+IR (KBr, cm
-1): the above digital proof gained of v1634. compound is the purpose product.
Embodiment 14:
Bu successively packs in the reaction flask
4NI (15mol%), and compound 1j (2mmol, 412mg), TBHP (11.6mmol), N, dinethylformamide (0.8mL), vinyl trichloride 8mL.This system heating after about 14 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3j, yield is 81%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.53-7.56 (m, 4H), 7.43-7.37 (m, 2H), 7.37-7.31 (m, 3H), 3.10 (s, 3H), 2.96 (s, 3H);
13CNMR (CDCl
3, 100MHz): δ 170.8,135.7, and 131.5,131.4,128.4,128.3,127.1,124.5,122.7,90.6,88.6,39.4,35.3; HRMS:Anal.Calcd.For C
17H
16NO:250.1232, Found:250.1237 (M+1)
+IR (KBr, cm
-1): the above digital proof gained of v1625. compound is the purpose product.
Embodiment 15:
The CuI (5mol%) that packs into successively in the reaction flask, and compound 1k (2mmol, 416mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), acetonitrile 8mL.This system heating after about 22 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3k, yield is 65%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.49-7.53 (m, 4H), 7.43-7.39 (m, 2H), 7.33-7.37 (m, 2H), 7.29-7.24 (m, 1H), 7.12-7.10 (m, 2H), 3.09 (s, 3H), 3.00 (s, 3H);
13CNMR (CDCl
3, 100MHz): δ 171.3,138.6, and 136.9,135.1,129.9,128.7,127.9,127.7,127.6,126.6,126.2,39.6,35.3; MS:Anal.Calcd.ForC
17H
18NO:252.1388, Found:252.1392 (M+1)
+IR (KBr, cm
-1): the above digital proof gained of v1622. compound is the purpose product.
Embodiment 16:
Bu successively packs in the reaction flask
4NI (20mol%), and compound 1l (2mmol, 380mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 13 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3l, yield is 90%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.70 (d, J=16.0Hz, 1H), 7.57 (d, J=8.4Hz, 2H), 7.45 (d, J=8.4Hz, 2H), 6.48 (d, J=16.0Hz, 1H), 3.83 (s, 3H), 3.13 (s, 3H), 3.01 (s, 3H);
13CNMR (CDCl
3, 100MHz): δ 170.7,167.1, and 143.7,137.9,135.5,128.0,127.9,127.6,127.4,119.0,51.7,39.4,35.3; MS:Anal.Calcd.For C
13H
16NO
3: 234, Found:234 (M+1)
+IR (KBr, cm
-1): v1627,1727. above digital proof gained compounds are the purpose product.
Embodiment 17:
Bu successively packs in the reaction flask
4NI (20mol%), and compound 1m (2mmol, 452mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 19 hours under 85 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3m, yield is 73%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 8.22-8.16 (m, 2H), 7.67-7.60 (m, 1H), 7.54-7.47 (m, 4H), 7.29-7.23 (m, 2H), 3.11 (s, 3H), 3.01 (s, 3H);
13CNMR (CDCl
3, 100MHz): δ 170.6,164.7, and 151.6,133.7,133.6,130.0,129.0,128.5,128.4,121.6,39.5,35.3; MS:Anal.Calcd.For C
16H
16NO
3: 270, Found:270 (M+1
+); IR (KBr, cm
-1): v1623,1744. above digital proof gained compounds are the purpose product.
Embodiment 18:
Bu successively packs in the reaction flask
4NI (25mol%), and compound 1n (2mmol, 552mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 23 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3n, yield is 90%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.79-7.57 (m, 2H), 7.38-7.27 (m, 4H), 7.08-6.92 (m, 2H), 3.08 (s, 3H), 2.94 (s, 3H), 2.45 (s, 3H).
13CNMR (75MHz, CDCl
3): δ 169.8,149.8, and 145.4,134.7,131.5,129.5,128.3,128.0,121.9,39.2,35.0,21.3; MS:Anal.Calcd.For C
16H
18NO
4S:320.0957, Found:320.0957 (M+1
+); IR (KBr, cm
-1): v1625.7,1402.2, the above digital proof gained of 1089.0. compound is the purpose product.
Embodiment 19:
Bu successively packs in the reaction flask
4NI (20mol%), compound 1o (2mmol 328mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), toluene 8mL.This system heating after about 15 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3o, yield is 79%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 8.11-7.99 (m, 2H), 7.54-7.40 (m, 2H), 3.92 (s, 3H), 3.11 (s, 3H), 2.94 (s, 3H);
13CNMR (CDCl
3, 101MHz): δ 170.4,166.2, and 140.5,130.8,129.5,126.8,52.1,39.2,35.1; MS:Anal.Calcd.For C
11H
14NO
3: 208, Found:208 (M+1)
+IR (KBr, cm
-1): v1627,1729.1402.2, the above digital proof gained of 1089.0. compound is the purpose product.
Embodiment 20:
BnMe successively packs in the reaction flask
3NI (20mol%), compound 1p (2mmol 326mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 4 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3p, yield is 86%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 8.21 (s, 1H), 7.47 (d, J=8.0Hz, 2H), 7.30 (d, J=8.0Hz, 2H), 3.11 (s, 3H), 3.01 (s, 3H), 2.17 (s, 3H);
13CNMR (CDCl
3, 75MHz): δ 177.0,174.8, and 145.4,135.7,133.0,124.7,45.0,40.8,29.5; MS:Anal.Calcd.For C
11H
15N
2O
2: 207, Found:207 (M+1)
+IR (KBr, cm
-1): v1634,1637. above digital proof gained compounds are the purpose product.
Embodiment 21:
Bu successively packs in the reaction flask
4NI (20mol%), compound 1q (2mmol 444mg), TBHP (11.6mmol), N, dinethylformamide (2.0mL), vinyl trichloride 8mL.This system heating after about 24 hours under 80 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3q, yield is 63%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.46-7.44 (m, 2H), 7.23-7.21 (m, 2H), 3.11 (s, 3H), 3.00 (s, 3H), 1.56 (s, 9H).
13CNMR (75MHz, CDCl
3): δ 170.2,151.4, and 151.0,133.3,128.1,120.8,83.4,39.2,34.9,27.2; MS:Anal.Calcd.For C
14H
20NO
4: 266.1392, Found:266.1397 (M+1)
+IR (KBr, cm
-1): v1636,1754. above digital proof gained compounds are the purpose product.
Embodiment 22:
I successively packs in the reaction flask
2(20mol%), compound 1r (2mmol 396mg), TBHP (11.6mmol), N, dinethylformamide (1.4mL), vinyl trichloride 8mL.This system heating after about 19 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3r, yield is 91%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.37-7.28 (m, 3H), 7.12-7.09 (m, 2H), 7.05-6.99 (m, 4H), 3.06 (s, 3H), 2.94 (s, 3H);
13CNMR (CDCl
3, 101MHz): δ 170.5,157.2, and 156.3,137.8,129.7,123.5,121.3,119.3,119.0,116.8,39.2,35.0; MS:Anal.Calcd.For C
15H
16NO
2: 242, Found:242 (M+1)
+IR (KBr, cm
-1): the above digital proof gained of v1627. compound is the purpose product.
Embodiment 23:
Hep successively packs in the reaction flask
4NI (20mol%), compound 1s (2mmol 240mg), TBHP (12mmol), N, dinethylformamide (3.4mL), vinyl trichloride 8mL.This system heating after about 18 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3s, yield is 80%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 7.17-7.06 (m, 4H), 3.04 (s, 3H), 2.73 (s, 3H), 2.20 (s, 3H);
13CNMR (CDCl
3, 75MHz): δ 171.2,136.4, and 133.6,130.0,128.4,125.6,125.5,38.1,34.2,18.6; MS:Anal.Calcd.For C
10H
13NO:163, Found:163 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1625. compound is the purpose product.
Embodiment 24:
Bu successively packs in the reaction flask
4NI (20mol%), compound 1t (2mmol 262mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), 1,2-ethylene dichloride 8mL.This system heating after about 16 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 3t, yield is 59%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 7.71-7.73 (m, 1H), 7.58-7.44 (m, 1H), 3.17 (s, 3H), 2.95 (s, 3H);
13CNMR (CDCl
3, 75MHz): δ 167.5,140.2, and 132.9,132.7,129.3,127.3,116.6,109.6,38.4,34.8; MS:Anal.Calcd.ForC
10H
10N
2O:174, Found:174 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1637. compound is the purpose product.
Embodiment 25:
The KI (20mol%) that packs into successively in the reaction flask, compound 4a (2mmol 192mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 70 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 4a, yield is 68%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.52-7.50 (m, 1H), 6.99-6.98 (m, 1H), 6.49-6.47 (m, 1H), 3.28 (s, 3H), 3.10 (s, 3H).
13CNMR (75MHz, CDCl
3): δ 159.8,147.5,143.4,115.5,110.7,37.9,35.9.MS:Anal.Calcd.ForC
7H
10NO
2: 140, Found:140 (M+1)
+IR (KBr, cm
-1): the above digital proof gained of v1630. compound is the purpose product.
Embodiment 26:
Bu successively packs in the reaction flask
4NI (20mol%), compound 4b (2mmol 346mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 21 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 4b, yield is 67%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 6.97 (d, J=3.4Hz, 1H), 6.43 (d, J=3.4Hz, 1H), 3.28 (s, 3H), 3.09 (s, 3H).
13CNMR (100MHz, CDCl
3): δ 158.8,149.6,124.0,118.3,113.0,38.0,36.3.MS:Anal.Calcd.ForC
7H
9 79BrNO
2: 218; C
7H
9 81BrNO
2: 220Found:218 (
79Br, M+1
+); 220 (
81Br, M+1
+); IR (KBr, cm
-1): the above digital proof gained of v1627. compound is the purpose product.
Embodiment 27:
Bu successively packs in the reaction flask
4NI (20mol%), compound 4c (2mmol 224mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 17 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 4c, yield is 74%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.44-7.42 (m, 1H), 7.36-7.31 (m, 1H), 7.02-7.04 (m, 1H), 3.16 (s, 6H);
13CNMR (100MHz, CDCl
3): δ 170.2,134.9, and 131.3,128.6,123.5,39.3,35.1; MS:Anal.Calcd.For C
7H
9NOS:155, Found:155 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1611. compound is the purpose product.
Embodiment 28:
I successively packs in the reaction flask
2(20mol%), compound 4d (2mmol 224mg), TBHP (12mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 20 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 4d, yield is 41%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.89 (d, J=3.0Hz, 1H), 7.53 (d, J=3.1Hz, 1H), 3.60 (s, 3H), 3.16 (s, 3H).
13CNMR (CDCl
3, 100MHz) δ 165.2,160.6,143.0,123.7,38.6,37.1.MS:Anal.Calcd.For C
6H
9N
2OS:157, Found:157 (M+1)
+IR (KBr, cm
-1): the above digital proof gained of v1624. compound is the purpose product.
Embodiment 29:
The KI (20mol%) that packs into successively in the reaction flask, compound 4e (2mmol 214mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 4e, yield is 65%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 8.69 (d, J=4.6Hz, 2H), 7.31 (d, J=4.5Hz, 2H), 3.12 (s, 3H), 2.96 (s, 3H).
13CNMR (CDCl
3, 100MHz): δ 168.7,149.9,143.7,121.0,38.9,34.9.MS:Anal.Calcd.For C
8H
11N
2O:151, Found:151 (M+1)
+IR (KBr, cm
-1): the above digital proof gained of v1633. compound is the purpose product.
Embodiment 30:
Me successively packs in the reaction flask
4NI (20mol%), compound 4f (2mmol 214mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 100 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 4f, yield is 53%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 8.57-7.18 (m, 4H), 3.06 (s, 3H), 3.00 (s, 3H).
13CNMR (100MHz, CDCl
3): δ 168.8,154.3,148.1,136.9,124.2,123.3,38.8,35.5.MS:Anal.Calcd.For C
8H
11N
2O:151, Found:151 (M+1)
+IR (KBr, cm
-1): the above digital proof gained of v1637. compound is the purpose product.
The embodiment hentriaconta-:
Bu successively packs in the reaction flask
4NI (20mol%), compound 4g (2mmol 140mg), TBHP (11.6mmol), N-methyl-N-benzyl methane amide (2.4mL), vinyl trichloride 8mL.This system heating after about 18 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 4g, yield is 67%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.41-7.14 (m, 5H), 7.01-6.94 (m, 1H), 6.34-6.25 (m, 1H), 4.61 (d, J=24.0Hz, 2H), 2.97 (s, 3H), 1.91-1.83 (m, 3H).
13CNMR (100MHz, CDCl
3): δ 142.0,141.9,128.7,128.4,127.9,127.4,127.1,126.3,121.5,53.1,50.9,34.7,33.9,18.1.MS:Anal.Calcd.ForC
12H
16NO:190, Found:190 (M+1)
+IR (KBr, cm
-1): v1617,1662. above digital proof gained compounds are the purpose product.
Embodiment 32:
The LiI (20mol%) that packs into successively in the reaction flask, compound 4h (2mmol 264mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 4h, yield is 80%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.66 (d, J=15.5Hz, 1H), 7.53-7.51 (m, 2H), 7.37-7.33 (m, 3H), 6.89 (d, J=15.4Hz, 1H), 3.14 (s, 3H), 3.05 (s, 3H).
13CNMR (100MHz, CDCl
3) δ 166.4,142.0,135.1,129.3,128.5,127.5,117.2,37.2,35.7.MS:Anal.Calcd.For C
11H
13NO:175, Found:175 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1629. compound is the purpose product.
Embodiment 33:
Bu successively packs in the reaction flask
4NI (20mol%), compound 4i (2mmol 260mg), TBHP (11.6mmol), N, dinethylformamide (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 4i, yield is 62%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.52-7.55 (m, 2H), 7.44-7.30 (m, 3H), 3.28 (s, 3H), 3.02 (s, 3H).
13CNMR (CDCl
3, 100MHz): δ 154.3,132.1,129.8,128.3,120.3,89.9,81.4,38.2,33.9.MS:Anal.Calcd.For C
11H
11NO:173, Found:173 (M)
+IR (KBr, cm
-1): the above digital proof gained of v1626. compound is the purpose product.
Embodiment 34:
Bu successively packs in the reaction flask
4NI (20mol%), compound 1a (2mmol 312mg), TBHP (11.6mmol), N, N-DEF (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 5b, yield is 68%.
Product is analyzed, and the result is following:
1HNMR (CDCl
3, 300MHz): δ 7.87-7.81 (m, 3H), 7.48-7.39 (m, 4H), 3.83-3.48 (m, 4H), 1.31-1.35 (m, 3H), 0.97-0.92 (m, 3H);
13CNMR (CDCl
3, 75MHz): δ 170.1,134.9, and 133.3,129.4,128.6,128.2,126.7,126.2,124.9,124.5,123.0,43.0,38.9,14.1,12.9; MS:Anal.Calcd.For C
15H
18NO:228, Found:228 (M+1)
+IR (KBr, cm
-1): the above digital proof gained of v1616. compound is the purpose product.
Embodiment 35:
The NaI (20mol%) that packs into successively in the reaction flask, compound 1a (2mmol), TBHP (20mmol), N-formylpyrrole (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 5c, yield is 74%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 7.86-7.84 (m, 3H), 7.65-7.36 (m, 4H), 3.78-3.57 (m, 2H), 3.12-3.08 (m, 2H), 1.97-1.73 (m, 4H);
13CNMR (CDCl
3, 75MHz): δ 169.1,135.5, and 133.3,129.0,128.9,128.2,126.8,126.1,125.0,124.7,123.5,48.3,45.5,25.8,24.4; MS:For C
15H
15NO:225, Found:225 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1633. compound is the purpose product.
Embodiment 36:
The LiI (20mol%) that packs into successively in the reaction flask, compound 1a (2mmol 312mg), TBHP (16mmol), N-N-formyl morpholine N-(2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 5d, yield is 72%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 7.88-7.84 (m, 3H), 7.59-7.34 (m, 4H), 4.08-3.75 (m, 4H), 3.51-3.48 (m, 2H), 3.16-3.20 (m, 2H);
13CNMR (CDCl
3, 75MHz): δ 169.3,133.5, and 133.3,129.4,129.2,128.3,127.0,126.4,125.0,124.4,123.8,66.9,66.8,47.4,42.0; MS:Anal.Calcd.For C
15H
16NO
2: 242, Found:242 (M+1)
+IR (KBr, cm
-1): the above digital proof gained of v1630. compound is the purpose product.
Embodiment 37:
Me successively packs in the reaction flask
4NI (20mol%), compound 1a (2mmol 312mg), TBHP (14mmol), N-formylpiperidine (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 5e, yield is 63%.
Product is analyzed, and the result is following:
1HNMR (300MHz, CDCl
3): δ 7.82-7.86 (m, 3H), 7.61-7.33 (m, 4H), 3.88-3.85 (m, 2H), 3.26-3.04 (m, 2H), 1.85-1.58 (m, 4H), 1.37-1.39 (m, 2H);
13CNMR (CDCl
3, 75MHz): δ 169.1,134.7, and 133.3,129.5,128.7,128.2,126.7,126.2,125.1,124.8,123.3,48.2,42.5,26.5,25.7,24.4; MS:Anal.Calcd.For C
16H
18NO:240, Found:240; IR (KBr, cm
-1): the above digital proof gained of v1629. compound is the purpose product.
Embodiment 38:
Bu successively packs in the reaction flask
4NI (20mol%), compound 1a (2mmol 312mg), TBHP (12mmol), N-methyl-N-benzyl methane amide (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 5f, yield is 82%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.94-7.82 (m, 3H), 7.58-7.23 (m, 9H), 4.90 (s, 1H), 4.31 (d, J=37.8Hz, 1H), 3.15 (s, 1.5H), 2.69 (s, 1.5H).
13CNMR (100MHz, CDCl
3): δ 170.6,170.3, and 136.6,135.6,134.1,133.8,133.0,132.9; 129.2,128.9,128.7,128.6,128.2,128.2,127.9,127.8; 127.1,126.6,126.5,126.0,125.9,124.7,124.6; 124.4,124.2,123.4,54.2,49.9,35.6,32.0.HRMS:Anal.Calcd.For C
19H
17NO:275.1310, Found:275.1311 (M)
+IR (KBr, cm
-1): the above digital proof gained of v1642. compound is the purpose product.
Embodiment 39:
The NaI (20mol%) that packs into successively in the reaction flask, compound 1a (2mmol 312mg), TBHP (8mmol), N-formyl NSC 20948 (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 60 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 5g, yield is 74%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.87-7.83 (m, 3H), 7.53-7.42 (m, 4H), 6.03-5.95 (m, 1H), 5.64-5.55 (m, 1H), 5.33-5.29 (m, 2H), 5.14-5.04 (m, 2H), 4.61-4.51 (m, 1H), 4.07-3.95 (m, 1H), 3.67-3.65 (m, 2H);
13CNMR (101MHz, CDCl
3): δ 170.8,134.1, and 133.4,132.9,132.7,129.5,129.0,128.3,126.9,126.3,124.9,124.7,123.4,118.0,117.9,50.5,46.3; HRMS:Anal.Calcd.ForC
17H
7NO:251.1310, Found:251.1305; IR (KBr, cm
-1): the above digital proof gained of v1628. compound is the purpose product.
Embodiment 40:
Bu successively packs in the reaction flask
4NI (20mol%), compound 1a (2mmol 312mg), TBHP (6mmol), N-formyl radical-4-hydroxy piperidine (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 5h, yield is 60%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.88-7.73 (m, 3H), 7.54-7.31 (m, 4H), 4.41-4.12 (m, 1H), 3.75 (s, 1H), 3.49-3.23 (m, 2H), 2.96-2.79 (m, 1H), 1.99-1.07 (m, 4H).
13CNMR (75MHz, CDCl
3): δ 168.9,133.8,132.9,128.9,128.6,128.0,126.6,126.1,124.7,124.2,123.0,65.5,44.0,38.5,33.9,33.2.MS:Anal.Calcd.For C
16H
18NO
2: 256, Found:256 (M+1)
+IR (KBr, cm
-1): the above digital proof gained of v1600. compound is the purpose product.
Embodiment 41:
Bu successively packs in the reaction flask
4NI (20mol%), compound 1a (2mmol 312mg), TBHP (11.6mmol), N-formyl radical-tert-butoxycarbonyl-piperazine (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 5i, yield is 61%.
Product is analyzed, and the result is following:
1HNMR (CDCl
3, 400MHz): δ 7.91-7.34 (m, 7H), 4.05-3.50 (m, 4H), 3.48-2.80 (m, 4H), 1.44 (s, 9H).
13CNMR (CDCl
3, 100MHz): δ 168.8,153.8,133.2,132.8,128.9,128.7,127.9,126.5,125.9,124.6,124.0,123.3,79.5,46.3,41.0,27.8.MS:Anal.Calcd.For C
20H
25N
2O
3: 341, Found:341 (M+1)
+IR (KBr, cm
-1): v1637,1686. above digital proof gained compounds are the purpose product.
Embodiment 42:
Bu successively packs in the reaction flask
4NI (20mol%), compound 1a (2mmol 312mg), TBHP (11.6mmol), N-formyl radical pyrazoles (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 5j, yield is 45%.
Product is analyzed, and the result is following:
1HNMR (CDCl
3, 400MHz): δ 8.47 (d, J=2.8Hz, 1H), 8.09-7.89 (m, 3H), 7.81 (d, J=7.1Hz, 1H), 7.75-7.53 (m, 3H), 7.53 (d, J=3.3Hz, 1H), 6.56-6.55 (m, 1H).
13CNMR (CDCl
3, 100MHz): δ 167.3,144.8,133.4,132.1,130.8,130.0,129.6,128.8,128.5,127.8,126.5,124.9,124.2,109.9.MS:Anal.Calcd.For C
14H
10N
2NaO:245, Found C
14H
10N
2NaO:245 (M+23)
+IR (KBr, cm
-1): v1636,1707. above digital proof gained compounds are the purpose product.
Embodiment 43:
Me successively packs in the reaction flask
4NI (20mol%), compound 1a (2mmol 312mg), TBHP (11.6mmol), N-formyl radical-L proline methyl ester (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 5k, yield is 52%.Above digital proof gained compound is the purpose product.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 8.18-7.80 (m, 3H), 7.60-7.45 (m, 4H), 4.89-4.75 (m, 1H), 3.86 (s, 3H), 3.37-3.15 (m, 2H), 2.40-2.02 (m, 2H), 2.00-1.79 (m, 2H).
13CNMR (100MHz, CDCl
3): δ 172.7,169.4,134.7,133.3,129.3,128.1,127.1,126.3,125.02,124.96,124.8,123.7,58.5,52.3,48.7,29.5,24.7.MS:Anal.Calcd.For C
17H
17NO
3: 283.1208, Found:283.1209 (M)
+IR (KBr, cm
-1): v1634,1673,1748. above digital proof gained compounds are the purpose product.
Embodiment 44:
Bu successively packs in the reaction flask
4NI (20mol%), compound 1a (2mmol 312mg), TBHP (6mmol), N, N-di-n-butyl methane amide (2.4mL), vinyl trichloride 8mL.This system heating after about 24 hours under 90 ℃ of conditions in air then, saturated sodium sulfite cancellation, washing, with ethyl acetate extraction (40mL * 3), through simple column chromatography get final product oxidation products 5l, yield is 70%.
Product is analyzed, and the result is following:
1HNMR (400MHz, CDCl
3): δ 7.87-7.82 (m, 3H), 7.52-7.39 (m, 4H), 3.82-3.47 (m, 2H), 3.06-3.00 (m; 2H), and 1.83-1.77 (m, 2H), 1.56-1.47 (m, 2H), 1.44-1.39 (m, 2H); 1.07-1.04 (m, 3H), 1.02-0.97 (m, 2H), 0.67-0.63 (m, 3H)
13CNMR (CDCl
3, 100MHz): δ 170.6,135.0, and 133.4,129.5,128.7,128.3,126.8,126.2,125.0,124.7,123.4,48.4,44.4,30.7,29.7,20.4,19.6,13.9,13.4; MS:Anal.Calcd.For C
19H
25NO:283, Found:283 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1616. compound is the purpose product.
Claims (6)
1. the preparation method of an acid amides, it is characterized in that: with aldehyde derivatives and carboxamides derivatives is reaction substrate, is catalyzer with iodide, trimethyl carbinol hydrogen peroxide is that oxygenant prepares acid amides through decarbonylation diradical cross-coupling reaction;
Wherein, the chemical structural formula of said aldehyde derivatives is:
In the formula, R
1Be selected from: naphthyl, heterocycle, alkylene or single substituted aryl
Wherein, R
2Be selected from: the ester group of hydrogen, methyl, methoxyl group, phenoxy, styryl, phenylacetylene base, methylthio group, cyanic acid, C1～C6, nitro, carboxamido-group, halogen, trifluoromethyl, the amino of Methyl benzenesulfonyl base protection, the hydroxyl of tertbutyloxycarbonyl protection;
Said heterocycle is selected from: thienyl, furyl, thiazolyl, pyridyl;
Said alkylene is selected from: allyl group, styryl, phenylacetylene base etc.;
The chemical structural formula of said carboxamides derivatives is:
Wherein, R
3, R
4Be selected from: the saturated chain type alkyl of C1～C4, benzyl, allyl group, the saturated five-ring of C4～C5, six-ring, heterocycle; Said heterocycle is selected from: morpholine, pyrazoles, piperazine;
Said iodide are selected from: Soiodin NaI, potassiumiodide KI, cuprous iodide CuI, lithium iodide LiI, elemental iodine I
2, tetrabutylammonium iodide Bu
4NI, four n-heptyl ammonium iodide Hep
4NI, Tetramethylammonium iodide Me
4NI, benzyltrimethylammonium iodide BnMe
3A kind of among the NI.
2. according to the preparation method of the said acid amides of claim 1, it is characterized in that: temperature of reaction is 60～100 ℃, and the reaction times is 12～24 hours.
3. according to the preparation method of the said acid amides of claim 1, it is characterized in that: catalyst consumption be the reaction substrate aldehyde derivatives amount of substance 5～40%.
4. according to the preparation method of the said acid amides of claim 1, it is characterized in that: the consumption of methane amide is 10～20 times of amount of substance of reaction substrate aldehyde derivatives.
5. according to the preparation method of the said acid amides of claim 1, it is characterized in that: solvent for use is: vinyl trichloride, toluene, acetonitrile, 1,2-ethylene dichloride or 1.
6. according to the preparation method of the said acid amides of claim 1, it is characterized in that: oxygenant is a peroxy tert-butyl alcohol, and the consumption of oxygenant is 1～10 equivalent.
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| CN103113247A (en) * | 2013-03-13 | 2013-05-22 | 苏州大学 | Method for preparing amino-acid ester |
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| CN104086345A (en) * | 2014-06-24 | 2014-10-08 | 苏州大学 | Method for synthesizing amide compound under catalysis of platinum nanowire |
| CN107266451A (en) * | 2016-04-07 | 2017-10-20 | 上海医药工业研究院 | The preparation method of sharp cloth intermediate of auspicious cloth former times |
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| CN110294686A (en) * | 2019-04-28 | 2019-10-01 | 苏州大学 | αThe environment-friendly preparation method thereof of -one amide |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102153470A (en) * | 2011-02-25 | 2011-08-17 | 苏州大学 | Method for preparing perester compound |
-
2012
- 2012-01-18 CN CN201210015922.0A patent/CN102584509B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102153470A (en) * | 2011-02-25 | 2011-08-17 | 苏州大学 | Method for preparing perester compound |
Non-Patent Citations (1)
| Title |
|---|
| SHULIN CHEN, ET AL.: "Direct Condensation of Sulfonamide and Formamide NaI-Catalyzed Synthesis of N-Sulfonyl Formamidine Using TBHP as Oxidant", 《ORGANIC LETTERS》, vol. 13, no. 23, 31 October 2011 (2011-10-31), pages 6152 - 6155 * |
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| CN103113247A (en) * | 2013-03-13 | 2013-05-22 | 苏州大学 | Method for preparing amino-acid ester |
| CN103274964A (en) * | 2013-06-13 | 2013-09-04 | 苏州大学 | Method for preparing alpha-dicyandiamide |
| CN103274964B (en) * | 2013-06-13 | 2014-07-02 | 苏州大学 | Method for preparing alpha-dicyandiamide |
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| CN111039813A (en) * | 2019-12-24 | 2020-04-21 | 江南大学 | Synthetic method of aromatic amide compound |
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| CN111620921A (en) * | 2020-05-25 | 2020-09-04 | 上海药明康德新药开发有限公司 | Method for preparing On-DNA amide compound through oxidative amidation in construction of DNA coding compound library |
| CN111620921B (en) * | 2020-05-25 | 2023-06-13 | 上海药明康德新药开发有限公司 | Method for preparing On-DNA amide compound by oxidative amidation in construction of DNA coding compound library |
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