CN102584509B - Preparation method of amide - Google Patents
Preparation method of amide Download PDFInfo
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- CN102584509B CN102584509B CN201210015922.0A CN201210015922A CN102584509B CN 102584509 B CN102584509 B CN 102584509B CN 201210015922 A CN201210015922 A CN 201210015922A CN 102584509 B CN102584509 B CN 102584509B
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- BZBUAYGDDUMLKJ-UHFFFAOYSA-N CC(CC1)C=CC1Cl Chemical compound CC(CC1)C=CC1Cl BZBUAYGDDUMLKJ-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 the chemical structural formula of the aldehyde derivative is shown in the description, 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 of preparing acid amides.
Background technology
Acid amides is the very important structural unit of a class, is extensively present in and has among the natural product of physiologically active, drug molecule, also often visible in synthetic intermediate.
At present, the method for preparing acid amides has catalyst levels larger, and price is comparatively expensive, and toxicity is larger, severe reaction conditions, the shortcoming that selectivity is low, substrate use range is narrow.For example:
(1) people such as J.M.J.Williams has reported that use carboxylic acid and derivative and amine linked reaction thereof prepare acid amides, (referring to: C.L.Allen, J.M.J.Williams, Chem.Soc.Rev 2011,40,3405);
(2) thus the people such as H.Alper reported by the ammonia carboxylation reaction of halogenated aryl hydrocarbon and can optionally synthesize a class 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 transition metal-catalyzed oxidation alcohol and the linked reaction of ammonia directly make reacting 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 effectively to build amido linkage as acylting agent, (referring to: P.E.Dawson, T.W.Muir, I.Clark-Lewis, S.B.Kent, Science 1994,266,776);
(5) Chinese invention patent that the patent No. is 01807450.2 discloses a kind of method of the 6-of preparation aminocaproamide, comprise 5-cyanovaleramide is reacted under the existence of metal catalyst with hydrogen, described metal catalyst is selected from the metal catalyst of carrier, sponge metal catalyst, the metal oxide of homogeneous catalyst and reduction, oxyhydroxide or carbonate catalyst, if wherein catalyzer is the carrier metal catalyst containing cobalt or nickel, and if carrier is through calcining, before using nickel or cobalt, calcine, wherein react in the situation that not there is not diox and carry out,
(6) the Chinese disclosure of the invention that the patent No. is 03803556.1 a kind of method of preparing acid amides under mild condition, shown in the following chemical formula of its reaction process:
Work as R
9while being methyl, ethyl or aryl, in the situation that there is Lewis acid, aprotic organic solvent and alkali, reaction can be carried out at 20～80 ℃; Or work as R
9while being hydrogen, in the situation that there is thionyl chloride, aprotic organic solvent and alkali, reaction can be carried out at 20～70 ℃;
(7) other methods that build 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 cyano group (referring to: S.-I.Murahashi, T.Naota, E.Saito, J.Am.Chem.Soc.1986,108,7846) and the method such as transition metal-catalyzed C-C bond cleavage solution (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 some institute's catalyzer that uses more expensive (as Ru, Rh, Pd, Ni, Cu) in these methods, some catalyst system is more loaded down with trivial details, some reactant preparation trouble, price is more expensive, the use range of substrate is narrow simultaneously, has larger limitation, has limited it and has applied on a large scale.
Therefore, need to find a kind of relative low price, toxicity is lower, and catalyst system easy and simple to handle replaces above catalyst system to prepare the method for acid amides.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of method of preparing acid amides, in guaranteeing that reaction is reacted under gentle condition, reduces the use expensive or catalyzer that toxicity is high, makes more environmental protection of preparation process, more economical.
To achieve the above object of the invention, the technical solution used in the present invention is: a kind of method of preparing acid amides, take aldehyde derivatives and carboxamides derivatives as reaction substrate, take iodide as catalyzer, trimethyl carbinol hydrogen peroxide is that oxygenant prepares acid amides by decarbonylation diradical cross-coupling reaction;
Wherein, the chemical structural formula of described aldehyde derivatives is:
in formula, R
1be selected from: naphthyl, heterocycle, alkylene or monosubstituted aryl
wherein, R
2be selected from: the hydroxyl that the ester group of hydrogen, methyl, methoxyl group, phenoxy group, styryl, phenylacetylene base, methylthio group, cyano group, C1～C6, nitro, amide group, halogen, trifluoromethyl, the amino that Methyl benzenesulfonyl base is protected, tertbutyloxycarbonyl are protected;
Preferably, heterocycle is selected from: thienyl, furyl, thiazolyl, pyridyl; Alkene is selected from: allyl group, styryl, phenylacetylene base etc.;
The chemical structural formula of described 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;
Described iodide are selected from: sodium iodide NaI, potassiumiodide KI, cuprous iodide CuI, lithium iodide LiI, elemental iodine I
2, tetrabutylammonium iodide, four n-heptyl ammonium iodides, Tetramethylammonium iodide, the one in benzyltrimethylammonium iodide.
In technique scheme, the temperature of reaction of the described method of preparing acid amides is 60～100 ℃, preferably 90 ℃; Reaction times is 2～24 hours, preferably 24 hours.
In technique scheme, the consumption of catalyzer be reaction substrate aldehyde derivatives amount of substance 5～40%, catalyst levels increases or reduces productive rate impact little; Preferably 20%.
In technique scheme, the consumption of methane amide is 10～20 equivalents of reaction substrate aldehyde derivatives amount of substance, 2～20 of the amount of substance of reaction substrate aldehyde derivatives times; Be preferably 15 equivalents.
In technique scheme, solvent used is: vinyl trichloride, toluene, acetonitrile, 1,2-ethylene dichloride or 1，1，1-trichloroethane.
In 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 technical scheme, react rear first with saturated sodium sulfite cancellation reaction, then with ethyl acetate or dichloromethane extraction, recycle silicon glue adsorbs vacuum and is spin-dried for solvent, then carries out simple column chromatography with the mixed solvent of ethyl acetate and sherwood oil and just can obtain final product.
In technique scheme, described catalyzer, reactant are all market-oriented commodity, can directly buy and obtain.
Because technique scheme is used, the present invention compared with prior art has following advantages:
1. because adopting iodide, the present invention prepares acid amides as catalyst, expensive traditionally catalyzer and the dangerous acid amides halogenide that is difficult to preservation are avoided using, make to react safer more green more economical, and reaction conditions gentleness, aftertreatment is simpler, carries out simple column chromatography and just can obtain final product after having reacted.
2. raw materials used aldehyde of the present invention and methane amide, catalyzer are all the commercially produced product of wide material sources, simple and easy to get, greatly improve the utilising efficiency of atom using aldehyde and methane amide as starting raw material compared to traditional method, met requirement and the direction of contemporary Green Chemistry development.
3. this catalyst system can be obtained good and even outstanding productive rate to general aldehyde and methane amide etc., and functional group's compatibility is high, and with respect to traditional method, the use range of substrate is comparatively extensive.
4. the present invention adopts the mode of free radical coupling directly to make acid amides first, utilizes first methane amide decarbonylation to obtain amino radical.
Embodiment
Below in conjunction with embodiment, the invention will be further described:
Embodiment mono-:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1a (2mmol, 312mg), TBHP (11.6mmol), DMF (2.4mL), acetonitrile 8mL.Then this system heats under 100 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3a by simple column chromatography, and yield is 79%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment bis-:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1a (2mmol, 312mg), TBHP (2mmol), DMF (2.4mL), toluene 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3a by simple column chromatography, and yield is 85%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment tri-:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1a (2mmol, 312mg), TBHP (2mmol), DMF (2.4mL), acetonitrile 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3a by simple column chromatography, and yield is 59%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment tetra-:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1a (2mmol, 312mg), TBHP (4mmol), DMF (2.4mL), 1,2-ethylene dichloride 8mL.Then this system heats under 70 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3a by simple column chromatography, and yield is 80%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment five:
In reaction flask, pack successively Me into
4nI (20mol%), compound 1a (2mmol, 312mg), TBHP (6mmol), DMF (2.4mL), 1，1，1-trichloroethane 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3a by simple column chromatography, and yield is 75%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment six:
In reaction flask, pack successively KI (20mol%) into, compound 1b (2mmol, 240mg), TBHP (11mmol), DMF (2.4mL), 1，1，1-trichloroethane 8mL.Then this system heats under 80 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3b by simple column chromatography, and yield is 63%.
Product is analyzed, and result is as follows:
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 172.6,139.4,133.1,128.7,126.9,39.3,35.1,21.2; MS:Anal.Calcd.ForC
10h
13nO:163, Found:163 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1622. compound is object product.
Embodiment seven:
In reaction flask, pack successively KI (20mol%) into, compound 1c (2mmol, 262mg), TBHP (20mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 60 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3c by simple column chromatography, and yield is 57%.
Product is analyzed, and result is as follows:
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 169.3,140.5,132.1,127.5,118.0,113.0,39.1,35.1; MS:Anal.Calcd.For C
10h
10n
2o:174, Found:174 (M
+); IR (KBr, cm
-1): v1630.Above digital proof gained compound is object product.
Embodiment eight:
In reaction flask, pack successively I into
2(20mol%), compound 1d (2mmol, 302mg), TBHP (18mmol), DMF (0.4mL), vinyl trichloride 8mL.Then this system heats under 70 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3d by simple column chromatography, and yield is 47%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment nine:
In reaction flask, pack successively NaI (20mol%) into, compound 1e (2mmol, 248mg), TBHP (11.6mmol), DMF (0.8mL), vinyl trichloride 8mL.Then this system heats under 100 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3e by simple column chromatography, and yield is 79%.
Product is analyzed, and result is as follows:
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 170.3,164.1,161.6,132.02,131.99,129.07,128.99,115.1,114.9,39.3,35.1; MS:Anal.Calcd.For C
9h
10fNO:167, Found:167 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1631. compound is object product.
Embodiment ten:
In reaction flask, pack successively LiI (10mol%) into, compound 1f (2mmol, 280mg), TBHP (11.6mmol), DMF (2.4mL), 1，1，1-trichloroethane 8mL.Then this system heats under 100 ℃ of conditions after approximately 12 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3f by simple column chromatography, and yield is 82%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 11:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1g (2mmol, 366mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 16 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3g by simple column chromatography, and yield is 76%.
Product is analyzed, and result is as follows:
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 170.3,134.9,131.4,131.4,128.6,123.6,39.3,35.2; 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 object product.
Embodiment 12:
In reaction flask, pack into successively (
nc
7h
15)
4nI (40mol%), compound 1h (2mmol, 348mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 60 ℃ of conditions after approximately 2 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3h by simple column chromatography, and yield is 74%.
Product is analyzed, and result is as follows:
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 169.9,139.8,131.3,130.97,127.2,125.3,125.24,125.20,125.16,124.9,122.2,39.1,35.0; 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 object product.
Embodiment 13:
In reaction flask, pack successively Bu into
4nI (30mol%), compound 1i (2mmol, 304mg), TBHP (11.6mmol), DMF (3.0mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 20 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3i by simple column chromatography, and yield is 84%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 14:
In reaction flask, pack successively Bu into
4nI (15mol%), compound 1j (2mmol, 412mg), TBHP (11.6mmol), DMF (0.8mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 14 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3j by simple column chromatography, and yield is 81%.
Product is analyzed, and result is as follows:
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 170.8,135.7,131.5,131.4,128.4,128.3,127.1,124.5,122.7,90.6,88.6,39.4,35.3; 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 object product.
Embodiment 15:
In reaction flask, pack successively CuI (5mol%) into, compound 1k (2mmol, 416mg), TBHP (11.6mmol), DMF (2.4mL), acetonitrile 8mL.Then this system heats under 90 ℃ of conditions after approximately 22 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3k by simple column chromatography, and yield is 65%.
Product is analyzed, and result is as follows:
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 171.3,138.6,136.9,135.1,129.9,128.7,127.9,127.7,127.6,126.6,126.2,39.6,35.3; 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 object product.
Embodiment 16:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1l (2mmol, 380mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 13 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3l by simple column chromatography, and yield is 90%.
Product is analyzed, and result is as follows:
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 170.7,167.1,143.7,137.9,135.5,128.0,127.9,127.6,127.4,119.0,51.7,39.4,35.3; 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 object product.
Embodiment 17:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1m (2mmol, 452mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 85 ℃ of conditions after approximately 19 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3m by simple column chromatography, and yield is 73%.
Product is analyzed, and result is as follows:
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 170.6,164.7,151.6,133.7,133.6,130.0,129.0,128.5,128.4,121.6,39.5,35.3; 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 object product.
Embodiment 18:
In reaction flask, pack successively Bu into
4nI (25mol%), compound 1n (2mmol, 552mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 23 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3n by simple column chromatography, and yield is 90%.
Product is analyzed, and result is as follows:
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 169.8,149.8,145.4,134.7,131.5,129.5,128.3,128.0,121.9,39.2,35.0,21.3; MS:Anal.Calcd.For C
16h
18nO
4s:320.0957, Found:320.0957 (M+1
+); IR (KBr, cm
-1): v1625.7, the above digital proof gained of 1402.2,1089.0. compound is object product.
Embodiment 19:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1o (2mmol 328mg), TBHP (11.6mmol), DMF (2.4mL), toluene 8mL.Then this system heats under 90 ℃ of conditions after approximately 15 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3o by simple column chromatography, and yield is 79%.
Product is analyzed, and result is as follows:
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 170.4,166.2,140.5,130.8,129.5,126.8,52.1,39.2,35.1; 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 object product.
Embodiment 20:
In reaction flask, pack successively BnMe into
3nI (20mol%), compound 1p (2mmol 326mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 4 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3p by simple column chromatography, and yield is 86%.
Product is analyzed, and result is as follows:
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 177.0,174.8,145.4,135.7,133.0,124.7,45.0,40.8,29.5; 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 object product.
Embodiment 21:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1q (2mmol 444mg), TBHP (11.6mmol), DMF (2.0mL), vinyl trichloride 8mL.Then this system heats under 80 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3q by simple column chromatography, and yield is 63%.
Product is analyzed, and result is as follows:
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 170.2,151.4,151.0,133.3,128.1,120.8,83.4,39.2,34.9,27.2; 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 object product.
Embodiment 22:
In reaction flask, pack successively I into
2(20mol%), compound 1r (2mmol 396mg), TBHP (11.6mmol), DMF (1.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 19 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3r by simple column chromatography, and yield is 91%.
Product is analyzed, and result is as follows:
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 170.5,157.2,156.3,137.8,129.7,123.5,121.3,119.3,119.0,116.8,39.2,35.0; 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 object product.
Embodiment 23:
In reaction flask, pack successively Hep into
4nI (20mol%), compound 1s (2mmol 240mg), TBHP (12mmol), DMF (3.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 18 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3s by simple column chromatography, and yield is 80%.
Product is analyzed, and result is as follows:
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 171.2,136.4,133.6,130.0,128.4,125.6,125.5,38.1,34.2,18.6; MS:Anal.Calcd.For C
10h
13nO:163, Found:163 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1625. compound is object product.
Embodiment 24:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1t (2mmol 262mg), TBHP (11.6mmol), DMF (2.4mL), 1,2-ethylene dichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 16 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 3t by simple column chromatography, and yield is 59%.
Product is analyzed, and result is as follows:
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 167.5,140.2,132.9,132.7,129.3,127.3,116.6,109.6,38.4,34.8; MS:Anal.Calcd.ForC
10h
10n
2o:174, Found:174 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1637. compound is object product.
Embodiment 25:
In reaction flask, pack successively KI (20mol%) into, compound 4a (2mmol 192mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 70 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 4a by simple column chromatography, and yield is 68%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 26:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 4b (2mmol 346mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 21 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 4b by simple column chromatography, and yield is 67%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 27:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 4c (2mmol 224mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 17 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 4c by simple column chromatography, and yield is 74%.
Product is analyzed, and result is as follows:
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 170.2,134.9,131.3,128.6,123.5,39.3,35.1; MS:Anal.Calcd.For C
7h
9nOS:155, Found:155 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1611. compound is object product.
Embodiment 28:
In reaction flask, pack successively I into
2(20mol%), compound 4d (2mmol 224mg), TBHP (12mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 20 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 4d by simple column chromatography, and yield is 41%.
Product is analyzed, and result is as follows:
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) and 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 object product.
Embodiment 29:
In reaction flask, pack successively KI (20mol%) into, compound 4e (2mmol 214mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 4e by simple column chromatography, and yield is 65%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 30:
In reaction flask, pack successively Me into
4nI (20mol%), compound 4f (2mmol 214mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 100 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 4f by simple column chromatography, and yield is 53%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 31:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 4g (2mmol 140mg), TBHP (11.6mmol), N-methyl-N-benzyl methane amide (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 18 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 4g by simple column chromatography, and yield is 67%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 32:
In reaction flask, pack successively LiI (20mol%) into, compound 4h (2mmol 264mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 4h by simple column chromatography, and yield is 80%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 33:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 4i (2mmol 260mg), TBHP (11.6mmol), DMF (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 4i by simple column chromatography, and yield is 62%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 34:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1a (2mmol 312mg), TBHP (11.6mmol), N, N-diethylformamide (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 5b by simple column chromatography, and yield is 68%.
Product is analyzed, and result is as follows:
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 170.1,134.9,133.3,129.4,128.6,128.2,126.7,126.2,124.9,124.5,123.0,43.0,38.9,14.1,12.9; 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 object product.
Embodiment 35:
In reaction flask, pack successively NaI (20mol%) into, compound 1a (2mmol), TBHP (20mmol), N-formylpyrrole (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 5c by simple column chromatography, and yield is 74%.
Product is analyzed, and result is as follows:
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 169.1,135.5,133.3,129.0,128.9,128.2,126.8,126.1,125.0,124.7,123.5,48.3,45.5,25.8,24.4; MS:For C
15h
15nO:225, Found:225 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1633. compound is object product.
Embodiment 36:
In reaction flask, pack successively LiI (20mol%) into, compound 1a (2mmol 312mg), TBHP (16mmol), N-N-formyl morpholine N-(2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 5d by simple column chromatography, and yield is 72%.
Product is analyzed, and result is as follows:
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 169.3,133.5,133.3,129.4,129.2,128.3,127.0,126.4,125.0,124.4,123.8,66.9,66.8,47.4,42.0; 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 object product.
Embodiment 37:
In reaction flask, pack successively Me into
4nI (20mol%), compound 1a (2mmol 312mg), TBHP (14mmol), N-formylpiperidine (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 5e by simple column chromatography, and yield is 63%.
Product is analyzed, and result is as follows:
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 169.1,134.7,133.3,129.5,128.7,128.2,126.7,126.2,125.1,124.8,123.3,48.2,42.5,26.5,25.7,24.4; MS:Anal.Calcd.For C
16h
18nO:240, Found:240; IR (KBr, cm
-1): the above digital proof gained of v1629. compound is object product.
Embodiment 38:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1a (2mmol 312mg), TBHP (12mmol), N-methyl-N-benzyl methane amide (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 5f by simple column chromatography, and yield is 82%.
Product is analyzed, and result is as follows:
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 170.6,170.3,136.6,135.6,134.1,133.8,133.0,132.9,129.2,128.9,128.7,128.6,128.2,128.2,127.9,127.8,127.1,126.6,126.5,126.0,125.9,124.7,124.6,124.4,124.2,123.4,54.2,49.9,35.6,32.0.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 object product.
Embodiment 39:
In reaction flask, pack successively NaI (20mol%) into, compound 1a (2mmol 312mg), TBHP (8mmol), N-formyl diallyl amine (2.4mL), vinyl trichloride 8mL.Then this system heats under 60 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 5g by simple column chromatography, and yield is 74%.
Product is analyzed, and result is as follows:
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 170.8,134.1,133.4,132.9,132.7,129.5,129.0,128.3,126.9,126.3,124.9,124.7,123.4,118.0,117.9,50.5,46.3; HRMS:Anal.Calcd.ForC
17h
7nO:251.1310, Found:251.1305; IR (KBr, cm
-1): the above digital proof gained of v1628. compound is object product.
Embodiment 40:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1a (2mmol 312mg), TBHP (6mmol), N-formyl radical-4-hydroxy piperidine (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 5h by simple column chromatography, and yield is 60%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 41:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1a (2mmol 312mg), TBHP (11.6mmol), N-formyl radical-tert-butoxycarbonyl-piperazine (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 5i by simple column chromatography, and yield is 61%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 42:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1a (2mmol 312mg), TBHP (11.6mmol), N-formyl radical pyrazoles (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 5j by simple column chromatography, and yield is 45%.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 43:
In reaction flask, pack successively Me into
4nI (20mol%), compound 1a (2mmol 312mg), TBHP (11.6mmol), N-formyl radical-L-Pro methyl esters (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 5k by simple column chromatography, and yield is 52%.Above digital proof gained compound is object product.
Product is analyzed, and result is as follows:
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 object product.
Embodiment 44:
In reaction flask, pack successively Bu into
4nI (20mol%), compound 1a (2mmol 312mg), TBHP (6mmol), N, N-di-n-butyl methane amide (2.4mL), vinyl trichloride 8mL.Then this system heats under 90 ℃ of conditions after approximately 24 hours in air, and saturated sodium sulfite cancellation, washing, be extracted with ethyl acetate (40mL × 3), gets final product to obtain oxidation products 5l by simple column chromatography, and yield is 70%.
Product is analyzed, and result is as follows:
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), 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 170.6,135.0,133.4,129.5,128.7,128.3,126.8,126.2,125.0,124.7,123.4,48.4,44.4,30.7,29.7,20.4,19.6,13.9,13.4; MS:Anal.Calcd.For C
19h
25nO:283, Found:283 (M
+); IR (KBr, cm
-1): the above digital proof gained of v1616. compound is object product.
Claims (5)
1. a preparation method for acid amides, is characterized in that: take aldehyde derivatives and carboxamides derivatives as reaction substrate, take iodide as catalyzer, tertbutyl peroxide is that oxygenant prepares acid amides by decarbonylation diradical cross-coupling reaction;
Wherein, the chemical structural formula of described aldehyde derivatives is:
; In formula, R
1be selected from: phenyl, naphthyl, heterocycle, alkylene or monosubstituted aryl
; Wherein, R
2be selected from: the hydroxyl that the ester group of methyl, methoxyl group, phenoxy group, styryl, phenylacetylene base, methylthio group, cyano group, C1～C6, nitro, halogen, trifluoromethyl, tertbutyloxycarbonyl are protected;
Described heterocycle is selected from: thienyl, furyl, thiazolyl, pyridyl;
Described alkylene is selected from: styryl;
The chemical structural formula of described carboxamides derivatives is:
,
,
,
,
,
,
,
;
Wherein, R
3, R
4be selected from: the saturated chain type alkyl of C1～C4, benzyl, allyl group;
Described iodide are selected from: sodium iodide 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
3one in NI.
2. the preparation method of acid amides according to claim 1, is characterized in that: temperature of reaction is 60～100 ℃, the reaction times is 12～24 hours.
3. the preparation method of acid amides according to claim 1, is characterized in that: the consumption of catalyzer is 5～40 % of the amount of substance of reaction substrate aldehyde derivatives.
4. the preparation method of acid amides according to claim 1, is characterized in that: the consumption of methane amide is 10～20 times of amount of substance of reaction substrate aldehyde derivatives.
5. the preparation method of acid amides according to claim 1, is characterized in that: solvent for use is: vinyl trichloride, toluene, acetonitrile, 1,2-ethylene dichloride or 1，1，1-trichloroethane.
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| CN103113247B (en) * | 2013-03-13 | 2014-05-14 | 苏州大学 | Method for preparing amino-acid ester |
| CN103274964B (en) * | 2013-06-13 | 2014-07-02 | 苏州大学 | Method for preparing alpha-dicyandiamide |
| CN104086345B (en) * | 2014-06-24 | 2016-06-08 | 苏州大学 | A kind of Pt nanowires catalyzes and synthesizes the method for amides |
| CN107266451B (en) * | 2016-04-07 | 2021-12-31 | 上海医药工业研究院 | Preparation method of rebuximab intermediate |
| CN109206335B (en) * | 2017-06-29 | 2020-10-30 | 沈阳中化农药化工研发有限公司 | Process for preparing ortho-trifluoromethylanilines and intermediates thereof |
| CN110294686B (en) * | 2019-04-28 | 2022-04-15 | 苏州大学 | Green preparation method of alpha-ketoamide |
| CN111039813B (en) * | 2019-12-24 | 2022-07-01 | 江南大学 | Synthetic method of aromatic amide compound |
| 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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| Title |
|---|
| Direct Condensation of Sulfonamide and Formamide NaI-Catalyzed Synthesis of N-Sulfonyl Formamidine Using TBHP as Oxidant;Shulin Chen, et al.;《Organic Letters》;20111031;第13卷(第23期);第6152-6155页 * |
| Shulin Chen, et al..Direct Condensation of Sulfonamide and Formamide NaI-Catalyzed Synthesis of N-Sulfonyl Formamidine Using TBHP as Oxidant.《Organic Letters》.2011,第13卷(第23期),第6152-6155页. |
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