CN101607923B - Aromatic nitrile compounds or derivatives of same and synthetic method and application thereof - Google Patents
Aromatic nitrile compounds or derivatives of same and synthetic method and application thereof Download PDFInfo
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- CN101607923B CN101607923B CN 200910088860 CN200910088860A CN101607923B CN 101607923 B CN101607923 B CN 101607923B CN 200910088860 CN200910088860 CN 200910088860 CN 200910088860 A CN200910088860 A CN 200910088860A CN 101607923 B CN101607923 B CN 101607923B
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Abstract
The invention discloses aromatic nitrile compounds or derivatives of same and a synthetic method and an application thereof and the synthetic method of aromatic nitrile compounds or derivatives of same comprises the following steps: using copper or copper compound as auxiliary agent, mixing arylmethane compound, sodium azide and organic solvent to perform aryl methyl cyanation reaction under the action of oxidant and obtaining the finished product. In the method of the invention, copper or copper compound is firstly used as auxiliary agent and arylmethane compound and sodium azide are reacted to prepare aromatic nitrile compounds by adopting iodobenzene acetate as oxidant. The synthetic method of the invention has the advantages of high yield, simple conditions, accessible raw materials, simple reaction equipments, easy realization of industrialized production and the like.
Description
Technical field
The present invention relates to the aromatic nitrile compounds or derivatives thereof, the invention still further relates to the compound method of aromatic nitrile compounds or derivatives thereof, belong to aryl nitrile compound field.
Background technology
The aryl nitrile is one type of biologically active, extensively is present in the central important molecule fragment of medicine and organism.The structure of aryl nitrile is the more interested research directions of people always, a large amount of bibliographical informations has the been arranged construction process of multiple aryl nitrile.But the compound method report that directly converts the aryl nitrile into from aromatic methane also is not a lot, although document (L ü cke, B.; Narayana, K.V.; Martin, A.;
; K.Adv.Synth.Catal.2004; 346; 1407.) compound method that ammonia oxidation has prepared the aromatic nitriles compound to arylmethane done play-by-play; But these methods all in various degree have a following defective, have much room for improvement: 1. the temperature higher (300-400 ℃) of reaction, the substrate functional group tolerance is poor; 2. need the preparation catalyzer, the complicated operation of reaction.Compare with previous methods, the inventive method reaction conditions gentle (room temperature reaction), substrate functional group is compatible wide, easy and simple to handle.
Summary of the invention
One of the object of the invention provides one type of new aromatic nitrile compounds or derivatives thereof;
Two of the object of the invention provides a kind of method of synthetic above-mentioned aromatic nitrile compounds or derivatives thereof;
The objective of the invention is to realize through following technical scheme:
One type of aromatic nitrile compounds and or derivatives thereof, its structural formula is shown in the following general formula I:
general formula I
R wherein
1Be selected from C
1-10Alkoxyl group, siloxy, trifluoromethoxy, phenyl, the hydroxyl of the amino or protection of protection; R
2Be selected from C
1-10Alkyl, C
1-10Alkoxyl group, hydroxyl, phenyl, halogen or the ester group of the amino or protection of protection.
Preferably, R
1Be selected from methoxyl group, oxyethyl group, 4 ' methyl-phenoxy, methoxymethoxy, tert-butyl diphenyl siloxy, tert.-butoxy carboxamido-group; R
2Be selected from methoxyl group, methoxy acyl group, methyl or bromine.
Above-mentioned compound of Formula I itself has certain physiologically active as a kind of important molecule stripping and slicing, also can for example synthesize anti-picornavirus bioactive molecule 1 through to the further synthetic compound with physiologically active of the conversion of functional group.The experiment report, anti-people's picornavirus IC of compound 1
80=0.2uM (J.Med.Chem.1993,36,3240.).
Another object of the present invention provides a kind of method of synthetic above-mentioned compound of Formula I;
Another object of the present invention realizes through following technical scheme:
A kind of method of synthetic above-mentioned compound of Formula I may further comprise the steps:
Under the oxygenant effect, be assistant agent with copper or copper-containing compound, fragrant methane compound, sodiumazide and organic solvent are mixed the reaction that is carried out to the aryl nitrile; Filter, desolventize, column chromatography is handled, and promptly gets.
In order to reach better synthetic effect, preferred, with copper or copper-containing compound assistant agent, aromatic base methane class compounds, oxygenant and sodiumazide are according to 1: (1-1000): (1-1000): mol ratio (1-1000) is carried out to the reaction of aryl nitrile; Preferred, with copper or copper-containing compound assistant agent, aromatic base methane class compounds, oxygenant and sodiumazide were according to 5: 100: 400: 320 mol ratio is carried out to the reaction of aryl nitrile.
In addition, when the inventor found under following condition, to carry out building-up reactions, effect was for best: with three parts of weight such as oxygenant, sodiumazide are divided into separately; Take out wherein portion and copper or copper-containing compound respectively, fragrant methane compound and organic solvent mixed stirring reaction two hours; Then other two parts of oxygenants and sodiumazide are joined in the reactant at twice, every two hours add once, reaction is accomplished after filtration desolventizes, and column chromatography is handled, and promptly gets;
The temperature of described one-tenth aryl nitrile reaction is preferably 0-100 ℃, more preferably 25 ℃.
Wherein, described oxygenant is preferably acetic acid iodobenzene and verivate thereof; Preferred, described oxygenant is the acetic acid iodobenzene;
Described copper-containing compound can be CuCl
2, CuCl, Cu (OAc)
2, Cu (acac)
2, Cu (OTf)
2, CuI
2, CuCN
2, CuSO
45H
2O or CuI etc.
Described aromatic methane compounds can be various substituted toluene compounds, and wherein, described substituting group can be C
1-10Alkoxyl group, siloxy, trifluoromethoxy, phenyl, the amino of protection, the hydroxyl of protection, C
1-10Alkyl, halogen or ester group.Preferably, described substituted toluene compounds comprises: 4-methoxy toluene, 4-oxyethyl group toluene, 3,4-dimethoxy-p; 2,4-dimethoxy-p, 2,4,6-trimethoxytoluene; 3-methoxy acyl group-4-methoxy toluene, 2-methyl-4-methoxy toluene, 4 ' methyl-4-phenoxytoluene, 4-methoxymethoxy toluene; 4-tert-butyl diphenyl siloxy toluene, 3-bromo-4-oxyethyl group toluene, 4-methoxyl group-1-methylnaphthalene, 4-tert.-butoxy carboxamido-group toluene or 4-phenyltolyl;
Described organic solvent is preferably 1,2-ethylene dichloride, methylene dichloride, ETHYLE ACETATE, acetone, Nitromethane 99Min. or acetonitrile; Acetonitrile more preferably;
The present invention is an assistant agent with price comparatively cheap copper or copper-containing compound, is oxygenant with the acetic acid iodobenzene, and aryl toluene and sodiumazide are generated aryl nitrile or derivatives thereof; Compound method of the present invention has the yield height, and condition is simple, and raw material is easy to get, and conversion unit is simple, is easy to plurality of advantages such as suitability for industrialized production.
Description of drawings
The synthetic route chart of Fig. 1 The compounds of this invention.
Embodiment
Further describe the present invention below in conjunction with specific embodiment, advantage of the present invention and characteristics will be more clear along with description.But these embodiment only are exemplary, scope of the present invention are not constituted any restriction.It will be understood by those skilled in the art that and down can make amendment with form or replace without departing from the spirit and scope of the present invention, but these modifications and replacing all fall in protection scope of the present invention the details of technical scheme of the present invention.
The preparation of embodiment 1 4-anisole formonitrile HCN
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 4-methoxy toluene 64mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 47mg, productive rate 71%.
IR：(KBr)ν
max?2969，2924，2854，2219，1606，1510，1461，1260，1176，1024，832cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝7.51(d，J＝8.9Hz，2H)，6.87(m，J＝8.9Hz，2H)，3.78(s，3H)；
13C?NMR(CDCl
3，75MHz)：δ＝162.8，133.9，119.2，114.7，103.9，55.5ppm；MS(70eV)：m/z(％)：133.1(M
+，100).
The preparation of embodiment 24-anisole formonitrile HCN
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 4-methoxy toluene 64mg, sodiumazide 130mg, acetic acid iodobenzene 515mg down; 4 milliliters of acetonitriles stir under room temperature, and reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 34mg, productive rate 53%.
IR：(KBr)ν
max?2969，2924，2854，2219，1606，1510，1461，1260，1176，1024，832cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝7.51(d，J＝8.9Hz，2H)，6.87(m，J＝8.9Hz，2H)，3.78(s，3H)；
13C?NMR(CDCl
3，75MHz)：δ＝162.8，133.9，119.2，114.7，103.9，55.5ppm；MS(70eV)：m/z(％)：133.1(M
+，100).
The preparation of embodiment 3 4-phenetole formonitrile HCNs
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 4-oxyethyl group toluene 69mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 48mg, productive rate 65%.
IR：(KBr)ν
max?2981，2220，1605，1507，1260，1172，1039，845，808cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝7.57(d，J＝9.2Hz，2H)，6.93(d，J＝9.2Hz，2H)，4.08(q，J＝7.0Hz，2H)，1.44(t，J＝7.0Hz，3H)；
13CNMR(CDCl
3，75MHz)：δ＝162.2，133.9，119.3，115.1，103.6，63.9，14.5ppm；HRMSm/z(ESI)calcd?for?C
9H
9NO(M+H)
+：148.0757，found148.0753.
Embodiment 43, the preparation of 4-dimethoxy cyanobenzene
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 3,4-dimethoxy-p 76mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 70mg, productive rate 86%.
IR：(KBr)ν
max?2972，2223，1599，1516，1271，1244，1138，1018，875，810，616cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝7.29(dd，J＝8.3Hz，J＝1.7Hz?1H)，7.08(s，1H)，6.91(d，J＝8.3Hz，1H)，3.94(s，3H)，3.91(s，3H)；
13C?NMR(CDCl
3，75MHz)：δ＝152.7，149.0，126.3，119.1，113.7，111.1，103.7，56.0ppm；MS(70eV)：m/z(％)163.1(M
+，100).
Embodiment 52, the preparation of 4-dimethoxy cyanobenzene
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 2,4-dimethoxy-p 76mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 78mg, productive rate 96%.
IR：(KBr)ν
max2220，1606，1508，1329，1288，1272，1216，1022，841，808cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝7.46(d，J＝8.5Hz，1H)，6.52(dd，J＝8.5Hz，J＝2.1Hz，1H)，6.46(d，J＝2.1Hz，1H)3.90(s，3H)，3.86(s，3H)；
13C?NMR(CDCl
3，75MHz)：δ＝164.5，162.7，134.7，116.9，105.7，98.3，93.7，55.9，55.6ppm；MS(70eV)：m/z(％)163.1(M
+，100).
Embodiment 62, the preparation of 4-dimethoxy cyanobenzene
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 2,4-dimethoxy-p 76mg, sodiumazide 130mg down; Acetic acid iodobenzene 515mg, 4 milliliters of acetonitriles stir under room temperature, and reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 56mg, productive rate 69%.
IR：(KBr)ν
max?2220，1606，1508，1329，1288，1272，1216，1022，841，808cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝7.46(d，J＝8.5Hz，1H)，6.52(dd，J＝8.5Hz，J＝2.1Hz，1H)，6.46(d，J＝2.1Hz，1H)3.90(s，3H)，3.86(s，3H)；
13C?NMR(CDCl
3，75MHz)：δ＝164.5，162.7，134.7，116.9，105.7，98.3，93.7，55.9，55.6ppm；MS(70eV)：m/z(％)163.1(M
+，100).
Embodiment 72, and 4, the preparation of 6-trimethoxy-benzonitrile
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 2,4,6-trimethoxytoluene 91mg down; Sodiumazide 44mg, acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 50mg, productive rate 52%.
IR：(KBr)ν
max?3398，2948，2849，2213，1609，1582，1470，1416，1229，1213，1158，1134，1051，1023，808cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝6.07(s，2H)，4.00-3.86(d，9H)；
13C?NMR(CDCl
3，75MHz)：δ＝165.3，163.7，114.6，90.3，56.0，55.6ppm；MS(70eV)：m/z(％)：193.2(M
+，100).
The preparation of embodiment 8 3-methoxy acyl groups-4-anisole formonitrile HCN
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 3-methoxy acyl group-4-methoxy toluene 90mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 30mg, productive rate 31%.
IR：(KBr)ν
max?3062，2958，2229，1696，1611，1502，1320，1273，1251，1019，817，794cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝8.10(d，J＝2.2Hz，1H)，7.76(dd，J＝8.8Hz，J＝2.2Hz，1H)，7.07(d，J＝8.8Hz，1H)，3.98(s，3H)，3.92(s，3H)；
13C?NMR(CDCl
3，75MHz)：δ＝164.6，162.0，137.1，135.8，121.0，118.1，112.7，103.8，56.4，52.4ppm；HRMSm/z(ESI)calcd?for?C
10H
9NO
3(M+H)
+：192.0655，found?192.0660.
The preparation of embodiment 9 2-methyl-4-anisole formonitrile HCN
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 2-methyl-4-methoxy toluene 68mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 56mg, productive rate 76%.
IR：(KBr)ν
max?2964，2219，1608，1500，1254，1110，1038，809，685cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝7.51(d，J＝8.4Hz，2H)，6.80-6.74(m，2H)，3.84(s，3H)，2.51(s，3H)；
13C?NMR(CDCl
3，75MHz)：δ＝162.6，144.0，134.1，118.5，115.6，112.0，104.4，55.4，20.6ppm；MS(70eV)：m/z(％)147.0(M
+，100).
The preparation of embodiment 10 4 ' methyl-4-phenoxy cyanobenzene
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 4 ' methyl-4-phenoxytoluene 99mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 87mg, productive rate 83%.
IR：(KBr)ν
max?2924，2221，2099，1900，1598，1499，1245，1167，833cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝7.58(d，J＝8.4Hz，2H)，7.21(d，J＝8.4Hz，2H)，7.00-6.93(m，4H)，2.37(s，3H)；
13C?NMR(CDCl
3，75MHz)：δ＝162.1，152.3，134.9，134.0，130.7，120.4，118.9，117.5，105.4，20.8ppm；MS(70eV)：m/z(％)209.0(M
+，100).
The preparation of embodiment 11 4-methoxymethoxy cyanobenzenes
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 4-methoxymethoxy toluene 77mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 41mg, productive rate 50%.
IR：(KBr)ν
max?2962，2226，1605，1508，1246，1154，1083，986，839cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝7.59(d，J＝9.0Hz，2H)，7.10(d，J＝9.0Hz，2H)，5.23(s，2H)，3.48(s，3H)；
13C?NMR(CDCl
3，75MHz)：δ＝160.4，133.9，119.0，116.7，105.0，94.0，56.3ppm；MS(70eV)：m/z(％)163.2(M
+，2)，121.1(100).
The preparation of embodiment 12 4-tert-butyl diphenyl siloxy cyanobenzenes
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 4-tert-butyl diphenyl siloxy toluene 173mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 167mg, productive rate 95%.
IR：(KBr)ν
max?2931，2858，2225，1601，1505，1286，12701，1115，916，701cm
-1；
1H?NMR(CDCl
3，400MHz)：δ＝7.70-7.65(m，4H)，7.48-7.42(m，2H)，7.41-7.35(m，6H)，6.81-6.76(m，2H)，1.10(s，9H)；
13C?NMR(CDCl
3，100MHz)：δ＝159.4，135.3，133.8，131.7，130.3，128.0，120.6，119.1，104.5，26.3，19.4ppm；HRMS?m/z(ESI)calcd?forC
23H
23NOSi(M+H)
+：358.1622，found?358.1635.
The preparation of embodiment 13 3-bromo-4-phenetole formonitrile HCNs
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 3-bromo-4-oxyethyl group toluene 108mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 33mg, productive rate 29%.
IR：(KBr)ν
max?2224，2120，1595，1495，1470，1295，1265，1052，1035，925，813，780cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝7.82(d，J＝2.0Hz，1H)，7.57(dd，J＝8.5Hz，J＝2.0Hz，1H)，6.92(d，J＝8.5Hz，1H)，4.17(q，J＝7.0Hz，2H)，1.51(t，J＝7.0Hz，3H)；
13C?NMR(CDCl
3，75MHz)：δ＝158.8，136.6，133.0，117.8，112.6，112.4，104.8，65.2，14.4ppm；MS(70eV)：m/z(％)225.1(M
+，
79Br，16)，227.1(M
+，
81Br，15)，40.1(100).HRMS?m/z(ESI)calcd?for?C
9H
8BrNO(M+H)
+：225.9862，found?225.9866.
The preparation of embodiment 144-methoxyl group-1-cyanic acid naphthalene
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 4-methoxyl group-1-methylnaphthalene 86mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 70mg, productive rate 77%.
IR：(KBr)ν
max?2212，2108，1578，1387，1277，1243，1222，1093，1018，817，756cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝8.28(d，J＝7.8Hz，1H)，8.13(d，J＝7.8Hz，1H)，7.81(d，J＝8.0Hz，1H)，7.66(t，J＝7.8Hz，1H)，7.55(t，J＝8.0Hz，1H)，6.78(d，J＝8.0Hz，1H)，4.03(s，3H)；
13CNMR(CDCl
3，75MHz)：δ＝159.3，134.0，133.3，128.8，126.6，125.0，124.8，122.7，118.4，103.2，101.7，55.9ppm；MS(70eV)：m/z(％)183.1(M
+，100).
The preparation of embodiment 15 4-tert.-butoxy carboxamido-group cyanobenzenes
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 4-tert.-butoxy carboxamido-group toluene 104mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 48mg, productive rate 44%.
IR：(KBr)ν
max?3368，2993，2925，2225，2113，1693，1523，1500，1152，832cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝7.57(d，J＝8.7Hz，2H)，7.49(m，J＝8.7Hz，2H)，6.88(br?s，1H)，1.52(s，9H)；
13C?NMR(CDCl
3，75MHz)：δ＝152.0，142.6，133.2，119.0，118.0，105.6，81.6，28.2ppm；MS(70e?V)：m/z(％)218.2(M
+，13)，57.1(100).
The preparation of embodiment 16 4-phenyl cyanobenzenes
Get a reaction tubes, nitrogen protection adds 6.2mg copper sulfate, 4-phenyltolyl 84mg, sodiumazide 44mg down; Acetic acid iodobenzene 175mg, 4 milliliters of acetonitriles stirred two hours under room temperature; After other two parts of sodiumazide (44mg * 2) and acetic acid iodobenzene (175mg * 2) are added, every two hours add once, reaction is accomplished after filter; Desolventize, column chromatography is handled and is obtained pure article 40mg, productive rate 45%.
IR：(KBr)ν
max?2224，1603，1482，1396，847，769，697cm
-1；
1HNMR(CDCl
3，300MHz)：δ＝7.76-7.64(m，4H)，7.61-7.55(m，2H)，7.52-7.38(m，3H)；
13C?NMR(CDCl
3，75MHz)：δ＝145.6，139.1，132.6，129.1，128.6，127.7，127.2，118.9，110.9ppm；MS(70eV)：m/z(％)179.2(M
+，100)。
Claims (10)
1. the method for a synthesizing aryl nitrile compounds comprises: under the oxygenant effect,, aromatic methane compounds, sodiumazide and organic solvent mixed carry out fragrant methyl-cyanide glycosylation reaction as assistant agent with copper or copper-containing compound; Reaction product is filtered, remove and desolvate, column chromatography is handled, and promptly gets;
Described aromatic nitrile compounds, its structural formula are shown in the general formula I:
R wherein
1Be selected from C
1-10Alkoxyl group; R
2Be selected from C
1-10Alkyl, C
1-10Alkoxyl group, halogen or ester group;
Described aromatic methane compounds is substituted toluene compounds, and wherein, described substituting group is C
1-10Alkoxyl group, C
1-10Alkyl, halogen or ester group.
2. according to the described method of claim 1; It is characterized in that: with copper or copper-containing compound assistant agent; The aromatic base methane compound, oxygenant and sodiumazide are according to 1: (1-1000): (1-1000): mol ratio proportioning (1-1000) is carried out fragrant methyl-cyanide glycosylation reaction.
3. according to the described method of claim 2, it is characterized in that: with copper or copper-containing compound assistant agent, aromatic base methane class compounds, oxygenant and sodiumazide were according to 5: 100: 400: 320 mol ratio proportioning is carried out fragrant methyl-cyanide glycosylation reaction.
4. according to each described method of claim 1-3, it is characterized in that: three parts of weight such as oxygenant, sodiumazide are divided into separately; Take out wherein portion and copper or copper-containing compound respectively, fragrant methane compound and organic solvent mixed stirring reaction two hours; Then other two parts of oxygenants and sodiumazide are joined in the reactant at twice, every two hours add once, reaction is accomplished after filtration desolventizes, and column chromatography is handled, and promptly gets.
5. according to each described method of claim 1-3, it is characterized in that: the temperature of reaction of described one-tenth aryl nitrile reaction is 0-100 ℃.
6. according to the described method of claim 5, it is characterized in that: the temperature of reaction of described one-tenth aryl nitrile reaction is 25 ℃.
7. according to the described method of claim 1, it is characterized in that: described oxygenant is an acetic acid iodobenzene or derivatives thereof.
8. according to the described method of claim 1, it is characterized in that: described copper-containing compound is selected from CuCl
2, CuCl, Cu (OAc)
2, Cu (acac)
2, Cu (OTf)
2, CuI
2, CuCN
2, CuSO
4Or CuI.
9. according to the described method of claim 2, it is characterized in that: described substituted toluene compounds is selected from 3, the 4-dimethoxy-p; 2; 4-dimethoxy-p, 3-methoxy acyl group-4-methoxy toluene, 2-methyl-4-methoxy toluene or 3-bromo-4-oxyethyl group toluene.
10. according to the described method of claim 1, it is characterized in that: described organic solvent is selected from 1,2-ethylene dichloride, methylene dichloride, ETHYLE ACETATE, acetone, Nitromethane 99Min. or acetonitrile.
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