CN101654439A - Ortho-position dihalogen substitution compound of aryl pyrimidine and preparing method thereof - Google Patents
Ortho-position dihalogen substitution compound of aryl pyrimidine and preparing method thereof Download PDFInfo
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Abstract
The invention relates to an ortho-position dihalogen substitution compound of aryl pyrimidine and a preparing method thereof. The compound has the following structural formula I: R1=H, p-Me, p-Cl, p-COOEt, p-CF3, m-Me, m-OMe, R2=H, 4-Ph, 5-Ph, X=Cl, Br. The invention comprises the following steps: dissolving aryl pyrimidine, palladium acetate, additive and halogenation calcium into acetic acid, stirring, and reacting until reaction raw material disappears; removing solvent, adding saturation sodium bicarbonate solution into a system, and extracting a product with ethyl acetate; obtaining a crude product by drying the organic phase and removing the solvent; purifying the product to obtain the corresponding ortho-position dihalogen substitution compound of aryl pyrimidine. The compound of the invention is a kind of important organic synthesis intermediate. The invention has easily obtained raw material, high reaction selectivity, and adopts calcium chloride and calcium bromide with low price as a halogen source, uses common solvent in reaction, and has simple operation, moderate reaction condition and environmentally friendly reaction, maximum reaction yield can reach 95%, so that the invention is very suitable for industrial production.
Description
Technical field
The present invention relates to a kind of aryl pyrimidine derivatives and preparation method thereof, particularly ortho-position dihalogen substitution compound of Arylpyrimidines and preparation method thereof.
Background technology
Halogenide extensively is present among the Nature, and especially in the ocean, the content of chlorine has reached 0.5M, and the content of bromine is about 0.1M, and the content of iodine also can reach 1 μ M.Because special biological activity, Organohalogen compounds also are simultaneously one of medicament sources widely, and for example a lot of halogenide all are excellent antibiotic medicine, antiphlogiston and antitumour drug.The metabolite Aeroplysinin-1 of cavernous body is a kind of antimicrobial drug; The 14-debromoprearaplysillin that extracts among the cavernous body Druinella purpurea, and the many bromophenols that extract among the cavernous body Dysidea also all have germicidal action; The diterpene Solenolide E that extracts from gorgonian has anti-inflammatory and antivirus action.The infection that the staphylococcus that chlorinated compound Teicoplanin and Teicoplanin Aglycon owing to usually be used for the treatment of produced by penicillinase causes, and be considered to resist the last defence line of this type of pathogenic agent.In addition, Organohalogen compounds also are often used as dyestuff, as famous dyestuff Tyrian purple and substituted indole etc.
As important organic intermediate, the application of halogenated aromatic is very extensive, and the approach of multiple simple and fast is provided for the structure of complex compound in the organic synthesis.For example, from the halogenide of Arylpyrimidines,,, can synthesize a series of aryl pyrimidine derivatives quickly and easily as Heck reaction, Suzuki reaction etc. by dissimilar organic chemical reactionses.Arylpyrimidines and derivative thereof occupy an important position in pharmaceutical chemistry, and its application in luminous organic material simultaneously is also very extensive, and general method is difficult to realize the efficient structure of Arylpyrimidines.
The two halid methods of the synthesizing aryl of reporting in the document mainly contain following several:
(1) the close electric halogenating reaction by aromatic hydrocarbons prepares.This method raw material sources are extensive, and applicable to synthesizing of most of aryl halides, still, selectivity is difficult to control, follow simultaneously to generate polysubstituted halogenide, and reaction is difficult to be controlled at two replacement halogenide stages of ortho position.
X=Cl,Br,I
(2) under the highly basic condition, prepare by lithiation.This method will be used highly basic such as butyllithium usually, and is bigger to the restriction ratio of substrate.Simultaneously, reaction conditions is relatively harsher, is not suitable for industrial production.
X=Cl,Br,I
(3) by transition metal-catalyzed carbon-hydrogen bond activation preparation.This class operation is simple, helps the control of regioselectivity, but existing method still is confined to the minority substrate, and contains substituent substrate for position between on the phenyl ring, and the two halogenating reactions of adjacent can't take place.
The DG=pyridine, acid amides etc.
X=Cl
In sum, the method for preparing aryl ortho-position dihalogen thing has a lot, but the regioselectivity of these reactions is wayward, is difficult to obtain single ortho-position dihalogen product.Reaction raw materials limitation in some reaction is bigger, and reaction yield is lower, and reaction reagent costliness and reaction conditions are comparatively harsh or the like.
Summary of the invention
One of purpose of the present invention is to provide a kind of ortho-position dihalogen substitution compound of Arylpyrimidines.
Two of purpose of the present invention is to provide the preparation method of this compound.
For achieving the above object, the reaction mechanism that the inventive method adopts is:
R
1=H,p-Me,p-Cl,p-COOEt,p-CF
3,m-Me,m-OMe
R
2=H,4-Ph,5-Ph
X=Cl,Br
According to above-mentioned reaction mechanism, the present invention has adopted following technical scheme:
A kind of ortho-position dihalogen substitution compound of Arylpyrimidines is characterized in that the structural formula of this compound is:
Wherein: R
1=H, p-Me, p-Cl, p-COOEt, p-CF
3, m-Me, m-OMe
R
2=H,4-Ph,5-Ph
X=Cl,Br。
A kind of method for preparing the ortho-position dihalogen substitution compound of above-mentioned Arylpyrimidines is characterized in that this method has following steps:
A. with Arylpyrimidines, additive and calcium halide by 1: (1.0~2.0): the mol ratio of (4.0~8.0) is dissolved in the acetic acid, and adds the palladium of catalyst levels, and stirring reaction to reaction raw materials disappears; The structural formula of described Arylpyrimidines is:
Wherein: R
1=H, p-Me, p-Cl, p-COOEt, p-CF
3, m-Me, m-OMe
R
2=H,4-Ph,5-Ph
X=Cl,Br;
Described calcium halide is calcium chloride or Calcium Bromide;
Described additive is: trifluoracetic acid copper;
B. after reaction finishes, remove solvent, add saturated sodium bicarbonate solution, use the ethyl acetate extraction product, organic phase is removed solvent after drying and is got crude product; This crude product is purified, promptly obtains the ortho-position dihalogen substitution compound of corresponding Arylpyrimidines.
The ortho-position dihalogen substitution compound of Arylpyrimidines of the present invention is the important organic reaction intermediate of a class, by dissimilar organic chemical reactionses, as Heck reaction, Suzuki reaction etc., can synthesize a series of aryl pyrimidine derivatives quickly and easily.Aryl pyrimidine derivatives not only occupies an important position in pharmaceutical chemistry, also is a kind of important luminous organic material simultaneously.
The inventive method raw material is easy to get, and adopts cheap calcium chloride and Calcium Bromide as the halogen source, uses conventional reaction solvent, operate very simple, mild condition, the reaction environmental protection, productive rate reaches as high as 97%, very suitable industrial production.
Embodiment
Embodiment one: the preparation of 2-(2, the 6-dichlorophenyl) pyrimidine
2-(2, the 6-dichlorophenyl) pyrimidine adopts following step: 1. in 250 milliliters of round-bottomed flasks, add 10 gram 2-phenyl pyrimidines, and 250 milligrams of palladium, 22 gram additive trifluoracetic acid copper, 35 gram calcium chloride, 150 milliliters of acetic acid are heated to 80 ℃.Follow the tracks of reaction with the thin-layer chromatography method, disappear to reaction raw materials 2-phenyl pyrimidine; 2. after reacting end, except that desolvating, add saturated sodium bicarbonate solution with Rotary Evaporators in system, use the ethyl acetate extraction product, solvent is removed with Rotary Evaporators in dry back, gets crude product; 3. crude product with column chromatography (sherwood oil: ethyl acetate=20: 1) purifying, obtain 14.4 gram 2-(2, the 6-dichlorophenyl) pyrimidines, productive rate is 96%.Fusing point: 130-132 ℃.
IR(KBr,cm
-1):3044,1587,1562,1466,1430,1406,780.
1H?NMR(CDCl
3,500MHz):δ8.92(d,J=5Hz,2H),7.42(d,J=8Hz,2H),7.37(t,J=5Hz,1H),7.32(t,J=8Hz,1H).
13C?NMR(CDCl
3,125MHz):δ164.5,157.6,137.7,134.1,130.4,128.3,120.2.MS(EI)m/z(%):226(41)(M
+,
37Cl),224(67)(M
+,
35Cl),191(33),189(100),173(37),171(54).Anal.Calcd.for?C
10H
6Cl
2N
2:C,53.36;H,2.69;N,12.45.Found:C,53.08;H,2.85;N,12.29.
Embodiment two: the preparation of 2-(2,6-two chloro-4-aminomethyl phenyls) pyrimidine
2-(2,6-two chloro-4-aminomethyl phenyls) pyrimidine adopts following step: 1. add 10 gram 2-(4-aminomethyl phenyl) pyrimidines in 250 milliliters of round-bottomed flasks, 370 milligrams of palladium, 17 gram additive trifluoracetic acid copper, 30 gram calcium chloride, 150 milliliters of acetic acid are heated to 80 ℃.Follow the tracks of reaction with the thin-layer chromatography method, disappear to reaction raw materials 2-(4-aminomethyl phenyl) pyrimidine; 2. after reacting end, except that desolvating, add saturated sodium bicarbonate solution with Rotary Evaporators in system, use the ethyl acetate extraction product, solvent is removed with Rotary Evaporators in dry back, gets crude product; 3. crude product with column chromatography (sherwood oil: ethyl acetate=20: 1) purifying, obtain 13.6 gram 2-(2,6-two chloro-4-aminomethyl phenyls) pyrimidines, productive rate is 97%.Fusing point: 117-119 ℃.
IR(KBr,cm
-1):3035,2964,2924,2863,1600,1560,1438,1409,793.
1H?NMR(CDCl
3,500MHz):δ8.91(d,J=5Hz,2H),7.34(t,J=5Hz,1H),7.23(s,2H),2.37(s,3H).
13C?NMR(CDCl
3,125MHz):δ166.6,157.5,141.1,134.8,133.6,128.8,120.1,21.1.MS(EI)m/z(%):240(48)(M
+,
37Cl),238(76)(M
+,
35Cl),205(33),203(100),187(25),185(38).Anal.Calcd.for?C
11H
8Cl
2N
2:C,55.26;H,3.37;N,11.72.Found:C,55.01;H,3.38;N,11.55.
Embodiment three: the preparation of 2-(2,6-two bromo-4-aminomethyl phenyls) pyrimidine
2-(2,6-two bromo-4-aminomethyl phenyls) pyrimidine adopts following step: 1. add 10 gram 2-(4-aminomethyl phenyl) pyrimidines in 250 milliliters of round-bottomed flasks, 500 milligrams of palladium, 50 gram additive trifluoracetic acid copper, 70 gram Calcium Bromides, 150 milliliters of acetic acid are heated to 80 ℃, follow the tracks of reaction with the thin-layer chromatography method, disappear to reaction raw materials 2-(4-aminomethyl phenyl) pyrimidine; 2. after reacting end, except that desolvating, add saturated sodium bicarbonate solution with Rotary Evaporators in system, use the ethyl acetate extraction product, solvent is removed with Rotary Evaporators in dry back, gets crude product; 3. crude product with column chromatography (sherwood oil: ethyl acetate=20: 1) purifying, obtain 18.3 gram 2-(2,6-two bromo-4-aminomethyl phenyls) pyrimidines, productive rate is 95%.Fusing point: 142-144 ℃.
IR(KBr,cm
-1):1594,1562,1537,1482,1408,745.
1H?NMR(CDCl
3,500MHz):δ8.91(d,J=5Hz,2H),7.45(s,2H),7.34(t,J=5Hz,1H),2.37(s,3H).
13C?NMR(CDCl
3,125MHz):δ166.8,157.5,141.7,138.2,132.4,122.3,120.1,20.8.MS(EI)m/z(%):330(17)(M
+,
81Br),328(36)[M
+,(
79Br,
81Br)],326(17)(M
+,
79Br),249(100)[M
+,(
79Br,
81Br)-
79Br],247(97)[M
+,(
79Br,
81Br)-
81Br].
Anal.Calcd.for?C
11H
8Br
2N
2:C,40.28;H,2.46;N,8.54.Found:C,40.32;H,2.47;N,8.39.
Embodiment four: the preparation of 2-(2,6-two chloro-4-carbethoxy phenyls) pyrimidine
2-(2,6-two chloro-4-carbethoxy phenyls) pyrimidine adopts following step: 1. add 10 gram 2-(4-carbethoxy phenyl) pyrimidines in 250 milliliters of round-bottomed flasks, 400 milligrams of palladium, 13 gram additive trifluoracetic acid copper, 39 gram calcium chloride, 150 milliliters of acetic acid are heated to 80 ℃, follow the tracks of reaction with the thin-layer chromatography method, disappear to reaction raw materials 2-(4-carbethoxy phenyl) pyrimidine; 2. after reacting end, except that desolvating, add saturated sodium bicarbonate solution with Rotary Evaporators in system, use the ethyl acetate extraction product, solvent is removed with Rotary Evaporators in dry back, gets crude product; 3. crude product with column chromatography (sherwood oil: ethyl acetate=15: 1) purifying, obtain 11.7 gram 2-(2,6-two chloro-4-carbethoxy phenyls) pyrimidines, productive rate is 90%.Fusing point: 156-158 ℃.
IR(KBr,cm
-1):3086,3046,2988,2940,2909,2871,1724,1563,1477,1448,1412,1379,1272,1156,805,762.
1H?NMR(CDCl
3,500MHz):δ8.93(d,J=5Hz,2H),8.07(s,2H),7.39(t,J=5Hz,1H),4.42(q,J=7Hz,2H),1.42(t,J=7Hz,3H).
13C?NMR(CDCl
3,125MHz):δ164.2,163.8,157.7,141.1,134.5,132.7,129.2,120.5,62.1,14.4.MS(ESI):296.7(M
+,
35Cl),298.7(M
+,
37Cl).
Anal.Calcd.for?C
13H
10Cl
2N
2O
2:C,52.55;H,3.39;N,9.43.Found:C,52.63;H,3.23;N,9.44.
Embodiment five: the preparation of 2-(2,6-two bromo-4-carbethoxy phenyls) pyrimidine
2-(2,6-two bromo-4-carbethoxy phenyls) pyrimidine adopts following step: 1. add 10 gram 2-(4-carbethoxy phenyl) pyrimidines in 250 milliliters of round-bottomed flasks, 350 milligrams of palladium, 24 gram additive trifluoracetic acid copper, 60 gram Calcium Bromides, 150 milliliters of acetic acid are heated to 80 ℃, follow the tracks of reaction with the thin-layer chromatography method, disappear to reaction raw materials 2-(4-carbethoxy phenyl) pyrimidine; 2. after reacting end, except that desolvating, add saturated sodium bicarbonate solution with Rotary Evaporators in system, use the ethyl acetate extraction product, solvent is removed with Rotary Evaporators in dry back, gets crude product; 3. crude product with column chromatography (sherwood oil: ethyl acetate=15: 1) purifying, obtain 13.5 gram 2-(2,6-two bromo-4-carbethoxy phenyls) pyrimidines, productive rate is 80%.Fusing point: 172-174 ℃.
IR(KBr,cm
-1):3079,3043,3000,2978,2931,1721,1562,1540,1470,1441,1409,1371,1279,1142,1113,1204,766,741.
1H?NMR(CDCl
3,500MHz):δ8.93(d,J=4.5Hz,2H),8.29(s,2H),7.39(t,J=5Hz,1H),4.41(q,J=7Hz,2H),1.42(t,J=7Hz,3H).
13C?NMR(CDCl
3,125MHz):δ166.2,163.9,157.7,144.5,133.1,132.9,122.9,120.5,62.1,14.4.MS(ESI):386.5(M
+,
79Br),388.5(M
+,
81Br).
Anal.Calcd.for?C
13H
10Br
2N
2O
2:C,40.45;H,2.61;N,7.26.Found:C,40.68;H,2.66;N,7.29.
Embodiment six: the preparation of 2-(2,6-dichlor-4-trifluoromethyl phenyl) pyrimidine
2-(2,6-dichlor-4-trifluoromethyl phenyl) pyrimidine adopts following step: 1. add 10 gram 2-(4-trifluoromethyl) pyrimidines in 250 milliliters of round-bottomed flasks, 400 milligrams of palladium, 15 gram additive trifluoracetic acid copper, 40 gram calcium chloride, 150 milliliters of acetic acid are heated to 80 ℃, follow the tracks of reaction with the thin-layer chromatography method, disappear to reaction raw materials 2-(4-trifluoromethyl) pyrimidine; 2. after reacting end, except that desolvating, add saturated sodium bicarbonate solution with Rotary Evaporators in system, use the ethyl acetate extraction product, solvent is removed with Rotary Evaporators in dry back, gets crude product; 3. crude product with column chromatography (sherwood oil: ethyl acetate=10: 1) purifying, obtain 11.4 gram 2-(2,6-dichlor-4-trifluoromethyl phenyl) pyrimidines, productive rate is 87%.Fusing point: 106-108 ℃.
IR(KBr,cm
-1):1565,1416,1325,1296,1134,874,798.
1H?NMR(CDCl
3,500MHz):δ8.94(d,J=5Hz,2H),7.69(s,2H),7.41(t,J=5Hz,1H),
19FNMR(CDCl
3,470MHz):δ-63.1(s,Ar-CF
3).
13C?NMR(CDCl
3,125MHz):δ163.4,157.8,140.8,135.1,132.9(q,
2J
C-F=33.75Hz),125.3(q,
3J
C-F=3.75Hz),122.6(q,
1J
C-F=272.5Hz),120.6.
MS(EI)m/z(%):294(41)(M
+,
37Cl),292(65)(M
+,
35Cl),259(32),257(100),241(35),239(61).
Anal.Calcd.for?C
11H
5Cl
2F
3N
2:C,45.08;H,1.72;N,9.56.Found:C,45.32;H,1.86;N,9.41.
Embodiment seven: the preparation of 2-(2,4, the 6-trichlorophenyl) pyrimidine
2-(2,4, the 6-trichlorophenyl) pyrimidine adopts following step: 1. add 10 gram 2-(4-chloro-phenyl-) pyrimidines in 250 milliliters of round-bottomed flasks, 400 milligrams of palladium, 15 gram additive trifluoracetic acid copper, 40 gram calcium chloride, 150 milliliters of acetic acid, be heated to 80 ℃, follow the tracks of reaction, disappear to reaction raw materials 2-(4-chloro-phenyl-) pyrimidine with the thin-layer chromatography method; 2. after reacting end, except that desolvating, add saturated sodium bicarbonate solution with Rotary Evaporators in system, use the ethyl acetate extraction product, solvent is removed with Rotary Evaporators in dry back, gets crude product; 3. crude product with column chromatography (sherwood oil: ethyl acetate=15: 1) purifying, obtain 10.5 gram 2-(2,4, the 6-trichlorophenyl) pyrimidines, productive rate is 77%.Fusing point: 145-146 ℃.
IR(KBr,cm
-1):3060,3034,1584,1561,1407,1373,1116,857,832,794.
1H?NMR(CDCl
3,500MHz):δ8.92(d,J=5Hz,2H),7.44(s,2H),7.38(t,J=5Hz,1H).
13C?NMR(CDCl
3,125MHz):163.7,157.7,136.3,135.4,134.8,128.3,120.4.
MS(EI)m/z(%):262(24),260(73),258(75),225(64),223(100),207(68),205(70),172(12),170(17),136(7),134(17).
Anal.Calcd.for?C
10H
5Cl
3N
2:C,46.28;H,1.94;N,10.79.Found:C,46.12;H,1.97;N,10.67.
Embodiment eight: the preparation of 2-(2,6-two bromo-4-chloro-phenyl-s) pyrimidine
2-(2,6-two bromo-4-chloro-phenyl-s) pyrimidine adopts following step: 1. add 10 gram 2-(4-chloro-phenyl-) pyrimidines in 250 milliliters of round-bottomed flasks, 400 milligrams of palladium, 15 gram additive trifluoracetic acid copper, 40 gram calcium chloride, 150 milliliters of acetic acid are heated to 80 ℃, follow the tracks of reaction with the thin-layer chromatography method, disappear to reaction raw materials 2-(4-chloro-phenyl-) pyrimidine; 2. after reacting end, except that desolvating, add saturated sodium bicarbonate solution with Rotary Evaporators in system, use the ethyl acetate extraction product, solvent is removed with Rotary Evaporators in dry back, gets crude product; 3. crude product with column chromatography (sherwood oil: ethyl acetate=15: 1) purifying, obtain 18.1 gram 2-(2,6-two bromo-4-chloro-phenyl-s) pyrimidines, productive rate is 90%.Fusing point: 139-141 ℃.
IR(KBr,cm
-1):3055,3019,1575,1560,1533,1404,1364,1115,864,816,744.
1H?NMR(CDCl
3,500MHz):δ8.92(d,J=4.5Hz,2H),7.66(s,2H),7.38-7.60(m,1H).
13C?NMR(CDCl
3,125MHz):166.1,157.7,139.7,135.8,131.8,123.0,120.4.
MS(EI)m/z(%):350(22)(M
+,
81Br),348(33)[M
+,(
79Br,
81Br)],346(14)(M
+,
79Br),271(27),269(100)[M
+,(
79Br,
81Br)-
79Br],267(79)[M
+,(
79Br,
81Br)-
81Br].
Anal.Calcd.for?C
10H
5Br
2ClN
2:C,34.47;H,1.45;N,8.04.Found:C,34.33;H,1.51;N,8.03.
Embodiment nine: the preparation of 2-(2,6-two chloro-5-aminomethyl phenyls) pyrimidine
2-(2,6-two chloro-5-aminomethyl phenyls) pyrimidine adopts following step: 1. add 1 gram 2-(3-aminomethyl phenyl) pyrimidine in 250 milliliters of round-bottomed flasks, 70 milligrams of palladium, 19 gram additive trifluoracetic acid copper, 27 gram calcium chloride, 150 milliliters of acetic acid are heated to 80 ℃, follow the tracks of reaction with the thin-layer chromatography method, disappear to reaction raw materials 2-(3-aminomethyl phenyl) pyrimidine; 2. after reacting end, except that desolvating, add saturated sodium bicarbonate solution with Rotary Evaporators in system, use the ethyl acetate extraction product, solvent is removed with Rotary Evaporators in dry back, gets crude product; 3. crude product with column chromatography (sherwood oil: ethyl acetate=20: 1) purifying, obtain 12.9 gram 2-(2,6-two chloro-5-aminomethyl phenyls) pyrimidines, productive rate is 92%.Fusing point: 70-72 ℃.
IR(KBr,cm-1):3043,2976,2924,2856,1562,1452,1423,1380,1148,812,799,703.
1H?NMR(CDCl
3,500MHz):δ8.93(d,J=5Hz,2H),7.37(t,J=5Hz,1H),7.32(d,J=8Hz,1H),7.27(d,J=8Hz,1H),2.41(s,3H).
13C?NMR(CDCl
3,125MHz):δ165.0,157.6,137.6,135.8,133.9,131.6,131.1,127.7,120.1,20.3.
MS(ESI):238.6(M
+,
35Cl),240.6(M
+,
37Cl).
Anal.Calcd.for?C
11H
8Cl
2N
2:C,55.26;H,3.37;N,11.72.Found:C,55.13;H,3.31;N,11.53.
Embodiment ten: the preparation of 2-(2,6-two chloro-5-p-methoxy-phenyls) pyrimidine
2-(2,6-two chloro-5-p-methoxy-phenyls) pyrimidine adopts following step: 1. add 10 gram 2-(3-p-methoxy-phenyl) pyrimidines in 250 milliliters of round-bottomed flasks, 65 milligrams of palladium, 18 gram additive trifluoracetic acid copper, 25 gram calcium chloride, 150 milliliters of acetic acid are heated to 80 ℃, follow the tracks of reaction with the thin-layer chromatography method, disappear to reaction raw materials 2-(3-p-methoxy-phenyl) pyrimidine; 2. after reacting end, except that desolvating, add saturated sodium bicarbonate solution with Rotary Evaporators in system, use the ethyl acetate extraction product, solvent is removed with Rotary Evaporators in dry back, gets crude product; 3. crude product with column chromatography (sherwood oil: ethyl acetate=20: 1) purifying, obtain 11.4 gram 2-(2,6-two chloro-5-p-methoxy-phenyls) pyrimidines, productive rate is 83%.Fusing point: 168-170 ℃.
IR(KBr,cm-1):2971,2939,2840,1563,1466,1454,1429,1396,1250,1033,813,781,706.
1H?NMR(CDCl
3,500MHz):δ8.92(d,J=5Hz,2H),7.37-7.34(m,2H),6.96(d,J=9Hz,1H),3.92(s,3H).
13C?NMR(CDCl
3,125MHz):δ164.4,157.6,154.4,138.6,128.4,124.9,122.8,120.2,112.9,56.8.
MS(ESI):254.7(M
+,
35Cl),256.7(M
+,
37Cl).
Anal.Calcd.for?C
11H
8Cl
2N
2O:C,51.79;H,3.16;N,10.98.Found:C,51.51;H,3.15;N,10.88.
Embodiment 11: the preparation of 2-(2, the 6-dichlorophenyl)-4-phenyl pyrimidine
2-(2, the 6-dichlorophenyl)-and the 4-phenyl pyrimidine adopts following step: 1. in 250 milliliters of round-bottomed flasks, add 10 grams 2,4-phenylbenzene pyrimidine, 400 milligrams of palladium, 15 gram additive trifluoracetic acid copper, 25 gram calcium chloride, 150 milliliters of acetic acid are heated to 80 ℃, follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials 2,4-phenylbenzene pyrimidine disappears; 2. after reacting end, except that desolvating, add saturated sodium bicarbonate solution with Rotary Evaporators in system, use the ethyl acetate extraction product, solvent is removed with Rotary Evaporators in dry back, gets crude product; 3. crude product with column chromatography (sherwood oil: ethyl acetate=20: 1) purifying, obtain 11.4 the gram 2-(2, the 6-dichlorophenyl)-4-phenyl pyrimidines, productive rate is 90%.Fusing point: 148-149 ℃.
IR(KBr,cm
-1):1572,1541,1494,1450,1427,1370,783,765.
1H?NMR(CDCl
3,500MHz):δ8.93(d,J=5.5Hz,1H),8.15-8.12(m,2H),7.73(d,J=5.5Hz,1H),7.53-7.50(m,3H),7.42(d,J=8.5Hz,2H),7.32(dd,J=8.5,2.5Hz,1H).
13C?NMR(CDCl
3,125MHz):δ164.8,164.4,158.0,138.0,136.6,134.3,131.3,130.2,129.2,128.3,127.6,115.8.
MS(ESI):300.7(M
+,
35Cl),302.7(M
+,
37Cl).
Anal.Calcd.for?C
16H
10Cl
2N
2:C,63.81;H,3.35;N,9.30.Found:C,63.73;H,3.37;N,9.34.
Embodiment 12: the preparation of 2-(2, the 6-dichlorophenyl)-5-phenyl pyrimidine
2-(2, the 6-dichlorophenyl)-and the 5-phenyl pyrimidine adopts following step: 1. in 250 milliliters of round-bottomed flasks, add 10 grams 2,5-phenylbenzene pyrimidine, 450 milligrams of palladium, 13 gram additive trifluoracetic acid copper, 30 gram calcium chloride, 150 milliliters of acetic acid are heated to 80 ℃, follow the tracks of reaction with the thin-layer chromatography method, to reaction raw materials 2,5-phenylbenzene pyrimidine disappears; 2. after reacting end, except that desolvating, add saturated sodium bicarbonate solution with Rotary Evaporators in system, use the ethyl acetate extraction product, solvent is removed with Rotary Evaporators in dry back, gets crude product; 3. crude product with column chromatography (sherwood oil: ethyl acetate=20: 1) purifying, obtain 11.7 the gram 2-(2, the 6-dichlorophenyl)-5-phenyl pyrimidines, productive rate is 90%.Fusing point: 132-134 ℃.
IR(KBr,cm
-1):3058,3032,1580,1560,1543,1467,1419,779;763.
1H?NMR(CDCl
3,500MHz):δ9.12(s,2H),7.70-7.67(m,2H),7.58-7.54(m,2H),7.52-7.48(m,1H),7.50-7.34(m,2H),7.34(dd,J=9,7.5Hz,1H).
13C?NMR(CDCl
3,125MHz):δ162.9,155.5,137.5,134.3,134.1,132.9,130.5,129.6,129.3,128.3,127.3.
MS(ESI):300.7(M
+,
35Cl),302.7(M
+,
37Cl).
Anal.Calcd.for?C
16H
10Cl
2N
2:C,63.81;H,3.35;N,9.30.Found:C,63.97;H,3.29;N,9.25.
Claims (2)
2. method for preparing according to the ortho-position dihalogen substitution compound of the described Arylpyrimidines of claim is characterized in that this method has following steps:
A. with Arylpyrimidines, additive and calcium halide by 1: (1.0~2.0): the mol ratio of (4.0~8.0) is dissolved in the acetic acid, and adds the palladium of catalyst levels, and stirring reaction to reaction raw materials disappears; The structural formula of described Arylpyrimidines is:
Wherein: R
1=H, p-Me, p-Cl, p-COOEt, p-CF
3, m-Me, m-OMe.
R
2=H,4-Ph,5-Ph
X=Cl,Br;
Described calcium halide is calcium chloride or Calcium Bromide;
Described additive is: trifluoracetic acid copper;
B. after reaction finishes, remove solvent, add saturated sodium bicarbonate solution, use the ethyl acetate extraction product, organic phase is removed solvent after drying and is got crude product; This crude product is purified, promptly obtains the ortho-position dihalogen substitution compound of corresponding Arylpyrimidines.
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---|---|---|---|---|
CN101812022A (en) * | 2010-04-20 | 2010-08-25 | 上海大学 | Ortho-monovinylphenyl substituted compound of aryl pyrimidine and synthesizing method thereof |
CN106279014A (en) * | 2016-08-11 | 2017-01-04 | 南京理工大学 | A kind of synthesis phenylglycine analog derivative and method |
-
2009
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CN101812022A (en) * | 2010-04-20 | 2010-08-25 | 上海大学 | Ortho-monovinylphenyl substituted compound of aryl pyrimidine and synthesizing method thereof |
CN106279014A (en) * | 2016-08-11 | 2017-01-04 | 南京理工大学 | A kind of synthesis phenylglycine analog derivative and method |
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