CN101585814B - Aryl pyrimidine ortho-single halogen substituted compound and synthetic method thereof - Google Patents
Aryl pyrimidine ortho-single halogen substituted compound and synthetic method thereof Download PDFInfo
- Publication number
- CN101585814B CN101585814B CN2009100538579A CN200910053857A CN101585814B CN 101585814 B CN101585814 B CN 101585814B CN 2009100538579 A CN2009100538579 A CN 2009100538579A CN 200910053857 A CN200910053857 A CN 200910053857A CN 101585814 B CN101585814 B CN 101585814B
- Authority
- CN
- China
- Prior art keywords
- reaction
- ortho
- pyrimidine
- arylpyrimidines
- halogen substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 0 C1C=CC(C2=*CCC=*2)=CC1 Chemical compound C1C=CC(C2=*CCC=*2)=CC1 0.000 description 2
Landscapes
- Liquid Crystal Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to an aryl pyrimidine ortho-single halogen substituted compound and a synthetic method thereof. The structural formula of the compound is R1=o-Me, m-Me, m-OMe, p-Me, p-Cl, p-COOEt, p-CF3R2=H, 4-Ph, 5-PhX=Cl, Br. The method has specific steps of dissolving aryl pyrimidine, palladium acetate, additive and calcium halide in acetic acid or mixture of acetic acid and acetic anhydride, stirring to react until the raw materials disappear; removing the solvent, adding in saturated sodium bicarbonate solution, extracting the product with ethyl acetate, drying organic phase, obtaining crude product after removing the solvent; and passivating the crude product, thus obtaining the corresponding aryl pyrimidine ortho-single halogen substituted compound. The aryl pyrimidine ortho-single halogen substituted compound is an important organically synthesized intermediate. The invention has easily obtained raw materials, high reaction selectivity, and cheap calcium chloride and calcium bromide as halogen sources. During reaction, the invention uses routine solvent, has simple operation, mild condition, environment-friendly reaction, and reaction yield up to 95%, and is very suitable for industrial production.
Description
Technical field
The present invention relates to the ortho-single halogen substituted compound and the synthetic method thereof of a kind of Arylpyrimidines and synthetic method thereof, particularly a kind of Arylpyrimidines.
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; 14-debromoprearaplysillin that extracts from cavernous body Druinella purpurea and the many bromophenols that extract from cavernous body Dysidea also all have germicidal action; The diterpene Solenolide E that extracts from gorgonian has anti-inflammatory and antivirus action.Chlorinated compound Teicoplanin and Teicoplanin Aglycon owing to be usually used in treats the infection that the staphylococcus that produced by penicillinase causes, is considered to resist last line of defense 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 halid method of the synthesizing aryl of reporting in the document mainly contains following several:
(1) the close electric halogenating reaction by aromatic hydrocarbons prepares.This method raw material sources are extensive, applicable to synthesizing of most of aryl halides.But the regioselectivity of reaction is difficult to control, generates polysubstituted product easily.
X＝Cl，Br，I
(2) obtain by the nucleophilic substitution reaction of halide reagent aryl diazonium salts.This method is had relatively high expectations to substrate, and operating process simultaneously is relatively more dangerous.
X＝Cl，Br，I
(3) the chlorine substitution reaction by sulfonic group, carboxyl, hydroxyl obtains.This method also is one of muriatic common method of preparation aryl, but the limitation of substrate is bigger.
FG＝SO
3H，COOH，OH
(4) obtain by corresponding boric acid compound reaction.Because the source of boric acid is limited and cost is higher, the limitation of this method is bigger.
X＝Br，I
(5) electron-deficient aromatic hydrocarbons can generate corresponding halogenated product under the effect of Lewis acid boron trifluoride.The regioselectivity of this class reaction is not high, and the electronic effect of substrate is had relatively high expectations, and certain limitation is arranged in application.
X＝Cl，Br，I
(6) 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 normally the steric effect by increasing reaction substrate and electronic effect wait and improve regioselectivity.
In sum, the method for preparing aryl halide has a lot, but the regioselectivity of these reactions is wayward, is difficult to obtain single halogenated products of high regioselectivity.Reaction raw materials limitation in some reaction is bigger, and halide reagent toxicity causes environmental pollution than Da Yi, and the productivity ratio of partial reaction is lower or reaction conditions is relatively harsh or the like.
Summary of the invention
One of purpose of the present invention is to provide a kind of ortho-single halogen substituted compound of Arylpyrimidines.
Two of purpose of the present invention is to provide the synthetic method of this compound.
For achieving the above object, the reaction mechanism that the inventive method adopts is:
R
1＝o-Me，m-Me，m-OMe，p-Me，p-Cl，p-COOEt，p-CF
3
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-single halogen substituted compound of Arylpyrimidines is characterized in that the structural formula of this compound is:
Wherein: R
1=o-Me, m-Me, m-OMe, p-Me, p-Cl, p-COOEt, p-CF
3
R
2＝H，4-Ph，5-Ph
X＝Cl，Br。
A kind of method for preparing the ortho-single halogen substituted compound of above-mentioned Arylpyrimidines is characterized in that this method has following steps:
A. with the mixture of acetic acid or acetic acid and acetic anhydride as solvent, the palladium that adds catalyst levels, and press Arylpyrimidines: additive: calcium halide=1: (1.0～2.0): the mol ratio of (2.0～6.0) adds Arylpyrimidines, additive and calcium halide, and the stirring reaction reaction raw materials disappears; The structural formula of described Arylpyrimidines is:
Wherein: R
1=o-Me, m-Me, m-OMe, p-Me, p-Cl, p-COOEt, p-CF
3
R
2＝H，4-Ph，5-Ph；
Described additive is: trifluoracetic acid copper;
Described calcium halide is calcium chloride or Calcium Bromide;
B. after reaction finishes, remove and desolvate, in reaction system, add saturated sodium bicarbonate solution, use ethyl acetate extraction, get crude product after organic phase drying, the removal; This crude product is purified, promptly obtains the ortho-single halogen substituted compound of corresponding Arylpyrimidines.
The ortho-single halogen substituted compound of the Arylpyrimidines that the present invention is prepared is a kind of intermediate of important organic synthesis, this compound is through dissimilar organic chemical reactionses, as Heck reaction, Suzuki reaction etc., can synthesize a series of aryl pyrimidine derivatives quickly and easily.And aryl pyrimidine derivatives not only occupies an important position in pharmaceutical chemistry, also is the very important luminous organic material of a class simultaneously.
The inventive method raw material is easy to get, the reaction preference height, and adopt cheap calcium chloride and Calcium Bromide as the halogen source.Use conventional solvent in the reaction, simple to operate, mild condition, reaction environmental protection, reaction yield reaches as high as 95%, is fit to very much industrial production.
Embodiment
Embodiment one: the preparation of 2-(2-chloro-4-carbethoxy phenyl) pyrimidine
2-(2-chloro-4-carbethoxy phenyl) pyrimidine adopts following step: 1. add 1 gram 2-(4-carbethoxy phenyl) pyrimidine in 250 milliliters of round-bottomed flasks, 500 milligrams of palladium, 16 gram additive trifluoracetic acid copper, 30 gram calcium chloride, 100 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 10.2 gram 2-(2-chloro-4-carbethoxy phenyl) pyrimidines, productive rate is 89%.Fusing point: 100-102 ℃.
IR(KBr，cm
-1)：3056，2982，2935，2872，1717，1567，1496，1447，141?8，1292，1246，1108，1017，828，765.
1H?NMR(500MHz，CDCl
3)：δ8.91(d，J＝4.5Hz，2H)，8.18(d，J＝1.5Hz，1H)，8.03(dd，J＝8，1.5Hz，1H)，7.82(d，J＝8Hz，1H)，7.34(d，J＝5Hz，1H)，4.41(q，J＝7Hz，2H)，1.42(t，J＝7Hz，3H).
13C?NMR(125MHz，CDCl
3)：δ165.3，165.1，157.3，141.5，133.1，132.6，131.9，131.8，127.9，119.9，61.7，14.4.
MS(ESI)：262.8(M
+，
35Cl)，264.8(M
+，
37Cl).
Anal.Calcd.for?C
13H
11ClN
2O
2：C，59.44；H，4.22；N，10.66.Found：C，59.30；H，4.05；N，10.63.
Embodiment two: the method for 2-(2-chloro-4-trifluoromethyl) pyrimidine
2-(2-chloro-4-trifluoromethyl) pyrimidine adopts following step: 1. add 1 gram 2-(4-trifluoromethyl) pyrimidine in 250 milliliters of round-bottomed flasks, 500 milligrams of palladium, 15 gram additive trifluoracetic acid copper, 32 gram calcium chloride, 100 milliliters of acetic acid, be heated to 80 ℃, follow the tracks of reaction, disappear to reaction raw materials 2-(4-trifluoromethyl) 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=10: 1) purifying, obtain 10.3 gram 2-(2-chloro-4-trifluoromethyl) pyrimidines, productive rate is 89%.Fusing point: 68-70 ℃.
IR(KBr，cm
-1)：1565，1504，1422，1389，1321，1180，1124，1079，841，806.
1H?NMR(500MHz，CDCl
3)：δ8.91(d，J＝5Hz，2H)，8.88(d，J＝8Hz，1H)，7.84(s，1H)，7.64(dd，J＝8，1.5Hz，1H)，7.35(t，J＝5Hz，1H).
19F?NMR(CDCl
3，470MHz)：δ-62.9(s，Ar-CF
3).
13C?NMR(125MHz，CDCl
3)：δ164.6，157.4，141.0，133.6，132.6(q，
2J
C-F＝32.5Hz)，132.4，127.8(q，
3J
C-F＝3.75Hz)，123.8(q，
3J
C-F＝3.75Hz)，123.3(q，
1J
C-F＝272.5Hz)，120.0.
MS(ESI)：258.7(M
+，
35Cl)，260.7(M
+，
37Cl).
Anal.Calcd.for?C
11H
6ClF
3N
2：C，51.08；H，2.34；N，10.83.Found：C，51.04；H，2.31；N，10.75.
Embodiment three: the preparation of 2-(2,4 dichloro benzene base) pyrimidine
2-(2, the 4-dichlorophenyl) pyrimidine adopts following step: 1. add 10 gram 2-(4-chloro-phenyl-) pyrimidines in 250 milliliters of round-bottomed flasks, 300 milligrams of palladium, 15 gram additive trifluoracetic acid copper, 26 gram calcium chloride, 100 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=20: 1) purifying, obtain 11.4 gram 2-(2,4 dichloro benzene base) pyrimidines, productive rate is 96%.
IR(KBr，cm
-1)：3059，3038，1587，1566，1479，1438，1415，1104，818，795.
1H?NMR(CDCl
3，500MHz)：δ8.88(d，J＝5Hz，2H)，7.73(d，J＝8.5Hz，1H)，7.53(d，J＝2Hz，1H)，7.37(dd，J＝8.5，2Hz，1H)，7.31(t，J＝5Hz，1H)
13C?NMR(CDCl
3，125MHz)：δ164.9，157.3，136.2，136.0，133.7，132.8，130.6，127.3，119.7.
MS(ESI)：224.7(M
+，
35Cl)，226.7(M
+，
37Cl).
Anal.Calcd.for?C
10H
6Cl
2N
2：C，53.36；H，2.69；N，12.45.Found：C，53.40；H，2.38；N，12.50.
Embodiment four: the preparation of 2-(2-chloro-6-aminomethyl phenyl) pyrimidine
2-(2-chloro-6-aminomethyl phenyl) pyrimidine adopts following step: 1. add 10 gram 2-(2-aminomethyl phenyl) pyrimidines in 100 milliliters of round-bottomed flasks, 200 milligrams of palladium, 20 gram additive trifluoracetic acid copper, 29 gram calcium chloride, 100 milliliters of acetic acid, be heated to 80 ℃, follow the tracks of reaction, disappear to reaction raw materials 2-(2-aminomethyl 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=20: 1) purifying, obtain 9.62 gram 2-(2-chloro-6-aminomethyl phenyl) pyrimidines, productive rate is 80%.
IR(KBr，cm
-1)：3042，2959，2923，2852，1597，1563，1447，1407，815，778.
1H?NMR(CDCl
3，500MHz)：δ8.90(d，J＝5Hz，2H)，7.33-7.29(m，2H)，7.25(t，J＝8Hz，1H)，7.18(d，J＝8Hz，1H)，2.11(s，3H).
13C?NMR(CDCl
3，125MHz)：δ166.4，157.5，138.3，138.1，132.6，129.6，128.7，127.1，119.6，20.1.
MS(ESI)：204.7(M
+，
35Cl)，206.7(M
+，
37Cl).
HRMS?m/z?calcd.for?C
11H
9ClN
2：204.0454，m/z?found：204.0453.
Embodiment five: the preparation of 2-(2-bromo-6-aminomethyl phenyl) pyrimidine
2-(2-bromo-6-aminomethyl phenyl) pyrimidine adopts following step: 1. add 10 gram 2-(2-aminomethyl phenyl) pyrimidines in 250 milliliters of round-bottomed flasks, 400 milligrams of palladium, 40 gram additive trifluoracetic acid copper, 75 gram Calcium Bromides, 150 milliliters of acetic acid, be heated to 80 ℃, follow the tracks of reaction, disappear to reaction raw materials 2-(2-aminomethyl 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=20: 1) purifying, obtain 11.4 gram 2-(2-bromo-6-aminomethyl phenyl) pyrimidines, productive rate is 78%.Fusing point: 61-63 ℃.
IR(KBr，cm
-1)：3043，2959，2923，1594，1562，1443，1405，813，777.
1H?NMR(CDCl
3，500MHz)：δ8.90(d，J＝5Hz，2H)，7.49(d，J＝8Hz，1H)，7.32(t，J＝5Hz，1H)，7.23-7.15(m，2H)，2.11(s，3H).
13C?NMR(CDCl
3，125MHz)：δ167.4，157.5，140.1，138.1，130.2，129.9，129.3，122.0，119.7，20.3.
MS(EI)m/z(％)：250(86)(M
+，
81Br)，248(89)(M
+，
79Br)，169(34)，168(100).
Anal.Calcd.for?C
11H
9BrN
2：C，53.04；H，3.64；N，11.25.Found：C，53.08；H，3.73；N，11.00.
Embodiment six: the preparation of 2-(2-chloro-5-aminomethyl phenyl) pyrimidine
2-(2-chloro-5-aminomethyl phenyl) pyrimidine adopts following step: 1. add 10 gram 2-(3-aminomethyl phenyl) pyrimidines in 250 milliliters of round-bottomed flasks, 80 milligrams of palladium, 20 gram additive trifluoracetic acid steel, 14 gram calcium chloride, 20 milliliters of acetic acid, be heated to 80 ℃, follow the tracks of reaction, disappear to reaction raw materials 2-(3-aminomethyl 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=20: 1) purifying, obtain 10.3 gram 2-(2-chloro-5-aminomethyl phenyl) pyrimidines, productive rate is 86%.
IR(KBr，cm
-1)：3036，2958，2921，2861，1602，1567，1556，1481，1422，1389，1114，813.
1H?NMR(CDCl
3，500MHz)：δ8.86(d，J＝5Hz，2H)，7.54(d，J＝1.5Hz，1H)，7.37(d，J＝8Hz，1H)，7.27(t，J＝5Hz，1H)，7.18(dd，J＝8.5，1.5Hz，1H)，2.36(s，3H).
13C?NMR(CDCl
3，125MHz)：δ165.8，157.1，137.3，136.9，132.3，131.4，130.4，129.6，119.4，20.9.
MS(EI)m/z(％)：206(32)(M
+，
37Cl)，204(100)(M
+，
35Cl)，169(87)，153(8)，151(26)，116(34).
HRMS?m/z?calcd.for?C
11H
9ClN
2：204.0454，m/z?found：204.0457.
Embodiment seven: the preparation of 2-(2-bromo-5-aminomethyl phenyl) pyrimidine
2-(2-bromo-5-aminomethyl phenyl) pyrimidine adopts following step: 1. add 1 gram 2-(3-aminomethyl phenyl) pyrimidine in 250 milliliters of round-bottomed flasks, 500 milligrams of palladium, 36 gram additive trifluoracetic acid copper, 75 gram Calcium Bromides, 150 milliliters of acetic acid, be heated to 80 ℃, follow the tracks of reaction, disappear to reaction raw materials 2-(3-aminomethyl 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=20: 1) purifying, obtain 12.6 gram 2-(2-bromo-5-aminomethyl phenyl) pyrimidines, productive rate is 86%.Fusing point: 46-48 ℃.
IR(KBr，cm
-1)：3036，2970，2921，2860，1598，1565，1557，1477，1421，1387，1023，811.
1H?NMR(CDCl
3，500MHz)：δ8.86(d，J＝5Hz，2H)，7.55(d，J＝8Hz，1H)，7.49(d，J＝1.5Hz，1H)，7.27(t，J＝5Hz，1H)，7.09(dd，J＝8，2Hz，1H)，2.11(s，3H).
13C?NMR(CDCl
3，125MHz)：δ166.7，157.1，139.9，137.5，133.6，132.2，131.5，119.4，118.2，20.9.
MS(EI)m/z(％)：250(25)(M
+，
81Br)，248(26)(M
+，
79Br)，169(100).
Anal.Calcd.for?C
11H
9BrN
2：C，53.04；H，3.64；N，11.25.Found：C，53.24；H，3.54；N，11.24.
Embodiment eight: the preparation of 2-(2-chloro-5-p-methoxy-phenyl) pyrimidine
2-(2-chloro-5-p-methoxy-phenyl) pyrimidine adopts following step: 1. add 10 gram 2-(3-p-methoxy-phenyl) pyrimidines in 250 milliliters of round-bottomed flasks, 600 milligrams of palladium, 18 gram additive trifluoracetic acid copper, 18 gram calcium chloride, 100 milliliters of acetic acid, be heated to 80 ℃, follow the tracks of reaction, disappear to reaction raw materials 2-(3-p-methoxy-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=20: 1) purifying, obtain 10.8 gram 2-(2-chloro-5-p-methoxy-phenyl) pyrimidines, productive rate is 91%.
IR(KBr，cm
-1)：3037，2958，2923，2852，1602，1558，1453，1420，1396，817.
1H?NMR(CDCl
3，500MHz)：δ8.88(d，J＝4.5Hz，2H)，7.39(d，J＝9Hz，1H)，7.29(t，J＝5Hz，1H)，7.27(d，J＝3Hz，1H)，6.94(dd，J＝9，3Hz，1H)，3.83(s，3H).
13C?NMR(CDCl
3，125MHz)：δ165.6，158.3，157.2，138.3，131.5，124.1，119.5，117.1，116.4，55.8.
MS(EI)m/z(％)：222(33)(M
+，
37Cl)，220(100)(M
+，
35Cl)，185(9)，169(5)，167(13)；HRMS?m/zcalcd.for?C
11H
9ClN
2O：220.0403，m/z?found：220.0401.
Embodiment nine: the preparation of 2-(2-bromo-5-p-methoxy-phenyl) pyrimidine
2-(2-bromo-5-p-methoxy-phenyl) pyrimidine adopts following step: 1. add 10 gram 2-(3-p-methoxy-phenyl) pyrimidines in 250 milliliters of round-bottomed flasks, 400 milligrams of palladium, 30 gram additive trifluoracetic acid copper, 68 gram Calcium Bromides, 150 milliliters of acetic acid, be heated to 80 ℃, follow the tracks of reaction, disappear to reaction raw materials 2-(3-p-methoxy-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=20: 1) purifying, obtain 13.5 gram 2-(2-bromo-5-p-methoxy-phenyl) pyrimidines, productive rate is 95%.
IR(KBr，cm
-1)：3039，2960，2935，2837，1596，1560，1450，1420，882，815.
1H?NMR(CDCl
3，500MHz)：δ8.86(d，J＝5Hz，2H)，7.55(d，J＝8.5Hz，1H)，7.28(t，J＝5Hz，1H)，7.22(d，J＝3.5Hz，1H)，6.86(dd，J＝9，3Hz，1H)，3.81(s，3H).
13C?NMR(CDCl
3，125MHz)：δ166.4，159.0，157.1，140.3，134.6，119.6，117.2，116.5，112.1，55.7.
MS(EI)m/z(％)：266(98)(M
+，
81Br)，264(100)(M
+，
79Br)，185(87).
HRMS?m/z?calcd.for?C
11H
9BrN
2O(M
+，
81Br)：265.9878，m/z?found：265.9875.
HRMS?m/z?calcd.for?C
11H
9BrN
2O(M
+，
79Br)：263.9898，m/z?found：263.9896.
Embodiment ten: the preparation of 2-(2-chloro-4-aminomethyl phenyl) pyrimidine
2-(2-chloro-4-aminomethyl phenyl) pyrimidine adopts following step: 1. add 10 gram 2-(4-aminomethyl phenyl) pyrimidines in 250 milliliters of round-bottomed flasks, 600 milligrams of palladium, 20 gram additive trifluoracetic acid copper, 26 gram calcium chloride, 60 milliliters of acetic acid, 50 milliliters of acetic anhydride 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 10.8 gram 2-(2-chloro-4-aminomethyl phenyl) pyrimidines, productive rate is 90%.
IR(KBr，cm
-1)：3035，2961，2920，2852，1605，1562，1499，1417，803.
1H?NMR(CDCl
3，500MHz)：δ8.86(d，J＝4.5Hz，2H)，7.65(d，J＝5Hz，2H)，7.32(s，1H)，7.25(t，J＝5Hz，1H)，7.17(d，J＝7.5Hz，1H)，2.38(s，3H).
13C?NMR(CDCl
3，125MHz)：δ165.8，157.1，141.1，134.9，132.4，131.7，131.2，127.8，119.2，21.2.
MS(EI)m/z(％)：206(33)(M
+，
37Cl)，204(100)(M
+，
35Cl)，169(78)，153(13)，151(38)，116(36).
HRMS?m/z?calcd.for?C
11H
9ClN
2：204.0454，m/z?found：204.0455.
Embodiment 11: the preparation of 2-(2-chloro-phenyl-)-4-phenyl pyrimidine
2-(2-chloro-phenyl-)-4-phenyl pyrimidine adopts following step: 1. add 10 grams 2 in 250 milliliters of round-bottomed flasks, 4-phenylbenzene pyrimidine, 400 milligrams of palladium, 11 gram additive trifluoracetic acid copper, 25 gram calcium chloride, 60 milliliters of acetic acid, 50 milliliters of acetic anhydride 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 10.3 the gram 2-(2-chloro-phenyl-)-4-phenyl pyrimidines, productive rate is 90%.Fusing point: 69-71 ℃.
IR(KBr，cm
-1)：1573，1544，1495，1439，1419，1373，755.
1H?NMR(CDCl
3，500MHz)：δ8.91(d，J＝5Hz，1H)，8.21-8.17(m，2H)，7.89-7.84(m，1H)，7.69(d，J＝5Hz，1H)，7.55-7.51(m，4H)，7.42-7.38(m，2H).
13C?NMR(CDCl
3，125MHz)：δ165.7，164.1，157.8，138.0，136.8，133.1，132.0，131.3，130.8，130.5，129.2，127.5，126.9，114.9.
MS(ESI)：266.7(M
+，
35Cl)，268.7(M
+，
37Cl).
Anal.Calcd.for?C
16H
11ClN
2：C，72.05；H，4.16；N，10.50.Found：C，71.80；H，4.16；N，10.41.
Embodiment 12: the preparation of 2-(2-chloro-phenyl-)-5-phenyl pyrimidine
2-(2-chloro-phenyl-)-5-phenyl pyrimidine adopts following step: 1. add 10 grams 2 in 250 milliliters of round-bottomed flasks, 5-phenylbenzene pyrimidine, 400 milligrams of palladium, 11 gram additive trifluoracetic acid copper, 25 gram calcium chloride, 60 milliliters of acetic acid, 50 milliliters of acetic anhydride 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 10.1 the gram 2-(2-chloro-phenyl-)-5-phenyl pyrimidines, productive rate is 88%.Fusing point: 109-110 ℃.
IR(KBr，cm
-1)：3059，3040，1580，1531，1477，1428，1378，758.
1H?NMR(CDCl
3，500MHz)：δ9.09(s，2H)，7.83-7.82(m，1H)，7.67-7.64(m，2H)，7.57-7.52(m，3H)，7.51-7.47(m，1H)，7.42-7.38(m，2H).
13C?NMR(CDCl
3，125MHz)：δ164.3，155.1，137.5，134.3，132.9，132.1，131.9，130.8，130.7，129.6，129.2，127.2，127.0.
MS(ESI)：266.8(M
+，
35Cl)，268.8(M
+，
37Cl).
Anal.Calcd.for?C
16H
11ClN
2：C，72.05；H，4.16；N，10.50.Found：C，71.98；H，4.11；N，10.39。
Claims (2)
1. the ortho-single halogen substituted compound of an Arylpyrimidines is characterized in that the structural formula of this compound is:
Wherein: R
1=o-Me, m-Me, m-OMe, p-Me, p-Cl, p-COOEt, p-CF
3
R
2＝H，4-Ph，5-Ph
X＝Cl，Br。
2. method for preparing the ortho-single halogen substituted compound of Arylpyrimidines according to claim 1 is characterized in that this method has following steps:
A. with the mixture of acetic acid or acetic acid and acetic anhydride as solvent, the palladium that adds catalyst levels, and press Arylpyrimidines: additive: calcium halide=1: (1.0～2.0): the mol ratio of (2.0～6.0) adds Arylpyrimidines, additive and calcium halide, and stirring reaction to reaction raw materials disappears; The structural formula of described Arylpyrimidines is:
Wherein: R
1=o-Me, m-Me, m-OMe, p-Me, p-Cl, p-COOEt, p-CF
3
R
2＝H，4-Ph，5-Ph；
Described additive is: trifluoracetic acid copper;
Described calcium halide is calcium chloride or Calcium Bromide;
B. after reaction finishes, remove and desolvate, in reaction system, add saturated sodium bicarbonate solution, use ethyl acetate extraction, get crude product after organic phase drying, the removal; This crude product is purified, promptly obtains the ortho-single halogen substituted compound of corresponding Arylpyrimidines.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100538579A CN101585814B (en) | 2009-06-26 | 2009-06-26 | Aryl pyrimidine ortho-single halogen substituted compound and synthetic method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100538579A CN101585814B (en) | 2009-06-26 | 2009-06-26 | Aryl pyrimidine ortho-single halogen substituted compound and synthetic method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101585814A CN101585814A (en) | 2009-11-25 |
| CN101585814B true CN101585814B (en) | 2011-08-10 |
Family
ID=41370266
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100538579A Expired - Fee Related CN101585814B (en) | 2009-06-26 | 2009-06-26 | Aryl pyrimidine ortho-single halogen substituted compound and synthetic method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101585814B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101812022B (en) * | 2010-04-20 | 2012-01-04 | 上海大学 | Ortho-monovinylphenyl substituted compound of aryl pyrimidine and synthesizing method thereof |
| CN102344410A (en) * | 2011-08-05 | 2012-02-08 | 上海大学 | Arylpyridine ortho-position monohalogenated compounds and synthesis method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1636000A (en) * | 2000-03-16 | 2005-07-06 | 神经能质公司 | 5-substituted arylpyrimidines |
-
2009
- 2009-06-26 CN CN2009100538579A patent/CN101585814B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1636000A (en) * | 2000-03-16 | 2005-07-06 | 神经能质公司 | 5-substituted arylpyrimidines |
Non-Patent Citations (3)
| Title |
|---|
| Kakiuchi F.et al.Palladium-Catalyzed Aromatic C-H Halogenation with Hydrogen Halides by Means of Electrochemical Oxidation.《J. AM. CHEM. SOC.》.2009,第131卷11310-11311. * |
| Kalyani D. et al.A Simple Catalytic Method for the Regioselective Halogenation of Arenes.《Org.Lett.》.2006,第8卷(第12期),2523-2526. * |
| Kalyani D.et al.Scope and selectivity in palladium-catalyzed directed C–H bond halogenation reactions.《Tetrahderon》.2006,第62卷11483-11498. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101585814A (en) | 2009-11-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Matos et al. | Synthesis of 3-arylcoumarins via Suzuki-cross-coupling reactions of 3-chlorocoumarin | |
| CN108069934B (en) | Method for preparing polyaromatic substituted naphthalene derivative by reaction of biphenyl type arone and tolane catalyzed by ruthenium | |
| CN107382856B (en) | Novel polysubstituted isoquinoline derivative and synthetic method thereof | |
| Fu et al. | Visible-light-mediated trifluoroethylation of N-arylacrylamides with trifluoroethyl iodide: synthesis of CF3-containing oxindoles | |
| CN110028403A (en) | A kind of method of synthesizing succinic acid class compound | |
| CN104910104B (en) | A kind of method of utilization copper catalysis synthesizing dihydro furan derivatives | |
| CN105801575A (en) | Synthetic method of imidazo[1,2-a]pyridine | |
| CN101585814B (en) | Aryl pyrimidine ortho-single halogen substituted compound and synthetic method thereof | |
| CN107973691B (en) | Method for preparing polyaromatic substituted naphthalene derivative by cyclization reaction of aromatic ketone and tolane catalyzed by ruthenium and application | |
| CN105085208B (en) | A kind of preparation method using palladium as catalyst benzfluorene ketone compounds | |
| CN110003011B (en) | Preparation method of nitroolefin derivative by taking nitrate as nitro source | |
| Wang et al. | 3-Butyl-1-methylimidazolinium borohydride ([bmim][BH4])—a novel reducing agent for the selective reduction of carbon–carbon double bonds in activated conjugated alkenes | |
| CN113185472B (en) | Method for synthesizing 4-alkoxy alkenyl isoxazole derivative | |
| CN107602452B (en) | Synthetic method of 3-acyl pyridine compound | |
| CN105622625A (en) | Synthesis method of benzopyrone and imidazopyridine compound | |
| CN101654439A (en) | Ortho-position dihalogen substitution compound of aryl pyrimidine and preparing method thereof | |
| CN108299340B (en) | Method for synthesizing 2-fluoro-N-substituted aryl acetamide compound | |
| CN105294476B (en) | The synthetic method of 2 acyloxy acrylamides | |
| CN112442008A (en) | Method for preparing 1, 4-dithiine and thiophene compounds by regulating elemental sulfur and active internal alkyne at temperature and conversion reaction of compound | |
| CN107880004B (en) | Preparation method of 5-phenoxyphthalide | |
| CN104311553B (en) | Ortho position monochloro substituted compound and the synthetic method thereof of N-aryl azaindole | |
| CN101812022B (en) | Ortho-monovinylphenyl substituted compound of aryl pyrimidine and synthesizing method thereof | |
| CN110294708B (en) | Preparation method of trifluoroethylselenophenanthridine and 3, 4-dihydroisoquinoline derivatives | |
| CN108129348B (en) | Nitrine trifluoromethoxy compound and its synthetic method | |
| CN102718694B (en) | 3-cyan substituted indole compound and synthetic method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20110810 Termination date: 20140626 |
|
| EXPY | Termination of patent right or utility model |