CN103172637B - Pyrimido [1, 2-a] benzimidazole compound and method for preparing same - Google Patents
Pyrimido [1, 2-a] benzimidazole compound and method for preparing same Download PDFInfo
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Abstract
The invention relates to a substituted benzimidazole compound. The substituted benzimidazole compound is characterized by having a structural formula as shown in the specification, R<1> represents a halogen, Ar, and R<2> represents p-Me, p-Cl, p-Br, p-I, p-COOEt, m-Me, o-Me and o-Cl. A method for preparing the substituted benzimidazole compound is characterized by comprising the following steps of: adding substituted N-phenyl-2-aminopyrimidine and PIFA into acetonitrile according to the molar ratio of 1:(1.2-1.8), stirring at room temperature for reaction until the raw materials disappear, removing a solvent to obtain a crude product of reaction, separating the crude product of reaction by column chromatography, and purifying to obtain the corresponding substituted benzimidazole compound. The raw materials are easy to obtain, the environment-friendly reaction yield is up to 97%, the substrate has a wide range of application, the conventional solvent is used during reaction, the operation is simple, the reaction condition is mild, and the method is very suitable for industrial production.
Description
Technical field
The present invention relates to a kind of benzimidazoles compound and preparation method thereof, particularly a kind of Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound and preparation method thereof.
Background technology
Nitrogen heterocyclic ring is a kind of important pharmacophoric group in pharmaceutical chemistry research, becomes one of important goal of current small-molecule drug research and development because majority has biological activity.In the brand medicine of first 25 of global sales in 2007, all there is nitrogen heterocyclic ring skeleton.The physiologically active such as antibacterial, antitumor that nitrogen-containing heterocycle compound has, and its significance in basic theory and applied research, make to synthesize this compounds and research its chemistry and biological nature, become a heat subject of organic chemistry and association area.
Various biological activity that the drug molecule that benzimidazoles compound is constructed because of it presents and be widely used for clinical treatment, its effect has hypertension, parasiticide, antibacterial, antimycotic, antiviral, anticancer, analgesia etc.Such as, stomach ulcer medicine rabeprazole and omeprazole is controlled; Antihypertensive drug telmisartan and Candesartan; Antiparasitic albendazole and mebendazole etc.Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound has many potential medicine medicinal actives.It has microbiotic and antiarrhythmic performance (see Forche Asobo, P.; Wahe, H.; Mbafor, J. T.; Nkengfack, A. E.; Fomum, Z. T.; Sopbue, E. F.; Dopp, D.
j. Chem. Soc., Perkin Trans. 12001,457-461.Other physiologically active is also had in medicine, as follows:
See with Publication about Document:
1. Lazareno, S.; Popham, A.; Birdsall, N. J. M.
Mol. Pharm. 2002,
62, 1492.
2. Galal, S. A.; Abd El-All, A. S.; Abdallah, M. M.; El-Diwani, H. I.
Bioorg. Med. Chem. Lett. 2009,
19, 2420.
3. Farghaly, T. A.; Abdel Hafez, N. A.; Ragab, E. A.; Awad, H. M.; Abdalla, M. M.
Eur. J. Med. Chem. 2010,
45, 492.
4. E. R. Squibb and Sons, Inc. Patent:
US 4072679 A1, 1978.
Due to the structural singularity of Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound, this compounds can as important organic synthesis intermediate.Relevant reaction is exemplified below:
1. form the new skeleton of a class after Kui Linpyrimido quinoline [1, the 2-a] benzimidazoles compound replaced and iodoethane reaction can replace an ethyl on nitrogen-atoms, find that it has the effect suppressing central nervous system and anti-inflammatory agent after deliberation.See: Lin, H.; Erhard, K.; Hardwicke, M. A.; Luengo, J. I.; Mack, J. F.; McSurdy-Freed, J.; Plant, R.; Raha, K.; Rominger, C. M.; Sanchez, R. M.; Schaber, M. D.; Schulz, M. J.; Spengler, M. D.; Tedesco, R.; Xie, R.; Zeng, J. J.; Rivero, R. A.
bioorg. Med. Chem 2012,
22, 2230-2234.
2. Kui Linpyrimido quinoline [1, the 2-a] benzimidazoles compound replaced, by the modification to its imidazole nitrogen atom, can synthesize a series of compound inhibited to cancer cells, have very large research potential.See: Da Settimo, A.; Primofiore, G.; Da Settimo, F.; Pardi, G.; Simorini, F.; Marini, A. M.
j. Heterocyclic Chem. 2002,
39, 1007-1011.
3. Kui Linpyrimido quinoline [1, the 2-a] benzimidazoles compound replaced and Sodium Nitrite reaction, can generate a series of new five-ring product, this compounds has antiviral activity.See: K ü nstlinger, M.; Breitmaier, E.
synthesis 1983, 161.
As can be seen here, development is a kind of can the novel method of efficient synthesizing benzimidazole compounds particularly Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound, has great importance.It can provide a kind of effective means for developing new benzimidazoles residues.
The method of synthesis Kui Linpyrimido quinoline [1, the 2-a] benzimidazoles compound reported in document, mainly contains following several:
(1) with 2-aminobenzimidazole and alkene ether for raw material obtains Kui Linpyrimido quinoline [1,2-a] benzoglyoxaline, see Zhang, Z.-T.; Qiu, L.; Xue, D.; Wu, J.; Xu, F.-F.
j. Comb. Chem. 2009,
12, 225.This kind of operation is simple, but productive rate is lower and raw material is very expensive, is unfavorable for industrial production.
Under basic conditions, with benzoglyoxaline and ketone for raw material obtains Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound, see: Bharate, S. B.; Mahajan, T. R.; Gole, Y. R.; Nambiar, M.; Matan, T. T.; Kulkarni-Almeida, A.; Balachandran, S.; Junjappa, H.; Balakrishnan, A.; Vishwakarma, R. A.
bioorg. Med. Chem. 2008,
16, 7167.
(2).But this reaction is very large to the restriction of raw material.
(3) under the catalysis of tosic acid, benzoglyoxaline and aldehyde compound obtain Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound
[10].But this reaction has higher requirements to raw material equally.
In sum, the method preparing Kui Linpyrimido quinoline [1,2-a] benzimidazoles compound has a lot, but the raw material of these reactions is difficult to obtain, and needs the synthesis step through more complicated; In some reaction, the limitation of reaction raw materials is comparatively large, and reaction yield is lower etc.
Summary of the invention
An object of the present invention is the benzimidazoles compound providing a kind of replacement.
Two of object of the present invention is the preparation method providing this compound.
For achieving the above object, the reaction mechanism that the inventive method adopts is:
Wherein: R
1=halogen, Ar;
R
2=
-Me，
-Cl，
-Br，-I，-COOEt；
PIFA is trifluoracetic acid iodobenzene.
According to above-mentioned reaction mechanism, present invention employs following technical scheme:
A kind of substituted benzimidazole compounds, is characterized in that the structural formula of this compound is:
Wherein: R
1=halogen, Ar;
R
2= -Me，
-Cl，
-Br，-I，-COOEt。
A kind of synthetic method preparing above-mentioned substituted benzimidazole compounds, it is characterized in that the method has following steps: join in acetonitrile by the N-phenyl-2-aminopyrimidine of replacement, PIFA by the mol ratio of 1:1.2 ~ 1.8, stirring at room temperature reaction disappears to raw material; Crude product is obtained except after desolventizing; This crude product, through separation and purification, namely obtains corresponding substituted benzimidazole compounds; The structural formula of the N-phenyl-2-aminopyrimidine of described replacement is:
.
Substituted benzimidazole compounds of the present invention is the important intermediate of synthesizing benzimidazole compounds, and its preparation method raw material is easy to get, and reaction yield is high, wide application range of substrates.Use Conventional solvents in reaction, simple to operate, mild condition, reaction environmental protection reaction yield, up to 97%, are very applicable to industrial production.
Embodiment
The preparation of embodiment one: 7-group-4 ethyl formate pyrimidine also [1,2-a] benzoglyoxaline
7-group-4 ethyl formate pyrimidine also [1,2-a] benzoglyoxaline adopts following step: in 250 milliliters of round-bottomed flasks, 1. add 9.7 grams of N-(4-group-4 ethyl formate phenyl)-2-amidino-pyridine, 25.8 grams of trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room temperature.Follow the tracks of reaction by thin-layer chromatography method, disappear to reaction raw materials N-(4-group-4 ethyl formate phenyl)-2-amidino-pyridine; 2., after reaction terminates, crude product is obtained with removing desolventizing with Rotary Evaporators after diatomite filtration; 3. crude product column chromatography (ethyl acetate) purifying, obtain 9.4 grams of 7-group-4 ethyl formate pyrimidines also [1,2-a] benzoglyoxaline, productive rate is 97%.Fusing point: 260-262 DEG C.
-1 3061, 1708, 1605, 1523, 1501, 1453, 1380;
1 H NMR (CDCl 3 , 500 MHz): δ 8.92-8.90 (m, 2H), 8.69 (d,
J= 0.5 Hz, 1H), 8.30 (dd,
J = 8.5, 1.5 Hz, 1H), 8.03 (d,
J= 8.5 Hz, 1H), 7.05 (dd,
J= 6.5, 4.5 Hz, 1H), 4.47 (q,
J= 7.0 Hz, 2H), 1.46 (t,
J= 7.5 Hz, 3H);
13 C NMR (CDCl 3 , 125 MHz):δ 166.4, 156.8, 152.3, 147.4, 133.8, 127.6, 126.5, 124.1, 120.1, 113.2, 107.4, 61.3, 14.4;
EI-MS
m/z (%):
241 (75) [M
+], 213 (32), 196 (100), 168 (34);
HRMS (EI):m/z Calcd. for C
13H
11N
3O
2: 241.0851, Found 241.0855.
The synthesis of raw material N-(4-group-4 ethyl formate phenyl)-2-amidino-pyridine, see: Schulte Ii, J. P.; Tweedie, S. R.
synlett 2007, 2331.
The preparation of embodiment two: 7-methylpyrimidine also [1,2-a] benzoglyoxaline
7-methylpyrimidine also [1,2-a] benzoglyoxaline adopts following step: in 250 milliliters of round-bottomed flasks, 1. add 9.3 grams of N-(4-aminomethyl phenyl)-2-aminopyrimidine, 25.6 grams of trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room temperature.Follow the tracks of reaction by thin-layer chromatography method, disappear to reaction raw materials N-(4-aminomethyl phenyl)-2-aminopyrimidine; 2., after reaction terminates, crude product is obtained with removing desolventizing with Rotary Evaporators after diatomite filtration; 3. crude product column chromatography (ethyl acetate) purifying, obtain 7.6 grams of 7-methylpyrimidines also [1,2-a] benzoglyoxaline, productive rate is 82%.Fusing point: 205-206 DEG C.
-1 3045, 1606, 1579, 1499, 1452, 1376, 804;
1 H NMR (CDCl 3 , 500 MHz): δ 8.80 (dd,
J= 6.5, 2.0 Hz, 1H), 8.75 -8.74 (m, 1H), 7.89 (d,
J= 8.5 Hz, 1H), 7.69 (s, 1H), 7.39 (dd,
J= 8.0, 1.0 Hz, 1H), 6.92 (dd,
J= 7.0, 4.0 Hz, 1H)，2.56 (s, 3H);
13 C NMR (CDCl 3 , 125 MHz):δ 154.9, 150.1, 142.1, 133.1, 132.4, 128.4, 126.8, 120.1, 110.2, 106.5, 21.92;
EI-MS
m/z (%):
183 (15) [M
+], 95 (100);
HRMS (EI):m/z Calcd. for C
11H
9N
3:183.0796, Found 183.0791.
The synthesis of raw material N-(4-aminomethyl phenyl)-2-aminopyrimidine, see: Takeuchi, H.; Watanabe, K.
j. Phys. Org. Chem. 1998,
11, 478.
The preparation of embodiment three: 7-bromo pyrimi piperidine also [1,2-a] benzoglyoxaline
7-bromo pyrimi piperidine also [1,2-a] benzoglyoxaline adopts following step: in 250 milliliters of round-bottomed flasks, 1. add 10 grams of N-(4-bromophenyl)-2-aminopyrimidine, 30 grams of trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room temperature.Follow the tracks of reaction by thin-layer chromatography method, disappear to reaction raw materials N-(4-bromophenyl)-2-aminopyrimidine; 2., after reaction terminates, crude product is obtained with removing desolventizing with Rotary Evaporators after diatomite filtration; 3. crude product column chromatography (ethyl acetate) purifying, obtain 8.1 grams of 7-bromo pyrimi piperidines also [1,2-a] benzoglyoxaline, productive rate is 81%.Fusing point: 270-272 DEG C.
-1 3095, 1625, 1523, 1496, 1458, 583;
1 H NMR (CDCl 3 , 500 MHz): δ 9.51 (dd,
J= 7.0, 2.0 Hz, 1H), 8.86-8.85 (m, 1H), 8.65 (d,
J= 1.5 Hz, 1H), 7.80 (d,
J= 8.5 Hz, 1H), 7.67 (dd,
J= 8.5, 2.0 Hz, 1H), 7.19 (dd,
J= 7.0, 4.5 Hz, 1H);
13 C NMR (CDCl 3 , 125 MHz):δ 157.5, 150.9, 142.8, 136.5, 129.4, 128.4, 121.4, 116.2, 113.5, 107.6;
EI-MS
m/z (%):
249 (95) [M
+(
81Br)], 247 (100) [M
+ (
79Br)];
HRMS (EI):m/z Calcd. for C
10H
6N
3Br: 246.9745, Found 246.9747.
The synthesis of raw material N-(4-bromophenyl)-2-aminopyrimidine, see: Delvos, L. B.; Begouin, J.-M.; Gosmini, C.
synlett 2011, 2325.
The preparation of embodiment four: 7-chloropyrimide also [1,2-a] benzoglyoxaline
7-chloropyrimide also [1,2-a] benzoglyoxaline adopts following step: in 250 milliliters of round-bottomed flasks, 1. add 9.2 grams of N-(4-chloro-phenyl-)-2-aminopyrimidine, 29 grams of trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room temperature.Follow the tracks of reaction by thin-layer chromatography method, disappear to reaction raw materials N-(4-chloro-phenyl-)-2-aminopyrimidine; 2., after reaction terminates, crude product is obtained with removing desolventizing with Rotary Evaporators after diatomite filtration; 3. crude product column chromatography (ethyl acetate) purifying, obtain 7.3 grams of 7-chloropyrimide also [1,2-a] benzoglyoxaline, productive rate is 79%.Fusing point: 319-320 DEG C.
-1 3051, 1614, 1524, 1497, 1460, 762;
1 H NMR (CDCl 3 , 500 MHz): δ 9.52 (dd,
J= 6.5, 2.0 Hz, 1H), 8.88-8.86 (m, 1H), 8.54 (d,
J= 2.0 Hz, 1H), 7.87 (d,
J = 9.0 Hz, 1H), 7.58 (dd,
J= 9.0, 2.0 Hz, 1H), 7.21 (dd,
J = 6.5, 4.0 Hz, 1H);
13 C NMR (CDCl 3 , 125 MHz):δ 157.5, 151.1, 142.6, 136.5, 127.9, 126.9, 125.9, 121.0, 113.3, 107.8;
EI-MS
m/z (%):
205 (33) [M
+ (
37Cl)], 203 (100) [M
+ (
35Cl)], 154 (44);
HRMS (EI):m/z Calcd. for C
10H
6N
3Cl: 203.0250, Found 203.0248.
The synthesis of raw material N-(4-chloro-phenyl-)-2-aminopyrimidine, see: Takeuchi, H.; Watanabe, K.
j. Phys. Org. Chem. 1998,
11, 478.
The preparation of embodiment five: 9-chloropyrimide also [1,2-a] benzoglyoxaline
9-chloropyrimide also [1,2-a] benzoglyoxaline adopts following step: in 250 milliliters of round-bottomed flasks, 1. add 9.2 grams of N-(2-chloro-phenyl-)-2-aminopyrimidine, 29 grams of trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room temperature.Follow the tracks of reaction by thin-layer chromatography method, disappear to reaction raw materials N-(2-chloro-phenyl-)-2-aminopyrimidine; 2., after reaction terminates, crude product is obtained with removing desolventizing with Rotary Evaporators after diatomite filtration; 3. crude product column chromatography (ethyl acetate) purifying, obtain 7.2 grams of 9-chloropyrimide also [1,2-a] benzoglyoxaline, productive rate is 78%.Fusing point: 262-264 DEG C.
-1 3075, 1623, 1598, 1500, 1480, 775;
1 H NMR (CDCl 3 , 500 MHz): δ 9.55 (dd,
J= 7.0, 1.5 Hz, 1H), 8.91-8.90 (m, 1H), 8.29 (d,
J= 8.5 Hz, 1H), 7.63 (d,
J= 8.0 Hz, 1H), 7.40 (t,
J = 8.0 Hz, 1H), 7.23 (dd,
J= 7.0, 4.5 Hz, 1H);
13 C NMR (CDCl 3 , 125 MHz):δ 157.8, 150.8, 141.0, 136.8, 128.5, 126.1, 123.2, 122.3, 112.2, 108.1;
EI-MS
m/z (%):
205 (5) [M
+ (
37Cl)], 203 (14) [M
+ (
35Cl)], 154 (100);
HRMS (EI):m/z Calcd. for C
10H
6N
3Cl: 203.0250, Found 203.0247.
The synthesis of raw material N-(2-chloro-phenyl-)-2-aminopyrimidine, see: Takeuchi, H.; Watanabe, K.
j. Phys. Org. Chem. 1998,
11, 478.
The preparation of embodiment six: 8-methylpyrimidine also [1,2-a] benzoglyoxaline
8-methylpyrimidine also [1,2-a] benzoglyoxaline adopts following step: in 250 milliliters of round-bottomed flasks, 1. add 9.3 grams of N-(3-aminomethyl phenyl)-2-aminopyrimidine, 25.6 grams of trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room temperature.Follow the tracks of reaction by thin-layer chromatography method, disappear to reaction raw materials N-(3-aminomethyl phenyl)-2-aminopyrimidine; 2., after reaction terminates, crude product is obtained with removing desolventizing with Rotary Evaporators after diatomite filtration; 3. crude product column chromatography (ethyl acetate) purifying, obtain 7.2 grams of 8-methylpyrimidines also [1,2-a] benzoglyoxaline, productive rate is 77%.Fusing point: 199-200 DEG C.
-1 3047, 1603, 1522, 1503, 1454, 1374, 792;
1 H NMR (CDCl 3 , 500 MHz): δ 8.78 (dd,
J= 7.0, 2.0 Hz, 1H), 8.73-8.72 (m, 1H), 7.77-7.75 (m,2H), 7.21 (d,
J= 8.5 Hz, 1H), 6.89 (dd,
J= 6.5, 4.0 Hz, 1H), 2.55 (s, 3H);
13 C NMR (CDCl 3 , 125 MHz):δ 155.1, 150.4, 144.0, 137.0, 133.3, 124.7, 123.9, 119.8, 110.3, 106.6, 22.13;
EI-MS
m/z (%):
183 (100) [M
+], 143 (82), 95 (87);
HRMS (EI):m/z Calcd. for C
11H
9N
3:183.0796, Found 183.0795.
The synthesis of raw material N-(3-aminomethyl phenyl)-2-aminopyrimidine, see: Takeuchi, H.; Watanabe, K.
j. Phys. Org. Chem. 1998,
11, 478.
The preparation of embodiment seven: 3-bromo pyrimi piperidine also [1,2-a] benzoglyoxaline
3-bromo pyrimi piperidine also [1,2-a] benzoglyoxaline adopts following step: in 250 milliliters of round-bottomed flasks, 1. add 10 grams of N-phenyl-2-amino-5-bromo pyrimi piperidines, 30 grams of trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room temperature.Follow the tracks of reaction by thin-layer chromatography method, disappear to reaction raw materials N-phenyl-2-amino-5-bromo pyrimi piperidine; 2., after reaction terminates, crude product is obtained with removing desolventizing with Rotary Evaporators after diatomite filtration; 3. crude product column chromatography) ethyl acetate) purifying, obtain 7.5 grams of 3-bromo pyrimi piperidines also [1,2-a] benzoglyoxaline, productive rate is 75%.Fusing point: 240-242 DEG C.
-1 3049, 1594, 1511, 1479, 1450, 558;
1 H NMR (CDCl 3 , 500 MHz): δ 9.93 (d,
J= 2.5 Hz, 1H), 8.87 (d,
J= 2.5 Hz, 1H), 8.33 (d,
J= 8.5 Hz, 1H), 7.86 (d,
J= 8.5 Hz, 1H), 7.58-7.55 (m, 1H), 7.44 (t,
J= 7.5 Hz, 1H);
13 C NMR (CDCl 3 , 125 MHz):δ 156.7, 148.6, 144.2, 136.3, 127.2, 126.9, 122.5, 119.8, 113.4, 101.7;
EI-MS
m/z (%):
249 (93) [M
+ (
81Br)] ,247 (100) [M
+(
79Br)], 168 (48);
HRMS (EI):m/z Calcd. for C
10H
6N
3Br: 246.9745, Found 246.9741.
The synthesis of raw material N-phenyl-2-amino-5-bromo pyrimi piperidine, see: Array Biopharma Inc. WO2007/146824 A2,
2007.
The preparation of embodiment eight: 7-iodine pyrimidine also [1,2-a] benzoglyoxaline
7-iodine pyrimidine also [1,2-a] benzoglyoxaline adopts following step: in 250 milliliters of round-bottomed flasks, 1. add 9 grams of N-(4-iodophenyl)-2-aminopyrimidine, 16 grams of trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room temperature.Follow the tracks of reaction by thin-layer chromatography method, disappear to reaction raw materials N-(4-iodophenyl)-2-aminopyrimidine; 2., after reaction terminates, crude product is obtained with removing desolventizing with Rotary Evaporators after diatomite filtration; 3. crude product column chromatography) ethyl acetate) purifying, obtain 5.8 grams of 7-iodine pyrimidines also [1,2-a] benzoglyoxaline, productive rate is 64%.Fusing point: 328-330 DEG C.
-1 3024, 1624, 1523, 1497, 1451, 582;
1 H NMR (CDCl 3 , 500 MHz): δ 9.50 (dd,
J= 6.5, 1.5 Hz, 1H), 8.85 (d,
J= 1.5 Hz, 1H), 8.78 (s, 1H), 7.81 (d,
J= 8.5 Hz, 1H), 7.67 (d,
J = 8.5 Hz, 1H), 7.17 (dd,
J= 6.5, 4.0 Hz, 1H);
13 C NMR (CDCl 3 , 125 MHz):δ 157.5, 150.5, 143.2, 136.5, 134.8, 129.0, 121.7, 121.6, 107.8, 84.7;
EI-MS
m/z (%):
295 (100) [M
+], 168 (30);
HRMS (EI):m/z Calcd. for C
10H
6N
3I: 294.9606, Found 294.9604.
The synthesis of raw material N-(4-iodophenyl)-2-aminopyrimidine, see: Toray Industries, Inc. WO2006/68213 A1,
2006
The preparation of embodiment nine: 9-methylpyrimidine also [1,2-a] benzoglyoxaline
9-methylpyrimidine also [1,2-a] benzoglyoxaline adopts following step: in 250 milliliters of round-bottomed flasks, 1. add 9.3 grams of N-(2-aminomethyl phenyl)-2-aminopyrimidine, 38.4 grams of trifluoracetic acid iodobenzenes, 200 milliliters of acetonitriles, stirring at room temperature.Follow the tracks of reaction by thin-layer chromatography method, disappear to reaction raw materials N-(2-aminomethyl phenyl)-2-aminopyrimidine; 2., after reaction terminates, crude product is obtained with removing desolventizing with Rotary Evaporators after diatomite filtration; 3. crude product column chromatography) ethyl acetate) purifying, obtain 4.9 grams of 9-methylpyrimidines also [1,2-a] benzoglyoxaline, productive rate is 53%.Fusing point: 195-196 DEG C.
-1 3067, 1619, 1597, 1500, 1377, 778;
1 H NMR (CDCl 3 , 500 MHz): δ 8.75-8.74 (m, 1H), 8.72 (dd,
J= 7.0, 2.0 Hz, 1H), 7.69 (d,
J= 8.0 Hz, 1H), 7.36 (d,
J= 7.0Hz, 1H), 7.30 (t,
J= 8.0 Hz, 1H), 6.87 (dd,
J= 6.5, 4.0 Hz, 1H), 2.79 (s, 3H)；
13 C NMR (CDCl 3 , 125 MHz):δ 155.0, 150.0, 143.5, 133.3, 130.8, 126.5, 126.3, 122.0, 107.9, 106.5, 17.1;
EI-MS
m/z (%):
183 (23) [M
+], 154 (100);
HRMS (EI):m/z Calcd. for C
11H
9N
3:183.0796, Found 183.0793.
The synthesis of raw material N-(2-aminomethyl phenyl)-2-aminopyrimidine, see: Takeuchi, H.; Watanabe, K.
j. Phys. Org. Chem. 1998,
11, 478.
Claims (1)
1. a preparation method for substituted benzimidazole compounds, the structural formula of this compound is:
Wherein: R
1=halogen, Ar;
R
2=-Me,
-cl,
-br ,-I ,-COOEt; It is characterized in that the method has following steps: join in acetonitrile by the N-phenyl-2-aminopyrimidine of replacement, trifluoracetic acid iodobenzene by the mol ratio of 1:1.2 ~ 1.8, stirring at room temperature reaction disappears to raw material; Crude product is obtained except after desolventizing; This crude product, through separation and purification, namely obtains corresponding substituted benzimidazole compounds; The structural formula of the N-phenyl-2-aminopyrimidine of described replacement is:
.
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