CN101993441A - 4-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-radical)-2-(2- aminopyridine) thiazole chiral crystal - Google Patents
4-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-radical)-2-(2- aminopyridine) thiazole chiral crystal Download PDFInfo
- Publication number
- CN101993441A CN101993441A CN2010105689224A CN201010568922A CN101993441A CN 101993441 A CN101993441 A CN 101993441A CN 2010105689224 A CN2010105689224 A CN 2010105689224A CN 201010568922 A CN201010568922 A CN 201010568922A CN 101993441 A CN101993441 A CN 101993441A
- Authority
- CN
- China
- Prior art keywords
- thiazole
- dimethyl
- dihydrobenzofuranes
- methoxyl group
- chiral crystal
- 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.)
- Pending
Links
Images
Abstract
The invention discloses the structure of 4-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-radical)-2-(2- aminopyridine) thiazole chiral crystal, the molecular structure is shown in drawings. The 4-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-radical)-2-(2- aminopyridine) thiazole chiral crystal belongs to a monoclinic system, wherein the chiral space group is C2; the cell parameters are as follows: a=18.1328(14) angstroms, b=5.5969(5) angstroms, c=19.2195(15) angstroms, beta=115.5420(10) degrees; Z=4, V=1759.9(2) angstrom<3>, Dc=1.334g/cm<3>, F (000)=744, mu=0.201mm<-1>, 2307 observable points [I>2sigma (I)], observable point refined final offset factor R = 0.035, wR = 0.111, (delta / sigma) max<0.001, S=1.15, (delta rho)max=0.216, (delta rho)min=-0.206e/angstrom<3>; and the Flack parameter is -0.03(10). The preparation method of the 4-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-radical)-2-(2- aminopyridine) thiazole chiral crystal is as follows: slowly crystallizing 4-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-radical)-2-(2- aminopyridine) thiazole in polar solvent.
Description
Technical field
The invention belongs to the crystallization technique field, particularly achiral molecule prepares the method for chiral crystal, specifically is 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal structure and preparation method thereof.
Background technology
In general, the monocrystalline of achiral molecule is non-chiral crystal; The monocrystalline of chiral molecules preparation is a chiral crystal.Some specific achiral molecule also can prepare chiral crystal [J.Am.Chem.Soc.1995,117,9083; Angew.Chem., Int.Ed.2003,42,1725; Chem.Eur.J.2003,9,4678].As achiral molecule 1-[4-(dimethylamino) Ben Yajiaji amino]-4-phenylthiourea [organic chemistry .2006,26,933; Organic chemistry .2008,28 (5), 903]; N '-the tertiary butyl-N '-substituted benzoyl-N-(chroman-5-formyl radical) hydrazine [organic chemistry .2009,29 (6), 891], 1; 3-two (3-phenyl-3-oxo vinylcarbinol) benzene [Acta PhySico-Chimica Sinica, 2008,24 (6); 955-960], 3-iodo-benzoic acid 3-phenylpropyl alcohol ammonium salt [Acta Cryst.2008; C64, o626] and xenyl carboxylic acid look ammonium salt [Tetrahedron Asymmetry, 1998; 9,1851] can prepare chiral crystal.Chinese patent has been described 4-(cumarone-5-yl)-2-virtue aminothiazole and insecticidal activity [CN 201010553848.9] thereof.
Originally the monocrystalline of discovering achiral molecule 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole is a chiral crystal.Utilize the solid state reaction of the chiral crystal of achiral molecule formation to provide another kind of opportunity for asymmetric synthesis.
Summary of the invention
The object of the present invention is to provide 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal structure.Its chiral crystal belongs to oblique system, and the chirality spacer is C2.Unit cell parameters is: a=18.1328 (14)
B=5.5969 (5)
C=19.2195 (15)
β=115.5420 (10) °; Z=4, V=1759.9 (2)
D
c=1.334g/cm
3, F (000)=744, μ=0.201mm
-1, 2307 considerable measuring points [I＞2 σ (I)], the final discrepancy factor R=0.035 of considerable measuring point refine, wR=0.111, (Δ/σ)
Max＜0.001, S=1.15, (Δ ρ)
Max=0.216, (Δ ρ)
Min=-0.206e/
The Flack parameter is-0.03 (10).4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole crystalline structure atom numbering is as follows:
The present invention also aims to provide (7-methoxyl group-2 at 4-, 2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-chiral crystal of 2-(2-pyridine amino) thiazole in, two molecule 4-(7-methoxyl groups-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole constituted R by two N-H...O hydrogen bonds
2 2(18) hydrogen bond ring.
The present invention also aims to provide 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-preparation method of 2-(2-pyridine amino) thiazole chiral crystal, it is characterized in that (7-methoxyl group-2 by achiral molecule 4-, 2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole in polar solvent slowly crystallization obtain; Polar solvent is one or more in methyl alcohol, ethanol, acetone, tetrahydrofuran (THF) or the ethyl acetate.
The present invention compared with prior art has following advantage:
1) provides achiral molecule 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole to cultivate first and made its chiral crystal through monocrystalline.4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal belongs to oblique system, spacer C2; Absolute configuration Flack parameter is-0.03 (10).
2) the invention provides (7-methoxyl group-2 at 4-, 2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal in, two molecule 4-(7-methoxyl groups-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole constituted R by two N-H...O hydrogen bonds
2 2(18) hydrogen bond ring makes that like this three substituting groups on the N can not overturn, and the result makes the chirality nitrogen of N atom on coming true; The achiral molecule that contains actual chirality nitrogen can form chiral crystal through the monocrystalline cultivation.
Description of drawings
Fig. 1 is the molecular structure of 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal.
Fig. 2 is the hydrogen bond figure of 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal.
Fig. 3 is the crystal accumulation figure of 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal.
Embodiment
Following examples are intended to illustrate the present invention rather than limitation of the invention further.
The preparation of embodiment 14-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal
4g4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole joins in 20mL methyl alcohol or the ethanol, stirring, heating for dissolving, the solution cooling, the room temperature that obtain are placed slowly volatilization, separate out 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal after 2～3 days.
The preparation of embodiment 24-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal
5.2g 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-the joining in 20mL acetone or the ethyl acetate of 2-(2-pyridine amino) thiazole, stirring, heating for dissolving, the solution cooling, the room temperature that obtain are placed slowly volatilization, separate out 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal after 3～4 days.
The chiral crystal structure of embodiment 34-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole
(1) the X-ray structure is measured
Choose the monocrystalline of 0.45mm * 0.43mm * 0.34mm, on BRUKER SMART APEX 1000CCD diffractometer, collect diffraction data, utilize the graphite monochromator monochromatization Mo K alpha-ray (λ=0.071073nm), under 293K with ω-
Scan mode is collected diffraction data.The SAINTPLUS program of utilization Bruker uses the SADABS program to carry out the experience absorption correction reduction of data simultaneously.Use SHELXS-97 and SHELXL-97 program [Sheldrick, G.M.SHELXS97and SHELXL97, University of
Germany, 1997] direct method parsing and refined structure.All non-hydrogen atoms adopt the complete matrix method of least squares to carry out structure refinement.All non-hydrogen atoms are all done the anisotropy refine.Theoretical hydrogenation, the correction of hydrogen atom isotropy thermal parameter.Crystal data and structural parameter are listed table 1 in.
The crystal data and the structural parameter of table 14-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole
(2) the chiral crystal structure of 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole
The non-hydrogen atom coordinate and the thermal parameter of 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole are listed in table 2, and part bond distance, bond angle and hydrogen bond are listed in table 3, table 4 and table 5.
The atomic coordinate (* 10 of table 24-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal
4) and thermal parameter (* 10
3 
)
The part bond distance of table 34-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal
The continuous table of going up
The part bond angle of table 44-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal (°)
The hydrogen bond of table 54-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal [
With °]
i：-x，y，-z+1
The molecular structure of 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal as shown in Figure 1; Hydrogen bond figure as shown in Figure 2; The structure cell accumulation graph as shown in Figure 3.
4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal belongs to oblique system, and the chirality spacer is C2.Unit cell parameters is: a=18.1328 (14)
B=5.5969 (5)
C=19.2195 (15)
β=115.5420 (10) °; Z=4, V=1759.9 (2)
D
c=1.334g/cm
3, F (000)=744, μ=0.201mm
-1, 2307 considerable measuring points [I＞2 σ (I)], the final discrepancy factor R=0.035 of considerable measuring point refine, wR=0.111, (Δ/σ)
Max＜0.001, S=1.15, (A ρ)
Max=0.216, (Δ ρ)
Min=-0.206e/
The Flack parameter is one 0.03 (10).
At 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal in, two molecule 4-(7-methoxyl groups-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole constituted R by two N-H...O hydrogen bonds
2 2(18) hydrogen bond ring (seeing accompanying drawing 2); Make three substituting groups on the N not overturn like this, the result makes the chirality nitrogen of N atom on coming true; The achiral molecule that contains actual chirality nitrogen can form chiral crystal through the monocrystalline cultivation.
Utilize the solid state reaction of the chiral crystal that achiral molecule forms to provide another kind of opportunity, have very important significance in that asymmetry catalysis is industrial for asymmetric synthesis.
4 pairs of mythimna separata cytotoxicities of embodiment are measured
1 for the examination target
Mythimna separata (Mythimna sepatara) is with fresh corn leaf raising sensitive strain for many years; Test is 3 instar larvaes with worm.Culture condition for examination target and test back target is 25 ± 5 ℃ of temperature, relative humidity 65 ± 5%, periodicity of illumination 12/12h (L/D).
2 test methods are with reference to " pesticide bioactivity is estimated SOP ".
The general sieve of mythimna separata: adopt spray method.In being lined with the culture dish of filter paper (Φ 90mm), put into the leaf of Semen Maydis section of big or small basically identical, insert 10 of third-instar larvaes again, be put under the Potter spray tower and spray.Spray amount 1ml/10 head, 2 repetitions.Dispose, be put into the observation indoor cultivation.Regularly observe.Check behind the 96h and the record death condition, calculate mortality ratio.
3 cytotoxicities
When effective constituent concentration was 1.0g/L, behind the dispenser 96h, 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole was 93.75% to the mortality ratio of mythimna separata.4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole has good insecticidal activity, can be used as the preparation sterilant.
Claims (3)
1.4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole chiral crystal, it is characterized in that 4-(7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-and 2-(2-pyridine amino) thiazole chiral crystal belongs to oblique system, and the chirality spacer is C2; Unit cell parameters is: a=18.1328 (14)
B=5.5969 (5)
C=19.2195 (15)
β=115.5420 (10) °; Z=4, V=1759.9 (2)
D
c=1.334g/cm
3, F (000)=744, μ=0.201mm
-1, 2307 considerable measuring points [I＞2 σ (I)], the final discrepancy factor R=0.035 of considerable measuring point refine, wR=0.111, (Δ/σ)
Max＜0.001, S=1.15, (Δ ρ)
Max=0.216, (Δ ρ)
Min=-0.206e/
The Flack parameter is-0.03 (10).
2. the described 4-of claim 1 (7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-chiral crystal of 2-(2-pyridine amino) thiazole in, two molecule 4-(7-methoxyl groups-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole constituted R by two N-H...O hydrogen bonds
2 2(18) hydrogen bond ring.
3. the described 4-of claim 1 (7-methoxyl group-2,2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-preparation method of 2-(2-pyridine amino) thiazole chiral crystal, it is characterized in that (7-methoxyl group-2 by achiral molecule 4-, 2-dimethyl-2,3-Dihydrobenzofuranes-5-yl)-2-(2-pyridine amino) thiazole in polar solvent slowly crystallization obtain; Polar solvent is one or more in methyl alcohol, ethanol, acetone, tetrahydrofuran (THF) or the ethyl acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105689224A CN101993441A (en) | 2010-12-02 | 2010-12-02 | 4-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-radical)-2-(2- aminopyridine) thiazole chiral crystal |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105689224A CN101993441A (en) | 2010-12-02 | 2010-12-02 | 4-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-radical)-2-(2- aminopyridine) thiazole chiral crystal |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210365183.8A Division CN102952127B (en) | 2010-12-02 | 2010-12-02 | 4-(2,3-dihydrobenzene benzofuran-5-yl)-2-(2-aminopyridine) chiral crystal |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101993441A true CN101993441A (en) | 2011-03-30 |
Family
ID=43784256
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010105689224A Pending CN101993441A (en) | 2010-12-02 | 2010-12-02 | 4-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-radical)-2-(2- aminopyridine) thiazole chiral crystal |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101993441A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101263130A (en) * | 2005-09-13 | 2008-09-10 | 詹森药业有限公司 | 2-aniline-4-aryl substituted thiazole derivatives |
| CN101337945A (en) * | 2008-08-11 | 2009-01-07 | 湖南大学 | 4-acetamino-3-(4-arylthiazole-2-amino)benzoate, method for preparing same and applications |
-
2010
- 2010-12-02 CN CN2010105689224A patent/CN101993441A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101263130A (en) * | 2005-09-13 | 2008-09-10 | 詹森药业有限公司 | 2-aniline-4-aryl substituted thiazole derivatives |
| CN101337945A (en) * | 2008-08-11 | 2009-01-07 | 湖南大学 | 4-acetamino-3-(4-arylthiazole-2-amino)benzoate, method for preparing same and applications |
Non-Patent Citations (1)
| Title |
|---|
| 胡艾希等: "2-氨基噻唑类化合物的合成", 《中国药物化学杂志》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Escuer et al. | Two new nickel (II) cubane compounds derived from pyridine-2-methoxide (Pym):{Ni4 (Pym) 4Cl4 (CH3OH) 4} and {Ni4 (Pym) 4 (N3) 4 (CH3OH) 4}. Crystal structures and magnetic properties | |
| CN103113420B (en) | A kind of dibutyl tin oxygen duster compound containing ferrocenyl and preparation method and application | |
| CN104230968B (en) | Cadmium-containing dual-core polymer with mixed-ligand and preparation method of cadmium-containing dual-core polymer | |
| CN104356072A (en) | 5-fluorouracil drug eutectic crystal and preparation method thereof | |
| CN102399246A (en) | Metal nickel-imidazole chiral nanometer cage complex and preparation method thereof | |
| CN102491931B (en) | 3-substituted indolone derivative and preparation method and application thereof | |
| CN105111164B (en) | The crystal formation of smart indoxacarb | |
| CN103087325B (en) | Ferrocenyl-containing tricyclohexyltin coordination polymer, and preparation method and application thereof | |
| CN105906558A (en) | Anti-fibrosis drug pirfenidone crystal forms and preparation method thereof | |
| CN104292247A (en) | Cadmium-containing two dimensional polymer having mixed ligand, and its preparation method | |
| CN101993441A (en) | 4-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-radical)-2-(2- aminopyridine) thiazole chiral crystal | |
| CN104130292B (en) | Three dimensional coordination polymer with double core structure and preparation method thereof | |
| CN102952127B (en) | 4-(2,3-dihydrobenzene benzofuran-5-yl)-2-(2-aminopyridine) chiral crystal | |
| CN103396437B (en) | Two (Tricyclohexyltin) dicarboxylic esters and preparation method and application | |
| CN102127066B (en) | 4-(7-methoxy-2,2,-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(3,4-xylylazoamino)thiazole chiral crystal | |
| CN107286184B (en) | A kind of zinc metal-organic framework materials and preparation method thereof | |
| CN103103602A (en) | Single-crystal structure of potassium nickel isopolyoxovanadate and preparation method | |
| Cai et al. | Spontaneous resolution of a chiral polyoxometalate: Synthesis, crystal structures and properties | |
| CN101870678B (en) | Pyrazole compound and preparation method thereof | |
| CN101020678B (en) | Trisubstituted dihydro agarofuran compound and its pesticidal activity | |
| CN108752383B (en) | Pyrazole carboxylate manganese complex with SOD activity and preparation method thereof | |
| CN102391314B (en) | 2,6-dipicolinic acid-(ferrocene monoformic acid)triphenyltin complex, preparation method and application thereof | |
| CN104086606A (en) | Structure and preparation method of nickel-bridged flexible ligand and polymolybdate hybridized material | |
| CN102766146A (en) | Difurandihydrodihydro esters compound and application thereof to prepare insecticide | |
| CN103012267B (en) | Novel crystalline object of benazepril hydrochloride and preparation method of crystalline object |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20110330 |