CN101885708B - 5-polyfluoroalkyl group substituted 2-aminothiazole compound, synthesis method and application thereof - Google Patents
5-polyfluoroalkyl group substituted 2-aminothiazole compound, synthesis method and application thereof Download PDFInfo
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- CN101885708B CN101885708B CN 201010220927 CN201010220927A CN101885708B CN 101885708 B CN101885708 B CN 101885708B CN 201010220927 CN201010220927 CN 201010220927 CN 201010220927 A CN201010220927 A CN 201010220927A CN 101885708 B CN101885708 B CN 101885708B
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- 0 [*+]c1nc(CCl)c[s]1 Chemical compound [*+]c1nc(CCl)c[s]1 0.000 description 2
- UCQJNHUDJFAASX-UHFFFAOYSA-N Cc1c(-c2cccc([N+]([O-])=O)c2)nc(N)[s]1 Chemical compound Cc1c(-c2cccc([N+]([O-])=O)c2)nc(N)[s]1 UCQJNHUDJFAASX-UHFFFAOYSA-N 0.000 description 1
- CHBDOPARQRNCDM-UHFFFAOYSA-N Nc1nc(-c2cccc([N+]([O-])=O)c2)c[s]1 Chemical compound Nc1nc(-c2cccc([N+]([O-])=O)c2)c[s]1 CHBDOPARQRNCDM-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention relates to a 5-polyfluoroalkyl group substituted 2-aminothiazole compound, a synthesis method and application thereof. In the invention, beginning from a corresponding substituted 2-aminothiazole compound or a corresponding salt thereof, a target product with a structural formula (disclosed in the specification) is obtained with a yield of 40-95 percent only through one-step reaction. The method has the advantages of simple and easily obtained reagent, moderate reaction condition, short time, simple operation, lower requirement on equipment and simple aftertreatment and has practical production significance, and the 2-aminothiazole compound can be used for preparing pesticides for preventing and treating weeds.
Description
Technical field
The present invention relates to thiazolamine compounds, synthetic method and application thereof that the 5-Polyfluoroalkyl replaces.
Background technology
Early stage patent US4992434 relates among the EP0279239 among the following general formula I I and Compound I I-a occurs, as sterilant.
Relate among the patent JP4279556 in the following general formula III and compound III-a occurs, as liquid crystal material.
Relate to following structure among the patent US2003199523 and have the calcium channel retardation.
Related separately to the thiazolamine class formation that the 5-Polyfluoroalkyl replaces among patent JP92-89534, EP662472, WO9637466, WO2001040227, WO2004081001, WO2006007998, WO2006072436, WO2006078621, WO2007040282, WO2008024980, WO2008084872, WO2009010455, WO2009020191, JP2010037337, WO2010012793, WO2010028193, the WO2010030811 etc., at material, agricultural chemicals, field of medicaments good application prospect has been arranged.
Relevant paper such as Oxidation Communications, (2003), 26 (2), 168-178; Journal of Medicinal Chemistry, (2006), 49 (3), 1118-1124; Bioorganic ﹠amp; Medicinal Chemistry Letters, (2010), 20 (2), 594-599; Bioorganic ﹠amp; Medicinal Chemistry Letters, (2010), 20 (2), 493-498; Bioorganic ﹠amp; Medicinal Chemistry Letters, (2010), 20 (2), 594-599; Antimicrobial Agents and Chemotherapy, (2010), 54 (3), 1315-1318.
Mainly be the thiazolamine that the 5-trifluoromethyl replaces in the top report, the not too many report of other Polyfluoroalkyl substitution compounds.The more important thing is, although the application report of this compound increase gradually, about it synthetic report seldom.The Hantzsch synthesis method is classical thiazole synthetic method, but the raw material of synthetic 2-amino-5-trifluoromethyl thiazole: and the preparation of 2-halogen-3-trifluoro propionic aldehyde does not have the yield report, is detected in WO2006078621.And react through 5 steps from Trifluoroacetic Acid Ethyl Ester, total recovery but is lower than 16%, as: Journal of Fluorine Chemistry. (1995), 73,83-86; Chem.Leg. (1985), 14,889; J.Chem.Soc, Perkin Trans. (1995), 1,2761-2766.From 2-amino-5-carboxyl thiazole, and the route that sulfur tetrafluoride, hydrogen fluoride reaction prepare 2-amino-5-trifluoromethyl sees WO9637466, do not have equally the report of yield.
Pass through FSO
2CF
2The route of COOMe/CuI trifluoromethylation sees WO2010030811, but does not have the yield report.
Pass through CF
3SiEt
3The route that/CuI linked reaction is introduced trifluoromethyl sees WO2010012793, yield about 4%.Moreover top two kinds of methods need to introduce in advance halogen atom, generally are to realize by relatively more expensive iodination reagent.
Synthetic method in sum, otherwise raw material prepares loaded down with trivial detailsly, and productive rate is not high, or severe reaction conditions, and is higher to equipment requirements.These reasons so that prepare in a large number thiazolamine that the 5-trifluoromethyl replaces and the cost of derivative higher, safety problem is outstanding.
In addition, the 5-Polyfluoroalkyl (for example-CF
2CF
3, C
4F
9, CF
2CF
2Cl, CF (CF
3)
2Deng) the synthetic of thiazolamine compounds that replace be difficult to realize by aforesaid method, but the introducing of full-fluorine group may have to the activity of compound very large change, for example by the Ryanicide acceptor inhibitor Flubendiamide of Japanese agricultural chemicals company, Beyer Co., Ltd's exploitation, wherein contain the aniline that seven fluorine sec.-propyls replace (referring to: EP1006107).
Therefore the method for preparing simply, efficiently the thiazolamine compounds of 5-Polyfluoroalkyl replacement has very important using value.
Summary of the invention
The problem that the present invention need to solve is to overcome above-mentioned defective, provide a kind of 5-Polyfluoroalkyl-the thiazolamine compounds;
Purpose of the present invention also provides the synthetic method of a kind of above-mentioned 5-Polyfluoroalkyl-thiazolamine compounds, and the method is a kind of method for preparing simply, efficiently the thiazolamine compounds of 5-Polyfluoroalkyl replacement.Use cheap, be easy to get, safety and easy-operating raw material, reagent and catalyzer, and with gentle, simple, high yield and selectivity, be difficult for producing a large amount of refuses, its aftertreatment also is that the reaction of economical and efficient is for basic.
Another object of the present invention provides the application of above-mentioned 5-Polyfluoroalkyl-thiazolamine compounds, and it can be for the preparation of the agricultural chemicals of controlling weeds.
The general structure of the thiazolamine compounds that the 5-Polyfluoroalkyl that the present invention relates to replaces is shown in (I):
R wherein
1And R
2Can be identical or different, and represent separately hydrogen atom, (C
1-C
12) alkyl, (C
3-C
8) cycloalkyl, hydroxyl (C
1-C
12) alkyl, hydroxycarbonyl group (C
1-C
12) alkyl, (C
1-C
6) alkyl-carbonyl (C
1-C
6) alkyl, (C
1-C
6) carbalkoxy (C
1-C
6) alkyl, halo (C
1-C
6) alkyl, cyano group (C
1-C
12) alkyl, nitro (C
1-C
12) alkyl, adamantyl, pyrroles, thiophene, furyl, by R
9, R
10, R
11Or/and R
12The pyridyl that replaces, by R
13, R
14, R
15, R
16Or/and R
17The phenyl that replaces, on ring by R
18, R
19, R
20, R
21Or/and R
22The benzyl that replaces, by R
23, R
24, R
25The pyrroles, thiophene or the furyl that replace; Described substituent R
9, R
10, R
11, R
12Can be identical or different, and be selected from hydrogen atom, cyano group, nitro, hydroxyl, halogen atom, (C
1-C
6) alkyl, halo (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, halo (C
1-C
6) alkoxyl group, (C
1-C
6) alkoxyl group (C
1-C
6) alkyl, halo (C
1-C
6) alkoxyl group (C
1-C
6) alkyl, (C
1-C
6) alkylthio, (C
1-C
6) alkylthio (C
1-C
6) alkyl, carboxyl, (C
1-C
6) carbalkoxy, (C
1-C
6) alkyl-carbonyl, halo (C
1-C
6) alkyl-carbonyl or pyridyl; Described substituent R
13, R
14, R
15, R
16, R
17Can be identical or different, and be selected from hydrogen atom, cyano group, nitro, halogen atom, (C
1-C
6) alkyl, halo (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, halo (C
1-C
6) alkoxyl group or (C
1-C
6) alkylthio; Described substituent R
18, R
19, R
20, R
21, R
22Can be identical or different, and be selected from hydrogen atom, cyano group, nitro, hydroxyl, halogen atom, (C
1-C
6) alkyl, halo (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, halo (C
1-C
6) alkoxyl group or (C
1-C
6) alkylthio; Described substituent R
23, R
24, R
25Can be identical or different, and be selected from hydrogen atom, cyano group, nitro, halogen atom, (C
1-C
6) alkyl or halo (C
1-C
6) alkyl; Perhaps R
1Be H, R
2Be (R
26R
27CH) (COOH) CH-, wherein R
26Be selected from hydrogen atom or (C
1-C
4) alkyl; R
27Be selected from hydroxyl, methylthio group (C
1-C
2) alkyl, sulfydryl, three benzylthios, hydroxycarbonyl group, hydroxycarbonyl group (C
1-C
2) alkyl, aminocarboxyl (C
1-C
2) alkyl, imidazolyl, indyl or by R
28, R
29, R
30, R
31, R
32The phenyl that replaces; Described substituent R
28, R
29, R
30, R
31, R
32Can be identical or different, and be selected from hydrogen atom, cyano group, nitro, hydroxyl, halogen atom, (C
1-C
6) alkyl, halo (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, halo (C
1-C
6) alkoxyl group or (C
1-C
6) alkylthio; Perhaps R
1R
2N-is selected from following substituting group:
Wherein said substituent R
33Be selected from hydroxyl, methoxyl group, oxyethyl group, tert.-butoxy or amino; R
34Be selected from hydrogen atom, ethanoyl, benzyl, trimethyl silicon based (TMS) or triethyl silica-based (TES); R
35Be selected from hydrogen atom, tert-butoxycarbonyl (Boc), methyl, ethyl or sec.-propyl;
R
3Be Polyfluoroalkyl substituting group or perfluoroalkyl, for example C
1-C
27Perfluoroalkyl, refer to that its whole hydrogen atoms are all replaced by fluorine atom, and the alkyl with 1-27 carbon atom, wherein said alkyl can be straight chain or side chain or ring-type, such as trifluoromethyl, pentafluoroethyl group, seven fluorine n-propyls, seven fluorine sec.-propyls, nine fluorine normal-butyls, 11 fluorine neo-pentyls, 11 fluorine n-pentyls, ten trifluoro n-hexyls, 25 fluorine dodecyls etc.; Also can be to contain the substituent Polyfluoroalkyls such as hydrogen, chlorine, bromine, sulfonic acid fluoride, as: the hexafluoro sec.-propyl ,-(CF
2)
mCF
2H ,-(CF
2)
mCF
2L, L=Cl wherein, Br; M=1,2,3,4,5,6,7,8,9;-CF
2CF
2OC
2F
4SO
2Other Polyfluoroalkyls such as F;
R
4Expression hydrogen atom, halogen atom, (C
1-C
12) alkyl, (C
3-C
8) cycloalkyl, cyano group (C
1-C
12) alkyl, nitro (C
1-C
12) alkyl, (C
1-C
6) alkyl-carbonyl (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, halo (C
1-C
6) alkoxyl group, (C
1-C
6) alkoxyl group (C
1-C
6) alkyl, halo (C
1-C
6) alkoxyl group (C
1-C
6) alkyl, (C
1-C
6) alkylthio, (C
1-C
6) alkylthio (C
1-C
6) alkyl, hydroxyl (C
1-C
6) alkyl, hydroxycarbonyl group (C
1-C
6) alkyl, (C
1-C
6) carbalkoxy (C
1-C
6) alkyl, amino (C
1-C
6) alkyl, aminocarboxyl (C
1-C
6) alkyl, thiazolyl, pyrimidyl, naphthyl, adamantyl ,-CR
36R
37R
38,-CR
5R
6R
7,-(CH
2)
nNR
39R
40, by R
41, R
42, R
43, R
44, R
45The phenyl that replaces, n=1,2,3,4, on ring by R
48, R
49, R
50, R
51, R
52The benzyl that replaces; R wherein
36, R
37Be selected from hydrogen atom, (C
1-C
6) alkyl or phenyl, R
38Be selected from halo (C
1-C
12) alkyl; Described substituent R
39, R
40Be selected from (C
1-C
6) alkyl or (C
3-C
8) cycloalkyl; Described substituent R
41, R
42, R
43, R
44, R
45Can be identical or different, and be selected from hydrogen atom, cyano group, nitro, halogen atom, (C
1-C
12) alkyl, (C
3-C
8) cycloalkyl, halo (C
1-C
12) alkyl, cyano group (C
1-C
12) alkyl, nitro (C
1-C
12) alkyl, (C
1-C
6) alkyl-carbonyl (C
1-C
6) alkyl, (C
1-C
12) alkoxyl group, halo (C
1-C
6) alkoxyl group, (C
1-C
6) alkoxyl group (C
1-C
6) alkyl, halo (C
1-C
6) alkoxyl group (C
1-C
6) alkyl, (C
1-C
6) alkylthio, (C
1-C
6) alkylthio (C
1-C
6) alkyl, hydroxyl (C
1-C
12) alkyl, hydroxycarbonyl group (C
1-C
12) alkyl, (C
1-C
6) carbalkoxy (C
1-C
6) alkyl, amino (C
1-C
12) alkyl, aminocarboxyl (C
1-C
12) alkyl or-(CH
2)
nNR
46R
47, n=1,2,3,4; Described substituent R
46, R
47Be selected from (C
1-C
6) alkyl or (C
3-C
8) cycloalkyl, described substituent R
48, R
49, R
50, R
51, R
52Be selected from hydrogen atom, cyano group, nitro, hydroxyl, halogen atom, (C
1-C
6) alkyl, halo (C
1-C
6) alkyl, (C
1-C
6) alkoxyl group, halo (C
1-C
6) alkoxyl group, (C
1-C
6) alkylthio, halo (C
1-C
6) alkylthio, carboxyl or (C
1-C
6) carbalkoxy; R
6, R
7Represent respectively hydrogen atom, (C
1-C
4) alkyl or phenyl, and R
5=R
3, R
3Described as defined above, but work as R
3During for the hexafluoro sec.-propyl, R
5Be seven fluorine sec.-propyls.
The preferential R that recommends
1, R
2, R
3, R
4Be defined as follows:
R wherein
1And R
2Can be identical or different, and represent separately hydrogen atom, (C
1-C
4) alkyl, hydroxycarbonyl group (C
1-C
4) alkyl, (C
1-C
4) alkyl-carbonyl (C
1-C
4) alkyl, (C
1-C
4) carbalkoxy (C
1-C
4) alkyl, by R
53, R
54, R
55, R
56The pyridyl that replaces, on ring by R
57, R
58, R
59, R
60, R
61The benzyl that replaces; Described substituent R
53, R
54, R
55, R
56Can be identical or different, and be selected from hydrogen atom, cyano group, nitro, hydroxyl, halogen atom, (C
1-C
4) alkyl, halo (C
1-C
4) alkyl, (C
1-C
4) alkoxyl group, halo (C
1-C
4) alkoxyl group, (C
1-C
4) alkoxyl group (C
1-C
4) alkyl, halo (C
1-C
4) alkoxyl group (C
1-C
4) alkyl, (C
1-C
4) alkylthio, (C
1-C
4) alkylthio (C
1-C
4) alkyl, carboxyl, (C
1-C
4) carbalkoxy, (C
1-C
4) alkyl-carbonyl, halo (C
1-C
4) alkyl-carbonyl or pyridyl, described substituent R
57, R
58, R
59, R
60, R
61Can be identical or different, and be selected from hydrogen atom, cyano group, nitro, hydroxyl, halogen atom, (C
1-C
4) alkyl, halo (C
1-C
4) alkyl, (C
1-C
4) alkoxyl group, halo (C
1-C
4) alkoxyl group or (C
1-C
4) alkylthio; Perhaps R
1Be H, R
2Be (R
26R
27CH) (COOH) CH-, wherein R
26Be selected from hydrogen atom or (C
1-C
4) alkyl; R
27Be selected from hydroxyl, methylthio group (C
1-C
2) alkyl, sulfydryl, three benzylthios, hydroxycarbonyl group, hydroxycarbonyl group (C
1-C
2) alkyl, aminocarboxyl (C
1-C
2) alkyl, imidazolyl, indyl or by R
62, R
63, R
64, R
65, R
66The phenyl that replaces; Described substituent R
62, R
63, R
64, R
65, R
66Can be identical or different, and be selected from hydrogen atom, cyano group, nitro, hydroxyl, halogen atom, (C
1-C
4) alkyl, halo (C
1-C
4) alkyl, (C
1-C
4) alkoxyl group, halo (C
1-C
4) alkoxyl group or (C
1-C
4) alkylthio; Perhaps R
1R
2N-is selected from following substituting group:
Wherein said R
33Be selected from hydroxyl, methoxyl group, oxyethyl group, tert.-butoxy or amino; R
34Be selected from hydrogen atom, ethanoyl, benzyl, trimethyl silicon based (TMS) or triethyl silica-based (TES); R
35Be selected from hydrogen atom, tert-butoxycarbonyl (Boc), methyl, ethyl or sec.-propyl;
R
3Be the alkyl of Polyfluoroalkyl substituting group or perfluor replacement, for example C
1-C
27Perfluoroalkyl, refer to that its whole hydrogen atoms are all replaced by fluorine atom, and the alkyl with 1-27 carbon atom, wherein said alkyl can be straight chain or side chain or ring-type, such as trifluoromethyl, pentafluoroethyl group, seven fluorine n-propyls, seven fluorine sec.-propyls, nine fluorine normal-butyls, 11 fluorine neo-pentyls, 11 fluorine n-pentyls, ten trifluoro n-hexyls, 25 fluorine dodecyls etc.; Also can be contain the substituent Polyfluoroalkyls such as hydrogen, chlorine, bromine, sulfonic acid fluoride, as: hexafluoro sec.-propyl ,-(CF
2)
mCF
2H ,-(CF
2)
mCF
2L or-CF
2CF
2OC
2F
4SO
2Other Polyfluoroalkyls such as F; L=Cl wherein, Br; M=1,2,3,4,5,6,7,8,9.
R
4Expression hydrogen atom, (C
1-C
4) alkyl, hydroxyl (C
1-C
4) alkyl, hydroxycarbonyl group (C
1-C
4) alkyl, (C
1-C
4) carbalkoxy (C
1-C
4) alkyl, thiazolyl, pyrimidyl, naphthyl, adamantyl, aminocarboxyl (C
1-C
4) alkyl ,-CR
67R
68R
69,-CR
5R
6R
7, by R
70, R
71, R
72, R
73, R
74The phenyl that replaces or on ring by R
77, R
78, R
79, R
80, R
81The benzyl that replaces, wherein said substituent R
67, R
68Be selected from hydrogen atom, (C
1-C
4) alkyl or phenyl, R
69Be selected from halo (C
1-C
4) alkyl; Described substituent R
70, R
71, R
72, R
73, R
74Can be identical or different, and be selected from hydrogen atom, cyano group, phenyl, nitro, halogen atom, (C
1-C
4) alkyl, halo (C
1-C
4) alkyl, cyano group (C
1-C
4) alkyl, (C
1-C
4) alkoxyl group, halo (C
1-C
4) alkoxyl group, (C
1-C
4) alkoxyl group (C
1-C
4) alkyl, halo (C
1-C
4) alkoxyl group (C
1-C
4) alkyl, (C
1-C
4) alkylthio, (C
1-C
4) alkylthio (C
1-C
4) alkyl, amino (C
1-C
4) alkyl, hydroxycarbonyl group, (C
1-C
4) carbalkoxy, aminocarboxyl, hydroxyl (C
1-C
4) alkyl, hydroxycarbonyl group (C
1-C
4) alkyl, (C
1-C
4) carbalkoxy (C
1-C
4) alkyl, aminocarboxyl (C
1-C
4) alkyl or-(CH
2)
nNR
75R
76N=1,2,3,4, described substituent R
75, R
76Be selected from (C
1-C
4) alkyl, described substituent R
77, R
78, R
79, R
80, R
81Be selected from hydrogen atom, cyano group, nitro, halogen atom, (C
1-C
4) alkyl, halo (C
1-C
4) alkyl, (C
1-C
4) alkoxyl group or halo (C
1-C
4) alkoxyl group; R
6, R
7Represent respectively hydrogen atom, (C
1-C
4) alkyl or phenyl, and R
5=R
3, R
3Described as defined above, but work as R
3During for the hexafluoro sec.-propyl, R
5Be seven fluorine sec.-propyls.
The present invention relates to thiazolamine derivative 5-position selectivity and introduce the method for Polyfluoroalkyl, have very high selectivity, reaction product is single, owing to be Polyfluoroalkyl with hydrogen atom directly, have very high Atom economy, compare with the method for reporting before, have obvious advantage.
In the description of the compounds of this invention, in each substituent definition, " alkyl group " or " alkyl " of expression alkyl can be straight chain or side chain unless otherwise defined; " (C
1-C
12) alkyl " refer to have the alkyl of 1-12 carbon atom; and can be; for example methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl, neo-pentyl, 1 2-dimethyl propyl, hexyl, heptyl, octyl group, decyl and dodecyl.
" halogen atom " refers to chlorine atom, bromine atoms, iodine atom or fluorine atom." halo (C
1-C
12) alkyl " refer to one or more hydrogen atoms by replace and the straight or branched alkyl that have 1-12 carbon atom of one or more identical or different halogen atoms, and can be such as difluoromethyl, trifluoromethyl, 2-chloroethyl, 2-bromotrifluoromethane etc.
" (C
3-C
8) cycloalkyl " refer to have the cyclic alkyl of 3-8 carbon atom, can be, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl and ring octyl group.
Polyfluoroalkyl can be perfluoroalkyl, also can be to contain the substituent Polyfluoroalkyls such as hydrogen, chlorine, bromine, sulfonic acid fluoride." (C for example
1-C
27) perfluoroalkyl " refer to what its whole hydrogen atoms were all replaced by fluorine atom; and have the alkyl of 1-27 carbon atom; wherein said alkyl can be straight chain or side chain or ring-type; and can be mingled with Sauerstoffatom, such as being: trifluoromethyl, pentafluoroethyl group, seven fluorine n-propyls, seven fluorine sec.-propyls, nine fluorine normal-butyls, 11 fluorine neo-pentyls, 11 fluorine n-pentyls, ten trifluoro n-hexyls, 25 fluorine dodecyls etc.; Also can be to contain the substituent Polyfluoroalkyls such as hydrogen, chlorine, bromine, sulfonic acid fluoride, as: the hexafluoro sec.-propyl ,-(CF
2)
mCF
2H ,-(CF
2)
mCF
2L, L=C1 wherein, Br; M=1,2,3,4,5,6,7,8,9;-CF
2CF
2OC
2F
4SO
2Other Polyfluoroalkyls such as F;
When a group contained " alkoxy base " or " alkoxyl group " part, these terms referred to straight chain or branched alkoxy." (C
1-C
6) alkoxyl group " refer to for example methoxyl group, oxyethyl group, isopropoxy, sec-butoxy, tert.-butoxy, 1,2-dimethyl propoxy-and hexyloxy." halo (C
1-C
6) alkoxyl group " refer to the straight or branched alkoxyl group that its one or more hydrogen atoms are replaced by one or more identical or different halogen atoms; for example can be difluoro-methoxy, trifluoromethoxy, 2-chloroethoxy, 2-bromine oxethyl, 2; 2,2-trifluoro ethoxy, 3-chlorine butoxy, 3-bromine butoxy, 1-chlorine pentyloxy, 1-chlorine hexyloxy and 6-bromine hexyloxy.
" (C
1-C
6) alkylthio " refer to for example methylthio group, ethylmercapto group, isopropyl sulfenyl, secondary butylthio, uncle's butylthio, 1,2-dimethyl propylene sulfenyl and own sulfenyl.
The representational method of the present invention can be described with following reaction, but never is limited.
R wherein
1, R
2, R
3, R
4As above definition.And R
8Expression hydrogen atom, halogen atom, thiazolyl, pyrimidyl, naphthyl, adamantyl, (C
1-C
4) alkyl, (C
3-C
8) cycloalkyl, halo (C
1-C
4) alkyl, (C
1-C
4) alkyl-carbonyl (C
1-C
4) alkyl, (C
1-C
4) alkoxyl group (C
1-C
4) alkyl, halo (C
1-C
4) alkoxyl group (C
1-C
4) alkyl, hydroxyl (C
1-C
4) alkyl, hydroxycarbonyl group (C
1-C
4) alkyl, (C
1-C
4) carbalkoxy (C
1-C
4) alkyl, amino (C
1-C
4) alkyl, aminocarboxyl (C
1-C
4) alkyl ,-(CH
2)
nNR
75R
76, n=1,2,3,4, by R
70, R
71, R
72, R
73, R
74The phenyl that replaces or on ring by R
77, R
78, R
79, R
80, R
81The benzyl that replaces, described substituent R
75, R
76Be selected from (C
1-C
4) alkyl; Described substituent R
70, R
71, R
72, R
73, R
74Can be identical or different, and be selected from hydrogen atom, cyano group, phenyl, nitro, halogen atom, (C
1-C
4) alkyl, halo (C
1-C
4) alkyl, cyano group (C
1-C
4) alkyl, (C
1-C
4) alkoxyl group, halo (C
1-C
4) alkoxyl group, (C
1-C
4) alkoxyl group (C
1-C
4) alkyl, halo (C
1-C
4) alkoxyl group (C
1-C
4) alkyl, (C
1-C
4) alkylthio, (C
1-C
4) alkylthio (C
1-C
4) alkyl, amino (C
1-C
4) alkyl, hydroxycarbonyl group, (C
1-C
4) carbalkoxy, aminocarboxyl, hydroxyl (C
1-C
4) alkyl, hydroxycarbonyl group (C
1-C
4) alkyl, (C
1-C
4) carbalkoxy (C
1-C
4) alkyl, aminocarboxyl (C
1-C
4) alkyl or-(CH
2)
nNR
87R
88, n=1,2,3,4, described substituent R
87, R
88Be selected from (C
1-C
4) alkyl, described substituent R
77, R
78, R
79, R
80, R
81Be selected from hydrogen atom, cyano group, nitro, halogen atom, (C
1-C
4) alkyl, halo (C
1-C
4) alkyl, (C
1-C
4) alkoxyl group or halo (C
1-C
4) alkoxyl group;
Corresponding thiazolamine raw material or their hydrochloride of the aminothiazole derivs that 5-Polyfluoroalkyl shown in the following formula replaces shown in can through type (IV), halogenide shown in the salt forms such as hydrobromate and the formula (V) is in the presence of reaction initiator, be with or without in the presence of the alkali, and obtaining being with or without reaction in the presence of the inert solvent.This reaction also can water and water-immiscible inert solvent as inert solvent, and carry out being with or without in the presence of the phase-transfer catalyst.
Above-mentioned representational reaction is described in detail as follows and the invention is not restricted to following special case.
Polyfluoro halides R in the formula
fX (V) has comprised polyfluoro uncle halides, the secondary halides of polyfluoro;
Wherein polyfluoro uncle halides can be the perfluor halides, is preferably iodine, the bromo-derivative of perfluoroalkyl; Such as CF3I, bromotrifluoromethane, PFEI, five fluorine monobromethanes, seven fluorine n-propyl iodides, seven fluorine positive propyl bromos, nine fluorine n-butyl iodides, nine fluorine n-butyl bromides, 11 fluorine n-amyl iodides, 11 fluorine n-amyl bromides, ten trifluoro n-hexyl iodine, ten trifluoro n-hexyl bromines, 25 fluorine dodecyl iodine, 25 fluorine lauryl bromides;
Also can be to contain the substituent Polyfluoroalkyl iodo things such as hydrogen, chlorine, bromine, sulfonic acid fluoride, as: I (CF
2)
mCF
2H, I (CF
2)
mCF
2L, L=Cl wherein, Br; M=1,2,3,4,5,6,7,8,9; ICF
2CF
2OC
2F
4SO
2F etc.
Wherein the secondary halides of polyfluoro has comprised the secondary halides of perfluor and has contained the secondary halides of the substituent polyfluoro of other non-fluorine atoms, such as seven fluorine isopropyl iodides, 1-chloro-2-iodine heptafluoro-propane, 1-bromo-2-iodine heptafluoro-propane, perfluor cyclopentyl iodine and tetrafluoro-1-trifluoromethoxy-1-iodoethane, 11 fluorine neopentyl iodides;
Wherein operable phase-transfer catalyst comprises, quaternary ammonium salt for example, and such as hydrogen sulfate TBuA and Tetrabutylammonium bromide, the organophosphorated salt compound, such as Xiuization 4-butyl-phosphonium and alkyl polyether alkyl ammonium compounds, three (methoxyethoxyethyl) amine for example; Reaction can be carried out under not with the condition of phase-transfer catalyst, but add in some cases phase-transfer catalyst better result can be arranged, the amount that add this moment is not particularly limited, but for 1 mole reaction raw materials (aminothiazole), be generally 1/500 to about 2 moles, preferentially be recommended as 1/50 to about 1 mole.
Reaction can be carried out under the condition of various radical initiators, such as optical radiation; Perhaps some reductive agents, the system, the zinc-sulfurous acid aqueous solution that form such as rongalite, V-Brite B, potassium hyposulfite, thiourea peroxide, Sodium Metabisulfite, sodium bisulfite or their mixture, zinc powder-six water nickelous chloride; The amount of reductive agent is not particularly limited, but the reaction raw materials (aminothiazole) with respect to 1 mole is generally about 1/100 to about 3 moles, preferably in the scope of 0.8-2.0 mole, adds more initiators to not impact of reaction;
The light source that is used for illumination is not particularly limited, as long as it can provide enough energy to come initiation reaction, such as being high voltage mercury lamp;
Reductive agent and optical radiation as reaction initiator both can be used separately, also can both be combined with;
The mineral alkali that can add suitable monovalence metal, as yellow soda ash, sodium bicarbonate, salt of wormwood, saleratus, sodium phosphate, Sodium phosphate dibasic, potassiumphosphate and or dipotassium hydrogen phosphate etc., also can be the organic basess such as triethylamine, pyridine, reaction also can be carried out under the condition that does not add alkali.The salt of described thiazolamine or its respective acids, R
fX, radical initiator and alkali mol ratio are 1.0: 1.0～4.0: 0.5～3.0: 0～4.0; Reaction is carried out in the mixed solvent of organic solvent and water, such as the acetonitrile-water mixed solvent; Dimethyl formamide-water; Halogenated hydrocarbon solvent-the water such as methylene dichloride, ethylene dichloride or chloroform; Dimethyl sulfoxide (DMSO)-water; Ethers-the water such as dioxane or tetrahydrofuran (THF); Ketone-the water such as acetone or mibk; Methyl alcohol, the mixed solvent of the alcohols-water such as ethanol or Virahol; It also can be the mixture of above-mentioned solvent.The optimum solvent of this reaction is the acetonitrile-water mixed solvent.Temperature of reaction is 0～90 ℃, and the reaction times is 15 minutes-8 hours.Adopt R as working as
fDuring I, temperature of reaction is that zero degree arrives room temperature, perhaps heating, and 30-90 ℃ of reaction, reaction can be carried out in autoclave; When being R
fDuring Br, temperature of reaction is 30～90 ℃, and reaction also can be carried out in autoclave.Thiazolamine, R
fThe molar ratio of X and radical initiator is recommended as 1.0: 1.0～and 3.0: 1.0～2.5.Final product can or be made other salt such as hydrochloride through silica gel column chromatography, underpressure distillation and be further purified.The compounds of this invention can be used for preparation and has phytotoxic agricultural chemicals.
Method reaction conditions of the present invention is gentle, time is short, simple to operate, requirement to equipment is lower, aftertreatment is simple, and the reagent that adopts is simple and easy to, and only produces the seldom refuse of amount, all be very favourable in environmental protection and economic aspect, therefore the invention provides the thiazolamine compounds that Polyfluoroalkyl with industrial production meaning and beneficial use replaces.
Embodiment
Following examples help to understand the present invention, but the present invention not merely is confined in the scope of following embodiment.
Embodiment 1
The preparation of 2-amino-4-methyl-5-trifluoromethyl thiazole
A) bromotrifluoromethane is as raw material
In the 2L autoclave, add 30g 2-amino-4-methylthiazol, 100g vat powder, 100g disodium hydrogen phosphate dodecahydrate, 1.2 rise acetonitrile, 400 ml waters, sealing and equipment mechanical stirring device are refrigerated to autoclave-78 ℃, vacuumize, with bromotrifluoromethane displaced air three times, vacuumize, be pressed into the 180g bromotrifluoromethane, after recovering room temperature, be heated to 90 ℃ of reactions 6 hours, stop to stir, be chilled to room temperature, vacuum is revolved most of acetonitrile, it is 8-10 that the sodium hydroxide saturated aqueous solution is regulated aqueous pH values, extracted with diethyl ether, anhydrous magnesium sulfate drying, concentrated, HPLC:95%.Also can be further purified (normal hexane: ethyl acetate=4: 1), get the sterling light yellow solid, yield 75% through column chromatography again.
B) CF3I is as raw material
In the 250ml reaction tubes, add 3.0g 2-amino-4-methylthiazol, the 2.5g sodium bicarbonate, 50 milliliters of acetonitriles, 50 milliliters of dimethyl formamides, 20 ml waters stir and make dissolution of solid.Then reaction solution is put into ice-water bath, be chilled to 3 ℃, add 15 milliliters of acetonitrile solutions of 10.0g CF3I, stirred two minutes.Add the 9.2g vat powder in half an hour in batches, stirred 2 hours, thin layer is analysed and is followed the tracks of reaction, complete rear decompression revolves acetonitrile, add appropriate amount of deionized water, sodium carbonate regulating solution is alkalescence, and 60 milliliters of ether divide three extractions, anhydrous magnesium sulfate drying, concentrate to get the orange-yellow liquid of thickness, column chromatography, (normal hexane: ethyl acetate=4: 1), get the sterling light yellow solid, yield 90%.
1H?NMR(300MHz，CDCl
3/TMS)δ：5.80(br，2H)，2.30(s，3H).
19F?NMR(282MHz，CDCl
3)δ：-51.96(s，3F).
MS (ESI positive ion): 183.1 (M+1);
Embodiment 2
The preparation of 2-amino-5-perfluor normal-butyl thiazole
In the 250ml reaction tubes, add the 1.0g thiazolamine, the 0.84g sodium bicarbonate, 50 milliliters of acetonitriles, 10 ml waters stir and make dissolution of solid.Then reaction solution is put into ice-water bath, be chilled to 3 ℃, add 0.76g perfluor butyl iodide, stirred two minutes.Add the 1.8g vat powder, stirred 2 hours, thin layer is analysed and is followed the tracks of reaction, complete rear decompression revolves acetonitrile, add appropriate amount of deionized water, sodium carbonate regulating solution is alkalescence, and 30 milliliters of ether divide three extractions, anhydrous magnesium sulfate drying, concentrated, column chromatography, (normal hexane: ethyl acetate=4: 1), get product, yield 86%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.39(s，1H)，5.52(br，2H).
19F?NMR(282MHz，CDCl
3)δ：-81.37(t，J＝9.3Hz，3F)，-101.26(t，J＝11.3Hz，2F)，-122.84(m，2F)，-125.94(m，2F).
MS (ESI positive ion): 318.9 (M+1);
Embodiment 3
The preparation of 2-amino-5-pentafluoroethyl group thiazole
In the 250ml reaction tubes, add the 1.0g thiazolamine, the 0.84g sodium bicarbonate, 50 milliliters of acetonitriles, 10 ml waters stir and make dissolution of solid.Then reaction solution is put into ice-water bath, be chilled to 3 ℃, add the 5ml acetonitrile solution of 3.7g PFEI, stirred two minutes.Add the 1.8g vat powder, stirred 2 hours, thin layer is analysed and is followed the tracks of reaction, complete rear decompression revolves acetonitrile, add appropriate amount of deionized water, sodium carbonate regulating solution is alkalescence, and 30 milliliters of ether divide three extractions, anhydrous magnesium sulfate drying, concentrated, column chromatography, (normal hexane: ethyl acetate=4: 1), get product, yield 55%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.39(s，1H)，5.61(br，2H).
19F?NMR(282MHz，CDCl
3)δ：-84.90(s，3F)，-104.24(s，2F).
MS (ESI positive ion): 218.9 (M+1);
Embodiment 4
The preparation of 2-amino-5-(4-chloro-octafluoro normal-butyl) thiazole
In the 250ml reaction tubes, add the 1.0g thiazolamine, the 0.84g sodium bicarbonate, 50 milliliters of acetonitriles, 10 ml waters stir and make dissolution of solid.Then reaction solution is put into ice-water bath, be chilled to 3 ℃, add 7.2gClC4F8I, stirred two minutes.Add the 1.8g vat powder, stirred 2 hours, thin layer is analysed and is followed the tracks of reaction, complete rear decompression revolves acetonitrile, add appropriate amount of deionized water, sodium carbonate regulating solution is alkalescence, and 30 milliliters of ether divide three extractions, anhydrous magnesium sulfate drying, concentrated, column chromatography, (normal hexane: ethyl acetate=4: 1), get buff powder, yield 75%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.38(s，1H)，5.65(br，2H).
19F?NMR(282MHz，CDCl
3)δ：-68.30(t，J＝13.4Hz，3F)，-101.10(t，J＝13.4Hz，2F)，-119.80(m，2F)，-121.237(m，2F).
MS (ESI positive ion): 334.9 (M+1);
Embodiment 5
The preparation of 2-(2-(thiazolamine-5-yl)-tetrafluoro oxyethyl group)-tetrafluoro sulfonic acid fluoride
In the 500ml reaction flask, add the 3.0g thiazolamine, the 2.5g sodium bicarbonate, 160 milliliters of acetonitriles, 70 ml waters stir and make dissolution of solid.Then reaction solution is put into ice-water bath, be chilled to 3 ℃, add 19.2g 2-(2-iodine tetrafluoro oxyethyl group)-tetrafluoro sulfonic acid fluoride, stirred two minutes.Add the 5.2g vat powder, stirred 2 hours, thin layer is analysed and is followed the tracks of reaction, complete rear decompression revolves acetonitrile, add appropriate amount of deionized water, sodium carbonate regulating solution is alkalescence, and 30 milliliters of ether divide three extractions, anhydrous magnesium sulfate drying, concentrated, column chromatography, (normal hexane: ethyl acetate=5: 1), get buff powder, yield 53%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.37(s，1H)，5.93(br，2H).
19F?NMR(282MHz，CDCl
3)δ：-82.37(s，2F)，-87.08(s，2F)，-104.77(s，2F)，-112.29(s，2F).
MS (ESI positive ion): 398.7 (M+1);
Embodiment 6
The preparation of 2-amino-5-seven fluorine sec.-propyl thiazoles
In the 100ml reaction flask, add the 500mg thiazolamine, the 118g sodium bicarbonate, 30 milliliters of acetonitriles, 10 ml waters stir and make dissolution of solid.Then reaction solution is put into ice-water bath, be chilled to 3 ℃, add 2.5g seven fluorine isopropyl iodides, stirred two minutes.Add the 2.4g vat powder, complete rear decompression revolves acetonitrile, adds appropriate amount of deionized water, and 60 milliliters of ether divide three extractions, and anhydrous magnesium sulfate drying is concentrated, column chromatography, (normal hexane: ethyl acetate=3: 1), get white solid, yield 85%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.33(s，1H)，5.44(br，2H).
19F?NMR(282MHz，CDCl
3)δ：-75.93(d，J＝9.3Hz，6F)，-167.60(m，1F).
MS (ESI positive ion): 269.0 (M+1);
Embodiment 7
The preparation of 2-amino-5-hexafluoro sec.-propyl thiazole
In the 500ml reaction flask, add the 5.0g thiazolamine, the 8.5g sodium bicarbonate, 260 milliliters of acetonitriles, 50 ml waters stir and make dissolution of solid.Then reaction solution is put into ice-water bath, be chilled to 3 ℃, add 15.5g seven fluorine isopropyl iodides, stirred two minutes.Add the 12.0g vat powder, 3 ℃ of lower reactions, complete rear decompression revolves acetonitrile, adds appropriate amount of deionized water, sodium carbonate regulating solution is alkalescence, 60 milliliters of ether divide three extractions, and anhydrous magnesium sulfate drying is concentrated, column chromatography, (normal hexane: ethyl acetate=3: 1), get white solid, yield 76%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.13(s，1H)，5.23(br，2H)，4.16-4.32(m，J＝7.9Hz，1H).
19F?NMR(282MHz，CDCl
3)δ：-67.31(d，J＝7.9Hz，1F).
MS (ESI positive ion): 250.9 (M+1);
Embodiment 8
The preparation of 2-amino-4-phenyl-5-perfluor normal-butyl thiazole
The same embodiment of step (2), buff powder, yield 61%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.37-7.46(m，5H)，6.03(br，2H).
19F?NMR(282MHz，CDCl
3)δ：-81.56(t，J＝9.3Hz，3F)，-95.96(t，J＝13.3Hz，2F)，-121.58(m，2F)，-126.27(m，2F).
MS (ESI positive ion): 395.0 (M+1);
Embodiment 9
The preparation of 2-amino-4-p-methylphenyl-5-perfluor normal-butyl thiazole
The same embodiment of step (2), light orange powder, yield 58%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.33(d，J＝7.5Hz?2H)，7.16(d，J＝7.8Hz2H)，6.26(br，2H)，2.37(s，3H).
19F?NMR(282MHz，CDCl
3)δ：-81.36(t，J＝9.3Hz，3F)，-95.68(t，J＝13.4Hz，2F)，-121.36(m，2F)，-126.07(m，2F).
MS (ESI positive ion): 408.9 (M+1);
Embodiment 10
The preparation of 2-amino-4-p-methoxyphenyl-5-perfluor normal-butyl thiazole
The same embodiment of step (2), light orange powder, yield 63%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.39(d，J＝8.1Hz，2H)，6.89(d，J＝8.7Hz2H)，5.99(br，2H)，3.83(s，3H).
19F?NMR(282MHz，CDCl
3)δ：-81.00(t，J＝9.3Hz，3F)，-95.19(t，J＝13.4Hz，2F)，-121.03(m，2F)，-125.75(m，2F).
MS (ESI positive ion): 424.9 (M+1);
Embodiment 11
The preparation of 2-amino-4-rubigan-5-perfluor normal-butyl thiazole
The same embodiment of step (2), buff powder, yield 75%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.37(m，4H)，5.93(br，2H).
19F?NMR(282MHz，CDCl
3)δ：-81.26(t，J＝9.3Hz，3F)，-95.78(t，J＝13.4Hz，2F)，-121.35(m，2F)，-126.00(m，2F).
MS (ESI positive ion): 428.9 (M+1);
Embodiment 12
The preparation of 2-pyridyl-4-phenyl-5-perfluor normal-butyl thiazole
The same embodiment of step (2), white solid, yield 85%.
1H?NMR(300MHz，CDCl
3/TMS)δ：10.91(br，1H)，8.31(d，J＝4.5Hz，1H)，7.61(d，J＝6.3Hz，2H)，7.34(m，3H)，7.21(t，J＝7.7Hz，1H)，6.82(t，J＝6.3z，1H)，5.87(d，J＝8.1Hz?1H).
19F?NMR(282MHz，CDCl
3)δ：-81.16(t，J＝8.7Hz，3F)，-95.46(t，J＝13.4Hz，2F)，-120.85(m，2F)，-125.85(m，2F).
MS (ESI positive ion): 471.8 (M+1);
Embodiment 13
The preparation of 2-pyridyl-4-phenyl-5-seven fluorine sec.-propyl thiazoles
The same embodiment of step (2), white solid, yield 87%.
1H?NMR(300MHz，CDCl
3/TMS)δ：10.85(br，1H)，8.31(d，J＝5.1Hz，1H)，7.54(d，J＝6.9Hz，2H)，7.34-7.31(m，3H)，7.22(t，J＝15.6Hz，1H)，6.81(d，J＝12.3Hz，1H)，5.88(d，J＝8.7Hz，1H).
19F?NMR(282MHz，CDCl
3)δ：-76.53(d，J＝9.9Hz，6F)，-174.89(m，1F).
MS (ESI positive ion): 421.9 (M+1);
Embodiment 14
The preparation of 2-amino-4-methyl-5-seven fluorine sec.-propyl thiazoles
The same embodiment of step (2), white solid, yield 60%.
1H?NMR(300MHz，CDCl
3/TMS)δ：5.32(br，2H)，2.33(s，3H).
19F?NMR(282MHz，CDCl
3)δ：-76.25(d，J＝9.3Hz，6F)，-17.80(m，1F).
MS (ESI positive ion): 282.9 (M+1);
Embodiment 15
The preparation of 2-amino-4-methyl-5-hexafluoro sec.-propyl thiazole
The same embodiment of step (6), white solid, yield 65%.
1H?NMR(300MHz，CDCl
3/TMS)δ：5.61(br，2H)，4.30(m，J＝7.8Hz，1H)，2.20(s，3H).
19F?NMR(282MHz，CDCl
3)δ：-66.70(d，J＝7.3Hz，6F).
MS (ESI positive ion): 265.0 (M+1);
Embodiment 16
The preparation of N-(2-hydroxybenzyl)-2-amino-5-perfluor normal-butyl thiazole
Make with the production method the same with embodiment (2).Pale yellow powder, yield 78%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.43(s，1H)，7.21(m，2H)，6.92(m，2H)，6.17(br，1H)，4.55(s，2H).
19F?NMR(282MHz，CDCl
3)δ：-80.98(t，3F).
MS (ESI positive ion): 424.9 (M+1);
Embodiment 17
The preparation of N-(2-hydroxybenzyl)-2-amino-5-trifluoromethyl thiazole
N-(2-hydroxybenzyl)-thiazolamine and CF3I preparation make with the production method the same with embodiment (1b).Yield 80%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.44(s，1H)，7.16-7.24(m，2H)，6.89-6.96(m，2H)，4.63(s，2H).
19F?NMR(282MHz，CDCl
3)δ：-55.22(s，3F).
MS (ESI positive ion): 274.9 (M+1);
Embodiment 18
The preparation of 1-(5-hexafluoro sec.-propyl-thiazol-2-yl)-piperazine
Make with the production method the same with embodiment (6), white is to pale yellow solid.Yield 80%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.22(s，1H)，4.28(m，J＝7.9Hz，1H)，3.50(t，J＝5.1Hz，4H)，3.01(t，J＝5.1Hz，4H)，2.50(br，1H).
19F?NMR(282MHz，CDCl
3)δ：-67.32(d，J＝7.9Hz，6F).
MS (ESI positive ion): 320.0 (M+1);
Embodiment 19
The preparation of 1-(5-trifluoromethyl-thiazol-2-yl)-piperazine
Production method is the same with embodiment (1)
A) bromotrifluoromethane is as raw material
In 100 milliliters of autoclaves, add 0.7g 1-(thiazol-2-yl)-piperazine, 1.4g vat powder, 1.4g disodium hydrogen phosphate dodecahydrate, 30 milliliters of acetonitriles, 8 ml waters, sealing and equipment mechanical stirring device, autoclave is refrigerated to-78 ℃, vacuumizes, with bromotrifluoromethane displaced air three times, vacuumize, be pressed into the 2g bromotrifluoromethane, after recovering room temperature, be heated to 90 ℃ of reactions 6 hours, stop to stir, be chilled to room temperature, vacuum is revolved most of acetonitrile, and it is 8-10 that the sodium hydroxide saturated aqueous solution is regulated aqueous pH values, 60 milliliters of ethyl acetate are divided three extractions, anhydrous magnesium sulfate drying, concentrated rear column chromatography, (methyl alcohol: ethyl acetate=1: 1), get the sterling white solid, yield 70%.
B) CF3I is as raw material
In the 250ml reaction tubes, add 0.7g 1-(thiazol-2-yl)-piperazine, the 0.4g sodium bicarbonate, 10 milliliters of acetonitriles, 10 milliliters of dimethyl formamides, 10 ml waters stir and make dissolution of solid.Then reaction solution is put into ice-water bath, be chilled to 0 ℃, add 5 milliliters of acetonitrile solutions of 1.5g CF3I, stirred two minutes.Add the 1.4g vat powder, thin layer is analysed and is followed the tracks of reaction, reacts complete rear decompression and revolves acetonitrile, adds appropriate amount of deionized water, sodium carbonate regulating solution is alkalescence, 60 milliliters of ethyl acetate are divided three extractions, and anhydrous magnesium sulfate drying concentrates to get oily liquids, column chromatography, (methyl alcohol: ethyl acetate=1: 1), get the sterling white solid, yield 95%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.47(s，1H)，3.50(t，J＝4.5Hz，4H)，2.99(t，J＝4.5Hz，4H)，1.91(s，1H).
19F?NMR(282MHz，CDCl
3)δ：-54.45(s，3F).
MS (ESI positive ion): 238.0 (M+1);
Embodiment 20
The preparation of 2-amino-4-(2,2,3,3,4,4,5,5,5-, nine fluorine n-pentyls)-5-perfluor normal-butyl thiazole
Make with the production method the same with embodiment (2).Yield 75%.
1H?NMR(300MHz，DMSO-d
6/TMS)δ：7.98(s，2H)，3.50(t，J＝18.5Hz，2H).
19F?NMR(282MHz，DMSO-d
6)δ：-81.19(m，6F)，-97.94(s，2F)，-111.31(s，2F)，-122.06(m，2F)，-124.65(m，2F)，-125.94(m，2F)，-126.07(m，2F).
MS (ESI positive ion): 550.8 (M+1);
Embodiment 21
The preparation of 2-(1-pyrryl)-5-hexafluoro sec.-propyl thiazole
Make with the production method the same with embodiment (6).White solid.Yield 72%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.22(t，J＝18.0Hz，2H)，4.23(m，1H)，3.45(t，J＝6.8Hz，4H)，2.04(t，J＝6.8Hz，4H).
19F?NMR(282MHz，CDCl
3)δ：-67.38(d，J＝8.2Hz，6F).
MS (ESI positive ion): 305.0 (M+1);
Embodiment 22
The preparation of 2-amino-4-phenyl-5-seven fluorine sec.-propyl thiazoles
Make with the production method the same with embodiment (2).Yield 84%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.37(m，5H)，5.70(br，2H).
19F?NMR(282MHz，CDCl
3)δ：-76.10(d，J＝10.4Hz，6F)，-174.33(m，1F).
MS (ESI positive ion): 345.0 (M+1);
Embodiment 23
The preparation of 2-amino-4-(2,2,2-trifluoroethyl)-5-trifluoromethyl thiazole
Make with the production method the same with embodiment (1a).White solid.Yield 84%.
1H?NMR(300MHz，CDCl
3/TMS)δ：6.02(br，2H)，3.47(quart，J＝10.1Hz，2H).
19F?NMR(282MHz，CDCl
3)δ：-51.71(s，3F，-CF
3)，-64.11(t，J＝9.7Hz，3F，-CH
2CF
3).
MS (ESI positive ion): 250.9 (M+1);
Embodiment 24
The preparation of 2-amino-4-(2,3,3,3-tetrafluoro-(2-trifluoromethyl) propyl group)-5-perfluor sec.-propyl thiazole
Make with the production method the same with embodiment (1a).White solid.Yield 75%.
1H?NMR(300MHz，DMSO-d
6/TMS)δ：7.83(s，2H)，3.56(d，J＝22.8Hz，2H).
19F?NMR(282MHz，DMSO-d
6)δ：-75.42(m，6F)，-76.24(d，J＝8.5Hz，6F)，-178.0(m，1F)，-181.8(m，1F).
MS (ESI positive ion): 449.99 (M+1);
Embodiment 25
The preparation of 2-amino-4-methylol-5-trifluoromethyl thiazole
Make with the production method the same with embodiment (1a).White solid.Yield 70%.
1H?NMR(300MHz，DMSO-d
6/TMS)δ：7.61(s，2H)，5.20(br，1H)，4.30(s，2H).
19F?NMR(282MHz，DMSO-d
6)δ：-48.70(s，3F).
MS (ESI positive ion): 199.1 (M+1);
Embodiment 26
Make with the production method the same with embodiment (2).Yield 76%.
1H?NMR(300MHz，CDCl
3/TMS)δ：8.39(s，1H)，8.28(d，J＝8.1Hz，1H)，7.82(d，J＝7.8Hz，1H)，7.58(t，J＝8.1Hz，1H)，5.40(s，2H).
19F?NMR(282MHz，CDCl
3)δ：-80.75(t，J＝8.7Hz，3F)，-95.46(t，J＝13.4Hz，2F)，-120.83(m，2F)，-125.48(m，2F).
MS (ESI positive ion): 439.9 (M+1);
Embodiment 27
The preparation (photoresponse) of 2-amino-5-perfluor normal-butyl thiazole
Add the 1.0g thiazolamine at the flask that is used for photoresponse, the 0.84g sodium bicarbonate, 50 milliliters of acetonitriles, 10 ml waters stir and make dissolution of solid.Add 0.76g perfluor butyl iodide, stirred two minutes.Mixing solutions is under high voltage mercury lamp radiation, stirring at room 2 hours, complete rear decompression revolves acetonitrile, adds appropriate amount of deionized water, sodium carbonate regulating solution is alkalescence, 30 milliliters of ether divide three extractions, and anhydrous magnesium sulfate drying is concentrated, column chromatography, (normal hexane: ethyl acetate=4: 1), get product, yield 40%.
Embodiment 28
The preparation of 2-amino-4-methyl-5-trifluoromethyl thiazole hydrochloride
Gained 2-amino among the embodiment 1-4-methyl-5-trifluoromethyl thiazole 5.0g stirs lower, the diethyl ether solution that adds excessive 2M hydrogenchloride, stirring at room is dissolved to get faint yellow clear liquor, desolventizing is revolved in decompression, drain and obtain yellowish solid, add 15 milliliters of ether, after shaking, suction filtration obtains yellowish solid, is 2-amino-4-methyl-5-trifluoromethyl thiazole hydrochloride.
Embodiment 29
The preparation of N-(2-(4,6-dimethoxy pyrimidine oxy base) benzyl)-2-amino-5-trifluoromethyl thiazole
(hereinafter to be referred as compound 29)
The product of gained among the embodiment 17, and 2-methylsulfonyl-4, the 6-dimethoxypyridin is in the presence of salt of wormwood, according to the preparation of (CN1853471) method, white solid, yield 30%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.17-7.46(m，4H)，6.47(br，1H)，5.79(s，1H)，4.48(s，2H)，3.79(s，6H).
19F?NMR(282MHz，CDCl
3)δ：-54.27(s，3F).
MS (ESI positive ion): 412.9 (M+1), 434.9 (M+Na);
Embodiment 30
The preparation of N-(2-(4,6-dimethoxy pyrimidine oxy base) benzyl)-2-amino-4-methyl-5-trifluoromethyl thiazole
(hereinafter to be referred as compound 30)
2-(4,6-dimethoxy pyrimidine oxy base)-phenyl aldehyde 1.0g, product 0.646g among the embodiment 1 is dissolved in 10 milliliters of dry tetrahydrofuran, add the 1.0g tetraisopropoxy titanium, stirring at room is reacted complete rear adding suitable quantity of water, the diatomite suction filtration, be directly used in next step after concentrated, perhaps through ethyl alcohol recrystallization.
Previous step gained dissolution of solid in 20 milliliters of ethanol, is added the 0.315g sodium borohydride under the zero degree, stirred 3 hours, adding shrend goes out, add aqueous ammonium chloride solution and be adjusted to neutrality, concentrated, ethyl acetate extraction, anhydrous sodium sulfate drying, column chromatography, (normal hexane: ethyl acetate=4: 1), get product, white solid, yield 68%.
1H?NMR(400MHz，CDCl
3/TMS)δ：7.42(d，J＝7.6，7.2Hz，1H)，7.34(t，J＝7.8，7.2Hz，1H)，7.22(t，J＝7.6Hz，1H)，7.15(d，J＝8.0Hz，1H)，5.77(s，1H)，4.43(s，2H)，3.76(s，6H)，2.20(s，3H).
19F?NMR(282MHz，CDCl
3)δ：-51.60(s，3F).
MS (ESI positive ion): 427.0 (M+1);
Embodiment 31
The preparation of N-(2-(4,6-dimethoxy pyrimidine oxy base) benzyl)-2-amino-5-hexafluoro sec.-propyl base thiazole
(hereinafter to be referred as compound 31)
With the method preparation identical with embodiment (30), white solid, yield 70%.
1H?NMR(300MHz，CDCl
3/TMS)δ：7.25(m，5H)，6.19(br，1H)，5.79(s，1H)，4.50(s，2H)，3.82(s，6H).
19F?NMR(282MHz，CDCl
3)δ：-66.29(d，J＝7.1Hz，6F).
MS (ESI positive ion): 495.0 (M+1);
Embodiment 32
The preparation of N-(2-(4,6-dimethoxy pyrimidine oxy base) benzyl)-2-amino-4-phenyl-5-seven fluorine sec.-propyl base thiazoles
(hereinafter to be referred as compound 32)
With the method preparation identical with embodiment (30), white solid, yield 73%.
1H?NMR(300MHz，CDCl
3/TMS)δ：8.20(br，1H)，7.25(m，5H)，5.79(s，1H)，3.93(s，2H)，3.71(s，6H).
19F?NMR(282MHz，CDCl
3)δ：-76.24(d，J＝8.2Hz，6F)，-173.60(m，1F).
MS (ESI positive ion): 589.3 (M+1);
Embodiment 33
Biological activity determination
Below implement to provide and use part of compounds of the present invention to carry out the example of biological activity determination, it is to be noted that the present invention not merely is confined in the scope of following example.
The weeding activity evaluation test is carried out according to following method:
Test is the sandy loam of preparation with soil, and the weeding activity test is 9.5cm with basin alms bowl diameter, and safety testing is 12.0cm with basin alms bowl diameter.
The basin alms bowl that test is processed behind the bud is cultivated after planting putting into the greenhouse, to broadleaved herb be 2 leaf periods, dogstail is to carry out foliar spray 2～3 leaf phases to process, the liquid of processing is the organic solvent dissolutions such as compound acetone, DMF, and adding the laboratory preparation of 0.5% tween-80, thin up is needs dosage again.
The compound treatment concentration of active determination test is 150gai/ha, after the basin alms bowl of processing leaves standstill 1 day, puts into the greenhouse, regularly waters the weeding activity of appearance method observed and recorded compound after 14～21 days.
With the weeding activity of hazard of plant symptom (inhibition, deformity, yellow, albefaction) performance degree range estimation compound, 0 expression does not have herbicidal effect or to crop safety, weeds or crop are killed in 100% expression fully.
Weeding activity and crop safety appearance method judgement criteria are as follows:
Weeds and the crop species of the biological activity determination test usefulness of selecting are as follows:
The weeding activity test-results that cauline leaf is processed behind table 1, the bud
Compound involved in the present invention itself or be converted into such as reference compound class in the table 1 all has certain phytotoxicity.
Claims (22)
1.5-the thiazolamine compounds that Polyfluoroalkyl replaces, its structural formula is shown in (I):
R wherein
1And R
2Be identical or different, and represent separately hydrogen atom, (C
1-C
4) alkyl or the ring on by R
57, R
58, R
59, R
60, R
61The benzyl that replaces; Described substituent R
57, R
58, R
59, R
60, R
61Identical or different, and be selected from hydrogen atom, hydroxyl, halogen atom, (C
1-C
4) alkyl or halo (C
1-C
4) alkyl;
R
3Be the Polyfluoroalkyl substituting group;
R
4Expression hydrogen atom, (C
1-C
4) alkyl ,-CR
5R
6R
7R
6, R
7Represent respectively hydrogen atom or (C
1-C
4) alkyl, and R
5=R
3But work as R
3During for the hexafluoro sec.-propyl, R
5Be seven fluorine sec.-propyls;
And work as R
1, R
2And R
4When being hydrogen atom, R
3It is not trifluoromethyl.
2. according to compound claimed in claim 1, it is characterized in that, in the general formula (I):
R wherein
1And R
2Can be identical or different, and represent separately hydrogen atom, (C
1-C
4) alkyl, benzyl or the benzyl that on ring, replaced by 1-3 identical or different group, the substituting group on the described benzyl rings is selected from hydroxyl or halogen atom;
R
3Be the Polyfluoroalkyl substituting group, and described Polyfluoroalkyl substituting group be the hexafluoro sec.-propyl ,-(CF
2)
mCF
2H ,-(CF
2)
mCF
2L or-CF
2CF
2OC
2F
4SO
2F; Wherein L=Cl or Br; M=1,2,3,4,5,6,7,8 or 9;
R
4Expression hydrogen atom, (C
1-C
4) alkyl or-CR
5R
6R
7R
6, R
7Represent respectively hydrogen atom, and R
5=R
3But work as R
3During for the hexafluoro sec.-propyl, R
5Be seven fluorine sec.-propyls;
But work as R
1, R
2And R
4When being hydrogen atom, R
3It is not trifluoromethyl.
3. according to compound claimed in claim 1, it is characterized in that described R
1And R
2Represent separately hydrogen atom or the ring on by R
57, R
58, R
59, R
60, R
61The benzyl that replaces; Described substituent R
57, R
58, R
59, R
60, R
61Identical or different, and be selected from hydrogen atom or hydroxyl.
4. according to compound claimed in claim 1, it is characterized in that described R
1And R
2Represent separately hydrogen atom.
5. according to compound claimed in claim 1, it is characterized in that, in the described structural formula (I):
R wherein
1And R
2Represent separately hydrogen atom;
R
3Be trifluoromethyl, pentafluoroethyl group, seven fluorine n-propyls, seven fluorine sec.-propyls, nine fluorine normal-butyls, hexafluoro sec.-propyl ,-CF
2CF
2OC
2F
4SO
2F or-(CF
2)
mCF
2L; Wherein L and m are described with claim 2;
R
4Expression (C
1-C
4) alkyl.
6. compound as claimed in claim 1 is characterized in that, R
3Be C
1-C
27Perfluoroalkyl.
7. the synthetic method of the thiazolamine compounds (I) that replaces of a 5-Polyfluoroalkyl, it is characterized in that in the mixed solvent of organic solvent and water, 0～90 ℃, exist or do not exist under the condition of alkali, add or during not with phase-transfer catalyst the R shown in the thiazolamine shown in the formula IV or its salt, the formula V
fX and radical initiator reaction 15 minutes-8 hours;
Described thiazolamine or its salt, R
fThe mol ratio of X, radical initiator, alkali and phase-transfer catalyst is 1.0:1.0～4.0:0.5～3.0:0～3.0:0～2.0;
Described R
fIt is the Polyfluoroalkyl substituting group;
Described X is Br or I;
Described radical initiator is hyposulfite, rongalite, thiourea peroxide, Sodium Metabisulfite, sodium bisulfite or their mixture;
Described alkali is mineral alkali and the organic bases of monovalence metal; The mineral alkali of described monovalence metal is yellow soda ash, sodium bicarbonate, salt of wormwood, saleratus, sodium phosphate, Sodium phosphate dibasic, potassiumphosphate and/or dipotassium hydrogen phosphate; Organic bases is triethylamine or pyridine;
Described phase-transfer catalyst is the alkyl polyether alkyl ammonium compounds of organophosphorated salt compound or three (methoxyethoxyethyl) amine of quaternary ammonium salt, the Xiuization 4-butyl-phosphonium of hydrogen sulfate TBuA or Tetrabutylammonium bromide; But for the thiazolamine reaction raw materials shown in 1 mole the formula IV, phase-transfer catalyst is 1/500 to about 2 moles;
In the general formula (I), R
1, R
2, R
3, R
4Be defined as follows:
R wherein
1And R
2Be identical or different, and represent separately hydrogen atom, (C
1-C
4) alkyl or the ring on by R
57, R
58, R
59, R
60, R
61The benzyl that replaces; Described substituent R
57, R
58, R
59, R
60, R
61Identical or different, and be selected from hydrogen atom, hydroxyl, halogen atom, (C
1-C
4) alkyl or halo (C
1-C
4) alkyl;
R
3Be the Polyfluoroalkyl substituting group;
R
4Expression hydrogen atom, (C
1-C
4) alkyl ,-CR
5R
6R
7; R
6, R
7Represent respectively hydrogen atom or (C
1-C
4) alkyl, and R
5=R
3But work as R
3During for the hexafluoro sec.-propyl, R
5Be seven fluorine sec.-propyls;
And work as R
1, R
2And R
4When being hydrogen atom, R
3It is not trifluoromethyl;
Among the general formula I V, R
1, R
2Described as defined above; And,
R
8Expression hydrogen atom, (C
1-C
4) alkyl, halo (C
1-C
4) alkyl.
8. method as claimed in claim 7 is characterized in that, R
3Be C
1-C
27Perfluoroalkyl; And R
fBe C
1-C
27Perfluoroalkyl.
9. method as claimed in claim 7 is characterized in that, described R
fTo be selected from lower group Polyfluoroalkyl substituting group :-(CF
2)
mCF
2H ,-(CF
2)
mCF
2L or-CF
2CF
2OC
2F
4SO
2F; Wherein L=Cl or Br; M=1,2,3,4,5,6,7,8 or 9.
10. method as claimed in claim 7 is characterized in that, described R
3Be be selected from lower group Polyfluoroalkyl substituting group be the hexafluoro sec.-propyl ,-(CF
2)
mCF
2H ,-(CF
2)
mCF
2L or-CF
2CF
2OC
2F
4SO
2F; Wherein L=Cl or Br; M=1,2,3,4,5,6,7,8 or 9.
11. method as claimed in claim 7 is characterized in that, described R
fTo contain the substituent Polyfluoroalkyl of hydrogen, chlorine, bromine or sulfonic acid fluoride;
And described R
3To contain the substituent Polyfluoroalkyl of hydrogen, chlorine, bromine or sulfonic acid fluoride.
12. method as claimed in claim 7 is characterized in that, for the thiazolamine reaction raw materials shown in 1 mole the formula IV, described phase-transfer catalyst is 1/50 to 1 mole.
13. synthetic method according to claim 7 is characterized in that described radical initiator is hyposulfite.
14. synthetic method according to claim 7 is characterized in that described R
fX is bromotrifluoromethane.
15. synthetic method according to claim 7 is characterized in that salt, the R of described thiazolamine or its respective acids
fThe mol ratio 1.0:1.0 of X, radical initiator and alkali～3.0:1.0～2.5:1.0～3.0.
16. synthetic method according to claim 7 is characterized in that described organic solvent is acetonitrile or methyl tertiary butyl ether.
17. synthetic method according to claim 7 is characterized in that reaction product through silica gel column chromatography, underpressure distillation or makes corresponding hydrochloride or acetate carries out purifying.
18. the according to claim 1 application of described compound is characterized in that the agricultural chemicals for the preparation of controlling weeds.
19. application as claimed in claim 18 is characterized in that, described compound is
20. a thiazolamine compounds is characterized in that, described compound is selected from lower group:
21. the purposes of compound as claimed in claim 20 is characterized in that, for the preparation of the agricultural chemicals of controlling weeds.
22. the compound of structural formula suc as formula 1, shown in formula 7 or the formula 22;
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| CN 201010220927 CN101885708B (en) | 2010-07-07 | 2010-07-07 | 5-polyfluoroalkyl group substituted 2-aminothiazole compound, synthesis method and application thereof |
| PCT/CN2011/000036 WO2011082660A1 (en) | 2010-01-08 | 2011-01-07 | 5-multifluoroalkyl- substituted 2-aminothiazole compounds, preparation methods and uses thereof |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1153512A (en) * | 1994-06-02 | 1997-07-02 | 曾尼卡有限公司 | Substd. pyrrolidone, thiazolidones or oxazolidones as herbicides |
| WO2006072436A1 (en) * | 2005-01-07 | 2006-07-13 | F. Hoffmann-La Roche Ag | [4-(heteroaryl) piperazin-1-yl]-(2,5-substituted -phenyl)methanone derivatives as glycine transporter 1 (glyt-1) inhibitors for the treatment of neurological and neuropsychiatric disorders |
-
2010
- 2010-07-07 CN CN 201010220927 patent/CN101885708B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1153512A (en) * | 1994-06-02 | 1997-07-02 | 曾尼卡有限公司 | Substd. pyrrolidone, thiazolidones or oxazolidones as herbicides |
| WO2006072436A1 (en) * | 2005-01-07 | 2006-07-13 | F. Hoffmann-La Roche Ag | [4-(heteroaryl) piperazin-1-yl]-(2,5-substituted -phenyl)methanone derivatives as glycine transporter 1 (glyt-1) inhibitors for the treatment of neurological and neuropsychiatric disorders |
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