CN102250081A - Imidazolidinyl- or thiazolidinyl-containing 1,3,4-thiadiazole compounds and preparation method thereof - Google Patents
Imidazolidinyl- or thiazolidinyl-containing 1,3,4-thiadiazole compounds and preparation method thereof Download PDFInfo
- Publication number
- CN102250081A CN102250081A CN2011101344296A CN201110134429A CN102250081A CN 102250081 A CN102250081 A CN 102250081A CN 2011101344296 A CN2011101344296 A CN 2011101344296A CN 201110134429 A CN201110134429 A CN 201110134429A CN 102250081 A CN102250081 A CN 102250081A
- Authority
- CN
- China
- Prior art keywords
- substituent
- alkyl
- group
- amino
- compound
- 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
Landscapes
- Lubricants (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses imidazolidinyl- or thiazolidinyl-containing 1,3,4-thiadiazole compounds and a preparation method thereof, and belongs to the technical field of organic synthesis. The invention is characterized in that: amino substituted 1,3,4-thiadiazole compounds are subjected to chloracetyl formation, and by utilizing a characteristic that tautomers of thiocyanate ions have different stabilities at different temperatures, cyclization reaction can be performed by controlling reaction conditions and the imidazolidinyl- and thiazolidinyl-containing 1,3,4-thiadiazole compounds are prepared. The invention has the advantage that: according to requirements, the imidazolidinyl- and thiazolidinyl-containing 1,3,4-thiadiazole compounds can be selectively developed from the amino substituted 1,3,4-thiadiazole compounds.
Description
Technical field
The invention belongs to technical field of organic synthesis, relate to 1,3 of amino replacement, the amino of 4-thiadiazole compound is after the chloroacetyl chloride acidylate is modified; again under different condition through ring-closure reaction, preparation contains imidazolidyl 1,3 respectively; 4-thiadiazoles or contain thiazolidyl 1,3, the 4-thiadiazole compound.
Background technology
Thiazole and thiadiazole compound are important component parts in the azole heterogeneous ring compound.Found 1,3 before more than 50 years, the 4-thiadiazole compound has the antibacterial-anti-inflammatory drug activity, and synthesizes the antibacterials acetazolamide.In recent years, containing nitrogen, sulphur atom heterogeneous ring compound is applied gradually, and has obtained breakthrough progress in industry, agricultural, medicine and other fields.In industrial aspect, thiazole derivative can be used as the inhibiter [J.Studies in Conservation, 1988,33 (2): 97-103] of the bronze historical relic of protection, ore floatation agent [P.US 4877518,1989].Agriculturally, the thiadiazole derivative can be absorbed by vegetable cell, as plant-growth regulator; Desinsection, sterilant; Also be used for weedicide.Aspect medical, thiazole and thiadiazole derivative, have very high physiologically active and pharmacologically active, for example: 1,3, the α-An Jilinsuan ester derivative of 4-thiadiazoles is higher to the fungicidal activity of Rhizoctonia solani Kuhn, and 3, the dibasic thiadiazole derivative of 5-also can be used for antidepressant, anxiety and has antitumour activity etc.This compounds has become research focus now.
Imidazole derivative has been widely used in fields such as medicine, plating, disinfectant use in agriculture and makeup.In pharmaceutical industries, imidazoles is as the intermediate [Fine Organic Chemical product technical manual (descending) 1992] of producing fungi medicine clotrimazole, econazole, KETOKONAZOL etc.LEVAMISOLE HCL once was used for LEVAMISOLE HCL assisting therapy [the J. Tramisol is used for the colorectal carcinoma postoperative adjuvant therapy, 1994,23 (4): 191-192] to the colorectal carcinoma postoperative for the wide spectrum anthelmintic has the people, had obtained curative effect preferably.Imidazoles also can be used to generate no cyanogen or the galvanized brightening agent of low cyanogen on electroplating industry, is used to produce the anti-dandruff makeup in recent years again and does precious plain.Go back mass production sterilant hymexazole in addition, execute security personnel, the imidazoles Huang is grand and presses down mould azoles etc.At home and abroad also use in a large number as curing agent for epoxy resin.For the preparation of imidazole derivative, major part is raw material with the imidazoles all, then it is carried out chemically modified, to obtain target compound at present.
Therefore containing imidazoles, thiazole and thiadiazole compound all has application corresponding at aspects such as industry, agricultural, medicine.Yet, but do not receive concern about imidazolidyl connection thiadiazoles and thiazolidyl connection thiadiazole compound, the synthetic method of related compound is also seldom reported.
Summary of the invention
The purpose of this invention is to provide and contain imidazolidyl 1,3,4-thiadiazole compound or contain thiazolidyl 1,3,4-thiadiazole compound and preparation method thereof.This method is according to two kinds of resonance hybrid structures of thiocyanate ion active different these characteristics under different condition, carries out cyclization with modified amino thiadiazole compound thing, and preparation contains imidazolidyl 1 thus, 3,4-thiadiazoles or contain thiazolidyl 1,3, the 4-thiadiazole compound.
Technical scheme of the present invention is:
Contain imidazolidyl 1,3,4 ,-thiadiazole compound, its structural formula are formula (1), (2), (3), (4), (5), (6), (7):
Contain thiazolidyl 1,3,4 ,-thiadiazole compound, its structural formula are formula (8), (9), (10), (11), (12), (13), (14):
R
1For hydrogen atom, halogen, alkyl, have substituent alkyl, amino, have substituent amino, sulfydryl, have substituent sulfydryl, hydroxyl, have substituent hydroxyl, aromatic base, have substituent aromatic base, vinyl, have substituent vinyl, alkynyl, have substituent alkynyl, nitro, itrile group, acyl group, have substituent fatty acyl group or have substituent aromaticacyl radical;
R
2For Sauerstoffatom, sulphur atom, methylene radical, have substituent methylene radical, imino-or have substituent imino-;
R
3For hydrogen atom, halogen, alkyl, have substituent alkyl, amino, have substituent amino, sulfydryl, have substituent sulfydryl, hydroxyl, have substituent hydroxyl, aromatic base, have substituent aromatic base, vinyl, have substituent vinyl, alkynyl, have substituent alkynyl, nitro, itrile group, acyl group, have substituent fatty acyl group or have substituent aromaticacyl radical.
Wherein said alkyl is C
1～C
10Alkyl; Substituting group is the group that halogen, nitro, amino, alkoxyl group, vinyl, alkynyl, hydroxyl or alkyl replaced, and the position on aromatic nucleus is ortho position, a position or contraposition, and the replacement mode is single replacement or polysubstituted.
The present invention contains imidazolidyl 1,3,4-thiadiazoles or contain thiazolidyl 1,3, and the preparation method of 4-thiadiazole compound may further comprise the steps:
With 1,3 of amino replacement, the chloroacetyl chloride of 4-thiadiazole compound and 1～5eq joins under ice bath in the container that has tail gas absorption and reflux, rises to room temperature then gradually, stirs 5～12h.After reaction finished, product got acid amides through recrystallization, yield 10%～95%.
Acid amides is dissolved in the appropriate solvent, under catalyst action, stirs 3～12h for 20 ℃～100 ℃ with the sulfocarbimide water-bath.Reaction solution is purified through column chromatography, gets target compound, yield 20%～90%
Its synthetic route is route 1 or route 2:
Wherein Tio is the substituting group that contains the thiadiazoles group
Route 1
Wherein Tio is the substituting group that contains the thiadiazoles group
Route 2
In described reaction, 1,3 of amino replacement, 4-thiadiazole compound structural formula is (15), (16), (17), (18), (19), (20), (21):
Selected solvent is methyl alcohol, ethanol, propyl alcohol, acetone, butanone, methylene dichloride, ethylene dichloride, acetonitrile, chloroform, dimethyl formamide, dimethyl sulfoxide (DMSO) etc., and requiring solvent load is substrate all to be dissolved; Catalyzer is that described quaternary ammonium salt catalyst is, its structural formula is suc as formula (22), catalyst levels be substrate molar weight 10～100%.
R
4, R
5, R
6, R
7Be C
1～C
10Alkyl, have substituent C
1～C
10Alkyl, substituting group is the group that halogen, nitro, amino, alkoxyl group, vinyl, alkynyl, hydroxyl or alkyl replaced, and the position on aromatic nucleus is ortho position, a position or contraposition, and the replacement mode is single replacement or polysubstituted; X is a halogen atom.
Sulfocarbimide is potassium sulfocyanate, Sodium Thiocyanate 99, ammonium thiocyanate etc.
Column chromatography adopts ethyl acetate/hexanaphthene or ethyl acetate/petroleum ether mixing solutions as developping agent, and volume ratio is 1～20: 5; Adopting the silica gel specification is 100 orders～500 orders.
The product of the present invention preparation through nucleus magnetic resonance (
1H NMR), structural characterization such as infrared spectra, proved conclusively the synthetic compound and be the set goal compound.
Effect of the present invention and benefit are can be by the temperature of control reaction, and then optionally synthesizing oxygen-containing generation, thiocarbamoyl imidazole alkyl thiadiazoles or contain the thiazolidyl thiadiazoles, have characteristics such as selectivity is strong, yield height.
Embodiment
Be described in detail the specific embodiment of the present invention below in conjunction with technical scheme.
Embodiment 1 compound 3-(5-(5-oxo-2-thiocarbamoyl imidazole alkane-1-yl)-2-sulfo--1,3,4-thiadiazoles-3 (2H)-yl) propionitrile (e
1) synthetic
In 10ml single port flask, with compound a
1(0.186g, 1mmol) molten DMF (2ml, 26.0eq) in, (0.34g, 3mmol 3eq) splash into reaction system under the ice-water bath, drip to finish slowly to rise to stirring at room, and TLC follows the tracks of reaction process and finishes until reaction with chloroacetyl chloride.Product gets compound c through recrystallization
1, yield 60.84%.With c
1(0.26g, (3ml 6eq), adds tetra-n-butyl ammonium bromide (0.1g again 1mmol) to be dissolved in acetonitrile, 0.3eq), heating in water bath to 20 ℃ stirs 15min, adds KSCN (0.1g, 1eq), behind the stirring 3h, be warmed up to 80 ℃ of stirrings, TLC follows the tracks of reaction process and finishes until reaction.Reaction solution is purified through column chromatography for separation, gets Verbindung
1, yield 56.14%.Its reaction equation is a route 3:
Route 3
Detect data: 162 ℃ of decomposition temperatures; IR (KBr) (v
Max, cm
-1): 3432.50 2273.51 1749.511625.47 1571.59 1175.21 1083.49;
1(400MHz, Acteone): (2H), 4.18 (s, 2H), 4.61 (2H), 11.05 (s 1H), is target compound e to δ (ppm) 3.16 to H NMR for t, J=2.4Hz for t, J=6.8Hz
1
Embodiment 2 compound 3-(5-(5-oxo-2-thiocarbamoyl imidazole alkane-1-yl)-2-sulfo--1,3,4-thiadiazoles-3 (2H)-yl) methyl propionate (e
2) synthetic
In 10ml single port flask, with compound a
2(0.22g, 1mmol) molten DMF (2ml, 26.0eq) in, (0.34g, 3mmol 3eq) splash into reaction system under the ice-water bath, drip to finish slowly to rise to stirring at room, and TLC follows the tracks of reaction process and finishes until reaction with chloroacetyl chloride.Product gets compound c through recrystallization
2, yield 87.84%.With c
2(0.3g, (3ml 6eq), adds tetra-n-butyl ammonium bromide (0.1g again 1mmol) to be dissolved in acetonitrile, 0.3eq), heating in water bath to 20 ℃ stirs 15min, adds KSCN (0.1g, 1eq), behind the stirring 3h, be warmed up to 80 ℃ of stirrings, TLC follows the tracks of reaction process and finishes until reaction.Reaction solution is purified through column chromatography for separation, gets Verbindung
2, yield 50.31%.Its reaction equation is a route 4:
Route 4
Detect data: 103～104 ℃ of fusing points; IR (KBr) (v
Max, cm
-1): 3420.12 2922.24 1738.171582.33 1251.89 1184.59 1078.94;
1(400MHz, Acteone): (2H), 3.67 (s, 3H), 4.16 (s, 2H), 4.52 (2H), 10.91 (s 1H), is target compound e to δ (ppm) 2.95 to H NMR for t, J=2.4Hz for t, J=7.2Hz
2
Embodiment 3 compound 3-(5-(5-oxo-2-thiocarbamoyl imidazole alkane-1-yl)-2-sulfo--1,3,4-thiadiazoles-3 (2H)-yl) butyl propionate (e
3) synthetic
In 10ml single port flask, with compound a
3(0.26g, 1mmol) molten DMF (2ml, 26.0eq) in, (0.34g, 3mmol 3eq) splash into reaction system under the ice-water bath, drip to finish slowly to rise to stirring at room, and TLC follows the tracks of reaction process and finishes until reaction with chloroacetyl chloride.Product gets compound c through recrystallization
3, yield 87.23%.With c
3(0.34g, (3ml 6eq), adds tetra-n-butyl ammonium bromide (0.1g again 1mmol) to be dissolved in acetonitrile, 0.3eq), heating in water bath to 20 ℃ stirs 15min, adds KSCN (0.1g, 1eq), behind the stirring 3h, be warmed up to 80 ℃ of stirrings, TLC follows the tracks of reaction process and finishes until reaction.Reaction solution is purified through column chromatography for separation, gets Verbindung
3, yield 42.77%.Its reaction equation is a route 5:
Route 5
Detect data: 132～134 ℃ of fusing points; IR (KBr) (v
Max, cm
-1): 3429.57 2957.40 1748.871633.53 1589.73 1266.31 1179.09 1084.57;
1H NMR (400MHz, Acteone): δ (ppm) 0.93 (t, J=6.4Hz, 3H), 1.40 (m, J=7.2Hz, 2H), 1.60 (m, J=6.8Hz, 2H), 2.95 (t, J=6.8Hz, 2H), 4.07 (t, J=6.8Hz, 2H), 4.10 (s, 2H), 4.52 (t, J=6.8Hz, 2H), 11.00 (s 1H), is target compound e
3
Embodiment 4 compound 3-(5-(4-oxo thiazolidine-2-Ji imino-)-2-sulfo--1,3,4-thiadiazoles-3 (2H)-yl) propionitrile (f
1) synthetic
In 10ml single port flask, with compound a
1(0.186g, 1mmol) molten DMF (2ml, 26.0eq) in, (0.34g, 3mmol 3eq) splash into reaction system under the ice-water bath, drip to finish slowly to rise to stirring at room, and TLC follows the tracks of reaction process and finishes until reaction with chloroacetyl chloride.Product gets compound c through recrystallization
1, yield 60.84%.With c
1(0.26g, 1mmol) be dissolved in DMF (2ml, 26eq), heating in water bath to 20 ℃ stirs 15min, (0.1g 1eq), is warmed up to 100 ℃ of stirrings, and TLC follows the tracks of reaction process and finishes until reaction to add KSCN.Reaction solution gets compound f through recrystallization
1, yield 71.68%.Its reaction equation is a route 6:
Route 6
Detect data: 206～208 ℃ of fusing points; IR (KBr) (v
Max, cm
-1): 3437.42,2924.39,2253.70,1747.04,1623.78,1173.72,1082.09;
1(400MHz, DMSO): (2H), 4.17 (s, 2H), 4.496 (2H), 12.48 (s 1H), is target compound f to δ (ppm) 3.110 to H NMR for t, J=6.4Hz for t, J=6.0Hz
1
Embodiment 5 compound 3-(5-(4-oxo thiazolidine-2-Ji imino-)-2-sulfo--1,3,4-thiadiazoles-3 (2H)-yl) methyl propionate (f
2) synthetic
In 10ml single port flask, with compound a
2(0.22g, 1mmol) molten DMF (2ml, 26.0eq) in, (0.34g, 3mmol 3eq) splash into reaction system under the ice-water bath, drip to finish slowly to rise to stirring at room, and TLC follows the tracks of reaction process and finishes until reaction with chloroacetyl chloride.Product gets compound c through recrystallization
2, yield 87.84%.With c
2(0.3g, 1mmol) be dissolved in DMF (2ml, 26eq), heating in water bath to 20 ℃ stirs 15min, (0.1g 1eq), is warmed up to 100 ℃ of stirrings, and TLC follows the tracks of reaction process and finishes until reaction to add KSCN.Reaction solution gets compound f through recrystallization
2, yield 71.18%.Its reaction equation is a route 7:
Route 7
Detect data: 161 ℃ of fusing points; IR (KBr) (v
Max, cm
-1): 3432.48,2939.13,1738.48,1581.54,1252.12,1185.17,1079.29;
1(400MHz, DMSO): (2H), 3.615 (s, 3H), 4.148 (s, 2H), 4.424 (2H), 12.43 (s 1H), is target compound f to δ (ppm) 2.905 to H NMR for t, J=6.8Hz for t, J=6.8Hz
2
Embodiment 6 compound 3-(5-(4-oxo thiazolidine-2-Ji imino-)-2-sulfo--1,3,4-thiadiazoles-3 (2H)-yl) butyl propionate (f
3) synthetic
In 10ml single port flask, with compound a
3(0.22g, 1mmol) molten DMF (2ml, 26.0eq) in, (0.34g, 3mmol 3eq) splash into reaction system under the ice-water bath, drip to finish slowly to rise to stirring at room, and TLC follows the tracks of reaction process and finishes until reaction with chloroacetyl chloride.Product gets compound c through recrystallization
3, yield 87.23%.With c
3(0.3g, 1mmol) be dissolved in DMF (2ml, 26eq), heating in water bath to 20 ℃ stirs 15min, (0.1g 1eq), is warmed up to 100 ℃ of stirrings, and TLC follows the tracks of reaction process and finishes until reaction to add KSCN.Reaction solution gets compound f through recrystallization
3, yield 60.84%.Its reaction equation is a route 8:
Route 8
Detect data: 154～155 ℃ of fusing points; IR (KBr) (v
Max, cm
-1): 3432.50,2960.02,1726.32,1634.07,1575.57,1244.95,1181.18,1082.63;
1H NMR (400MHz, DMSO): δ (ppm) 0.86 (t, J=4Hz, 3H), 1.28 (m, J=8Hz, 2H), 1.54 (m, J=8Hz, 2H), 2.90 (t, J=8Hz, 2H), 4.02 (t, J=8Hz, 2H), 4.15 (s, 2H), 4.42 (t, J=8Hz, 2H), 12.44 (s 1H), is target compound f
3
Embodiment 7 compound 3-(5-(5-oxo-2-thiocarbamoyl imidazole alkane-1-yl)-1,3,4-thiadiazoles-2-base sulfenyl) propionitrile (g
1) synthetic
In 10ml single port flask, with compound b
1(0.186g, 1mmol) molten DMF (2ml, 26.0eq) in, (0.34g, 3mmol 3eq) splash into reaction system under the ice-water bath, drip to finish slowly to rise to stirring at room, and TLC follows the tracks of reaction process and finishes until reaction with chloroacetyl chloride.Product gets compound d through recrystallization
1, yield 90.85%.With d
1(0.26g, 1mmol) be dissolved in DMF (2ml, 26eq), heating in water bath to 20 ℃ stirs 15min, (0.1g 1eq), is warmed up to 100 ℃ of stirrings, and TLC follows the tracks of reaction process and finishes until reaction to add KSCN.Reaction solution gets compound g through recrystallization
1, yield 67.38%.Its reaction equation is a route 9:
Route 9
Detect data: 196～198 ℃ of fusing points; IR (KBr) (v
Max, cm
-1): 3451.85 2230.71 1734.941569.13 1166.96 1053.87;
1(400MHz, Acteone): (2H), 3.63 (2H), 4.11 (s, 2H), 10.90 (s 1H), is target compound g to δ (ppm) 3.10 to H NMR for t, J=6.8Hz for t, J=6.8Hz
1
Embodiment 8 compound 3-(5-(5-oxo-2-thiocarbamoyl imidazole alkane-1-yl)-1,3,4-thiadiazoles-2-base sulfenyl) methyl propionate (g
2) synthetic
In 10ml single port flask, with compound b
2(0.22g, 1mmol) molten DMF (2ml, 26.0eq) in, (0.34g, 3mmol 3eq) splash into reaction system under the ice-water bath, drip to finish slowly to rise to stirring at room, and TLC follows the tracks of reaction process and finishes until reaction with chloroacetyl chloride.The product recrystallization gets compound d
2, yield 92.57%.With d
2(0.3g, (3ml 6eq), adds tetra-n-butyl ammonium bromide (0.1g again 1mmol) to be dissolved in acetonitrile, 0.3eq), heating in water bath to 20 ℃ stirs 15min, adds KSCN (0.1g, 1eq), behind the stirring 3h, be warmed up to 80 ℃ of stirrings, TLC follows the tracks of reaction process and finishes until reaction.Reaction solution is purified through column chromatography for separation, gets compound g
2, yield 75.39%.Its reaction equation is a route 10:
Route 10
Detect data: 165～167 ℃ of fusing points; IR (KBr) (v
Max, cm
-1): 3448.57 2923.78 1734.641595.59 1174.18 1073.48;
1(400MHz, Acteone): (2H), 3.53 (2H), 3.67 (s, 3H), 4.10 (s, 2H), 10.90 (s 1H), is target compound g to δ (ppm) 2.89 to H NMR for t, J=8Hz for t, J=6Hz
2
Embodiment 9 compound 3-(5-(5-oxo-2-thiocarbamoyl imidazole alkane-1-yl)-1,3,4-thiadiazoles-2-base sulfenyl) butyl propionate (g
3) synthetic
In 10ml single port flask, with compound b
3(0.26g, 1mmol) molten DMF (2ml, 26.0eq) in, (0.34g, 3mmol 3eq) splash into reaction system under the ice-water bath, drip to finish slowly to rise to stirring at room, and TLC follows the tracks of reaction process and finishes until reaction with chloroacetyl chloride.Product gets compound d through recrystallization
3, yield 82.82%.With d
3(0.34g, (3ml 6eq), adds tetra-n-butyl ammonium bromide (0.1g again 1mmol) to be dissolved in acetonitrile, 0.3eq), heating in water bath to 20 ℃ stirs 15min, adds KSCN (0.1g, 1eq), behind the stirring 3h, be warmed up to 80 ℃ of stirrings, TLC follows the tracks of reaction process and finishes until reaction.Reaction solution is purified through column chromatography for separation, gets compound g
3, yield 41.68%.Its reaction equation is a route 11:
Route 11
Detect data: 110～113 ℃ of fusing points; IR (KBr) (v
Max, cm
-1): 3432.49 2961.50 1734.071598.80 1259.14 1175.37 1090.35;
1H NMR (400MHz, Acteone): δ (ppm) 0.92 (t, J=6.8Hz, 3H), 1.40 (m, J=6.8Hz, 2H), 1.61 (m, J=7.2Hz, 2H), 2.89 (t, J=6.8Hz, 2H), 3.53 (t, J=6.8Hz, 2H), 4.10 (t, J=6.8Hz, 2H), 4.10 (s, 2H), 10.89 (s 1H), is target compound g
3
Embodiment 10 compound 3-(5-(4-oxo thiazolidine-2-Ji imino-)-2-sulfo--1,3,4-thiadiazoles-3 (2H)-yl) propionitrile (h
1) synthetic
In 10ml single port flask, with compound b
1(0.186g, 1mmol) molten DMF (2ml, 26.0eq) in, (0.34g, 3mmol 3eq) splash into reaction system under the ice-water bath, drip to finish slowly to rise to stirring at room, and TLC follows the tracks of reaction process and finishes until reaction with chloroacetyl chloride.Product gets compound d through acetone-water system recrystallization
1, yield 90.85%.With d
1(0.26g, 1mmol) be dissolved in DMF (2ml, 26eq), heating in water bath to 20 ℃ stirs 15min, (0.1g 1eq), is warmed up to 100 ℃ of stirrings, and TLC follows the tracks of reaction process and finishes until reaction to add KSCN.Reaction solution gets compound h through recrystallization
1, yield 63.52%.Its reaction equation is a route 12:
Route 12
Detect data: 208～210 ℃ of fusing points; IR (KBr) (v
Max, cm
-1): 3432.37,2933.01,2245.27,1735.76,1651.97,1561.88,1168.39;
1(400MHz, DMSO): (2H), 3.545 (2H), 4.114 (s, 2H), 12.35 (s 2H), is target compound h to δ (ppm) 3.054 to H NMR for t, J=6.4Hz for t, J=6.4Hz
1
Embodiment 11 compound 3-(5-(4-oxo thiazolidine-2-Ji imino-)-1,3,4-thiadiazoles-2-base sulfenyl) methyl propionate (h
2) synthetic
In 10ml single port flask, with compound b
2(0.22g, 1mmol) molten DMF (2ml, 26.0eq) in, (0.34g, 3mmol 3eq) splash into reaction system under the ice-water bath, drip to finish slowly to rise to stirring at room, and TLC follows the tracks of reaction process and finishes until reaction with chloroacetyl chloride.Product gets compound d through recrystallization
2, yield 92.57%.With d
2(0.3g, 1mmol) be dissolved in DMF (2ml, 26eq), heating in water bath to 20 ℃ stirs 15min, (0.1g 1eq), is warmed up to 100 ℃ of stirrings, and TLC follows the tracks of reaction process and finishes until reaction to add KSCN.Reaction solution gets compound h through recrystallization
2, yield 65.32%.Its reaction equation is a route 13:
Route 13
Detect data: 176～177 ℃ of fusing points; IR (KBr) (v
Max, cm
-1): 3430.17,2924.89,1732.68,1597.79,1251.20,1173.35,1071.13;
1(400MHz, DMSO): (2H), 3.452 (2H), 3.627 (s, 3H), 4.109 (s, 2H), 12.33 (s 1H), is target compound h to δ (ppm) 2.849 to H NMR for t, J=6.8Hz for t, J=6.8Hz
2
Embodiment 123-(5-(4-oxo thiazolidine-2-Ji imino-)-1,3,4-thiadiazoles-2-base sulfenyl) butyl propionate (h
3) synthetic
In 10ml single port flask, with compound b
3(0.22g, 1mmol) molten DMF (2ml, 26.0eq) in, (0.34g, 3mmol 3eq) splash into reaction system under the ice-water bath, drip to finish slowly to rise to stirring at room, and TLC follows the tracks of reaction process and finishes until reaction with chloroacetyl chloride.Product gets compound d through recrystallization
3, yield 87.82%.With d
3(0.3g, 1mmol) be dissolved in DMF (2ml, 26eq), heating in water bath to 20 ℃ stirs 15min, (0.1g 1eq), is warmed up to 100 ℃ of stirrings, and TLC follows the tracks of reaction process and finishes until reaction to add KSCN.Reaction solution gets compound h through recrystallization
3, yield 71.60%.Its reaction equation is a route 14:
Route 14
Detect data: 111～112 ℃ of fusing points; IR (KBr) (v
Max, cm
-1): 3405.58,2958.29,1732.24,1594.60,1171.47,1248.37,1056.72;
1H NMR (400MHz, DMSO): δ (ppm) 0.88 (t, J=8Hz, 3H), 1.33 (m, J=8Hz, 2H), 1.55 (m, J=8Hz, 2H), 2.84 (t, J=4Hz, 2H), 3.45 (t, J=8Hz, 2H), 4.05 (t, J=8Hz, 2H), 4.11 (s, 2H), 12.33 (s 1H), is target compound h
3
Claims (4)
1. contain imidazolidyl 1,3, the 4-thiadiazole compound is characterized in that, its structural formula is formula (1), (2), (3), (4), (5), (6) or (7):
Contain thiazolidyl 1,3,4-thiadiazole compound, its structural formula are formula (8), (9), (10), (11), (12), (13) or (14).
2. the imidazolidyl 1,3 that contains according to claim 1,4-thiadiazole compound or contain thiazolidyl 1,3, the 4-thiadiazole compound is characterized in that:
R
1For hydrogen atom, halogen, alkyl, have substituent alkyl, amino, have substituent amino, sulfydryl, have substituent sulfydryl, hydroxyl, have substituent hydroxyl, aromatic base, have substituent aromatic base, vinyl, have substituent vinyl, alkynyl, have substituent alkynyl, nitro, itrile group, acyl group, have substituent fatty acyl group or have substituent aromaticacyl radical;
R
2For Sauerstoffatom, sulphur atom, methylene radical, have substituent methylene radical, imino-or have substituent imino-;
R
3For hydrogen atom, halogen, alkyl, have substituent alkyl, amino, have substituent amino, sulfydryl, have substituent sulfydryl, hydroxyl, have substituent hydroxyl, aromatic base, have substituent aromatic base, vinyl, have substituent vinyl, alkynyl, have substituent alkynyl, nitro, itrile group, acyl group, have substituent fatty acyl group or have substituent aromaticacyl radical.
3. the imidazolidyl 1,3 that contains according to claim 2,4-thiadiazole compound or contain thiazolidyl 1,3, the 4-thiadiazole compound is characterized in that: described alkyl is C
1～C
10Alkyl; Substituting group is the group that halogen, nitro, amino, alkoxyl group, vinyl, alkynyl, hydroxyl or alkyl replaced, and the position on aromatic nucleus is ortho position, a position or contraposition, and the replacement mode is single replacement or polysubstituted.
4. claim 1, the 2 or 3 described imidazolidyls 1 that contain, 3,4-thiadiazole compound or contain thiazolidyl 1,3, the preparation method of 4-thiadiazole compound is characterized in that: with 1 of amino replacement, 3, the chloroacetyl chloride of 4-thiadiazole compound and 1～5eq joins under ice bath in the container that has tail gas absorption and reflux, rises to room temperature then gradually, stirs 5～12h; After reaction finished, product got acid amides through recrystallization; Acid amides is dissolved in the solvent, under the quaternary ammonium salt katalysis, stirs 3～12h for 20 ℃～100 ℃ with the sulfocarbimide water-bath; Reaction solution is purified through column chromatography, gets target compound.
1,3 of described amino replacement, 4-thiadiazole compound structural formula is (15), (16), (17), (18), (19), (20), (21):
Described solvent is methyl alcohol, ethanol, propyl alcohol, acetone, butanone, methylene dichloride, ethylene dichloride, acetonitrile, chloroform, dimethyl formamide, dimethyl sulfoxide (DMSO), and requiring solvent load is substrate all can be dissolved;
Described quaternary ammonium salt catalyst is, its structural formula is suc as formula (22), catalyst levels be substrate molar weight 10～100%;
R
4Be C
1～C
10Alkyl, have substituent C
1～C
10Alkyl, substituting group is the group that halogen, nitro, amino, alkoxyl group, vinyl, alkynyl, hydroxyl or alkyl replaced, and the position on aromatic nucleus is ortho position, a position or contraposition, and the replacement mode is single replacement or polysubstituted;
R
5Be C
1～C
10Alkyl, have substituent C
1～C
10Alkyl; Substituting group is the group that halogen, nitro, amino, alkoxyl group, vinyl, alkynyl, hydroxyl or alkyl replaced, and the position on aromatic nucleus is ortho position, a position or contraposition, and the replacement mode is single replacement or polysubstituted;
R
6Be C
1～C
10Alkyl, have substituent C
1～C
10Alkyl; Substituting group is the group that halogen, nitro, amino, alkoxyl group, vinyl, alkynyl, hydroxyl or alkyl replaced, and the position on aromatic nucleus is ortho position, a position or contraposition, and the replacement mode is single replacement or polysubstituted;
R
7Be C
1～C
10Alkyl, have substituent C
1～C
10Alkyl; Substituting group is the group that halogen, nitro, amino, alkoxyl group, vinyl, alkynyl, hydroxyl or alkyl replaced, and the position on aromatic nucleus is ortho position, a position or contraposition, and the replacement mode is single replacement or polysubstituted;
X is a halogen atom;
Described sulfocarbimide is potassium sulfocyanate, Sodium Thiocyanate 99, ammonium thiocyanate;
Described column chromatography adopts ethyl acetate/hexanaphthene or ethyl acetate/petroleum ether mixing solutions as developping agent, and volume ratio is 1～20: 5; Adopting the silica gel specification is 100 orders～500 orders.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011101344296A CN102250081A (en) | 2011-05-23 | 2011-05-23 | Imidazolidinyl- or thiazolidinyl-containing 1,3,4-thiadiazole compounds and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011101344296A CN102250081A (en) | 2011-05-23 | 2011-05-23 | Imidazolidinyl- or thiazolidinyl-containing 1,3,4-thiadiazole compounds and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102250081A true CN102250081A (en) | 2011-11-23 |
Family
ID=44977689
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011101344296A Pending CN102250081A (en) | 2011-05-23 | 2011-05-23 | Imidazolidinyl- or thiazolidinyl-containing 1,3,4-thiadiazole compounds and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102250081A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4036848A (en) * | 1976-03-15 | 1977-07-19 | Velsicol Chemical Corporation | 1-Thiadiazolyl-5-furfuryl and tetrahydrofurfuryl aminoimidazolidinones |
| US4111949A (en) * | 1976-03-25 | 1978-09-05 | Velsicol Chemical Company | Thiadiazolylimidazolidinone esters of tetrahydrofuryl substituted acids |
| CN101397297A (en) * | 2007-09-27 | 2009-04-01 | 天津药物研究院 | Aminothiazole derivates, preparation method and use thereof |
-
2011
- 2011-05-23 CN CN2011101344296A patent/CN102250081A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4036848A (en) * | 1976-03-15 | 1977-07-19 | Velsicol Chemical Corporation | 1-Thiadiazolyl-5-furfuryl and tetrahydrofurfuryl aminoimidazolidinones |
| US4111949A (en) * | 1976-03-25 | 1978-09-05 | Velsicol Chemical Company | Thiadiazolylimidazolidinone esters of tetrahydrofuryl substituted acids |
| CN101397297A (en) * | 2007-09-27 | 2009-04-01 | 天津药物研究院 | Aminothiazole derivates, preparation method and use thereof |
Non-Patent Citations (1)
| Title |
|---|
| POOJA MULLICK,等: "Synthesis, Characterization and Antimicrobial Activity of New Thiadiazole Derivatives", 《SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2007254255B2 (en) | Crystalline forms and processes for the preparation of phenyl-pyrazoles useful as modulators of the 5-HT2A serotonin receptor | |
| CA2870062A1 (en) | Pyrrolopyrazone inhibitors of tankyrase | |
| EP3658552B1 (en) | Process for preparing n-(5-((4-(4-((dimethylamino)methyl)-3-phenyl-1h-pyrazol-1-yl)pyrimidin-2-yl)amino)-4-methoxy-2-morpholinophenyl)acrylamide by reacting the corresponding amine with a 3-halo-propionyl chloride | |
| Gan et al. | Imidazolium chloride-catalyzed synthesis of benzimidazoles and 2-substituted benzimidazoles from o-phenylenediamines and DMF derivatives | |
| Proenca et al. | One-pot approach to the synthesis of novel 12H-chromeno [2′, 3′: 4, 5] imidazo [1, 2-a] pyridines in aqueous media | |
| CN112480079B (en) | Compounds and their use for treating cancer | |
| Sakram et al. | Benzo [h] thiazolo [2, 3-b] quinazolines by an efficient p-toluenesulfonic acid-catalyzed one-pot two-step tandem reaction | |
| CN112079826A (en) | Steroid synthetase inhibitor and treatment application thereof | |
| RU2051153C1 (en) | Derivatives of 6-aryl-5,6-dihydroimidazo-[2,1-b]-thiazole or their pharmaceutically acceptable acidic salts, or their stereochemical isomeric forms showing immunostimulating activity, method of synthesis, 2-iminothiazole derivatives or their pharmaceutically acceptable acidic salts, or their stereochemical isomeric forms as intermediate products for synthesis of derivatives of 6-aryl-5,6-dihydroimidazo-[2,1-b]-thiazole, immunostimulating composition | |
| Pellegatti et al. | Synthesis of [1, 2, 4, 5] tetrazino [6′, 1′: 2, 3] imidazo [4, 5-c] isoquinolin-5-ones by microwave-assisted three-component reaction | |
| CN102250081A (en) | Imidazolidinyl- or thiazolidinyl-containing 1,3,4-thiadiazole compounds and preparation method thereof | |
| JP5198562B2 (en) | Synthesis of substituted-3-aminopyrazoles | |
| Li et al. | Synthesis and bioactivity of a novel series of 3, 6-disubstituted 1, 2, 4-triazolo [3, 4-b]-1, 3, 4-thiadiazoles | |
| WO2015129813A1 (en) | Deuteration method and deuteration catalyst | |
| TWI716060B (en) | Regioselective one-step process for synthesizing 2-hydroxyquinoxaline | |
| oglu Askerov et al. | New 2, 4-dihydro-1H-1, 2, 4-triazole-3-selones and 3, 3′-di (4H-1, 2, 4-triazolyl) diselenides. Synthesis, biological evaluation, and in silico studies as antibacterial and fungicidal agents | |
| Lashmanova et al. | Nitrosation of 5 H-thiazolo [3, 2-a] pyrimidin-3 (2 H)-ones | |
| Gaafar et al. | Chemical synthesis of some novel 6-aminouracil-2-thiones and their glycoside analogues | |
| JP4030683B2 (en) | Synthesis method of benzamide derivatives | |
| Zheng et al. | Facile Synthesis, Single‐Crystal Structure, and Biological Evaluation of Novel Pyrazolo [5, 1‐d][1, 2, 5] triazepin‐4‐ones | |
| Komarova et al. | Synthesis of derivatives of a new heterocyclic system pyrazolo [3, 4-b] pyrido [1′, 2′: 1, 2] imidazo [4, 5-d] pyridine | |
| CN104693198B (en) | 3 (1,2,4 triazoles simultaneously [4,3 a] 3 base of pyridine) 4 (3 base of 1H indoles) maleimide analog derivative and its preparation method and application | |
| Shashiprabha et al. | A novel reaction of 2-phenacyl mercaptoimidazole with acetic anhydride: formation of an imidazothiazole with loss of a phenyl group | |
| Liu et al. | Synthesis of some new substituted ethanone hydrazones containing 1H‐1, 2, 4‐triazole and thiazole | |
| Kumar et al. | Synthesis of novel 1, 3, 4-oxadiazole analogues with expected antibacterial activity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20111123 |