CN116283827A - Preparation method of N-acyl 2-aminobenzothiazole and derivatives thereof - Google Patents
Preparation method of N-acyl 2-aminobenzothiazole and derivatives thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims description 32
- 239000003054 catalyst Substances 0.000 claims description 29
- 239000007800 oxidant agent Substances 0.000 claims description 29
- 230000001590 oxidative effect Effects 0.000 claims description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 15
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 9
- 239000007810 chemical reaction solvent Substances 0.000 claims description 8
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 101001053401 Arabidopsis thaliana Acid beta-fructofuranosidase 3, vacuolar Proteins 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims description 2
- 239000012969 di-tertiary-butyl peroxide Substances 0.000 claims description 2
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- UHGULLIUJBCTEF-UHFFFAOYSA-N 2-aminobenzothiazole Chemical compound C1=CC=C2SC(N)=NC2=C1 UHGULLIUJBCTEF-UHFFFAOYSA-N 0.000 abstract description 9
- 238000005691 oxidative coupling reaction Methods 0.000 abstract description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
- 239000007787 solid Substances 0.000 description 11
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 108010070743 3(or 17)-beta-hydroxysteroid dehydrogenase Proteins 0.000 description 1
- GUCPYIYFQVTFSI-UHFFFAOYSA-N 4-methoxybenzamide Chemical class COC1=CC=C(C(N)=O)C=C1 GUCPYIYFQVTFSI-UHFFFAOYSA-N 0.000 description 1
- 102100034067 Dehydrogenase/reductase SDR family member 11 Human genes 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- RFPQSFCICWNNNL-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)-3-methylbenzamide Chemical compound CC1=CC=CC(C(=O)NC=2SC3=CC=CC=C3N=2)=C1 RFPQSFCICWNNNL-UHFFFAOYSA-N 0.000 description 1
- AILFLXLQHGXWAO-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)-4-chlorobenzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NC1=NC2=CC=CC=C2S1 AILFLXLQHGXWAO-UHFFFAOYSA-N 0.000 description 1
- FTKQRUKADZDJIM-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=NC2=CC=CC=C2S1 FTKQRUKADZDJIM-UHFFFAOYSA-N 0.000 description 1
- WAWUISYKAPVPKW-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)-4-methylbenzamide Chemical compound C1=CC(C)=CC=C1C(=O)NC1=NC2=CC=CC=C2S1 WAWUISYKAPVPKW-UHFFFAOYSA-N 0.000 description 1
- GOKOILBJPWVKQU-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)-4-nitrobenzamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)NC1=NC2=CC=CC=C2S1 GOKOILBJPWVKQU-UHFFFAOYSA-N 0.000 description 1
- FZVLVMRGZRRBFD-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)benzamide Chemical compound N=1C2=CC=CC=C2SC=1NC(=O)C1=CC=CC=C1 FZVLVMRGZRRBFD-UHFFFAOYSA-N 0.000 description 1
- UWUNYOLFEWOXPK-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)pyridine-3-carboxamide Chemical compound N=1C2=CC=CC=C2SC=1NC(=O)C1=CC=CN=C1 UWUNYOLFEWOXPK-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229960004181 riluzole Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/82—Nitrogen atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Catalysts (AREA)
Abstract
The invention provides a preparation method of N-acyl 2-aminobenzothiazole and derivatives thereof, which is characterized in that FeCl 3 And in the presence of TBHP, the oxidative coupling reaction of aldehyde and 2-aminobenzothiazole is smoothly carried out, so that the corresponding product is generated, and the yield is good.
Description
Technical Field
The invention relates to pharmaceutical chemistry, in particular to a preparation method of N-acyl 2-aminobenzothiazole and derivatives thereof.
Background
Functionalized 2-aminobenzothiazoles are an important class of heterocycles that exist in many biologically active natural products and drugs. Such as riluzole (P.Jimonet, F.Audiau, M.Barreau, J.Med.Chem.1999,42,2828) for use in the treatment of Amyotrophic Lateral Sclerosis (ALS). 2-aminobenzothiazoles replace the inner ring nitrogen with potential biological properties. In functionalized N-acyl 2-aminobenzothiazoles, the 4-methoxybenzamide derivative is an inhibitor of 17- β -hydroxysteroid dehydrogenase 1 (R.Hartmann, M.Frotscher, S.Marchais-Oberwinkler, PCT Int. Appl., WO 2012025638,Mar 1,2012.).
Because of the wide range of biological properties exhibited by such compounds, the development of a simple and easy-to-implement 2-aminobenzothiazole functional synthesis strategy has attracted considerable attention from organic chemists. The traditional synthetic method for N-acyl 2-aminobenzothiazoles is the reaction of 2-aminobenzothiazoles with the corresponding carboxylic acid/derivative (r.m. de Figueiredo, j. -s.supplo and j. -M.Campagne, chem.Rev.,2016,116.). In most cases, this process requires coupling reagents and produces stoichiometric by-products.
Main content
The invention aims to provide a preparation method of N-acyl 2-aminobenzothiazole and derivatives (formula III) thereof.
In order to achieve the above purpose, the technical scheme of the invention is as follows:
the preparation method of the N-acyl 2-aminobenzothiazole and the derivatives thereof is prepared by reacting a compound shown in a formula I with a compound shown in a formula II under the action of a catalyst and an oxidant, and the synthetic route is as follows:
wherein R is H, one or more C 1-6 Alkyl or cycloalkyl, one or more OC 1-6 Alkoxy, phenyl, nitro, one or more halogens or one or more halogen substituted halogenated C 1-6 An alkyl group.
The catalyst is selected from CuI and CuCl 2 、FeCl 3 、NiCl 2 One or a combination of a plurality of the above;
the oxidant is selected from TBHP, H 2 O 2 One or more of DTBP and TEMPO.
Further, in the above method, the catalyst is selected from CuCl 2 、FeCl 3 、NiCl 2 One or a combination of more than one of the above, wherein the oxidant is selected from TBHP.
Further, in the above method, the catalyst is selected from FeCl 3 The oxidizing agent is selected from TBHP.
Further, in the above method, the catalyst is used in an amount of 0.1 to 0.2mol%.
Further, in the above method, the amount of the oxidizing agent is 1 to 4 equivalents.
Further, in the above method, the compound of formula II is used in an amount of 1 to 2 equivalents.
Further, in the above method, the reaction temperature is 80 to 100 ℃.
Further, in the above method, the reaction solvent is 1, 2-dichloroethane or toluene.
The above compound of formula III is selected from the following compounds:
the preparation method of the compound of the formula IV-3 is characterized in that the compound of the formula IV-1 and the compound of the formula IV-2 react under the action of a catalyst and an oxidant, and the synthetic route is as follows:
the catalyst is selected from FeCl 3 The oxidant is selected from TBHP; the catalyst is used in an amount of 0.1-0.2mol%, the oxidant is used in an amount of 1-4 equivalents, the compound of formula IV-2 is used in an amount of 1-2 equivalents, the reaction temperature is 80-100 ℃, and the reaction solvent is 1, 2-dichloroethane or toluene.
The preparation method of the compound of the formula V-3 is characterized in that the compound of the formula V-1 and the compound of the formula V-2 react under the action of a catalyst and an oxidant, and the synthetic route is as follows:
the catalyst is selected from FeCl 3 The oxidant is selected from TBHP; the catalyst is used in an amount of 0.1-0.2mol%, the oxidant is used in an amount of 1-4 equivalents, the compound of formula V-2 is used in an amount of 1-2 equivalents, the reaction temperature is 80-100 ℃, and the reaction solvent is 1, 2-dichloroethane or toluene.
The preparation method of the compound of the formula VI-3 is characterized in that the compound of the formula VI-1 and the compound of the formula VI-2 react under the action of a catalyst and an oxidant, and the synthetic route is as follows:
the catalyst is selected from FeCl 3 The oxidant is selected from TBHP; the catalyst is used in an amount of 0.1 to 0.2mol percentThe amount of the oxidant is 1-4 equivalents, the amount of the compound of the formula VI-2 is 1-2 equivalents, the reaction temperature is 80-100 ℃, and the reaction solvent is 1, 2-dichloroethane or toluene.
The beneficial effects are that:
the invention provides a method for efficiently synthesizing N-acyl-2-aminobenzothiazole. In FeCl 3 And in the presence of TBHP, the oxidative coupling reaction of aldehyde and 2-aminobenzothiazole is smoothly carried out, so that the corresponding product is generated, and the yield is good.
Detailed Description
The present invention is described in detail below by way of specific examples, which are given herein for the purpose of further illustration only and are not to be construed as limiting the scope of the present invention, as many insubstantial modifications and variations of the present invention will become apparent to those skilled in the art in light of the foregoing disclosure. The raw materials and the reagents used in the invention are all commercial products. Except for special descriptions, the parts are parts by weight, and the percentages are mass percentages.
Example 1
Into a 25ml round bottom flask was charged 2-aminobenzothiazole 1a (0.7 mmol,1.0 equiv), benzaldehyde 2a (1.05 mmol,1.5 equiv) derivatives, TBHP (2.1 mmol,3 equiv) and FeCl 3 (0.07 mmol,0.1 equiv) in 1, 2-dichloroethane as solvent was stirred at 100deg.C for 6h. After the reaction was completed, the mixture was extracted with saturated NaCl solution and dichloromethane, and the organic layer was extracted with anhydrous Na 2 SO 4 And (5) drying. After the solvent is removed under reduced pressure, petroleum ether/ethyl acetate is used as an eluent, and the purified product is obtained through column chromatography separation.
Results and discussion
Referring to the procedure of example 1, in a preliminary experiment, benzaldehyde and 2-aminobenzothiazole were treated with CuI as a catalyst in the presence of TBHP and the progress of the reaction was monitored by TLC. However, under this condition, the yield of N-acyl-2-aminobenzothiazole was only 35% (Table 1, entry 1). The influence of other conditions on the reaction was investigated later, and FeCl can be seen from the table 3 The catalytic effect of (a) is best (Table 1, entries 2-4). The reaction was then affected by exposure to TBHP and temperature,experiments have shown that when the TBHP is 3 equivalents, the reflection is optimal when the temperature is raised to 100 ℃ (Table 1, entries 5-7). Further experiments have found that when FeCl 3 When the amount of (a) was reduced from 0.2 to 0.1 equivalents, almost the same yield was obtained (table 1, item 8). Other oxidants were then tried on this basis, and the results indicate that only TBHP can effect the synthesis of N-acyl-2-aminobenzothiazole.
TABLE 1 optimization of reaction conditions a
a Reaction conditions: 1a (0.7 mmol,1.0 equiv), 2a (1.05 mmol,1.5 equiv), solvent (2 ml), 6h.
b The yield was isolated.
To verify the versatility of the reaction scheme, reaction studies were performed on a variety of aldehydes under optimized reaction conditions. Containing electron donors (-CH) 3 ,-OCH 3 ) Or electron withdrawing groups (-Cl, -Br, and-NO) 2 ) Has good tolerance and provides the corresponding products in moderate to excellent yields (3 a-3 f). Under this condition, excellent yields (3 g, 3 h) can also be provided when the benzene ring is exchanged for pyridine ring and naphthalene ring. In addition, isobutyraldehyde can also participate in this reaction with a yield of 81% (3 k).
TABLE 2 substrate extension
It can be seen that in the present invention, in FeCl 3 And in the presence of TBHP, the oxidative coupling reaction of aldehyde and 2-aminobenzothiazole is smoothly carried out, so that the corresponding product is generated, and the yield is good.
Nuclear magnetic data
N-(benzo[d]thiazol-2-yl)benzamide(3a).white solid(0.160g,92％yield).
1 H NMR(600MHz,DMSO-d 6 )δ12.90(s,1H),8.18–8.13(m,2H),8.03(dd,J＝7.9,1.2Hz,1H),7.80(d,J＝8.0Hz,1H),7.70–7.64(m,1H),7.58(t,J＝7.8Hz,2H),7.48(ddd,J＝8.3,7.2,1.3Hz,1H),7.35(td,J＝7.7,7.2,1.1Hz,1H). 13 C NMR(151 MHz,DMSO)δ166.40,159.20,133.35,132.37,132.01,129.12,128.80,126.66,124.17,122.22,120.91.
N-(benzo[d]thiazol-2-yl)-4-methylbenzamide(3ba).white solid(0.16g,87％).
1 H NMR(600 MHz,DMSO-d 6 )δ12.81(s,1H),8.09–8.05(m,2H),8.05–8.00(m,1H),7.79(d,J＝8.1 Hz,1H),7.47(ddd,J＝8.3,7.2,1.3 Hz,1H),7.38(d,J＝8.0 Hz,2H),7.35(ddd,J＝8.1,7.2,1.1 Hz,1H),2.41(s,3H). 13 C NMR(151 MHz,DMSO)δ166.16,143.69,132.03,129.68,128.84,126.62,124.10,122.18,120.88,21.58.
N-(benzo[d]thiazol-2-yl)-3-methylbenzamide(3bb).white solid(0.15g,84％).
1 H NMR(600 MHz,DMSO-d6)δ12.83(s,1H),8.03(dd,J＝8.1,1.2 Hz,1H),8.01–7.98(m,1H),7.96(dd,J＝7.4,1.7 Hz,1H),7.80(d,J＝8.1 Hz,1H),7.51–7.43(m,3H),7.35(ddd,J＝8.2,7.2,1.2 Hz,1H),2.41(s,3H). 13 C NMR(151 MHz,DMSO)δ166.49,159.28,138.51,133.93,132.33,131.98,129.33,129.00,126.64,125.91,124.14,122.21,120.85,21.35.
N-(benzo[d]thiazol-2-yl)-2-methylbenzamide(3bc).white solid(0.15g,83％).
1 H NMR(600 MHz,DMSO-d 6 )δ12.75(s,1H),8.05–8.00(m,1H),7.79(d,J＝8.0Hz,1H),7.63(dt,J＝7.8,1.8 Hz,1H),7.46(dddd,J＝7.6,6.3,5.0,1.3 Hz,2H),7.37–7.31(m,3H),2.45(s,3H) 13 C NMR(151 MHz,DMSO)δ168.69,158.68,148.96,136.91,134.23,131.97,131.35,131.34,128.63,126.63,126.20,124.15,122.18,121.01,20.10.
N-(benzo[d]thiazol-2-yl)-4-methoxybenzamide(3c).white solid(0.15g,79％).
1 H NMR(600 MHz,DMSO-d 6 )δ12.72(s,1H),8.19–8.14(m,2H),8.01(d,J＝7.9Hz,1H),7.78(d,J＝8.1 Hz,1H),7.46(t,J＝7.6 Hz,1H),7.33(t,J＝7.5 Hz,1H),7.12–7.07(m,2H),3.86(s,3H). 13 C NMR(151 MHz,DMSO)δ165.63,163.41,159.42,132.03,130.92,126.58,124.35,124.02,122.14,120.78,114.43,56.02.
N-(benzo[d]thiazol-2-yl)-4-nitrobenzamide(3d).white solid(0.19g,95％).
1 H NMR(600 MHz,DMSO-d 6 )δ13.28(s,1H),8.39–8.34(m,4H),8.03(d,J＝7.9Hz,1H),7.78(d,J＝8.1 Hz,1H),7.49(ddd,J＝8.2,7.2,1.3 Hz,1H),7.36(td,J＝7.6,1.1 Hz,1H). 13 C NMR(151 MHz,DMSO)δ150.21,130.39,126.87,124.40,124.10,122.43.
N-(benzo[d]thiazol-2-yl)-4-chlorobenzamide(3e).white solid(0.18g,94％).
1 H NMR(600 MHz,DMSO-d 6 )δ12.98(s,1H),8.17–8.14(m,2H),8.04–7.99(m,1H),7.79(d,J＝8.1 Hz,1H),7.67–7.61(m,2H),7.47(ddd,J＝8.3,7.2,1.3 Hz,1H),7.34(td,J＝7.6,7.2,1.1 Hz,1H). 13 C NMR(151 MHz,DMSO)δ138.24,131.88,130.74,129.21,126.71,124.23,122.27,120.85.
N-(benzo[d]thiazol-2-yl)-4-bromobenzamide(3f).white solid(0.21g,94％).
1 H NMR(600 MHz,DMSO-d 6 )δ12.99(s,1H),8.11–8.05(m,2H),8.03(dd,J＝8.1,1.2 Hz,1H),7.82–7.76(m,3H),7.48(ddd,J＝8.2,7.2,1.3 Hz,1H),7.35(ddd,J＝8.1,7.2,1.1 Hz,1H). 13 C NMR(151 MHz,DMSO)δ132.17,130.87,127.32,126.72,124.24,122.28.
N-(benzo[d]thiazol-2-yl)nicotinamide(3g).white solid(0.16g,96％).
1 H NMR(600 MHz,DMSO-d 6 )δ12.21(s,1H),8.80(dd,J＝4.7,1.5 Hz,1H),8.23(dt,J＝7.8,1.1 Hz,1H),8.13(td,J＝7.7,1.7 Hz,1H),8.06(dd,J＝8.0,1.2 Hz,1H),7.83(d,J＝8.0 Hz,1H),7.76(ddd,J＝7.6,4.7,1.1 Hz,1H),7.49(ddd,J＝8.2,7.2,1.3 Hz,1H),7.40–7.33(m,1H). 13 C NMR(151 MHz,DMSO)δ163.97,157.85,
149.53,149.07,148.25,138.79,132.21,128.43,126.76,124.40,123.66,122.33,121.31.
N-(benzo[d]thiazol-2-yl)-2-naphthamide(3h).white solid(0.19g,95％).
1 H NMR(600 MHz,DMSO-d 6 )δ13.04(s,1H),8.86(d,J＝1.8 Hz,1H),8.18(dd,J＝8.5,1.8 Hz,1H),8.12–8.06(m,2H),8.06–8.01(m,2H),7.81(d,J＝8.0 Hz,1H),7.67(dddd,J＝22.9,8.1,6.8,1.3 Hz,2H),7.48(ddd,J＝8.3,7.2,1.3 Hz,1H),7.38–7.32(m,1H). 13 C NMR(151 MHz,DMSO)δ135.29,132.47,131.99,130.01,129.78,128.98,128.75,128.19,127.51,126.68,124.80,124.17,122.25,120.84.
N-(benzo[d]thiazol-2-yl)-2-methylpropanamide(3k).white solid(0.12g,81％).
1 H NMR(600 MHz,DMSO-d 6 )δ12.32(s,1H),7.98(d,J＝7.9 Hz,1H),7.76–7.72(m,1H),7.44(dd,J＝8.2,7.0 Hz,1H),7.30(t,J＝7.6 Hz,1H),2.81(p,J＝6.9 Hz,1H),1.16(d,J＝6.9 Hz,6H). 13 C NMR(151 MHz,DMSO)δ176.58,158.54,149.02,131.94,126.51,123.88,122.11,120.88,34.50,19.48.。
Claims (9)
1. The preparation method of the N-acyl 2-aminobenzothiazole and the derivatives thereof (formula III) comprises the steps of reacting a compound of formula I with a compound of formula II under the action of a catalyst and an oxidant, wherein the synthetic route is as follows:
wherein R is H, one or more C 1-6 Alkyl or cycloalkyl, one or more OC 1-6 Alkoxy, phenyl, nitro, one or more halogens or one or more halogen substituted halogenated C 1-6 An alkyl group;
the catalyst is selected from CuI and CuCl 2 、FeCl 3 、NiCl 2 One or a combination of a plurality of the above;
the oxidant is selected from TBHP, H 2 O 2 One or more of DTBP and TEMPO.
2. The method of claim 1, wherein: the catalyst is selected from CuCl 2 、FeCl 3 、NiCl 2 One or a combination of more than one of the above, wherein the oxidant is selected from TBHP.
3. The method of claim 1, wherein: the catalyst is selected from FeCl 3 The oxidizing agent is selected from TBHP.
4. A method according to any one of claims 1-3, wherein: the catalyst is used in an amount of 0.1 to 0.2mol%; the dosage of the oxidant is 1-4 equivalents; the compound of formula II is used in an amount of 1-2 equivalents.
5. The method of claim 4, wherein: the reaction temperature is 80-100 ℃; the reaction solvent is 1, 2-dichloroethane or toluene.
6. A method according to any one of claims 1-3, wherein: the compound of formula III is selected from the following compounds:
7. the preparation method of the compound of the formula IV-3 is characterized in that the compound of the formula IV-1 and the compound of the formula IV-2 react under the action of a catalyst and an oxidant, and the synthetic route is as follows:
the catalyst is selected from FeCl 3 The oxidant is selected from TBHP; the catalyst is used in an amount of 0.1-0.2mol%, the oxidant is used in an amount of 1-4 equivalents, the compound of formula IV-2 is used in an amount of 1-2 equivalents, the reaction temperature is 80-100 ℃, and the reaction solvent is 1, 2-dichloroethane or toluene.
8. The preparation method of the compound of the formula V-3 is characterized in that the compound of the formula V-1 and the compound of the formula V-2 react under the action of a catalyst and an oxidant, and the synthetic route is as follows:
the catalyst is selected from FeCl 3 The oxidant is selected from TBHP; the catalyst is used in an amount of 0.1-0.2mol%, the oxidant is used in an amount of 1-4 equivalents, the compound of formula V-2 is used in an amount of 1-2 equivalents, the reaction temperature is 80-100 ℃, and the reaction solvent is 1, 2-dichloroethane or toluene.
9. The preparation method of the compound of the formula VI-3 is characterized in that the compound of the formula VI-1 and the compound of the formula VI-2 react under the action of a catalyst and an oxidant, and the synthetic route is as follows:
the catalyst is selected from FeCl 3 The oxidant is selected from TBHP; the catalyst is used in an amount of 0.1 to 0.2mol%, the oxidant is used in an amount of 1 to 4 equivalents, the compound of the formula VI-2 is used in an amount of 1 to 2 equivalents, the reaction temperature is 80 to 100 ℃, and the reaction solvent is 1, 2-dichloroethane or toluene.
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| CN108976216A (en) * | 2018-09-07 | 2018-12-11 | 江苏工程职业技术学院 | A kind of preparation method of prucalopride |
| CN114591320A (en) * | 2020-12-05 | 2022-06-07 | 鲁南制药集团股份有限公司 | Preparation method of zolpidem |
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