CN117756746A - Preparation method of cyclic sulfonamide compound - Google Patents
Preparation method of cyclic sulfonamide compound Download PDFInfo
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- CN117756746A CN117756746A CN202310475339.6A CN202310475339A CN117756746A CN 117756746 A CN117756746 A CN 117756746A CN 202310475339 A CN202310475339 A CN 202310475339A CN 117756746 A CN117756746 A CN 117756746A
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- borane
- heterocyclic carbene
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- -1 cyclic sulfonamide compound Chemical class 0.000 title claims abstract description 85
- 229940124530 sulfonamide Drugs 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- 239000002904 solvent Substances 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 19
- ADLVDYMTBOSDFE-UHFFFAOYSA-N 5-chloro-6-nitroisoindole-1,3-dione Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC2=C1C(=O)NC2=O ADLVDYMTBOSDFE-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229910000085 borane Inorganic materials 0.000 claims abstract description 18
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000003054 catalyst Substances 0.000 claims abstract description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 239000012043 crude product Substances 0.000 claims abstract description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
- 125000004185 ester group Chemical group 0.000 claims abstract description 3
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
- 150000002367 halogens Chemical class 0.000 claims abstract description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 3
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract 4
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 2
- RSVHGEGGKUXRBR-UHFFFAOYSA-N methylideneboron Chemical compound C=[B] RSVHGEGGKUXRBR-UHFFFAOYSA-N 0.000 claims abstract 2
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 238000010898 silica gel chromatography Methods 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000003208 petroleum Substances 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 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical group [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 239000002274 desiccant Substances 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- HDXFCPZKMFTOLH-UHFFFAOYSA-N 1-amino-2,3-dihydroinden-1-ol Chemical compound C1=CC=C2C(N)(O)CCC2=C1 HDXFCPZKMFTOLH-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 230000008901 benefit Effects 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 2
- 230000009467 reduction Effects 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- 238000012512 characterization method Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- LAQFLZHBVPULPL-UHFFFAOYSA-N methyl(phenyl)silicon Chemical compound C[Si]C1=CC=CC=C1 LAQFLZHBVPULPL-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- UZZFAJJFAZNWOO-UHFFFAOYSA-N 2-amino-1H-inden-1-ol Chemical compound NC=1C(C2=CC=CC=C2C1)O UZZFAJJFAZNWOO-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- KLYCPFXDDDMZNQ-UHFFFAOYSA-N Benzyne Chemical compound C1=CC#CC=C1 KLYCPFXDDDMZNQ-UHFFFAOYSA-N 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 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
- 230000002349 favourable effect Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- PBDBXAQKXCXZCJ-UHFFFAOYSA-L palladium(2+);2,2,2-trifluoroacetate Chemical group [Pd+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F PBDBXAQKXCXZCJ-UHFFFAOYSA-L 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000001010 sulfinic acid amide group Chemical group 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
The invention relates to a preparation method of a cyclic sulfonamide compound, which specifically comprises the following steps: stirring the cyclic imine and the solvent at room temperature, and then adding a catalyst nitrogen heterocyclic carbene borane for reaction; extracting after the reaction is finished, and purifying the residual crude product to obtain an amine compound; the reaction equation is as follows:r in the cyclic imine and amine compound 1 Comprising hydrogen atoms, ester groups, C1-C4 alkyl or aryl groups, X 1 Comprising oxygen atoms or sulfur atoms directly attached to carbon atoms at both ends, R 2 And X 2 Selecting one of the connections, R 2 Comprising hydrogen atoms, methoxy groups, C1-C4 alkyl or aryl groups, X 2 Is halogen; the molecular structural formula of the N-heterocyclic carbene borane is as follows:the N-heterocyclic carbene boraneR in (B) 3 Including C1-C4 alkyl or aryl. Compared with the prior art, the method has the advantages of rapid reduction of the cyclic imine compound, mild reaction conditions, simple and efficient process and high total yield.
Description
Technical Field
The invention belongs to the technical field of organic chemistry and medical intermediates, and relates to a preparation method of a cyclic sulfonamide compound.
Background
The sulfonamide compound is an important skeleton structure of a plurality of drug molecules, and has important significance in a plurality of chemical fields such as organic synthesis, biochemistry and the like.
The existing preparation method of the cyclic sulfonamide compound mainly comprises the following steps:
(1)
(2)
the first method (bioorg. Med. Chem.2006,14, 8386-8395.): the cyclic imine was dissolved in methanol solvent under argon, cooled to 0 ℃, and 1.1 equivalent of sodium borohydride was added to react for 30min, to obtain 43% yield. The reaction is rapid and relatively simple, but the yield is low.
The second method (Eur.J.Org.chem.2019, 38, 6550-6556.): cyclic imine and 0.05mol% of B (C) 6 F 5 ) 3 Toluene was added via syringe and stirred for 5min, 4 equivalents of methylphenylsilane were added and reacted at 25℃for 24h, yielding 99% yield. The reaction achieves high yield and has wider applicability to cyclic imines. However, the reaction operation is relatively complicated, the required equivalent weight of the methylphenyl silane is large, and the reaction time is long.
Thus, the method II has relatively wide applicability and high yield, but the method I has certain practicability under the condition that the yield is not pursued, but at least one defect of long reaction time, complex operation and low yield exists in the two routes.
Patent CN101665470a discloses a method for stereospecifically synthesizing cyclic sulfoxide imine, sulfinamide and sulfonamide, under the condition of room temperature, reacting sulfinimide and a benzyne precursor for 1-15h under the initiation of CsF in an organic solvent to generate cyclic sulfoxide imine; when the cyclic sulfoxide imine contains sulfonyl, the cyclic sulfoxide imine contains Mg/HOAc/AcONaDMF/H 2 Under the condition of O, the sulfonyl in the molecule can be smoothly removed to obtain the cyclic sulfoxide imine; cyclic sulfoximines are formed in HCl (Dioxane) Under the condition, the catalyst can be smoothly converted into cyclic sulfinamide; the cyclic sulfonamide is oxidized by mCPBA to give the cyclic sulfonamide. However, the preparation process of the patent uses a benzene alkyne precursor, and also prepares HCl (Dioxane) solution, and the reaction is carried out at the temperature of minus 78 ℃ under relatively harsh conditions.
Patent CN101260085a discloses a method for synthesizing chiral gamma-sultam by catalytic asymmetric hydrogenation, wherein the catalytic system used is a chiral biphosphine complex of palladium. The reaction can be carried out under the following conditions, temperature: 25-75 ℃; solvent: 2, 2-trifluoroethanol; pressure: 35-40 atmospheres; time: and 10-12h. The ratio of substrate to catalyst was 50:1; the metal precursor of the catalyst is palladium trifluoroacetate; the chiral ligand is chiral biphosphine ligand; the preparation method of the catalyst comprises the following steps: the metal precursor of palladium and chiral biphosphine ligand are stirred in acetone at room temperature, then vacuum concentration is carried out to obtain a catalyst, and the corresponding chiral three-position substituted gamma-sultam can be obtained by hydrogenating the cyclic sulfimide. However, the reaction in this patent requires pressurization and a special device; noble metals and chiral ligands are needed in the system, and a certain cost is increased.
Disclosure of Invention
The invention aims to overcome at least one defect in the prior art and provide a preparation method of a cyclic sulfonamide compound.
The aim of the invention can be achieved by the following technical scheme:
the technical scheme of the invention is that a preparation method of a cyclic sulfonamide compound is provided, and the method comprises the following steps:
(1) Under the room temperature condition, adding cyclic imine (compound I) and Solvent (Solvent) into a reactor, stirring, and then adding a catalyst N-heterocyclic carbene borane (NHC-boron) for reaction, wherein the N-heterocyclic carbene borane is simultaneously used as a hydrogen source;
(2) Extracting after the reaction is finished, and purifying the residual crude product to obtain an amine compound (compound II);
the reaction equation is as follows:
r in the cyclic imine and amine compound 1 Comprising hydrogen atoms, ester groups, C1-C4 alkyl or aryl groups, X 1 Comprising oxygen atoms or sulfur atoms directly attached to carbon atoms at both ends (i.e. X 1 Not present), R 2 And X 2 Selecting one of the connections, R 2 Comprising hydrogen atoms, methoxy groups, C1-C4 alkyl or aryl groups, X 2 Is halogen;
the molecular structural formula of the N-heterocyclic carbene borane is as follows:
r in the N-heterocyclic carbene borane 3 Including C1-C4 alkyl or aryl.
Further, R in the cyclic imine and amine compound 1 Comprising hydrogen atoms, methyl, ethyl groups, phenyl groups or substituted phenyl groups, R 2 Comprising hydrogen atoms, methyl, methoxy or benzyl groups, X 2 Including chlorine or bromine.
As a preferable technical scheme, R in the cyclic imine and amine compound 1 Comprising hydrogen atoms or ethyl groups, R 2 Comprising hydrogen atoms, methyl groups or methoxy groups, X 2 Is bromine.
Further, R in the N-heterocyclic carbene borane 3 Including methyl, ethyl, propyl or isopropyl.
As a preferred technical scheme, R in the N-heterocyclic carbene borane 3 Is methyl.
Further, the molar ratio of the cyclic imine to the N-heterocyclic carbene borane is 1 (0.3-1.0), and the dosage ratio of the cyclic imine to the solvent is 1mol (1-4L).
Further, the reaction time is 0.5-2.0h.
Further, in the step (1), the solvent is an alcohol.
Further, the solvent in the step (1) comprises methanol, ethanol, isopropanol or aminoindanol.
As a preferable technical scheme, the solvent in the step (1) is methanol.
Further, the extractant in the step (2) comprises ethyl acetate or dichloromethane.
Further, the step (2) specifically comprises: after the reaction is finished, the reaction solution is concentrated, extracted, washed with water, dried, and then the residual crude product is subjected to silica gel column chromatography purification.
Further, the water washing agent is saturated saline, the drying agent is anhydrous sodium sulfate or anhydrous magnesium sulfate, the silica gel column chromatography eluent is a mixed solution of ethyl acetate and petroleum ether, and the volume ratio of the ethyl acetate to the petroleum ether is 1 (2-4).
Compared with the prior art, the invention has the following advantages:
the method for preparing the sulfonamide compound by adopting the reduction imine uses the N-heterocyclic carbene borane to provide a hydrogen source, reduces the imine in an alcohol solvent, has mild reaction condition, rapid reaction and high yield, does not need complex reagents, has small dosage of the N-heterocyclic carbene borane, is green and economic, is favorable for industrial production, and can create larger economic benefit.
Detailed Description
The present invention will be described in detail with reference to specific examples. The present embodiment is implemented on the premise of the technical scheme of the present invention, and a detailed implementation manner and a specific operation process are given, but the protection scope of the present invention is not limited to the following examples.
The equipment used in the following examples is representative of conventional equipment in the art unless otherwise specified; unless otherwise indicated, all reagents used are commercially available or prepared by methods conventional in the art, and all of the following examples, not specifically described, are accomplished by means of conventional experimentation in the art.
Solvents, extractants, water washes, desiccants, and the like used in the examples were all purchased from a research platform, and the cyclic imines were prepared according to literature methods (org. Lett.2016,18 (4): 692-695), and the azacarbene boranes were prepared according to literature methods (j. Am. Chem. Soc.2010,132 (7): 2350-2358).
Example 1:
a cyclic sulfonamide compound and a preparation method thereof, wherein the reaction equation is as follows:
the method comprises the following specific steps:
cyclic imine I-a (45.75 mg,0.25 mmol) was dissolved in anhydrous methanol solvent (1.0 mL) at room temperature and R was added with stirring 3 Methyl substituted N-heterocyclic carbene borane catalyst (9.625 mg,0.0875 mmol), stirring at room temperature for 30min, concentrating the reaction solution by rotary evaporator, extracting with dichloromethane (10 mL×3), saturated saline washing, drying with anhydrous sodium sulfate, purifying the crude product by silica gel column chromatography to obtain white solid product amine compound II-a (42.5 mg, yield 92%).
The nuclear magnetic characterization data are as follows:
1 H NMR(400MHz,Chloroform-d)δ7.29(t,J＝7.9Hz,1H),7.20–7.08(m,2H),6.94(d,J＝8.3Hz,1H),4.91(s,1H),4.62(s,2H). 13 C NMR(101MHz,Chloroform-d)δ151.60,129.23,126.58,125.26,118.55,118.21,46.36.
examples 2 to 4:
a process for preparing cyclic sulfonamide compounds, which is substantially the same as in example 1, except that different R's are used 3 The reaction results are shown in Table 1.
TABLE 1 reaction results of I-a in different catalysts
| Examples | Substituent R 3 | Yield rate a (％) |
| 2 | Ethyl group | 85 |
| 3 | Propyl group | 80 |
| 4 | Isopropyl group | 75 |
In Table 1, the superscript a indicates the isolation yield.
Examples 5 to 7:
a process for preparing cyclic sulfonamide compounds was substantially the same as in example 1, except that different solvents were used, and the reaction results were as shown in Table 2.
TABLE 2 reaction results of I-a in different solvents
| Examples | Solvent(s) | Yield rate a (％) |
| 5 | Ethanol | 86 |
| 6 | Isopropyl alcohol | 80 |
| 7 | Amino indenol | 76 |
In Table 2, the superscript a indicates the isolation yield.
Examples 8 to 10:
a process for preparing cyclic sulfonamides is essentially the same as in example 1, except that different amounts of the N-heterocyclic carbene borane catalyst are used and the reaction results are shown in Table 3.
TABLE 3 reaction results of I-a in different amounts of catalyst
| Examples | Amount of substance (mmol) | Yield rate a (％) |
| 8 | 0.125 | 93 |
| 9 | 0.25 | 93 |
| 10 | 0.075 | 85 |
In Table 3, the superscript a indicates the isolation yield.
As shown in tables 1 to 3, 0.0875mmol of methyl-substituted azacyclo-carbene borane catalyst, 1.0mL of methanol solvent, is the optimal reaction condition for the reaction of 0.25mmol of I-a (example 1), under which the yield of the product can reach 92%. Although examples 8 and 9 gave slightly higher yields, the amount of N-heterocyclic carbene borane was greater (insufficient) at this time, with example 1 being the optimal reaction condition.
Example 11:
a cyclic sulfonamide compound and a method for producing the same are substantially the same as in example 1 except that a different cyclic imine I-b (53.80 mg,0.25 mmol) is used, and the reaction equation is as follows:
the product amine compound II-b (48.9 mg, 91%) was obtained as a white solid.
The nuclear magnetic characterization data are as follows:
1 H NMR(400MHz,Chloroform-d)δ7.10(t,J＝8.0Hz,1H),6.89(d,J＝8.1Hz,1H),6.69(d,J＝7.8Hz,1H),4.80–4.71(m,1H),4.66(d,J＝7.9Hz,2H),3.87(s,3H). 13 C NMR(101MHz,Chloroform-d)δ144.03,137.27,132.78,130.10,125.01,120.99,45.58,21.66.
example 12:
a cyclic sulfonamide compound and a method for producing the same are substantially the same as in example 1, except that a different cyclic imine I-c (49.70 mg,0.25 mmol) is used, and the reaction equation is as follows:
the product amine compound II-c (45.8 mg, 92%) was obtained as a white solid.
The nuclear magnetic characterization data are as follows:
1 H NMR(400MHz,Chloroform-d)δ7.04–6.90(m,2H),6.80(s,1H),4.75(s,1H),4.61(s,2H),2.34(s,3H). 13 C NMR(101MHz,Chloroform-d)δ151.55,139.80,126.14,126.06,118.89,115.04,46.31,21.00.
example 13:
a cyclic sulfonamide compound and a method for producing the same are substantially the same as in example 1, except that a different cyclic imine I-d (53.80 mg,0.25 mmol) is used, and the reaction equation is as follows:
the product amine compound II-d (49.7 mg, 92.5%) was obtained as a white solid.
The nuclear magnetic characterization data are as follows:
1 H NMR(400MHz,Chloroform-d)δ7.01(d,J＝8.6Hz,1H),6.73(dd,J＝8.6,2.5Hz,1H),6.51(d,J＝2.5Hz,1H),4.85(s,1H),4.58(s,2H),3.78(s,3H). 13 C NMR(101MHz,Chloroform-d)δ160.27,152.43,127.06,109.93,103.57,46.03.
example 14:
a cyclic sulfonamide compound and a method for producing the same are substantially the same as in example 1, except that a different cyclic imine I-e (49.70 mg,0.25 mmol) is used, and the reaction equation is as follows:
the product amine compound II-e (45.8 mg, 92%) was obtained as a white solid.
The nuclear magnetic characterization data are as follows:
1 H NMR(400MHz,Chloroform-d)δ7.09(dd,J＝8.4,2.1Hz,1H),6.92(s,1H),6.87(d,J＝8.4Hz,1H),4.81(t,J＝8.2Hz,1H),4.59(d,J＝7.9Hz,2H),2.32(s,3H). 13 C NMR(101MHz,Chloroform-d)δ149.62,135.04,129.84,126.66,118.36,117.73,46.48,20.64.
example 15:
a cyclic sulfonamide compound and a method for producing the same are substantially the same as in example 1, except that a different cyclic imine I-f (53.80 mg,0.25 mmol) is used, and the reaction equation is as follows:
the product amine compound II-f (49.5 mg, 92%) was obtained as a white solid.
The nuclear magnetic characterization data are as follows:
1 H NMR(400MHz,Chloroform-d)δ6.91(d,J＝9.1Hz,1H),6.82(dd,J＝9.1,3.0Hz,1H),6.61(d,J＝2.9Hz,1H),4.85(d,J＝7.8Hz,1H),4.59(d,J＝6.0Hz,2H),3.78(s,3H). 13 C NMR(101MHz,Chloroform-d)δ156.68,145.44,119.54,118.94,114.89,110.95,55.77,46.58.
example 16:
a cyclic sulfonamide compound and a method for producing the same are substantially the same as in example 1, except that a different cyclic imine I-g (66.00 mg,0.25 mmol) is used, and the reaction equation is as follows:
the product amine compound II-g (60.1 mg, 93%) was obtained as a white solid.
The nuclear magnetic characterization data are as follows:
1 H NMR(400MHz,DMSO-d6)δ8.63(d,J＝6.5Hz,1H),7.60–7.51(m,2H),7.08(d,J＝8.7Hz,1H),4.59(d,J＝5.2Hz,2H). 13 C NMR(101MHz,DMSO-d6)δ151.02,132.18,130.32,121.89,120.61,117.00,45.26.
example 17:
a cyclic sulfonamide compound and a method for producing the same are substantially the same as in example 1, except that a different cyclic imine I-h (63.57 mg,0.25 mmol) is used, and the reaction equation is as follows:
the product amine compound II-h (58.5 mg, 91%) was obtained as a white solid.
The nuclear magnetic characterization data are as follows:
1 H NMR(400MHz,Chloroform-d)δ7.50(d,J＝7.9Hz,1H),7.37(t,J＝7.8Hz,1H),7.21(t,J＝7.6Hz,1H),7.05(d,J＝8.3Hz,1H),5.55(d,J＝8.5Hz,1H),5.46(d,J＝8.3Hz,1H),4.41(q,J＝7.1Hz,2H),1.40(td,J＝7.2,1.5Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ167.40,151.23,130.46,126.34,125.63,119.56,116.20,63.68,58.73,14.08.
example 18:
a cyclic sulfonamide compound and a method for producing the same are substantially the same as in example 1 except that a different cyclic imine I-i (83.59 mg,0.5 mmol) is used, the amount of the substance is doubled, the amounts of the reagents used in the other reactions are 2 times those in example 1, and the reaction equation is as follows:
the product amine compound II-i (78.68 mg, 93%) was obtained as a white solid.
The nuclear magnetic characterization data are as follows:
1 H NMR(400MHz,Chloroform-d)δ7.74(d,J＝7.8Hz,1H),7.58(t,J＝7.5Hz,1H),7.48(t,J＝7.6Hz,1H),7.36(d,J＝7.7Hz,1H),5.05(s,1H),4.50(s,2H). 13 C NMR(101MHz,Chloroform-d)δ136.91,135.49,132.98,129.11,124.81,121.24,45.69.
example 19:
a cyclic sulfonamide compound and a method for producing the same are substantially the same as in example 18, except that a different cyclic imine I-j (83.59 mg,0.5 mmol) is used, and the reaction equation is as follows:
the product amine compound II-j (84.3 mg, 92%) was obtained as a white solid.
The nuclear magnetic characterization data are as follows:
1 H NMR(400MHz,Chloroform-d)δ7.74(d,J＝8.1Hz,1H),7.39(d,J＝9.4Hz,1H),5.24(s,1H),4.56(s,2H),2.54(s,3H). 13 C NMR(101MHz,Chloroform-d)δ144.03,137.27,132.78,130.10,125.01,120.99,45.58,21.66.
the previous description of the embodiments is provided to facilitate a person of ordinary skill in the art in order to make and use the present invention. It will be apparent to those skilled in the art that various modifications can be readily made to these embodiments and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above-described embodiments, and those skilled in the art, based on the present disclosure, should make improvements and modifications without departing from the scope of the present invention.
Claims (10)
1. A method for preparing a cyclic sulfonamide compound, which is characterized by comprising the following steps:
(1) Stirring the cyclic imine and the solvent at room temperature, and then adding a catalyst nitrogen heterocyclic carbene borane for reaction;
(2) Extracting after the reaction is finished, and purifying the residual crude product to obtain an amine compound;
the reaction equation is as follows:
r in the cyclic imine and amine compound 1 Comprising hydrogen atoms, ester groups, C1-C4 alkyl or aryl groups, X 1 Comprising oxygen atoms or sulfur atoms directly attached to carbon atoms at both ends, R 2 And X 2 Selecting one of the connections, R 2 Comprising hydrogen atoms, methoxy groups, C1-C4 alkyl or aryl groups, X 2 Is halogen;
the molecular structural formula of the N-heterocyclic carbene borane is as follows:
r in the N-heterocyclic carbene borane 3 Including C1-C4 alkyl or aryl.
2. The method for producing a cyclic sulfonamide compound according to claim 1, wherein R is selected from the group consisting of 1 Comprising methyl, ethyl, phenyl or substituted phenyl, R 2 Comprising methyl, methoxy or benzyl groups, X 2 Including chlorine or bromine.
3. The method for preparing cyclic sulfonamide compound according to claim 1, wherein R in the N-heterocyclic carbene borane is as follows 3 Including methyl, ethyl, propyl or isopropyl.
4. The preparation method of the cyclic sulfonamide compound according to claim 1, wherein the molar ratio of the cyclic imine to the N-heterocyclic carbene borane is 1 (0.3-1.0), and the dosage ratio of the cyclic imine to the solvent is 1mol (1-4L).
5. The method for producing a cyclic sulfonamide compound according to claim 1, wherein the reaction time is 0.5 to 2.0 hours.
6. The method for producing a cyclic sulfonamide compound according to claim 1, wherein the solvent in the step (1) is an alcohol.
7. The method according to claim 6, wherein the solvent in the step (1) comprises methanol, ethanol, isopropanol or aminoindanol.
8. The method for producing a cyclic sulfonamide compound according to claim 1, wherein the extractant in the step (2) comprises ethyl acetate or methylene chloride.
9. The method for producing a cyclic sulfonamide compound according to claim 1, wherein the step (2) is specifically: after the reaction is finished, the reaction solution is concentrated, extracted, washed with water, dried, and then the residual crude product is subjected to silica gel column chromatography purification.
10. The method for preparing the cyclic sulfonamide compound according to claim 9, wherein the water washing agent is saturated saline solution, the drying agent is anhydrous sodium sulfate or anhydrous magnesium sulfate, the silica gel column chromatography eluent is a mixed solution of ethyl acetate and petroleum ether, and the volume ratio of the ethyl acetate to the petroleum ether is 1 (2-4).
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