CN118388382A - Preparation method and application of sulfinyl compound - Google Patents
Preparation method and application of sulfinyl compound Download PDFInfo
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- CN118388382A CN118388382A CN202410501592.9A CN202410501592A CN118388382A CN 118388382 A CN118388382 A CN 118388382A CN 202410501592 A CN202410501592 A CN 202410501592A CN 118388382 A CN118388382 A CN 118388382A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- -1 sulfinyl compound Chemical class 0.000 title abstract description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 18
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 34
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- 239000003054 catalyst Substances 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 239000003446 ligand Substances 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000003205 fragrance Substances 0.000 claims description 2
- 239000000575 pesticide Substances 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- 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 1
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- 150000001501 aryl fluorides Chemical class 0.000 abstract description 2
- 125000000524 functional group Chemical group 0.000 abstract 1
- 229910052751 metal Inorganic materials 0.000 abstract 1
- 239000002184 metal Substances 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 description 14
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical class [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XBHPFCIWRHJDCP-UHFFFAOYSA-N (2-trimethylsilylphenyl) trifluoromethanesulfonate Chemical compound C[Si](C)(C)C1=CC=CC=C1OS(=O)(=O)C(F)(F)F XBHPFCIWRHJDCP-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COTNUBDHGSIOTA-LHHVLQQYSA-N CO.[2H]OC([2H])([2H])[2H] Chemical class CO.[2H]OC([2H])([2H])[2H] COTNUBDHGSIOTA-LHHVLQQYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- LQBCXNSDCBYQCQ-UHFFFAOYSA-N OS(=O)(=O)S(=O)S(O)(=O)=O Chemical class OS(=O)(=O)S(=O)S(O)(=O)=O LQBCXNSDCBYQCQ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000005520 diaryliodonium group Chemical group 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000002577 pseudohalo group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to a preparation method and application of a sulfinyl compound, in particular to a sulfinyl compound which is obtained by the reaction of sulfoxyfolid and aryl fluoride sulfate under the catalysis of metal palladium, has simple process conditions, good yield and wide functional group tolerance.
Description
Technical Field
The invention belongs to the field of chemical medicines, and relates to a preparation method and application of a sulfinyl compound.
Background
The sulfo subunit subunits have been demonstrated to be multifunctional building blocks in synthetic organic chemistry because of their easy accessibility, scaffold stability and unique reactivity. Recent advances have shown that the sulfosubunit subunit can effectively participate in a wide range of organic transformations as an attractive alternative to potentially dangerous diazo compounds.
In general, the commonly used α -monosubstituted α -carbonylsulfinyls can be readily synthesized by acylation of a trimethylsulfoxide halide with an acid chloride/anhydride or an amide under basic conditions. In contrast, the synthesis of disubstituted sulfosulfoxide onium ylides is relatively challenging, particularly for the preparation of α -aryl α -carbonyl sulfoethers, which are important precursors for obtaining a variety of synthetically useful α -aryl substituted carbonyl compounds.
The Burtoloso group reports the first arylation of β -ketosulfonyloxy ylide (org. Lett.2018,20, 7206-7211) by using 2- (trimethylsilyl) phenyltriflate (2-TMSC 6H4 OTf) as a benzyl alkyne precursor and an arylating agent in the presence of CsF.
And co-workers successfully achieved coupling of alpha-ester sulfo xonium ylide with aryl halides and pseudohalides under palladium catalysis (j.org.chem.2020, 85, 1126-1137.).
The Murphy/Burtoloso group describes the catalytic coupling of diaryliodonium salts, which can also be derived from Cu (I) -mesitylene, with alpha-carbonylsulfonium ylide (adv. Synth. Catalyst. 2024,366, 396-401.).
The invention provides a method for obtaining a sulfinyl compound by reacting sulfoxyfolid with aryl fluoride sulfate under the catalysis of metallic palladium.
Disclosure of Invention
In one aspect, the present invention provides a process for preparing a compound of formula C
Comprising the step of reacting a compound represented by formula A with a compound represented by formula B in the presence of a palladium catalyst,
Wherein Ar 1 is selected from aryl, wherein said aryl is optionally substituted with one or more substituents selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, halo C 1-6 alkoxy;
Ar 2 is selected from aryl or heteroaryl optionally substituted with one or more substituents selected from halogen, cyano, nitro, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, halo C 1-6 alkoxy, -COR 1;
Each R 1 is independently selected from C 1-6 alkyl or C 1-6 alkoxy.
In some embodiments, the palladium catalyst is Pd 2(dba)3.
In some embodiments, ar 1 in the compound of formula A is selected from phenyl optionally substituted with one or more substituents selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, halo C 1-6 alkoxy.
In some embodiments, ar 1 in the compound of formula A is selected from phenyl optionally substituted with one or more substituents selected from halogen, C 1-6 alkyl, C 1-6 alkoxy.
In some embodiments, ar 1 in the compound of formula A is selected from naphthyl optionally substituted with one or more substituents selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, halo C 1-6 alkoxy.
In some embodiments, the compound of formula a is selected from:
In some embodiments, ar 2 in the compound of formula B is selected from phenyl optionally substituted with one or more substituents selected from halogen, cyano, nitro, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, halo C 1-6 alkoxy, -COR 1.
In some embodiments, ar 2 in the compound of formula B is selected from phenyl optionally substituted with one or more substituents selected from halogen, cyano, nitro, C 1-6 alkyl, C 1-6 alkoxy, -COR 1.
In some embodiments, ar 2 in the compound of formula B is selected from naphthyl optionally substituted with one or more substituents selected from halogen, cyano, nitro, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, halo C 1-6 alkoxy, -COR 1.
In some embodiments, ar 2 in the compound of formula B is selected from pyridine optionally substituted with one or more substituents selected from halogen, cyano, nitro, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, halo C 1-6 alkoxy, -COR 1.
In some embodiments, the compound of formula B is selected from:
The palladium catalyst is used in the method of the invention in an amount of 5 to 15 percent of the molar amount of the compound shown in the formula B, including but not limited to 5 percent, 6 percent, 7 percent, 8 percent, 9 percent, 10 percent, 11 percent, 12 percent, 13 percent, 14 percent, 15 percent or any value between two. In some embodiments, the palladium catalyst is used in the process in an amount of 10% of the molar amount of the compound of formula B.
In another aspect, the reaction of the present invention also contains a catalyst ligand, such as X-phos.
In some embodiments, the catalyst ligand is used in the reaction in an amount 1 to 4 times the molar amount of catalyst, including but not limited to 1.0、1.1、1.2、1.3、1.4、1.5、1.6、1.7、1.8、1.9、2.0、2.1、2.2、2.3、2.4、2.5、2.6、2.7、2.8、2.9、3.0、3.1、3.2、3.3、3.4、3.5、3.6、3.7、3.8、3.9、4.0 or values between any two. In some embodiments, the catalyst ligand is used in the reaction in an amount 2 times the molar amount of catalyst.
In another aspect, csF is present in the reaction described herein. In some embodiments, the amount of CsF in the reaction is 1 to 3 times the molar amount of the compound of formula B, including but not limited to 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, or a value between any two. In some embodiments, the catalyst ligand is used in the reaction in an amount 2 times the molar amount of catalyst.
Further, the reaction of the present invention is carried out in a solvent selected from acetonitrile or tetrahydrofuran.
In some embodiments, the reaction is performed in acetonitrile.
In another aspect, the molar ratio of the compound of formula B to the compound of formula A in the process is from 1:1 to 1:4 (including 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, or any value therebetween). In some embodiments, the molar ratio of the compound of formula B to the compound of formula a in the process is from 1:1 to 1:2. In some embodiments, the molar ratio of the compound of formula B to the compound of formula a in the process is 1:1.5.
The reaction temperature may be 60 to 100 ℃ (60 ℃, 65 ℃, 70 ℃, 75 ℃, 80 ℃, 85 ℃, 90 ℃, 95 ℃ or 100 ℃).
In some embodiments, the reaction temperature is 80 ℃.
In a preferred embodiment, the process for preparing the compound of formula C comprises: comprising the step of reacting a compound represented by formula B with a compound represented by formula A in the presence of Pd 2(dba)3, X-Phos and CsF,
The invention also provides the application of the preparation method of the sulfinyl compound shown in the formula C in the preparation of medicines, fragrances or pesticides.
Unless stated to the contrary, the terms used in the specification and claims have the following meanings.
The term "alkyl" refers to a saturated aliphatic hydrocarbon group which is a straight or branched chain group containing from 1 to 6 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1-dimethylpropyl, and various branched isomers thereof, and the like. The alkyl group may be substituted or unsubstituted, and when substituted, the substituent may be substituted at any available point of attachment, preferably one or more of the following groups, such as halogen.
The term "aryl" refers to a 6 to 14 membered all-carbon monocyclic or fused polycyclic (i.e., rings sharing adjacent pairs of carbon atoms) group having a conjugated pi-electron system, preferably 6 to 10 membered, such as phenyl and naphthyl.
Aryl groups may be substituted or unsubstituted, and when substituted, the substituents are preferably one or more groups independently selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy.
The term "heteroaryl" refers to a heteroaromatic system containing from 1 to 4 heteroatoms, from 5 to 14 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur and nitrogen. Heteroaryl is preferably 5 to 12 membered, such as imidazolyl, furanyl, thienyl, pyrazolyl, pyrrolyl, pyridinyl, and the like.
Heteroaryl groups may be optionally substituted or unsubstituted, and when substituted, the substituents are preferably one or more groups independently selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy.
The term "alkoxy" refers to-O- (alkyl) and-O- (unsubstituted cycloalkyl), wherein alkyl is as defined above. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy. The alkoxy groups may be optionally substituted or unsubstituted, and when substituted, the substituents are preferably one or more of the following groups, such as halogen.
The term "cyano" refers to-CN.
The term "nitro" refers to-NO 2.
The term "halogen" includes: fluorine, chlorine, bromine or iodine.
"Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs or does not. For example, "a heterocyclic group optionally substituted with an alkyl group" means that an alkyl group may be, but is not necessarily, present, and the description includes cases where the heterocyclic group is substituted with an alkyl group and cases where the heterocyclic group is not substituted with an alkyl group.
"Substituted" means that one or more hydrogen atoms, preferably up to 5, more preferably 1 to 3 hydrogen atoms in the group are independently substituted with a corresponding number of substituents. It goes without saying that substituents are only in their possible chemical positions, and that the person skilled in the art is able to determine (by experiment or theory) possible or impossible substitutions without undue effort. For example, amino or hydroxyl groups having free hydrogen may be unstable when bound to carbon atoms having unsaturated (e.g., olefinic) bonds.
The reagents used in the present invention are commercially available.
The structure of the compounds is determined by Nuclear Magnetic Resonance (NMR) or/and Mass Spectrometry (MS). The NMR shift (. Delta.) is given in units of 10 -6 (ppm). NMR was performed using a Bruker AVANCE-400 nuclear magnetic resonance apparatus with deuterated dimethyl sulfoxide (DMSO-d 6), deuterated chloroform (CDCl 3), deuterated Methanol (Methanol-d 4) as the solvent and Tetramethylsilane (TMS) as the internal standard.
Detailed Description
The present invention will be explained in detail below with reference to specific examples, so that those skilled in the art more fully understand the present invention by way of illustration of the technical scheme of the present invention only, and do not limit the present invention in any way.
Example 1: preparation condition screening
Phenyl 2- (dimethyl (oxo) -lambda 6 -sulphite) acetate (1 a,127mg,0.6mmol,1.5 equiv.), fluorobenzene ester (2 a,70mg,0.4mmol,1.0 equiv.), catalyst (10 mol%), X-Phos (20 mol%), csF (122 mg,0.8mmol,2.0 equiv.) were added to acetonitrile and the reaction was heated with stirring (80 ℃,12 h), the reaction yield was estimated by NMR detection, or the yield was calculated by column chromatography purification, specific data are as follows:
TABLE 1
Note that: a NMR detection estimates the reaction yield; b Pd 2(dba)3 (5 mol%); separation yield
1H NMR(400MHz,CDCl3):δ＝7.47–7.42(m,2H),7.40–7.34(m,2H),7.34–7.27(m,3H),7.16–7.11(m,1H),7.10–7.04(m,2H),3.46(s,6H)ppm.
13C NMR(100MHz,CDCl3):δ＝164.5,151.4,133.7,131.6,129.0,128.4,127.3,124.7,122.3,70.7,42.9ppm.
Example 2
127Mg phenyl 2- (dimethyl (oxo) -lambda 6 -sulphite) acetate (1 a,0.6mmol,1.5 equiv.) 4-nitrofluorobenzene ester (2 b,88mg,0.4mmol,1.0 equiv.) catalyst Pd 2(dba)3
(10 Mol%), X-Phos (20 mol%), csF (122 mg,0.8mmol,2.0 equiv.) were added to acetonitrile, stirred and heated to 80℃for reaction for 12h, and after completion of TLC detection, the target product was purified by column chromatography, yield: 83%.
1H NMR(400MHz,CDCl3):δ＝8.19–8.14(m,2H),7.62–7.57(m,2H),7.39–7.33(m,2H),7.21–7.16(m,1H),7.09(dd,J＝8.6,1.2Hz,2H),3.58(s,6H)ppm.
13C NMR(100MHz,CDCl3):δ＝163.4,150.7,145.0,139.4,132.0,129.1,125.0,123.0,121.9,69.4,43.3ppm.
IR(KBr):＝3018,2913,1679,1633,1584,1504,1329,854cm-1
HRMS(m/z):calcd for C16H16NO5S+[M+H]+334.0744,found:334.0740.
Example 3
Referring to the procedure of example 2, phenyl 2- (dimethyl (oxo) -lambda 6 -sulfinyl) acetate, compound 2c-2k, catalyst Pd 2(dba)3, X-Phos, csF and acetonitrile were added sequentially to a reaction flask. Heating and stirring to react at 80 ℃, and after TLC detection reaction is completed, purifying by column chromatography to obtain target products, and respectively calculating the yields, wherein specific data are as follows:
Example 4
Referring to the method of example 2, in a reaction flask, compound 1b-j, thiophenyl fluoride (2 a), catalyst Pd 2(dba)3, X-Phos, csF and acetonitrile were sequentially added. Heating and stirring to react at 80 ℃, and after TLC detection reaction is completed, purifying by column chromatography to obtain target products, and respectively calculating the yields, wherein specific data are as follows:
Claims (10)
1.A process for preparing a compound of formula C,
Comprising the step of reacting a compound of formula A with a compound of formula B in the presence of a palladium catalyst, preferably Pd 2(dba)3,
Wherein Ar 1 is selected from aryl, wherein said aryl is optionally substituted with one or more substituents selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, halo C 1-6 alkoxy;
Ar 2 is selected from aryl or heteroaryl optionally substituted with one or more substituents selected from halogen, cyano, nitro, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, halo C 1-6 alkoxy, -COR 1;
Each R 1 is independently selected from C 1-6 alkyl or C 1-6 alkoxy.
2. The process of claim 1, wherein the solvent used in the reaction is selected from acetonitrile or tetrahydrofuran.
3. A process according to claim 1 or 2, wherein the palladium catalyst is used in an amount of 5% to 15%, preferably 10% of the molar amount of the compound of formula B.
4. A process according to any one of claims 1 to 3, wherein the reaction further comprises a catalyst ligand, preferably X-phos, further wherein the catalyst ligand is used in an amount of 1 to 4, preferably 2 times the molar amount of catalyst.
5. The process according to any one of claims 1 to 4, wherein the reaction further comprises CsF, and further wherein CsF is used in an amount of 1 to 3 times, preferably 2 times the molar amount of the compound of formula B.
6. The method of any one of claims 1-5, wherein the compound of formula B is selected from the group consisting of:
7. the method of any one of claims 1-6, wherein the compound of formula a is selected from the group consisting of:
8. The method of any one of claims 1-7, wherein the molar ratio of the compound of formula II to the compound of formula III is 1:1 to 1:4, preferably 1:1 to 1:2, e.g. 1:1.5.
9. A process according to any one of claims 1 to 8, wherein the reaction temperature is 60 to 100 ℃, preferably 70 to 90 ℃, such as 80 ℃.
10. Use of the method of any one of claims 1-9 in the preparation of a medicament, fragrance or pesticide.
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