CN114920633A - 一种醛酮类化合物的合成工艺 - Google Patents
一种醛酮类化合物的合成工艺 Download PDFInfo
- Publication number
- CN114920633A CN114920633A CN202210706077.5A CN202210706077A CN114920633A CN 114920633 A CN114920633 A CN 114920633A CN 202210706077 A CN202210706077 A CN 202210706077A CN 114920633 A CN114920633 A CN 114920633A
- Authority
- CN
- China
- Prior art keywords
- reaction
- synthesis
- aldehyde ketone
- alcohol
- added
- 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.)
- Granted
Links
- -1 aldehyde ketone compound Chemical class 0.000 title claims abstract description 51
- 238000000034 method Methods 0.000 title claims abstract description 37
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 32
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 31
- 230000008569 process Effects 0.000 title claims abstract description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 19
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 13
- 239000003513 alkali Substances 0.000 claims abstract description 9
- 125000001741 organic sulfur group Chemical group 0.000 claims abstract description 9
- 239000002585 base Substances 0.000 claims abstract description 7
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 5
- 239000002994 raw material Substances 0.000 claims abstract description 5
- 150000007530 organic bases Chemical group 0.000 claims abstract description 4
- 150000007529 inorganic bases Chemical class 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 118
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 54
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 46
- 238000004440 column chromatography Methods 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 238000001308 synthesis method Methods 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 9
- UNGVHYYDHXGTTP-UHFFFAOYSA-N C[S](C)Br Chemical group C[S](C)Br UNGVHYYDHXGTTP-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 230000002194 synthesizing effect Effects 0.000 claims description 8
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 239000007810 chemical reaction solvent Substances 0.000 claims description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 229910052736 halogen Inorganic materials 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
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 150000003141 primary amines Chemical class 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 238000007670 refining Methods 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 5
- 238000007254 oxidation reaction Methods 0.000 abstract description 5
- 230000009471 action Effects 0.000 abstract description 3
- 125000000524 functional group Chemical group 0.000 abstract description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 abstract 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 abstract 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 20
- 239000012153 distilled water Substances 0.000 description 16
- 238000000605 extraction Methods 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 16
- 238000010791 quenching Methods 0.000 description 16
- 238000002390 rotary evaporation Methods 0.000 description 16
- 239000000047 product Substances 0.000 description 15
- 238000003756 stirring Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 12
- 238000001228 spectrum Methods 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- OOCCDEMITAIZTP-QPJJXVBHSA-N (E)-cinnamyl alcohol Chemical compound OC\C=C\C1=CC=CC=C1 OOCCDEMITAIZTP-QPJJXVBHSA-N 0.000 description 8
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 8
- SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical compound O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 8
- 238000007792 addition Methods 0.000 description 7
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- MFGWMAAZYZSWMY-UHFFFAOYSA-N (2-naphthyl)methanol Chemical compound C1=CC=CC2=CC(CO)=CC=C21 MFGWMAAZYZSWMY-UHFFFAOYSA-N 0.000 description 6
- VFZRZRDOXPRTSC-UHFFFAOYSA-N 3,5-Dimethoxybenzaldehyde Chemical compound COC1=CC(OC)=CC(C=O)=C1 VFZRZRDOXPRTSC-UHFFFAOYSA-N 0.000 description 6
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 6
- 239000012965 benzophenone Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- AUDBREYGQOXIFT-UHFFFAOYSA-N (3,5-dimethoxyphenyl)methanol Chemical compound COC1=CC(CO)=CC(OC)=C1 AUDBREYGQOXIFT-UHFFFAOYSA-N 0.000 description 4
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 description 4
- SQAINHDHICKHLX-UHFFFAOYSA-N 1-naphthaldehyde Chemical compound C1=CC=C2C(C=O)=CC=CC2=C1 SQAINHDHICKHLX-UHFFFAOYSA-N 0.000 description 4
- PJKVFARRVXDXAD-UHFFFAOYSA-N 2-naphthaldehyde Chemical compound C1=CC=CC2=CC(C=O)=CC=C21 PJKVFARRVXDXAD-UHFFFAOYSA-N 0.000 description 4
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 4
- ISDBWOPVZKNQDW-UHFFFAOYSA-N 4-phenylbenzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CC=CC=C1 ISDBWOPVZKNQDW-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- OOCCDEMITAIZTP-UHFFFAOYSA-N allylic benzylic alcohol Natural products OCC=CC1=CC=CC=C1 OOCCDEMITAIZTP-UHFFFAOYSA-N 0.000 description 4
- YMNKUHIVVMFOFO-UHFFFAOYSA-N anthracene-9-carbaldehyde Chemical compound C1=CC=C2C(C=O)=C(C=CC=C3)C3=CC2=C1 YMNKUHIVVMFOFO-UHFFFAOYSA-N 0.000 description 4
- WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical compound C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 description 4
- ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical compound C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 description 4
- 229940117916 cinnamic aldehyde Drugs 0.000 description 4
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 description 4
- YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 229940081310 piperonal Drugs 0.000 description 4
- SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- PBLNHHSDYFYZNC-UHFFFAOYSA-N (1-naphthyl)methanol Chemical compound C1=CC=C2C(CO)=CC=CC2=C1 PBLNHHSDYFYZNC-UHFFFAOYSA-N 0.000 description 3
- AXCHZLOJGKSWLV-UHFFFAOYSA-N (4-phenylphenyl)methanol Chemical compound C1=CC(CO)=CC=C1C1=CC=CC=C1 AXCHZLOJGKSWLV-UHFFFAOYSA-N 0.000 description 3
- WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical compound CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 description 3
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 3
- KMTDMTZBNYGUNX-UHFFFAOYSA-N 4-methylbenzyl alcohol Chemical compound CC1=CC=C(CO)C=C1 KMTDMTZBNYGUNX-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- JCJNNHDZTLRSGN-UHFFFAOYSA-N anthracen-9-ylmethanol Chemical compound C1=CC=C2C(CO)=C(C=CC=C3)C3=CC2=C1 JCJNNHDZTLRSGN-UHFFFAOYSA-N 0.000 description 3
- QILSFLSDHQAZET-UHFFFAOYSA-N diphenylmethanol Chemical compound C=1C=CC=CC=1C(O)C1=CC=CC=C1 QILSFLSDHQAZET-UHFFFAOYSA-N 0.000 description 3
- AFMVESZOYKHDBJ-UHFFFAOYSA-N fluoren-9-ol Chemical compound C1=CC=C2C(O)C3=CC=CC=C3C2=C1 AFMVESZOYKHDBJ-UHFFFAOYSA-N 0.000 description 3
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 3
- VEDDBHYQWFOITD-UHFFFAOYSA-N para-bromobenzyl alcohol Chemical compound OCC1=CC=C(Br)C=C1 VEDDBHYQWFOITD-UHFFFAOYSA-N 0.000 description 3
- 150000003463 sulfur Chemical class 0.000 description 3
- ZPHGMBGIFODUMF-UHFFFAOYSA-N thiophen-2-ylmethanol Chemical compound OCC1=CC=CS1 ZPHGMBGIFODUMF-UHFFFAOYSA-N 0.000 description 3
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 244000028419 Styrax benzoin Species 0.000 description 2
- 235000000126 Styrax benzoin Nutrition 0.000 description 2
- 235000008411 Sumatra benzointree Nutrition 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical group [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 229960002130 benzoin Drugs 0.000 description 2
- VTHIKKVKIVQWHV-UHFFFAOYSA-N chromium(6+) oxygen(2-) pyridine Chemical compound [O-2].[O-2].[O-2].[Cr+6].C1=CC=NC=C1 VTHIKKVKIVQWHV-UHFFFAOYSA-N 0.000 description 2
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 2
- 235000019382 gum benzoic Nutrition 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 150000003333 secondary alcohols Chemical class 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- KDNYCTPSPZHJQF-UHFFFAOYSA-N 3-phenylbutan-2-ol Chemical compound CC(O)C(C)C1=CC=CC=C1 KDNYCTPSPZHJQF-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 102100032373 Coiled-coil domain-containing protein 85B Human genes 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
- 101000868814 Homo sapiens Coiled-coil domain-containing protein 85B Proteins 0.000 description 1
- BHUIUXNAPJIDOG-UHFFFAOYSA-N Piperonol Chemical compound OCC1=CC=C2OCOC2=C1 BHUIUXNAPJIDOG-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- XPNGNIFUDRPBFJ-UHFFFAOYSA-N alpha-methylbenzylalcohol Natural products CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- MOFLDTNKLMFGSU-UHFFFAOYSA-N bromobenzene;methanol Chemical compound OC.BrC1=CC=CC=C1 MOFLDTNKLMFGSU-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 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
- 239000013078 crystal Substances 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 229940043276 diisopropanolamine Drugs 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/30—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with halogen containing compounds, e.g. hypohalogenation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/06—Formation or introduction of functional groups containing oxygen of carbonyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/48—Aldehydo radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/54—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
Abstract
本发明公开了一种醛酮类化合物的合成工艺;本工艺在氮气保护下,醇类化合物和有机硫试剂在碱的作用下进行氧化反应形成醛酮类化合物;其中有机硫试剂为溴化二甲基溴化硫;碱为有机碱或无机碱,醇类化合物为脂肪醇,芳香醇,以及与不饱和碳碳双键、羰基相连的醇,或带有其他官能团或杂原子的醇类化合物;该方法条件温和、原料简单易得、操作简单,具有较高的应用价值。
Description
技术领域
本发明涉及有机中间体合成技术领域,尤其涉及一种醛酮类化合物的合成工艺。
背景技术
醛酮类化合物是自然界中常见的物质,广泛存在于具有生物、药理活性的天然产物和人工合成的化合物中,在日常生产生活中可以用作香料、药物以及化工原料。该类物质可以发生几乎所有类型的有机转化,如氧化、还原、缩合、加成、环加成、偶联以及聚合反应等,可见醛酮类化合物在有机合成以及工业应用等领域具有不可替代的作用,因此该类的物质的高效合成具有重要的理论意义和实用价值。目前,醛酮类物质大多数由醇氧化直接得到,具体方法有:
方法一:以三氧化铬·吡啶的晶体为氧化剂,以二氯甲烷为溶剂,将醇氧化生成醛酮类物质。
该方法的弊端是需要使用过量(约6当量)的重金属氧化剂三氧化铬·吡啶,该反应原子利用率低,三废排放量大,严重污染环境。
方法二:以四氯化碳作溶剂,先使用氯气和二甲基硫在0℃条件下生成硫盐中间体,该硫盐然后在三乙胺作为碱,温度为-25℃的条件下与醇反应生成醛酮类物质。
该方法的弊端在于反应所需的氯气、四氯化碳均具有毒性,容易对人体造成伤害,污染环境,使用也不便,所用硫盐不太稳定,只能原位生成并使用。
方法三:在80℃条件下,以醋酸钯作催化剂,醇类化合物在氧气和二甲亚砜的共同作用下反应生成醛酮类物质。
该方法的弊端在于需要使用的重金属钯催化剂价格较为昂贵,回收困难,所用的二甲亚砜较难处理,反应所需时间较长。
方法四:在室温和DMF作溶剂的条件下,醇类化合物受到催化剂TEMPO和助催化剂CuCl 的共同作用,转化为醛酮类物质。
该反应的不足之处是使用DMF作溶剂,虽然对活泼的伯醇能有效地氧化,但对仲醇的氧化效果不佳,甚至不反应,底物范围的限制性很大。
发明内容
针对上述存在的问题,本发明目的在于提供一种成本低廉、操作简便、反应条件温和,易于在工业生产推广的醛酮类化合物的合成工艺。
为了达到上述目的,本发明采用的技术方案如下:一种醛酮类化合物的合成工艺,所述工艺的合成方法如下:
其中,有机硫试剂为溴化二甲基溴化硫;碱为有机碱或无机碱;
R为取代基,取代基选自:C2-C20烯基、包含二级取代基的C6-C20芳基、包含1-5个O、N、S杂原子的5-10元杂芳基或共轭羰基;二级取代基选自:卤素、C1-C20烷基或共轭羰基。
本发明的取代基R优选包含二级取代基的C6-C20芳基、包含1-5个O、N、S杂原子的5-10元杂芳基,其中,二级取代基选自:卤素、C1-C20烷基或苯环;当取代基R为芳基或5-10元杂芳基时,通过本工艺生产出的产品收率最高。
本发明所述的合成方法中有机硫试剂和醇类化合物的摩尔比为1~2:1;优选的摩尔比为 1.2:1或1.5:1;当有机硫试剂和醇类化合物的摩尔比为1.2:1或1.5:1时,最终产品的收率较高。
本发明所述的合成方法中碱和有机硫试剂的摩尔比为1~2:1,优选的的摩尔比为2:1;当碱和有机硫试剂的摩尔比为2:1时,最终产品的收率达到最高。
本发明所述的合成方法中反应溶剂为四氢呋喃或二氯甲烷;原料醇类化合物在反应溶剂中摩尔浓度为0.1mmol/mL;本发明在单一有机溶剂的体系中进行;如果需要,体系中也可以存在其它有机溶剂,但是从反应产率、操作的简洁性角度考虑,优选为不加其它有机溶剂,即以单一有机溶剂作为反应溶剂。
本发明所述的合成方法中有机碱为一级胺、二级胺、三级胺、吡啶、DMAP、DBU中的一种。本发明所述的合成方法中无机碱为碳酸钾、碳酸钠、碳酸铯、磷酸钾、磷酸钠中的一种;优选的碱为DBU。
本发明所述的合成方法中反应温度为0℃~-78℃,优选-78℃;反应时间为15min~18h,优选30min。本发明的反应温度和反应时间可以由技术人员按照不同的醇类化合物,根据实际需要自行确定。
本发明提供一种醛酮类化合物的精制方法,其精制方法如下:反应完成后,用水洗涤反应液并用乙酸乙酯萃取三次,经柱层析分离,得到精制后的醛酮类化合物。
本发明的优点在于:本发明用简单易得的醇类化合物作为反应底物,用商业可购买、制作简单且对空气不易敏感的溴化二甲基溴化硫作为反应试剂,采用廉价易得的DBU作为碱,反应温度为-78℃逐渐恢复至室温,在氮气条件下简单而高效地合成了醛酮类化合物。与其它合成醛酮类化合物的方法相比,本发明的反应条件温和、所使用的的反应原料(包括醇、溴化二甲基溴化硫、DBU)均廉价易得、不需要使用金属催化剂、反应产率高,具有节约成本、环境友好、可工业推广的特点。
本发明是一种适用范围广的醛酮合成的方法,对于芳香醛酮、脂肪醛酮、α,β-不饱和醛酮、杂芳基醛酮的合成都具有良好的适用性。因此实际上对于醇类化合物及其衍生物中的取代基的个数和种类没有特别严格的限制,进而对于醛酮类化合物中的取代基的个数和种类也没有特别严格的限制。
本发明对于多种醇类化合物均可适用,这也包括仲醇或烯丙醇,进而可以制得多种多样的醛酮类化合物;本发明可以广泛应用于工业和学术界的药物合成、天然产物的全合成中,具有较高的应用价值。
附图说明
图1为实施例1所述对甲氧基苯甲醛的核磁氢谱图;
图2为实施例1所述对甲氧基苯甲醛的核磁碳谱图;
图3为实施例2所述3,5-二甲氧基苯甲醛的核磁氢谱图;
图4为实施例3所述胡椒醛的核磁氢谱图;
图5为实施例5所述4-联苯甲醛的核磁氢谱图;
图6为实施例10所述1-萘甲醛的核磁氢谱图;
图7为实施例11所述2-萘甲醛的核磁氢谱图;
图8为实施例12所述9-蒽甲醛的核磁氢谱图;
图9为实施例13所述二苯甲酮的核磁氢谱图;
图10为实施例13所述二苯甲酮的核磁碳谱图;
图11为实施例15所述9-芴酮的核磁氢谱图;
图12为实施例15所述苯偶酰的核磁氢谱图。
具体实施方式
下面结合附图说明和具体实施方式对本发明作进一步详细的描述。
以下具体实施例中所用的原料均可商业购买,各试剂必要时采用本领域公知的手段进行纯化后使用。
在本发明中,“醛酮类化合物”具有本领域技术人员所通常理解的含义,即含有羰基(-CO-) 或醛基(-CHO)的化合物,例如对甲氧基苯甲醛、肉桂醛、苯乙酮、二苯甲酮及其各种衍生物。
在本发明中,“醇类化合物”具有本领域技术人员所通常理解的含义,即含有与羟基上的氧原子连接的烷基、烯基、苯基、杂环结构的化合物,例如对甲氧基苯甲醇、对溴苯甲醇、肉桂醇、2-吡啶甲醇、1-苯乙醇及其各种衍生物。
以下具体实施例中所用的原料均可商业购买,各试剂必要时采用本领域公知的手段进行纯化后使用。
1H NMR和13C NMR均采用Bruker Avance 400spectrometer仪器进行测定。测试温度为室温,溶剂为氘代氯仿,选取参考:1H NMR:CHCl3为7.260ppm;13C NMR:CHCl3为77.000ppm。
实施例1:对甲氧基苯甲醛的合成
在氮气保护的Schlenk反应管中加入对甲氧基苯甲醇(124.2mg,110μL)和DCM(4.5mL)溶解形成对甲氧基苯甲醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0mg,1.5equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10 分钟内逐滴加入对甲氧基苯甲醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到对甲氧基苯甲醛35.9mg,产率为88%。
产物对甲氧基苯甲醛:1H NMR(400MHz,CDCl3)δ9.88(s,1H),7.87–7.79(m,2H),7.05– 6.93(m,2H),3.88(s,3H)ppm.13C NMR(101MHz,CDCl3)δ190.8,190.8,164.5,131.9,129.9, 114.3,55.5ppm.
实施例2:3,5-二甲氧基苯甲醛的合成
在氮气保护的Schlenk反应管中加入3,5-二甲氧基苯甲醇(151.3mg)和DCM(4.5mL),溶解形成3,5-二甲氧基苯甲醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0mg,1.5equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入3,5-二甲氧基苯甲醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0 equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到3,5- 二甲氧基苯甲醇39.8mg,产率为80%。
产物3,5-二甲氧基苯甲醛:1H NMR(400MHz,CDCl3)δ9.89(s,1H),7.00(d,J=2.4Hz, 2H),6.69(s,1H),3.83(s,6H)ppm.13C NMR(101MHz,CDCl3)δ191.9,161.2,138.3,107.1, 107.0,55.6ppm.
实施例3:胡椒醛的合成
在氮气保护的Schlenk反应管中加入胡椒醇(137.2mg)和DCM(4.5mL),溶解形成胡椒醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0mg,1.5equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入胡椒醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到胡椒醛37.8mg,产率为84%。
产物胡椒醛:1H NMR(400MHz,CDCl3)δ9.79(s,1H),7.39(m,J=7.9,1.6Hz,1H),7.31(d, J=1.5Hz,1H),6.91(d,J=7.9Hz,1H),6.06(s,2H)ppm.13C NMR(101MHz,CDCl3)δ190.3, 153.0,148.6,131.8,128.6,108.3,106.8,102.1ppm.
实施例4:对溴苯甲醛的合成
在氮气保护的Schlenk反应管中加入对溴苯甲醇(168.8mg)和DCM(4.5mL),溶解形成对溴苯甲醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0mg, 1.5equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入对溴苯甲醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30 分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3 次,每次10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到对溴苯甲醛26mg,产率为 47%。
产物对溴苯甲醛:1H NMR(400MHz,CDCl3)δ9.97(s,1H),7.78–7.64(m,4H)ppm.13CNMR(101MHz,CDCl3)δ191.1,135.0,132.4,130.9,129.8ppm.
实施例5:4-联苯甲醛的合成
在氮气保护的Schlenk反应管中加入4-联苯甲醇(124.6mg,110μL)和DCM(4.5mL),溶解形成4-联苯甲醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0 mg,1.5equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入4-联苯甲醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到4-联苯甲醛27.3mg,产率为50%。
产物4-联苯甲醛:1H NMR(400MHz,CDCl3)δ10.06(s,1H),8.02–7.89(m,2H),7.82–7.72(m,2H),7.64(m,J=4.4,3.5,1.9Hz,2H),7.54–7.38(m,3H)ppm.13C NMR(101MHz,CDCl3)δ191.9,147.1,139.6,135.1,130.2,129.0,128.4,127.6,127.3ppm.
实施例6:对甲基苯甲醛的合成
在氮气保护的Schlenk反应管中加入对甲基苯甲醇(108.1mg)和DCM(4.5mL),溶解形成对甲基苯甲醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0 mg,1.5equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入对甲基苯甲醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到对甲基苯甲醛15.2mg,产率为42%。
产物对甲基苯甲醛:1H NMR(400MHz,CDCl3)δ9.96(s,1H),7.78(d,J=8.1Hz,2H),7.33 (d,J=8.0Hz,2H),2.44(s,3H)ppm.13C NMR(101MHz,CDCl3)δ192.0,145.5,134.1,129.8, 129.7,21.9ppm.
实施例7:苯乙酮的合成
在氮气保护的Schlenk反应管中加入1-苯乙醇(123.1mg,123μL)和DCM(4.5mL),溶解形成1-苯乙醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0mg, 1.5equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入1-苯乙醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到苯乙酮25.8mg,产率为64%。
产物苯乙酮:1H NMR(400MHz,CDCl3)δ7.70–7.60(m,2H),7.28–7.20(m,1H),7.17–7.05(m,2H),2.24(s,3H)ppm.13C NMR(101MHz,CDCl3)δ196.8,136.3,132.2,127.7,127.4,25.6ppm.
实施例8:2-吡啶甲醛的合成
在氮气保护的Schlenk反应管中加入2-吡啶甲醇(98.0mg,87μL)和DCM(4.5mL),溶解形成2-吡啶甲醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0 mg,1.5equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入2-吡啶甲醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液 30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3 次,每次10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到2-吡啶甲醛11.9mg,产率为37%。
实施例9:2-噻吩甲醛的合成
在氮气保护的Schlenk反应管中加入2-噻吩甲醇(103.0mg,85μL)和DCM(4.5mL),溶解形成2-噻吩甲醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0 mg,1.5equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10mins内逐滴加入2-噻吩甲醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到2-噻吩甲醛14.1mg,产率为42%。
实施例10:1-萘甲醛的合成
在氮气保护的Schlenk反应管中加入1-萘甲醇(142.4mg)和DCM(4.5mL),溶解形成1-萘甲醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0mg,1.5 equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入 1-萘甲醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次 10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到1-萘甲醛30.0.mg,产率为64%。
产物1-萘甲醛:1H NMR(400MHz,CDCl3)δ10.30(s,1H),9.24(m,J=8.6,0.6Hz,1H),7.96(d,J=8.2Hz,1H),7.93–7.00(m,5H)ppm.13C NMR(101MHz,CDCl3)δ193.2,136.4,134.9,133.3,130.9,130.1,128.7,128.2,126.6,124.5ppm.
实施例11:2-萘甲醛的合成
在氮气保护的Schlenk反应管中加入2-萘甲醇(124.3mg)和DCM 4.5mL,溶解形成2-萘甲醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0mg,1.5 equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入 2-萘甲醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次 10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到2-萘甲醛35.6mg,产率为76%。
产物2-萘甲醛:1H NMR(400MHz,CDCl3)δ10.16(s,1H),8.33(s,1H),8.04–7.86(m,4H), 7.62(m,J=16.2,6.9,1.3Hz,2H)ppm.13C NMR(101MHz,CDCl3)δ192.2,136.4,134.5,134.0, 132.6,129.5,129.1,129.1,128.0,127.1,122.7ppm.
实施例12:9-蒽甲醛的合成
在氮气保护的Schlenk反应管中加入9-蒽甲醇(187.4mg)和DCM(4.5mL),溶解形成9-蒽甲醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0mg,1.5 equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入 9-蒽甲醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次 10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到9-蒽甲醛34.7mg,产率为56%。
产物9-蒽甲醛:1H NMR(400MHz,CDCl3)δ11.52(s,1H),8.99(d,J=9.0Hz,2H),8.69(s, 1H),8.06(d,J=8.4Hz,2H),7.68(m,J=8.3,7.3Hz,2H),7.62–7.48(m,2H)ppm.13C NMR(101MHz,CDCl3)δ193.0,135.3,132.2,131.1,129.3,129.2,125.7,123.6.
实施例13:二苯甲酮的合成
在氮气保护的Schlenk反应管中加入二苯甲醇(165.8mg)和DCM(4.5mL),溶解形成二苯甲醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0mg,1.5 equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入二苯甲醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到二苯甲酮50.8mg,产率为93%。
产物二苯甲酮:1H NMR(400MHz,CDCl3)δ7.81(m,J=8.4,1.6Hz,2H),7.63–7.54(m,1H),7.53–7.43(m,2H)ppm.13C NMR(101MHz,CDCl3)δ196.7,137.5,132.3,130.0,128.2ppm.
实施例14:9-芴酮的合成
在氮气保护的Schlenk反应管中加入9-芴醇(162.2mg)和DCM(4.5mL),溶解形成9-芴醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0mg,1.5equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入9-芴醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到9-芴酮43.3mg,产率为80%。
产物9-芴酮:1H NMR(400MHz,CDCl3)δ7.62(d,J=7.4Hz,1H),7.55–7.38(m,2H),7.33–7.21(m,1H)ppm.13C NMR(101MHz,CDCl3)δ193.8,144.3,134.6,134.0,129.0,124.2,120.2ppm.
实施例15:苯偶酰的合成
在氮气保护的Schlenk反应管中加入安息香(191.8mg)和DCM(4.5mL),溶解形成安息香的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0mg,1.5equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入安息香溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到苯偶酰56.8mg,产率为90%。
产物苯偶酰:1H NMR(400MHz,CDCl3)δ8.00–7.95(m,4H),7.65(m,J=10.7,4.2Hz,2H),7.51(t,J=7.7Hz,4H)ppm.13C NMR(101MHz,CDCl3)δ194.6,134.9,132.9,129.8,129.0ppm.
实施例16:肉桂醛的合成
在氮气保护的Schlenk反应管中加入肉桂醇(120.8mg,116μL)和DCM(4.5mL),溶解形成肉桂醇的溶液。另在装有磁力搅拌子的Schlenk反应管中加入溴化二甲基溴化硫(100.0mg,1.5 equiv),在氮气保护氛围下放置于-78℃的低温反应槽中冷却10分钟,再于10分钟内逐滴加入肉桂醇溶液(1.5mL,1.0equiv)和DBU(137.0mg,132μL,3.0equiv),滴加后搅拌溶液30分钟。反应完成后取出反应管恢复至室温,加入蒸馏水以淬灭反应,用乙酸乙酯进行萃取3次,每次 10mL,合并有机相,经过旋蒸浓缩然后进行柱层析得到肉桂醛28.6mg,产率为72%。
产物肉桂醛:1H NMR(400MHz,CDCl3)δ9.52–9.46(m,1H),7.36–7.31(m,2H),7.26–7.18(m,4H),6.54–6.45(m,1H)ppm.13C NMR(101MHz,CDCl3)δ192.8,151.9,133.3,130.5,128.4,127.8,127.7ppm.
从实施例1-16可知,本发明的方法是从各类廉价易得的醇类化合物出发,以商业可购买的溴化二甲基溴化硫作为反应试剂,使用廉价易得的DBU作为有机碱,在氮气条件下于-78℃至室温时逐渐发生反应,得到所述的醛酮类化合物。该方法无论对于芳香醛酮、脂肪醛酮、α, β-不饱和醛酮、杂芳基醛酮以及含其他官能团或杂原子的醛酮类化合物均具有良好的适用性,是一种条件温和、操作简单的醛酮类化合物的通用合成方法。
实施例17:对甲氧基苯甲醛的合成条件优化
标准条件:1 0.3mmol(1.0eq.),碱0.9mmol(3.0eq.),溶剂3.0mL,-78℃.分离产率.
DBU=1,8-二氮杂双环[5.4.0]十一碳-7-烯;
THF=四氢呋喃;
DCM=二氯甲烷;
DIPA=二异丙醇胺;
DIPEA=N,N-二异丙基乙基胺.
需要说明的是,上述仅仅是本发明的较佳实施例,并非用来限定本发明的保护范围,在上述实施例的基础上所做出的任意组合或等同变换均属于本发明的保护范围。
Claims (9)
2.如权利要求1所述的醛酮类化合物的合成工艺,其特征在于,所述的合成方法中取代基R优选包含二级取代基的C6-C20芳基、包含1-5个O、N、S杂原子的5-10元杂芳基;
其中,二级取代基选自卤素、C1-C20烷基或苯环。
3.如权利要求1或2所述的醛酮类化合物的合成工艺,其特征在于,所述的合成方法中有机硫试剂和醇类化合物的摩尔比为1~2:1;优选的摩尔比为1.2:1或1.5:1。
4.如权利要求1或2所述的醛酮类化合物的合成工艺,其特征在于,所述的合成方法中碱和有机硫试剂的摩尔比为1~2:1,优选的的摩尔比为2:1。
5.如权利要求1或2所述的醛酮类化合物的合成工艺,其特征在于,所述的合成方法中反应溶剂为四氢呋喃或二氯甲烷;原料醇类化合物在反应溶剂中摩尔浓度为0.1mmol/mL。
6.如权利要求1或2所述的醛酮类化合物的合成工艺,其特征在于,所述的合成方法中有机碱为一级胺、二级胺、三级胺、吡啶、DMAP、DBU中的一种。
7.如权利要求1或2所述的醛酮类化合物的合成工艺,其特征在于,所述的合成方法中无机碱为碳酸钾、碳酸钠、碳酸铯、磷酸钾、磷酸钠中的一种;优选的碱为DBU。
8.如权利要求1或2所述的醛酮类化合物的合成工艺,其特征在于,所述的合成方法中反应温度为0℃~-78℃,优选-78℃;反应时间为15min~18h,优选30min。
9.一种如权利要求1或2所述的合成工艺生产的醛酮类化合物的精制方法,其特征在于,反应完成后,用水洗涤反应液并用乙酸乙酯萃取三次,经柱层析分离,得到精制后的醛酮类化合物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210706077.5A CN114920633B (zh) | 2022-06-21 | 2022-06-21 | 一种醛酮类化合物的合成工艺 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210706077.5A CN114920633B (zh) | 2022-06-21 | 2022-06-21 | 一种醛酮类化合物的合成工艺 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114920633A true CN114920633A (zh) | 2022-08-19 |
CN114920633B CN114920633B (zh) | 2024-04-02 |
Family
ID=82814630
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210706077.5A Active CN114920633B (zh) | 2022-06-21 | 2022-06-21 | 一种醛酮类化合物的合成工艺 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114920633B (zh) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114426507A (zh) * | 2021-12-30 | 2022-05-03 | 南京师范大学 | 一种甲基硫亚甲基酯类化合物的合成方法 |
-
2022
- 2022-06-21 CN CN202210706077.5A patent/CN114920633B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114426507A (zh) * | 2021-12-30 | 2022-05-03 | 南京师范大学 | 一种甲基硫亚甲基酯类化合物的合成方法 |
Non-Patent Citations (4)
Title |
---|
E.J. COREY等: "A METHOD FOR SELECTIVE CONVERSION OF ALLYLIC AND BENZYLIC ALCOHOIS TO HALIDES UNDER NEUTRAL CONDITIONS", TETRAHEDRON LETTERS, no. 42, pages 4339 - 4342, XP002156483, DOI: 10.1016/S0040-4039(01)94310-2 * |
RAJESH CHEBOLU等: "An unusual chemoselective oxidation strategy by an unprecedented exploration of an electrophilic center of DMSO: a new facet to classical DMSO oxidation", CHEM. COMMUN., vol. 51, pages 15438 - 15441 * |
陈文抗: "十一醇选择氧化合成十一醛的研究", 安徽化工, vol. 41, no. 1 * |
黄壹俊: "活化二甲亚砜选择性氧化醇的反应", 大学化学, vol. 18, no. 4, pages 55 - 57 * |
Also Published As
Publication number | Publication date |
---|---|
CN114920633B (zh) | 2024-04-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPS633854B2 (zh) | ||
CN111233795A (zh) | 一种手性γ-丁内酯类化合物及其衍生物的制备方法及其应用 | |
CN114920633A (zh) | 一种醛酮类化合物的合成工艺 | |
JPS6247190B2 (zh) | ||
CN115322100A (zh) | 一种δ,ε-烯基酮类化合物及其制备方法与应用 | |
CN110804012B (zh) | 一种还原缩硫醛或缩硫酮脱硫的方法 | |
CN112047842A (zh) | 一种1,4-二烯烃类化合物及其制备方法与应用 | |
CN114874105B (zh) | 一种可见光和水促进的高烯丙基胺类化合物的制备方法 | |
CN110015996B (zh) | 一种合成2′-螺环基取代三元碳环核苷的方法 | |
CN115028568B (zh) | 一种可见光促进3-硒基吲哚类化合物的合成方法 | |
CN111499524B (zh) | 一种利用卤代中间体制备氨基醇化合物的方法 | |
CN114516823B (zh) | 一种微波辅助制备α-溴代亚砜类化合物的绿色方法 | |
CN114805208A (zh) | 一种4-三氟甲基-4,5-二氢吡唑衍生物及其制备方法 | |
CN115785104A (zh) | 一种一价金催化的螺[吲哚啉-3,3’-吡咯烷]衍生物的合成方法 | |
CN115260122A (zh) | 一种萘并噻唑类衍生物及其合成方法 | |
SONE et al. | Effect of ring substituent on the stability of the epoxide derived from phenyl vinyl ether | |
CN115417767A (zh) | 一种卡龙酸酐及其中间体的制备方法 | |
JPH0253749A (ja) | カリックスアレーン誘導体の製造方法 | |
JPS6021150B2 (ja) | 環状尿素誘導体およびその製造方法 | |
CN111205264A (zh) | 一种合成同位羟基和甲磺酰甲基化合物的新方法 | |
Weiner et al. | Synthesis of Indole Derivatives Attached to Polyethylene Oxides | |
JPH05213922A (ja) | ラクトン誘導体の新規製造方法 | |
CN111116506A (zh) | 一种芳巯基二唑类衍生物的合成方法 | |
JPS62205074A (ja) | 4−アルコキシ−2−ブテニルラクトンの製造方法 | |
JPS647973B2 (zh) |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |