CN102140080A - Method for synthesizing sulfoacid organic compounds in one step - Google Patents
Method for synthesizing sulfoacid organic compounds in one step Download PDFInfo
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- CN102140080A CN102140080A CN2011100253162A CN201110025316A CN102140080A CN 102140080 A CN102140080 A CN 102140080A CN 2011100253162 A CN2011100253162 A CN 2011100253162A CN 201110025316 A CN201110025316 A CN 201110025316A CN 102140080 A CN102140080 A CN 102140080A
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- 238000000034 method Methods 0.000 title claims abstract description 12
- 230000002194 synthesizing effect Effects 0.000 title abstract description 3
- 150000002894 organic compounds Chemical class 0.000 title abstract 3
- -1 aldehyde ketone Chemical class 0.000 claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 150000001728 carbonyl compounds Chemical class 0.000 claims abstract description 5
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims abstract description 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims abstract description 3
- 235000010262 sodium metabisulphite Nutrition 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 239000012434 nucleophilic reagent Substances 0.000 claims description 6
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical group O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 claims description 4
- 229950009041 edaravone Drugs 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- 229910010082 LiAlH Inorganic materials 0.000 claims description 2
- 150000001336 alkenes Chemical class 0.000 claims description 2
- WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 150000003460 sulfonic acids Chemical class 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- 239000007864 aqueous solution Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 239000000758 substrate Substances 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000005580 one pot reaction Methods 0.000 abstract 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 abstract 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- GNTDGMZSJNCJKK-UHFFFAOYSA-N divanadium pentaoxide Chemical compound O=[V](=O)O[V](=O)=O GNTDGMZSJNCJKK-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
- 238000005352 clarification Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 125000000542 sulfonic acid group Chemical group 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000001132 ultrasonic dispersion Methods 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-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
- 239000005864 Sulphur Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 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
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000000524 functional group Chemical group 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
- 150000002500 ions Chemical class 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000000203 mixture Substances 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
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000007344 nucleophilic reaction Methods 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a new method for synthesizing sulfoacid organic compounds in one step, which comprises the step of reacting active hydrogen-containing compounds serving as a substrate with carbonyl compounds such as aldehyde ketone in solution of sodium hydrogensulfite or sodium pyrosulfite to prepare the sulfoacid organic compounds in a one-pot way. The method has mild reaction condition and high yield of products, and is suitable for large-scale industrial production.
Description
Technical field
The present invention relates to the novel method that a kind of simple and efficient prepares the organic sulfonic acid compounds.
Background technology
Sulfonic compound is the important organic synthesis intermediate of a class.Difference according to introducing the sulfonic acid group condition mainly contains following several:
1,, carries out oxidation again and obtain the sulfonic acid functional group by introducing sulfur-bearing functional group.As mercaptan oxidation (Tetrahedron Letters, 2008,49 (20) 3291-3293), lsothiocyanates oxidation (Acta Chemica Scandinavica, Series B:OrganicChemistry and Biochemistry, 1982,36 (10), 669-674) etc., it be the mercaptan and the lsothiocyanates of breath malodor that this class methods limitation at first need substrate conversion to be, oxidising agent is chlorine that severe toxicity or strong oxidation are arranged, hydrogen peroxide etc.
2, the sulfonated reaction of electron-withdrawing group such as carbonyl, ester group adjacent.Sulfonated (Synthesis as propionyl benzene; German; 1979; 699-700).These class methods need be used highly acid sulphur trioxide/dioxane mixture, this reagent preparation difficulty and have severe corrosive.
3, carry out nucleophilic substitution reaction under halides and the S-WAT high temperature and obtain corresponding sulfoacid compound.(Bioorganic ﹠amp; Medicinal Chemistry Letters, 2004,14 (20), 5145-5150) this class methods require substrate to introduce halogen atom in advance and halides has higher activity, and reaction needed is being carried out more than 200 ℃.
The condition of above-mentioned reaction is gentle inadequately, agents useful for same is also comparatively expensive, and environment is had certain pollution.Therefore, be necessary to seek a kind of new, mild condition, reagent are inexpensive, environmental friendliness and the high new method of yield.
Summary of the invention:
The object of the present invention is to provide a kind of highly effective to prepare the novel method of sulfonic compound.Reaction conditions gentleness, yield height, agents useful for same is inexpensive and environmentally friendly.
Technical scheme of the present invention with carbonyl compound reacting by heating in sodium bisulfite or metabisulfite solution, can prepare sulfonic acid class organic compound for being substrate to contain compound bearing active hydrogen.
The described compound bearing active hydrogen that contains is the compound that hydrogen atom is contained at the electron-withdrawing group ortho position in the compound structure.
Described electron-withdrawing group is nitro, cyano group, ester group or carbonyl.
Described carbonyl compound is to contain ketone carbonyl and aldehyde carbonyl in the compound structure.
Described preparation method may further comprise the steps
Wherein
Form intermediate product 2 under solutions of weak acidity fast, intermediate product is heated and sloughs a part water and form final product 3 with nucleophilic reagent.
R wherein
1Be selected from H, C
1-6Alkyl, C
1-6Substituted alkyl, C
6-12Aryl, C
6-12The aryl of replacement, the substituting group of alkyl and aryl is halogen, nitro, amino, acyl group;
R
2Be selected from H, C
1-6Alkyl, C
1-6Substituted alkyl, C
6-12Aryl, C
6-12The aryl of replacement, the substituting group of alkyl and aryl is halogen, nitro, amino, acyl group, and R
1, R
2Be not hydrogen simultaneously;
On behalf of reagent and carbon atom, the affinity of Nu-nucleophilic reagent (refer generally to R
+) the bonded ability, according to document: Wang Fan, the affinity of reagent and alkalescence in the nucleophilic reaction, " Qujing teachers training school journal ", and 1992 the 2nd phases (total o. 11th), 61 pages classification, nucleophilic reagent usually can be divided into following six classes:
A, all negative ion.As: OH
-,-CN ,-NH
2,-OR, RCOO-, H
-Deng.
B, alkene class and aromatic hydroxy compound.
C, reductive agent are as Na, Sn
2+, LiAlH
4, NaBH
4, BH
3Deng.
D, has the not molecule of share electron pair, as RNH
2, ROR, ROH, R
2NH, R
3N etc.
E, bases.As NaOH, KNH
2, RONa, NaH etc.
F, organometallics are as RMgX, RLi, RNa etc.
Further, the R among above-mentioned A, C, D, E, the F is suitable group, is generally alkyl, substituted alkyl, the aryl of aryl, replacement, the heteroaryl of heteroaryl, replacement, the heterocyclic radical of heterocyclic radical, replacement.
" alkyl " refers to represent the saturated aliphatic radical of 1-20 carbon atom, comprise straight chain and the branched group (digital scope of mentioning in the application's book, for example " 1-20 ", be meant this group, be alkyl this moment, can contain 1 carbon atom, 2 carbon atoms, 3 carbon atoms etc., until comprising 20 carbon atoms).The alkyl that contains 1-4 carbon atom is called low alkyl group.When low alkyl group does not have substituting group, be called unsubstituted low alkyl group.More preferably, alkyl is the medium sized alkyl that 1-10 carbon atom arranged, for example methyl, ethyl, propyl group, 2-propyl group, normal-butyl, isobutyl-, the tertiary butyl, amyl group etc.Preferably, alkyl is the low alkyl group that 1-4 carbon atom arranged, for example methyl, ethyl, propyl group, 2-propyl group, normal-butyl, isobutyl-or the tertiary butyl etc.Alkyl can be that replace or unsubstituted.When being the alkyl that replaces, this substituting group preferably one or more, more preferably 1-3,1 or 2 substituting group most preferably, they are independently preferably from following group: halogen, hydroxyl, lower alkoxy, aryl, aryloxy, heteroaryl, heterocyclic radical.
" aryl " refers to the full carbon monocycle or the fused polycycle group of 5 to 12 carbon atoms, has the πDian Zi system of total conjugated.The limiting examples of aryl has phenyl, naphthyl and anthryl.Aryl can be that replace or unsubstituted.The substituting group of aryl is selected from halogen, nitro, amino, C
1-6Alkyl, C
1-6Alkoxyl group, halo C
1-6Alkyl, halo C
1-6Alkoxyl group, C
3-6Cycloalkyl, halo C
3-6Cycloalkyl, phenyl.
" heteroaryl " refers to the undersaturated carbocyclic ring of 5 to 12 annular atomses, and wherein one or more carbon are by for example displacements such as oxygen, nitrogen, sulphur of heteroatoms.Heteroaryl can be a monocycle, also can be dicyclo, promptly condenses by two rings to form.Concrete heteroaryl can be a pyridyl, pyrimidyl, pyrazinyl, isoxazolyl, isothiazolyl, pyrazolyl, thiazolyl, oxazolyl and imidazolyl etc.Heteroaryl can be that replace or unsubstituted.The substituting group of heteroaryl is selected from halogen, nitro, amino, C
1-6Alkyl, C
1-6Alkoxyl group, halo C
1-6Alkyl, halo C
1-6Alkoxyl group, C
3-6Cycloalkyl, halo C
3-6Cycloalkyl, phenyl.
" heterocyclic radical " refers to monocycle or fused rings group, has 5 to 9 annular atomses in ring, and one of them or two annular atomses are the heteroatomss that are selected from N, O or S (O) m (wherein m is 0 to 2 integer), and all the other annular atomses are C.These rings can have one or more pair of key, but these rings do not have the πDian Zi system of total conjugated.The limiting examples of unsubstituted heterocyclic has pyrazolinyl, pyrrolidyl, piperidino-(1-position only), Piperazino, morpholino base, thiomorpholine for base, high Piperazino etc.Heterocycle can be that replace or unsubstituted.The substituting group of heterocyclic radical can be one or more, and substituting group is selected from halogen, nitro, amino, C
1-6Alkyl, C
1-6Alkoxyl group, halo C
1-6Alkyl, halo C
1-6Alkoxyl group, C
3-6Cycloalkyl, halo C
3-6Cycloalkyl, phenyl.
" halogen " expression fluorine, chlorine, bromine or iodine are preferably fluorine or chlorine.
The preferred Edaravone of nucleophilic reagent of the present invention.
Temperature of reaction is 60～100 ℃, and the reaction times is 12-24h.
Beneficial effect of the present invention is:
One, step is simple, and single step reaction can be finished preparation sulfonic acid class organic compound;
Two, reaction conditions gentleness, yield height, agents useful for same is inexpensive and environmentally friendly.
Embodiment:
Content of the present invention is further elaborated by following embodiment and accompanying drawing, but does not limit the scope of the invention.
Embodiment 1: sodium 1-hydroxyl-2-(3-methyl-5-oxo-1-phenyl-4,5-dihydro-1 h-pyrazole-4-yl) propane-2-sulfonic acid (1)
With 150g NaHSO
3Be dissolved in the 500ml water, add 200ml 1-pyruvic alcohol, add the 50g Edaravone, be warming up to 80 ℃ of reaction 16h, the reaction solution clarification stops heating, be cooled to room temperature, with 200ml*3 extractive reaction liquid of ethyl acetate, the water intaking phase, water is concentrated into dried, add methyl alcohol 500ml, separate out white solid, filter, get filtrate, filtrate is concentrated into dried; After getting the Virahol ultra-sonic dispersion that concentrates 5 times of amounts of sample adding of doing, leave standstill 30min, filter, get white solid, the HPLC purity assay adds Vanadium Pentoxide in FLAKES vacuum-drying 24h more than 97%, promptly gets target product 1 (yield 85%).
MS(ESI)：311.1[M-Na]
+。
The NMR spectrogram
Embodiment 2: sodium 2-(3-methyl-5-oxo-1-phenyl-4,5-dihydro-1 h-pyrazole-4-yl) propane-2-sulfonic acid (2)
With 150g NaHSO
3Be dissolved in the 500ml water, add 200ml acetone, add the 50g Edaravone, be warming up to 90 ℃ of reactions and spend the night, the reaction solution clarification stops heating, be cooled to room temperature, with 200ml*3 extractive reaction liquid of ethyl acetate, the water intaking phase, water is concentrated into dried, add methyl alcohol 500ml, separate out white solid, filter, get filtrate, filtrate is concentrated into dried; After getting the Virahol ultra-sonic dispersion that concentrates 5 times of amounts of sample adding of doing, leave standstill 30min, filter, get white solid, the HPLC purity assay adds Vanadium Pentoxide in FLAKES vacuum-drying 24h more than 97%, promptly gets 2 (yield 83%).
The product that makes is tested, and the result is as follows:
NMR spectrogram 7.84 (d, 2H), 7.34 (d, 2H), 7.09 (t, 1H), 5.21-6.92 (br, 1H), 2.22 (s, 3H), 1.51 (s, 6H).
MS(ESI)：295.3[M-Na]
+。
Claims (7)
1. single stage method prepares the method for organic sulfonic acid compounds, it is characterized in that: heat in aqueous solution of sodium bisulfite or metabisulfite solution to contain compound bearing active hydrogen and carbonyl compound.
2. preparation method according to claim 1 is characterized in that: containing compound bearing active hydrogen is the compound that hydrogen atom is contained at the electron-withdrawing group ortho position in the compound structure.
3. preparation method according to claim 2 is characterized in that: electron-withdrawing group is nitro, cyano group, ester group or carbonyl.
4. preparation method according to claim 1 is characterized in that: carbonyl compound is to contain ketone carbonyl and aldehyde carbonyl in the compound structure.
5. preparation method according to claim 1 is characterized in that may further comprise the steps
，
R wherein
1Be selected from H, C
1-6Alkyl, C
1-6Substituted alkyl, C
6-12Aryl, C
6-12The aryl of replacement, the substituting group of alkyl and aryl is halogen, nitro, amino, acyl group;
R
2Be selected from H, C
1-6Alkyl, C
1-6Substituted alkyl, C
6-12Aryl, C
6-12The aryl of replacement, the substituting group of alkyl and aryl is halogen, nitro, amino, acyl group, and R
1, R
2Be not hydrogen simultaneously;
Nu
-Be nucleophilic reagent, Nu
-Be selected from OH
-,-CN ,-NH
2,-OR, RCOO-, H
-, alkene class and aromatic hydroxy compound, Na, Sn
2+, LiAlH
4, NaBH
4, BH
3, RNH
2, ROR, ROH, R
2NH, R
3N, NaOH, KNH
2, RONa, NaH, RMgX, RLi, RNa; R is selected from alkyl, substituted alkyl, the aryl of aryl, replacement, the heteroaryl of heteroaryl, replacement, the heterocyclic radical of heterocyclic radical, replacement; The substituting group of alkyl, aryl, heteroaryl and heterocyclic radical is selected from halogen, nitro, amino, C
1-6Alkyl, C
1-6Alkoxyl group, halo C
1-6Alkyl, halo C
1-6Alkoxyl group, C
3-6Cycloalkyl, halo C
3-6Cycloalkyl, phenyl.
6. preparation method according to claim 5 is characterized in that described nucleophilic reagent is an Edaravone.
7. preparation method according to claim 5 is characterized in that temperature of reaction is 60 ~ 100 ℃, and the reaction times is 12-24h.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101759605A (en) * | 2009-09-17 | 2010-06-30 | 常熟市瑞凯添加剂科技有限公司 | Preparation method of amino-substituted hydrocarbyl sulfonic acid |
| CN101805292A (en) * | 2010-04-27 | 2010-08-18 | 江苏先声药物研究有限公司 | Pyrazolines compound as well as application and preparation method thereof |
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| CN101759605A (en) * | 2009-09-17 | 2010-06-30 | 常熟市瑞凯添加剂科技有限公司 | Preparation method of amino-substituted hydrocarbyl sulfonic acid |
| CN101805292A (en) * | 2010-04-27 | 2010-08-18 | 江苏先声药物研究有限公司 | Pyrazolines compound as well as application and preparation method thereof |
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