CN103804152B - (2R, 3R)-or (2S, 3S)-Isosorbide-5-Nitrae-dimethoxy-1, Isosorbide-5-Nitrae, the preparation method of 4-tetraphenyl-2,3-butanediol - Google Patents
(2R, 3R)-or (2S, 3S)-Isosorbide-5-Nitrae-dimethoxy-1, Isosorbide-5-Nitrae, the preparation method of 4-tetraphenyl-2,3-butanediol Download PDFInfo
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- CN103804152B CN103804152B CN201410053033.2A CN201410053033A CN103804152B CN 103804152 B CN103804152 B CN 103804152B CN 201410053033 A CN201410053033 A CN 201410053033A CN 103804152 B CN103804152 B CN 103804152B
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- tetraphenyl
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- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- MYAYWOOOHKPAPF-UHFFFAOYSA-N 1-benzo[a]anthracen-1-ylbutane-2,3-diol Chemical compound C1(=CC=CC2=CC=C3C=C4C=CC=CC4=CC3=C12)CC(C(C)O)O MYAYWOOOHKPAPF-UHFFFAOYSA-N 0.000 title claims description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 39
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims abstract description 26
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 26
- -1 methoxyl group Chemical group 0.000 claims abstract description 19
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 17
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract description 11
- OTEKOJQFKOIXMU-UHFFFAOYSA-N 1,4-bis(trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=C(C(Cl)(Cl)Cl)C=C1 OTEKOJQFKOIXMU-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000000903 blocking effect Effects 0.000 claims abstract description 8
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims abstract description 8
- 238000006467 substitution reaction Methods 0.000 claims abstract description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- 239000003513 alkali Substances 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- BQFCCCIRTOLPEF-UHFFFAOYSA-N chembl1976978 Chemical compound CC1=CC=CC=C1N=NC1=C(O)C=CC2=CC=CC=C12 BQFCCCIRTOLPEF-UHFFFAOYSA-N 0.000 claims 2
- GLASTLWSBGGJCS-UHFFFAOYSA-N 4-benzo[a]anthracen-1-ylbutane-1,1,1,2-tetrol Chemical compound C1(=CC=CC2=CC=C3C=C4C=CC=CC4=CC3=C12)CCC(C(O)(O)O)O GLASTLWSBGGJCS-UHFFFAOYSA-N 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 abstract description 5
- 230000003287 optical effect Effects 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- AXJXOZFACYIMBU-NSOVKSMOSA-N (2S,3S)-1,4-dimethoxy-1,1,4,4-tetraphenylbutane-2,3-diol Chemical compound COC([C@H]([C@@H](C(C1=CC=CC=C1)(C1=CC=CC=C1)OC)O)O)(C1=CC=CC=C1)C1=CC=CC=C1 AXJXOZFACYIMBU-NSOVKSMOSA-N 0.000 abstract description 3
- YSAVZVORKRDODB-UHFFFAOYSA-N Diethyl tartrate Chemical compound CCOC(=O)C(O)C(O)C(=O)OCC YSAVZVORKRDODB-UHFFFAOYSA-N 0.000 abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000005815 base catalysis Methods 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 229910010082 LiAlH Inorganic materials 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000012429 reaction media Substances 0.000 description 3
- 229940095064 tartrate Drugs 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 238000001311 chemical methods and process Methods 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 230000007096 poisonous effect Effects 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001638 boron Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Chemical Kinetics & Catalysis (AREA)
Abstract
The invention discloses one (2R, 3R)-or (2S, 3S)-1, 4-dimethoxy-1, 1, 4, 4-tetraphenyl-2, the preparation method of 3-butyleneglycol: optical pure tartaric acid diethyl ester is obtained (2R after phenylating, 3R)-or (2S, 3S)-1, 1, 4, 4-tetraphenyl butantetraol, react with sulfur oxychloride and generate (4R, 5R)-or (4S, 5S)-4, the two hexichol chloromethyl cyclic sulfite of 5-, in the presence of a base, methoxyl group is introduced with methyl alcohol generation substitution reaction in appropriate medium, obtained (4R, 5R)-or (4S, 5S)-4, 5-bi-methoxy diphenyl-methyl cyclic sulfite, again in the presence of a base, slough sulfinyl blocking groups in appropriate medium and obtain (2R, 3R)-or (2S, 3S)-1, 4-dimethoxy-1, 1, 4, 4-tetraphenyl-2, 3-butyleneglycol.The method raw material is easy to get, easy and simple to handle, and with low cost.
Description
Technical field
The present invention relates to C
2the preparation method of Symmetric Chiral glycol, belongs to preparation method's technical field of chipal compounds, specifically discloses one (2R, 3R)-or (2S, 3S)-Isosorbide-5-Nitrae-dimethoxy-1, Isosorbide-5-Nitrae, the preparation method of 4-tetraphenyl-2,3-butanediol.
Background technology
C
2chiral diol as pure in mapping dinaphthol [(a) Whitesell, J.K.Chem.Rev.1989,89,1581; (b) Brunel, J.M.Chem.Rev.2005,105,857-897; (c) Chen, Y.; Yekta, S.; Yudin, A.K.Chem.Rev.2003,103,3155 – 3212; (d) Periasamy, M.Aldrichim.Acta.2002,35,89.] and TADDOLs [(a) Pellissier, H.Tetrahedron2008,64,10279; (b) Seebach, D.; Beck, A.K.; Heckel A.Angew.Chem.Int.Ed.2001,40,92.] etc. be widely used in asymmetric catalysis synthesis and supramolecular chemistry.The C that tartrate is derivative
2chiral diol (2R, 3R)-Isosorbide-5-Nitrae-dimethoxy-1, Isosorbide-5-Nitrae, 4-tetraphenyl-2,3-butanediol is as chiral auxiliary(reagent), and especially the protecting group of chirality boric acid ester, is widely used in asymmetric synthesis.[(a)Vahabi,R.;Frey,W.;Pietruszka,J.J.Org.Chem.2013,78,11549.(b)Berg,C.A.;Eichenauer,N.C.;Pietruszka,J.Pure Appl.Chem.2012,84,2339.(c)Fernández,E.;Frey,W.;Pietruszka,J.Synlett2010,1386;(d)Luithle,J.;Pietruszka,J.J.Org.Chem.2000,65,9194.]
(2R, 3R)-and (2S, 3S)-Isosorbide-5-Nitrae-dimethoxy-1, Isosorbide-5-Nitrae, 4-tetraphenyl-2,3-butanediol is by Nakayama andRainier obtained [Nakayama, K. the earliest; Rainier, J.D.Tetrahedron1990,46,4165.]: from Threaric acid ester, through 5 step reactions, target product total recovery is 38%.Wherein crucial step is that the protection and going of tartrate secondary hydroxyl is protected and the program that methylates of tert-hydroxyl, sloughs blocking group and will use reagent D DQ costly and LiAlH
4, methylation reaction is then realized by NaH/MeI system.2008, [Bischop, the M. such as Pietruszk, J.; Cmrecki, V.; Ophoven, V.; Pietruszk, J.Synthesis2008,2488.] this preparation method is improved: instead of expensive poisonous DDQ with cheap inorganic salt and be oxidized, but still will LiAlH be used
4.Recently, our study group has developed boron chemical process preparation (2R, 3R)-and (2S, 3S)-Isosorbide-5-Nitrae-dimethoxy-1,1,4,4-tetraphenyl-2,3-butanediol [Authorization Notice No.: CN101921181B]: tartrate and phenyl grignard reagent react obtained chirality 1,1,4,4-tetraphenyl butantetraol, is reacted with boric acid ester and generates chirality spiral shell borate, then methylated by NaH/MeI system, finally obtain (2R with HF/MeOH hydrolysis, 3R)-or (2S, 3S)-Isosorbide-5-Nitrae-dimethoxy-1,1,4,4-tetraphenyl-2,3-butanediol.Although we avoid oxidation, reducing program at this boron chemical process of research and development, do not use expensive poisonous DDQ, LiAlH
4deng reagent, but still have employed NaH/MeI system and methylate, and be hydrolyzed with HF, in cost and environment, still there is many problems.
Based on above-mentioned condition, the invention provides one with optical pure tartaric acid ester for chiral source, by sulfinyl chiral 1, 1, 4, 2 of 4-tetraphenyl butantetraol, 3-position secondary hydroxyl carries out protecting and go protection, by (4R, 5R)-or (4S, 5S)-4, methoxyl group is introduced in the two hexichol chloromethyl cyclic sulfite of 5-and methyl alcohol generation substitution reaction, avoid traditional NaH/MeI to methylate program, (the 4R obtained, 5R)-or (4S, 5S)-4, 5-bi-methoxy diphenyl-methyl cyclic sulfite removes sulfinyl blocking groups group under finite concentration base catalysis, obtained (2R, 3R)-or (2S, 3S)-1, 4-dimethoxy-1, 1, 4, 4-tetraphenyl-2, 3-butyleneglycol, there is not been reported for this synthetic method.
Summary of the invention
For the deficiencies in the prior art, one has been the object of the present invention is to provide to prepare (2R, 3R) or (2S, 3S)-Isosorbide-5-Nitrae-dimethoxy-1, Isosorbide-5-Nitrae, efficient, the convenient method of 4-tetraphenyl-2,3-butanediol.The method raw material is easy to get, easy and simple to handle and with low cost.
Principle of the present invention: phenyl grignard reagent and optical pure tartaric acid diethyl ester are obtained by reacting (2R; 3R)-or (2S, 3S)-1,1; 4; 4-tetraphenyl butantetraol, reacts obtained (4R, 5R)-or (4S with sulfur oxychloride; 5S)-4; the two hexichol chloromethyl cyclic sulfite of 5-, introduces methoxyl group with methyl alcohol generation substitution reaction then, then under base catalysis, sloughs sulfinyl blocking groups obtain target compound.Wherein, (4R, 5R)-or (4S, 5S)-4, the two hexichol chloromethyl cyclic sulfite of 5-can according to previous patent (Dan Zixing, Hu Xiaoyun, patent publication No. CN102603705A) by (2R, 3R)-or (2S, 3S)-1, Isosorbide-5-Nitrae, 4-tetraphenyl butantetraol and sulfur oxychloride react obtained, see embodiment 6 and the embodiment 7 of this patent application.
Technical scheme of the present invention: optical pure tartaric acid diethyl ester is through the obtained (2R of phenylating, 3R)-or (2S, 3S)-1, Isosorbide-5-Nitrae, 4-tetraphenyl butantetraol, obtained (the 4R of regioselective reaction is carried out again with sulfur oxychloride, 5R)-or (4S, 5S)-4,5-pairs of hexichol chloromethyl cyclic sulfites.In the presence of a base, in suitable reaction medium, introduce methoxyl group with methyl alcohol generation substitution reaction; obtained (4R, 5R)-or (4S, 5S)-4; 5-bi-methoxy diphenyl-methyl cyclic sulfite, then under base catalysis, in suitable solvent, slough sulfinyl blocking groups obtain (2R; 3R)-or (2S, 3S)-Isosorbide-5-Nitrae-dimethoxy-1; 1; 4,4-tetraphenyl-2,3-butanediol.
According to the present invention, (2R, 3R)-or (2S, 3S)-1, 4-dimethoxy-1, 1, 4, 4-tetraphenyl-2, the preparation of 3-butyleneglycol is to (2R by sulfinyl, 3R)-or (2S, 3S)-1, 1, 4, 2 of 4-tetraphenyl butantetraol, 3-position secondary hydroxyl carries out protection and de-protected, and by (4R, 5R)-or (4S, 5S)-4, methoxyl group is introduced in the substitution reaction of the two hexichol chloromethyl cyclic sulfite of 5-and methyl alcohol, obtained (4R, 5R)-or (4S, 5S)-4, 5-bi-methoxy diphenyl-methyl cyclic sulfite, avoid NaH/MeI methylation method traditional at present.The going to protect of sulfinyl removes under base catalysis, goes protection process unresolvable tartaric acid chiral skeleton that racemization does not occur at this.
According to the present invention, (4R, 5R)-or (4S, 5S)-4,5-pairs of hexichol chloromethyl cyclic sulfites and methyl alcohol carry out substitution reaction alkali used by Py, NEt
3select Deng in organic bases, alkali is (1-10) with the mol ratio of (4R, 5R)-or (4S, 5S)-4,5-pairs of hexichol chloromethyl cyclic sulfites: 1; Reaction medium is selected in THF, acetonitrile, methyl alcohol.
According to the present invention, (4R, 5R)-or (4S, 5S)-4,5-bi-methoxy diphenyl-methyl cyclic sulfite slough the alkali that uses in the reaction of sulfinyl blocking groups by NaOH, KOH, K
2cO
3, Na
2cO
3middle selection, alkali and (4R, 5R)-or (4S, 5S)-4,5-the mol ratio of bi-methoxy diphenyl-methyl cyclic sulfite be (2-10): 1; Reaction medium is tetrahydrofuran (THF), any one or two or more mixtures in acetonitrile, dimethyl formamide, ethanol, water.
Compared with prior art, advantage of the present invention and beneficial effect are:
(the 2R that the present invention describes, 3R)-and (2S, 3S)-1, 4-dimethoxy-1, 1, 4, 4-tetraphenyl-2, 3-butyleneglycol preparation method is with sulfinyl chiral 1, 1, 4, the secondary hydroxyl of 4-tetraphenyl butantetraol carries out protecting and go protection, with (4R, 5R)-or (4S, 5S)-4, methoxyl group is introduced in the substitution reaction of the two hexichol monochloromethyl cyclic sulfite of 5-and methyl alcohol, obtained (4R, 5R)-or (4S, 5S)-4, 5-bi-methoxy diphenyl-methyl cyclic sulfite, under finite concentration base catalysis, remove sulfinyl blocking groups obtain target compound, go protection process unresolvable tartaric acid chiral skeleton that racemization does not occur at this.The method raw material is easy to get, and relative to current existing preparation method, synthetic route is short, does not use DDQ, LiAlH
4expensive or the toxic reagent with HF etc., and do not need NaH and MeI or Me
2sO
4deng methylating reagent, do not need specific installation, easy and simple to handle and with low cost, there is industrial prospect.
Accompanying drawing explanation
Fig. 1 is (4R, 5R)-4,5-single crystal structure figure of bi-methoxy diphenyl-methyl cyclic sulfite that embodiment 1 step 3 obtains.
Embodiment
Applicant will be described in further detail the inventive method in conjunction with specific embodiments below.
Embodiment 1:(2R, 3R)-Isosorbide-5-Nitrae-dimethoxy-1, Isosorbide-5-Nitrae, the preparation method of 4-tetraphenyl-2,3-butanediol, step is as follows:
Step one: (2R, 3R)-1, Isosorbide-5-Nitrae, the preparation of 4-tetraphenyl butantetraol
The tetrahydrofuran solution of (2R, 3R)-diethyl tartrate is added drop-wise in the tetrahydrofuran solution of the phenyl-magnesium-bromide that stirred of 6 equivalents, after having reacted; use saturated aqueous ammonium chloride cancellation; extracted with diethyl ether, concentrated, by obtaining (2R after silica gel column chromatography; 3R)-1; Isosorbide-5-Nitrae, 4-tetraphenyl butantetraol; yield: 50%, m.p.:149-150 DEG C; [α]
d 25=+154.0 (c1.2, CHCl
3); IR (KBr): 3436,3058,2916,1598,1492,1447,1063,698;
1h-NMR (CDCl
3, 300MHz): δ 7.37 – 7.13 (m, 20H, Ar-H); 4.65 (d, J=7.2Hz, 2H, OH) 4.41 (d, J=4.7Hz, 2H, CH); 3.77 (d, J=5.3Hz, 2H, OH).
13c-NMR (CDCl3,75MHz) δ 143.8; 142.7; 134.6; 131.5; 129.3; 128.3; 128.2; 127.9; 127.5; 126.7; 125.5; 81.3,69.7.
Step 2: the preparation of (4R, 5R)-4,5-pairs of hexichol chloromethyl cyclic sulfites
(2R, 3R)-1, Isosorbide-5-Nitrae, 4-tetraphenyl butantetraol and sulfur oxychloride under triethylamine exists (mol ratio is 1:4:8) react 3 hours in THF, and add water stopped reaction, extracted with diethyl ether, and after concentrated, column chromatography obtains white solid, yield: 90%, m.p.:187-189 DEG C, [α]
d 20=+12.5 (c0.50, EA).
1h-NMR (300MHz, CDCl
3): δ 7.43-7.49 (m, 4H), 7.27-7.35 (m, 10H), 7.14-7.18 (m, 6H), 6.06 (d, J=1.2Hz), 5.82 (d, J=1.8Hz).
13c-NMR (75MHz, CDCl
3): δ 141.4,140.1,129.2,129.0,128.5,128.2,128.1,127.9,87.5,87.3,78.6.
Step 3: (4R, 5R)-4,5-preparation of bi-methoxy diphenyl-methyl cyclic sulfite
(4R, 5R)-4, the two hexichol chloromethyl cyclic sulfite of 5-and methyl alcohol is (mol ratio is 1:3:3) 70 DEG C of heating after 3 hours in anhydrous THF under pyridine exists, concentrated, be chilled to room temperature and separate out (4R, 5R)-4,5-bi-methoxy diphenyl-methyl cyclic sulfite, yield: 96%, m.p.:126-129 DEG C, [α]
d 20=-210 (c1, CH
2cl
2).
1h-NMR (300MHz, CDCl
3): δ 7.46-7.25 (m, 20H), 5.87 (d, J=1.8Hz, 1H), 5.55 (d, J=1.5Hz, 1H), 3.00 (s, 3H), 2.64 (s, 3H).
13c-NMR (75MHz, CDCl
3): δ 134.9,134.1,133.9,133.6,132.5,132.3,132.2,131.9,90.8,88.9,57.9,56.5.
Single crystal data: empirical formula, C30H28O5S; Formula weight, 500.58; Calculateddensity, 1.241g/cm
3; Volume (V), 2679 (3)
crystal system, Orthorhombic; Space group, P2 (1) 2 (1) 2 (1); Z=4; Unit cell dimensions, a=9.171 (5), b=16.692 (10), c=17.498 (10), ° β=90 °, α=90, γ=90 °; Absorption coefficient (μ), 0.158mm
-1; Index ranges-10≤h≤11 ,-20≤k≤20 ,-21≤l≤21; F (000), 1056; GOF, No. 1.043.CCDC: 979502, its structure is shown in Fig. 1 in accompanying drawing.
Step 4: (2R, 3R)-Isosorbide-5-Nitrae-dimethoxy-1, Isosorbide-5-Nitrae, the preparation of 4-tetraphenyl-2,3-butanediol
(4R, 5R)-4,5-bi-methoxy diphenyl-methyl cyclic sulfite and solid NaOH(mol ratio be 1:3) to be dissolved in the mixed solvent of acetonitrile and water in (acetonitrile: water volume ratio is 6:1), 80 DEG C of reacting by heating 5 hours, then remove reaction solvent, add dilute hydrochloric acid acidifying and separate out (2R, 3R)-Isosorbide-5-Nitrae-dimethoxy-1,1,4,4-tetraphenyl-2,3-butanediol, yield: 98%, m.p.:78-80 DEG C, [α]
d 15=+59.6 (c0.08, CHCl
3),
1h NMR (300MHz, CDCl
3): δ 7.25-7.44 (m, 20H, Ph-H), 4.71 (d, J=3.3Hz, 2H, CH), 3.16 (s, 6H, OCH
3), 2.74 (br, 2H, OH).
13c NMR (75MHz, CDCl
3): δ 142.8,141.5,129.0,128.3,128.1,128.0,127.5,127.7,85.4,71.3,53.7.ESI:477 [M+23].
Embodiment 2:(2S, 3S)-Isosorbide-5-Nitrae-dimethoxy-1, Isosorbide-5-Nitrae, the preparation of 4-tetraphenyl-2,3-butanediol, step is as follows:
Step one and step 2: only change raw material (2R, 3R)-diethyl tartrate into (2S, 3S)-diethyl tartrate, all the other operations, all with embodiment 1, obtain (4S, 5S)-4,5-pairs of hexichol chloromethyl cyclic sulfites.
Step 3: (4S, 5S)-4,5-preparation of bi-methoxy diphenyl-methyl cyclic sulfite
(4S, 5S)-4, the two hexichol chloromethyl cyclic sulfite of 5-and triethylamine (mol ratio is 1:4) are dissolved in anhydrous methanol, and 70 DEG C of heating are after 3 hours, concentrated, be chilled to room temperature and separate out (4S, 5S)-4,5-bi-methoxy diphenyl-methyl cyclic sulfite, yield: 95%, m.p.:125-128 DEG C, [α]
d 20=+209 (c1, CH
2cl
2).
1h-NMR (300MHz, CDCl
3): δ 7.46-7.25 (m, 20H), 5.87 (d, J=1.8Hz, 1H), 5.55 (d, J=1.5Hz, 1H), 3.00 (s, 3H), 2.64 (s, 3H).
13c-NMR (75MHz, CDCl
3): δ 134.9,134.1,133.9,133.6,132.5,132.3,132.2,131.9,90.8,88.9,57.9,56.5.
Step 4:(2S, 3S)-Isosorbide-5-Nitrae-dimethoxy-1, Isosorbide-5-Nitrae, the preparation of 4-tetraphenyl-2,3-butanediol
(4S, 5S)-4,5-bi-methoxy diphenyl-methyl cyclic sulfite and K
2cO
3(mol ratio is 1:5) to be dissolved in the mixed solvent of dimethyl formamide and water in (dimethyl formamide: water volume ratio is 9:1), 90 DEG C are heated 7 hours, and then in impouring dilute hydrochloric acid, (2S, 3S)-1 is separated out in acidifying, 4-dimethoxy-1, Isosorbide-5-Nitrae, 4-tetraphenyl-2,3-butyleneglycol, yield: 97%, m.p.:78-80 DEG C, [α]
d 15=-59.2 (c0.1, CHCl
3),
1h NMR (300MHz, CDCl
3): δ 7.25-7.44 (m, 20H, Ph-H), 4.71 (d, J=3.3Hz, 2H, CH), 3.16 (s, 6H, OCH3), 2.74 (br, 2H, OH).
13c NMR (75MHz, CDCl
3): δ 142.8,141.5,129.0,128.3,128.1,128.0,127.5,127.7,85.4,71.3,53.7.ESI:477 [M+23].
Specific embodiment described in this specification sheets is only to the explanation for example of the present invention's spirit.Those skilled in the art can make various amendment or supplement or adopt similar mode to substitute to described specific embodiment, but can't depart from spirit of the present invention or surmount the scope that appended claims defines.
Claims (3)
1. one kind (2R, 3R)-or (2S, 3S)-1,4-dimethoxy-1, Isosorbide-5-Nitrae, the preparation method of 4-tetraphenyl-2,3-butanediol: in solvent orange 2 A, under alkali A exists, (4R, 5R)-or (4S, 5S)-4, methoxyl group is introduced in the two hexichol chloromethyl cyclic sulfite of 5-and methyl alcohol generation substitution reaction, obtained (4R, 5R)-or (4S, 5S)-4,5-bi-methoxy diphenyl-methyl cyclic sulfite; Next in solvent B, under alkali B exists, (4R, 5R)-or (4S, 5S)-4,5-bi-methoxy diphenyl-methyl cyclic sulfite is sloughed sulfinyl blocking groups and is obtained (2R, 3R)-or (2S, 3S)-1,4-dimethoxy-1, Isosorbide-5-Nitrae, 4-tetraphenyl-2,3-butanediol;
Described solvent orange 2 A is any one in tetrahydrofuran (THF), acetonitrile, methyl alcohol;
Described solvent B is any one or two or more mixtures in tetrahydrofuran (THF), acetonitrile, dimethyl formamide, ethanol, water;
Described alkali A is pyridine or triethylamine;
Described alkali B is NaOH, KOH, K
2cO
3or Na
2cO
3.
2. preparation method according to claim 1, is characterized in that: described alkali A is (1-10) with the mol ratio of (4R, 5R)-or (4S, 5S)-4,5-pairs of hexichol chloromethyl cyclic sulfites: 1.
3. preparation method according to claim 1, is characterized in that: described alkali B and (4R, 5R)-or (4S, 5S)-4,5-the mol ratio of bi-methoxy diphenyl-methyl cyclic sulfite be (2-10): 1.
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| Facile Synthesis and Unusual Methanesulfonylation Reaction of (2R,3R)-1,4-Dimethoxy-1,1,4,4-tetrasubstituted-2,3-butanediols;Sankareswaran Srimurugan et al.;《Synthetic Communications》;20070809;第37卷;2483–2490 * |
| MORRIS J . ROBINS,et al..Nucleic acid related compounds. 66. Improved syntheses of 5"-chloro-5"-deoxy- and 5"-S-aryl(or alky1)-5"-thionucleosides.《Canadian Journal of Chemistry》.1991,第69卷1468-1474. * |
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