CN108276256A - The preparation method of (2R, 3R) -2,3- dimethoxy -1,1,4,4- tetraphenyl -1,4- butanediols - Google Patents
The preparation method of (2R, 3R) -2,3- dimethoxy -1,1,4,4- tetraphenyl -1,4- butanediols Download PDFInfo
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- CN108276256A CN108276256A CN201810138381.8A CN201810138381A CN108276256A CN 108276256 A CN108276256 A CN 108276256A CN 201810138381 A CN201810138381 A CN 201810138381A CN 108276256 A CN108276256 A CN 108276256A
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- isosorbide
- nitrae
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/16—Preparation of ethers by reaction of esters of mineral or organic acids with hydroxy or O-metal groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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Abstract
The present invention relates to one kindC 2 The preparation method of Symmetric Chiral glycol belongs to chipal compounds and prepares chemical field, specifically discloses a kind of (2R, 3R) 2,3 dimethoxy 1, Isosorbide-5-Nitrae, the preparation method of 4 tetraphenyl Isosorbide-5-Nitrae butanediols：Threaric acid diethylester is made (2 through phenylatingR,3R) 1, Isosorbide-5-Nitrae, 4 tetraphenyl erythrol, in certain temperature and suitable reaction medium, the reaction of 2,3 di-methylation of high regioselectivity occurs with NaH and methylating reagent, (2R, 3R) 2,3 dimethoxy 1 is made, Isosorbide-5-Nitrae, 4 tetraphenyl Isosorbide-5-Nitrae butanediols.This method raw material is easy to get, easy to operate and of low cost.
Description
Technical field
The present invention relates to a kind of C2The preparation method of Symmetric Chiral glycol belongs to chipal compounds and prepares chemical field, specifically
Disclose the preparation method of one kind (2R, 3R) -2,3- dimethoxy -1,1,4,4- tetraphenyl -1,4- butanediols.
Background technology
C2The pure dinaphthol of chiral diol such as mapping [(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. have been widely used for asymmetric catalysis synthesis and supermolecule
In chemistry.C derived from tartaric acid2Chiral diol (2R, 3R) -2,3- dimethoxy -1,1,4,4- tetraphenyl -1,4- butanediols exist
It is used as chiral hosts [J.Chem.Soc.Perkin Trans.2,1993,2359-2361] in chiral supramolecular chemistry.At present
Dimethoxy -1 (2R, 3R) -2,3-, Isosorbide-5-Nitrae, the preparation method of 4- tetraphenyls -1,4-butanediol are led to using tartrate as raw material
It crosses NaH/MeI pairs of two free hydroxyls to be etherified, then be reacted with Grignard Reagent, introduce four phenyl.Wherein, etherificate is anti-
It is 91% to answer yield, and Grignard Reagent reaction yield only 20% (the low yield of the step is related with grignard post-reaction treatment program), always
Yield is 18% [J.Chem.Soc.Perkin Trans.2,1993,2359-2361], the preparation method target compound yield
It is relatively low.
Based on the above situation, the present invention is by Threaric acid ester, (2R, 3R) -1 is synthesized using " one-step method ", Isosorbide-5-Nitrae,
4- tetraphenyl erythrol passes through (2R, 3R) -1, Isosorbide-5-Nitrae, the regioselectivity of 4- tetraphenyls erythrol and NaH and methylating reagent
2,3- di-methylations react, and realize (2R, 3R) -1, Isosorbide-5-Nitrae, 4- tetraphenyls erythrol 2, and 3- secondary hydroxyls methylate, and Isosorbide-5-Nitrae -
Position tert-hydroxyl is unaffected, to which dimethoxy -1 (2R, 3R) -2,3-, Isosorbide-5-Nitrae, tetra- benzene of 4- efficiently be made with 43% total recovery
Base -1,4-butanediol, there is not been reported for the synthetic method.
Invention content
For the deficiencies in the prior art, the object of the present invention is to provide one kind (2R, 3R) -2,3- dimethoxies
The high efficiency preparation method of base -1,1,4,4- tetraphenyl -1,4- butanediols.This method raw material is easy to get, easy to operate and of low cost.
The principle of the present invention：(2R, 3R) -1,1,4,4- tetraphenyls fourth four is made through phenylating in Threaric acid diethylester
Alcohol, (2R, 3R) -1, Isosorbide-5-Nitrae, 4- tetraphenyls erythrol at a temperature of 0-25 DEG C, tetrahydrofuran, ether, toluene, dichloromethane or
It is reacted with NaH in the media such as ethyl acetate, the intramolecular hydrogen bond effect using Isosorbide-5-Nitrae-position tert-hydroxyl and four phenyl substituents
Steric hindrance effect shields Isosorbide-5-Nitrae-position tert-hydroxyl, to allow 2,3- secondary hydroxyls selectivity and NaH effects, then with
CH3The methylating reagents such as I or dimethyl suflfate react, and Isosorbide-5-Nitrae-position tert-hydroxyl is unaffected, to which (2R, 3R)-efficiently be made
2,3- dimethoxy -1,1,4,4- tetraphenyl -1,4- butanediols.
Technical scheme of the present invention：(2R, 3R) -1,1,4,4- tetraphenyls erythrol is in certain temperature and reaction medium
In, it is reacted with NaH and methylating reagent generation area 2,3- of selectivity di-methylations, (2R, 3R) -2,3- dimethoxys-is made
1, Isosorbide-5-Nitrae, 4- tetraphenyls -1,4-butanediol, product isolates and purifies in the following way：Distilled water is added, reaction, ether extraction is quenched
It takes, grease is concentrated into after dry, then recrystallized with 80% ethyl alcohol (volume ratio).
Further, described (2R, 3R) -1, Isosorbide-5-Nitrae, 4- tetraphenyls erythrol is by Threaric acid diethylester through phenylating system
, specific method is：The tetrahydrofuran solution of (2R, 3R)-ethyl tartrate is added drop-wise to the tetrahydrochysene of the phenyl-magnesium-bromide of 6 equivalents
It in tetrahydrofuran solution, after the completion of reaction, is quenched with saturated aqueous ammonium chloride, ether extraction, concentration, by being obtained after silica gel column chromatography
(2R, 3R) -1,1,4,4- tetraphenyl erythrol.
Further, the reaction medium is tetrahydrofuran, ether, toluene, dichloromethane or ethyl acetate.
Further, certain temperature is 0-25 DEG C, further, (2R, 3R) -1, Isosorbide-5-Nitrae, 4- tetraphenyl erythrol
It it is 25 DEG C with the temperature that methylating reagent reacts.
Further, the molar ratio of described (2R, 3R) -1, Isosorbide-5-Nitrae, 4- tetraphenyls erythrol and NaH, methylating reagent are 1：
(2-3)：(2-3).
Further, the methylating reagent is CH3I or dimethyl suflfate.
Compared with prior art, the advantages of the present invention are：
Utilize intramolecular hydrogen bond effect and the phenyl of 1,4- tert-hydroxyls in (2R, 3R) -1,1,4,4- tetraphenyl erythrol
The shielding action of substituent group makes Isosorbide-5-Nitrae-position tert-hydroxyl not reacted under this condition with NaH, and 2,3- secondary hydroxyls are by selectively
It reacts away, is then reacted with methylating reagent and generate target compound.It is efficiently obtained (2R, 3R) -1,1 by " single step reaction ",
4,4- tetraphenyl erythrol pass through (2R, 3R) -1, Isosorbide-5-Nitrae, the high regioselectivity 2 of 4- tetraphenyl erythrol, 3- di-methylations
Target compound (2R, 3R)-dimethoxy -1 2,3-, Isosorbide-5-Nitrae, 4- tetraphenyls-Isosorbide-5-Nitrae-fourth two is made with 43% high yield in reaction
Alcohol.
Specific implementation mode
Embodiment 1：One kind dimethoxy -1 (2R, 3R) -2,3-, Isosorbide-5-Nitrae, the preparation method of 4- tetraphenyls -1,4-butanediol,
Steps are as follows：
Step 1：The preparation of (2R, 3R) -1,1,4,4- tetraphenyl erythrol
The tetrahydrofuran solution of (2R, 3R)-ethyl tartrate is added drop-wise to the tetrahydrofuran of the phenyl-magnesium-bromide of 6 equivalents
In solution, after the completion of reaction, be quenched with saturated aqueous ammonium chloride, ether extraction, concentration, by obtained after silica gel column chromatography (2R,
3R) -1, Isosorbide-5-Nitrae, 4- tetraphenyl erythrol, yield：48%, m.p.:149-150℃；[α]D 25=+154.0 (c 1.2, CHCl3)；
IR(KBr):3436,3058,2916,1598,1492,1447,1063,698；1H-NMR(CDCl3,300MHz):δ7.37–7.13
(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)δ143.8；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 (2R, 3R) -2,3- dimethoxy -1,1,4,4- tetraphenyl -1,4- butanediols
At 0 DEG C, the NaH of 3 equivalents is added in anhydrous THF, stir about 5 minutes, then by (2R, 3R) -1, Isosorbide-5-Nitrae, 4- tetra-
The THF solution of phenyl erythrol is added in the THF solution of NaH, continues stirring 2 hours, the CH of 3 equivalents is then added3I rises to
Room temperature (25 DEG C) stirs 3 hours, and distilled water is added and is quenched reaction, and ether extraction is concentrated into grease after drying, then with
80% ethyl alcohol (volume ratio) is recrystallized to give 2,3- dimethoxy -1,1,4,4- tetraphenyl -1,4- butanediols.Yield:89%,
m.p.123-125℃,[α]D 25=-151 (c 0.8, CHCl3).1H NMR(300MHz,CDCl3):7.63-7.55(m,8H,Ph-
), H 7.43 (t, J=7.5Hz, 4H), 7.32-7.12 (m, 8H), 4.91 (s, 2H, disappeared after adding
D2O),4.43(s,2H),2.53(s,6H).13C NMR(75MHz,CDCl3):145.9,145.0,128.7,128.2,127.5,
127.0,126.3,126.2,126.1,85.62,85.57,80.19,61.35,61.26.ES-MS:454([M455-1]+)。
Embodiment 2：One kind dimethoxy -1 (2R, 3R) -2,3-, Isosorbide-5-Nitrae, the preparation method of 4- tetraphenyls -1,4-butanediol,
Steps are as follows：
Step 1：The preparation of (2R, 3R) -1,1,4,4- tetraphenyl erythrol
The tetrahydrofuran solution of (2R, 3R)-ethyl tartrate is added drop-wise to the tetrahydrofuran of the phenyl-magnesium-bromide of 6 equivalents
In solution, after the completion of reaction, be quenched with saturated aqueous ammonium chloride, ether extraction, concentration, by obtained after silica gel column chromatography (2R,
3R) -1, Isosorbide-5-Nitrae, 4- tetraphenyl erythrol, yield：48%, m.p.:149-150℃；[α]D 25=+154.0 (c 1.2, CHCl3)；
IR(KBr):3436,3058,2916,1598,1492,1447,1063,698；1H-NMR(CDCl3,300MHz):δ7.37–7.13
(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)δ143.8；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 (2R, 3R) -2,3- dimethoxy -1,1,4,4- tetraphenyl -1,4- butanediols
At 25 DEG C, the NaH of 2 equivalents is added in anhydrous THF, stir about 5 minutes, then by (2R, 3R) -1, Isosorbide-5-Nitrae, 4-
The THF solution of tetraphenyl erythrol is added in the THF solution of NaH, continues stirring 2 hours, and the dimethyl suflfate of 2 equivalents is added,
Stirring 3 hours is added distilled water and reaction is quenched, and ether extraction is concentrated into grease, then with 80% ethyl alcohol (volume after dry
Than) it is recrystallized to give 2,3- dimethoxy -1,1,4,4- tetraphenyl -1,4- butanediols.Yield:89%, m.p.123-125 DEG C,
[α]D 25=-151 (c 0.8, CHCl3).1H NMR(300MHz,CDCl3):7.63-7.55 (m, 8H, Ph-H), 7.43 (t, J=
7.5Hz,4H),7.32-7.12(m,8H),4.91(s,2H,disappeared after adding D2O),4.43(s,2H),
2.53(s,6H).13C NMR(75MHz,CDCl3):145.9,145.0,128.7,128.2,127.5,127.0,126.3,
126.2,126.1,85.62,85.57,80.19,61.35,61.26.ES-MS:454([M455-1]+)。
Claims (6)
1. one kind (2R,3R) -2,3- dimethoxy -1,1,4,4- tetraphenyl -1,4- butanediols preparation method：(2R,3R) -
1, in certain temperature and reaction medium, with NaH and methylating reagent height region choosing occurs for Isosorbide-5-Nitrae, 4- tetraphenyls erythrol
Selecting property 2,3- di-methylations reaction, is made dimethoxy -1 (2R, 3R) -2,3-, Isosorbide-5-Nitrae, 4- tetraphenyls -1,4-butanediol.
2. preparation method according to claim 1, it is characterised in that：Described (2R,3R) -1,1,4,4- tetraphenyls fourth four
Alcohol is made by Threaric acid diethylester through phenylating.
3. preparation method according to claim 2, it is characterised in that：The reaction medium is tetrahydrofuran, ether, first
Benzene, dichloromethane or ethyl acetate.
4. preparation method according to claim 2, it is characterised in that：Certain temperature is 0-25 DEG C.
5. preparation method according to claim 2, it is characterised in that：(2R, the 3R) -1,1,4,4- tetraphenyls fourth four
The molar ratio of alcohol and NaH, methylating reagent are 1：2-3：2-3.
6. preparation method according to claim 5, it is characterised in that：The methylating reagent is CH3I or dimethyl suflfate.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114057559A (en) * | 2020-07-31 | 2022-02-18 | 中南民族大学 | Preparation method of diaryl ketone |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060276410A1 (en) * | 2005-05-25 | 2006-12-07 | Campbell David A | Compounds and methods for selective inhibition of dipeptidyl peptidase-iv |
| CN101921181B (en) * | 2010-02-09 | 2013-05-15 | 武汉大学 | Preparation method of (2R,3R)-1,4-dimethoxyl-1,1,4,4-tetraphenyl-2,3-butanediol and (2S,3S)-1,4-dimethoxyl-1,1,4,4-tetraphenyl-2,3-butanediol |
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2018
- 2018-02-10 CN CN201810138381.8A patent/CN108276256A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060276410A1 (en) * | 2005-05-25 | 2006-12-07 | Campbell David A | Compounds and methods for selective inhibition of dipeptidyl peptidase-iv |
| CN101921181B (en) * | 2010-02-09 | 2013-05-15 | 武汉大学 | Preparation method of (2R,3R)-1,4-dimethoxyl-1,1,4,4-tetraphenyl-2,3-butanediol and (2S,3S)-1,4-dimethoxyl-1,1,4,4-tetraphenyl-2,3-butanediol |
Non-Patent Citations (1)
| Title |
|---|
| BENITA BARTON等: "Discrimination between o-xylene, m-xylene, p-xylene and ethylbenzene by host compound (R,R)-(â)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol", 《TETRAHEDRON》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114057559A (en) * | 2020-07-31 | 2022-02-18 | 中南民族大学 | Preparation method of diaryl ketone |
| CN114057559B (en) * | 2020-07-31 | 2023-10-03 | 中南民族大学 | Preparation method of diaryl ketone |
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Application publication date: 20180713 |