CN1358717A - Optics decomposing method for coumarin dimer - Google Patents
Optics decomposing method for coumarin dimer Download PDFInfo
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- CN1358717A CN1358717A CN 01126762 CN01126762A CN1358717A CN 1358717 A CN1358717 A CN 1358717A CN 01126762 CN01126762 CN 01126762 CN 01126762 A CN01126762 A CN 01126762A CN 1358717 A CN1358717 A CN 1358717A
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Abstract
The present invention relates to an optical resolution method of coumarin dimer. In said invention, TADDOL-6 with optical purity is used to selectively combine with one kind of enantiomorph or racemic coumarin dimer to form molecular crystal to separate out, after treatment N,N-dimethyl formamide is reacted with it to release out product, through after treatment, the coumarin dimer with optical activity can be obtained. Said method is simple in operation, good in reproducibility, and its chiral resolution reagent is easy to be recovered, it implements high-effective optical resolution of raceme, and is suitable for large amount of preparation.
Description
Technical field
The present invention relates to the optical isomer new method for splitting in the chiral technology.
Background technology
In four kinds of photosynthetic dimer 2-5 of tonka bean camphor 1, have only anti-head-to-head dimer 5 (the following coumarin dimer that all abbreviates as) to have optical activity.In coumarin dimer 5 molecules, both had C
2Symmetric tetra-atomic ring skeleton, but simultaneously lactone again open loop be derivatized to a series of compound [Yonezawa, N. with multiple functional group; Hasegawa, M.Bull.Chem.Soc.Jpn.1983,56,367-368].As can be used for building-up reactions [Hayashi, the M. of catalytic amino acid by the Rh complex compound of its deutero-biphosphine ligand; Hashimoto, Y.; Takezaki, H.; Watanabe, Y.; Saigo, K.Tetrahedron:Asymmetry 1998,1863-1866]; It and some diamine compounds optically active polymeric amide that has that forms of deriving has good chiral recognition ability, and the chiral stationary phase that has been used as high performance liquid chromatography (HPLC) is used for separating chiral compound [Saigo, K.; Chen, Y.; Yonezawa, N.; Kanoe, T.; Tachibuna, K.; Hasegawa, M.Macromolecules 1986,19,1552-1558] [Chen, Y.; Saigo, K.; Yonezawa, N.; Hasegawa, M.Bull.Chem.Soc.Jpn.1987,60,1895-1902] [Chen, Y.; Saigo, K.; Yonezawa, N.; Tachibana, K.Bull.Chem.Soc.Jpn.1987,60,3341-3345] [Chen, Y.; Shiao, M-T.Bull.Chem.Soc.Jpn.1992,65,3423-3429].Therefore optical purity coumarin dimer 5 will be a kind of chiral synthon and chiral ligand synthetic key intermediate with significant application value.Wherein the structural formula of 1-5 is as follows respectively:
The high-level efficiency of anti-head-to-tail syn-head-to-tail syn-head-to-head anti-head-to-head racemize coumarin dimer (±)-5 is three-dimensional single-minded synthesizes and was seen in report [Kraus, C.H. in 1966; Farid, S.and Schenk, G.O.Chem.Ber.1966,99,625], reaction formula is:
And its optical resolution to 1985 year just realizes [Saigo, K. first; Yonezawa, N.; Sekimoto, K.; Hasegawa, M.; Ueno, K.; Nakanish, H.Bull.Chem.Soc.Jpn.1985,58,1000-1005], this method is at first reacted the acid amides non-enantiomer derivative that forms open loop by racemic coumarin dimer (±)-5 and optical purity α-Ben Yian, adopt the method for fractional crystallization again, obtain single optical isomer, obtain optical purity 5 through hydrolysis and ring closure reaction then, the shortcoming of this method is to need to transform through the multistep chemical reaction, step is long, efficient is low, and needs the optical purity α-Ben Yian of two molar equivalents, the report that does not also have the resolution reagent α-Ben Yian to reclaim.Another method that obtains optical purity coumarin dimer 5 is to utilize optically active TADDOL (-)-6a (i.e. (R, R)-(-) trans-4,5-pair-(hydroxy benzophenone base)-2,2-dimethyl-1, the 3-dioxolane) forms molecular crystal with tonka bean camphor 1, obtain the molecular crystal that optical purity dimer 5 and (-)-6a form by solid-state light reaction is three-dimensional then, the yield of reaction and enantioselectivity be near 100%[Tanaka single-mindedly, K.; Toda, F.; Mochizuki, E.; Yasui, N.; Kai, Y.; Miyahara, K.H.Angew.Chem.Int.Ed.1999,38,3523-3525], still, the first step (-)-6a and tonka bean camphor 1 form the extremely difficult control of condition of molecular crystal in this method, poor repeatability, and yield is low, and the solid-state light reaction of second step is difficult to realize a large amount of preparations.Because the present preparation method difficulty of optical purity coumarin dimer 5, therefore influenced the application in producing of its exploitation in asymmetry catalysis research and futurity industry.
Summary of the invention
For the problem of the preparation method difficulty that solves above-mentioned optical purity coumarin dimer 5, the invention provides easy, the optical isomer new method for splitting efficiently of a kind of racemize coumarin dimer (±)-5.
The present invention is according to the supramolecular chemistry principle, utilize the weak interaction between the additional mutually and group on the three-dimensional space between main body (HOST) molecule and object (GUEST) molecule, the two optionally forms stable molecular crystal by molecular recognition, thereby has realized the high-level efficiency optical resolution to racemic modification.
In organic solvent, optically pure 6 optionally with racemize coumarin dimer (±)-5 in (+)-5 or (-)-5 enantiomorph combine and form molecular crystal, wherein optically pure 6 with the mol ratio of racemize coumarin dimer (±)-5 be 1-3: 1, temperature of reaction 0-150 ℃, reaction times 2-10h.Described optically pure 6 is (+)-6 or (-)-6, and the structural formula of wherein (+)-6 is
The structural formula of (-)-6 is
The alkyl of R or R '=H, C1～C10, cycloalkyl, phenyl or substituted-phenyl etc. in the formula, alkyl, cycloalkyl, phenyl or the substituted-phenyl of recommendation R or R '=H, C1～C6; Ar=phenyl, substituted-phenyl or naphthyl; The substituting group of described substituted-phenyl is the alkyl, hydroxyl, benzyloxy, dimethylin of thiazolinyl, the C1～C3 of hydroxyalkyl, the C1～C3 of C1～C3 etc., and the concrete structure of above-mentioned (+)-6 or (-)-6 is for example shown in (+)-6a～u and (-)-6a～u:
(+)-6 TADDOLs 6a-u (-)-6(+)-6R R′ Ar (-)-6R R′ Ara Me Me Ph a Me Me Phb Me Ph Ph b Me Ph Phc (CH
2)
4 Ph c (CH
2)
4 Phd (CH
2)
5 Ph d (CH
2)
5 Phe Me Me 1-Nph e Me Me 1-Nphf Me Me 2-Nph f Me Me 2-Nphg Ph Ph Ph g Ph Ph Phh Ph H Ph h Ph H Phi tBu H Ph i tBu H Phj Me Me 3，5-Me
2C
6H
3 j Me Me 3，5-Me
2C
6H
3k Et Et Ph k Et Et Phl Et Et 3，5-Me
2C
6H
3 l Et Et 3，5-Me
2C
6H
3m Me Me 4-HOC
6H
4 m Me Me 4-HOC
6H
4n Me Me 4-C
6H
5CH
2OC
6H
4n Me Me 4-C
6H
5CH
2OC
6H
4o H H 4-(Me
2N)C
6H
4 o H H 4-(Me
2N)C
6H
4p 4-(HOCH
2)C
6H
4 H Ph p?4-(HOCH
2)C
6H
4 H Phq 4-(CH
2＝CH)C
6H
4?H Ph q?4-(CH
2＝CH)C
6H
4H Phr 4-(CH
2＝CH)C
6H
4?H 1-Nph r?4-CH
2＝CH)C
6H
4?H 1-Nphs 4-(CH
2＝CH)C
6H
4?H 2-Nph s?4-CH
2＝CH)C
6H
4?H 2-Npht 4-(CH
2＝CH)C
6H
4?Me Ph t?4-(CH
2＝CH)C
6H
4Me Phu 4-(CH
2＝CH)C
6H
4?Ph Ph u?4-(CH
2＝CH)C
6H
4Ph Ph
The structural formula of described optically pure coumarin dimer (+)-5 be (+)-
, the structural formula of (-)-5 is
The yield of the molecular crystal that above-mentioned reaction obtains can reach 85-90%, enantiomeric excess (ee) can reach 88.5-92%.Wherein reactant is (+)-6 o'clock, and it combines with (+)-5, the molecular crystal that obtains from mother liquor, separate out and with organic solvent once more recrystallization promptly obtain optical purity molecular crystal A ', i.e. 2 (+)-6 (+)-5, (-)-5 then are retained in the mother liquor; Reactant is (-)-6 o'clock, and it combines with (-)-5, the molecular crystal that obtains from mother liquor, separate out and with organic solvent once more recrystallization promptly obtain optical purity molecular crystal A, i.e. 2 (-)-6 (-)-5, (+)-5 enantiomorph then is retained in the mother liquor.
Molecular crystal A ' or A N then, and the mixed solvent of dinethylformamide (DMF) and water (volume ratio is 2-5: 1) recrystallization, and per 1 mole of A ' or A need 5-10 to rise solvent, and the amount of increase solvent does not hinder reaction; The recrystallization temperature of reaction is 0-150 ℃, reaction times 1-10h.When wherein reactant is A ', by reaction (+)-6 discharge (+)-5 backs and and N, dinethylformamide (DMF) forms new molecular crystal C ', i.e. (+)-6DMF, reclaim molecular crystal C ' then, the mother liquor of reaction concentrate the back with ethyl acetate/normal hexane recrystallization promptly with the yield of 60-80% and＞99% enantiomeric excess obtains (+)-5, [α] D21=+9.0 (c=1.00, benzene) of (+)-5; When reactant is A, discharge back, (-)-5 and form new molecular crystal C by reaction (-)-6 with DMF, i.e. (-)-6DMF, reclaim molecular crystal C then, the mother liquor of reaction concentrate the back with ethyl acetate/normal hexane recrystallization promptly with the yield of 60-80% and＞99% enantiomeric excess obtains (-)-5, [α] of (-)-5
D 21=-9.0 (c=1.00, benzene).
Stay after the reaction of the above-mentioned the first step in the mother liquor and to use DMF/H after unreacted (-)-5 or (+)-5 concentrate
2O (2-5: 1) recrystallization, wherein a small amount of optically pure 6 form molecular crystal C ' with DMF or C removes, and filtrate concentrates the back and promptly obtains optically pure (-)-5 or (+)-5, yield 60-80%, enantiomeric excess＞99% with ethyl acetate/normal hexane recrystallization.
Merge resulting molecular crystal C ' twice, to wash with water behind the acetic acid ethyl dissolution, removing desolvates can reclaim (+)-6; Merge resulting molecular crystal C twice, to wash with water behind the acetic acid ethyl dissolution, removing desolvates can reclaim (-)-6.The above-mentioned rate of recovery can＞90%, and reusable, do not influence it and split efficient.
Above-mentioned organic solvent is ethyl acetate, benzene, toluene, ether, tetrahydrofuran (THF), acetonitrile, methylene dichloride, chloroform or acetone.
In the raw material of the present invention, racemize coumarin dimer 5 can be according to document [Kraus, C.H.; Farid, S.and Schenk, G.O.Chem.Ber.1966,99,625] the method high-level efficiency three-dimensional single-minded synthetic.
The present invention uses the resolution reagent that is easy to get that the coumarin dimer racemic modification with tetra-atomic ring skeleton is split, and method for splitting of having reported more or preparation method have following advantage:
1. method for splitting is different from existent method (as forming non-mapping derivative, direct reaction to light).Present method is according to the supramolecular chemistry principle, utilize the weak interaction between the additional mutually and group on the three-dimensional space between host molecule and the guest molecule, the two optionally forms stable molecular crystal by molecular recognition, thereby has realized the high-level efficiency optical resolution to racemic modification.
2. method economy.Optical resolution can be carried out to 1 mole of racemic modification in chiral selectors (+)-6 or (-)-6 that need only 1 mole, and chiral selectors reclaims (rate of recovery＞90%) easily, reusable and do not influence fractionation efficient, so the consumption of resolution reagent is very low.
3. it is higher to split efficient.Because high molecule distinguishability is arranged, cause isolating (-)-5 and (+)-5 isomer to have very high optical purity (88.5%-92%ee), need only a recrystallization, the enantiomeric excess of chirality coumarin dimer 5 can reach＞and 99%, total recovery reaches 60-80%.
4. simple to operate, good reproducibility can prepare in a large number.The involved operation of the inventive method is as filtering, extraction, and recrystallizations etc. all belong to the simple operations in the organic synthesis.Scale-up is the result show, therefore the be not put to the test influence of scale of the yield of product and optical purity is used in a large amount of preparations.
Description of drawings
Reaction method of the present invention such as accompanying drawing are illustrated in figures 1 and 2.
Fig. 1 is to be the reaction method of raw material with (+)-6 and racemize coumarin dimer 5, and among the figure: A ' is a molecular crystal 2 (+)-6 (+)-5; B ' is a mother liquor; C ' is molecular crystal (+)-6DMF; D is DMF/H
2O (5: 1) recrystallization E is for filtering, and filtrate concentrates; F is ethyl acetate/normal hexane recrystallization; G is an ethyl acetate extraction, washing.
Fig. 2 is to be the reaction method of raw material with (-)-6 and racemize coumarin dimer 5, and among the figure: A is a molecular crystal 2 (-)-6 (-)-5; B is a mother liquor; C is molecular crystal (-)-6DMF; D is DMF/H
2O (5: 1) recrystallization E is for filtering, and filtrate concentrates; F is ethyl acetate/normal hexane recrystallization; G is an ethyl acetate extraction, washing.
Embodiment
Help to understand the present invention by following examples, but be not limited to the present invention.
The high-level efficiency of embodiment one racemize coumarin dimer (±)-5 is three-dimensional single-minded synthetic
250mL benzene (analytical pure) solution that in a 250mL liquid phase photoreactor, adds 29.0g tonka bean camphor 1,5.04g benzophenone, earlier in system, blasted argon gas 0.5 hour, carried out illumination 10 hours with 400W Hg Lamp then, stopped reaction, the white crystal suction filtration of separating out is got the 21.5g product, 6.40g white crystal (±)-5 again after filtrate concentrates, total recovery is 96.0%.m.p.176-177℃；IR(KBr，cm
-1)：ν＝1760，1490，1450，775，765cm
-1；
1H?NMR(CDCl
3，300MHz)：δ＝3.90(4H，d)，7.1-7.4(8H，m)。Recyclable benzophenone 4.57g of while, the rate of recovery is 91.4%.
The method for optical resolution of embodiment two coumarin dimers
Be equipped with in the round-bottomed flask of 250mL of reflux condensing tube one, add 9.34g (20mmol) (-)-6a respectively, 5.85g (20mmol) racemize coumarin dimer (±)-5 and 120mL ethyl acetate, said mixture is reflux 4 hours under agitation, be cooled to room temperature then, filter the flakes white crystalline solid that is generated, and carry out recrystallization once more with ethyl acetate (100mL), resulting white crystal (9.20g, 75%) is through being characterized by 2: 1 the molecular crystal A that (-)-6a and coumarin dimer (-)-5 form
a: 2 (-)-6a (-)-5.M.p.228-232 ℃; [α]
D 21=-72.0 (c=1.00, benzene); [α]
435 21=-157.5 (c=1.00, benzene);
1H NMR (CDCl
3, 300MHz): δ=1.05 (12H, s), 3.9-4.0 (8H, m), 4.60 (4H, s), 7.1-7.6 (48H, m); C
80H
72O
12, calculated value: C, 71.37%; H, 3.99%.Measured value: C, 71.64%; H, 3.82%.Coumarin dimer (+)-5 item is stayed in the mother liquor.
Be equipped with in the round-bottomed flask of 250mL of reflux condensing tube one, add 9.85g (20mmol) (-)-6b respectively, 5.85g (20mmol) racemize coumarin dimer (±)-5 and 120mL ethyl acetate, said mixture is reflux 4 hours under agitation, be cooled to room temperature then, filter the flakes white crystalline solid that is generated, and carry out recrystallization once more with ethyl acetate (100mL), resulting white crystal (8.94g, 70%) is through being characterized by 2: 1 the molecular crystal A that (-)-6b and coumarin dimer (-)-5 form
b: 2 (-)-6b (-)-5.M.p.198-202 ℃; [α] D25=-24.3 (c=1.00, chloroform); [α] 36525=-63.8 (c=1.00, chloroform); 1H NMR (CDCl3,300MHz): δ=1.3-1.5 (16H, s), 3.6-4.0 (8H, m), 4.7 (4H, s), 7.2-7.7 (48H, m); C84H76O12, calculated value: C, 78.97%; H, 6.00%.Measured value: C, 78.88%; H, 6.02%.Coumarin dimer (+)-5 item is stayed in the mother liquor.
Be equipped with in the round-bottomed flask of 250mL of reflux condensing tube one, add 10.13g (20mmol) (-)-6c, other condition during with aforementioned (-)-6a is identical, resulting white crystal (9.79g, 75%) is through being characterized by 2: 1 the molecular crystal A that (-)-6c and coumarin dimer (-)-5 form
c: 2 (-)-6c (-)-5.M.p.226--230 ℃; [α] D25=-65.1 (c=1.00, chloroform); 1H NMR (CDCl3,300MHz): δ=1.1-1.6 (20H, m), 3.9-4.1 (44H, m), 4.55 (4H, s), 7.1-7.6 (48H, m).C86H80O12, calculated value: C, 79.12%; H, 6.18%.Measured value: C, 79.21%; H, 6.23%.Coumarin dimer (+)-5 item is stayed in the mother liquor.
Be equipped with in the round-bottomed flask of 250mL of reflux condensing tube one, add 10.13g (20mmol) (-)-6d, other condition during with aforementioned (-)-6a is identical, and resulting white crystal (9.79g, 5%) is through being characterized by 2: 1 the molecular crystal A that (-)-6d and coumarin dimer (-)-5 form
d: 2 (-)-6d (-)-5.M.p.226--230 ℃; [α] D25=-65.1 (c=1.00, chloroform); 1H NMR (CDCl3,300MHz): δ=1.1-1.6 (20H, m), 3.9-4.1 (44H, m), 4.55 (4H, s), 7.1-7.6 (48H, m).C86H80O12, calculated value: C, 79.12%; H, 6.18%.Measured value: C, 79.21%; H, 6.23%.Coumarin dimer (+)-5 item is stayed in the mother liquor.
Be equipped with in the round-bottomed flask of 250mL of reflux condensing tube one, add 13.33g (20mmol) (-)-6e, other condition during with aforementioned (-)-6a is identical, resulting white crystal (12.68g, 78%) is through being characterized by 2: 1 the molecular crystal A that (-)-6e and coumarin dimer (-)-5 form
e: 2 (-)-6e (-)-5.M.p.222--225 ℃; [α]
D 25=-245.3 (c=1.00, ethyl acetate);
1H NMR (CDCl
3, 300MHz): δ=0.19 (4H, s), 3.9-4.0 (4H, s), 5.45 (4H, s), 7.2-7.6 (48H, m), 8.3-8.8 (56H, m).C
112H
88O
12, calculated value: C, 82.74%; H, 5.46%.Measured value: C, 82.62%; H, 5.40%.Coumarin dimer (+)-5 item is stayed in the mother liquor.
Be equipped with in the round-bottomed flask of 250mL of reflux condensing tube one, add 10.30g (20mmol) (-)-6h, other condition during with aforementioned (-)-6a is identical, resulting white crystal (9.91g, 75%) is through being characterized by 2: 1 the molecular crystal A that (-)-6h and coumarin dimer (-)-5 form
h: 2 (-)-6h (-)-5.M.p.198--202 ℃; [α]
D 25=-19.8 (c=1.00, chloroforms);
1H NMR (CDCl
3, 300MHz): δ=2.15 (2H, s), 3.27 (2H, s), 3.9-4.0 (4H, m), 5.1-5.4 (6H, m), 7.0-7.7 (58H, m).C
88H
72O
12, calculated value: C, 79.98%; H, 5.49%.Measured value: C, 80.04%; H, 5.40%.Coumarin dimer (+)-5 item is stayed in the mother liquor.
Be equipped with in the round-bottomed flask of 250mL of reflux condensing tube one, add 17.82g (20mmol) (-)-6n, other condition during with aforementioned (-)-6a is identical, resulting white crystal (8.60g, 80%) is through being characterized by 2: 1 the molecular crystal A that (-)-6n and coumarin dimer (-)-5 form
n: 2 (-)-6n (-)-5.M.p.206--208 ℃; [α]
D 25=-43.0 (c=1.00, chloroforms);
1H NMR (CDCl
3, 300MHz): δ=1.05 (12H, s), 3.9-4.0 (8H, m), 4.48 (4H, s), 5.01 (8H, s), 5.06 (8H, s), 6.8-7.0 (16H, m), 7.10-7.50 (64H, m).C
136H
120O
20, calculated value: C, 78.74%; H, 5.83%.Measured value: C, 78.54%; H, 5.80%.Coumarin dimer (+)-5 item is stayed in the mother liquor.
Be equipped with in the round-bottomed flask of 250mL of reflux condensing tube one, add 12.20g (20mmol) (-)-6o respectively, 5.85g (20mmol) racemize coumarin dimer (±)-5 and 120mL ethyl acetate, said mixture is reflux 4 hours under agitation, be cooled to room temperature then, filter the flakes white crystalline solid that is generated, and carry out recrystallization once more with ethyl acetate (100mL), resulting white crystal (12.0g, 80%) is through being characterized by 2: 1 the molecular crystal A that (-)-6o and coumarin dimer (-)-5 form
o: 2 (-)-6o (-)-5.M.p.164--168 ℃; [α]
D 25=-53.4 (c=1.00, chloroforms);
1H NMR (CDCl
3, 300MHz): δ=2.54 (4H, s), 2.90 (48H, d), 3.90 (4H, d), 4.63 (4H, s), 4.95 (4H, s), 6.5-6.7 (16H, d), 7.1-7.4 (24H, m).C
92H
104N
4O
12, calculated value: C, 75.79%; H, 7.19%; N, 3.84%.Measured value: C, 75.70%; H, 7.09%; N, 3.76%.Coumarin dimer (+)-5 item is stayed in the mother liquor.
Be equipped with in the round-bottomed flask of 250mL of reflux condensing tube one, add 10.90g (40mmol) (-)-6p respectively, 5.85g (20mmol) racemize coumarin dimer (±)-5 and 120mL toluene or methylene dichloride, said mixture is reflux 2 hours under agitation, be cooled to room temperature then, filter the flakes white crystalline solid that is generated, and carry out recrystallization once more with toluene or methylene dichloride (100mL), resulting white crystal (11.05g, 80%) is through being characterized by 2: 1 the molecular crystal A that (-)-6p and coumarin dimer (-)-5 form
p: 2 (-)-6p (-)-5.M.p.158--162 ℃; [α]
D 25=-24.2 (c=1.00, chloroforms);
1H NMR (CDCl
3, 300MHz): δ=1.66 (2H, t), 2.25,3.36 (4H, s), 3.90 (4H, d), 4.61 (4H, d), 5.12 (2H, d), 5.16 (2H, s), 5.30 (2H, d), 7.1-7.5 (56H, m).C
90H
76O
14, calculated value: C, 78.24%; H, 5.54%.Measured value: C, 78.35%; H, 5.48%.Coumarin dimer (+)-5 item is stayed in the mother liquor.
In the round-bottomed flask of 250mL, add 10.81g (20mmol) (-)-6q respectively, 5.85g (20mmol) racemize coumarin dimer (±)-5 and 120mL acetone or tetrahydrofuran (THF), said mixture low-grade fever reaction under agitation 10 hours, be cooled to room temperature then, filter the flakes white crystalline solid that is generated, and carry out recrystallization once more with acetone or tetrahydrofuran (THF) (100mL), resulting white crystal (10.3g, 75%) is through being characterized by 2: 1 the molecular crystal A that (-)-6q and coumarin dimer (-)-5 form
q: 2 (-)-6q (-)-5.M.p.138--140 ℃; [α]
D 25=-55.3 (c=1.00, chloroforms);
1H NMR (CDCl
3, 300MHz): δ=2.15,3.26 (4H, s), 3.90 (4H, d), 5.1-5.2 (4H, m), 5.22 (2H, dd), 5.31 (2H, d), 5.70 (2H, dd), 6.65 (2H, dd), 7.1-7.6 (56H, m).C
92H
76O
12, calculated value: C, 80.44%; H, 5.58%.Measured value: C, 80.34%; H, 5.50%.Coumarin dimer (+)-5 item is stayed in the mother liquor.
Embodiment three coumarin dimer esterification by ring opening carry out HPLC and measure
With above-mentioned molecular crystal A
a10.0g use 5mL DMF/H
2O (5: 1) carries out recrystallization, forms colourless acicular crystal C
a(8.6g, 99%) filters, and concentrated filtrate, resistates are used ethyl acetate/normal hexane recrystallization again, obtain 2.1g clear crystal (-)-5, yield 89%, ee＞99%;
With above-mentioned molecular crystal A
d10.0g use 5mL DMF/H
2O (5: 1) row recrystallization forms colourless acicular crystal C
d(8.43g, 95%) filters, and concentrated filtrate, resistates are used ethyl acetate/normal hexane recrystallization again, obtain 2.00g clear crystal (-)-5, yield 89%, ee＞99%;
With above-mentioned molecular crystal A
e10.0g use 5mL DMF/H
2O (5: 1) carries out recrystallization, forms colourless acicular crystal C
e(8.73g, 96%) filters, and concentrated filtrate, resistates are used ethyl acetate/normal hexane recrystallization again, obtain 1.70g clear crystal (-)-5, yield 95%, ee＞99%;
With above-mentioned molecular crystal A
h10.0g use 5mL DMF/H
2O (5: 1) carries out recrystallization, forms colourless acicular crystal C
h(8.54g, 96%) filters, and concentrated filtrate, resistates are used ethyl acetate/normal hexane recrystallization again, obtain 2.10g clear crystal (-)-5, yield 95%, ee＞99%;
With above-mentioned molecular crystal A
n10.4g use 5mL DMF/H
2O (5: 1) carries out recrystallization, forms colourless acicular crystal C
n(9.06g, 94%) filters, and concentrated filtrate, resistates are used ethyl acetate/normal hexane recrystallization again, obtain 1.30g clear crystal (-)-5, yield 88%, ee＞99%;
With above-mentioned molecular crystal A
o7.56g use 5mL DMF/H
2O (5: 1) carries out recrystallization, forms colourless acicular crystal C
o(6.28g, 92%) filters, and concentrated filtrate, resistates are used ethyl acetate/normal hexane recrystallization again, obtain 1.31g clear crystal (-)-5, yield 90%, ee＞99%;
With above-mentioned molecular crystal A
p6.90g use 5mL DMF/H
2O (5: 1) carries out recrystallization, forms colourless acicular crystal C
p(5.87g, 95%) filters, and concentrated filtrate, resistates are used ethyl acetate/normal hexane recrystallization again, obtain 1.30g clear crystal (-)-5, yield 89%, ee＞99%;
With above-mentioned molecular crystal A
q6.90g use 10mL DMF/H
2O (2: 1) carries out recrystallization, forms colourless acicular crystal C
q(5.65g, 92%) filters, and concentrated filtrate, resistates are used ethyl acetate/normal hexane recrystallization again, obtain 1.34g clear crystal (-)-5, yield 80%, ee＞99%, m.p.168.5-169 ℃; [α]
D 21=-9.0 (c=1.00, benzene); [α]
435 21=-65.8 (c=1.00, benzene); IR (KBr, cm
-1): ν=1760,1490,1450,775,765cm
-1 1H NMR (CDCl
3, 300MHz): δ=3.90 (4H, d), 7.1-7.4 (8H, m);
More than obtain derive again ester cpds 7 for open loop of clear crystal (-)-5 and carry out HPLC and measure, reaction formula is as follows:
(condition determination: Chiralcel AD Column, eluent are Virahol/normal hexane=15: 85, and flow velocity is 0.80mL/min, retention time: t
(+)=8.00min, t
(-)=11.24min.)。
The recovery of embodiment four resolution reagents (-)-6
Colourless acicular crystal C with above-mentioned gained
a5.40g to wash (8mL * 3), anhydrous sodium sulfate drying behind the 15mL acetic acid ethyl dissolution with water three times; Remove desolvate white solid (-)-6a 4.50g, the rate of recovery＞90%, further recrystallization is promptly reusable.M.p.195-196 ℃; [α]
D 21=-87.0 (c=1.00, benzene); [α]
435 21=-183.0 (c=1.00, benzene);
1H NMR (CDCl
3, 300MHz): δ=1.0 (6H, s), 3.95 (2H, s), 4.60 (2H, s), 7.2-7.6 (20H, m);
Colourless acicular crystal C with above-mentioned gained
d5.80g to wash (8mL * 3), anhydrous sodium sulfate drying behind the 15mL acetic acid ethyl dissolution with water three times; Remove desolvate white solid (-)-6d 4.80g, the rate of recovery＞90%, further recrystallization is promptly reusable.M.p.195-196 ℃; [α]
D 25=-74.4 (c=1.00, chloroforms);
1H NMR (CDCl
3, 300MHz): δ=1.1-1.6 (10H, m), 3.95 (20H, s), 4.55 (2H, s), 7.1-7.6 (20H, m).
Colourless acicular crystal C with above-mentioned gained
e7.40g to wash (8mL * 3), anhydrous sodium sulfate drying behind the 15mL acetic acid ethyl dissolution with water three times; Remove desolvate white solid (-)-6e 6.54g, the rate of recovery＞90%, further recrystallization is promptly reusable.M.p.195-196 ℃; [α]
D 25=-283.4 (c=1.00, ethyl acetate);
1H NMR (CDCl
3, 300MHz): δ=0.19 (2H, s), 5.45 (2H, s), 7.40 (20H, br), 8.28-8.74 (28H, m).
Colourless acicular crystal C with above-mentioned gained
h5.88g to wash (8mL * 3), anhydrous sodium sulfate drying behind the 15mL acetic acid ethyl dissolution with water three times; Remove desolvate white solid (-)-6h 4.85g, the rate of recovery＞90%, further recrystallization is promptly reusable.M.p.173-174 ℃; [α]
D 25=-22.6 (c=1.00, chloroforms);
1H NMR (CDCl
3, 300MHz): δ=2.15 (1H, s), 3.27 (1H, s), 5.13 (1H, d), 5.18 (1H, s), 5.33 (1H, d), 7.0-7.7 (25H, m).
Colourless acicular crystal C with above-mentioned gained
n9.64g to wash (8mL * 3), anhydrous sodium sulfate drying behind the 15mL acetic acid ethyl dissolution with water three times; Remove desolvate white solid (-)-6n 8.46g, the rate of recovery＞90%, further recrystallization is promptly reusable.M.p.176-178 ℃; [α]
D 25=-49.2 (c=1.00, chloroforms);
1H NMR (CDCl
3, 300MHz): δ=1.05 (6H, s), 4.00 (2H, s), 4.48 (2H, s), 5.01 (4H, s), 5.06 (4H, s), 6.8-7.0 (8H, m), 7.20-7.50 (28H, m).
Colourless acicular crystal C with above-mentioned gained
o6.83g to wash (8mL * 3), anhydrous sodium sulfate drying behind the 15mL acetic acid ethyl dissolution with water three times; Remove desolvate white solid (-)-6o 6.05g, the rate of recovery＞90%, further recrystallization is promptly reusable.M.p.135-137 ℃; [α]
D 25=-61.0 (c=1.00, chloroforms);
1H NMR (CDCl
3, 300MHz): δ=2.54 (2H, s), 2.90 (24H, d), 4.63 (2H, s), 4.95 (2H, s), 6.5-6.7 (8H, d), 7.2-7.4 (8H, d).
Colourless acicular crystal C with above-mentioned gained
p6.20g to wash (8mL * 3), anhydrous sodium sulfate drying behind the 15mL acetic acid ethyl dissolution with water three times; Remove desolvate white solid (-)-6p 5.42g, the rate of recovery＞90%, further recrystallization is promptly reusable.M.p.128-132 ℃; [α]
D 25=-28.2 (c=1.00, chloroforms);
1H NMR (CDCl
3, 300MHz): δ=1.66 (1H, t), 2.25,3.36 (2H, 2s), 4.61 (2H, d), 5.12 (1H, d), 5.16 (1H, s), 5.30 (1H, d), 7.13-7.54 (24H, m).
Colourless acicular crystal C with above-mentioned gained
q6.14g to wash (8mL * 3), anhydrous sodium sulfate drying behind the 15mL acetic acid ethyl dissolution with water three times; Remove desolvate white solid (-)-6q 5.36g, the rate of recovery＞90%, further recrystallization is promptly reusable.M.p.104-105 ℃; [α]
D 25=-63.2 (c=1.00, chloroforms);
1H NMR (CDCl
3, 300MHz): δ=2.15,3.26 (2H, 2s), 5.1-5.2 (2H, m), 5.22 (1H, dd), 5.31 (1H, d), 5.70 (1H, dd), 6.65 (1H, dd), 7.12-7.56 (24H, m).
Claims (10)
1. the method for optical resolution of a coumarin dimer, it is characterized in that in organic solvent, optically pure 6 with racemize coumarin dimer (±)-5 reaction, wherein optically pure 6 with the mol ratio of racemize coumarin dimer (±)-5 be 1-3: 1, temperature of reaction 0-150 ℃, reaction times 2-10h, the molecular crystal that obtains of reaction from mother liquor, separate out and with organic solvent once more recrystallization obtain optical purity molecular crystal A ' or A, described optically pure 6 is (+)-6 or (-)-6, and (+)-6 structural formula is
The structural formula of (-)-6 is
The alkyl of R or R '=H, C1～C10, cycloalkyl, phenyl or substituted-phenyl in the formula; Ar=phenyl, substituted-phenyl or naphthyl, described A ' are 2 (+)-6 (+)-5, and described A is 2 (-)-6 (-)-5, and the structural formula of described optically pure coumarin dimer (+)-5 is
The structural formula of (-)-5 is
2. the method for optical resolution of coumarin dimer as claimed in claim 1, it is characterized in that optical purity molecular crystal A ' or A mixed solvent recrystallization with DMF/ water, form new molecular crystal C ' or C, reclaim molecular crystal C ' or C, the mother liquor of reaction concentrates the back recrystallization and obtains optically pure (-)-5 or (+)-5, described C ' is (+)-6DMF, and described C is (-)-6DMF, and described A ', A, (-)-5 or (+)-5 are according to claim 1.
3. the method for optical resolution of coumarin dimer as claimed in claim 1 is characterized in that reaction raw materials is (+)-6 and racemize coumarin dimer (±)-5, and described (+)-6 according to claim 1.
4. the method for optical resolution of coumarin dimer as claimed in claim 1 is characterized in that reaction raw materials is (-)-6 and racemize coumarin dimer (±)-5, and described (-)-6 according to claim 1.
5. the method for optical resolution of coumarin dimer as claimed in claim 1, the substituting group that it is characterized in that described substituted-phenyl is hydroxyalkyl, the thiazolinyl of C1～C3, the alkyl of C1～C3, hydroxyl, benzyloxy, the dimethylin of C1～C3.
6. the method for optical resolution of coumarin dimer as claimed in claim 1 is characterized in that described organic solvent is ethyl acetate, benzene, toluene, ether, tetrahydrofuran (THF), acetonitrile, methylene dichloride, chloroform or acetone.
7. the method for optical resolution of coumarin dimer as claimed in claim 1 is characterized in that staying in the reaction (1) in the mother liquor and to use DMF/H after unreacted (-)-5 or (+)-5 concentrate
2The O recrystallization, recrystallization gets optically pure (-)-5 or (+)-5 after the filtering and concentrating.
8. the method for optical resolution of coumarin dimer as claimed in claim 1, the volume ratio that it is characterized in that DMF/ water is 2-5: 1.
9. the method for optical resolution of coumarin dimer as claimed in claim 1 is characterized in that [α] of described (+)-5
D 21=+9.0 (c=1.00, benzene), [α] of described (-)-5
D 21=-9.0 (c=1.00, benzene).
10. the method for optical resolution of coumarin dimer as claimed in claim 1, it is characterized in that (+)-6 or (-)-6 reclaim and reuse, described (+)-6 or (-)-6 is according to claim 1.
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| JP2013113935A (en) * | 2011-11-25 | 2013-06-10 | Jsr Corp | Liquid crystal aligning agent, liquid crystal aligning layer, method for forming liquid crystal aligning layer, liquid crystal display element and compound |
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