CN1089334C

CN1089334C - Optical decomposing process of 2-amino-2'-hydroxyl-1,1'-dinaphthalene

Info

Publication number: CN1089334C
Application number: CN99101178A
Authority: CN
Inventors: 丁奎岭
Original assignee: Zhengzhou University
Current assignee: Zhengzhou University
Priority date: 1999-01-18
Filing date: 1999-01-18
Publication date: 2002-08-21
Anticipated expiration: 2019-01-18
Also published as: CN1255490A

Abstract

The invention provides an optical resolution method of 2-amino-2'-hydroxyl-1,1'-binaphthyl. This method is the first example of splitting aminophenols using chiral quaternary ammonium salts. Based on the principle of supramolecular chemistry, it utilizes the three-dimensional complementarity between the host (HOST) molecule and the guest (GUEST) molecule and the group The weak interaction between them can selectively form stable supramolecular crystals through molecular recognition, thereby achieving high-efficiency optical resolution of racemates. Compared with the prior art, the method is more advanced; more economical, less reagent consumption, easy to recycle, reuse without affecting the resolution efficiency; resolution efficiency is high, the ee value reaches 99%, and the yield reaches 85- 90%; the operation is simple, the repeatability is good, and it can be prepared in large quantities.

Description

2-amino-2 '-hydroxyl-1,1 '-method for optical resolution of dinaphthalene

The invention belongs to the optical isomer method for splitting in the chiral technology.

2-amino-2 '-hydroxyl-1,1 '-dinaphthalene at first was synthesized and split success and (see Smrcina, M. in 1992; Lorenc, M.; Hanus, V.; Sedmera, P.; Kocovsky, P.:J.Org.Chem.1992,57,1917-1920).Existing method for optical resolution has three kinds: first method be by racemize 2-amino-2 '-hydroxyl-1,1 '-dinaphthalene and Cu (II) and optical activity α-Ben Yian formation diastereomer complex compound, the method of employing fractional crystallization realizes, through three recrystallizations, gained chirality 2-amino-2 '-hydroxyl-1,1 '-enantiomeric excess (ee) of dinaphthalene can reach more than 97%.But the shortcoming of this method is to need a large amount of optical purity α-Ben Yians (10 molar equivalent), and the rate of recovery extremely low (～20%), poor repeatability; Second method is to split by forming diastereomer with camphorsulfonic acid, but this method is very responsive to crystallization condition, poor repeatability, and gained chirality 2-amino-2 '-hydroxyl-1,1 '-the ee value of dinaphthalene (sees Smrcina, M. between 30-95%; Vyskocil, S.; Polivkova, J.; Polakova, J.:Collect.Czech.Chem.Commun.1996,61,1520-1524.); The third method adopts kinetic resolution, at first with racemize 2-amino-2 '-hydroxyl-1,1 '-dinaphthalene is transformed into the Shiff base derivative of salicylic aldehyde, then with the reaction of Chiral Amine or amino alcohol, obtain optical activity 2-amino-2 '-hydroxyl-1,1 '-dinaphthalene and Shiff base derivative thereof, but the ee value of products therefrom is between 27-70%, obviously this method operation more complicated prepares difficulty in a large number and (sees Mahmound, H.; Han, Y.; Segal, B.M.; Cai, L.:Tetrahedron:Asymmetry, 1998,9,2035-2042).

2-amino-2 '-hydroxyl-1,1 '-the dinaphthalene molecule in, both had the symmetric dinaphthalene system of C2, have simultaneously the functional group of amino alcohol again, so it is that a kind of key intermediate of crucial synthesis of chiral part (is seen Smrcina, M.; Lorenc, M.; Hanus, V.; Sedmera, P.; Kocovsky, P.:J.Org.Chem.1992,57,1917-1920).Existing studies have shown that is that the effective catalyst of asymmetric aldol reaction (is seen a.Carreira, E.M. with its some Shiff base derivative as the transition metal complex of part; Singer, R.A.; Lee, W.:J.Am.Chem.Soc.1994,116,8837-8838.b.Carreira，E.M.；Lee，W.；Singer，R.A.：J.Am.Chem.Soc.1995，117，3649-3650。C.Singer, R.A.; Carreira, E.M.:J.Am.Chem.Soc.1995,117,12360-12361), be applied to (seeing a.Carreira, E.M. in some natural product and physiologically active substance synthetic; Singer, R.A.:Tetrahedron Lett., 1997,38,927-930.b.Li，K.W.；Wu，J.；Xing，W.；Simon，J.A.：J.Am.Chem.Soc.，1996，118，7237-7238。C.Rychnovsky, S.D.; Khire, U.R.Yang, G.:J.Am.Chem.Soc., 1997,119,2058-2059), so its application prospect is very wide.As mentioned above, present 2-amino 2 '-hydroxyl-1,1 '-the common limitation of the method for splitting of dinaphthalene is that efficient is low, complicated operation, poor repeatability, prepare difficulty etc. in a large number, this has obviously influenced its application in asymmetric synthesis research and futurity industry are produced.In order to address the above problem, we developed a kind of synthetic racemize 2-amino-2 '-hydroxyl-1,1 '-novel method of dinaphthalene (sees Ding, K.; Xu, Q.; Wang, Y.; Liu, J.; Yu, Z.; Du, B.; Wu, Y.; Koshima, H.; Matsuura, T.:Chem.Commun.1997,693-694), this method is reaction medium with water, has characteristics such as raw material is cheap and easy to get, yield is high, selectivity is good, simple to operate, can prepare, realize clean production in a large number, has environment protection significance.But the gordian technique of adopting said method be how to racemize 2-amino 2 '-hydroxyl-1,1 '-dinaphthalene carries out optical resolution.

Purpose of the present invention just provide a kind of 2-amino-2 '-hydroxyl-1,1 '-the high-level efficiency method for optical resolution of dinaphthalene.

The present invention is achieved by the following technical solutions:

In methyl alcohol (or acetonitrile or acetone or ethyl acetate), with 0.5 mole N-benzyl chlorination cinchonine pyridine 2 optionally with 1 mole of racemize 2-amino-2 '-hydroxyl-1,1 '-R enantiomorph combination in the dinaphthalene 1, forming molecular crystal (R)-(+)-12 with quantitative yield separates out, and from mother liquor, separate after filtering, (S)-(-)-1 then stay in the mother liquor; After the molecular crystal that will separate from mother liquor (R)-(+)-12 usefulness dilute hydrochloric acid decomposes, with the water-fast organism of ethyl acetate extraction, solid after concentrating promptly makes optical purity (R)-(+)-1 with the benzene recrystallization again, and yield is 85-90%, enantiomeric excess＞99%; The above-mentioned water of producing behind the optical purity (R)-(+)-1 neutralizes with saturated sodium bicarbonate solution, through concentrating, reclaim N-benzyl chlorination cinchonine pyridine 2 after the cooling, crystallization, and the rate of recovery＞95%, the N-benzyl chlorination cinchonine pyridine 2 after the recovery is reusable; After staying (S)-(-)-1 in the mother liquor and concentrating, get its pure product through the benzene recrystallization, yield is 85-90%, enantiomeric excess＞99%.

Compared with prior art, the invention has the advantages that: 1, more advanced.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 selectively forms stable molecular crystal mutually, thereby realizes the high-level efficiency optical resolution to racemic modification.2, more economical.Chiral selectors that need only 1/2 mole can carry out optical resolution to 1 mole of racemic modification, and chiral selectors reclaims (rate of recovery＞95%), reusable and do not influence fractionation efficient easily, so the consumption of resolution reagent is extremely low.3, split the efficient height.Since the highly selective of molecular recognition, R-1 after causing separating and S-1 isomer have very high optical purity (～95%ee), need only a recrystallization, chirality 2-amino-2 '-hydroxyl-1,1 '-enantiomeric excess of dinaphthalene can reach 99% yield and reach 85-90%.4, simple to operate, good reproducibility can prepare in a large number.Involved in the present invention to operation such as filtration, extraction, recrystallization etc. all belong to simple operations in the organic synthesis.Scale-up shows that the yield of product and optical purity are not subjected to the influence of experimental size size.

Accompanying drawing is a method for splitting synoptic diagram of the present invention.

The invention will be further described below in conjunction with accompanying drawing.

In the accompanying drawings, 1 be 2-amino-2 '-hydroxyl-1,1 '-dinaphthalene, 2 is the pyridine of N-benzyl chlorination cinchonine, 3 are Molecular crystal, 4 is mother liquor, 5 be (R)-(+)-2-amino-2 '-hydroxyl-1,1 '-dinaphthalene, 6 be (S)-(-)-2-amino-2 '-hydroxyl-1,1 '-dinaphthalene, A is that watery hydrochloric acid decomposes, and B is ethyl acetate extraction, and C is the benzene recrystallization, and D is for full With the sodium bicarbonate solution neutralization, E is concentrated, cooling, crystallization.

Principle of the present invention is: according to the supramolecular chemistry principle, utilize main body (HOST) molecule and visitor Weak mutual work between body (GUEST) molecule between the mutual additional and group on the three dimensions With, the two optionally forms stable supramolecular complex by molecular recognition, thereby realizes racemic The high efficiency optical resolution of body.

As shown in the figure, in methyl alcohol (or acetonitrile or acetone or ethyl acetate), with 0.5 mole N-benzyl chloride Change cinchonine pyridine 2 optionally with 1 mole of racemic 2-amino-2 '-hydroxyl-1,1 '-R-enantiomer in the dinaphthalene 1 In conjunction with, form molecular crystal 3 ((R)-(+)-12) with quantitative yield and separate out, and after filtering from mother Separate in the liquid 4, (S)-(-)-1 then stay in the mother liquor 4.

After the molecular crystal 3 that will separate from mother liquor ((R)-(+)-12) decomposes (A) with dilute hydrochloric acid, with the water-fast organism of ethyl acetate extraction (B), solid after concentrating promptly makes optical purity 5 ((R)-(+)-1) through benzene recrystallization (C), yield is 85-90%, enantiomeric excess (ee)＞99%.

Above-mentionedly produce water behind the optical purity 5 with saturated sodium bicarbonate solution neutralization (D), through concentrate, recovery N-benzyl chlorination cinchonine pyridine 2 after the cooling, crystallization (E), the rate of recovery＞95%, the N-benzyl chlorination cinchonine pyridine 2 after the recovery is reusable;

After staying (S)-(-)-1 in the mother liquor 4 and concentrating, through benzene recrystallization (C) its pure product, yield is 85-90%, enantiomeric excess (ee)＞99%.

Embodiment:

Be equipped with in the 250mL round-bottomed flask of reflux condensing tube one, add respectively the pyridine of 4.20g (10mmol) N-benzyl chlorination cinchonine, racemize 2-amino-2 '-hydroxyl-1,1 '-dinaphthalene 5.70g (20mmol) and 100mL acetone, said mixture is reflux 4h under agitation, be cooled to room temperature then, filter the white crystalline solid generated, and with washing with acetone three times (3 * 10mL), standby after the seasoning in the air.The white crystalline solid that is generated through be characterized by the pyridine of N-benzyl chlorination cinchonine with (S)-(+)-2-amino-2 '-hydroxyl-1,1 '-1: 1 molecular crystal that dinaphthalene forms: (R)-(+)-12.℃ m.p.＞250; C ₄₆H ₄₄ClN ₃O ₂, calculated value: C, 78.22; H, 6.28; N, 5.95%.Measured value: C, 78.15; H, 6.30; N, 6.04%.(S)-(-)-2-amino-2 '-hydroxyl-1,1 '-dinaphthalene then stays in the mother liquor.

Above-mentioned white crystalline solid is suspended in the mixing solutions that 50mL 1N hydrochloric acid and 100mL ethyl acetate formed, being stirred to white solid under the room temperature disappears, after the organic layer of telling (water keeps, to reclaim the pyridine of N-benzyl chlorination cinchonine) is used the water washing of 20mL saturated common salt, anhydrous Na ₂SO ₄Dry.Decompression removes down and desolvates, residual solid gets 2.51g white needle-like crystals (R)-(+)-1 with the benzene recrystallization, yield 88%, (HPLC measures ee＞99%, Chiralcel OD-H post, eluent: hexane/isopropyl alcohol=90: 10, flow velocity: 0.6mL/min., retention time: S=21.22min., R=25.04min.): m.p.167-169 ℃; [α] _D ²⁵=+117.0 (c=1.0, THF), ¹H NMR (300MHz, CDCl ₃, TMS): δ=3.72 (bs, 2H), 5.14 (s, 1H), 7.05-7.39 (m, 8H), 7.74-7.92 (m, 4H); ¹³C NMR (125.7MHz, DMSO-d ₆): δ=111.36,115.00,118.53,118.87,120.89,122.33,122.66,123.53,124.20,125.82,126.26,127.10,127.91,129.19,128.54,129.23,133.73,134.10,144.00,153.38; IR (KBr, cm ^-1): ν=3408,3326,3225,1622,1599,816,756; C ₂₀H ₁₅NO, calculated value: C, 84.18; H, 5.30; N, 4.91%.Measured value: C, 84.50; H, 5.31; N, 4.77%.

Mother liquor is concentrated into dried, is dissolved in again in the 50mL ethyl acetate, and respectively with after 10mL 1N hydrochloric acid and the water washing of 20mL saturated common salt, anhydrous Na ₂SO ₄Dry.According to the treatment process of above-mentioned R enantiomorph, get 2.43g white needle-like crystals (S)-(-)-1, yield 85%, ee＞99% (measuring method is the same): m.p.167-169 ℃; [α] _D ²⁵=-117.0 (c=1.0, THF).

Merge above-mentioned water, with saturated NaHCO ₃Be neutralized to alkalescence (pH＞11), heating evaporation is removed most of water, after the cooling crystal of separating out is filtered and washs with less water, gets N-benzyl chlorination cinchonine pyridine (2) white crystal 4.0g, the rate of recovery 95%.It is promptly reusable to need not further recrystallization.

Claims

1. An optical resolution method of 2-amino-2'-hydroxyl-1,1'-binaphthyl, characterized in that:

a. In methanol or acetonitrile or acetone or ethyl acetate, use 0.5 mole of N-benzyl cinchonidine chloride 2 selectively with 1 mole of racemic 2-amino-2'-hydroxyl-1,1'- The R enantiomer in binaphthyl 1 combines to precipitate the molecular crystal (R)-(+)-1·2, which is separated from the mother liquor after filtration, while (S)-(-)-1 remains in in the mother liquor;

b. Decompose the molecular crystal (R)-(+)-1.2 separated from the mother liquor with dilute hydrochloric acid, extract the water-insoluble organic matter with ethyl acetate, and recrystallize the concentrated solid with benzene to obtain Optically pure (R)-(+)-1;

c. The aqueous phase after the above preparation of optically pure (R)-(+)-1 is neutralized with saturated sodium bicarbonate solution, N-benzyl cinchonidine chloride 2 is recovered after concentration, cooling and crystallization, and the recovered N-benzyl cinchonidine chloride 2 can be reused;

d. After the (S)-(-)-1 remaining in the mother liquor is concentrated, it is recrystallized from benzene to obtain its pure product.