CN113754605B - Nitrogen-containing ligand, and preparation method and application thereof - Google Patents
Nitrogen-containing ligand, and preparation method and application thereof Download PDFInfo
- Publication number
- CN113754605B CN113754605B CN202010507170.4A CN202010507170A CN113754605B CN 113754605 B CN113754605 B CN 113754605B CN 202010507170 A CN202010507170 A CN 202010507170A CN 113754605 B CN113754605 B CN 113754605B
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- reaction
- sodium
- route
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1815—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine with more than one complexing nitrogen atom, e.g. bipyridyl, 2-aminopyridine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/02—Preparation of sulfones; Preparation of sulfoxides by formation of sulfone or sulfoxide groups by oxidation of sulfides, or by formation of sulfone groups by oxidation of sulfoxides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/70—Oxidation reactions, e.g. epoxidation, (di)hydroxylation, dehydrogenation and analogues
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/70—Complexes comprising metals of Group VII (VIIB) as the central metal
- B01J2531/72—Manganese
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of organic synthesis, in particular relates to a nitrogen-containing ligand, a preparation method and application thereof, and particularly discloses a compound shown in a formula (I), wherein L is selected from- (CH) 2 ) n ‑、n is selected from 0 to 6; r is selected from C 1‑6 Alkyl, C 6‑10 An aryl group; the invention also provides a synthesis method of the compound and application of the compound in asymmetric reaction; the compound has higher reactivity and enantioselectivity in asymmetric oxidation reaction.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a nitrogen-containing organic ligand compound, a preparation method thereof and application of the ligand in asymmetric oxidation reaction of thioether.
Background
To date, asymmetric oxidation of thioethers is the most practical method for preparing chiral sulfoxides, a very active area of research for over thirty years.
In 1984, the Kagan group achieved asymmetric oxidation of thioethers for the first time using modified Sharpless epoxidation catalysts (Synthesis, 1984,325-326;Tetrahedron Lett.1984,25,1049-1052). Based on the research results of the Kagan system, a series of catalytic systems based on metallic titanium, vanadium, aluminum, iron, copper, etc. have been developed in succession (Tanaka, t.; saito, b.; katsuki, T.TetrahedronLett.2002,43,3259;Katsuki,T.J.Am.Chem.Soc.2007,129,8940;OMahony,G.E.; ford, a.; maguire, A.R.J.Org.Chem.2012,77,3288;Matsumoto,K.; yamaguchi, t.; katsuki, t.chem. Commum.2008, 1704.) only to achieve some relatively simple substrate conversions.
In 2013, the conversion of a substrate that is challenged by a large steric, long-chain or branched class was successfully achieved by Gao using a complex of a chiral tetradentate nitrogen organic ligand and a metal manganese compound as a catalyst and hydrogen peroxide as an oxidizing agent (Dai, w.; li, j.; chen, b.; li, g.; lv, y.; wang, l.; gao, s.org. lett.2013,15,5658).
Based on the research of the prior art, the inventor designs and synthesizes a novel chiral nitrogen-oxygen ligand, inspects the catalytic performance of the ligand in thioether asymmetric oxidation reaction, and obtains unexpected effects.
Disclosure of Invention
The invention provides a nitrogen-containing ligand compound which can be applied to asymmetric oxidation reaction of thioether, and the enantioselectivity of the product can reach more than 95%, thereby providing a new choice for synthesizing compounds or medicaments.
According to the above object, the present invention provides the following technical solutions:
a compound represented by the formula (I),
l is selected from- (CH) 2 ) n -、n is selected from 0 to 6;
r is selected from C 1-6 Alkyl, C 6-10 Aryl groups.
Preferably, L is selected from- (CH) 2 ) n -、n is selected from 0-2.
Preferably, R is selected from methyl, ethyl, isopropyl, tert-butyl, phenyl.
The present invention also provides a method for preparing the ligand compound shown in the formula (I).
In an embodiment, a method for preparing a ligand compound represented by formula (I) is provided, the reaction route being as follows:
wherein L and R are as described above.
Preferably, L is selected from- (CH) 2 ) n -、n is selected from 0-2;
r is selected from methyl, ethyl, isopropyl, tertiary butyl and phenyl.
The route of the invention comprises the following steps:
step 1) preparing a compound of formula (III) by substitution reaction of the compound of formula (II);
step 2) preparing a compound of formula (IV) from a compound of formula (III) through amidation reaction;
step 3) the compound of formula (I) is prepared from the compound of formula (IV) by cyclization.
Preferably, the route described method has any one or more of the following features 1) to 6):
1) In step 1, a compound of formula (II)Carrying out substitution reaction under the action of alkali to prepare a compound of a formula (III); the base is preferably a hydroxide or a hydrate thereof, more preferably lithium hydroxide, lithium hydroxide monohydrate, sodium hydroxide or potassium hydroxide;
2) The reaction solvent in the step 1 is a hydrophilic solvent, preferably any one of water, ethanol, glycerol and propylene glycol, and more preferably water;
3) Step 2 the compound of formula (III) is reacted withCarrying out amidation reaction to obtain a compound of formula (IV); the condensing agent is selected from 2- (7-azabenzotriazol) -N, N '-tetramethyluronium Hexafluorophosphate (HATU), 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (edc.hcl) and/or 1-Hydroxybenzotriazole (HOBT), dicyclohexylcarbodiimide (DCC), benzotriazol-N, N' -tetramethyluronium Hexafluorophosphate (HBTU), preferably 1-Hydroxybenzotriazole (HOBT) and Dicyclohexylcarbodiimide (DCC);
4) The reaction solvent in the step 2 is selected from tetrahydrofuran, 1, 4-dioxane, methylene dichloride, diethylene glycol dimethyl ether or toluene;
5) In the step 3, the compound of the formula (IV) is cyclized in an organic solvent in the presence of an organic base and a catalyst to prepare the compound of the formula (I); the catalyst is triphenylphosphine and FeCl 3 Sodium p-toluenesulfonate or triacetoxyborohydride, preferably triphenylphosphine; the base is an organic amine, more preferably triethylamine or ethylenediamine;
6) The reaction solvent of step 3 is selected from carbon tetrachloride, chloroform, methylene chloride, acetonitrile, ethyl acetate, isopropyl acetate or butyl acetate.
According to another embodiment, a method for preparing a ligand compound of formula (I), scheme 2 is as follows:
wherein L and R are as described above.
Preferably, L is selected from- (CH) 2 ) n -、n is selected from 0-2;
r is selected from methyl, ethyl, isopropyl, tertiary butyl and phenyl.
The route 2 of the invention comprises the following steps:
compounds of formula (V)Carrying out reduction reaction under the action of a reducing agent to prepare a compound shown in a formula (I);
preferably, the reducing agent is selected from sodium triacetoxyborohydride, sodium cyanoborohydride, or sodium borohydride; the reaction solvent is selected from one or more of methanol, ethanol, n-propanol and isopropanol.
According to another embodiment, a method for preparing a ligand compound of formula (I), scheme 3 is as follows:
wherein L and R are as described above.
Preferably, L is selected from- (CH) 2 ) n -、n is selected from 0-2;
r is selected from methyl, ethyl, isopropyl, tertiary butyl and phenyl.
In the route 3 of the present invention, the method comprises the following steps:
1) Compounds of formula (V)(x=br, I, OMs, OTf) under the action of a base to produce a compound of formula (I); OMs are CH 3 -SO 2 -O-, OTf is CF 3 -SO 2 -O-。
2) The alkali is selected from one or more of Triethylamine (TEA), sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide or sodium ethoxide;
3) The reaction solvent is selected from tetrahydrofuran, 1, 4-dioxane, methylene dichloride, diethylene glycol dimethyl ether or toluene.
The invention also provides the use of the ligand compound of formula (I) in an asymmetric oxidation reaction of a substrate. The preferred compounds of the invention are Ig and Ii, the structural formulas of which are shown in the examples, and the enantioselective ee value of the products can reach more than 95% when the compounds are used in thioether asymmetric oxidation reactions.
The substrate for the asymmetric oxidation reaction is thioether. The asymmetric oxidation reaction is a manganese catalyzed asymmetric oxidation reaction. The thioether is illustratively selected from the group consisting of compounds represented by any of the following formulas:
the compound of the formula I is applied to the asymmetric oxidation reaction of thioether, the enantioselectivity of the product can reach more than 95%, and a new choice is provided for the synthesis of the compound or the drug.
Detailed Description
The following describes specific steps of the present invention in detail by way of examples, which should not be construed as limiting the scope of the invention.
Examples 1-9 ligand compounds were synthesized according to scheme 1 below.
Example 1 Synthesis of ligand Compound Ia (R is isopropyl and L is selected from- (CH) 2 ) n -，n＝0)
A25 ml round bottom reaction flask was taken and was charged with anthranilic acid (1.0 g,7.2 mmol), 5ml water, sodium hydroxide (288 mg,7.2 mmol), 1, 2-dibromoethane (0.32 ml,3.6 mmol), heated to reflux for 16h, pH adjusted to 4-5 with dilute hydrochloric acid, extracted with ethyl acetate, the solvent was dried to give a white solid which was washed sequentially with hot water, diethyl ether, and filtered to give a white solid (940 mg, 87%).
The above white solid (200 mg,0.67 mmol) was added to a 25ml round bottom flask, HOBt (199mg, 1.5 mmol), L-valinol (165 mg,1.6 mmol) and 5ml tetrahydrofuran were added sequentially, cooled to-5℃followed by DCC (608 mg,2.9 mmol) and stirred at this temperature for 1h, then stirred at room temperature overnight, the solvent was turned off, and the compound (298 mg, 92%) was purified by direct column chromatography (PE: EA=3:1-EA).
The compound (200 mg,0.42 mmol) obtained in the previous step was placed in a 10ml reaction tube, triphenylphosphine (420 mg,1.6 mmol), 3ml acetonitrile, carbon tetrachloride (0.16 ml,1.6 mmol) and triethylamine (0.22 ml,1.6 mmol) were added in this order, stirred overnight at room temperature, the solvent was removed by stirring, and the mixture was purified by column chromatography (PE: EA=20:1-10:1) to give a white solid (130 mg, 76%).
1 H NMR(400MHz,CDCl 3 ):δ＝8.75(s,2H),7.72(dd,J＝7.8,1.3Hz,2H),7.29(m,2H),6.73(d,J＝8.4Hz,2H),6.62(t,J＝7.5Hz,2H),4.30(dd,J＝8.8,7.8Hz,2H),4.00(ddd,J＝29.6,15.3,7.9Hz,4H),3.58(s,4H),1.67(dq,J＝13.4,6.7Hz,2H),0.89(dd,J＝21.9,6.7Hz,12H).
13 C NMR(100MHz,CDCl 3 ):δ＝163.7,160.3,149.0,132.4,129.8,14.5,110.2,108.7,72.8,68.8,42.4,33.3,18.8.
LRMS(ESI):435.2(M+H) + .
HRMS(ESI):calcd for C 26 H 34 N 4 O 2 (M+H) + :435.2755,found:435.2774.
EXAMPLE 2 Synthesis of ligand Compound Ib (R is isopropyl)Radical L is selected from- (CH) 2 ) n -，n＝1)
The synthesis of ligand Ib is described in example 1, with the difference that 1, 3-dibromopropane is used instead of 1, 2-dibromoethane. Compound Ib was obtained as a white solid. The total yield was 58%.
1 H NMR(400MHz,CDCl 3 ):δ＝8.63(s,2H),7.70(dd,J＝7.9,1.5Hz,1H),7.30–7.24(m,3H),6.69(dd,J＝8.2,3.5Hz,2H),6.59(t,J＝7.2,2H),4.30(t,J＝8.0,2H),4.14–4.02(m,2H),3.97(t,J＝8.0,2H),3.40(dd,J＝11.9,6.7Hz,4H),2.10(p,J＝6.8Hz,2H),1.74(tt,J＝13.4,6.6Hz,2H),0.99(dd,J＝6.8Hz,6H),0.91(dd,J＝6.8Hz,6H).
LRMS(ESI):449.2(M+H) + .
Example 3 Synthesis of ligand Compound Ic (R is isopropyl and L is selected from- (CH) 2 ) n -，n＝2)
The synthesis of ligand Ic is described in example 1, with the difference that 1, 4-dibromobutane is used instead of 1, 2-dibromoethane. Compound Ic was obtained as a white solid. The total yield was 55%.
1 H NMR(400MHz,CDCl 3 ):δ8.62(s,2H),7.68(dd,J＝7.5,1.6Hz,2H),7.28-7.22(m,J＝7.5,2.5Hz,2H),6.65(dd,J＝7.9,2.6Hz,2H),6.56(t,J＝7.4Hz,2H),4.30(t,J＝8.0,2H),4.14–4.02(m,2H),3.97(t,J＝8.0,2H),3.28–3.16(m,4H),1.81–1.55(m,6H),1.00(dd,J＝6.8,1.5Hz,6H),0.90(dd,J＝6.8,1.4Hz,6H).
LRMS(ESI):463.2(M+H) + .
EXAMPLE 4 Synthesis of ligand Compound Id (R is isopropyl and L is selected from)
The synthesis of ligand Id is described in example 1, with the difference that 1, 3-bis (bromomethyl) benzene is used instead of 1, 2-dibromoethane. Compound Id was obtained as a white solid. The total yield was 66%.
1 H NMR(400MHz,CDCl 3 ):δ＝8.94(t,J＝5.2Hz,2H),7.65(dd,J＝7.8,1.5Hz,2H),7.33(s,1H),7.24–7.12(m,5H),6.54(t,J＝8.2Hz,4H),4.39(m,4H),4.23(dd,J＝9.1,8.0Hz,2H),4.03–3.95(m,2H),3.90(t,J＝7.9Hz,2H),1.65(dq,J＝13.4,6.7Hz,2H),0.84(dd,J＝20.3,6.7Hz,12H).
13 C NMR(100MHz,CDCl 3 ):δ＝163.5,148.6,139.6,131.9,129.5,128.8,125.7,115.6,114.5,110.6,109.1,72.9,68.7,47.1,33.2,18.6.
LRMS(ESI):511.2(M+H) + .
HRMS(ESI):calcd for C 32 H 38 N 4 O 2 (M+H) + :511.3068,found:511.3083.
Example 5 Synthesis of ligand Compound Ie (R is methyl and L is selected from- (CH) 2 ) n -，n＝1)
The synthesis of ligand Ie is described in example 2, with the difference that L-alaninol is used instead of L-valinol. Compound Ie was obtained as a white solid. The total yield was 48%.
LRMS(ESI):393.2(M+H) + .
Example 6 Synthesis of ligand Compound If (R is tert-butyl and L is selected from- (CH) 2 ) n -，n＝1)
The synthesis of ligand If is described in example 2, with the difference that L-tertiary leucinol is used instead of L-valinol. Compound If was obtained as a white solid. The total yield was 63%.
LRMS(ESI):477.2(M+H) + .
EXAMPLE 7 Synthesis of ligand Compound Ig (R is phenyl and L is selected from- (CH) 2 ) n -，n＝1)
The synthesis of ligand Ig is described in reference to example 2, with the difference that L-phenylglycine is used instead of L-valine. Compound Ig was obtained as a white solid. The total yield was 56%.
LRMS(ESI):517.2(M+H) + .
EXAMPLE 8 Synthesis of ligand Compound Ih (R is tert-butyl and L is selected from)
The synthesis of ligand Ih is described in reference to example 4, except that L-tertiary leucinol is used instead of L-valinol. Compound Ih was obtained as a white solid. The total yield was 70%.
LRMS(ESI):539.3(M+H) + .
Example 9 Synthesis of ligand Compound Ii (R is phenyl, n=0 and phenyl)
The synthesis of ligand Ii is described in example 4, with the difference that L-phenylglycine is used instead of L-valine. Compound Ii was obtained as a white solid. The total yield was 64%.
LRMS(ESI):579.2(M+H) + .
Example 10 (R is benzyl and L is selected from- (CH) 2 ) n -，n＝0)
The compound shown above was produced in a total yield of 61% by using L-phenylalaninol instead of L-valinol in reference to example 1.
1 H NMR(400MHz,CDCl 3 ):δ＝8.90(dd,J＝8.5,0.8Hz,2H),7.86(dd,J＝7.9,1.6Hz,2H),7.49±7.55(m,2H),7.11±7.34(m,12H),6.60(t,J＝7.5Hz,2H),4.30(dd,J＝8.6,7.5Hz,2H),4.00(m,4H),3.57(s,4H),3.38(dd,J＝13.8,5.0Hz,2H),2.88(dd,J＝13.9,8.6Hz,2H)
LRMS(ESI):531.2(M+H) + .
Example 11 (R is benzyl and L is selected from- (CH) 2 ) n -，n＝1)
The compound shown above was produced in a total yield of 57% by using L-phenylalaninol instead of L-valinol in reference to example 2.
1 H NMR(400MHz,CDCl 3 ):δ＝8.87(dd,J＝8.6,0.8Hz,2H),7.82(dd,J＝7.8,1.5Hz,2H),7.47-7.53(m,2H),7.10-7.32(m,12H),6.59(t,J＝7.5Hz,2H),4.30(dd,J＝8.6,7.5Hz,2H),4.00(m,4H),3.40(dd,J＝11.9,6.7Hz,4H),2.10(p,J＝6.8Hz,2H),3.37(dd,J＝13.6,5.0Hz,2H),2.88(dd,J＝13.8,8.5Hz,2H)
LRMS(ESI):545.2(M+H) + .
Example 12 (R is benzyl and L is selected from)
The compound shown above was produced in a total yield of 68% by using L-phenylalaninol instead of L-valinol in reference example 4.
LRMS(ESI):607.2(M+H) + .
Example 13 (R is methyl and L is selected from)
The compound shown above was produced in a total yield of 60% by using L-alaninol instead of L-valinol in reference example 4.
LRMS(ESI):455.2(M+H) + .
Examples 14-16 ligand compounds were synthesized according to scheme 2 below.
EXAMPLE 14 Synthesis of ligand Compound Ia (R is isopropyl and L is selected from- (CH) 2 ) n -，n＝0)
To a 50ml round bottom flask under nitrogen protection was added (S) -2- (2-aminophenyl) -4- (isopropyl) -4, 5-dihydrooxazole (408 mg,2.0 mmol), 10ml of absolute ethanol, 40% glyoxal (114 uL,1.0 mmol), sodium triacetoxyborohydride (848 mg,4 mmol) and after completion of the reaction the solvent was removed and purified by direct column chromatography (PE: EA=10:1-5:1) to give white solid Ia (640 mg, 70%).
EXAMPLE 15 Synthesis of ligand Compound Ib (R is isopropyl and L is selected from- (CH) 2 ) n -，n＝1)
Referring to example 14, malondialdehyde was used instead of glyoxal to give compound Ib as a white solid. The total yield was 76%.
EXAMPLE 16 Synthesis of ligand Compound Ic (R is isopropyl and L is selected from- (CH) 2 ) n -，n＝2)
Referring to example 14, 1, 4-butanedial was used instead of glyoxal to give compound Ic as a white solid. The total yield was 62%.
Examples 17-19 ligand compounds were synthesized according to scheme 3 below.
EXAMPLE 17 Synthesis of ligand Compound Ib (R is isopropyl and L is selected from- (CH) 2 ) n -，n＝1)
25ml of a reaction tube was taken, followed by addition of (S) -2- (2-aminophenyl) -4- (isopropyl) -4, 5-dihydrooxazole (313 mg,3.0 mmol), 10ml of diethylene glycol dimethyl ether, 1, 3-dibromopropane (102 ul,1.0 mmol), potassium carbonate (552 mg,4 mmol), reaction at 140℃for 24 hours, cooling to room temperature, addition of saturated ammonium chloride solution, extraction with ethyl acetate, spin-off of the solvent, purification by direct column chromatography (PE: EA=30:1-10:1) to give compound Ib (226 mg, 58%).
EXAMPLE 18 Synthesis of ligand Compound Ic (R is isopropyl and L is selected from- (CH) 2 ) n -，n＝2)
Referring to example 17, 1, 4-dibromobutane was used instead of 1, 3-dibromopropane to obtain compound Ic as a white solid. The total yield was 62%.
EXAMPLE 19 Synthesis of ligand Compound Id (R is isopropyl, L is selected from)
Reference example 17 1, 3-bis (bromomethyl) benzene was used instead of 1, 3-dibromopropane. Compound Id was obtained as a white solid. The total yield was 78%.
EXAMPLE 20 use of ligand Compounds in asymmetric Oxidation
To the reaction tube were added manganese (II) triflate (3.5 mg,0.01 mmol) and ligand (0.011 mmol), dichloromethane (5 mL), and stirred for 1h. The reaction mixture was cooled to-10℃and then added with phenyl sulfide (1.0 mmol) and glacial acetic acid (5.0 mmol) and 30% hydrogen peroxide (1.5 mmol) was added dropwise, the organic phase was separated after completion of the reaction, dried over sodium sulfate and the product was obtained by column chromatography.
The reaction results are shown in Table 1 below.
TABLE 1 test results of ligand compounds in thioether asymmetric Oxidation reactions
| Ligand compound | Yield (%) | ee(％) |
| Ib | 57 | 69 |
| Id | 76 | 81 |
| Ie | 78 | 66 |
| If | 65 | 87 |
| Ig | 73 | 95 |
| Ih | 68 | 91 |
| Ii | 85 | 97 |
From experimental results, it can be found that the ligand compound of the invention can be used for asymmetric oxidation of thioether, especially for ligand compounds Ig and Ii, and the enantioselectivity of the product can reach more than 95%.
The invention designs and synthesizes a new ligand compound containing nitrogen, and experimental results show that the new ligand compound containing nitrogen can obtain very high enantioselectivity and very good activity, namely good results, when being used in asymmetric oxidation reaction of thioether.
Claims (15)
1. A compound of formula (I) having the structure:
l is selected from- (CH) 2 ) n -、n is selected from 0-2;
r is selected from C 1-6 Alkyl, C 6-10 Aryl groups.
2. A compound according to claim 1, wherein R is selected from methyl, ethyl, isopropyl, tert-butyl, phenyl.
3. A process for the preparation of a compound of formula (I) according to claim 1, characterized in that it is selected from scheme 1, scheme 2 or scheme 3:
route 1:
route 2:
route 3:
l, R is as claimed in claim 1.
4. A method according to claim 3, wherein the method of route 1) has any one or more of the following features 1) to 6):
1) In step 1, a compound of formula (II)Carrying out substitution reaction under the action of alkali to prepare a compound of a formula (III);
2) The reaction solvent in the step 1 is a hydrophilic solvent;
3) In step 2, the compound of formula (III) is reacted withCarrying out amidation reaction to obtain a compound of formula (IV); the condensing agent is selected from 2- (7-aza-benzotriazol) -N, N '-tetramethyl urea Hexafluorophosphate (HATU), 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (edc.hcl) and/or 1-Hydroxybenzotriazole (HOBT), dicyclohexylcarbodiimide (DCC), benzotriazol-N, N' -tetramethyl urea Hexafluorophosphate (HBTU);
4) The reaction solvent in the step 2 is selected from tetrahydrofuran, 1, 4-dioxane, methylene dichloride, diethylene glycol dimethyl ether or toluene;
5) In the step 3, the compound of the formula (IV) is cyclized in an organic solvent in the presence of an organic base and a catalyst to prepare the compound of the formula (I); the catalyst is triphenylphosphine and FeCl 3 Sodium p-toluenesulfonate or triacetoxyborohydride; the alkali is organic amine;
6) The reaction solvent of step 3 is selected from carbon tetrachloride, chloroform, methylene chloride, acetonitrile, ethyl acetate, isopropyl acetate or butyl acetate.
5. The method of claim 4, wherein the base in step 1 is selected from the group consisting of hydroxides and hydrates thereof.
6. The method of claim 5, wherein the base in step 1 is selected from the group consisting of lithium hydroxide, lithium hydroxide monohydrate, sodium hydroxide, and potassium hydroxide.
7. The method according to claim 4, wherein the hydrophilic solvent in step 1 is selected from any one of water, ethanol, glycerol, and propylene glycol.
8. The method of claim 7, wherein the hydrophilic solvent in step 1 is water.
9. The method of claim 5, wherein the condensing agent in step 2 is 1-Hydroxybenzotriazole (HOBT) or Dicyclohexylcarbodiimide (DCC).
10. The process of claim 5 wherein in step 3 the catalyst is triphenylphosphine; the organic amine is triethylamine or ethylenediamine.
11. The method of claim 4, wherein the method of route 2 comprises: compounds of formula (V)Carrying out reduction reaction under the action of a reducing agent to prepare a compound shown in a formula (I); the reducing agent is selected from sodium triacetoxyborohydride, sodium cyanoborohydride or sodium borohydride; the reaction solvent is selected from one or more of methanol, ethanol, n-propanol and isopropanol.
12. The method of claim 4, wherein the method of route 3 comprises: compounds of formula (V)Carrying out substitution reaction under the action of alkali to prepare a compound shown in a formula (I); the alkali is selected from one or more of Triethylamine (TEA), sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide or sodium ethoxide; the reaction solvent is selected from tetrahydrofuran, 1, 4-dioxane, methylene dichloride, diethylene glycol dimethyl ether or toluene.
13. Use of a compound of formula (I) according to claim 1 as chiral ligand in an asymmetric oxidation reaction of a thioether.
14. The use according to claim 13, wherein the thioether is selected from the group consisting of compounds of any one of the following formulas:
15. the use according to claim 13, wherein the asymmetric oxidation reaction is a manganese catalyzed asymmetric oxidation reaction.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010507170.4A CN113754605B (en) | 2020-06-05 | 2020-06-05 | Nitrogen-containing ligand, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010507170.4A CN113754605B (en) | 2020-06-05 | 2020-06-05 | Nitrogen-containing ligand, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113754605A CN113754605A (en) | 2021-12-07 |
| CN113754605B true CN113754605B (en) | 2023-10-03 |
Family
ID=78785129
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010507170.4A Active CN113754605B (en) | 2020-06-05 | 2020-06-05 | Nitrogen-containing ligand, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113754605B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115260217B (en) * | 2022-08-19 | 2024-06-07 | 大连理工大学 | Bridged bisoxazoline rare earth metal catalyst, preparation method and application |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104119288A (en) * | 2013-04-26 | 2014-10-29 | 中国科学院大连化学物理研究所 | Synthetic method for nitrogen-containing tetra-dentate organic ligand |
| CN104119352A (en) * | 2013-04-26 | 2014-10-29 | 中国科学院大连化学物理研究所 | Asymmetric epoxidation method for alkenes |
| CN104356098A (en) * | 2014-11-10 | 2015-02-18 | 舒兰市金马化工有限公司 | Preparation method of chiral epoxy chloropropane |
| CN104447440A (en) * | 2013-09-12 | 2015-03-25 | 中国科学院大连化学物理研究所 | Method for catalyzing asymmetric oxidation of thioether |
| CN104447692A (en) * | 2013-09-12 | 2015-03-25 | 中国科学院大连化学物理研究所 | Preparation method of chiral sulfoxide medicament though catalysis of asymmetric oxidation of sulfides compound |
| CN105503673A (en) * | 2014-09-25 | 2016-04-20 | 中国科学院大连化学物理研究所 | Method for preparing chiral sulfoxide through catalysis of asymmetric oxidation of thioether |
| CN106831508A (en) * | 2015-12-04 | 2017-06-13 | 中国科学院大连化学物理研究所 | A kind of method for being catalyzed asymmetric oxidation thioether |
-
2020
- 2020-06-05 CN CN202010507170.4A patent/CN113754605B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104119288A (en) * | 2013-04-26 | 2014-10-29 | 中国科学院大连化学物理研究所 | Synthetic method for nitrogen-containing tetra-dentate organic ligand |
| CN104119352A (en) * | 2013-04-26 | 2014-10-29 | 中国科学院大连化学物理研究所 | Asymmetric epoxidation method for alkenes |
| CN104447440A (en) * | 2013-09-12 | 2015-03-25 | 中国科学院大连化学物理研究所 | Method for catalyzing asymmetric oxidation of thioether |
| CN104447692A (en) * | 2013-09-12 | 2015-03-25 | 中国科学院大连化学物理研究所 | Preparation method of chiral sulfoxide medicament though catalysis of asymmetric oxidation of sulfides compound |
| CN105503673A (en) * | 2014-09-25 | 2016-04-20 | 中国科学院大连化学物理研究所 | Method for preparing chiral sulfoxide through catalysis of asymmetric oxidation of thioether |
| CN104356098A (en) * | 2014-11-10 | 2015-02-18 | 舒兰市金马化工有限公司 | Preparation method of chiral epoxy chloropropane |
| CN106831508A (en) * | 2015-12-04 | 2017-06-13 | 中国科学院大连化学物理研究所 | A kind of method for being catalyzed asymmetric oxidation thioether |
Non-Patent Citations (1)
| Title |
|---|
| 18F‑Labeled Benzyldiamine Derivatives as Novel Flexible Probes for Positron Emission Tomography of Cerebral β‑Amyloid Plaques;Zijing Li等;J. Med. Chem.;第59卷;10577-10585 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113754605A (en) | 2021-12-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105801575A (en) | Synthetic method of imidazo[1,2-a]pyridine | |
| CN113754605B (en) | Nitrogen-containing ligand, and preparation method and application thereof | |
| CN111925356B (en) | Synthesis method and application of chiral quinoline-imidazoline ligand | |
| CN113636950B (en) | Preparation method of chiral 4-aryl-beta-amino acid derivative | |
| CN113754604B (en) | Nitrogen-containing chiral ligand and application thereof in asymmetric oxidation reaction of thioether | |
| KR101130818B1 (en) | Method for preparing chiral amino acid from azlactones using bifunctional bis-cinchona alkaloid thiourea organo catalysts | |
| EP2958893B1 (en) | Asymmetric synthesis of a substituted pyrrolidine-2-carboxamide | |
| CN112645833A (en) | Synthesis method of (S) -2, 6-diamino-5-oxohexanoic acid | |
| JP6548214B2 (en) | Catalyst having an aminosalicylaldimine ligand coordinated to metal and method for producing iodocyclic compound using the same | |
| JP5622019B2 (en) | Asymmetric organic molecular catalyst having amino alcohol derivative salt structure and method for producing optically active compound using said asymmetric organic molecular catalyst | |
| CN107602418B (en) | Method for synthesizing amidine compound by copper (II) catalyzed aryl methyl ketone oxidation amidation | |
| CN105820174A (en) | Polysubstituted thienoindole derivative and preparation method thereof | |
| CN110698426B (en) | Method for preparing 1, 3-benzothiazole derivative by efficient catalysis of potassium tert-butoxide | |
| CN114315609A (en) | Process for preparing cis-2-aminocyclohexanol | |
| CN110028448B (en) | Preparation method of 3-hydroxy-2,3-dihydroisoquinoline-1, 4-diketone compound | |
| CN110003083B (en) | Process method for preparing S-indoline-2-carboxylic acid by using Ir catalyst | |
| WO2020220651A1 (en) | Method for synthesizing chiral 2-hydroxy-1,4-dicarbonyl compound and pantolactone | |
| US6610855B2 (en) | Synthesis of 3-amino-3-aryl propanoates | |
| CN116023359B (en) | Synthesis method of aminothiophene compound and aminothiophene compound | |
| CN114478242B (en) | Salen-Ti complex catalyst and method for catalyzing asymmetric hydrogen atom transfer reaction by using same | |
| CN114988976B (en) | Method for synthesizing chiral cyclopentenones by organically catalyzing Nazarov cyclization | |
| JP4529419B2 (en) | Optically active fluorine-containing compounds and methods for producing them | |
| JP4956614B2 (en) | Novel process for producing 3-amino-5-fluoro-4-dialkoxypentanoic acid ester | |
| CN116589376A (en) | Method for synthesizing chiral alpha- (N-hydroxy) amino acid amide under mild condition | |
| CN106278968B (en) | A kind of method for synthesizing sulfo-amino acid derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |