CN108948077A - A kind of the a-amino acid esters compound and its synthetic method of α-phosphorylated - Google Patents
A kind of the a-amino acid esters compound and its synthetic method of α-phosphorylated Download PDFInfo
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- CN108948077A CN108948077A CN201810899993.9A CN201810899993A CN108948077A CN 108948077 A CN108948077 A CN 108948077A CN 201810899993 A CN201810899993 A CN 201810899993A CN 108948077 A CN108948077 A CN 108948077A
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- amino acid
- acid esters
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- phosphorylated
- esters compound
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- 238000010189 synthetic method Methods 0.000 title claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- -1 glycine ester Chemical class 0.000 claims abstract description 17
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000004471 Glycine Substances 0.000 claims abstract description 5
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 239000000758 substrate Substances 0.000 claims abstract description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 36
- 238000003756 stirring Methods 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 229910001914 chlorine tetroxide Inorganic materials 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 229910021580 Cobalt(II) chloride Inorganic materials 0.000 claims description 2
- 229910021592 Copper(II) chloride Inorganic materials 0.000 claims description 2
- 230000008859 change Effects 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 238000002390 rotary evaporation Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims 4
- 150000001335 aliphatic alkanes Chemical group 0.000 claims 2
- 238000005160 1H NMR spectroscopy Methods 0.000 abstract description 10
- 238000006356 dehydrogenation reaction Methods 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 9
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000005859 coupling reaction Methods 0.000 abstract description 4
- 230000001590 oxidative effect Effects 0.000 abstract description 3
- 229910052723 transition metal Inorganic materials 0.000 abstract description 3
- 230000008878 coupling Effects 0.000 abstract description 2
- 238000010168 coupling process Methods 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 2
- 239000001257 hydrogen Substances 0.000 abstract description 2
- 239000007800 oxidant agent Substances 0.000 abstract description 2
- 150000003624 transition metals Chemical class 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 238000004896 high resolution mass spectrometry Methods 0.000 abstract 1
- 238000011017 operating method Methods 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- 239000012298 atmosphere Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 239000007787 solid Substances 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000007445 Chromatographic isolation Methods 0.000 description 9
- 238000012512 characterization method Methods 0.000 description 9
- 238000011097 chromatography purification Methods 0.000 description 9
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 6
- IVUBSBGDEVPYGG-UHFFFAOYSA-N cobalt perchloric acid hydrate Chemical compound [Co].Cl(=O)(=O)(=O)O.O IVUBSBGDEVPYGG-UHFFFAOYSA-N 0.000 description 5
- 238000006880 cross-coupling reaction Methods 0.000 description 5
- 235000013495 cobalt Nutrition 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- AIUIJBDEQKTMHT-UHFFFAOYSA-N perchloric acid;hydrate Chemical compound O.OCl(=O)(=O)=O AIUIJBDEQKTMHT-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- JXBAVRIYDKLCOE-UHFFFAOYSA-N [C].[P] Chemical compound [C].[P] JXBAVRIYDKLCOE-UHFFFAOYSA-N 0.000 description 1
- XCQQWDCKLLORFE-UHFFFAOYSA-N [O].C1(=CC=CC=C1)PC1=CC=CC=C1 Chemical compound [O].C1(=CC=CC=C1)PC1=CC=CC=C1 XCQQWDCKLLORFE-UHFFFAOYSA-N 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 150000001868 cobalt Chemical class 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- BVXOPEOQUQWRHQ-UHFFFAOYSA-N dibutyl phosphite Chemical compound CCCCOP([O-])OCCCC BVXOPEOQUQWRHQ-UHFFFAOYSA-N 0.000 description 1
- ZJIPHXXDPROMEF-UHFFFAOYSA-N dihydroxyphosphanyl dihydrogen phosphite Chemical compound OP(O)OP(O)O ZJIPHXXDPROMEF-UHFFFAOYSA-N 0.000 description 1
- CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical compound COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 description 1
- NFORZJQPTUSMRL-UHFFFAOYSA-N dipropan-2-yl hydrogen phosphite Chemical compound CC(C)OP(O)OC(C)C NFORZJQPTUSMRL-UHFFFAOYSA-N 0.000 description 1
- NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 1
- 239000003063 flame retardant Substances 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000005691 oxidative coupling reaction Methods 0.000 description 1
- 230000000361 pesticidal effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000008301 phosphite esters Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
- C07F9/4009—Esters containing the structure (RX)2P(=X)-alk-N...P (X = O, S, Se)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4075—Esters with hydroxyalkyl compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a kind of a-amino acid esters compound of α-phosphorylated and its synthetic method, the method for the present invention be in the presence of a transition metal catalyst, in organic solvent,NAryl glycine ester and phosphite ester compound carry out heating and react the a-amino acid esters compound that α-phosphorylated is made, the structure warp of such compound1H NMR、13The methods of C NMR and HR-MS are characterized and are confirmed.The method of the present invention is not necessarily to preparatory function dough reaction substrate, using the oxygen in air as Green Oxidant, directly passes through two reaction substratesNTwo carbon-hydrogen links in aryl glycine ester and phosphite ester compound carry out intersecting dehydrogenation coupling, are prepared for a kind of a-amino acid esters compound of α-phosphorylated.Synthetic method atom utilization of the invention is high, synthetic route is brief and environmental-friendly.Synthetic reaction condition is mild, operating procedure is simple, Atom economy is high.It is applicable to fairly large synthesis, with good application prospect.
Description
Technical field
The invention belongs to organic synthesis fields, are related to the synthesis of alpha-substituted alpha-amido acid compounds, in particular to α-ammonia
Base acid derivative α-phosphorylated synthetic method.
Background technique
Dehydrogenation cross-coupling (Dehydrogenative Cross-Coupling) reaction is used as one kind under oxidative conditions,
Directly it is coupled that form new carbon-carbon bond or carbon-heterodesmic novel organic using two carbon-hydrogen links progress dehydrogenation in reaction substrate
Favor of the synthetic reaction by chemists.Compared with traditional methodology of organic synthesis, such reaction is not needed to reaction substrate
Preparatory function dough, keeps synthetic route easier, and atom utilization is higher, and reaction efficiency improves.In recent years, transition metal is urged
The development in modern organic synthesis chemistry of the dehydrogenation cross-coupling reaction of change is swift and violent.Phosphorus-containing matter is prevalent in bioactivity
In molecule, fire retardant, extractant and phosphorus-containing ligand, it is undoubtedly using transition metal-catalyzed dehydrogenation cross-coupling and constructs carbon-phosphorus
Synthetic method the most simple and effective.
A-amino acid is widely present in the natural products and bioactive molecule of nature.Wherein, alpha-amido phosphoric acid
Ester type compound makes it through building C-P bond and obtains alpha-amido phosphate because of its important bioactivity and pesticide activity etc.
Class compound has very important application value.However, up to the present, utilizing transition metal-catalyzed a-amino acid esters
It is rare to close progress α-phosphorylated intersection dehydrogenation coupling reaction building C-P bond report.2013, Yang Shangdong et al. reported copper
It is catalyzed the oxidative coupling reaction synthesizing imine base phosphate of α-aminoketone and diphenylphosphine oxygen compound.2016, Li Chao army class
Topic group reportsNThe dehydrogenation cross-coupling reaction of aryl glycine amide and diphosphite.ButNAryl glycine ester
It cannot effectively carry out intersecting dehydrogenation coupling in the reaction system.As far as we know, catalysis a-amino acid esters chemical combination carries out α-
The intersection dehydrogenation coupling reaction of phosphorylated yet there are no any patent and document report.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of transition metal-catalyzed alpha-amino acid derivatives to carry out α-acyl Asia
Amination prepares α-phosphorylated a-amino acid esters compound green synthesis method.It is a kind of α-ammonia of novel synthesis alpha-substituted
The important method of base acid derivative.Using the transition metal salt that is commercially easy to get as catalyst, air aoxidizes this method as terminal
Agent is coupled by the direct intersection dehydrogenation of α-aminoacidesters and phosphite ester, and α-phosphorylated of one-step synthesis α-aminoacidesters produces
Object.In order to solve the above technical problems, the present invention provides a kind of synthetic method of a-amino acid esters compound α-phosphorylated,
Chemo-selective is good, Atom economy is high and environmental-friendly.Mild, easy to operate, the green ring of this synthesising method reacting condition
It protects, while product purity is high, is convenient for separating-purifying, is applicable to fairly large synthesis application.
The present invention adopts the following technical scheme: a kind of a-amino acid esters compound of α-phosphorylated, structural formula such as formula
(I) shown in:
(I)
Wherein, R1It can be electron-donating group or electron-withdrawing group.Preferably, the electron-donating group can be alkyl；It is described
Electron-withdrawing group can be phenyl.R2It is various alkyl or allyl.Work as R2When being alkyl, methyl, ethyl, isopropyl can be
Base, tert-butyl or benzyl.
R3It can be various alkyl or benzyls.Preferably, the alkyl may be, for example, methyl, ethyl, different in non-limiting manner
Propyl, tert-butyl.
A kind of synthetic method of a-amino acid esters compound α-phosphorylated of the present invention, comprising the following steps: in catalyst
In the presence of, in organic solvent, useNAryl glycine ester (II) and diphosphite class compound (III) are as reaction bottom
Object is stirred to react 12 hours, until TLC detects fully reacting, through column chromatography for separation after concentrated by rotary evaporation, product α-phosphorus can efficiently be made
Acylated a-amino acid esters compound (I).Reaction formula is as follows:
(II) (III) (I)
In preparation method of the present invention, the catalyst is CoO, CoCl2、Co(OAc)2、Co(ClO4)2•6H2O、
CuO、CuCl2Or Cu (OTf)2, preferably Co (ClO4)2•6H2O；By mole meter, the amount of catalyst is formula (III) institute
Show 10 mol % of compound.
Preferably, the organic solvent in the step is acetonitrile or 1,2- dichloroethanes, most preferably acetonitrile.
Preferably, the temperature in the step is room temperature to 100 DEG C, most preferably 80 DEG C.
In preparation method of the present invention, formula (II) compound represented and formula (III) compound represented are rubbed
You are than being preferably 1:1-10, most preferably 1:8.
Compared to the prior art, the present invention has the following advantages and beneficial effects: a kind of a-amino acid esters of the present invention
Closing object α-phosphorylated synthetic method is a kind of with easy to operate, reaction condition is mild, Atom economy is high and environment is friendly
The process flow of the advantages that good.The present invention makees catalyst using the cobalt salt that business is easy to get, and air is terminal oxidant, operation
Simplicity, mild condition and environmentally protective, product is easy to separate and purify, is applicable to fairly large preparation, has preferable
Application prospect.
Specific embodiment
Below by way of specific embodiment, invention is further described in detail, but embodiments of the present invention are not limited to
This.
Embodiment 1
It will under air atmosphereN- 4- tolyl glycine ethyl ester (0.2 mmol), diethyl phosphite (1.6 mmol) and six
Perchloric acid hydrate cobalt (0.02 mmol) is added in the dry reaction test tube with stirring magneton.Then it is added into test tube
Reaction tube is simultaneously placed in 80 in air atmosphere by acetonitrile solvent (2 mL)oIt is reacted 12 hours under C oil bath.To after reaction,
It is cooled to room temperature, solvent is evaporated under reduced pressure with Rotary Evaporators and is removed, and residue obtains pure yellowish through column chromatographic isolation and purification
Color solid 3a, yield 83%.The structural characterization data of 3a compound are as follows:
3a
light yellow solid; mp 75.2-76.4 °C; 1H NMR (400 MHz, CDCl3): δ7.00 (d, J
= 6.4 Hz, 2H), 6.61 (dd, J = 5.4 Hz, J = 1.4 Hz, 2H), 4.47 (d, J = 18.4 Hz,
1H), 4.27-4.17 (m, 6H), 2.24 (s, 3H), 1.36-1.31 (m, 6H), 1.27 (t, J = 5.6 Hz,
3H); 13C NMR (100 MHz, CDCl3): δ168.5 (d, J = 2.4 Hz), 143.8 (d, J = 9.0 Hz),
129.8, 128.8, 114.2, 64.2 (d, J = 4.5 Hz), 63.6 (d, J = 4.7 Hz), 62.2, 56.8
(d, J = 118.0 Hz), 20.5, 16.5 (d, J = 4.8 Hz), 16.4 (d, J = 5.4 Hz), 14.1;
HRMS (ESI) calcd for C15H25NO5P (M+H)+ 330.1465, found 330.1467.
Embodiment 2
It will under air atmosphereN- 4- tolyl glycine ethyl ester (0.2 mmol), dimethylphosphite (1.6 mmol) and six
Perchloric acid hydrate cobalt (0.02 mmol) is added in the dry reaction test tube with stirring magneton.Then it is added into test tube
Reaction tube is simultaneously placed in 80 in air atmosphere by acetonitrile solvent (2 mL)oIt is reacted 12 hours under C oil bath.To after reaction,
It is cooled to room temperature, solvent is evaporated under reduced pressure with Rotary Evaporators and is removed, and residue obtains pure yellowish through column chromatographic isolation and purification
Color solid 3b, yield 95%.The structural characterization data of 3b compound are as follows:
3b
light yellow solid; mp 69.2-70.1 °C; 1H NMR (400 MHz, CDCl3): δ7.01 (d, J
= 6.4 Hz, 2H), 6.61 (dd, J = 6.8 Hz, 2H), 4.52 (d, J = 19.2 Hz, 1H), 4.30-
4.23 (m, 2H), 3.86 (s, 3H), 3.84 (s, 3H), 2.24 (s, 3H), 1.28 (t, J = 6.4 Hz,
3H); 13C NMR (100 MHz, CDCl3): δ168.3 (d, J = 2.6 Hz), 143.7 (d, J = 9.4 Hz),
129.9, 129.0, 114.3, 62.4, 56.5 (d, J = 119.4 Hz), 54.5 (d, J = 4.6 Hz), 53.9
(d, J = 5.3 Hz), 20.5, 14.1; HRMS (ESI) calcd for C13H19NO5P (M-H)- 300.1006,
found 300.1003.
Embodiment 3
It will under air atmosphereN- 4- tolyl glycine ethyl ester (0.2 mmol), diisopropyl phosphite (1.6 mmol) and
Six perchloric acid hydrate cobalts (0.02 mmol) are added in the dry reaction test tube with stirring magneton.Then add into test tube
Enter acetonitrile solvent (2 mL) and reaction tube is placed in 80 in air atmosphereoIt is reacted 12 hours under C oil bath.To the end of reacting
Afterwards, it is cooled to room temperature, solvent is evaporated under reduced pressure with Rotary Evaporators and is removed, and residue obtains pure light through column chromatographic isolation and purification
Yellow solid 3c, yield 76%.The structural characterization data of 3c compound are as follows:
3c
light yellow solid; mp 67.9-68.6 °C; 1H NMR (400 MHz, CDCl3): δ6.99 (d, J
= 6.4 Hz, 2H), 6.59 (dd, J = 8.8 Hz, J = 2.0 Hz, 2H), 4.85-4.76 (m, 2H), 4.41
(d, J = 19.2 Hz, 1H), 4.22 (q, J = 6.4 Hz, 2H), 2.23 (s, 3H), 1.36-1.31 (m,
6H), 1.37-1.29 (m, 12H), 1.26 (t, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
168.8 (d, J = 1.6 Hz), 144.1 (d, J = 10.6 Hz), 129.8, 128.6, 114.2, 72.9 (d,J = 6.3 Hz), 72.4 (d, J = 5.8 Hz), 61.9, 57.8 (d, J = 119.6 Hz), 24.3 (d, J =
3.3 Hz), 24.0 (d, J = 2.9 Hz), 23.8 (d, J = 4.3 Hz), 23.7 (d, J = 3.5 Hz),
20.5, 14.1; HRMS (ESI) calcd for C17H29NO5P (M+H)+ 358.1778, found 358.1776.
Embodiment 4
It will under air atmosphereN- 4- tolyl glycine ethyl ester (0.2 mmol), dibutyl phosphite (1.6 mmol) and six
Perchloric acid hydrate cobalt (0.02 mmol) is added in the dry reaction test tube with stirring magneton.Then it is added into test tube
Reaction tube is simultaneously placed in 80 in air atmosphere by acetonitrile solvent (2 mL)oIt is reacted 12 hours under C oil bath.To after reaction,
It is cooled to room temperature, solvent is evaporated under reduced pressure with Rotary Evaporators and is removed, and residue obtains pure yellowish through column chromatographic isolation and purification
Color oily liquids 3d, yield 62%.The structural characterization data of 3d compound are as follows:
3d
light yellow oil; 1H NMR (400 MHz, CDCl3): δ6.99 (d, J = 6.4 Hz, 2H),
6.60 (dd, J = 8.8 Hz, J = 2.0 Hz, 2H), 4.48 (d, J = 18.8 Hz, 1H), 4.23 (d, J
= 6.4 Hz, 2H), 4.19-4.05 (m, 4H), 2.23 (s, 3H), 1.71-1.61 (m, 4H), 1.46-1.28
(m, 4H), 1.26 (t, J = 5.6 Hz, 3H), 0.96-0.89 (m, 6H); 13C NMR (100 MHz,
CDCl3): δ168.6 (d, J = 1.8 Hz), 143.9 (d, J = 10.1 Hz), 129.8, 128.7, 114.2,
67.7 (d, J = 6.1 Hz), 67.1 (d, J = 5.8 Hz), 65.5 (d, J = 5.1 Hz), 62.1, 56.7
(d, J = 118.7 Hz), 32.5 (d, J = 5.6 Hz), 32.4 (d, J = 5.0 Hz), 20.4, 18.7,
18.6 (d, J = 1.4 Hz), 14.1, 13.5; HRMS (ESI) calcd for C19H31NO5P (M-H)-
384.1945, found 384.1942.
Embodiment 5
It will under air atmosphereN- 4- tolyl glycine methyl ester (0.2 mmol), diethyl phosphite (1.6 mmol) and six
Perchloric acid hydrate cobalt (0.02 mmol) is added in the dry reaction test tube with stirring magneton.Then it is added into test tube
Reaction tube is simultaneously placed in 80 in air atmosphere by acetonitrile solvent (2 mL)oIt is reacted 12 hours under C oil bath.To after reaction,
It is cooled to room temperature, solvent is evaporated under reduced pressure with Rotary Evaporators and is removed, and residue obtains pure yellowish through column chromatographic isolation and purification
Color solid 3e, yield 78%.The structural characterization data of 3e compound are as follows:
3e
light yellow solid; mp 73.5-74.8 °C; 1H NMR (400 MHz, CDCl3): δ7.00 (d, J
= 6.8 Hz, 2H), 6.60 (d, J = 6.8 Hz, 2H), 4.50 (d, J = 18.8 Hz, 1H), 4.27-4.17
(m, 4H), 3.78 (s, 3H), 2.24 (s, 3H), 1.35 (t, J = 5.2 Hz, 3H), 1.32 (t, J =
5.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ169.5 (d, J = 2.4 Hz), 143.8 (d, J =
9.6 Hz), 129.9, 128.9, 114.2, 64.1 (d, J = 4.7 Hz), 63.7 (d, J = 5.4 Hz),
56.6 (d, J = 119.0 Hz), 53.0, 20.4, 16.4 (d, J = 6.4 Hz), 16.3; HRMS (ESI)
calcd for C14H23NO5P (M+H)+ 316.1308, found 316.1311.
Embodiment 6
It will under air atmosphereN- 4- tolyl glycine isopropyl ester (0.2 mmol), diethyl phosphite (1.6 mmol) and
Six perchloric acid hydrate cobalts (0.02 mmol) are added in the dry reaction test tube with stirring magneton.Then add into test tube
Enter acetonitrile solvent (2 mL) and reaction tube is placed in 80 in air atmosphereoIt is reacted 12 hours under C oil bath.To the end of reacting
Afterwards, it is cooled to room temperature, solvent is evaporated under reduced pressure with Rotary Evaporators and is removed, and residue obtains pure light through column chromatographic isolation and purification
Yellow solid 3f, yield 69%.The structural characterization data of 3f compound are as follows:
3f
light yellow solid; mp 76.0-77.5 °C;1H NMR (400 MHz, CDCl3): δ7.00 (d, J
= 6.4 Hz, 2H), 6.60 (d, J = 6.0 Hz, 2H), 5.11-5.07 (m, 1H), 4.44 (d, J = 18.4
Hz, 1H), 4.25-4.20 (m, 4H), 2.24 (s, 3H), 1.35 (t, J = 5.4 Hz, 3H), 1.32 (t,J = 5.6 Hz, 3H), 1.27 (d, J = 5.2 Hz, 3H), 1.27 (d, J = 4.8 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ168.0 (d, J = 2.0 Hz), 143.9 (d, J = 9.0 Hz), 129.8,
128.7, 114.3, 70.0, 64.0 (d, J = 6.2 Hz), 63.4 (d, J = 5.7 Hz), 56.9 (d, J =
118.1 Hz), 21.8, 21.6, 20.5, 16.5 (d, J = 4.1 Hz), 16.4 (d, J = 5.2 Hz); HRMS
(ESI) calcd for C16H27NO5P (M+H)+ 344.1621, found 344.1619.
Embodiment 7
It will under air atmosphereN- 4- tolyl tert-butyl glycinate (0.2 mmol), diethyl phosphite (0.2 mmol) and
Six perchloric acid hydrate cobalts (0.02 mmol) are added in the dry reaction test tube with stirring magneton.Then add into test tube
Enter acetonitrile solvent (2 mL) and reaction tube is placed in 80 in air atmosphereoIt is reacted 12 hours under C oil bath.To the end of reacting
Afterwards, it is cooled to room temperature, solvent is evaporated under reduced pressure with Rotary Evaporators and is removed, and residue obtains pure light through column chromatographic isolation and purification
Yellow oily liquid 3g, yield 67%.The structural characterization data of 3g compound are as follows:
3g
light yellow oil;1H NMR (400 MHz, CDCl3): δ7.00 (d, J = 6.4 Hz, 2H), 6.61
(d, J = 6.0 Hz, 2H), 4.37 (d, J = 18.0 Hz, 1H), 4.26-4.12 (m, 4H), 2.24 (s,
3H), 1.46 (s, 9H), 1.36 (t, J = 5.8 Hz, 3H), 1.31 (t, J = 5.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3): δ167.4 (d, J = 1.3 Hz), 144.2 (d, J = 8.2 Hz), 129.8,
128.5, 114.2, 83.1, 63.9 (d, J = 5.9 Hz), 63.3 (d, J = 6.0 Hz), 57.5 (d, J =
119.2 Hz), 27.9, 20.5, 16.5 (d, J = 4.4 Hz), 16.4 (d, J = 5.4 Hz); HRMS (ESI)
calcd for C17H29NO5P (M+H)+ 358.1778, found 358.1776.
Embodiment 8
It will under air atmosphereN- 4- tolyl glycine benzyl ester (0.2 mmol), diethyl phosphite (0.2 mmol) and six
Perchloric acid hydrate cobalt (0.02 mmol) is added in the dry reaction test tube with stirring magneton.Then it is added into test tube
Reaction tube is simultaneously placed in 80 in air atmosphere by acetonitrile solvent (2 mL)oIt is reacted 12 hours under C oil bath.To after reaction,
It is cooled to room temperature, solvent is evaporated under reduced pressure with Rotary Evaporators and is removed, and residue obtains pure yellowish through column chromatographic isolation and purification
Color oily liquids 3h, yield 80%.The structural characterization data of 3h compound are as follows:
3h
light yellow oil;1H NMR (400 MHz, CDCl3): δ7.33-7.30 (m, 5H), 6.98 (d, J
= 6.8 Hz, 2H), 6.59 (d, J = 6.8 Hz, 2H), 5.24-5.16 (m, 2H), 4.54 (d, J = 18.8
Hz, 1H), 4.23-4.06 (m, 4H), 2.23 (s, 3H), 1.36-1.31 (m, 6H), 1.26 (t, J = 5.6
Hz, 3H), 1.25 (t, J = 5.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ168.5 (d, J =
2.5 Hz), 143.8 (d, J = 10.0 Hz), 135.1, 129.9, 128.9, 128.5, 128.4, 114.3,
67.8, 64.3 (d, J = 6.1 Hz), 63.7 (d, J = 5.8 Hz), 62.2, 56.8 (d, J = 118.4
Hz), 20.5, 16.4 (d, J = 4.0 Hz), 16.3 (d, J = 3.9 Hz); HRMS (ESI) calcd for
C20H27NO5P (M+H)+ 392.1621, found 392.1621.
Embodiment 9
It will under air atmosphereN- 4- (1,1'- xenyl) glycine ethyl ester (0.2 mmol), diethyl phosphite (0.2
Mmol it) is added in the dry reaction test tube with stirring magneton with six perchloric acid hydrate cobalts (0.02 mmol).Then to
Acetonitrile solvent (2 mL) is added in test tube and reaction tube is placed in 80 in air atmosphereoIt is reacted 12 hours under C oil bath.To
After reaction, it is cooled to room temperature, solvent is evaporated under reduced pressure with Rotary Evaporators and is removed, and residue is obtained through column chromatographic isolation and purification
Pure pale yellow oily liquid 3i, yield 65%.The structural characterization data of 3i compound are as follows:
3i
light yellow oil; 1H NMR (400 MHz, CDCl3): δ7.52 (dd, J = 6.8 Hz, J = 0.8
Hz, 2H), 7.45 (dd, J = 5.2 Hz, J = 1.6 Hz, 2H), 7.39 (t, J = 6.2 Hz, 2H),
7.29-7.26 (m, 1H), 6.76 (dd, J = 5.2 Hz, J = 1.6 Hz, 2H), 4.68 (brs, 1H),
4.56 (d, J = 18.4 Hz, 1H), 4.31-4.18 (m, 6H), 2.24 (s, 3H), 1.36-1.31 (m,
6H), 1.36 (t, J = 5.6 Hz, 3H), 1.33 (t, J = 5.6 Hz, 3H), 1.29 (t, J = 5.6 Hz,
3H); 13C NMR (100 MHz, CDCl3): δ168.4 (d, J = 1.6 Hz), 145.6 (d, J = 8.3 Hz),
140.9, 132.4, 128.7, 128.0, 126.5, 114.3, 64.2 (d, J = 4.7 Hz), 63.7 (d, J =
6.1 Hz), 62.4, 56.8 (d, J = 117.3 Hz), 20.5, 16.5 (d, J = 5.3 Hz), 16.4,
14.2; HRMS (ESI) calcd for C20H27NO5P (M+H)+392.1621, found 392.1627.
Claims (8)
1. a kind of a-amino acid esters compound of α-phosphorylated, which is characterized in that shown in its structural formula such as formula (I):
(I)
Wherein, R1For electron-donating group or electron-withdrawing group；R2For alkyl or benzyl；R3For alkyl or benzyl.
2. the a-amino acid esters compound of α-phosphorylated according to claim 1, which is characterized in that the R1To supply
When electron group, specifically methyl；The R1When for electron-withdrawing group, specifically phenyl.
3. the a-amino acid esters compound of α-phosphorylated according to claim 1, which is characterized in that the R2It is alkane
When base, specially methyl, ethyl, isopropyl, tert-butyl, benzyl.
4. the a-amino acid esters compound of α-phosphorylated according to claim 1, which is characterized in that the R3It is alkane
When base, specially methyl, ethyl, isopropyl, tert-butyl.
5. a kind of synthetic method of a-amino acid esters compound α-phosphorylated, comprising the following steps:
In the presence of a catalyst, it in organic solvent, usesNAryl glycine ester (II) and bi-ester of phosphite (III) conduct
Reaction substrate stirs 12 hours, until TLC detects fully reacting, through column chromatography for separation after concentrated by rotary evaporation, product α-phosphinylidyne can be made
The a-amino acid esters compound (I) of change, reaction formula is as follows:
(II) (III) (I)
A kind of synthetic method of a-amino acid esters compound α-phosphorylated according to claim 5, which is characterized in that institute
Stating catalyst is CoO, CoCl2、Co(OAc)2、Co(ClO4)2•6H2O、CuO、CuCl2Or Cu (OTf)2；By mole
Meter, the amount of catalyst are 10 mol % of compound shown in formula (III).
6. a kind of synthetic method of a-amino acid esters compound α-phosphorylated according to claim 5, which is characterized in that
Organic solvent in the step is acetonitrile or 1,2- dichloroethanes.
7. a kind of synthetic method of a-amino acid esters compound α-phosphorylated according to claim 5, which is characterized in that
Temperature in the step is room temperature to 100 DEG C.
8. a kind of synthetic method of a-amino acid esters compound α-phosphorylated according to claim 5, which is characterized in that
The molar ratio of formula (II) compound represented and formula (III) compound represented is 1:1-10.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114487169A (en) * | 2022-01-05 | 2022-05-13 | 宁波大学 | Chiral amino acid detection method |
| CN115611693A (en) * | 2022-05-12 | 2023-01-17 | 常州大学 | Method for catalytically synthesizing isochroman-1-ketone or aromatic ketone compounds |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017183734A1 (en) * | 2016-04-18 | 2017-10-26 | Taisho Pharmaceutical Co., Ltd. | Prodrug of amino acid derivative |
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| WO2017183734A1 (en) * | 2016-04-18 | 2017-10-26 | Taisho Pharmaceutical Co., Ltd. | Prodrug of amino acid derivative |
Non-Patent Citations (5)
| Title |
|---|
| HUIZHEN ZHI 等: "Phosphorylation of Glycine Derivatives via Copper(I)-Catalyzed Csp3-H Bond Functionalization", 《ADV. SYNTH. CATAL.》 * |
| JULIEN A. BROWN: "Synthesis of N-aryl indole-2-carboxylates via an intramolecular palladium-catalysed annulation of didehydrophenylalanine derivatives", 《TETRAHEDRON LETTERS》 * |
| KAZUO YAMAZAKI 等: "Immobilized α-diazophosphonoacetate as a versatile key precursor for palladium catalyzed indole synthesis on a polymer support", 《CHEM. COMMUN.》 * |
| LEIGH FERRIS 等: "N-H Insertion reactions of rhodium carbenoids. Part 2.1 Preparation of N-substituted amino(phosphoryl)acetates (N-substituted phosphorylglycine esters)", 《J. CHEM. SOC. PERKIN TRANS.》 * |
| MARCOS SAN SEGUNDO 等: "Co-Catalyzed C(sp3)-H Oxidative Coupling of Glycine and Peptide Derivatives", 《ORGANIC LETTERS》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114487169A (en) * | 2022-01-05 | 2022-05-13 | 宁波大学 | Chiral amino acid detection method |
| CN114487169B (en) * | 2022-01-05 | 2024-01-16 | 宁波大学 | Chiral amino acid detection method |
| CN115611693A (en) * | 2022-05-12 | 2023-01-17 | 常州大学 | Method for catalytically synthesizing isochroman-1-ketone or aromatic ketone compounds |
| CN115611693B (en) * | 2022-05-12 | 2023-11-28 | 常州大学 | Method for catalytic synthesis of isochroman-1-one or aromatic ketone compound |
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