CN104892610B - A kind of preparation method of 8-ester group caffeine derivative - Google Patents
A kind of preparation method of 8-ester group caffeine derivative Download PDFInfo
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- GEAPJXCYRWKERW-UHFFFAOYSA-N CCCCOC(c1nc(N(C)C(N(C)C2=O)=O)c2[n]1CCC1C=CC=CC1C)=O Chemical compound CCCCOC(c1nc(N(C)C(N(C)C2=O)=O)c2[n]1CCC1C=CC=CC1C)=O GEAPJXCYRWKERW-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/10—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 3 and 7, e.g. theobromine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/12—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1, 3, and 7, e.g. caffeine
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- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses the preparation method of a kind of 8 ester group caffeine derivative, comprise the steps: caffeine compounds, alcohol, catalyst, oxidant to be put into and organic solvent carries out C H key direct carbonylation in CO atmosphere, after having reacted, obtain 8 ester group caffeine derivative by column chromatography for separation.The present invention directly carries out carbonylation to caffeine C H key, avoid the pre-functionalization of raw material, and use CO as carbon source, there is very atom economy, meeting Modern Green Chemistry demand for development, the 8 ester group caffeine derivative simultaneously prepared have potential medical value.
Description
Technical field
The invention belongs to Minute Organic Synthesis field, be specifically related to the synthetic method of a kind of 8-ester group caffeine derivative.
Background technology
Caffeine derivative is the organic nitrogen-containing heterocyclic compound that a class is important, drug world, bioscience, biological doctor
Learn the aspects such as research and have important application.May be used for molecular recognition as caffeine derivative has autofluorescence and make
Become fluorescence imaging probe.Although having many luminescent probes such as organic dyestuff, inorganic nanoparticles, rare earth compounding, bioluminescence
Albumen can be used in bio-imaging, but this type of little fluorescent tag molecule of caffeine has hypotoxicity and excellent biocompatibility,
It it is one important developing direction of bio-imaging aspect.And for example the substituted caffeine derivative of 8-ester group has for treatment DKA
Well pharmacological action.Owing to caffeine analog derivative has important use, so the becoming of preparation of caffeine analog derivative
One of study hotspot of scholar.
The method of synthesis 8-ester group caffeine derivative has an example (Pinto, Ivan Leo at present；Rahman,Shahzad
Sharooq；Nicholson,Neville Hubert.World WO 2005-EP1449).The method is divided into two steps: first coffee
Coffee, because losing 8-position proton under LiHMDS effect, then generates the substituted caffeine derivative of 8-ester group with acyl chloride reaction.Should
Method uses stoichiometric reagent, can generate a large amount of by-product inorganic lithium salt and hydrochloric acid, and reaction condition is the most severe after reaction
Carve, be difficult to operation.
Carbonylation refers to that introducing carbonyl in organic compound molecule becomes a class reaction of oxygenatedchemicals, is changing
Industrial and commercial bank's industry is widely used.Carbon monoxide (CO) is a kind of common C1 chemical resource.The carbonylation of CO catalytic activation is ground
Study carefully and have significant economic benefit and environmental benefit.And, CO inserts carbonyl reaction great majority as the carbonylation in carbon back source
Belong to atom economy reaction, meet the requirement of Modern Green Chemistry development, be the important of current C1 resource higher value application
One of research direction.
Summary of the invention
A kind of method that it is an object of the invention to provide green easy one-step synthesis 8-ester group caffeine derivative.
For achieving the above object, the present invention adopts the following technical scheme that
The preparation method of a kind of 8-ester group caffeine derivative, comprises the following steps: by caffeine class in CO atmosphere
Compound, alcohol, catalyst, oxidant are put into and are carried out c h bond direct carbonylation in organic solvent, by post layer after having reacted
Analysis isolated 8-ester group caffeine derivative；
The structural formula of described caffeine compounds is as shown in (II):
The structural formula of described alcohols material is as shown in (III):
R3-OH (III)；
The structural formula of described 8-ester group caffeine derivative is as shown in (I):
In the structural formula of described (I) and (II), any one in the following radicals of R1: methyl, ethyl, propyl group or alkene
Propyl group；Can also is that positive brombutyl or benzyl；
Described R2Any one in following radicals: normal-butyl, ethyl, benzyl, 3-cyclobutenyl or isopropyl；Also may be used
To be methyl, propyl group, pi-allyl or positive brombutyl；
In the structural formula of described (I) and (III), R3Any one in following radicals: methyl, ethyl, butyl, benzyl
Base, 3-cyclobutenyl or isopropyl.
Described catalyst is Pd (OAc)2、PdCl2、PdCl2(PPh3)2、PdCl2(CH3CN)2Or [PdCl (cinnamy)]2
In one.
Described oxidant is Cu (OAc)2,、Ag2CO3、AgOAc、K2S2O8, one in Oxone or benzene a kind of jade.
Described organic solvent is toluene, N,N-dimethylformamide, dimethyl sulfoxide, DMAC N,N' dimethyl acetamide or 1,4-
One in dioxane.
Described reaction temperature is 100～140 DEG C.
The described response time is 24～48 hours.
In described preparation method, the consumption of alcohol is the 1170-1950% of caffeine compounds mole dosage, described catalysis
The consumption of agent is the 10% of caffeine compounds mole dosage, the consumption of described oxidant be caffeine compounds mole with
The 200% of amount, the consumption of described organic solvent is for ensureing that catalyst and caffeine compounds are completely dissolved.
After described carbonylation completes, before column chromatography for separation, product is concentrated.
Described concentration uses rotary evaporation method and is spin-dried for by solvent, and described column chromatography is to be with 200～300 mesh silica gel
Separation resin, the eluent of described column chromatography is petroleum ether and ethyl acetate mixtures, and its volume ratio is 2-5:1.
Further, described preparation method specifically comprises the following steps that addition caffeine compounds in Schlenk reaction tube,
Catalyst, oxidant, substitute gas three times with CO gas, afterwards with syringe injection alcohol and organic solvent, then substitute gas three with CO
Secondary, in the oil bath of 100～140 DEG C, then react 24～48h, after having reacted, use Rotary Evaporators to be concentrated to give thick product
Thing, described crude product volume ratio is the petroleum ether of 2-5:1 and ethyl acetate mixtures makees eluant, with 200～300 mesh silica gel
Carry out column chromatography for separation for separation resin and obtain 8-ester group caffeine derivative；
Wherein, described catalyst, oxidant, the consumption of alcohol are respectively the 10% of caffeine compounds mole dosage,
200%, 300～600%, the consumption of described organic solvent is for ensureing that catalyst and caffeine compounds are completely dissolved, described
The consumption of silica gel is 150-200mL.
Further, described preparation method specifically comprises the following steps that addition 0.2mmol in the Schlenk reaction tube of 25mL
Caffeine compounds, 0.02mmol [PdCl2(PPh3)2], 0.4mmol Cu (OAc)2, substitute gas three times with CO gas, afterwards
Inject 0.2～0.3mL alcohol and 1mL Isosorbide-5-Nitrae-dioxane with syringe, then substitute gas three times with CO, then the oil bath of 120 DEG C
Middle reaction 24h, after having reacted, uses Rotary Evaporators to be concentrated to give crude product, and described crude product volume ratio is 2-5:1's
Petroleum ether and ethyl acetate mixtures make eluant, carry out column chromatography for separation with 200～300 mesh silica gel for separation resin and obtain 8-
Ester group caffeine derivative, the consumption of described silica gel is 150-200mL.
The present invention uses above technical scheme, directly from caffeine c h bond, using CO as C1 source, with alcohols material
There is direct carbonylation synthesis 8-ester group caffeine derivative.The preparation method tool of 8-ester group caffeine derivative of the present invention
Have the advantage that 1) react without caffeine raw material functionalization in advance such as being generated halogenated compound, but directly from caffeine
C h bond sets out one-step synthesis 8-ester group caffeine derivative；2) reaction is with CO as carbon source, and byproduct of reaction is water, has plateau
Subeconomy, meets Modern Green Chemistry demand for development；3) reaction CO used is an atmospheric pressure, operates relative ease；4) urge
Agent system is strong to the universality of substrate, applied range, can design the various 8-ester group caffeine of synthesis according to actual needs and spread out
Biological.
Detailed description of the invention
By describing the technology contents of the present invention, the purpose realized and effect in detail, below in conjunction with specific embodiment to this
Invention is described further.
The preparation method of a kind of 8-ester group caffeine derivative, comprises the following steps:
In the Schlenk reaction tube of 50mL, caffeine compounds (II) is added, catalysis according to the proportioning raw materials of table 1
Agent, oxidant and organic solvent, substitute gas three times with CO gas, injects alcohol (III) and organic solvent with syringe afterwards, then uses
CO substitutes gas three times, then reacts 24～48h (concrete reaction condition is as shown in table 2), reaction in the oil bath of 100～140 DEG C
After completing, using Rotary Evaporators to be concentrated to give crude product, described crude product volume ratio is petroleum ether and the acetic acid second of 2-5:1
Eluant made by ester mixed liquor, with 200～300 mesh silica gel for separation resin carry out column chromatography for separation obtain 8-ester group caffeine derive
Thing；
Wherein, described catalyst, oxidant, the consumption of alcohol are respectively the 10% of caffeine compounds mole dosage,
200%, 1170-1950%, the consumption of described organic solvent is for ensureing that catalyst and caffeine compounds are completely dissolved, described
The consumption of silica gel is (150-200mL.
Reaction equation is as follows:
Table 1 raw material and consumption
In table 1, Me is methyl, and Et is ethyl, and Pr is propyl group, and n-Bu is normal-butyl, and Bn is benzyl, and 3-Br-Pr is 3-bromine
Propyl group, Allyl is pi-allyl, and 3-Buten is 3-cyclobutenyl, and i-Pr is isopropyl.
Table 2 reaction condition and product
Specific embodiment 1-12 is carried out according to table 1, table 2
Embodiment 1
By embodiment 1 synthesis obtain compound nuclear magnetic resonance, NMR (1H NMR and13C NMR) detection data be:
1H NMR(400MHz,CDCl3) δ 4.43 (t, J=6.9Hz, 2H), 4.36 (s, 3H), 3.63 (s, 3H), 3.43 (s,
3H), 1.82 (dt, J=14.8,7.0Hz, 2H), 1.53 1.38 (m, 2H), 0.99 (t, J=7.4Hz, 3H).13C NMR
(101MHz,CDCl3)δ158.52,155.62,151.44,146.84,139.14,110.42,66.47,34.75,30.55,
30.02,28.22,19.09,13.71.
So embodiment 1 compound that obtains of synthesis be 1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-
1H-purine-8-butyl carboxylate, its structural formula is as shown in (I-1):
Embodiment 2
The nuclear magnetic resonance, NMR of the compound obtained by the 2-in-1 one-tenth of embodiment (1H NMR and13C NMR) detection data be:
1H NMR(400MHz,CDCl3) δ 4.88 (q, J=7.1Hz, 2H), 4.44 (t, J=6.9Hz, 2H), 3.63 (s,
3H), 3.43 (s, 3H), 1.82 (dq, J=8.9,7.0Hz, 2H), 1.53 1.40 (m, 5H), 0.99 (t, J=7.4Hz, 3H)
.13C NMR(101MHz,CDCl3)δ158.35,155.20,151.48,147.03,138.41,109.72,66.47,43.07,
30.55,30.02,28.23,19.09,16.53,13.71.
So the compound that the 2-in-1 one-tenth of embodiment obtains is 1,3-dimethyl-7-ethyl-2,6-dioxo-2,3,6,7-four
Hydrogenation-1H-purine-8-butyl carboxylate, its structural formula is as shown in (I-2):
Embodiment 3
By embodiment 3 synthesis obtain compound nuclear magnetic resonance, NMR (1H NMR and13C NMR) detection data be:
1H NMR(400MHz,CDCl3) δ 4.85 4.74 (m, 2H), 4.43 (t, J=7.0Hz, 2H), 3.63 (s, 3H),
3.43 (s, 3H), 1.94 1.76 (m, 4H), 1.47 (dd, J=15.1,7.5Hz, 2H), 0.98 (td, J=7.4,6.4Hz,
6H).13C NMR(101MHz,CDCl3)δ158.43,155.26,151.46,146.95,138.67,110.02,66.45,
48.91,30.53,30.02,28.23,24.69,19.08,13.70,10.73.
So the compound that embodiment 3 synthesis obtains is 1,3-dimethyl-7-propyl group-2,6-dioxo-2,3,6,7-four
Hydrogenation-1H-purine-8-butyl carboxylate, its structural formula is as shown in (I-3):
Embodiment 4
By embodiment 4 synthesis obtain compound nuclear magnetic resonance, NMR (1H NMR and13C NMR) detection data be:
1H NMR(400MHz,CDCl3) δ 7.35 7.27 (m, 5H), 6.09 (s, 2H), 4.40 (t, J=6.9Hz, 2H),
3.63 (s, 3H), 3.43 (s, 3H), 1.81 1.70 (m, 2H), 1.47 1.34 (m, 2H), 0.95 (t, J=7.4Hz, 3H).13C
NMR(101MHz,CDCl3)δ158.50,155.40,151.40,147.12,138.84,136.29,128.73,128.11,
127.50,109.90,77.37,77.05,76.73,66.54,50.03,30.49,30.04,28.32,19.01,13.68.
So the compound that embodiment 4 synthesis obtains is 1,3-dimethyl-7-benzyl-2,6-dioxo-2,3,6,7-four
Hydrogenation-1H-purine-8-butyl carboxylate, its structural formula is as shown in (I-4):
Embodiment 5
By embodiment 5 synthesis obtain compound nuclear magnetic resonance, NMR (1H NMR and13C NMR) detection data be:
1H NMR(400MHz,CDCl3) δ 5.03 4.89 (m, 2H), 4.45 (t, J=7.0Hz, 2H), 3.63 (s, 3H),
3.47 (t, J=6.7Hz, 2H), 3.43 (s, 3H), 2.50 2.40 (m, 2H), 1.87 1.78 (m, 2H), 1.54 1.42 (m,
2H), 0.99 (t, J=7.4Hz, 3H).13C NMR(101MHz,CDCl3)δ157.27,154.18,150.27,146.01,
137.71,108.82,65.57,45.53,32.64,29.42,28.95,27.90,27.18,17.97,12.61.
So the compound that embodiment 5 synthesis obtains is 1,3-dimethyl-7-(3-bromopropyl)-2,6-dioxo-2,3,
6,7-tetrahydro-1H-purine-8-butyl carboxylates, its structural formula is as shown in (I-5):
Embodiment 6
By embodiment 6 synthesis obtain compound nuclear magnetic resonance, NMR (1H NMR and13C NMR) detection data be:
1H NMR(400MHz,CDCl3) δ 4.44 (t, J=6.9Hz, 2H), 4.36 (s, 3H), 4.10 (q, J=7.1Hz,
2H), 3.62 (s, 3H), 1.82 (dq, J=8.8,7.0Hz, 2H), 1.54 1.40 (m, 2H), 1.26 (t, J=7.1Hz, 3H),
0.99 (t, J=7.4Hz, 3H).13C NMR(101MHz,CDCl3)δ157.27,154.18,150.27,146.01,137.71,
108.82,65.57,45.53,32.64,29.42,28.95,27.90,27.18,17.97,12.61.
So the compound that embodiment 6 synthesis obtains is 3,7-dimethyl-1-ethyl-2,6-dioxo-2,3,6,7-four
Hydrogenation-1H-purine-8-butyl carboxylate, its structural formula is as shown in (I-6):
Embodiment 7
By embodiment 7 synthesis obtain compound nuclear magnetic resonance, NMR (1H NMR and13C NMR) detection data be:
1H NMR(400MHz,CDCl3) δ 4.43 (t, J=6.9Hz, 2H), 4.36 (s, 3H), 4.02 3.94 (m, 2H),
3.61 (s, 3H), 1.82 (dt, J=14.8,7.0Hz, 2H), 1.76 1.62 (m, 3H), 1.47 (dd, J=15.1,7.5Hz,
2H), 0.98 (q, J=7.4Hz, 6H).13C NMR(101MHz,CDCl3)δ158.54,155.52,151.21,146.85,
139.06,110.48,66.43,43.20,34.72,30.54,29.92,21.24,19.08,13.70,11.33.
So the compound that embodiment 7 synthesis obtains is 3,7-dimethyl-1-propyl group-2,6-dioxo-2,3,6,7-four
Hydrogenation-1H-purine-8-butyl carboxylate, its structural formula is as shown in (I-7):
Embodiment 8
By embodiment 8 synthesis obtain compound nuclear magnetic resonance, NMR (1H NMR and13C NMR) detection data be:
1H NMR(400MHz,CDCl3) δ 5.99 5.85 (m, 1H), 5.34 5.17 (m, 2H), 4.64 (d, J=5.8Hz,
2H), 4.44 (t, J=6.9Hz, 2H), 4.36 (s, 3H), 3.62 (s, 3H), 1.89 1.76 (m, 2H), 1.47 (dd, J=
15.1,7.5Hz, 2H), 0.99 (t, J=7.4Hz, 3H).13C NMR(101MHz,CDCl3)δ158.49,155.18,151.00,
146.99,139.23,131.93,117.90,110.41,66.46,43.59,34.77,30.54,29.97,19.07,13.70.
So the compound that embodiment 8 synthesis obtains is 3,7-dimethyl-1-pi-allyl-2,6-dioxo-2,3,6,7-
Tetrahydro-1H-purine-8-butyl carboxylate, its structural formula is as shown in (I-8):
Embodiment 9
By embodiment 9 synthesis obtain compound nuclear magnetic resonance, NMR (1H NMR) detection data be:
1H NMR(400MHz,CDCl3) δ 4.50 (q, J=7.1Hz, 2H), 4.37 (s, 3H), 3.63 (s, 3H), 3.43 (s,
3H), 1.47 (t, J=7.1Hz, 3H).
So embodiment 9 compound that obtains of synthesis be 1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-
1H-purine-8-carboxylic acid, ethyl ester, its structural formula is as shown in (I-9):
Embodiment 10
By embodiment 10 synthesis obtain compound nuclear magnetic resonance, NMR (1H NMR) detection data be:
1H NMR(400MHz,CDCl3)δ7.43-7.38(m,5H),5.68(s,2H),4.36(s,3H),3.63(s,3H),
3.43 (s, 3H), 1.47 (t, J=7.1Hz, 3H).
So embodiment 10 compound that obtains of synthesis be 1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-
1H-purine-8-benzyl carboxylate, its structural formula is as shown in (I-10):
Embodiment 11
By embodiment 11 synthesis obtain compound nuclear magnetic resonance, NMR (1H NMR) detection data be:
1H NMR(400MHz,CDCl3) δ 5.87 (m, 1H), 5.07-4.92 (m, 2H), 4.62 (t, J=4.6Hz, 2H),
4.37(s,3H),3.63(s,3H),3.43(s,3H),2.47(m,2H).
So embodiment 11 compound that obtains of synthesis be 1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-
1H-purine-8-carboxylic acid 3-butene esters, its structural formula is as shown in (I-11):
Embodiment 12
By embodiment 12 synthesis obtain compound nuclear magnetic resonance, NMR (1H NMR) detection data be:
1H NMR(400MHz,CDCl3)δ5.06-5.01(m,1H),4.37(s,3H),3.63(s,3H),3.43(s,3H),
1.09(s,3H),1.08(s,3H).
So embodiment 12 compound that obtains of synthesis be 1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-
1H-purine-8-carboxylic acid isopropyl, its structural formula is as shown in (I-12):
The foregoing is only embodiments of the invention, not thereby limit the scope of the claims of the present invention, every utilize this
The equivalents that bright description is made, or directly or indirectly it is used in relevant technical field, the most in like manner it is included in this
In bright scope of patent protection.
Claims (6)
1. the preparation method of a 8-ester group caffeine derivative, it is characterised in that: it comprises the steps: will in CO atmosphere
Caffeine compounds, alcohol, catalyst, oxidant are put into and are carried out c h bond direct carbonylation, reaction temperature in organic solvent
It is 100～140 DEG C, after having reacted, obtains 8-ester group caffeine derivative by column chromatography for separation；
The structural formula of described caffeine compounds is as shown in (II):
The structural formula of described alcohols material is as shown in (III):
R3-OH (III)；
The structural formula of described 8-ester group caffeine derivative is as shown in (I):
In the structural formula of described (I) and (II), R1Any one in following radicals: methyl, ethyl, propyl group or pi-allyl；
Described R2Any one in following radicals: normal-butyl, ethyl, benzyl, 3-cyclobutenyl or isopropyl；
In the structural formula of described (I) and (III), R3Any one in following radicals: ethyl, butyl, benzyl, 3-butylene
Base or isopropyl；
Described catalyst is Pd (OAc)2、PdCl2、PdCl2(PPh3)2、PdCl2(CH3CN)2Or in cinnamyl Palladous chloride. dimer
One；
Described oxidant is Cu (OAc)2,、Ag2CO3、AgOAc、K2S2O8, one in potassium hydrogen persulfate or benzene a kind of jade；
In described preparation method, the consumption of alcohol is the 1170-1950% of caffeine compounds mole dosage, described catalyst
Consumption is the 10% of caffeine compounds mole dosage, and the consumption of described oxidant is caffeine compounds mole dosage
200%, the consumption of described organic solvent is for ensureing that catalyst and caffeine compounds are completely dissolved.
The preparation method of 8-ester group caffeine derivative the most according to claim 1, it is characterised in that: described organic solvent
For the one in toluene, N,N-dimethylformamide, dimethyl sulfoxide, DMAC N,N' dimethyl acetamide or 1,4-dioxane.
The preparation method of 8-ester group caffeine derivative the most according to claim 1, it is characterised in that: the described response time
It it is 24～48 hours.
The preparation method of 8-ester group caffeine derivative the most according to claim 1, it is characterised in that: described carbonylation is anti-
After should completing, before column chromatography for separation, product is concentrated.
The preparation method of 8-ester group caffeine derivative the most according to claim 4, it is characterised in that: described concentration uses
Be that solvent is spin-dried for by rotary evaporation method, described column chromatography is with 200～300 mesh silica gel as separation resin, described column chromatography
Eluent be petroleum ether and ethyl acetate mixtures, its volume ratio is 2-5:1.
The preparation method of 8-ester group caffeine derivative the most according to claim 1, it is characterised in that: described preparation method
Specifically comprise the following steps that addition caffeine compounds, catalyst, oxidant in Schlenk reaction tube, substitute gas with CO gas
Three times, afterwards with syringe injection alcohol and organic solvent, then substitute gas three times with CO, then anti-in the oil bath of 100～140 DEG C
Answering 24～48h, after having reacted, use Rotary Evaporators to be concentrated to give crude product, described crude product volume ratio is 2-5:1's
Petroleum ether and ethyl acetate mixtures make eluant, carry out column chromatography for separation with 200～300 mesh silica gel for separation resin and obtain 8-
Ester group caffeine derivative；
Wherein, described catalyst, oxidant, the consumption of alcohol are respectively the 10%, 200% of caffeine compounds mole dosage,
1170-1950%, the consumption of described organic solvent is for ensureing that catalyst and caffeine compounds are completely dissolved.
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|---|---|---|---|---|
| GB8601371D0 (en) * | 1986-01-21 | 1986-02-26 | Beecham Group Plc | Compounds |
| WO2005077950A2 (en) * | 2004-02-14 | 2005-08-25 | Smithkline Beecham Corporation | Medicaments with hm74a receptor activity |
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2015
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