CN108707093A - A kind of synthetic method of guanidine compound - Google Patents
A kind of synthetic method of guanidine compound Download PDFInfo
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- CN108707093A CN108707093A CN201810727582.1A CN201810727582A CN108707093A CN 108707093 A CN108707093 A CN 108707093A CN 201810727582 A CN201810727582 A CN 201810727582A CN 108707093 A CN108707093 A CN 108707093A
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- guanidine compound
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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Abstract
The present invention discloses a kind of synthetic method of guanidine compound, the palladium bichloride of 0.01 mmol, the benzamide of 0.1 mmol, the tert-butyl isonitrile of 0.3 mmol, 0.1 mmol cesium carbonates and 2 mL solvent acetonitriles are added in tube sealing, it is passed through air or opening, 2 h, TLC tracking reactions are reacted at 70 DEG C；After complete reaction, it is cooled to room temperature, product at reduced pressure is removed into solvent, product is purified to obtain through Flash silica column chromatography.The method of the present invention is using benzamide and tert-butyl isonitrile as raw material, under the action of palladium catalyst, the guanidine compound that is played an important role to industrial production by one-step synthesis method.This method raw material is easy to get, easy to operate, and yield is considerable, there is good application prospect.
Description
Technical field
The present invention relates to the synthetic method of compound, the synthetic method of specifically a kind of guanidine compound.
Background technology
Guanidine compound have good bioactivity, have the effects that sterilization with it is antiviral.Yellow Sunyu reports hydrochloric acid
Poly- hexamethyl guanidine list guanidine compound has good inhibiting effect to salmonella, Escherichia and glucose coccus etc., right
Skin is non-stimulated, has the characteristics that bactericidal effect wide spectrum, stability are high（《The poly- hexamethyl guanidine disinfectant progress of hydrochloric acid》,
2005,4,324-325）.Yang Xiao reports chlorohexidene and gathers（Pregnancy support group biguanides）Hydrochloride biguanide compound is to golden yellow
The gram negatives such as the gram-positives such as glucose coccus bacterium and Escherichia coli bacterium and mould have bactericidal effect（《Novel biguanides are anti-
Application study of the microbial inoculum in silica gel cat litter》, 2006,33,18-20）.Zhao Shenggui, Zhong Hong report antiviral guanidine drug salts
Sour moroxydine, acyclovir are by inhibiting the synthesis of viral DNA or protein to reach antivirus action（《The system of guanidine compound
Preparation Method and its application》, 2006,36,7-10）.Wang Jinghui reports guanidine derivatives creatine, as a kind of battalion that human body is important
One of agent is supported, to promoting the synthesis of nucleic acid, protein, increases the deposit of human body interior energy quantity of material, promotes the increasing of human muscle's volume
Greatly, it and relieves fatigue etc. and to play an important roll（《The preparation research of disodium creatine phosphate》, 2004）.
The common synthetic method of guanidine compound has：Rowley reports amino nitrile or bromination nitrile synthesis guanidine compound,
Amino nitrile or bromination nitrile react synthesis guanidine compound with amine in water phase（Journal of the American Chemical
Society, 1971, 93(12):5542-5551.）.Kim is reported synthesizes guanidine compound by amido imido grpup methanesulfonic acid,
Amido imido grpup sulfinic acid is first oxidized to amido imido grpup methanesulfonic acid with Peracetic acid, then is reacted from different aminated compounds
To guanidine compound（Tetrahedron Letters, 1988, 29(26):3183-3186.）.It is different that Su Weiguo reports methyl
Thiocarbamide synthesizes guanidine compound, and methyl isothiourea is in HgCl2Under the action of reacted with amine synthesis guanidine compound（Synthetic
Communications, 1996, 26(2):407-413.）.Existing synthetic method, complicated for operation and low-yield are serious to make
The about extensive use of guanidine compound.Therefore, the yield for improving guanidine compound receives the concern of all researchers.
Invention content
The object of the present invention is to provide a kind of new methods of synthesis guanidine compound, are with benzamide and tert-butyl isonitrile
Raw material, by one-step synthesis method guanidine compound, yield is considerable.
Realizing the technical solution of the object of the invention is：
A kind of synthetic method of guanidine compound, synthetic method general formula are as follows：
The synthesis universal method of the guanidine compound is：
The palladium bichloride of 0.01 mmol, the benzamide of 0.1 mmol, the tert-butyl isonitrile of 0.3 mmol, 0.1 are added in tube sealing
Mmol cesium carbonates and 2 mL solvent acetonitriles, are passed through air or opening, and 2 h, TLC tracking reactions are reacted at 70 DEG C；It waits having reacted
Quan Hou is cooled to room temperature, and product at reduced pressure is filtered and removes solvent, and residue purifies to obtain guanidine chemical combination through Flash silica column analysis layer
Object.
The Flash silica column chromatography purifying, eluant, eluent is ethyl acetate: petroleum ether=1: 20.
The structural formula of the guanidine compound of synthesis is as follows：
。
The present invention discloses a kind of new method of synthesis guanidine compound, using benzamide and tert-butyl isonitrile as raw material,
Under the action of palladium catalyst, the guanidine compound that is played an important role to industrial production by one-step synthesis method.This method raw material
It is easy to get, easy to operate, yield is considerable, there is good application prospect.
Specific implementation mode
The content of present invention is made with reference to the preparation and Characterization of The Products of five kinds of guanidine compounds of embodiment further
Illustrate, but is not limitation of the invention.
Embodiment 1
N-(N,N'Di-t-butyl aminoiminomethyl) -2- methyl benzamides synthesis：
0.01 mmol is added in tube sealing（0.0018 g）Palladium bichloride, 0.1 mmol (0.0326 g) cesium carbonate, 0.1
mmol（0.0136 g）O-methyl-benzene formamide, 0.3 mmol（33.9 μL）Tert-butyl isonitrile and 2 mL acetonitriles, be passed through air or
Opening reacts 2 h, TLC tracking reactions at 70 DEG C；After complete reaction, it is cooled to room temperature, it is molten that product at reduced pressure is filtered removing
Agent, residue are purified through Flash silica column analysis layer（Ethyl acetate: petroleum ether=1: 20）Obtain product as white solid 3b 25.5
Mg, yield 88%；
1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 7.4 Hz, 1H), 7.30 – 7.12 (m, 3H),
2.62 (s, 3H), 1.46 (s, 18H)；
13C NMR (100 MHz, CDCl3) δ 179.6 (s), 158.4 (s), 139.8 (s), 137.5 (s),
130.8 (s), 129.5(s), 128.8 (s), 124.9 (s), 50.9 (s), 29.9 (s), 21.4 (s) 。
Embodiment 2
N-(N,N'Di-t-butyl aminoiminomethyl) -4- chlorobenzamides synthesis：
0.01 mmol is added in tube sealing（0.0018 g）Palladium bichloride, 0.1 mmol (0.0326 g) cesium carbonate, 0.1
mmol（0.0156 g）To chlorobenzamide, 0.3 mmol（33.9 μL）Tert-butyl isonitrile and 2mL acetonitriles are passed through air or spacious
Mouthful, 2 h, TLC tracking reactions are reacted at 70 DEG C；After complete reaction, it is cooled to room temperature, it is molten that product at reduced pressure is filtered removing
Agent, residue are purified through Flash silica column analysis layer（Ethyl acetate: petroleum ether=1: 20）Product as white solid 3c 26.8mg are obtained,
Yield 87%；
1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.4 Hz,
2H), 4.45 (s, 1H), 1.46 (s, 18H)；
13C NMR (100 MHz, CDCl3) δ 175.0 (s), 158.7 (s), 137.8 (s), 136.6 (s),
130.1 (s), 127.8 (s), 50.9 (s), 29.8(s)。
Embodiment 3
N-(N,N'Di-t-butyl aminoiminomethyl) -4- t-butylbenzamides synthesis：
0.01 mmol is added in tube sealing（0.0018 g）Palladium bichloride, 0.1 mmol (0.0326 g) cesium carbonate, 0.1
mmol（0.0177 g）To t-butylbenzamide, 0.3 mmol（33.9 μL）Tert-butyl isonitrile and 2 mL acetonitriles, are passed through air
Or it is open, 2 h, TLC tracking reactions are reacted at 70 DEG C；After complete reaction, it is cooled to room temperature, product at reduced pressure is filtered and is removed
Solvent, residue are purified through Flash silica column analysis layer（Ethyl acetate: petroleum ether=1: 20）Obtain product as white solid 3d 33.2
Mg, yield 84%；
1H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.4 Hz,
2H), 1.48 (s, 18H), 1.33 (s, 9H)；
13C NMR (100 MHz, CDCl3) δ 176.2 (s), 158.7 (s), 153.7 (s), 136.6 (s),
128.6 (s), 124.6 (s), 50.8 (s), 34.7(s), 31.2(s), 29.9 (s).
Embodiment 4
N-(N,N'Di-t-butyl aminoiminomethyl) -2- furyl formamides synthesis：
0.01 mmol is added in tube sealing（0.0018 g）Palladium bichloride, 0.1 mmol (0.0326 g) cesium carbonate, 0.1
mmol（0.0111 g）2- furoamides, 0.3 mmol（33.9 μL）Tert-butyl isonitrile and 2 mL acetonitriles, are passed through air or opening,
2 h, TLC tracking reactions are reacted at 70 DEG C；After complete reaction, it is cooled to room temperature, product at reduced pressure is filtered and removes solvent, is remained
Excess is through the analysis layer purifying of Flash silica column（Ethyl acetate: petroleum ether=1: 20）Obtain product as white solid 3e 21.8mg, yield
82%；
1H NMR (400 MHz, CDCl3) δ 10.21 (s, 1H), 7.45 (s, 1H), 6.97 (d, J = 3.2
Hz, 1H), 6.38 (dd, J= 3.1, 1.6 Hz, 1H), 4.37 (s, 1H), 1.41 (s, 18H)；
13C NMR (100 MHz, CDCl3) δ 167.9 (s), 158.4 (s), 153.2 (s), 144.2 (s),
113.3 (s), 111.1 (s), 52.1 (s), 29.8 (s)。
Embodiment 5
N-(N,N'Di-t-butyl aminoiminomethyl) -3- nitrobenzamides synthesis：
0.01 mmol is added in tube sealing（0.0018 g）Palladium bichloride, 0.1 mmol (0.0326 g) cesium carbonate, 0.1
mmol（0.0164 g）M-nitro formamide, 0.3 mmol（33.9 μL）Tert-butyl isonitrile and 2 mL acetonitriles, be passed through air or
Opening reacts 2 h, TLC tracking reactions at 70 DEG C；After complete reaction, it is cooled to room temperature, it is molten that product at reduced pressure is filtered removing
Agent, residue are purified through Flash silica column analysis layer（Ethyl acetate: petroleum ether=1: 20）Product as white solid 3f 26.0mg are obtained,
Yield 82%；
1H NMR (400 MHz, CDCl3) δ 10.50 (s, 1H), 9.04 (s, 1H), 8.47 (d, J = 7.6
Hz, 1H), 8.26 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 7.9 Hz, 1H), 4.57 (s, 1H),
1.50 (s, 18H)；
13C NMR (100 MHz, CDCl3) δ 173.31 (s), 158.7 (s), 148.1 (s), 141.2 (s),
134.4 (s), 128.7 (s), 125.1 (s), 123.9 (s), 52.5 (s), 29.9 (s)。
Claims (3)
1. a kind of synthetic method of guanidine compound, which is characterized in that its synthetic method general formula is as follows：
The synthesis universal method of the guanidine compound is：
The palladium bichloride of 0.01 mmol, the benzamide of 0.1 mmol, the tert-butyl isonitrile of 0.3 mmol, 0.1 are added in tube sealing
Mmol cesium carbonates and 2 mL solvent acetonitriles, are passed through air or opening, and 2 h, TLC tracking reactions are reacted at 70 DEG C；It waits having reacted
Quan Hou is cooled to room temperature, and product at reduced pressure is filtered and removes solvent, and residue purifies to obtain guanidine chemical combination through Flash silica column analysis layer
Object.
2. the synthetic method of guanidine compound according to claim 1, which is characterized in that the Flash silica column chromatography is pure
Change, eluant, eluent is ethyl acetate: petroleum ether=1: 20.
3. the synthetic method of guanidine compound according to claim 1, which is characterized in that the knot of the guanidine compound of synthesis
Structure formula is as follows：
。
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109293585A (en) * | 2018-11-22 | 2019-02-01 | 云南师范大学 | A method of halobenzamides rapid synthesis quinazolinones are utilized under microwave condition in water phase |
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- 2018-07-05 CN CN201810727582.1A patent/CN108707093B/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109293585A (en) * | 2018-11-22 | 2019-02-01 | 云南师范大学 | A method of halobenzamides rapid synthesis quinazolinones are utilized under microwave condition in water phase |
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