CN109836375A - A kind of 4- methoxyl group -2,3, the preparation method of 5- trimethylpyridine - Google Patents
A kind of 4- methoxyl group -2,3, the preparation method of 5- trimethylpyridine Download PDFInfo
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- CN109836375A CN109836375A CN201711207334.6A CN201711207334A CN109836375A CN 109836375 A CN109836375 A CN 109836375A CN 201711207334 A CN201711207334 A CN 201711207334A CN 109836375 A CN109836375 A CN 109836375A
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- trimethylpyridine
- methoxyl group
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Abstract
The invention belongs to chemical intermediate preparation fields, and in particular to a kind of 4- methoxyl group -2,3, the preparation method of 5- trimethylpyridine.The present invention includes the following steps: first to obtain 4- methoxyl group -2,3,5- trimethylpyridine -NOxide, after obtain 4- methoxyl group -2,3,5- trimethylpyridine.Therefore the characteristics of this preparation method has high income, and raw material is cheap, and process is simple, good product quality has certain application value.
Description
Technical field
The invention belongs to chemical intermediate preparation fields, and in particular to a kind of 4- methoxyl group -2,3,5- trimethylpyridine
Preparation method.
Background technique
4- methoxy -2,3,5- trimethylpyridine are a kind of important organic synthesis intermediates, and it is difficult to understand to be applied to synthesis in recent years
Beauty draws azoles (Omeprazole) and a series of new anti-ulcer medicament.
It has been reported that synthetic method only with 3- amino-2-methyl -2- butenoic acid ethyl and 2- methylmalonic acid diethyl
Ester is starting material, through cyclization, hydrolysis, decarboxylation, chlorination, reduction, methoxylation and be made.This method raw material sources are difficult, instead
Answer condition harsh, separating difficulty is big, and yield is low, total recovery 43%.
Summary of the invention
The purpose of the present invention is to provide a kind of 4- methoxyl group -2,3, the preparation method of 5- trimethylpyridine, this method is received
Rate is high, and synthesis is simple, is suitble to industrialized production.
To achieve the goals above, the present invention adopts the following technical scheme:
A kind of 4- methoxyl group -2,3, the preparation method of 5- trimethylpyridine, the preparation method method include the following steps:
Step 1: by 4- nitro -2,3,5- trimethylpyridine -N2 oxides are added in sodium methoxide-methanol solution and methanol solution,
Mixture is heated to reflux, vacuum distillation recycling methanol, residue diluted with water, and ethyl acetate extraction merges organic phase, anhydrous sulphur
Sour magnesium is dry, is distilled to recover solvent, and cooling and solidifying is recrystallized with thiacyclohexane, obtains yellowish crystal 4- methoxyl group -2,3,5- trimethyl
Pyridine-N2 oxides.
Step 2:4- methoxyl group -2,3,5- trimethylpyridine -N2 oxides are dissolved in 100mL chloroform, are placed in anti-
It answers in bottle, mixture is cooled to 0~5 DEG C, and phosphorus trichloride is added dropwise, is added dropwise, and continues to stir 1h, in 5% aqueous sodium carbonate
With, water layer chloroform extraction, organic layer merging, saturated sodium-chloride water solution washing, anhydrous magnesium sulfate drying, vacuum distillation
Chloroform is recycled, colorless oil 4- methoxyl group -2,3,5- trimethylpyridine are obtained.
A kind of 4- methoxyl group -2,3,5- trimethylpyridine preparation method, sodium methoxide-methanol solution is dense in the step 1
Degree is 30%.
A kind of 4- methoxyl group -2,3,5- trimethylpyridine preparation method, the temperature in the step 2 are maintained at 0-5 DEG C.
Compared with prior art, effect of the invention is that: this preparation method have high income, raw material is cheap, at technique
Therefore the characteristics of reason is simple, good product quality has certain application value.
Specific embodiment
The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, for the skill of this field
For art personnel, the invention may be variously modified and varied.All within the spirits and principles of the present invention, made any to repair
Change, equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.
Embodiment 1
By 0.2mol 4- nitro -2,3,5- trimethylpyridine -N30% sodium methoxide of 0.3mol/methanol and 150mL is added in 2 oxides
In methanol solution, mixture is heated to reflux 5h, vacuum distillation recycling methanol, residue diluted with water, the acetic acid second of 100mL × 2
Ester extraction merges organic phase, and anhydrous magnesium sulfate is dry, is distilled to recover solvent, and cooling and solidifying is recrystallized with thiacyclohexane, obtained yellowish
Crystal 4- methoxyl group -2,3,5- trimethylpyridine -N2 oxide 30.1g, yield 90%, m.p.35~37 DEG C;
1HNMR (CDCl3) δ: 2.21 (s, 3H, CH3), 2.25 (s, 3H, CH3), 2.48 (s, 3H, CH3), 3.75 (s, 3H,
OCH3), 8.05 (s, 1H, CH);13CNMR (CDCl3) δ: 155.66,147.11,138.09,127.58,126.42,60.26,
13.98,12.98,12.32；IR (KBr) ν: 2927,1307,1258,1097,1033,1307,1002,705cm-1。
By 33.4g (0.2mol) 4- methoxyl group -2,3,5- trimethylpyridine -NOxide is dissolved in 100mL chloroform
In, it is placed in a reaction flask, mixture is cooled to 0~5 DEG C, and 30.2g (0.22mol) phosphorus trichloride is added dropwise, and process temperature is added dropwise and protects
It holds and is added dropwise for 0~5 DEG C of, continue to stir 1h, 5% aqueous sodium carbonate neutralizes, the chloroform extraction of water layer 100mL × 2
It takes, organic layer merges, and saturated sodium-chloride water solution washing, anhydrous magnesium sulfate is dry, and vacuum distillation recycling chloroform obtains colourless
Grease 4- methoxyl group -2,3,5- trimethylpyridine 28.0g, yield 92%.
1HNMR (CDCl3) δ: 2.19 (s, 3H, CH3), 2.22 (s, 3H, CH3), 2.46 (s, 3H, CH3), 3.74 (s, 3H,
OCH3), 8.16 (s, 1H, CH);13CNMR (CDCl3) δ: 163.72,157.10,148.70,124.34,123.88,59.91,
22.69,13.26,11.71;IR (KBr) ν: 2956,2924,2852,1476,1358,1262,1096,1001,863cm-1。
Embodiment 2
By 0.15mol 4- nitro -2,3,5- trimethylpyridine -N2 oxides be added 30% sodium methoxide of 0.25mol/methanol and
In 150mL methanol solution, mixture is heated to reflux 5h, vacuum distillation recycling methanol, residue diluted with water, the acetic acid of 100mL
Ethyl ester extraction merges organic phase, and anhydrous magnesium sulfate is dry, is distilled to recover solvent, and cooling and solidifying is recrystallized with thiacyclohexane, obtained light
Citrine body 4- methoxyl group -2,3,5- trimethylpyridine -N2 oxide 29.2g, yield 90%, m.p.35~37 DEG C；
By 0.18mol 4- methoxyl group -2,3,5- trimethylpyridine -NOxide is dissolved in 100mL chloroform, is placed in anti-
It answers in bottle, mixture is cooled to 0~5 DEG C, and 0.22mol phosphorus trichloride is added dropwise, and process temperature is added dropwise and remains 0~5 DEG C, drips
Finish, continues to stir 1h, 5% aqueous sodium carbonate neutralizes, and the chloroform extraction of water layer 100mL × 2, organic layer merges, saturation
Sodium-chloride water solution washing, anhydrous magnesium sulfate is dry, and vacuum distillation recycling chloroform obtains methoxyl group -2 colorless oil 4-,
3,5- trimethylpyridine 27.5g, yield 91.8%, m.p.35~37 DEG C.
Claims (3)
1. a kind of 4- methoxyl group -2,3, the preparation method of 5- trimethylpyridine, which is characterized in that the preparation method includes following step
It is rapid:
Step 1: by 4- nitro -2,3,5- trimethylpyridine -N2 oxides are added in sodium methoxide-methanol solution and methanol solution,
Mixture is heated to reflux, vacuum distillation recycling methanol, residue diluted with water, and ethyl acetate extraction merges organic phase, anhydrous sulphur
Sour magnesium is dry, is distilled to recover solvent, and cooling and solidifying is recrystallized with thiacyclohexane, obtains yellowish crystal 4- methoxyl group -2,3,5- trimethyl
Pyridine-NOxide；
Step 2:4- methoxyl group -2,3,5- trimethylpyridine -N2 oxides are dissolved in 100mL chloroform, are placed in reaction flask
In, mixture is cooled to 0~5 DEG C, and phosphorus trichloride is added dropwise, is added dropwise, and continues to stir 1h, 5% aqueous sodium carbonate neutralizes, water
Layer chloroform extraction, organic layer merge, and saturated sodium-chloride water solution washing, anhydrous magnesium sulfate is dry, vacuum distillation recycling
Chloroform obtains colorless oil 4- methoxyl group -2,3,5- trimethylpyridine.
2. a kind of 4- methoxyl group -2,3 according to claim 1,5- trimethylpyridine preparation method, which is characterized in that institute
Stating sodium methoxide-methanol solution concentration in step 1 is 30%.
3. a kind of 4- methoxyl group -2,3 according to claim 1,5- trimethylpyridine preparation method, which is characterized in that institute
The temperature for stating step 2 is maintained at 0-5 DEG C.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303018A (en) * | 2020-03-16 | 2020-06-19 | 浙江华洲药业有限公司 | Synthetic method of omeprazole intermediate |
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- 2017-11-27 CN CN201711207334.6A patent/CN109836375A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303018A (en) * | 2020-03-16 | 2020-06-19 | 浙江华洲药业有限公司 | Synthetic method of omeprazole intermediate |
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Application publication date: 20190604 |