CN105646334A - Preparation method of 2,6-pyridinedimethanol - Google Patents

Abstract

The invention relates to a preparation method of a compound 2,6-pyridinedimethanol. The preparation method comprises the steps: a raw material 2,6-dimethylpyridine is oxidized by using potassium permanganate, 2,6-pyridinedicarboxylic acid is generated and is reduced by a sodium borohydride/iodine system, and the 2,6-pyridinedimethanol with higher yield is obtained. Compared with the prior art, the method has the advantages that the steps are simplified, the reaction condition is mild, the operation is safe, simple and convenient, the products are easy to separate, the yield is higher and the like.

Description

A kind of preparation method of 2,6-pyridine dimethanol

Technical field

The present invention relates to a kind of chemical intermediate and technology of preparing, the preparation method being specially 2,6-pyridine dimethanols.

Background technology

2,6-disubstituted pyridines are the organic synthesis intermediates that a class is important, and especially the application of 2,6-pyridine dimethanols is very strong. Hydroxyl can derive as other functional groups many such as aldehyde radical, halogenated hydrocarbons, amino, and then synthesizes other important compound. And owing to being the replacement of 2,6, macrocyclic compound therefore can also be generated, in synthesis, Application comparison is extensive, has higher researching value.

At present, the route synthesizing 2,6-pyridine dimethanols more classical is for raw material with 2,6-lutidines, and being oxidized is 2,6-pyridinedicarboxylic acids, is then esterified, then ester is reduced to alcohol, obtain target product. This synthetic route is three-step reaction, is usually made methyl ester when pyridinedicarboxylic acid is esterified by second step, as then needed concentrated sulphuric acid to be catalyst with classical esterification process, is corrosive, and response time length (is generally more than 24 hours) and productivity is not high. If acid is reacted with thionyl chloride, then can improve productivity with alcohol esterification again after making acyl chlorides, but reagent to carry out Non-aqueous processing, and thionyl chloride has very strong zest, also can generate SO in reaction₂And HCl gas, poisonous and harmful and being corrosive, tail gas absorption need to be carried out so that operating procedure is relatively complicated, add the difficulty of reaction.

Reduction step in 2,6-pyridine dimethanol preparation process has mainly been simplified by the present invention. With NaBH₄/I₂As reduction system, can be 2,6-pyridine dimethanols by 2,6-pyridinedicarboxylic acid direct-reductions, it is not necessary to restore after acid is esterified, original three-step reaction is reduced to two steps. And NaBH₄/I₂System productivity is high, and does not need to use concentrated sulphuric acid and thionyl chloride etc. to be corrosive and irritating reagent. Preparation 2 provided by the invention, the method of 6-pyridine dimethanol is compared with the conventional method, there is reactions steps simplify, simple and safe operation, product is easily separated, and productivity is high relatively, is 2,6-pyridine dimethanol this provide a stronger route of operability at widely used products in field such as basic research and industrialized production researchs, there is good realistic meaning and economic worth.

Summary of the invention

The method of preparation 2, the 6-pyridine dimethanol of a kind of improvement provided by the invention, it specifically comprises the following steps that

By commercially available 2 in four-hole bottle, 6-lutidines mixes with a certain amount of water, under stirring, a certain amount of potassium permanganate is dividedly in some parts wherein, and is maintained between 60-100 degree Celsius, react 2-10 hour, it is down to room temperature, sucking filtration reactant, the material that elimination is insoluble, add concentrated hydrochloric acid and regulate pH value for acidity, precipitate out 2,6-pyridinedicarboxylic acid solids.2,6-pyridinedicarboxylic acids are mixed with THF, under 0 degree-room temperature, adds NaBH₄, question response drips the THF solution of a certain amount of iodine completely afterwards, dropwises and stops after back flow reaction a period of time, post-treated obtains product 2,6-pyridine dimethanol. This route steps is few, and reaction condition is gentle, avoids the use of hazardous chemical as far as possible, and productivity is higher, and product is easily isolated, it is easy to laboratory and commercial operations.

Detailed description of the invention

With embodiment, the present invention is further illustrated below.

Embodiment 1

(1) 2, the synthesis of 6-pyridinedicarboxylic acid:

Equipped with, in the 2L flask of agitator and reflux condensing tube, adding 800mL water, 53.5gKMnO₄, 16.7g2,6-lutidines, heating, to backflow, works as KMnO₄Color fade time, add other 53.5gKMnO₄With 200mL water, continue to be back to color and take off completely (about 2h), cooling, filter out MnO₂, the insoluble matter leached is put in the hot water of 500mL wash, filter, merging filtrate, concentrate the filtrate to 200-300mL, filter, then with dense HCl acidifying, cooling, have Precipitation, filter, dry obtain 2,6-pyridinedicarboxylic acids. Productivity: 80%, is consistent with document by m.p.220 DEG C.

(2) 2, the synthesis of 6-pyridine dimethanol:

Adding 2,6-pyridinedicarboxylic acid 8.8g (0.05mol) and 200mLTHF in 500mL there-necked flask, cryosel bath is cooled to-5 degrees Celsius, is dividedly in some parts 3.8g (0.1mol) NaBH under stirring₄. React half an hour after adding, treat not regeneration gas. 0.05mol iodine is dissolved in 80mLTHF, instills wherein, dropwise recession deicing bath, be naturally warmed up to room temperature, stop after reacting 1.5 hours. Adding the salt acid for adjusting pH of 3mol/L to neutral, sucking filtration removes solid, and solution is spin-dried for, and extracts with ethyl acetate concussion, and anhydrous magnesium sulfate revolves steaming after drying, obtains white crystal 5g, productivity 72%. M.p.111-112 DEG C, it is consistent with document.

Embodiment 2

(1) 2, the synthesis of 6-pyridinedicarboxylic acid:

In 500 four-hole bottles equipped with agitator and reflux condensing tube, adding 300mL water, 10.7g (0.1mol) 2,6-lutidines, heating is to 60 degree. By 0.5molKMnO₄Adding on a small quantity, temperature control, at 85-90 degree, continues reaction to color and takes off (about 2h) completely in batches. Cooling, filters out MnO₂, wash with in the hot water of 100mL, filter, merging filtrate, be concentrated into 100-130mL, then with dense HCl acidifying, cooling has Precipitation, filters, and dries and obtains 2,6-pyridinedicarboxylic acids. Productivity: 78%, is consistent with document by m.p.220 DEG C.

2) synthesis of 2,6-pyridine dimethanols:

500mL there-necked flask adds 2,6-pyridinedicarboxylic acid 8.8g (0.05mol) and 200mLTHF, is stirred at room temperature down and is dividedly in some parts 7.6g (0.2mol) NaBH₄. React half an hour after adding, treat not regeneration gas. Being dissolved in 80mLTHF by 0.05mol iodine, instill wherein under ice bath, dropwise recession deicing bath, back flow reaction stopped after 1 hour. Adding the salt acid for adjusting pH of 3mol/L to neutral, sucking filtration removes solid, and solution is spin-dried for, and extracts with ethyl acetate concussion, and anhydrous magnesium sulfate revolves steaming after drying, obtains white crystal 5.7g, productivity 82%. M.p.111-112 DEG C, it is consistent with document.

Claims (3)

1. the method preparing 2,6-pyridine dimethanols, the method is initial feed by 2,6-lutidines, synthesizes 2,6-pyridine dimethanols (shown in formula 1) as follows:

The synthesis of formula 12,6 pyridine dimethanol

It is characterized in that including following reactions steps:

2,6-lutidines mixes with a certain amount of water, controls at a certain temperature, is dividedly in some parts potassium permanganate, control stoichiometric number hour at a certain temperature, being down to room temperature, sucking filtration after reacting completely, acidification of filtrate obtains product 2,6-pyridinedicarboxylic acid, this compound with sodium borohydride/iodine reduction system, post-treated obtains target product 2,6-pyridine dimethanol.

2. the method that one according to claim 1 prepares 2,6-pyridine dimethanols, it is characterised in that the thing mass ratio of 2,6-described lutidines and oxidant potassium permanganate is 1: 3-1: 12, and reaction temperature is 60-100 degree Celsius.

3. the method that one according to claim 1 prepares 2,6-pyridine dimethanols, it is characterised in that 2,6-described pyridine dimethanols: sodium borohydride (thing mass ratio)=1: 2-1: 12,2,6-pyridine dimethanol: I₂(thing mass ratio)=1: 0.5-1: 4, reaction temperature be 0 degree to solvent refluxing.