What is 4-Cyanotetrahydropyran?

4-Cyanotetrahydropyran is a valuable element as a starting material or a man-made intermediate for medicine, farming chemical substances, etc, developed for making nitrile compound, carboxylic acidity compound or carboxylate compound.

Utilization of 4-Cyanotetrahydropyran

4-Cyanotetrahydropyran can be utilized to synthetize 4-aminomethyltetrahydropyran and its acidity salt 4-aminomethyltetrahydropyran hydrochloride.

4-aminomethyltetrahydropyran (CAS NO. 130290-79-8) and 4-aminomethyltetrahydropyran hydrochloride (CAS No. 389621-78-7) are valuable compounds that could be starting materials or man-made intermediates of medicines, farming chemical substances, and so on.

Synthesis of 4-aminomethyltetrahydropyran

Within an autoclave made of stainless outfitted having a stirring device, a thermometer along with a pressure gauge and getting an inner volume of 200 ml were filled 10 g (90. mmol) of four-cyanotetrahydropyran, 50 g of twenty-two Percent by weight ammonia-methanol solution and 2 g (17. mmol when it comes to a nickel atom) of developed Raney nickel, and also the mixture was responded under hydrogen atmosphere (.51 to .61MPa) at 45 to 55°C for 17 hrs under stirring. After completing the response, insoluble materials were strained, and also the filtrated material was cleaned with 30 ml of methanol. The filtrate and also the cleaned solution were combined and concentrated under reduced pressure, after which, the concentrate was distilled under reduced pressure (73 to 74°C, 2.67 kPa) to provide 7.94 g (Isolation yield 76.6%) of 4-aminomethyltetrahydropyran in the form of color liquid.

The current invention further pertains to a procedure for planning a 4-aminomethyltetrahydropyran as well as an acidity salt thereof from the 4-cyanotetrahydropyran. The nitrile compound, the carboxylic acidity compound or even the carboxylic acidity ester compound, some-replaced tetrahydropyran (4-cyanotetrahydropyran, tetrahydropyran-4-carboxylic acidity) and also the 4-aminomethyltetrahydropyran as well as an acidity salt thereof are helpful compounds as a beginning material or a synthetic intermediate of medications, farming chemicals, etc.

As a technique for preparing 4-aminomethyltetrahydropyran as well as the acidity salt from 4-cyanotetrahydropyran, there has been known of a technique, for instance, by which 4-cyanotetrahydropyran and hydrogen are responded in the existence of Raney nickel in anhydrous ethanol (for instance, see Worldwide Patent Publication No. 94/05639). However, based on this process, yield from the objective product, 4-aminomethyltetrahydropyran, is low, and a lot of a by-product (bis(4-tetrahydropyranylmethyl)amine) is created, etc., to ensure that this is not satisfying as an industrial process for preparing 4-aminomethyltetrahydropyran as well as its acidity salt.

Synthesis of 4-aminomethyltetrahydropyran hydrochloride
Within an autoclave made of stainless outfitted having a stirring device, a thermometer along with a pressure gauge and an inner volume of 25L were filled 1685.8 g (containing 15.2 mol of 4-cyanotetrahydropyran) of 65.9% by weight 4-cyanotetrahydropyran-toluene solution, 8.8 kg of 5.86% by weight ammonia-methanol solution, 337.2 g (2.86 mmol when it comes to a nickel atom) of developed Raney nickel (offered by Nikki Chemical Co., Ltd. sponge nickel N154D) and a pair of.1 L of methanol, and also the mixture was responded under hydrogen atmosphere (.51 to .61 MPa) at 50 to 60°C for 7 hrs under stirring. After completing the response, insoluble materials were strained, the filtrated material was cleaned with 2 L of methanol, and also the filtrate and the cleaned solution were combined and concentrated under reduced pressure.

To some reaction vessel made of glass outfitted having a stirring tool and a thermometer and an inner volume of 3 L were filled with the previously-stated concentrate and 833 ml of tetraethylenepentamine, the mixture was stirred at 105 to 115°C for two hrs. After completing the stirring, the stated solution was distilled under reduced pressure (70 to 80°C, 1.73 to 4.67 kPa) to acquire 1430.2 g 4-aminomethyltetrahydropyran from the distilled solution .

4-Cyanotetrahydropyran can be used to synthetize 4-acyltetrahydropyran

For a process to prepare 4-acyltetrahydropyran, there has been revealed a method that, for instance, 2,2'-dichloroethyl ether and cyanoethyl acetate are responded to synthesize ethyl 4-cyanotetrahydropyran-4-carboxylate. The resulting compound is hydrolyzed to organize 4-cyanotetrahydropyran-4-carboxylic acidity, then, the acidity is heated under high temperature to synthesize 4-cyanotetrahydropyran (Approaches for creating alkyl 3-(4-tetrahydropyranyl)-3-oxopropionate compound and 4-acyltetrahydropyran)

Ways to synthetize 4-cyanotetrahydropyran
Inside a flask made of glass outfitted having a stirring device, a thermometer, a shedding funnel along with a reflux condenser and an inner volume of 2L were filled, under nitrogen atmosphere, 4.6 g (31.9 mmol) of copper(I) oxide and 200 g of pyridine. The temperature of the mixture was elevated to 100°C under stirring. Then, 200 g (1.28 mol) 4-cyanotetrahydropyran-4-carboxylic acidity with wholesomeness of 99% dissolved in 400 g of pyridine was progressively added dropwise towards the above mixture while the temperature of the reaction mixture is maintained 100 to 110°C, under which the mixture was responded for one hour. After completing the response, the response mixture was cooled to 70 degrees, and 500 ml water, 650 ml (7.80 mol) of concmuriatic acidity and 500 ml of toluene were successively put in to the mixture under stirring. After separating the aqueous layer and also the organic layer (the toluene layer), the aqueous layer was removed three times with 500 ml of toluene, then, the stated organic layer of toluene extracts were combined and also the mixture was concentrated under reduced pressure. The acquired concentrate was distilled under reduced pressure (100 to 120°C, 2. to 2.7 kPa) to provide 133.5 g (Isolation yield: 93%) of 4-cyanotetrahydropyran with wholesomeness of 99%

After completing the response, the response mixture was cooled to 0°C, and 1760 g (22. mol) of the 50% sodium hydroxide aqueous solution was progressively added dropwise. After completing the dropwise addition, the mixture was exposed to hydrolysis at 70°C for one hour. After completing the response, the response mixture was cooled to 0°C, and a pair of.21 L (26.5 mol) of 35% muriatic acidity was progressively added dropwise thereto. After completing the dropwise addition, the mixture was stirred at 70°C for half an hour.