HU185909B - Process for preparing tertiary alkylnitrites - Google Patents

Abstract

FIELD OF THE INVENTION The present invention relates to a novel process for the preparation of tertiary alkyl nitrites of the formula (I): Rt, R and R3 are the same or different C1-C2 alkyl radicals from tertiary alkanol in the presence of an alkali metal nitrite in the presence of a tertiary alkanol of formula II. - R 1 (R 2 and R 3 are reacted with alkali metal nitrite in the presence of a strong organic acid of from 0 to 20 ° C, preferably from 5 to 10 ° C, at a temperature of 0 to 4 ° C, in the formula I). Compared to known processes, it is well suited for industrial applications, since it can be carried out with much lower heat production, in a more concentrated medium, at a higher temperature and shorter time than is known so far. chiral sulfate organic acids are used C-0 ~ N = 0 -1-

Description

The present invention relates to a novel process for the preparation of tertiary alkyl nitrites of the formula I, wherein R _n R ₅ and R _{3 represent the} same or different C 1 -C 2 alkyl groups, with tertiary alkanol in the presence of an acid such that alkanol - R _{1 (} R ₂ and R ₃ ) are reacted with alkali metal nitrite in the presence of a strong organic acid having a pK value of 0-4 at a temperature of 0 to 20 ° C, preferably 5 to 10 ° C, as defined in formula I.

The advantage of the process of the invention over the known processes is that they are industrially applicable since they can be carried out with significantly lower heat production, in a more concentrated medium, at higher temperatures and in a shorter time than previously known.

A further advantage of the process, especially from an industrial point of view, is the use of substantially less coirose organic acids instead of the generally highly corrosive sulfuric acid.

C = 0 ~ N 0

-1ί 85.909

The present invention relates to a process for the preparation of tertiary alkyl nitrites of formula (I) - R ', R' and R 'represent the same or different C 1-2 alkyl groups from 2 tertiary alkanols in the presence of alkali metal nitrite such that tertiary alkanol - R -, R - and R 1 - are reacted with an alkali metal nitrite in the presence of a strong organic acid having a pKs of 0-4 at a temperature of 0 to 20 ° C, preferably 5 to 10 ° G.

The compounds of formula (I) have gained importance as an oxime former for the incorporation of a hydroxymino group in synthetic organic chemistry, particularly in special cases where the oxime group is to be added to the carbon atom of the carbonyl group of nitric acid-sensitive compounds, e.g. German Federal Publication discloses a process for reacting 14-oxo-B-homoeburnan with tert-butyl nitrite and utilizing 14-oxo-15-hydroxyimino-E-homoeburnan produced in the pharmaceutical industry. for the production of compounds having a cerebral vasodilator, eburnan skeleton. Only tertiary alkyl nitrite is capable of oxidizing weakly loosened methylene groups without simultaneously causing adverse oxidation side reactions.

The preparation of tertiary alkyl nitrites is described in the literature. Coe. T. F. Dovmani: J .Am.Chem.Soc. 7θ> 1516/1948/7 generally used for the preparation of alkyl nitrite / old. Synth. Coll. II. 1087 Write it down. The process involves reacting the corresponding alcohol with aqueous sodium nitrite in the presence of aqueous sulfuric acid at a temperature of about 0 ° C, separating the organic ester formed, drying and, if necessary, distilling it. However, this process has several disadvantages in the case of the preparation of tertiary alkyl nitrites. .

During the process, very large amounts of poorly water-soluble inorganic salts, such as aqueous sulfuric acid, are formed using sodium sulfate decahydrate. The inorganic salt can be removed by filtration from the biphasic poisonous reaction mixture under conditions and at a loss, so that water is added to keep the inorganic salt formed in solution and, after completion of the reaction, the aqueous phase containing the inorganic salt contains , separated from the organic phase. However, since the inorganic salt formed is poorly soluble in water, a large amount of water is required to keep it in solution. '>'

The process is extremely exothermic. The temperature can be maintained within the prescribed + 1 ° G, especially if larger quantities of material are used, only by extending the reaction time. The exothermic reaction on an industrial scale can only be achieved by applying low temperatures and allowing only small temperature differences, which will result in very poor heat transfer conditions, and by the use of high dilution and long reaction times, resulting in the heat transfer slows down and the capacity utilization of the unit will be very poor.

At higher temperatures, tertiary alkyl nitrites are particularly sensitive to aqueous mineral acid media. Easily hydrolyzed, so when using larger quantities of material to burn eaetleges local warming and the temperature is called the "megszaladáBa ¹ 'rapidly reduce the yield. experiments

According to -2185.909, the yield was only 10% at 20 ° C. For lower straight chain alkyl nitrite such as methyl, ethyl or propyl nitrite, a solution has been described whereby a volatile product which is less sensitive to heating by sulfuric or hydrochloric acid is distilled from the reaction mixture / Houben-Weyl: Methoden dér.Org. Chem. VI / 2, Thieme Verlag 1965 Stuttgart 554 p.7. However, this method is not applicable to non-volatile acid-heating tertiary alkyl nitrites.

In J.Am.Chem.Soc. 77, 5528-55 /ref.C.A. 50, 6589 (f), only tert-butyl nitrite is produced from silver nitrate and tert-butyl chloride. Apart from producing only one compound, tert-butyl nitrite, this process is not at all an industrial process and, more importantly, has a very low yield.

No. 2,759,166. United States Patent / ref. C.A. 50, 15,575 g / process for the preparation of alkyl nitrites at 25-50 ° C with 0.75 mol of nitrogen dioxide are disclosed. At the end of the reaction, the product still has to be distilled, which is a serious disadvantage.

No. 2,955,151. U.S. Pat. C.A. 55, 9280 (a) discloses the preparation of only one material, tertiary amyl nitrite, by hydrogenation of 5-methyl-1-butyn-5-ol nitrite esters under high pressure. One disadvantage of the process is that the starting material is difficult to access.

Mem. Def. Acad., Mafch. Phys. Chem. Eng. Yokosuka Japan, 15 / 5-4 /. 411-25 / 1975 / ief. C.A. 81, 5281 a, alkyl chlorides are passed through nitrate ion exchange resins. The process produces nitro-paraffin besides alkyl nitrite which is disadvantageous and is not an industrial process.

SUMMARY OF THE INVENTION The present invention is directed to a process which, by eliminating the drawbacks described, permits the industrial preparation of compounds of formula (I).

In our experiments, it was surprisingly found that the use of strong organic acids with a pKg of less than 4, instead of sulfuric or hydrochloric acid, has the advantage that during the reaction, the alkali metal and the organic Because of the significantly improved solubility of the acid salt, significantly less water is required to keep them in solution, thus reducing the reaction volume to 40% of the sulfuric acid reaction volume and, surprisingly, significantly reducing the exo-volume of the reaction. According to our calorimetric measurements, while 1 mole of sodium nitrite, tertiary butanol and sulfuric acid reacts to produce 17.1 Kcal, the reaction heat when using a strong organic acid such as formic acid is only 5.25 Kcal.

A further advantage of using strong organic acids is that the resulting tertiary alkyl nitrite is much less sensitive to a mixture of strong organic acids and water, such as aqueous formic acid, than aqueous sulfuric acid. Preferably, the reaction temperature may be increased by 5 to 10 ° C to complete the reaction without simultaneously reducing the amount of product formed. A further advantage is that the reaction time can be reduced by increasing the reaction temperature in this way.

-3185.909

In the process of the invention, 1-2 moles of strong organic acid may be used per tertiary alkanol of the formula (YL).

The process according to the invention can be carried out at a temperature of 0-20 ° C, preferably 5-10 ° G.

The process of the invention may be carried out in a water immiscible inert organic solvent such as aromatic hydrocarbons, preferably toluene, but may be carried out without a solvent.

After completion of the reaction, the organic phase containing tertiary alkyl nitrite (1) is separated from the reaction mixture and evaporated. Deacidification can be accomplished with solid alkali metal carbonate, such as sodium or potassium carbonate.

In a preferred embodiment of the process of the invention, the compound of formula (I) obtained can be isolated at the end of the reaction using an inert, water immiscible organic solvent, preferably toluene, and the separated organic phase can then be acidified by treatment with solid anhydrous alkali metal carbonate. The stabilized toluene solution thus obtained may be used without further purification for any subsequent reaction requiring tertiary alkyl nitrite and may be stored for a longer period without decomposition. The use of toluene is also particularly advantageous because it is further possible to carry out the nitrosation in this solvent with tertiary alkyl nitrides.

The use of the process according to the invention also provides considerable progress, since the process can be carried out with significantly lower heat production, in a more concentrated system, at higher temperatures and in a shorter time than previously known.

The process of the present invention allows for significant cooling energy savings and significantly improved device utilization. Another advantage, which is particularly significant from an industrial point of view, is that the organic acids used in place of sulfuric acid are significantly less corrosive.

The process according to the invention represents an improvement over the previously known processes because they are well controlled. it is easy to implement and can be implemented in standard devices on an industrial scale.

To illustrate the invention in greater detail and without limiting its scope, the following embodiments are set forth.

Example 1

Tertiary butyl nitrite

To a solution of sodium nitrite (506 g, 7.5 mol) in water (670 ml) was added tert-butanol (541 g, 9 x 9 ml, 7 mol / 5 mol), cooled to + 5 ° C, then +5 and + 10 ° C. 460 g / 577 mL of 10 M formic acid / pKs = 5.75 / dropwise. After stirring for 50 minutes at this temperature, the upper organic layer was separated, washed with water (500 mL), stirred with solid anhydrous sodium carbonate (100 g) for 40 minutes, filtered.

The filtrate gave 62Q g of crude tertiary butyl nitrite.

Yield: 82.5%.

Melting point: 61-65 ° C.

-4185.909 • χ = 1.565 - 1.570.

Example 2

Tertiary amyl nitrite

To a solution of 506 g / 7.5 mol / l sodium nitrite in 670 mL water is added 650 g / 800 mL, 7.5 mol / l tertiary aryl alcohol, the mixture is cooled to +50 ° C and then +5 and +10 ° C. 94-5 g (10 mol) of monochloroacetic acid (pKs = 2.86) are added. The reaction mixture is kept at 50 ° C / 50 ° C for 50 minutes. After stirring at + 10 ° C, the upper organic layer was separated, washed with 500 ml of water, stirred with 10 g of solid anhydrous sodium carbonate for 50 minutes, filtered. The filtrate was 74-5 g of tertiary amyl nitrite.

Yield: 87% ·

Boiling point: 92-94 ° C. m.p. = 1.583.

5 · Example

Tertiary butyl nitrite in toluene solution

Following the procedure of Example 1, only after stirring for 50 minutes after the reaction, 74-0 ml of toluene are added to the reaction mixture, and the upper organic phase is separated off, which is then washed with 500 ml of water * 100 g of solid anhydrous sodium carbonate. stir for a minute and filter. This gives 1500 ml of a solution of tertiary butyl nitrite in toluene containing 50% tertiary butyl nitrite by gas chromatography (corresponding to 85% yield). The toluene solution thus prepared is well stored and useful for the nitrosation reaction,

Example 4

Tertiary amyl nitrite

The procedure is the same as in Example 2 except that dichloroacetic acid is used in place of monochloroacetic acid (pks = 1.50).

The physical constants of the title product are the same as in Example 2.

Claims (4)

Patent claims A process for the preparation of tertiary alkyl nitrites of formula (I) - wherein R 1, R p and R 4 are the same or different C 1-2 alkyl groups - from tertiary alkanol with alkyl metal nitrite in the presence of an acid, wherein tertiary alkanol of formula R 1, R p and R 1 are reacted with an alkali metal nitrile in the presence of a strong organic acid having a pK 5 value of 0-4 at a temperature of 0 ° C to 20 ° C, preferably 5 ° C to 10 ° C. -5185.909 2. The sexual process of claim 1, wherein the strong organic acid is a C 1 -C 5 alkane carboxylic acid optionally substituted with a halogen atom, preferably formic acid. Process according to any one of claims 1 and 2, characterized in that for 1 mol of tertiary alkanol - Rt, Rp and Rj are 1-2 molar strong organic acids as defined in claim 1. A compound according to any one of claims 1-3 · d. characterized in that the reaction is carried out in the presence of a water immiscible inert organic solvent, preferably an aromatic hydrocarbon, preferably toluene.