HU203516B - Process for producing 1-naphtyl-acetic acid - Google Patents

Abstract

Naphthyl-acetic-acid is prepd. from naphthalin via two intermediate, namely 1-chloro-methyl-naphthalene and 1-naphthyl-acetonitrile. The sequence of reaction steps occurs in a heterogeneous system without separating intermediates from the reaction mix. Chloro-methyl-naphthalene is prepd. first in closed system at 70-85 deg.C with an excess pressure of gaseous hydrochloric acid. It is then converted to 1-naphthyl-aceto-nitrile in an azeotropic solvent mixt. of iso-propanol and water, containing 5-20wt.% of water and in the presence of potassium-iodide. - The prod. is finally hydrolysed to 1-naphthyl-acetic acid in the presence of satd. aq. sodium-hydroxide at 100-140 deg.C. The prod. - is purified by fractional precipitation in a function of pH.

Description

The present invention relates to a process for the production of 1-naphthyl acetic acid, an important plant hormone, which regulates the ratio of vegetative and generative organs, and has an anti-diuretic and root-stimulating effect. Due to its properties it is very important in apple and plum cultivation, but it is also advantageous for other orchards, by spraying a properly formed solution or in the form of other plant protection products.

The most important methods of its production:

A) From naphthalene and chloroacetic acid in the presence of catalysts

B) Friedel-Crafts naphthalene from naphthylmethyl ketone via 1-naphthylacetamide

Through the hydrolysis of 1-naphthylacetonitrile from 1-chloromethylnaphthalene from QNaphthalene

A) The Friedel-Crafts reaction of naphthalene and chloroacetic acid gives 1-naphthylacetic acid in a yield of 21-35%. German patent for the preparation of iron oxides and catalysts. halides, and alkali metal halides as promoters. The best yield was reported using FeCl ₃ catalyst (GB 692 341), where 50-55% of this crude product was obtained.

The problem with these processes is that the starting compounds (a significant amount of the triple excess naphthalene and chloroacetic acid) cannot be regenerated, thus causing additional costs.

B) Naphthyl methyl ketone is prepared from my naphtha by a Friedel-Crafts reaction which is converted to 1-naphthylacetamide by the Wülgerodt reaction (heated at 150-200 ° C in aqueous medium) and then is heated to reflux for 6 hours with 1% NaOH solution [J. A. Bashakov, Ν. N. Melnyikov: Zbur.Priklad.Khim., 28 (10) (1955)]

The disadvantage of this process is that the Willgerodt reaction is of low yield.

Q The easiest to do in laboratory scale [A. Cambron; Can. J. Research, T7B (1939), 10] a naphthalene (I) - »1-chloromethyl-naphthyl (II) - * 1-naphthylacetonitrile (O) -» 1-naphthylacetamide (IV) - »1 naphthyl acetic acid (V), such that the individual intermediates [01], (D1)] are clearly isolated.

The following methods are known for carrying out each reaction step:

Conversion of naphthalene to l-chloromethylnaphthalene

The processes are described in U.S. Pat. are based on a German patent where naphthalene, formaldehyde and cc. HCl is reacted in a stoichiometric ratio, as described, in 54% yield.

Glacial acetic acid is used as a solvent. using paraformaldehyde in place of the aqueous solution of formaldehyde, Al2O ₃ + ZnCl ₂ catalyst, the yield could be increased to more than 70% (JP 156 697).

The main problem with this step is the 1.4- Refers to the formation of a 1,5bis (chloromethyl) derivative which leads to unwanted secondary reactions and the formation of naphthylene 2 diacetic acid (s) in subsequent reactions [R. H. F. Manske, A

E. Ledingham: Can. J. Research, 17B (1939), 14]

Conversion of 1-chloromethyl-naphthalene

1-tetralone-acetonitrile via:

Methanol or ethanol containing 30-401% water was performed with KCN or NaCN according to U.S. Pat. according to Czechoslovakian patent, with a yield of 62%, while catalyzing the process in 25% aqueous NaCN solution with organic bases (dimethylamine, methylamine, triethylamine, etc.) 86% (GB 1200970).

Preparation of 1-naphthyl acetic acid

1-naphthyl acetonitrile:

Hydrolysis of the nitrile can be accomplished with mineral acids (e.g., U.S. Pat. No. 2,489,348), including an alkaline solution: 92% hydrolysis of 1-naphthylacetonitrile using a 40% potassium hydroxide solution over 6 hours. C. J. Olivier, J. Wit: Rec. Trav. Chim. 56, 853 (1937).

The naphthalene yield of the above reaction sequence is reported in the literature [J. N. Kapoor, J. M. Sarkar: Proc. 7. (1970) No. 4, 172] and isolation of intermediates is complicated.

In our experiments, it was surprisingly found that intermediates (Π), 0Π) are not suitable for isolation because they form a low melting point eutectic with unreacted naphthalene and 0V) and (V) formed during hydrolysis It is easily dispersible with concentrated NaOH, thus greatly increasing the rate of heterogeneous phase hydrolysis.

The system remains in a well dispersed state until the formation of the (V) excellent Na salt separates the reactive phases. (The Na-salt of 1-naphthyl acetic acid, present in about 90%, is not soluble in the concentrated alkali at higher temperatures, but is separated from it in solid form and contains all by-products as inclusion.) The NaOH solution is clearly separated and in subsequent batches reusable.

On the one hand, the chlorocyanic exchange is optimum when carried out in azeotropic (88:12) isopropanol-water. Increasing the ratio of water to above 20% greatly favors side reactions or reducing the rate significantly slows the reaction. The azeotropic water-isopropanol dissolves the alkali metal cyanide to such an extent that the heat of the exothermic reaction can provide the system with the required temperature so that the substitution reaction becomes autothermic.

On the other hand, K ¹ addition can also optimize the reaction for the following reasons.

Generally, the reaction of alkyl halides with metal cyanides involves the formation of nitriles and isonitriles through two pathways:

_y RC = N (S _n 2)

R-X + ~ C = N - <f ^X R- ⁺ N = C (S _N 1)

R = aliphatic primary alkyl, benzyl

X = halogen

HU 203 516 Β

The desired S-? 2 reaction occurs most closely with the partner with the highest nucleophilicity, but the nucleophilic power of the strongly basic but poorly polarizable CT ions is low, in contrast to the less basic but easily polarizable I ions. so it flows in parallel

R-C1 + IR-I + C1 'reaction which does not proceed with secondary chlorine derivatives. The resulting RI compound reacts faster with CN ions or, when reconstituted, speeds up the process again, catalyzing the desired S _N 2 reaction.

The formation of the bis (chloromethyl) derivatives is facilitated by the higher temperature and the long reaction time, while keeping the conditions optimal, the material is essentially bis-free but still containing (I), which is well separated from the aqueous phase.

The process according to the invention is characterized in that the reaction sequence (I) -> (II) -> (in - »(IV) -» (V) is always carried out in a heterogeneous phase without intensive preparation of the intermediates so that the chlorine methylation of the reactants after the addition of the reactants at room temperature in a closed apparatus under a slight overpressure of 70-90'C (preferably 75-80'C) up to a maximum of 85% conversion of naphthalene, The organic phase is separated from the reaction mixture, washed with neutral and then treated with a solid alkali metal cyanide and potassium iodide in a 83-93% aqueous solution of isopropanol to give a solution of the resulting 1-naphthylacetonitrile, naphthalene and by-products, filtered at 100-120 ° C. is hydrolysed directly at room temperature (preferably at 120 ° C) with saturated sodium hydroxide solution, and at the beginning of the hydrolysis, the pure alcohol is distilled off and reused. After completion of the lysis, the alkaline solution is clearly separated and reused The solid mass obtained in the reactor is mixed with water to dissolve the Na-salt of 1-naphthylacetic acid and recover the final product by fractional pH adjustment. According to our procedure (calculated on naphthalene) in a yield of 70% min. 95% purity of 1-naphthylacetic acid can be obtained and the process can be carried out using standard apparatus. The material thus obtained also contains, on average, 3% by weight of 1-naphthylacetamide, which has similar phytophysiological properties to the main product [W. J. Lord, D. G White; Proc. Am. Soc. Horticult. Sci. 80, 350 (1962), ill. J. Hugard; Ann. Amélior.Plantes, 72 (3), 1972 (1962)].

The invention is illustrated by the following non-limiting Examples, which are not to be construed as limiting the scope of the invention.

Example 7:

In a 2000 ml round bottom flask equipped with a stirrer and a thermometer, 41.5 g paraformaldehyde, 400 ml cc. HCl and 640 g of naphthalene are then sealed and the mixture is stirred at 75 ° C for 3 hours. The organic phase was separated after cooling and washed with saturated _NaHCO3 -solution and then distilled until acid free. with the help of water. The product contains 66% of 1-chloromethylnaphthalene and 34% of naphthalene, and cannot be measured by gas chromatography of the bis derivative.

To this product (80.2 g) (containing 0.33 M 1-chloromethylnaphthalene) was added 24.4 g (0.375 M) KCN and 2.5 g KI. It is suspended in 100 ml of azeotropic isopropanol / water and heated to 82 ° C, maintained at this temperature with vigorous stirring for 3 hours, and the inorganic salts are filtered off. The solution contains 53.5 g of 1-naphthylacetonitrile and is stirred with a solution of 25 g of NaOH in 25 g of water at 110 ° C, and isopropanol is distilled off on heating. The dispersion separates into two phases after two hours. The alkaline solution was drained and the solid was distilled to 50 ml. water, then the insoluble material is filtered off. A brown aqueous solution was obtained which was adjusted to pH 6.0 with mineral acid and the impurities precipitated were then separated by precipitation of 1-naphthylacetic acid (pH 25 for the third step) by addition of excess acid to pH 3.0. 25 g 90.7%). Gross yield (calculated on naphthalene: 58%).

Example 2:

9.6 kg of naphthalene and 3.39 kg of paraformaldehyde are added to a standard glass reactor 1, followed by 30137% w / v of HCl. The apparatus is sealed and brought to 80 ° C with stirring and stirred vigorously for 6 hours. At the end of the reaction, the organic phase contained 86% by weight of 1-chloromethylnaphthalene and the proportion of the bis-chloromethyl derivative was less than 31%. The organic phase was washed with water to remove acid and add 347 gNaCNo, 47 g ΚΙ per kg of 1-chloromethylnaphthalene, and isopropanol and water to give a water-isopropanol mixture of the azetropic composition. (2.55 L of isopropanol and 0.281 water). Stirring was started by refluxing the reactor and refluxing the solvent for 120 minutes. The inorganic salts are then precipitated and the solution is pumped into a distillation autoclave (91% yield for the second step). 1.8 kg of water are added based on 1 g of 1-naphthene acetonitrile and the alkaline solution is added to the autoclave. During heating and stirring, the isopropanol is distilled off and the hydrolysis is continued until the evolution of ammonia gas has ceased, raising the temperature to 120 ° C. After stopping the stirrer, the concentrated alkali was drained and the autoclave was dissolved in water (301), placed in a stirring tank and acid was added until pH 6.0 until the impurities precipitated. The light brown solution was separated from the precipitate and precipitated with excess acid, white crystalline 1-naphthyl acetic acid (pH 3.0), filtered and washed with anhydrous water. Yield for the third step 88% (9.58 kg 1-naphthylacetic acid, m.p. 126-130 ° C). Yield 69% based on naphthalene.

Claims (1)

Patent Claim Point A process for the preparation of 1-naphthyl acetic acid from naphthalene via intermediates of 1-chloromethylnaphthalene, 1-naphthylacetonitrile and 1-naphthylacetamide, characterized in that naphthalene is reacted with 1.4 to 1.6 moles of naphthalene. amount of paraphor3 After removal of the unaltered salts, a 5 to 10 molar solution of sodium hydroxide relative to the compound of formula (ΙΠ) in the solution is added and After hydrolysis at 100-120 ° C, the solid precipitated The material is dissolved in water and the solution is precipitated by the gradual addition of mineral acid, first to the impurities and finally to the pure final product. maldehyde and 3-5 moles of concentrated hydrochloric acid at 70-90 ° C in a closed system up to a maximum of 85% conversion of the starting material and then to the organic phase of the reaction mixture, based on the compound of formula (Π) 3 molar alkali metal cyanide, 0.01-0.1 molar potassium iodide and 83-93% aqueous isopropanol solution are added and the reaction mixture is refluxed