DE1076112B - Process for the production of ª ‡, ª ‡ -Bis- (chlorophenyl) -alkanols - Google Patents

Description

GERMAN

The invention relates to a process for the preparation of a, a-bis (chlorophenyl) alkanols, which additionally to the alkanol group in the chlorophenyl group May contain 0 to 4 substituents. The chlorine atom can be in o-, ni- or p-position to the Are alkanol substituents. These compounds can be expressed by the following formula:

OH

IO

wherein R has 0 to 4 chlorine atoms or saturated or unsaturated aliphatic radicals and R 'is substituted or unsubstituted aliphatic or cycloaliphatic radical with fluorine and chlorine as permissible substituents or a carbalkoxy radical (—C (O) OR '"), where R"' is an alkyl group of up to 9 carbon atoms in the chain.

The method according to the invention is based on the assumption that it is proportionate cheap raw materials, such as. B. p-dichlorobenzene, magnesium and an ester, from and gives a, a-bis (chlorophenyl) alkanols in good yield.

According to the invention, the α, α-bis (chlorophenyl) alkanols prepared by mixing a chlorophenyl halide, preferably the chloride, with magnesium and an ester in the presence of a cyclic ether as the reaction medium.

The cyclic ether is a substituted or unsubstituted non-aromatic heterocyclic oxygen compound with 5 or 6 ring atoms, of which only one may be oxygen, while the rest Ring atoms are carbon atoms with the permissible exception that one of the ring oxygen atom is through 2 carbon atoms separate · ring carbon atom can be replaced by a substituted nitrogen atom, at least one being the ring oxygen atom adjacent carbon atom is free of any substituent except hydrogen.

The heterocyclic compounds can contain a single unsaturated bond, as is the case with dihydropyran the case is. Compounds falling under this definition are e.g. B. tetrahydrofuran, tetrahydropyran, 2-methyltetrahydrofuran, 2-ethoxytetra-

Method of manufacture
of α, α-bis (chlorophenyl) alkanols

Applicant:

Metal & Thermit Corporation,
Carteret, NJ (V.St.A.)

Representative: Dipl.-Ing. A. Bohr, Munich 5,

Dr.-Ing. H. Fincke, Beriin-Lichterfelde, Drakestr. 51,

and Dipl.-Ing. H. Bohr, Munich 5, patent attorneys

Claimed priority:
V. St. v. America November 28, 1955

Hugh Edwin Ramsden, Scotch. Plains, NJ (V. St Α.),
has been named as the inventor

hydropyran, tetrahydrofurfuryl ethyl ether, dihydropyran and n-methylmorpholine. Permissible substituents are groups which neither with the organic Magnesium chlorides still react with the other components and products of the reaction mixtures. These include substituted and unsubstituted Alkyl, aryl, alkoxy and aryloxy groups in which any substituents likewise do not react with the other components of the reaction mixture to be allowed to. In the case where a carbon atom is replaced by nitrogen, the hydrogen must be on the nitrogen atom may be substituted by a group that neither with the reactants nor reacts with the reaction products.

A Grignard reagent is preferably first prepared in a known manner by reacting Magnesium with the chlorophenyl halide and then converts this with the ester. You can go with any chloroaromatic halides such as p-dichlorobenzene, p-bromochlorobenzene, etc., and with any Esters of aliphatic acids, such as. B. ethyl acetate, butyl acetate, benzyl acetate, phenyl acetate and the like., Work.

The conversions can be given by the following equations to express:

X + Mg ..

nQ

Cl

909 757/495

R'COOR "+ 2 / Cl

In these equations, X denotes a halogen atom, namely chlorine, bromine or iodine, which are in the In the order of their preferred application. R and R 'have the meaning given above, and R ″ denotes a substituted or unsubstituted hydrocarbon radical associated with the others Components of the reaction mixture or the reaction products do not react in any other way. The compound Q is the cyclic ether.

It is already known to use Grignard compounds, such as. B. Phenylmagnesiumbromid, with esters to the corresponding to implement secondary alcohols. However, this reaction has so far been more aliphatic in the presence Ether, such as ethyl ether. Apart from the fact that working with diethyl ether in represents a source of danger on a technical scale, it was possible to use this simple ether not to react aromatic chlorides with magnesium. Rather, one was on the expensive bromides and iodides. Recently it was found that monochlorobenzene in the presence of tetrahydrofuran can be reacted with magnesium to phenylmagnesium chloride. Implementation of the in the present process used chlorine or polychloroaryl halides with magnesium in the presence cyclic ether has not yet been described, and in particular it was not known whether these halogen derivatives could be converted to Grignard compounds in such a way that only one of the halogen atoms reacts, as must be the case in the process according to the invention. Like right now was found, on the one hand, the cheap di- and polychlorobenzene derivatives in the presence of a compound Q can be implemented in the desired sense with good yields. On the other hand, if you have chloraryl bromides or iodides used in the process according to the invention are compared to the previous state technology achieves higher yields of end products with significantly shorter conversion times, and one can often even grignard and follow-up at the same time in one step perform what was previously not possible because of the large amounts of by-products. Of course the use of the cheap di- or polychlorobenzene derivatives, which also lead to good yields leads, generally preferred for economic reasons «In addition, the inventive Process general validity, and it enables the production of all alcohols of the described type, d. H. including those that have not yet been made.

The method according to the invention is preferably carried out in two stages, which correspond to the above equations (1) and (2) correspond.

Under certain circumstances, especially when X is bromine or iodine, the two reactions can also be carried out at the same time. The reactants are preferably used in equivalent amounts used, but other proportions can also be used. One of the possible ways of working is the following:

The chlorophenyl halide is dissolved in the cyclic ether and a small amount of the solution becomes together with a small iodine crystal and a few ecm of ethyl bromide added to the magnesium, which is located in a three-necked flask with anchor stirrer and reflux condenser. As soon as the temperature as a result of the The heat of reaction increases if the rest of the solution of the chlorophenyl halide is added to the ether at such a rate that the temperature quickly reaches the boiling point of the liquid. In certain In some cases, this requires an external supply of heat. The reflux temperature is during the Addition of the rest of the solution and more

Stop for 1 or 2 hours. The reaction is usually 2 to 3 hours after the start of the additions completed.

In the second stage, which corresponds to equation (2), the cooled reaction mixture is the Stage 1 mixed with the ester. The temperature used here depends on the respective Reactants and the working conditions, and they can reach the level of the reflux temperature. Usually it is ensured that the temperature does not rise too high, preferably not above 40 ° C by cooling the reaction mixture in an ice bath. When the reaction is complete, it becomes dilute Acid added. The reaction liquid separates into two layers, of which the upper, non-aqueous layer contains the product. From this Layer, solvents and by-products are driven off, the crude α, α-bis (chlorophenyl) -alkanpl ! is omitted. The crude product can be purified by recrystallizing one or more times.

example 1

147 g (1 mole) of p-dichlorobenzene were added in 216 g (3 moles) of tetrahydrofuran dissolved. 24 g (1 g atom) of magnesium turnings were poured into an anchor stirrer, Thermometer, burette and reflux condenser equipped 1-1 three-necked flask abandoned. The air was displaced from the flask by nitrogen. Then an iodine crystal was entered and the apparatus flushed again with nitrogen. On that were

2 ecm of ethyl bromide and 9 ecm of the solution described above were added and the stirrer started. The temperature rose immediately to 45 ° C. Further starting solution was slowly added to the reaction vessel through the burette. After 10 minutes, 60 ecm of the starting solution had been added, the temperature was 77 ° C., and the mixture boiled under gentle reflux. The rest of the starting solution was used in the course of the next. Added at about an hour under constant reflux, the temperature rising to 85.degree. The reaction mixture was refluxed for a further IVa hours and then cooled to 12 ° C. in an ice bath. 44 g (0.5 mol) of ethyl acetate, dissolved in 40 ecm of tetrahydrofuran, were then added over the course of 15 minutes, the temperature being kept at 30 to 40 ° C. by cooling in an ice bath. After the addition had ended, the reaction mixture was kept at 30 ° C. for V2 hours in order to complete the reaction and then cooled. A solution of 20 ecm sulfuric acid and 250 ecm water was then slowly added over the course of 15 minutes.

The reaction mixture now separated into two layers and was poured into a 3-1 flask. The excess of acid was with sodium bicarbonate

nat neutralized. The upper, organic layer was separated and nitrated. The aqueous layer was extracted with tetrahydrofuran, and after filtration, the extract was added to the filtrate of the organic layer. Tetrahydrofuran and ethyl alcohol were driven off in vacuo from the combined filtrates, 125 g of crude α, α-bis (p-chlorophenyl) -ethanol remained '. It was found by analysis that this product had a purity of over 90%. The yield was about 90%.

Example 2

In this procedure, the two reactions were carried out simultaneously. The starting solution consisted of 191.5 g (1 mol) ■ p-bromochlorobenzene, 300 ecm tetrahydropyran and 44 g (Va mol) ethyl acetate.

According to Example 1, 24 g (1 g atom) of magnesium were obtained by adding an iodine crystal and 1 ecm Ethyl bromide activated in 10 ecm of ethyl ether. After a few minutes the temperature rose. Well was started with the addition of the starting solution, the addition rate being set in such a way that that the mixture was under reflux for most of the time. The addition lasted IV2 hours, whereupon the reaction mixture was refluxed for a further hour. The next Day the reaction mixture was cooled and mixed with dilute sulfuric acid. This formed two layers. After neutralizing the excess acid, the organic layer was separated, washed, filtered and the solvent driven off.

The product consisted of 100 g of a brown liquid which was analyzed to be crude α, α-bis (p-chlorophenyl) ethanol proved.

Example 3

115.5 g of crude α, ct-bis (p-chlorophenyl) ethanol were obtained from 191.5 g (1 mol) of p-bromochlorobenzene, 44 g ( ¹ Zz mol) of ethyl acetate and 24 g (1 g atom) of magnesium manufactured. The procedure was essentially the same as in Example 2 with the exception that the reaction medium used was 300 ecm tetrahydrofuran instead of 300 ecm tetrahydropyran.

Example 4

24 g of magnesium were activated in the manner described using iodine, ethyl bromide and ether. As soon as the reaction had started, which was noticeable by a rise in temperature, were in the course of 10 minutes 50 ecm of a solution of 191.5 g of p-bromochlorobenzene in 300 ecm of chlorobenzene in let the reaction vessel run in ·. The remainder of the p-bromochlorobenzene solution was made with 58.1 g of butyl acetate mixed in 40 ecm chlorobenzene and the mixture of the reaction mass in the course of about Added for 2½ hours. The reaction vessel was Enough heat is applied to the mixture under mild conditions during the addition and an additional 28 hours To hold reflux.

A significant amount of unreacted magnesium was then screened out. The liquid part the reaction mixture was worked up according to the above procedure.

As the solvent was driven off, crystals separated out. Some agglomerations crystals were filtered off. The first deposit appeared to be in large part from p-bromochlorobenzene to exist, and the last, as determined by analysis, consisted of crude α, α-bis (chlorophenyl) ethanol, which was contaminated with some p-bromochlorobenzene.

Example 5 Bis-p-chlorophenyl fluoropropyl carbinol

2 moles of p-chlorophenyl magnesium chloride were added as quickly as possible to a solution of 1 mole of ethyl perfluorobutyrate in 200 ecm of tetrahydropyran at reflux temperature. The mixture was then refluxed for a further 2 to 3 hours, cooled, and a solution of 200 ecm of concentrated hydrochloric acid in 400 ecm of water was added. The two layers were separated and the solvent was distilled off from the organic layer to a pressure of 200 mm and a temperature of 80 ° C. There ^- behind remained bis-p-chlorphenylperfluorpropylcarbinol. -

Example 6 Bis-p-chlorophenyl perfluorononyl carbinol

According to Example 5, ethyl perfluorocaprate is obtained in a solution of 2-methyltetrahydrofuran Bis-p-chlorophenyl perfluorononyl carbinol.

Example 7 Bis-p-chlorophenyltrichloromethylcarbinol

According to Example 5, ethyl trichloroacetate is obtained in a solution of 2-ethoxytetrahydropyran Bis-p-chlorophenyltrichloromethylcarbinol.

Example 8 Octyl dichlorobenzilicate

According to Example 5, ρ, ρ'-dichlorobenzilic acid octyl ester is obtained from dioctyl oxalate in a solution of dihydropyran.

Example 9 Octyl pjp'-dichlorobenzilicate

According to Example 5, dioctyl oxalate is obtained in a solution of tetrahydrofurfuryl ethyl ether octyl pjp'-dichlorobenzilicate.

Example 10 Pip'-dichlorobenzilic acid ethyl ester

5 moles of p-chlorophenyl magnesium chloride were slowly added to a 2.5 mole solution in a flask Diethyl oxalate added in 15 mol of tetrahydrofuran. The reaction was initiated and the mixture kept at a temperature between 10 and 20 ° C during the addition. After the In addition, the mixture was left to stand for 3 hours, cooled, and sulfuric acid was added. The layers were separated and the organic layer was freed from the solvent by vacuum distillation, where ρ, ρ'-dichlorobenzilic acid ethyl ester remained behind.

Example 11 Di (p-chlorophenyl) trifluoromethyl carbinol

53.7 g of ethyl trifluoroacetate were slowly added to a flask with constant stirring A solution of 500 ecm of p-chlorophenyl magnesium chloride in tetrahydrofuran was added. Then the mixture became Heated for 1 hour on the reflux condenser, with ice

and sulfuric acid were hydrolyzed, and the two layers were separated from each other. From the organic layer, the solvent was distilled off at mm pressure and 160 ° C, whereby di- (pchlorphenyl) -trifluoromethylcarbinol was obtained.

Claims (4)

PATENT CLAIMS: 1. Process for the preparation of α, α-bis (chlorophenyl) alkanols by converting Grignard ίο compounds with esters of aliphatic carboxylic acids in the presence of ethers, characterized in that a cyclic ether is used as the ether which has 5 or 6 ring atoms, of which only one may be oxygen, while the remaining ring atoms are carbon atoms, with one of the ring oxygen atom through 2 carbon atoms separated ring carbon atom replaced by a substituted nitrogen atom can be. 2. The method according to claim 1, characterized in that it is carried out in two stages, by first combining the chlorophenyl halide with magnesium to form chlorophenyl magnesium halide and then adding the ester to the reaction mixture. 3. The method according to claim 1 and 2, characterized in that ρ - chlorpheny! Magnesium chloride is reacted with ethyl acetate. 4. The method according to claim 1 to 3, characterized in that one is used as a reactant on the one hand p-dichlorobenzene and magnesium or p-chlorophenylmagnesium chloride and on the other hand Ethyl perfluorobutyrate or ethyl perfluorocaprate or ethyl trichloroacetate or dioctyl oxalate or diethyl oxalate or ethyl trifluoroacetate. Considered publications:
German patent specifications No. 860 362, 868 296. © 909757/495 2.60