DE1136715B - Process for the preparation of 4,4'-dihydroxy-2 "-amino-triphenylmethane and its derivatives - Google Patents

Description

GERMAN

'i

PATENT OFFICE

T18284IVb / 12q

REGISTRATION DATE: 26. A P R I L 1960

NOTICE ABOUT REGISTRATION AND ISSUE OF EDITORIAL: SEPTEMBER 20, 1962

The invention relates to a process for the production of '^' - pihydroxy ^^ - amino-trqiiienyjmethan and its derivatives of the general formula I

NHR '

OR '

where R and R ', which can be the same or different, represent a hydrogen atom, a lower alkyl or acyclic radical and R "denotes hydrogen or a group which can be converted into hydrogen, in particular a lower alkyl radical, an optionally substituted benzenesulfonic acid radical or the benzyl radical! 4,4'-dihydroxy-2 "-amihd-triphenylmethane was already known. Tansescü and Simonescü (Journ. Prakt. Chem., NF, Vol. 141, p. 321 [1934I) obtained a substance with a melting point of 195 ° C. by condensation of oil / nitrobenzaldehyde with phenol and reduction of the nitro compound formed. However, this process is unsuitable for the production of this compound on an industrial scale, since one is dependent on the one hand on the use of o-nitrobenzaldehyde, which is difficult to prepare and expensive, and on the other hand the product is usually heavily resinified (Archiv der Pharmazie, Vol. 64, p. 693 [1 959]) in moderate yield and, as can be seen from the low melting point, highly contaminated.

It has now been found that you can easily and economically with good yield Compounds according to the invention obtained by a carbinol of the general formula ΪΙ Process for the production of

^^ - Dihyiiroxy ^^ - amino-triphenylmethane

and its derivatives

Applicant:

Dr. Karl Thomae

Limited liability company, Biberach / Riß

Dipl.-Chem. Dr. Ernst Seeger, Biberach / Riß, has been named as the inventor

II

NHR '

in which R and R "have the meaning given above, riiit" a phenol of the formula III '""' ^:

OR '

in which R 'has the meaning given above, condensed with elimination of water. To carry out d. Acid condensing agents such as sulfuric acid, hydrochloric acid, Perchloric acid, phosphoric acid, zinc chloride, boron trifluoride, tin tetrachloride and the like.

The smooth feasibility of the method according to the invention is quite surprising, since in the Archiv der Pharmazie, Vol. 64 (1959), on p. 692 it is stated that the corresponding condensation of 2-amiho-benzaldehyde cannot be carried out with phenol. So it was by no means to be expected that a 2-amino-diphenylcarbinol with phenol can condense easily, in the mentioned literature reference is therefore also for the preparation the dihydroxy-aminö-triphenylmethäns the cumbersome and technically unsatisfactory acid azide degradation proposed by Curtius. According to the invention one works at room temperature, but it can be recommended the implementation also under cooling, z. B. with the Verwehdung of sulfuric acid or under moderate Heating, e.g. B. when using phosphoric acid, tin tetrachloride or aluminum chloride, perform.

Pie condensation can optionally also in the presence of a suitable solvent such as Benzene, toluene, xylene or glacial acetic acid can be made.

If a compound is obtained in which R undyöder R 'and / or R "have a meaning other than' hydrogen, ¹ this can be done subsequently

209 657/265

3 4

in a known manner in 4,4'-dihydroxy-2 "-amino- Example 2

triphenylmethane are converted; O-alkylderi-

vate, for example, by heating with iodine water- A solution of 25 g of o-amino-p'-methoxy-di-

chemical acid, pyridine hydrochloride, etc., for example phenylcarbinol and 35 g of phenol in 50 ml of glacial acetic acid O-acyl or N-acyl compounds by treating 5 are added with stirring and cooling to 10 ° C with aqueous alkalis, N-benzenesulfonyl or dropwise with 25 ml of conc. Sulfuric acid. To N-tosyl compounds by heating with acids, standing for 12 hours, the reaction mixture with N-benzyl compounds diluted by treatment with kata water, strongly alkaline with sodium hydroxide solution lyrically excited hydrogen. made and filtered. By adding hydrochloric acid

A particularly preferred embodiment for 10 to the filtrate up to the acidic reaction and blunt representation of 4,4'-dihydroxy-2 "-amino-triphenyl- with sodium carbonate, the crude 4-hydroxymethane consists in that o-amino-p '-methoxy-4'-methoxy-2"-amino-triphenylmethane from which diphenylcarbinol with phenol in benzene was collected, washed with water, condensed in the air with hydrochloric acid gas at room temperature and then dried with a little cold benzene sated. From the reaction mixture is obtained after 15 is left to stand for some time. Concentration and treatment with a suitable one gives 26 g of colorless crystals, which are filtered off with suction and the crystalline solvents, such as acetone or ether, washed with benzene. They melt the hydrochloride of 4-hydroxy-4-methoxy-2 "-amino- at 85 to 87 ° C and contain crystal benzene, triphenylmethane, which can easily be converted into 4,4'-25 g of the crystals in 30 ecm of glacial acetic acid with hydroxy - 2 " - amino - triphenylmethane converted 20 30 ecm hydriodic acid (70 ° / ₀ ig) 10 minutes. The said condensation is heated under long reflux. Water is then added. Heating is carried out, so one and a little sodium bisulfite is already added, and partial cleavage of the ether group is caused by the addition. of caustic soda and neutralized with sodium

The compounds produced according to the invention carbonate. The resulting precipitate is sucked are valuable therapeutics, especially a good 25, wash it off with water and crystallize it Laxatives. from 70% ethanol. Here one obtains

The carbinols of the general formula II are 16 g of 4,4'-dihydroxy-2 "-amino-triphenylmethane vom easily accessible in the usual way by reducing the corresponding ketones with a melting point of 215 to 217 ° C. So you get

for example the o-amino-p'-methoxy-diphenylcar- 30 Example 3

binol (m.p. 53 to 54 ° C, from cyclohexane)

Handling of o-amino-p-methoxy-benzophenone To 25 g of o-amino-p'-methoxy-diphenylcarbinol and with hydrogen in the presence of Raney nickel, 35 g of phenol are added at room temperature under moderately increased pressure and slightly increased stirring 30 ml of a 35% solution at Bortri temperature, z. B. 50 atü and 50 ° C. The o-amino 35 fluoride in glacial acetic acid and leaves the reaction mixture p-hydroxy-diphenylcarbinol, which is kept under stirring for 24 hours, production of o-amino-p-hydroxy-benzophenone- Then you dilute with a little water, give so long will keep, melts at 128 ° C. Sodium hydroxide solution until the precipitate forms

. is dissolved, filtered, make the filtrate with hydrochloric acid

Example 1 ^ _{0 acidic and} neutralized by adding sodium to a solution of 56 g of o-amino-p-methoxycarbonate. The deposited precipitate is collected diphenylcarbinol and 70 g of phenol in 500 ml of benzene, washed with water and then passed in with stirring for 2 hours of chlorine drying at room temperature with a little cold hydrogen, the benzene being treated by slight cooling. This gives crystal benzene temperature of the reaction mixture to 20 ° C. 45 containing colorless crystals of 4-hydroxy-4'-meth, and then the reaction mixture oxy-2 "-amino-triphenylmethane melting point is allowed to stand for 12 hours 85 to 87 ^° C. in a yield of 28 g. Of viscous precipitate, from which the benzeneic precipitate is separated off using 20 ecm of 70% pearl solution after a short 50 of boron trifluoride-glacial acetic acid, the same formation is obtained.

which are suctioned off and then washed with a little acetone. 40 g of phosphoric acid are used as a condensate wash will. The yield is 47.5 g. The sating agent, heated to 50 ° C for 4 hours separated benzene solution is to about and lets the batch stand for 24 hours, so 100 ecm concentrated and mixed with 150 ecm ether. 15 g of 4-hydroxy-4'-methoxy-2 "-amino-man are obtained after standing for a while receives another 10 g of triphenylmethane. colorless crystals with a melting point of 225 to 232 ° C. Example 4

50 g of the hydrochloride obtained as above

it is heated with 50 ml of glacial acetic acid and 80 ml of 48% strength 5 g of o-amino-p'-methoxy-diphenylcarbinol, 6.5 g Hydrobromic acid under reflux until a clear 60 phenol and 30 ml of tin tetrachloride are heated Solution arises, what after about 10 minutes of the 12 hours to 70 to 90 ° C. After this time Case is. Then you dilute with a little water, decant the supernatant liquid and Makes alkaline with sodium hydroxide solution, acidifies with salt - treats the residue several times with 2% strength acid and neutralized with sodium carbonate. Hydrochloric acid, which is then discarded. To the Reini-Den the precipitate is crystallized and the crude product is dissolved in dilute sodium bicarbonate Ethanol — water around. 37 g of alkali are obtained in this way, filtered, and hydrochloric acid is added until the reaction is acidic 4,4 '- dihydroxy - 2 "- amino - triphenylmethane from added, neutralized with potassium carbonate, sucks the Melting point 215 to 217 ° C. the precipitate formed and rubbed off

overdrying with a little benzene. 5 g of crystals with a melting point of 85 to 87 ° C. are obtained.

Example 5

A mixture of 5 g of o-amino-p'-methoxy-diphenylcarbinol, 6.5 g of phenol, 30 ml of benzene and 5 g anhydrous aluminum chloride is heated for 12 hours at about 70 ° C and then poured Benzene layer, which is discarded. The residue is taken up in sodium hydroxide solution and filtered and then acidify the filtrate weakly by adding acetic acid. After vacuuming, Washing with water and trituration with a little benzene gives 4.4 g of crystals with a melting point 85 to 87 ° C.

Example 6

4.3 g of o-amino-p'-hydroxy-diphenylcarbinol and 9 g of phenol are mixed with 10 ml of 70% perchloric acid while stirring and cooling slightly. To After standing for 12 hours at room temperature, water is added and caustic soda is added alkaline, filtered and the 4,4'-dihydroxy-2 "-amino-triphenylmethane precipitates by adding acetic acid the end. The precipitate is filtered off with suction, washed out with water and crystallized from ethanol. Water around. 3.5 g of colorless crystals with a melting point of 215 to 217 ° C. are obtained.

Claims (5)

PATENT CLAIMS: 1. Process for the preparation of 4,4'-dihydroxy-2 "-amino-triphenylmethane and its derivatives of the general formula I 30th OR NHR " 35 40 wherein R and R ', which can be the same or different, denote a hydrogen atom, a lower alkyl or acyl radical and R "denotes hydrogen or a group which can be converted into hydrogen, in particular a lower acyl radical, an optionally substituted benzenesulfonic acid radical or the benzyl radical, characterized in that that a carbinol of the general formula II NHR where R and R "have the meaning given above, with a phenol of the formula III OR ' in which R 'has the meaning given above, with elimination of water, preferably in the presence an acidic condensing agent and optionally in the presence of a solvent condensed and that if necessary, if a compound is obtained in which the R and / or R 'and / or R "radicals have a meaning other than hydrogen, these optionally subsequently in a manner known per se in a connection with free phenolic Hydroxyl groups or transferred with a free amino group. 2. The method according to claim 1, characterized in that the reaction in one Temperature range between 0 and 100 ° C. 3. The method according to claim 1 and 2, characterized in that optionally as Solvent benzene, toluene, xylene or glacial acetic acid used. 4. The method according to claim 1 to 3, characterized in that the acidic condensing agent Sulfuric acid, hydrochloric acid, perchloric acid, phosphoric acid, zinc chloride, boron trifluoride or tin tetrachloride is used. 5. The method according to claim 1 to 4, characterized in that the reaction is carried out in benzene and carried out with the introduction of gaseous hydrogen halide. © 209 657/268 9.62