NO831680L - PYROGALL-DERIVATIVES. - Google Patents

Description

IN

the present invention relates to new core-substituted pyrogallol derivatives with the general formula

I where R and R2 can be the same or different and means I hydrogen or lower alkyl and R

in

j

j (|i) hydrogen or

(yikes)

whileI

IN

(ji) when R is hydrogen, X, Y and Z are hydrogen, halogen, or nitro, with the proviso that not all three are simultaneously hydrogen, and with the further proviso that

when R 1 , R 2 , X and Z are hydrogen, Y cannot be any NO 2 group; j

In and

(jii) a) when R means the group

are R^ and R^ the same or different and mean hydrogen or lower | alkvl, X, Y and Z are likewise the same or different and mean hydrogen, halogen or nitro, n is zero, j 1 or 2, R,- hydrogen, oxiranyl, mono- or dji-i hydroxyalkyl, N-(dihydroxyalkyl) - amino-hydroxy.y-alkyl, carboxy, carbaloxy, carbamyl, N-alkylki ar-i akbmaamridyboalmk, ysNilmg,Nr, u-odppkiaesnlimks yeaslmktaeir nrrbaeemlsylt elr o, gdcsyå iaanklka, yn .A lva2 æc-erime taidelan , zmoideletintte-!t2 -yl, heterocyclic ring with a total of two heteroatoms;<1>or in b) X is hydrogen or allyl, Y, Z, R^ and R^ are hydrogen and n is zero, R^ denotes the group

wherein Rg may be hydrogen or lower

alkyl or together with R^ forms a five- or six-membered<j>t saturated heterocyclic ring, containing a maximum of two he, hetero-

gene atoms, R^ means alkyl, alkenyl, alkynyl, alkoxyalkyl,

cycloalkyl, dialkylaminoalkyl, aryl, aralkyl, heteroalkyl, carbamoylalkyl or a five- or six-membered and likewise condensed heterocyclic radical with a maximum of three heterogen-

atoms;

as well as their salts with inorganic or organic acids or

! bases.

in

In addition, the invention relates to a method for production

hence.

in

According to the invention, the new compounds can be prepared as follows:

IN

in

a) Compounds with formula

^yCX.,

wherein R 1 , R 2 , X, Y and Z have the meaning given under (i).

is produced by treating a 4^-hydroxy-1, 3-benzodioc-

sol with the general formula

h; where R, and R0 have the meaning mentioned above, preferably an inert solvent or solvent mixture in a one- or two-step reaction, possibly during_use

of acid-binding additives and/or catalysts, with halogenating and/or nitrating agents.

in

; in

ib) Pyrogallol ethers of the general formula

:hyor X, R^, R,,, Rg and R^ has the meaning given under (ii) b), as well as their salts and optically active isomers are prepared by reacting a 4-hydroxy-1,3-benzodioxdl with the general formula where R 1 , R 2 and X have the above-mentioned meaning, or j ' an alkali salt thereof with an epihalohydrin, treat the thereby produced product with the general formula

— v

wherein Rg means -CHOH.CH2Qor

i i where Q is a halogen atom, with an amine of the general formula <1>i

(in which Rg and R^ have the meaning given above, and if desired, split the thereby obtained derivative with the general

formula (Ib) in the optical antipodes and/or optionally

in

transfers it in a salt with a physiologically tolerable acid

or base.

I I

1

c) i Derivatives of pyrogallole ethers of the general formula i

jhyori R^, R,,, R-^, R^, R^, X, Y, Z and n has the meaning given under (iij a)<:>, is produced by reacting a pyro-I! g_aillol derivative with the general formula Ihyor R1, R2, X, Y and Z have the above-mentioned meaning,] .or a phenolate thereof, preferably an inert solvent!in gel; ler solvent mixtures, with a compound with deI n<!>j ! general formula

in which R^, R^ and n have the above meaning, R,-1 has the same meaning as R,, or means a CH.CN group and A means in jhalogen, a sulfonyloxy acid residue or in the case that R^ and R ^<;>is hydrogen, n = zero and R,.' is a CH.CN group, eri means a double bond with the neighboring carbon atom, possibly I i! an.obtained derivative with.the general formula ..(Ic) exceeds

eh In group R<. in another group R_ and in the case that X , and1/

or Y and/or Z means hydrogen, treats the obtained

compound with the general formula (Ic) if desired with halogenating and/or nitrating agents.

IN

No<i>en of the new compounds according to the invention, special

with formula (Ia) and (Ic) are, on the one hand, valuable raw materials for the production of agricultural chemicals or are such in themselves, on the other hand - after hydrolytic cleavage of the dioxolane ring - they can be used to produce otherwise difficult-to-access core-substituted

pyirogallol derivatives.

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They can be used for the production of medicines, X-ray contrast agents and photosensitizers.

; j The new compounds of formula (Ib) are available with advantage

in] form of their salts with ion exchangers.

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These new pyrogallole ethers of formula (Ib) as well as their salts and optically active isomers can be used as /S-blocking and analgesic drugs. The use of such is preferred

medicines in the form of salts with ion exchangers.

Under the term "lower alkyl" is meant especially methyl, et1<y>l,<!>propyl, butyl, pentyl, hexyl, heptyl and octyl as well as branched residues such as isopropyl, tert.butyl and 2,2-dimethylpropyl.j i<!> ! in

As heteroatoms for the ring formation with

IN

comer l I

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[oxygen, nitrogen or sulfur in consideration.

Sloim ge sasylrtdear nnsåensodm e kfo.mepkosn. eNn-tceyr kkloahn ekensyteln suflyfasmioinlosgyrian , s<fo>a<r>l<d>t<r>s<a>y<I>r<g>e<e->

iO.I. are used or also optically active acids, which enable j i i en . racemate cleavage such as (+)-camphor-10-sulfonic acid {f>), di-tbenzoyl-D-tartaric acid and other but also acidic cation exchangers with preferably macroporous structure, which form resinates with the derivatives of the general formula (I), from which works

[

.s.., the toffet is released retardedly after application. When the residue R',, contains an acidic group (such as, for example -COOH), can also

an inorganic or organic base serve as a salt former

component such as e.g. sodium hydroxide, dimethylaminoethanol,

NjI-methyl 1-glucamine and the like.

Naturally occurring and synthetic pyrogallole ethers and their derivatives have different pharmacological actions (Airzneim.-Forsch. 13, 226 (1963)). This also applies to such bonds where two ortho-oxygen atoms are bound together to form a 1,3-benzodioxole ring, such as e.g. by that apiol or

myristicin that occurs in spice oils, the first nine of which are antipyretic and induce labor, while the latter is given

a psychotropic effect. A pyrogallol ether containing I

nitrogen in the ether residue, "Gallamine" is a ganglion blocker bg

muscle relaxant.

IN

Basic pyrogallole ethers of the general formula (Ib) are, with the exception of an intermediate (C. Casagrande et al., Boll. Chim. Pharm. 112, 445 (1973)) hitherto unknown. The new Pyrogallol ethers according to the invention turn out to be S-adrenoceptor-blocking compounds which, in contrast to the known S-blocking phenoxyisopropanolamine derivatives, also have a strong anagetic effect.

!Especially in view of the application as -blockers in j 1 1 h' pancreatic infarction, migraine and glaucoma, the simultaneous analg!e-; ;t! istic effect increased importance. ]in

i (thus, for example, the hydrochloride of 2,2-dimethyl-4-(21 - 1 i

jhydroxy-3'-tert.butylaminopropoxy)-1,3-benzodioxole on<j>j ! awake dogs a 40-fold stronger weakening of the positive' Ik' ronotropic isoprenaline effect than the known -blocker ji !atenolol in the same dosage and gives in Writhing trials according toiHuntingdon with an ED 50 of only 8 mg/kg (mouse, oral) a

in good analgesic effect. If you compare this in Writhing test with the equivalent for known analgesics, the new active ingredient proves to be superior:

The starting products with the general formula (II) are either known or can be prepared by methods known per se. A compound of the general formula (II) in which R, and R„ means methyl, is used in large quantities as an intermediate in the production of insecticides (Chem.Abstr. 71, 38941m (1969); i 78 72110u (1973); 84 , 105250u (1976);85, 192700c (1976)^

I 8 6, 51598j (1977)).

In i

' jIjmSbeeeelnkllv aelmr iogpm nnfui: bntger"oWtsmgyidrriukntpstiptnegoelner fn f"e e, ar v 1in k. ejAPn eunfkt flaljpne. raw zne1ane9g8sscur2ohb, uksttjIneizmd- tuuiukssantjd orln iiaSemovcmehed arrdåbdahln aeint lgoPgfse-l(ansanj-mze-n-

;schutz e.V.), and core halogenated side products of the compound with the general formula (Ia) are claimed in patents but not described (AT-PSen 283 812, 296 983) core-j I substituted derivatives with the general formula (Ia) occur initially from a product prepared by the nitration of myristicinaldehyde

I (J. Chem.Soc. 95, 1161 (1909)) so far not in the literature.

According to the procedure for the preparation of compounds (Iia) in 4-hydroxy-1,3-benzodioxole can either only be halogenated or nitrated or first halogenated and then nitrated, respectively first nitrated and then halogenated. One first

In the introduced core substituent can also be replaced by another in the subsequent I step. With the agents that can be used j for halogenation and nitration, it is about! i i i such as are known in and of themselves for sales of aromatics! spoon

In hydrocarbons or phenols.

<I>Nuclear substituted pyrogallol derivatives with the generalj J ; formula (Ia) can also serve for the synthesis of other pharmacologically active compounds of formula (I) or for the production of photosensitizers (compare British patent 1 109! 305). Nuclear iodinated substances with the general formula (Ia)ejr _ mMfjue.delkiigsshi. entaenn even esntfodyrr eklaeigns ve veenfd doer klfsjere nemanv ssktasipllekt ine g tdiael v raivt røadtneetgr n ehninkeonteennrtorfacoyr sktmhluiidmskalneer-.

r,ing in human experiments is not split (Pestic. Sei. 12, 6|38, 645 (1981)).

l

l Through the following examples, the invention shall be made clearer, but not limited to these. Temperature-

the data always refer to degrees Celsius.

IN

1

Example 1: 2,2-dimethyl-4-hydroxy-1,3-benzodipic acid and 22 g of NaHCO 3 in 150 ml of carbon tetrachloride stirred at 0° C. 19.24 g of bromine are slowly added. The conversion that has been found can be seen on a thin-layer chromatogram (Layer: Silica <l>6.1 0 F 254 , Eluent: Chlor. oform/methanol = 9 : 1). After filtration, the filtrate is evaporated on a rotary evaporator. The residue crystallizes with delay and can be recrystallized from petroleum ether. The 2,2-dimethyl-4-hydroxy-5,7-dibromo-1,3-benzo-diioxole contained therein melts at 59 - 61°C.

The sodium salt of this compound is obtained by mixing a methanolic solution with an equivalent of a 30% solution

of sodium methylate in methanol, evaporate the mixture and treat the solid residue with isopropyl ether. The dried sodium salt does not melt up to 320°C, but only turns brown.

l Example 2 A solution of 30 g of 2,2-dimethyl-4-hydroxy-1,3-benzodioxbl in 600 ml of chloroform cooled to -5°C is mixed with stirring dropwise with 14.8 ml of a 65% nitric acid (D: 1.40)1,

whereby the temperature rises to +2 oC. On thin layer chromate bgram

(Layer: Silica gel 60 F 254, Eluent: Chloroform/methanol = 9 : i)

one can then see two new products, one of which (5-nitro derivative) j 1'■ igger directly above the starting point and eo t (7-nitro derivative) r^i etti I below. The reaction is allowed to finish at 10 C and the mixture is then extracted three times with water, during which initial crystallization can be determined. By evaporation of the solution heated in I ! in o■g filtered with active carbon and celite it crystallizes in heavier soluble 2,2-dimethyl-4-hydroxy-7-nitro-1,3-benzo-! dioxol out. This melts after recrystallization from CHC1-.

lved 193-195°C.

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In ;

In order to isolate 5-nitroderivatives, the CHCl3 mother liquors are evaporated to dryness, and the residue is taken up in isopropanol. When the solution is cold, 2,2-dimethyl-4-hydroxy-5-nitropl,3-

benzodioxole out, which melts at 150-151°C.

The position of the nitro groups is evident from the NMR spectra of the two isomers: While the OH groups of the 5-nitro derivative in CDCl^ at 2-50 MHz show a signal at 10.42 ppm, the OH group of

The 7pnitro compound under the same conditions has a sliding resonance between 4.6 and 6.2 ppm.

in

Both isomers give heating in aqueous solution as a result of hydrolysis of the dioxolane ring the known 4-nitro-pyrogallol,

m.p.: 165 - 166°C (Literature: Fp. 162°C).

in

Example 3

A solution of 5 g of the sodium j-s■ all of 2,2-dimethyl-4-hydroxy-5,7-diborom-1,3-benzodioxypil in 10<0>ml of chloroform is mixed at 0 to 5 C dropwise with 2.4 ml conc. HNO^. Underneath, a precipitate first falls out, which to a large extent again dissolves. The orange-red mixture is shaken several times without water, the chloroform phase is dried N.a2SO^, filtered after stirring with active carbon and evaporated in vacuo. The remaining oil crystallizes on stirring with water. After recrystallization of the crude product from acetic ester, 2,2-dimethyl-4-hydroxy-5-nitro-7-bromo-1,3-benzo-

dioxol as a yellow powder with a m.p. 93 - 95°C.

The separation of the bromide during the reaction can be demonstrated by reaction with AgNO^. The N02 group's position is evident from the NMR- i spectrum (CDC1j .,, 250 MHz) because the neighboring OH group e ii

shows a signal at 10.27 ppm (compare Example 2).

in

Example 4. To a mixture of 3 g of 2,2-dimethyl-4-hydroxy-7-nitro-1,3-benzodioxole prepared according to example 2, a solution of 4 g of bromine is added dropwise while stirring at 0 o C in 20 ml of CCl^. After warming to room temperature, the mixture is allowed to stand overnight. A thin-layer chromatogram shows complete turnover. After filtration of inorganic material, the filtrate is evaporated in vacuo and the crystalline residue is recrystallized from illite chloroform. The obtained 2,2-dimethyl-4-hydroxy-5-bromo-7-j nitro-1,3-benzodioxole melts at 185 - 188°C after | it has shown a crystal transformation at 155°C. _ _|

Avoid heating an aqueous solution of this compound!

is formed as a result of hydrolysis of the dioxalane ring that sow

In Q

4;-bromo-6-nitro-pyrogallol (M.P. 133 - 135 C) which is also formed

I I by hydrolysis of the isomers obtained according to example 3.

!

in Example 5

! A solution of 10 g of 2,2-dimethyl-4-hydroxy-1,3-benzodioxole J i! 100 ml of chloroform are mixed with stirring at 12 to 14°C J idl dropwise with 10 ml of 65% HNO-. and after 15 minutes at the same temperature with a further 48 ml of 65% HNO^. On the thin-layer I chromatogram (compare example 2) you can see that they first

in 1 I ! formed mononitrated products pass into one that is even lying

j under the 7-nitro derivative. After a further 15 minutes of reaction time, the chloroform solution is shaken three times with water, dried over Na2SO4 and the filtrate evaporated in vacuo. The residue crystallizes by trituration with isopropanol. Recrystallized

■from ethanol the obtained 2,2-dimethyl-4-hydroxy-15,7-dinitro-1,3-benzodioxole melts at 203 - 205°C.

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I'

j Example 6

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: A solution of 10 g of 2,2-dimethyl-4-hydroxy--1,3-benzodiaxole

:i il ! ii 200 ml of CC1. mixed with 20 g of a powdered cation exchange

I! teir (with -COONa as active groups) and to that is added drå-! !peivis with stirring at room temperature a solution of 5.4 ml of sulfuryl chloride in 20 ml of CCl.. After 3 hours, add dropwise

In II

In another solution of 2.7 ml of S0,,C12 in 10 ml of CCl^. After a further 3 hours of stirring, the thin-layer chromatogram shows I j ! (srnl. example 1) almost complete turnover. The solution sucked off by the ion exchanger is washed with water, dried sicc'.

i ■ ' 11i over Na2SOijog is evaporated. By recrystallization of the residue from

petroleum ether using activated carbon gives 2,27-dimethyl-4-hydroxy-5-chloro-1,3-benzodioxole with freezing point

!81-83°C.

in i

in the chlorine atom's position is the result that both the aromatic

1 j pav ri ontoanterir umi fNeMnoR-laspteekt ti reCt D^(OCDD Ce1l-.l, is 250 of MHezt )k, oompgsleå kes tmteed r dean nne|eulros|e-

pi, um connection practically does not exhibit any "shift1'1-

'effect.

Example 7

One solution of 5 g of 2,2-dimethyl-4-hydroxy-1,3-benzodioxycycline in 100 ml of CCl 2 is mixed with an iodine crystal and 10 g of sodium bicarbonate and cooled to 0°C. A solution of 8.5 g of chlorine in 80 ml of CC14 is added drop by drop while stirring at 0 - 3°C. As soon as no starting product no longer appears in a thin-layer chromatogram (cf. example), excess chlorine is removed by blowing in nitrogen. The filtrate of the reaction mixture is evaporated in vacuo and the residue is stirred with petroleum ether, after which crystallization sets in. The crude product is precipitated using activated carbon from methanol/water. Thus few

nian a colorless powder of 2 , 2-dimethyl-4-hydroxy-5 , 6 , 7-tri-chloro-1,3-benzodioxole, which melts at 150-152°C.

In the NMR spectrum of this compound, there are no signals for Ii|

nuclear protons.

Example 8

A solution of 25.4 g of iodine is added dropwise while stirring at room temperature to a solution of 8.4 g of 2,2-dimethyl-4-hydroxy-1,3-benzO|dioxol in 400 ml of 0.5 N NaOH and 30 g of potassium iodide in; 150 ml of water. After standing overnight, the formation of a new product can be determined by thin-layer chromatogram (layer: silica gel 60 F 254, eluent: ethyl acetate/methanol/2n NH 2 OH = 25 : 8 : 3). The filtered solution is stirred at 2-5°C with saturated aqueous NaHSO 3 solution until pH 5, and then shaken for 1 h with chloroform. The with NaSO^ dried and after addition ; of active carbon filtered chloroform solution leaves a yellow oil after evaporation. After ..precipitation from methanol/! water or recrystallization from petroleum ether gives 2,2-dI i-',i methyl-4-hydroxy-5,7-diiodo-1,3-benzodioxole with m.p. 52-55°C.: Example 9

A mixture of 12.2 g of 2,2-dimethyl-4-hydroxyl,3-benzodioc-

I in sol, 24 g NaHCO3, 0.05 g FeCl3 and 400 ml carbon tetrachloride) | a solution of 11 g chlorine in ■ 150 ml CCl^ is added dropwise while stirring at 0 o C. As soon as the thin-layer chromatogram (see example 8) shows complete reaction, the mixture is filtered and the filtrate is evaporated. The rest is precipitated after filtering. The solution is dissolved with activated carbon from methanol/water, and then recrystallized from isopropyl ether/petroleum ether. You thus get 2.24

dimethyl-4-hydroxy-5,7-dichloro-1,3-benzodioxole with m.p.

IN

1i72-17<4>°C. in

Dsee g tore gskå jeskrnielkle lorfera rte hvdeerarnivdare tevr ed frda eereks semRpfe-vl er6i, d7 . oUg nde9 r<ljb>aer-

the conditions for the thin-layer chroma described in example 8

tlo<g>ram you get:

Example 10 A solution of 113.5 g of 2,2-dimethyl-4-hydroxy-1,3-benzodioxole in 400 ml of methanol is mixed dropwise with stirring with 123 g of a 30% solution of sodium methylate in methanol, where >when the mixture becomes dark colored. The oil obtained by evaporation on the rotas<i><j>ons■ evaporator at 50 o C (140 g) is taken up in 180 ml •<j>epichlorohydrin and the solution is stirred for 3 hours at 55°C after the addition of 15 g benzyltriethylammonium chloride. With a thin-layer chromatogram (finished plate: silica gel 60 F 254, eluent: benzene/dioxane/glacial acetic acid, 90 : 25 : 4 vol.parts) no starting product can be detected anymore. Surplus epichlor-j hydride is evaporated on the rotary evaporator at 60°C and the residue is taken up in hot ethyl acetate. After adding some active carbon to the cooled solution, it is sucked off through a Celite filter aid and the filter is evaporated. ate in vacuum. One |in few. thus 151 g (99.5%) of crude 2,2-dimethyl 1-4-(2',3'-epoxy-j propoxy)-1,3-benzodioxole as a yellow oil, which is sufficiently ready for further turnover with bases. i I<i>\I I ! 10 g of crude 2,2-dimethyl-4-(2',3<1->epoxy-propoxy)-1,3-benzpdioxole are heated in 20 ml of ethanol after the addition of 10 ml| tert.butylamine for 3 hours under reflux. A sample visa

in

then by thin-layer chromatogram (finished plate: silica gel 60 Fl

2-5 4, eluent: ethyl acetate/methanol) 2n NH.OH, 25 : 8 : 31

- y' olumdeler) complete turnover. The solution is evaporated on a rotary evaporator at 50 C, the oily residue is taken up in some vinegar and evaporated again. The oil obtained is dissolved in vinegar and the solution is washed by shaking with saturated aqueous NaCl solution. The acetic acid solution is then extracted with 2n HC1, the acidic aqueous solution is filtered and activated carbon is added, the filtrate is made alkaline with! 5n NaOH to pH 10 and extract several times with chloroform. The chloroform solution dried with Na2S04 leaves behind an oil after evaporation, which crystallizes on standing. Recrystallized from n-hexane gives 10.5 g (79% of the theoretical) colorless crystals of 2,2-dimethyl 1-4-(|2 '-hydroxy-3'-tert.butylaminopropoxy)-1,3- benzodioxol with

m.p. 75-76°C.

in

IN

The hydrochloride of this compound precipitates from an isopropyl ether solution when mixed with alcoholic HCl. Recrystallized from isopropanol, the hydrochloride melts at 124-126 o C'.

J Example li

I A solution of 10 g of the 1,3-benzodioxole starting product obtainable according to example 10 in 20 ml of ethanol is mixed with 8^,24

in g of benzhydrylamine and boiled for 5 hours under reflux. j The residue that remains after evaporation of the mixture is dissolved in some acetone and the solution is mixed with alcoholic HCl and isopropyl ether. The oily bottom that precipitates becomes crystalline on standing. After recrystallization—

<>><n>en from isopropanol (using activated carbon and | I filtration) gives 18 g (90.5%) hydrochloride of 2,2-dimethyl-I ! li i 4-(2'-Hydroxy-3'-diphenyl-1-methylamino-propoxy)-1,3-benzodi-

'oiksol, which melts at 136-139°C.

in

in

; Example 12

I A solution of 10 g of the :1,3-r obtainable according to example 10

benzodioxole starting product and 4.15 g of 2-methyl-3-butyn-2-,yl- | amine (90%) in 20 ml of ethanol is allowed to stand for 3 days at room temperature. The evaporation residue is dissolved in diethyl ether and the solvent is removed. hVveod rvaevd the queue liong lje utskskryisltlear llli:siesge-

I! The hydrochloride of 2,2-dimethyl-4-[2'-hydroxy-3'-(2"-methyl)

3''-butyn-2"-ylamino)-propoxy]-1, 3-benzodioxole. Mp. 153-

155 C. Yield: 12.5 g (81.3%).

i Yield: 12.5 g

in [ Eki sample 13

A solution of 22.1 g of 2-methoxy-2-methyl-4-hydroxy-1,3-benzo-1 dioxol in 60 ml of methanol is mixed dropwise with stirring

21 in .8 g of a 30% solution of sodium methylate in methanol, whereby the mixture is colored dark. The by evaporation on photic j-

fo! rvapor at 50°C oil obtained is taken up in 50 ml of epichlorhydrin and the mixture is stirred after adding 3.5 g of benzyl

Ytriethylammonium chloride for 3 hours at 60°C. One evaporates over-

tsåki yr ternedse ten epoikpp loi rhyvdarrmit n peå tylroacteastajton. sEfottredar mpteilresn etvneid ng 60 of C noo!eg Ij active carbon to the cooled solution is sucked off by C-

Ilite filter aid and evaporates the filtrate in a vacuum. Mon

thus obtaining 28.5 g (98.6%) of crude 2-methoxy-2-methyl-4-(2S3'-iepoxypropoxy)-1,3-benzodioxole as a brown oil, which is sufficiently pure for further turnover with bases.

A solution of 10 g of 2-methoxy-2-methyl-4-(2',3'-epoxy-prop:oc-j!sy)-1,3-benzodioxole in 20 ml of ethanol is heated after the addition of 10 ml isopropylamine under reflux until jen sample on thin-layer chromatogram (finished plate: silica gel 60 j I1 G{• 2 54, eluent: chloroform/methanol, 9 : 1 parts by volume eli ler! ! 1edi diester/methanol/2n NH 4 OH, 25 : 8 : 3 volume fractions) shows in | [complete turnover. The one after the evaporation of the solution

i !ptoå n roog tabs ljoannds efos rmdeamd peen r tløislbnaikneg balv ive8n,d5 e g røcyde kloohlejke sylølsseus lfai m^ince- -|j

in I acid in acetone. On standing of the mixture at 4 C, the cyclamate of 2-methoxy-2-methyl-4-(2'-hydroxy-3'-isopropylamino-propoxy)-1,3-benzodioxole, which after cross-

y! st 1 allisate ion from isopropanol melts at 139-142°C. Dividend:}i I i 12! .6 g (63% of the theoretical). !j

\ Example 14 j i: A solution of 10 g of the 2,2- obtainable according to example 10; dimethyl-4-(2',3'-epoxy-propoxy)-1,3-benzodioxole in 20 ml

-ethanol is heated after adding 10 ml of isopropylamine| in__

3 for hours under reflux and then evaporated in va-*i kjuum. The yellow oil thus obtained is taken up in isopropyl ether. On mixing the solution with alcoholic HCl, the hydrochloride of 2,2-dimethyl-4-(2'-hydroxy-3'-isopropylamino-propyl)-1,3-benzodioxole precipitates out (12, 0 g, 83.9%), which after recrystallization from isopropanol melts at 157-159°C. The jtil-j

corresponding free base melts at 91-93°C.

IN; a solution of 10 g of the hydrochloride obtained in 140 ml of distilled water is introduced with stirring in portions of 20 g| of a finely powdered polystyrene cation developer, which contains

-SO^Na as active groups. Stir for a further 24 hours, suck off, wash the precipitate on the filter several times with distilled water and, after drying in a vacuum at 70°C, obtain 25.5 g

r^esinate.

After oral administration of this resinate e.g. in gastric juice

resistant capsules release the active substance delayed.

Example 15

A mixture of 20 g of p-chlorphentermine hydrochloride, 150 ml of saturated NaHCO-j solution and 200 ml of chloroform is stirred intensively for 1:14 me, then the phases are separated, the CHClj^-phase is dried sicc. above ! l Na-jSO^ and evaporated in vacuo, the p-chlorphentermine base became jer- j

h! old as yellow oil. y!

8.3 g of this oil was heated with 10 g of the 2,2-dimethyl-4-(2<1>,3'-epoxy-propoxy)-i j obtainable according to: example 10

1,3-benzodioxole in 20 ml of ethanol for 8 hours under reflux. j The yellowish oil remaining after the evaporation of the solution on a rotary evaporator was taken up in acetone and the solution mixed with alcoholic HC1. That by this precipitated' i

in hydrochloride of 2,2-dimethyl-4-[3'-(a,a-dimethyl-p-chlorophenethyl-i

amino)-2'-hydroxy-propoxy]-1,3-benzodioxole (15.7 g, 7.8 , 9 !

%) was recrystallized from ethanol. Temp. 212-215°C.

Following procedures analogous to those described in Examples 10-15, further derivatives of the general formula (Ib) were obtained. These are compiled in the following_Jta-_ beiler I and II.

Example 16 a.) A mixture of 120 g of 2,2-dimethyl 1-4-hydroxy-1,3-benzpdi--ioxole, 319.6 g of allyl bromide, 533 g of K^SO^ and 2600 ml of acetone is boiled for 5 hours under reflux and then filtered. The filtrate's evaporation residue is shaken with isopropyl ether and the diluted jNaOH, the ether solution is washed with water, dried sicc. with Na 2 SO 4 ; and filtered after treatment with activated carbon. Evaporation of the filtrate yields a greenish-yellow oil which boils at 122-124°C/10 torr and consists of 2,*2-dimethyl 1-4-allyloxy-j,1,3-benzodioxole. Yield: 132 g (88.6%).

|b.) A solution of 132 g of 2,2-dimethyl-4-allyloxy-1,3-benzodioxole in 300 g of 1,2-dichloro-benzene is heated for 4 hours in,un-! where stirring to 180°C, extract the cooled solution several I times with ln NaOH, acidify the combined aqueous-alkaline' in extracts while cooling with dilute HC1 and immediately shake out I with chloroform. The dried chloroform solution leaves after evaporation 105.3 g (79.8%) of a yellow oil, which

consists of 2, 2-dimethyl-4-hydroxy-5-allyl-1, 3-benzodioxol. I Rf value on silica gel 60 F 254 (eluent: chloroform/methanol

=9:1) : 0.66. Rf value that for allyl rearrangement introduced

allyl ethers under the same DC conditions: 0.73.

c1,.) 3-bTeinl zoene dioleksonl ing in a1v 50 1m05l ,m3 eg tan2o,l 2-dtiimlesteyttle-s 4-hunydderor ksryø-ri5n-ga]lylI-9,1.7 g of a 30%' methanol solution of CH^ONa. After 2 hours

if the solution is evaporated, the dark residue is taken up in 100 ml of epichlorohydrin while adding 11.2 g of benzyltriethylammonium-r

kilorid, stirs for 5 hours and leaves the solution overnight.

The evaporation residue is distributed between water and ethyl acetate. The acetic ester solution is shaken out several more times with water, dried and evaporated. 127 g (94.8%) of 2,2-di-jmethyl-4-(2',31-epoxy-propoxy)-5-allyl-1,3-benzodioxole are thus obtained as a yellow oil, which under the step b.) described DC conditionsi

exhibits an Rf value of 0.74.

IN

d■ .) 20 g of 2,2-dimethyl-4-(2',3'-epoxy-propoxy)-5-allyl-1,3<->benzodioxole and 25 ml of tert. butylamine is stirred in 25 ml of ethanol in ' i 2! days at room temperature. The residue obtained after evaporation of the solvent is taken up in isopropyl ether and the solution is mixed with alcoholic HCl, after which the hydrochloride of 2,2-dimethyl-1-4-(2'-hydroxy-3'- tert-butylamino-propoxy)-5-allyl-1,3-j

jbénzodioxol precipitates. After recrystallization from isopropyl ether/ethyl acetate (3:1), the product melts at 129 - 1:32°C.

j Yield: 18.9 g (66.6 %).

In !Corresponding to the entries listed in example 16, one gets| ' they ■j

i1 Table III listed compounds.

Example 17

To a solution of 10 g of 2,2-dimethyl-4->hydroxy-1,3-benzodioxol in 50 ml of methanol, 10.8 g of a 30% solution of CH^ONa is added dropwise while stirring in methanol. The dark colored mixture is then added dropwise to a solution of 12.55 g of bromine ethyl acetate in 15 ml of methanol. Stir at room temperature until the thin-layer chromatogram (layer: silica gel 60 F

254, eluent: chloroform/methanol =9:1) no longer shows any starting product, evaporates on the rotary evaporator

and takes up the remainder in chloroform. The filtered chloroform solution is shaken out twice with 1N NaOH and three times with water, dried over Na^SO^ and evaporated. The first that oil obtained

2i2-Dimethyl-4-(carbethoxy-methoxy)-1,3-benzodioxole crystal-

lyses on standing and then melts at 46-48°C.

in f

In Example 18

i i ■ I A solution of 11.3 g of the ester obtained according to example 17 in 100 ml of ethanol is added dropwise after the addition of 20 ml in water while stirring 8 g of a 30% solution of CH30Na in meta-'no! l■ . After stirring for 1 hour at room temperature, the thin-layer chromatogram (layer: silica gel 60 F 254, eluent: acetic ester/methanol/2n NH^OH = 25 : 8 : 3) shows complete reaction. J The solution is evaporated in a vacuum, the remainder is dissolved in water. It vid ain-I

jacidification of the aqueous solution with HC1 precipitating precipitate ]I: is suctioned off, washed with water and dried in vacuum. After recrystallization from CHC13/CC14, 2,2-dimethyl-4-(carboxy-

the imethoxy)-1,3-benzodioxole which melts at 138-141°C.

in

in

The sodium salt of this compound can be obtained e.g. by| reacting a methanolic solution of the free acid with one equivalent of sodium methylate, evaporating the mixture and treating the residue with isopropyl ether. It melts at 256-! 2 in! 60°C during decomposition.

Example 19 A mixture of 4 g of the <ar~j carboxylic acid obtainable according to example 18, 8 g of NaHCO 3 and 100 ml of CC 4 is mixed after adding-! ning of an iodine crystal with stirring at -5°C with a solution j of 4.5 g chlorine in 100 ml CC14. The reaction is allowed to finish at 0°C and then filtered. The precipitate obtained is extracted mi ed \; CHC13, the extract is combined with the CCl4 filtrate and evaporated in! vacuum. The evaporation residue is treated with CHC13/H20, ! j separates the phases and evaporates the CHCl3 phase. The crystalline residue is recrystallized from CC14, whereby 2,2-dimethyl-4-(carboxymethoxy)-5,7-dichloro-1,3-benzodioxole is obtained with melt- I

point 143-145°C.

Example 20

The product from Example 19 is also available at the following

manner:

l

In 2,2-dimethyl-4-hydroxy-5,7-dichloro-1,3-benzodioxole react' - ' In

according to the method described in example 17 to 2,2-di-1-methyl-4-(carboxy-methoxy)-5,7-dichloro-1,3-benzodioxole; as

melts at 82 - 84°C.

in

in

jD! this ester gives after saponification according to example 18 the til<->! corresponding free acid, which shows what was stated in example 19

I in the melting point.

; Example 21

A mixture of 6.5 g of the ester obtainable according to example 17, 8 g of morpholine, 6 ml of dimethylformamide and 20 ml of benzene

is heated under reflux until the thin-layer chromatogram (cf. example 18) no longer shows any starting product. The residue oim-j obtained after evaporation of the solution is crystallized from isopropyl ether, consists of 2,2-dimethylr4-1-(morpholino-carbomethoxy)-1, 3-benzodioxole and melts at i912-9<3>°C.

in i

in Example 22

A solution of 6.3 g of 2,2-dimethyl 1-4-hydroxy-1,3-benzodioxole in 30 ml of acrylonitrile is mixed with 2 drops of a 40% methanol

mleiss k delørestntieng r auv ndbeer nrzyørltirng imettiyl latmimlbonakiemlø-hpy, drionknstyid l obg aroe ppsypoar r-ii<1><*>

i of starting product can be detected on the thin-layer chromatogram \i (cf. example 17). The evaporation residue is taken up in vinegar/

; water, the mixture is filtered, the acetate phase is shaken out with i ■ 1 n NaOH and further with water and that with Na2S0^dry' tea '■'

! acetic ester solution is evaporated.

in

in

IN

in ben oily residue, 2,2-dimethyl-4-(2<1->cyanethoxy)-1,3-benzodioxole is used for the following reaction with hydroxyl-

amine.

In i

A solution is added to this during external cooling with water

in i

of 3.5 g of hydroxylamine hydrochloride in 15 ml of methanol under

stirring dropwise 9 g of a 30%<1>ig methanolic NaOCH^ solutionJ

and sucks off from precipitated NaCl. The solution obtained in this way is added dropwise to a solution kept under reflux and stirred adv

6.2 g of 2,2-dimethyl-4-(2'-cyanoethoxy)-1,3-benzodioxole in 25 ml of ethanol. After a further 15 minutes of reflux, according to the thin-layer chromatogram (cf. example 1|7) everything has been converted. The filtered solution is evaporated. The oily one

residue crystallizes from isopropanol consists of 2,2-dimethyl 1-4;<->

j(2 '-carbamidoxime-ethoxy)-1, 3-benzodioxole and melts at

100 - 103°C.

" Example 23

The solution of 10 g of the sodium salt of 2,2-dimethyl-4-hydroxyf-5,7i-

Dibromo-1,3-benzodioxole and 0.7 g of benzyltriethylammonium chloride in 40 ml of chloroacetonitrile are stirred under reflux until the thin-layer chromatogram (cf. example ] shows

in full turnover. One evaporates in a vacuum, takes up the residue in vinegar or shakes it out with ln NaOH and then with water. The residue remaining after evaporation of the acetic ester solution crystallizes on standing in a refrigerator, bm crystallized from petroleum ether, the obtained 2,2-dimethyl1-4-

; : ci yanmethoxy-5,7-dibromo-1,3-benzodioxole at 64-66 oC. !<!>

[ Example 24

! A solution of 2.2 g of hydroxylamine hydrochloride in 15 ml of meta-j I hol is mixed with stirring at 12°C dropwise with 5.7 g of a j I 30%<1>ig methanolic solution of NaOCH^. The filtrate of it is- I

In the above mixture, while stirring, a reflux boiling solution of 7.4 g of 2,2-dimethyl-4-cyanometh- ioxy-5,7-dibromo-1,3-benzodioxole is added dropwise in 25 ml ethanol. About. 15j mi-' hi otter is later evaporated on a rotary evaporator. The residue is treated with acetone and the resulting precipitate is recrystallized from isopropanol. The obtained 2,2-dimethyl-4-(urea-oxime-methoxy)-5,7-dibromo-1,3-benzodioxole melts at 153-

155°C.

in

in

Example 25

IN

I A solution of 10 g of 2 , 2-dimethyl-4-hydroxy-5,7-diiodo-1,3pben-

zodioxol in 50 ml of methanol is mixed with 4.3 g of a 30%

methanolic solution of NaOCH-, and then evaporated in vacuo.

[ The residue is taken up in 50 ml of ethanol and the solution is heated under i

In reflux after the addition of 2.65 g of 3-chloro-1,2-propanediol, in the thin-layer chromatogram (cf. Example 17) only traces of the starting product appear. The solution filtered over Celite is evaporated in vacuo, the residue is taken up in CHCl/Ho0, CHCl-.-phase I 3 ^ J I jdried with Na 2 SO 4 and evaporated. The residue crystallizes from isopropanol after filtering the hot solution with aq.

iptriovpt okksay rb)o-n5,. 7-Ddeit joodpp-slt,å3-tbtee nz2o,d2i-odkimseotl yslm-e4-lt(e2r 1,v3e'd -ep1o1k2-sy1-14°C.

IN

in

Example 26 The sodium salt of 5 g of 2,2-dimethyl-4-hydroxy-5,7-diiodo-1,3-benzodioxole is prepared in methanol by adding 2.15 g of a 30% methanolic NaOCH^ solution and evaporation of !

the mixture. The residue is taken up after the addition of 0.5 g of triethylbenzylammonium chloride in 30 ml of epichlorohydrin and allowed to stand overnight. The evaporation residue is then treated with hot vinegar and the filtered solution is evaporated. You get sole-

i jdoeds -15,,6 3-bg en2 z, o2d-idoimkesoty l 1-so4m -(g2 u1 l , 3 o'-ldjeih. ydPå roktysnyn-psrjoikpotkss-ykr)-om5 a, t7ipj--di-grammet ( cf. example 18) it rises somewhat higher than uti- j

the gang product and turns out to be pure. In the event of respite,

stagnates the product and then melts at 64-67°C.

in

Example 2 7

To a solution of 1.7 g of 2,2-dimethyl-4-(carboxy-methoxy)-5,7-diiodo-1,3-benzodioxole in 25 ml of freshly distilled dimethyl-formamide, 1 ml of thionyl chloride is added dropwise while stirring J i On the next day, a 33% solution of methylamine is added; i ! absolute ethanol until the mixture reacts alkaline and! I let this stand further overnight. The solution is concentrated

in vacuum and then combine with saturated sodium chloride solution. The precipitate obtained is recrystallized from ethanol/water. It: ■ dry 2,2-dimethyl-4-(N-methyl-carbamyl-methoxy)-5,7-diioide-

1,3-benzodioxole melts at 146-148°C.

Example 28 Following the procedure according to example 23, 2,2-dimethyl-4-cyanomethoxy-1,3-benzodioxole is obtained from the sodium salt of 2,2-dimethyl-4-hydroxy-1,3-benzodioxole as orange colored oil.

: I

10 g of this oil is heated after adding 0.1 g of sulfur in 20 ml of ethylenediamine for 1 hour to 100°C. Evaporation jre-acetic acid, the filtered solution is shaken out several times with water and

then extracted with 2n HCl. The acidic aqueous phase is made alkaline with the addition of NaOH and shaken out with chloroform.

After evaporating it with Na2S04 sicc. dried chloroform solution gives a yellowish powder. Recrystallized from iso-propanol, the resulting 2,2-dimethyl-4-(A 2 -imidaIzo-.ilin-2-yl-methoxy)-1, 3-benzodioxole forms colorless small leaves which

melts at 158-161°C.

:Example l 29

;5 g sodium salt of 2,2 dimethyl-4-hydroxy-5 , 7-dibromo-1 ,|3- | in benzodioxol is stirred after the addition of 0.4 g of benzoyltri'ethyl-■ammonium chloride in 10 ml of butyl bromide for 2 hours at 100 C.Tnn-J |the evaporation residue of the reaction mixture is then taken up ! in acetic acid, the solution is washed with ln NaOH and with water and, in I then evaporated. The remaining yellowish oil consists of 2,2-dimethyl-4-butoxy-5,7-dibromo-1,3-benzodioxole, which | 2 3'

has a refractive index = 1.5468 and on silica gel 60 F. 254

1 with eluent: chloroform/methanol (9:1) shows an R1 f-!i

value of 0.82.

in

Example 30

A solution of 10 g of what can be obtained according to example 26! 2,2-dimethyl-4-(2',3'-epoxy-propoxy)-5,7-diiodo-1,3-benzodioxole in 50 ml of ethanol is boiled with 2.2 g of 2-amino-2-methyl-1 , 3-pro-j pandiol under reflux until the turnover according to j

.thin-layer chromatogram (cf. example ]8) is finished.j Then the evaporation residue is taken up in vinegar, the solution is first shaken out with water and then with 2n HC1, whereby eh out-

in the falling oil is again brought into solution by the addition of water. The acidic aqueous solution is treated with active carbon, filter-

res, made alkaline with NaOH and shaken out with chloroform. ! The one with Na2S04 sicc. dried chloroform solution leaves after evaporation an oil, which after dissolution in acetic ester and addition of alcoholic HCI gives a crystalline

in iproduct. This melts after the recrystallization from iso1-1<j>propanol or acetonitrile at 205-208°C and consists of the hydrochloride of 2,2-dimethyl-4-[31-(a,a-dihydroxymethyl-ethyl-i |amino)-2'-hydroxy-propoxy]-5,7-diiodo-1,3-benzodioxole.

. Example 31

A solution of 10 g of 2,2-dimethyl-4-hydroxy-1,3-benzodioxole in 20 ml of methanol is added dropwise with stirring to 10.83 g of a 30% methanolic NaOCH^ solution and then evaporated.: The residue is taken up in 15 ml of chloroacetaldehyde-dimethyl acetal and mixed, then heated after the addition of 1 g of tetrabutylammonium bromide for several days under reflux until the conversion According to thin-layer chromatogram (layer: silica gel 60 F 254!, i j eluant: cyclohexane/acetone =3:1) is almost complete!

The solution of the evaporation residue in acetic acid is washed with dilute NaOH, dried sicc. over Na-jSO^, filtered after addition of active carbon and evaporated. The thus obtained

oil is distilled (boiling point 155-157°C/12 torr) and consists| of 2, 2-dimethyl-4(21,21-dimethoxy-ethoxy)-1,3-benzodioxole.| On

1 thin's liquid chromatogram (s.o.) shows an Rf value of 0.44,

the output product a value of 0.30. The refractive index of

24

the dimethyl acetal obtained: nD = 1.4971.

1 Example 32. I

If 7.6 g of 2-amino-2-methyl-1,3-propanediol (serinol) is introduced instead of 2-amino-2-methyl-1,3-propanedione according to example 30, one or a similar method yields the hydrochloride aVj 2,2-dimethyl-4-[31-(1,3"-dihydroxyisopropylamino)-2'-hydroxy-propoxy]-5,7-diiodo-1,3-benzodioxole, which is recrystallized

from acetonitrile/methanol and melts at 190 195°C.

1 Example 33

A suspension of 10 g of the 2,2-dimethyl-4-(carboxy-methoxy)-1,3-benzodioxole obtainable according to example 18 in 150'

ml of CH2C12 is mixed with stirring with 3.3 g of acetone oxime and then a solution of 9.2 g of N,N-dicyclohexy1-car-i in bodiimide in 80 ml of CH_C10 is added dropwise. After 30 minutes, the reaction is complete according to the thin-layer chromatogram (layer: silica gel—60—1I I jF 254, eluant: cyclohexane/acetone = 1:1)

The evaporation residue is taken up in isopropyl ether, the precipitate that has fallen out overnight is sucked off and the filtrate is evaporated. The crystalline residue is recrystallized from isopropyl ether. pet

.thus obtained acetone-O-(2,2-dimethyl-1,3-benzodioxole-4-oxyj-

<i>acetyl)-oxime melts at 73 - 75°C.

The following new pyrogallol ethers with the general formula

in

was obtained as described in Examples 17 to 33:

IN

Claims (9)

L. New pyrogallol derivatives of the general formula where R1 and R2 may be the same or different and mean hydrogen or lower alkyl, and R is (i) hydrogen or i (jii) i i i i under which (;i) when R means hydrogen, X, Y and Z means hydrogen, halogen or nitro with the proviso that not all three at the same time j are hydrogen, and with the further proviso that when Rj_, R2, X and Z mean hydrogen, Y cannot be any N02 groups; in and (■ii) a) now R means the group are R^ and R^ equal or different and means hydrogen or lower alkyl, X, Y and Z are likewise the same or different and mean hydrogen, halogen or nitro, n stands for zero, 1 or 2, R,- hydrogen, oxiranyl, mono- or dihydroxyalkyl , N-(dihydroxyalkyl)-amino-hydroxy4 alkyl, carboxy, carbaloxy, carbam2 yl, N-alkylcarbamyl, N , N-dia 1 alkyl carbamyl, cyan, A -imidazolin-;12-yl, amidoxy ester or dialkyl acetal, wherein the amine residue of the carbamyl group may also be a metiate in heterocyclic ring with a total of two heteroatoms; or b) X is hydrogen or -allyl, Y, Z, R^ and R4 are-hydrogen-Jog—' n is zero, means the group in which Rg kajn jbe hydrogen or lower alkyl or] is together with R-, forms a five- or six-membered heterocyclic ring, which maximally i ! 7 I inynI nle, hoalldkoer ksytao lkhyetle, rocgyeknlaoatolmkyerl, , dR^ i'ablekytylar mainlokayllk, yall, kaenryyll, , <a> ar <l> a <ki> lk <-> yl, ! Heterogeneous alkyl, carbamoylalkyl or a five- or six-membered and similarly condensed heterocyclic radical with a maximum of three heteroatoms, as well as their salts with inorganic or organic acids or bases. in i ! IN p.j Compound according to claim 1, characterized y ; |ie d that it is 2,2-dimethyl-4-(2'-hydroxy-3'-tert.butyl-laminopropoxy)-1,3-benzodioxole or its salt with a pharmaceutically acceptable acid, preferably the hydrochloride. in ;3 .j iUse of new nucleus-substituted pyrogallol derivatives with the general formula where R., R„, X, Y and Z have that in claim 1 under (i) indicated 1 2 .. in meaning as well as their salts with bases as agrochemicalsj or as raw materials in the manufacture of a^ v such. 4.' Use of new core-substituted pyrogallol derivatives with the general formula (I a) specified in claim 3, wherein ! R^ , R,,, X, Y and Z have the meaning indicated there, as well as there-es j salts with bases as raw materials in the manufacture of medicines, in X-ray contrast agents or photosensitizers. in ! 5' ., ! Use of new core-substituted pyrogallol derivatives with the general formula where R^ , R^' x' Rg°9 R7 when the meaning stated in claim 1 under (ii) b), possibly in the form of optically active isomers such as p-blockers and analgesics. I I 6.1 Use of new core-substituted pyrogallol derivatives with the formula (Ib) stated in claim 5 in the form of salts with ion exchangers as β-blockers and analgesics. in i7.| Process for the production of new pyrogallol derivatives with the general formula (Ia), characterized by treating a 4-hydroxy-1, 3-benzodioxole iride the general formula In hyor R, and R has the meaning stated in claim 1, preferably ' ! in meaning, j i i , an inert solvent or solvent mixture, in a one-j or two-stage reaction, optionally using acid,e-j binding additives and/or catalysts, with halogen-j Ings and/or nitrating agents. 8.]Procedure for the production of new pyrogallole ethers with the general formula In <1> ihyor X, R^ , R , R- and R7 have the meaning given in claim 1 under (ii) b) 'as well as their salts and optically active isomers, in iki characterized by converting a 4- hydroxy-1,3-benzodioxole of the general formula in I in which R-^ , R^ and X have the meaning given above, or an alkali salt thereof with an epihalohydrin, it treats thereby obtained product with the general formula i represents a halogen atom, with an amine of the general formula i i l in which R,, and R-, have the meaning indicated above, and if desired, the derivative thus obtained cleaves with the general formula i(Ib) with respect to the optical antipodes and/or optionally | with a physiologically tolerable acid or base transfers in a salt. in 9. Method according to claim 8, characterized in that an ion exchanger is used as a physiologically tolerable acid for salt formation. <:> i |l0. Procedure for the preparation of new derivatives of pyrogallo ethers with the general formula where R1# R2 , R3 , R4 , R5 , X, Y, Z and n have the meaning specified in claim 1 linder (ii) a) characterized by reacting a pyrogallol derivative with the gene- I real formula i i i i in in where R , R 2 , X, Y and Z have the above meaning, or a phenolate thereof, preferably in an inert solution In agent or solvent mixtures, with a compound of the general formula in bhveotyr dRni^n, g R^ as and Rn ,- healr leor vbenentyevr ntee n CbHet.CydNn-ginrgup, pRe ^o' g dA en hasalmomgeein, heyn drsouglefnon, yn lo= ksynurelsl t and elR ler ' ei n dCeHt .CtNi -lgfreulplpeet , abt eRty^ r and a Rd4 ober beltpj bond with the neighboring carbon atom, optionally in a I in iI derivative obtained with the general formula (Ic). transfer a | group R5 in another group R^ , and in the case that xjog/ or Y and/or Z is hydrogen, treat the obtained compound of the general formula (Ic) if desired with h<i> halogenating and/or nitrating agents. IN IP vro <q> allol derivative is of the general formula (I) where R, and R2 are independently hydrogen or lower alkyl, and R (i) hydrogen or while I(i) when R is hydrogen, X, Y and Z are hydrogen, halogen or nitrogen but not all together hydrogen, and they are not NCX, when R-^, R 2 , X and Z are hydrogen; and (ii) A) when R is the group is R, and R, independently hydro gen or lower alkyl, X, Y and Z independently hydrogen, halogen or NC>2 , n 0, 1 or 2, R^ hydrogen, oxiranyl, mono- or dihydroxyalkyl, N-(dihydroxyalkyl)-amino-hydroxyalkyl, carboxy, caralkyloxy . or b) X is hydrogen or allyl, Y, Z, R, and R- are hydrogen and n is zero, R;- means where Rg is hydrogen or lower in I alkyl or together with R, forms a 5- or 6-membered saturated I heterocyclic ring with max. 2 heteroatoms, R^ a hydrocarbon residue, alkoxyalkyl, dialkylaminoalkyl, heteroalkyl, carbamoylalkyl i or five- or six-membered and optionally condensed heterocyclic residue I with max. 3 heteroatoms, I as well as their salts with acids or bases. in Preparation of the compounds is described. The compounds are usable as agrochemicals or as raw materials for the production of these on the one hand and as raw materials for the production of pharmaceuticals, X-ray contrast agents or photosensitizers on the other hand. Some compounds of formula (I) in the form of salts with ion exchangers are valuable ji -blockers and analgesics. in i