RING-SUBSTITUTED DERIVATIVES OF PYROGALLOL

DERIVES DE PYROGALLOL SUBSTITUES SUR L'ANNEAU

English Abstract

ABSTRACT
Pyrogallol derivatives of general formula:
<IMG>
wherein R1 and R2 may be the same or different and re-
present hydrogen or lower alkyl,
R represents hydrogen or a group <IMG>
in the case where R represents hydrogen, each of X, Y and
Z represent hydrogen, halogen or nitro, with the proviso
that not all of X, Y and Z are simultaneously hydrogen
and with the further proviso that, when R1, R2, X and Z
are hydrogen then Y cannot be nitro, and with the further
proviso that, when R1, R2, Y and Z are hydrogen, then X
cannot be a bromine atom; in the case where R represents
a group
<IMG>

R3 and R4 may be the same or different and represent
hydrogen or lower alkyl; X, Y and Z may be the same or
different and represent hydrogen, halogen or nitro; n is
an integer from 0 - 2 inclusive; and R5 represents hydro-
gen, oxiranyl, mono- or dihydroxyalkyl, N-(dihydroxy-
alkyl)-amino-hydroxyalkyl, carboxy, carbalkoxy, carbamyl,
N-alkylcarbamyl, N,N-dialkylcarbamyl, cyano, .DELTA.2-
imidazolin-2-yl, amidoxime, oxime ester or dialkyl
acetal, the amino radical of the carbamyl groups being
also a saturated hetero-ring having in total two hetero
atoms; and their salts with inorganic or organic acids
and bases, with the proviso that R1 to R5 and Z cannot
be simultaneously hydrogen when X and Y are chlorine
atoms, and with the further proviso, that R1 to R5
cannot be hydrogen simultaneously; are useful as
agricultural chemicals or intermediates for such and
have activity against Botrytis, Plasmopara viticola
and Alternaria.

Claims

The embodiments of the invention in which an exclusive
property or privilege is claimed are defined as follows:
1. New pyrogallol derivatives of general formula:
<IMG> (I)
wherein R1 and R2 may be the same or different and represent
hydrogen or lower alkyl,
R represents hydrogen or a group <IMG>
in the case where R represents hydrogen, each of X,
Y and Z represents hydrogen, halogen or nitro, with the
proviso that not all of X, Y and Z are simultaneously hydrogen
and with the further proviso that, when R1, R2, X and Z are
hydrogen then Y cannot be nitro, and with the further proviso
that, when R1, R2, Y and Z are hydrogen, then X cannot be
a bromine atom;
in the case where R represents a group
<IMG>
R3 and R4 may be the same or different and
represent hydrogen or lower alkyl; X, Y and Z may be the same
or different and represent hydrogen, halogen or nitro;
- 21 -

n is an integer from 0 - 2 inclusive;
and R5 represents hydrogen, oxiranyl, mono-
or dihydroxyalkyl, N-(dihydroxyalkyl)-amino-hydroxy-
alkyl, carboxy, carbalkoxy, carbamyl, N-alkylcarbamyl,
N,N-dialkylcarbamyl, cyano, .DELTA.2-imidazolin-2-yl,
amidoxime, oxime ester or dialkyl acetal, the amino
radical of the carbamyl groups being also a saturated
hetero-ring having in total two hetero atoms; and
their salts with inorganic or organic acids and bases,
with the proviso that R1 to R5 and Z cannot be
simultaneously hydrogen, when X and Y are chlorine
atoms, and with the further proviso that R1 to R5
cannot be hydrogen simultaneously.
- 22 -

2. New pyrogallol derivatives according to claim 1 and
of general formula:
<IMG> I(a)
and metal salts thereof, wherein R1 and R2 may be
the same or different and are hydrogen or lower alkyl,
X, Y and Z each are hydrogen, halogen or nitro,
with the proviso that not all of X, Y and Z can be
simultaneously hydrogen, and with the further proviso that
Y cannot be nitro if R1, R2, X and Z are all hydrogen, and with
the further proviso that, when R1, R2, Y and Z are all hydrogen
X cannot be a bromine atom.
- 23 -

3. Pyrogallol derivatives according to claim 2 wherein
each of R1 and R2 is selected from hydrogen and straight
chain and branched chain alkyl radicals having from 1-8 carbon
atoms.
4. 2,2-dimethyl-4-hydroxy-5,7-dibromo-1,3-benzodioxol, and
the sodium salt thereof.
5. Pyrogallol derivatives of formula I(a) according to
claim 2, wherein one of X and Z represents nitro and the other
of X and Z represents hydrogen, Y represents hydrogen and both
R1 and R2 represent methyl.
6. 2,2-dimethyl-4-hydroxy-5-nitro-7-bromo-1,3-benzodioxol.
7. 2,2-dimethyl-4-hydroxy-5-bromo-7-nitro-1,3-benzodioxol.
8. 2,2-dimethyl-4-hydroxy-5,7-dinitro-1,3-benzodioxol.
9. 2,2-dimethyl-4-hydroxy-5-chloro-1,3-benzodioxol.
10. 2,2-dimethyl-4-hydroxy-5,6,7-trichloro-1,3-benzodioxol.
11. 2,2-dimethyl-4-hydroxy-5,7-diiodo-1,3-benzodioxol.
12. 2,2-dimethyl-4-hydroxy-5,7-dichloro-1,3-benzodioxol.
- 24 -

13. A process for preparing pyrogallol derivatives of
formula 1(a) shown in claim 2, which comprises treating a
4-hydroxy-1,3-benzodioxol of the general formula:
<IMG> (II)
wherein R1 and R2 are as defined in claim 2, with
halogenation and/or nitration agents appropriately chosen to
effect the desired aromatic-nuclear substitution.
14. The process of claim 13 which is effected in an inert
solvent or solvent mixture.
15. The process of claim 13 or claim 14 in which a compound
of formula (II) as shown in claim 13 is reacted with halogen or
a halogen releasing agent to obtain a mono-, di- or tri-halo
nuclear substituted product of formula 1(a) as shown in claim 2.
16. The process of claim 13 or claim 14 in which a compound
of formula II is reacted with nitric acid, to obtain a nitro
nuclear substituted product of formula 1(a) as shown in claim 2.
17. A process for preparing pyrogallol derivatives of
formula I(a) shown in claim 2 in which one of X, Y and Z
represents halogen and another of X, Y and Z represents nitro,
which comprises reacting a compound of formula 1(a) shown in
claim 2 and in which two of X, Y and Z represent halogen, with
nitric acid.
- 25 -

18. A process for preparing pyrogallol derivatives of
formula 1(a) shown in claim 2 in which one of X, Y and z
represents halogen and another of X, Y and Z represents nitro,
which comprises reacting a compound of formula 1(a) shown in
claim 2 in which one of X, Y and Z is nitro and the others are
hydrogen, with halogen.
19. Derivatives of pyrogallol ethers of general formula:
<IMG> (1c)
wherein R1, R2, R3 and R4 may be the same or different
and each represents hydrogen or lower alkyl;
X, Y and Z may be the same or different, and are
hydrogen, halogen or nitro;
n is 0, 1 or 2;
R5 is hydrogen, oxiranyl, mono- or dihydroxyalkyl,
N-(dihydroxyalkyl)-amino-hydroxyalkyl, carboxy, carbalkoxy,
carbamyl, N-alkylcarbamyl, N,N-dialkylcarbamyl, cyano,
a 2-imidazolin-2-yl, amidoxime, oxime ester or dialkyl
acetal, the amino radical of the carbamyl group being also a
saturated heteroring having totally two hetero atoms.
20. 2,2-dimethyl-4-(carbethoxy-methoxy)-1,3-benzodioxol.
- 26 -

21. 2,2-dimethyl-4-(carboxy-methoxy)-1,3-benzodioxol.
22. 2,2-dimethyl-4-(carboxymethoxy)-5,7-dichloro-
1,3-benzodioxol.
23. 2,2-dimethyl-4-(morpholino-carbomethoxy)-1,3-benzodioxol.
24. 2,2-dimethyl-4-(2'-carbamidoxim-ethoxy)-1,3-
benzodioxol.
25. 2,2-dimethyl-4-cyanomethoxy-5,7-dibromo-1,3-
benzodioxol.
26. 2,2-dimethyl-4-(carbamidoxime-methoxy)-5,7-dibromo-
1,3-benzodioxol.
27. 2,2-dimethyl-4-(2 ,3 -epoxy-propoxy)-5,7-diiodo-
1,3-benzodioxol.
28. 2,2-dimethyl-4-(2',3'-dihydroxy-propoxy)-5,7-
diiodo-1,3-benzodioxol.
29. 2,2-dimethyl-4-(N-methylcarbamylmethoxy)-5,7-diiodo-
1,3-benzodioxol.
30. 2,2-dimethyl-4-(.DELTA.2imidazolin-2-yl-methoxy)-1,3-
benzodioxol.
- 27 -

31. 2,2-dimethyl-4-butoxy-5,7-dibromo-1,3-benzodioxol.
32. 2,2-dimethyl-4-[3?( ?,? -dihydroxymethyl-ethylamino)-
2 -hydroxy-propoxy]-5,7-diiodo-1,3-benzodioxol.
33. 2,2-dimethyl-4-(2',2'-dimethoxy-ethoxy)-1,3-
benzodioxol.
34. 2,2-dimethyl-4-[3'-(1",3"-dihydroxy-isopropylamino)
-2'-hydroxy-propoxy]-5,7-diiodo-1,3-benzodioxol.
35. Acetone-0-(2,2-dimethyl-1,3-benzodioxol-4-oxyacetyl)-
oxime.
36. Pyrogallol ether derivatives according to claim 19,
wherein R1 and R2 both represent methyl, R3 and R4 both
represent methyl or hydrogen, n is zero and R5 represents COOH.
37. Pyrogallol ether derivatives according to claim 19,
wherein R1 and R2 both represent methyl, R3 and R4 both
represent hydrogen, n is zero, and R5 is selected from
<IMG> CHOH. CH2OH
and <IMG> .
- 28 -

38. A process for preparing pyrogallol ethers of the
general formula
<IMG> (1c)
where each of R1, R2, R3, R4, R5, n, X, Y and Z have
the meanings given in claim 19, which comprises reacting a
pyrogallol derivative of formula:
<IMG>
wherein X, Y, Z, R1 and R2 are as defined above, or a
phenolate thereof, with a compound of the general formula
<IMG>
wherein R3, R4 and n are as defined above, R5' has the
meaning of R5 above or is a group CH.CN, and A is halogen, a
sulfonyloxy group or, if R3 and R4 are hydrogen, n = 0 and
R5 is a group CH.CN, A is a double bond with the adjacent
carbon atom, optionally converting the group R5 in the product
- 29 -

to a different group R5, and, if X and/or Y and/or Z
are hydrogen, optionally treating the compound so
obtained with halogenation and/or nitration agents.
- 30 -

39 . A process for preparing pyrogallol derivatives of
general formula:
<IMG> (I)
wherein R1 and R2 may be the same or different and represent
hydrogen or lower alkyl,
R represents hydrogen or a group <IMG>
in the case where R represents hydrogen, each of X,
Y and Z represents hydrogen, halogen or nitro, with the
proviso that not all of X, Y and Z are simultaneously hydrogen
and with the further proviso that, when R1, R2, X and Z are
hydrogen then Y cannot be nitro, and with the further proviso
that, when R1, R2, Y and Z are hydrogen, then X cannot be
a bromine atom;
in the case where R represents a group
<IMG>
R3 and R4 may be the same or different and
represent hydrogen or lower alkyl; X, Y and Z may be the same
or different and represent hydrogen, halogen ox nitro;
- 31 -

n is an integer from 0 - 2 inclusive;
and R5 represents hydrogen, oxiranyl, mono-
or dihydroxyalkyl, N-(dihydroxyalkyl)-amino-hydroxy-
alkyl, carboxy, carbalkoxy, carbamyl, N-alkylcarbamyl,
N,N-dialkylcarbamyl, cyano, .DELTA.2-imidazolin-2-yl,
amidoxime, oxime ester or dialkyl acetal, the amino
radical of the carbamyl groups being also a saturated
hetero-ring having in total two hetero atoms; and
their salts with inorganic or organic acids and bases,
with the proviso that R1 to R5 and Z cannot be
simultaneously hydrogen, when X and Y are chlorine
atoms, and with the further proviso that R1 to R5
cannot be hydrogen simultaneously, comprising:
a) when R in formula (I) represents hydrogen,
treating a 4-hydroxy-1,3-benzodioxol of the general
formula:
<IMG> (II)
wherein R1 and R2 are as defined above with at least
one agent selected from halogenation and nitration
agents appropriately chosen to effect the desired
aromatic-nuclear substitution, or
- 32 -

b) when R in formula (I) represents said group:
<IMG>
reacting a pyrogallol derivative of formula:
<IMG>
wherein X, Y, Z, R1 and R2 are as defined above, or a
phenolate thereof, with a compound of the general formula
<IMG>
wherein R3, R4 and n are as defined above, R5' has the
meaning of R5 above or is a group CH.CN, and A is halogen, a
sulfonyloxy group or, if R3 and R4 are hydrogen, n = 0 and
R5 is a group CH.CN, A is a double bond with the adjacent
carbon atom, optionally converting the group R5 in the product
to a different group R5, and, if X and/or Y and/or Z are
hydrogen, optionally treating the compound so obtained with
at least one agent selected from halogenation and nitration
agents.
- 33 -

Description

~ 2 ~
- 1 -
The present invention relates to new ring
. substituted derivatives of pyrogallol and their pre-
paration.
: Thus in one aspect of the invention there is
provided new pyrogallo derivatives of general formula:
~o\~
OR
wherein Rl and R2 may be the same or different and
.. represent hydrogen or lower alkyl,
.; 13 -
R represents hydrogen or a group - f (CH2 ) n~R5;
~ ~4
' ' 1
. 10 in the case where R represents hydrogen, each of X, Y
and Z represents hydrogen, halogen or nitro, with the
proviso that not all of X, Y and Z are simultaneously
~;` hydrogen and with the further proviso that, when Rl,
R21 X and Z are hydrogen then Y cannot be nitro, and
with the further proviso that, when Rl, R2, Y and Z
a.re hydrogen, then X cannot be a bromine atom;
in the case where R represents a group
.' .
y''"'~
~,,,,,",~s

~ 2~3 ~ 8 1
13
- C - (C~2)n~R5;
R4
R3 and R4 may be the same or dif-ferent and represent
hydrogen or lower alkyl; X, Y and Z may be the same or
different and represent hydrogen, halogen or nitro;
n is an integer from 0 - 2 inclusive; and R5 represents
hydrogen, oxiranyl, mono- or dihydroxyalkyl, N-(dihydroxy-
alkyl)-amino-hydroxylalkyl, carboxy, carbalkoxy,
carbamyl, N-alkylcarbamyl, N,N,-dialkylcarbamyl, cyano,
-imidazolin-2-yl, amidoxime, oxime ester or dialkyl
acetal, the amino radical of the carbamyl groups being
also a saturated hetero~ring having in total two hetero
atoms and their salts with inorganic or organic acids
' and bases, with the proviso that Rl to R5 and Z cannot
b~ simultaneously hydrogen, when X and Y are chlorine
atoms, and with the further proviso that Rl to R5 can
not be hydrogen simultaneously.
In one particular embodiment the invention pro-
vides compounds of formula I(a), within the scope of
~.
formula (I) above, in which R is a hydrogen atom,
and metal salts thereof.
In another particular embodiment the invention
; provides compounds of formula I(c), within the scope
" , '~s

~ ~3~
-- 3
of formula (I) in which R is said group of formula:
,R3
C, (C 2)n R5
R~
According to the present invention the new
compounds Ita) can be prepared by treating a 4-hydroxy-
1,3-benzodioxol of the formula (II):
C~o/ ~ R (II)
0~ :
wherein Rl and R2 are as defined above, preferably in ;
an inert solvent or solvent mixture, in a single or :
multistage reaction, optionally with use o-f acid bind-
10 ing additives and/or catalysts, with halogenation .
; and/or nitration agents.
Derivatives of pyrogallol ethers of the formula --
I(c) are obtained by reacting a pyrogallol derivative
of the formula (Ia):
z
X ~ j - / < R (Ia)

1 ~3 ~ 8 1
-- 4 --
wherein Rl, R2, X, Y and Z axe as defined above, or a
phenolate thereof, preferably in an inert solvent or
solvent mixture, with a compound o:E the general
formula:
A I - tCH2 ) - R ~ (VII) ,
wherein R3, R~ and n are as defined above, R5' has the
same meaning as R5 or is a group CH.CN and A is halogen,
a sulfonyloxy group or, if R3 and R4 are hydrogen, n =
0 and R5' is a group ~CH.CN, A is a double bond with
the adjacent carbon atom, optionally converting in an
obtained derivative of the general formula I(c) a group
R5 into another group R5 and, if X and/or Y and/or Z
are hydrogen, treating, if desired, an obtained com-
pound of the general formula I(c) with halogenation
and/or nitration agents.
The new compounds of the invention, of the
formula (Ia) and (Ic), are useful raw materials for
the preparation of agricultural chemicals or represent
themselves such agricultural chemicals~
In particular the compounds (Ia) and (Ic~ are found to
be active against Botrytis, Plasmopara viticola and
Alternaria.
~, ~

12~3~
- 4a - ;
The formulae ~Ia) and (Ic) are as follows: `.
'''''
2 . 1
/ \ R~
i
I O R !':
x ~ o / R I(c)
o~C--~C~ Rs
;.

I ~ 3 ~
! - 5 ~
The expression "lower alkyl" as used herein
comprises especially methyl, ethyl, propyl, butyl,
pentyl, hexyl, heptyl and octyl as well as branched
radicals, for example, isopropyl, t-butyl and 2,2-di~
methylpropyl.
In the definition of R5 the heteroatoms for
the saturated hetero ring are suitably selected from
; oxygen, nitrogen and sulfur.
The starting compounds of the general formula
(II) are either known or may be obtained according to
known methods. A compound of general formula (II),
' wherein Rl and R2 are methyl, is used in grea-t amounts
as intermediate for the preparation of insecticides
(Chem. Abstr. 71, 38941m (1969); 78 7211u (1973); 84,
10525u (1976); 85, 192700c (1976); 86, 51598j (1977)).
Although the effect of a ring-substitution
with halogen or nitro groups is known in the field of
agricultural chemlcals (see "Wirkstoffe in
Pflanzenschuts- und Schadlingsbekampfungsmitteln", 1st
edition 1982, Industrieverband Pflanzenschutz e.V.) and
ring~halogenated reaction products from compounds of
general formula (Ia) are claimed in patents, but not
; described (Austrian patent specifications 283 812 and
, 296,983) ring-substituted derivatives of the ~eneral
formula are not reported in the literature, with the
exception of a product obtained by nitration of
myristicinic aldehyde (J. Chem. Soc. 95, 1161 (1909)).
.

. 1233181
-- 6
According to the process for the preparation
of compounds of formula (Ia) a 4-hydroxy-1,3-benzodi
oxol only can be halogenated or nitrated or first halo-
genated and then nitrated or first nitrated and then
halogenated resp. A ring-substituent in-troduced first
can be substituted in a subsequent step by another
substituent. The agents used for the halogenation or
nitration resp. are such which are known per se for the
reaction with aromatic hydrocarbons or phenols.
The following examples illustrate the
invention without any limitation thereto. Temperatures
are given in C.
Example 1: 19.2~ g of bromine are dropped slowly into
a suspension of 10 g of 2,2-dimethyl-4-hydroxy-1,3-
benzodioxol and 22 g oE NaHCO3 in 150 ml of carbon
tetrachloride stirred at 0. The completed reaction
can be seen by thin layer chromatography (TLC) (plate.
silicagel 60 F 254*, eluent: chloroform/methanol 9:1).
After filtration of the mixture the filtrate is
evaporated on the rotary evaporator. The residue
crystallizes on standing and is to be recrystallized
from petrol ether. The obtained 2,2-dimethyl-4-
hydroxy-5,7-dibromo-1,3-benzodioxol has a melting
point o~ 59-61.
* trade mark

~233~8~
7 --
The sodium salt of this compound is obtained
by adding an equivalent of a 30% solution of sodium
methylate in methanol to a methanolic solution,
evaporating the mixture a~d treating the solid residue
with isopropylether. The dried sodium salt does not
melt below 320, but only gets a brown color.
Example 2: 14.8 ml of a 65% nitric acid (D: 1.40) are
added dropwise to a solution of 30 g of 2,2-dimethyl-4-
hydroxy-1,3-benzodioxol in 600 ml of chloroform cooled
at -5C, the temperature raising up to +2. The TLC
(plate: silicagel 60 F 254*, eluent: chloroform/
methanol 9:1) shows two new products, one appearing
- ahove (5-nitro derivative) and the other closely below
(7-nitro
:'
'
*trademar]c

i ~33 1 ~ ~
-- 8 --
derivative) the starting cornpound. The reaction is allowed to continue
at 10 and then it is extracted 3--times with water, whereby begin-
ning crystallization ~ay be o~served. By concentration of the solu-
tion warmed up and filtered with activated carbon and celite the
5 more difficultly soluble 2,2-dimethyl-4-hydroxy-7-~itro-1,3-benzodi-
oxol crystallizes out. AEter recrystallization from CHCl3 it melts
at 193-195~.
For obtaining the 5-nitro derivative the CHCl3-mother
liquor is evaporated to dryness and the residue is taken up into
l0 isopropanol. Af-ter allowing the solution to stand in the cold the
2,2-dimethyl-4-hydroxy-5-nitro-1,3-benzodioxol crystallizes out
and has a melting point of 150-151.
The posi-tion of the nitro groups can be seen from the
N.M.R. spectra o~ the two isomers: Whereas the O~l-group of the
~15 5-nltro derivative shows in CDCl3 at 250 MHz a signal at 10,42 ppm,
the OH-group of the 7-nitro compound gives under the same condltions
a sliding resonance between 4,6 and 6,2 ppm.
When heated in aqueous solution both isomers give the
; knowr 4-nitrop~rogallol, m.p. 165-166 (literature m.p. i62") due
20 to hydrolysis of the dioxolane ring.
E x a m p l e 3: 2,4 ml of concentrated HNO3 are added dropwise
to a solution of 5 g of the sodium salt of 2,2-dimethyl-4-hydroxy-
5,7-dibromo-1,3-benzodioxol obtained according to Example 1 in
100 ml of chlorofor~ at 0 to 5. First a precipitate is obtained
25 which then substantially dissolves. The orange colored mixture
is extracted several times with water, the chloro~orm phase is
dried with Na2SO~, filtered with activa-ted carbon after stirring
and evaporated in vacuo. The remaining oil crystallizes when stir-
r~d ~1ith water. ~ ~er rec~ystall' zatJ on of tl;e crude product from
acetic ester the ~,2-dinlethyl-q-hydroxy-5-nitro-7-bromo-1,3-bellzo-
~.....
* 'rr~rlP ~-n-k

t
1 2 3 ~
dioxol is obtained in form oE a yellow powder, m.p. 93-95.
The separation of bromide during the reaction can be
proved by reaction with ~gNO3. The position of the group NO2 can
be seen from the N.M.R. spectr~n (CDCl3, 250 MHz), since the adja-
cent group OH shows a signal at 10,27 ppm ~see Example 2).E x a m p l e 4: A solution of 4 g of bromine in 20 ml CCl4 is
dropped into a mixture of 3 g of the 2,2-dimethyl-4-hydroxy-7-
nitro-1,3~benzodioxol, 7 g NaHCO3 and 200 ml CC14 stirred at 0.
After warming up to room temperature the mixture is allowed to
stand over night. Then a complete reaction can be seen by thin
layer chromatography. After filtration of inorganic material the
filtrate is evaporated in vacuo and the crystalline residue is
recrystallized from a small amount of chloroform. The obtained
2,2-dimethyl-4-hydroxy-5-bromo-7-nitro-1,3~benzodioxol melts at
185-188 after a crystal conversion at 155~.
If an aqueous solution of this compound is heated, due
to hydrolysis of the dioxolane ring the same 4~~romo-6-nitro-pyro-
gallol ~m.p. 133-135) is formed, which is obtained also by hydro-
lysis of the isomer obtained according to Example 3.
E x a m p l e 5: 10 ml of 65 % HNQ3 are added dropwise to a solu-
tion of 10 g of 2,2-dimethyl-4-hydroxy-1,3-benzodioxol in 100 ml
of chloroform with stirring at 12 to 14; after 15 minukes at the
same temperature additional 48 ml of 65 % HNO3 are added. Thin
layer chromatography (see Example 2) shows that the mono-nitrated
products formed first are converted into a product which appears
sti].l below the 7-nitro-derivative.Aftera reaction time o further
15 minutes the chloroform solu-tion is extracted 3-times w:ith water,
dried over Na2SO~ and the ~iltrate is evaporated in vacuo. The
residue crystalllze~ a-t trituratiGn witll isopro~anol~ After recry-
stallization ~rom ethanol -the obtained 2,2-dimethyl-~-hydroxy-

~ ~ 3 ~
- 10
-5,7-dinitro-1,3-benzodioxol has a m.p. of 203-205.
E x a m p l e 6: 20 g of a powdered eation exehanger (having
-COONa as active groups) are added to a solution of 10 gof 2,2-
dimethyl-4-hydroxy-1,3-benzodioxol in 200 ml of CCl4 and a solu-
tion of 5,4 ml sulfuryl chloride in 20 ml of CC14 is dropped inwith stirring at room temperature. After 3 hours also a solution
of 2,7 ml of SO2Cl2 in 10 ml of CCl4 is dropped in. After stirring
during further 3 hours thin la~er ehromatography (see Example 1)
shows substantially complete reaetion. The solution sueked off
from the ion exchanger is washed with water, dried over dry Na2SO4
and evaporated. By recrystallization of the residue from petrol
ether with use of activated carbon the 2,2-dimethyl-4-hydroxy-
5-chloro-1,3-benzodioxol is obtained, m.p. 81-83.
The position of the chlorine atom results from the faet
15 that the two aromatic protons in the N.M.R. spectrum (CDCl3, 250
MHz) practieally do not show any "shift"-effect also after forma-
tion of the sodium phenolate in CD30D or of a complex with an euro-
pium compound.
E x a m p l e 7 : One iodine crystal and 10 g of sodium bicarbo-
20 nate are added to a solution of 5 g of 2,2-dimethyl-4-hydroxy-
1,3-benzodioxol in 100 ml of CCl4 and eooled to 0. A solution
of 8,5 g of chlorine in 80 ml of CCl4 is dropped in with stirring
at 0 to 3. As soon as no starting material appears by thin layer
ehromatography (see Example 1) any excess of chlorine is removed
25 by blowing in nitrogen. The filtrate of the reaction mixtuxe is
evaporated in vacuo and -the residue is stirred with petrol ether,
by whleh erystalllzatlon begins. The crude product is repreeipi-
tated wlth use o~ activated earbon from methanol~water. Thus, a
colorless powder o~ 2,2-dlmethyl~ ydroxy-5,6,7-triehloro 1,3-
30 be~zodioxol is obtalned, m.p. 150-152.
C~

1~31~1
No signals of nuclear protons appear in the N.M.R. spec-
trum of this compound.
E x a m p l e 8 : A solution of 25,4 g of iodine and 30 g of po-tas-
sium iodide in 150 ml of water is dropped with stirring to a solu-
tion of 8,4 g of 2,2-dimethyl-4-hydroxy-1,3-benzodioxol in 400 ml
of 0,5 N NaOH. After standing over night the ~ormation of a new
product can be seen by thin layer chromatography (silicagel 60 F
254, eluent: ethylacetate/methanol/2N NH40H 25 : 8 : 3) The filte-
red solution is stirred with saturated aqueous NaHS03-solution
at 2 to 5 up to pH 5 and then extracted with chloroform. The chlo-
roform solution dried with Na2S04 and filtered after addition of
; activated carbon leaves a~ter evaporation a yellow oil. After repre-
cipitation from methanol/water or recrystallization from petrol
ether 2,2-dimethyl-4-hydroxy-5,7-diiodo-1,3-benzodioxol is ob-
tained, m.p. 52-55.
E x a m p 1 e 9: A solution of 11 ~ of chlorine in 150 ml CC14
is added dropwise to a mixture oE 12,2 g of 2,2-dimethyl-4-hydroxy-
1,3-benzodioxol, 24 g of Na~C03, 0,05 g of FeCl3 and 400 ml of
carbon tetrachloride with stirring at 0. As soon as thin layer
chromatography (see Example 8) indicates complete reaction, the
mixture is filtered and the filtrate is evaporated. Aftqr fil~ra-
tion of the solution the residue is reprecipitated with activated
carbon from methanol/water and then recrystallized from isopropyl-
ether/petrol ether. Thus, 2,2-dimethyl-4-hydroxy-5,7-dichloro-
1,3-benzodioxol is obtained, m.p. 172-174.
The -three ring-chlori.nated derivatives of examples 6,
7 and 9 can be distinguished also by their Rf-values. Under the
conditions oE thin layer chroma-koyraphy as described in Example
~ the ~ollowin~J results:

- 12 -
Derlvative:Example: Rf-value:
5-chloro- 6 0,82
5,7-dichloro- 9 0,73
5,6,7-trichloro- 7 0,67
_ _ _ .
J,~ ..''t,'
E x a m p l e l0 : 10,8 g of a 30 % solution o~ CH3ONa in metha-
nol are dropped into a solution of 10 g of 2,2-dimethyl-4-hydroxy-
1,3-benzodioxol in 50 ml of methanol with stirring. 12,55 g of
bromoacetic acid ethylester in 15 ml of methanol are added drop~
`::
wise to the dark colored mixture. It is stirred at room *empe~
;10 rature, until no starting material appears by thin layer chr~ma~
tography (plate: silicagel 60 F 25~, eluent: chloroform/methanol
9 : 1). Then it is evaporated on the rotary evaporator and the
~esidue is taken up il~tO chloroform. Th~ filtered chloroform so-
lution is extracted twice with 1N NaOH and trice with water,
~ .
"

- l233l8~ !
- 13 -
dried over Na2S04 and evaporated. The 2,2-dimethyl 4-(carbethoxy-
methoxy)-1,3-benzodioxol obtained first in form of an oil cry-
stallizes on standing and has then a m.p. of 46-48.
E x a m p l e ll : After addition of 20 ml of water 8 g of a
5 30 % solution of CH30Na in methanol are added dropwise to a solu-
tion of 11,3 g of the ester obtained according to Example lO in
100 ml of ethanol with stirring After stirring for 1 hour at
room temperature thin layer chromatography ~plate: silicagel 60
F 254,* eluent: acetic ester/methanol/2N NH40H 25 : 8 : 3~ indica-
lO tes complete reaction. The solution is evaporated in vacuo and~the residue is dissolved in water. The precipitate obtained by
acidification of the aqueous solution with HCl is sucked off,
washed with water and dried in vacuo. After recrystallization
from CHCl3/CCl4 the 2,2-dimethyl-4-(carboxy-methoxy)-1/3-benzo-
15 dioxol is obtained, m.p. i38-141.
The sodium salt of this compound may be obtained e.g.
hy reaction of a methanolic solution of the free acid with one
equivalent of sodium methylate, evaporation of the mixture and
treatment of the residue with isopropylether, m.p. 256-260 with
20 decomposition.
E x a m p l e 12 : After addition of one iodine crystal a solu-
tion of 4,5 g of chlorine in 100 ml of CC14 is added dropwise to
a mixture of 4 g of the carboxylic acid obtained according to
Example ll, 8 g of NaHC03 and 100 ml of CC14 with stirring at
25 -5. The reaction is allowed to continue at 0 and then it is ~il-
tered. The obtained precipitate is extracted hot with CHCl3, the
extract is combined with the CCl~-filtrate and evaporated in vacuo.
The residue of the evaporation is treated with CIICl3/M~0, the pha-
ses are separated and the C~Cl3-phase is evaporated rrhe crystal-
* Trade Mark ;
,~ ~

- ll2~318~
line residue is recrystallized from CCl4 and the 2t2-dimethyl- ;;
4-(carboxymethoxy)-5,7-dichloro-1,3-benzodioxol, m.p. 143-145, ~;~
is obtained.
E x a m p 1 e l3 : The product of Example12 may be obtained
5 also by the ~ollowing method: ~ -
2,2-dimethyl-4-hydroxy-5,7-dichloro-1,3-benzodicxol is
reacted according to the process described in Example 10 to give
the 2,2-dimethyl-4-(carbethoxy-methoxy)-5,7-dichloro-1,3-benzo-
dioxol, m.p. 82-84.
After saponification according to Example 1] this ester
yields the corresponding free acid, which shows the melting po:int
mentioned in Example :L2.~ ~
E x a m p 1 e 14 : A mixture of ~,5~of the ester obtained by
Example l0, 8 g o~ morpholine, 6 ml of dimethylformamide and
20 ml of benzene is heated under reflux, until thin layer chro-
matography ~see Example ll) does not show any starting material.
The residue obtained by evaporation of the solution is recrystal-
lized from isopropylether, is 2,2-dimethyl-~-(morpholino-carbo-
methoxy)-1,3-benzodioxol and has a m.p. of 92-93.
E x a m p 1 e 15 Two drops of a 40 % methanolic solution of
benzyltrimethylammonium hydroxide are added to a solution of
6,3 g of 2,2-dimethyl-4-hydroxy-1,3-benzodioxol in 30 ml of
acrylonitrile and then heated under reflux with stirring, until -
thin layer chromatography (see Example In) only shows traces of
the starting material. The residue after evaporation is taken up
into acetic ester/water, the mixture is filtered, and the acetic
ester phase is re-extracted with 1N NaOH and water and the acetic
ester solution dried with Na2S~ is evapol-ate~.
The oily residue, 2,2-dimethyl-4-(2'-cyanoethoxy)-1,3-
:
r~

' 3 ~ t 8 1 '
benzodioxol,is used for the subsequent reaction with hydro~yl-
amine.
For that purpose 9 g of a 30 ~ methanolic solution of
NaOCH3 are added dropwise to a solution of 3,5 g of hydroxylamine
hydrochloride in 15 ml of methanol with stirring and cooling from
outside with water and then it is sucked off from precipitated
NaCl. The solution thus obtained is added dropwise to a solution
of 6,2 g of 2,2-dimethyl-4-(2'-cyano-ethoxy)-1,3-benzodioxol in
25 ml of ethanol kept under reflux and stirred. After further 15
minutes under reflux according to thin layer chromatography (see
`Example l0) all has been reacted. The filtered solution is evapo-
rated. The oily residue crystallizes from isopropanol, is 2,2-
- dimethyl-4-(2'-carbamidoxim-ethoxy)-1,3-benzodioxol and has a
m.p. of 100-103. '
E x a m p l e l6 : The solution of 10 g of the sodium salt of
2,2-dimethyl-4-hydroxy-5,7-dibromo-1,3-benzodioxol and 0,7 g
of benzyltriethylammoniumchloride in 40 ml of chloroacetonitrile
is stirred under reflux, until thin layer-chromatography (see
Example l0 ) shows complete reaction. It is evaporated in vacuo,
the residue is taken up into acetic ester and it is extracted
with 1N NaOH and then with water. The residue obtained by evapo-
ration of the acetic ester solution crystallizes on standing
in the refrigerator. By recrystallization from petrol ether the
obtained 2,2-dimethyl-4-cyanomethoxy-5,7-dibromo~1,3-benzodioxol
25 melts at 64-66.
E x a m p l e l7 : 5,7 g of a 30 % methanolic solution of NaOCH3 ~`
are added dropwise to a solutlon of 2,2 ~ of hydroxylamine hydro-
chloride ln 15 ml of methanol wlth s~:lrrin~ at 12~. rrhe f'ilt~ate
of the obtained mixture is dropped to a solution oE 7,~ g 2,2-

; 1 2 3`~ 1 8 ~
- 16 -
-dimethyl-4-cyanomethoxy-5,7-dibromo-1,3-benzodioxol in 25 ml
of ethanol boiling under reflux with stirring. After about 15
minutes it is evaporated on the rotary evaporator. The xesidue
is treated with'acetone and the obtained precipitate is recry-
5 stallized from isopropanol. The obtained 2,2-dimethyl-4-(carb-
amidoxime-methoxy)-5,7-dibromo-1,3-benzodioxol has a m.p. of
153-155.
E x a m p l e 18: 4.3 g of a 30 ~ methanolic solution of NaOCH3
are added to a solution of 10 ~ o~ 2,2-dimethyl-4-hydroxy-5,7-
l0 diiodo-1,3-benzodioxol in 50 ml of methanol and then evaporated
'in vacuo. The residue is taken u~ into 50 ml of ethanol and after
addition of 2.65 g of 3-chloro-1,2-propanediol the solution is
' heated under reflux, until thin layer chromatography (see'Example
I0) shows only traces of starting product. The solution filtered ~'~
15 over Celite is evaporated in vacuo, the residue is taken up into
CHCl3~H2O, the CHCl3~phase is dried with Na2SO4'and evaporated.
After filtration of the hot solution with activated carbon the
residue crystallizes'from isopropanol~ The obtained 2,2-dimethyi-
4-(2',3'~dihydroxy-propoxy)-5,7-diiodo-l,3-benzodioxolhas a m.p.
20 of 11Z-114.
E x a m p l e l9 : The sodium salt of 5 g of 2,2-dimethyl-4- ''
hydroxy-5,7-diiodo-1,3-benzodioxol is prepared in methanol by
addition of 2.15 g of 30 % methanolic NaOCH -~ solution and evapo-
ration of the mixture. After addition of 0.5 g of triethylbenzyl-
ammoniumchloride the residue is taken up into 30 ml epichloro-
hydrine and allowed to stand over night. Then the residue of
evaporation is treated with hot acetic ester and th~ filtered
solution is evaporated. ~rhus, 5.6 g of 2,2-di~ethyl-~-~2',3'-
epoxy propoxy)-5,7-diLodo-l,3-benzodioxol in form of a yel:Low
oil are ob-tained. rrhin layer chroma-to~raphy ~see Example l~

~2~3~
. ~ .
.
shows that it migrates somewhat higher than the starting material;
it proves to be pure. On standing the product crystallizes and
melts then at 64-67~.
E x a m p 1 e 20:1 ml of thionyl chloride is dropped into a ;
solution of 1,7 g of 2,2-dimethyl~4-(carboxy methoxy)-5,7-diiodo-
I,3-benzodio~ol in 25 ml of freshly distilled dimethylformamide.
On the next day a 33 % solution of methylamine in absolute etha-
nol is addedr until an alkaline reaction of the mixture occurs;
then the mixture is allowed to stand again over night. The solu-
tion is concentrated in vacuo and then precipitated with sa-tura-
~ted brine solution. The obtained precipitate is recrystallized
from ethanol/water. The dried 2,2-dimethyl-4-~N-methylcarbamyl-
methoxy)-5,7-diiodo-1,3-benzodioxol melts at 1~6-148.
E x a m p 1 e 21 : According to the process of Examplel6 2,2-
dimethyl-4-cyanomethoxy-1,3-benzodioxol in form of an orange
colored oil is obtained from the sodium salt of 2,2-dimethyl-
~-hydroxy -1,3-benzodioxol.
After addition of 0,1 q of sulfurin 20 ml of ethylene
diamine 10 g of this oil are heated for I hour to 100. The re-
sidue after evaporation of the reaction mixture is taken up intoacetic ester, the filtered solution is extracted several times
with water and then extracted with 2N HCl. The acid aqueous
phase is made alkaline by addition of NaOH and extracted with
chloroform. After evaporation of the chloroform solution dried
25 with dry Na2S04 a yellowish powder is obtained. By recrystalli-
zation from isopropanol the obtained 2,2-dimethyl-4-(~2-~midazo- ;
lin-2-yl-methoxy)-1,3-benzodioxol forms colorless plates melting
at 158-161. !'
E x a m p 1 e 22 : After addition of 0,4 g of benzyltriethyl-
amrnoniumchloride in 10 ml of buty] bromide 5 ~ of the sodium salt
H

~ 23~
- 18 -
of 2,2-dimethyl-4-hydroxy-5,7-dibromo-1,3-benzodioxol are stir-
red at 100 for 2 hours. The residue of the evaporation of the
reaction mixture is taken up into acetic ester, the solution
is washed with 1N NaOH and with water and then evaporated. The
5 remaining yellowish oil is 2,2-dimethyl-4-butoxy-5,7-dibromo-
1,3-benzodioxol having a refractive index nD3= 1,5468; on sili-
cagel 6G F 254 with the eluent chloroform/methanol (9 : 1) it
shows a Rf-value of 0,82.
E x a m p l e 23 : A solution of 10 g of 2,2-dimethyl-4-(2',3'-
epoxy-propoxy)-5,7-diiodo-1,3-benzodioxol obtained according
to Example 19 in 50 ml of ethanol is boiled with 2,2 g of 2-
amino-2~methyl-1,3-propane diol under reflux, until thin layer
chromatography ~see Examplell ) shows that the reaction is com-
pleted. Then the residue of the evaporation is taken up into
acetic ester, the solution is extracted first with water and
then with 2N HCl; any precipitating oil is brought again into
solution by addition of water. T~e acid aqueous solution is
treated with activated carbon, filtered, made alkaline with NaOH
and extracted with chloroform. After evaporation the chloroform
solution dried with dry Na2SO4 gives an oil which after dissol-
ving in acetic ester and adding of alcoholic ~Cl results in a
crystalline product. After recrystallization from isopropanol
or acetonitrile this product melts at 205-208 and is the hydro- ,.
chloride of 2,2-dimethyl-4-[3'-(~,r~-dihydroxymethyl-ethylamino)-
2'-hydroxy-prcpoxy] 5,7-diiodo-1,3-benzodioxol.
E x a m p l e 24 : 10,83 g of a 30 ~ methanolic NaOCH3-solution
are added dropwise to a solution of 10 g of 2,2-dimethyl-4-hydro- '
xy-li3-benzodioxol :ln 20 ml of methanol with stirring and then
evaporatr?d. The resldue is taken up into 15 ml oE chloroacetal-
dehyde dimethylacrtal and after addition of 1 g of tetrabutyl-
' ~

~3~1~1 , ;
-- 19 --
ammoniumbromide the mixture is hea-ted for several days under
reflux, until according to thin layer chromatography (silica-
gel 60 F 254, eluent: cyclohexane/acetone 3 : I) the reaction
is practically completed. ;'
The solution of the residue of evaporation in acetic
ester is washed with diluted NaOH, dried over dry Na2SO4, filte-
red after addition o~ activated carbon and evaporated. The oil
thus obtained is distilled (b.p. 155-157/12 Torr) and is 2,2~
dimethyl-4~l(2',2'-dimethoxy-ethoxy)-1,3-benzodioxol. Thin layer
chromatography shows a Rf-value of 0,44 and for the starting
material a Rf-value of 0,30. The refractive index of the obtained ;
dimethylacetal n24 = 1,4971.
E x a m p 1 e 25: By operating according to the method of Exam-'
ple 23 b~lt using 7,6 g of 2-amino-1,3-propandiol tSerinol) in-
stead of 2-amino-2-methyl-1,3-propandiol the hydrochloride of
2,2-dimethyl-4-[3'-(1",3"-dihydroxy-isopropylamino)-2'-hydroxy-
propoxy]-5,7-diiodo-1,3-benzodioxol is obtained, which is recry-
stalllzed from acetonitrile/methanol, m.p 190-195.
E x a m p l e 26 : 3,3 g of acetone oxime are added to a suspen-
sion of 10 g of the 2,2-dimethyl-4-(carboxy-methoxy)-1,3-benzodi-
oxol in 150 ml of CH2Cl2 obtained according to Examplell , where-
after is added dropwise a solution of 9,2 g of N,N-dicyclohexyl-
carbodiimide in 80 ml of CH2Cl2. According to thin layer chromato-
graphy (plate: silicagel 60 F 254, eluent: cyclohexane/acetone
1 : 1) the reaction is completed after 30 minutes. The residue
of evaporation is taken up into isopropylether, the precipitate
obtained over nic3ht ls sucked o~f and the ~:Lltrate i5 evaporated.
The crystalline xesldue i5 recrys~all;lzed ~rom lsopropyl ethel.
The acetone-0 (2,2-dlmethyl--1,3-benzodLoxol-4-oxyaaetyl)-oxi.me
khus obtained has a m.p~ of 73-75.
S~

~ ~33 1 ~ ~ `
- 20 -
The new pyrogallol ethers of the general formula (Ic)l ',
~R1
(Ic)
X ~ R~ 2
f - (cH2)n R5 .
l R4 :!
mentioned in the following table are obtained such as described
in examples l0 to 26O ;,~
= ' ~ ~
: R1, R2 = CH3 3, R4 H
__ __ __ _ ~ __
Br H Br O COOH 175-178 ;~
I. H I O COOH 198-200 ~ ~
Cl H H O COOH 118-120 ~ ;
- NO2 H H O COOH 123-125
.. H H NO2 COOH 165-167
H H H O ~ NH2 130-i.34
H H H O CO.N ~ -C~3 106-108
H H H O CHOH.CH2OH 68-70
~-- l
Cl H H O ~ J . HCl 195-205
N (Decomp.)
.~ __ _ ~ ~
R1, R2, R3~ R4 - CH3
-- -I ' ' I ~ ','
~r ll ¦ ~r O COOH 161-1G~
I ~l I O COOII 190~ 3 i;
, _~~