PYROCATECHOL ETHERS

ETHERS DE PYROCATECHINE

English Abstract

ABSTRACT OF THE DISCLOSURE
New and valuable pyrocatechol ethers having the
formula
<IMG>
where
R1 is hydrogen or lower alkyl; R2 is lower alkyl, lower alkyl
substituted by halogen, methoxy, ethoxy, or benzyl; R3 is phenyl,
lower alkyl, cycloalkyl, .beta.-chloroethyl, alkoxyalkyl, lower alkenyl,
lower alkynyl or acyl; R1 and R2 together with the carbon atom
whose substituents they are and R1 and R3 together with the carbon
or oxygen atom whose substituents they are denote a five-membered
or six-membered ring, and processes for their production. The
new compounds arc important intermediates for the production of
active ingredients for plant protection agents and pharmaceutical
and veterinary products.

Claims

The embodiments of the invention in which an exclusive
property or privilege is claimed are defined as follows:
1. A process for the production of a pyrocatechol
ether of the formula
<IMG>
where
R1 is hydrogen or lower alkyl; R2 is lower alkyl, lower alkyl
substituted by halogen, methoxy, ethoxy, or benzyl; R3 is phenyl,
lower alkyl, cycloalkyl, .beta.-chloroethyl, alkoxyalkyl, lower alkenyl,
lower alkynyl or acyl; R1 and R2 together with the carbon atom
whose substituents they are and R1 and R3 together with the carbon
or oxygen atom whose substituents they are denote a five-membered
or six-membered ring, wherein pyrocatechol is reacted, in the
presence of a catalytic amount of a substance having an acid
action, with a vinyl ether of the formula ROR3, where R is vinyl
or vinyl bearing lower alkyl and R3 has the above meanings, or,
in the presence of an organic or inorganic base, with an .alpha.-haloether
of the formula:
<IMG>
where Hal is Cl, Br or I and R1, R2 and R3 have the above meanings.
2. Process as claimed in claim 1, wherein the bisether
obtained and having the formula:
<IMG>
in which R1, R2 and R3 have the meanings given in claim 1 is
reacted with pyrocatechol.

3. Process as claimed in claim 1, characterized in
that pyrocatechol is reacted, in the presence of a catalytic
amount of a substance having an acid action, with vinyl methyl
ether to obtain O-(1-methoxyethoxy)-phenol.
4. Process as claimed in claim 1, characterized in
that pyrocatechol is reacted with twice the molar amount of vinyl
methyl ether to obtain pyrocatechol-bis-[(1-methoxy)-ethyl]-ether.
5. Process as claimed in claim 4, wherein pyrocatechol-
bis-[(1-methoxy)-ethyl]-ether obtained is reacted with pyrocate-
chol to obtain O-(1-methoxyethoxy)-phenol.
6. Process as claimed in claim 1, characterized in that
pyrocatechol is reacted, in the presence of a catalytic amount of
a substance having an acid action, with ethyl vinyl ether to obtain
O-(1-ethoxyethoxy)-phenol.
7. Process as claimed in claim 1, characterized in
that pyrocatechol is reacted with twice the molar amount of ethyl
vinyl ether to obtain pyrocatechol-bis-[(1-ethoxy)-ethyl]- ether.
8. Process as claimed in claim 7, wherein pyrocatechol-
bis-[(1-ethoxy)-ethyl]-ether is reacted with pyrocatechol to
obtain O-(1-ethoxyethoxy)-phenol.
9. Process as claimed in claim 1, characterized in that
pyrocatechol is reacted, in the presence of a base, with chlorome-
thyl methyl ether to obtain O-(methoxymethoxy)-phenol.
10. Process as claimed in claim 1, characterized in that
pyrocatechol is reacted, in the presence of a base, with chlorome-
thyl isopropyl ether to obtain O-(2-methoxy-isopropoxy)-phenol.
11. A pyrocatechol ether of the formula:
<IMG>
16

where
R1 is hydrogen or lower alkyl; R2 is lower alkyl, lower alkyl
substituted by halogen, methoxy, ethoxy, or benzyl; R3 is phenyl,
lower alkyl, cycloalkyl, .beta.-chloroethyl, alkoxyalkyl, lower alke-
nyl, lower alkynyl or acyl; R1 and R2 together with the carbon atom
whose substituents they are and R1 and R3 together with the carbon
or oxygen atom whose substituents they are denote a five-membered
or six-membered ring, whenever obtained by a process as claimed
in claims 1 or 2 or its obvious chemical equivalents.
12. O-(1-methoxyethoxy)-phenol whenever obtained by
a process as claimed in claims 3 or 5 or its obvious chemical
equivalents.
13. O-(1-ethoxyethoxy)-phenol whenever obtained by
a process as claimed in claims 6 or 8 or its obvious chemical
equivalents.
14. O-methoxymethoxyphenol whenever obtained by a
process as claimed in claim 9 or its obvious chemical equivalents.
15. O-(2-methoxyisopropoxy)-phenol whenever obtained
by a process as claimed in claim 10 or its obvious chemical
equivalents.
17

Description

103661Z o.z. 29,~8~ -
PYROCATECHOL ETHERS
The present invention relates to new and valuable pyrocate-
chol ethers and processes for their production.
German Patent No. 566,033 discloses that alcoholic or phenolic
hydroxyl groups are capable o~ reacting with vinyl ~r l-halo- ` ;
ethers with the ~ormation of acetals which are stable to alkali
(cf. also Houben-Weyl, "Methoden der organischen Chemie", -
volume 6/3, pages 186 and 229).
It is also known (for example ~rom B~J.Chem.Soc., 1927, 1664;
US Patent No. 3,202,573) that in an attempt to carry out a partial
alkylation of only one hydroxyl group of pyrocatechol this latter
and the alkylating agent are lost in considerable quantities due ~ :
to the formation, as byproduct, of the non~ploitable diether.
We have ~ound that the valuable new ethers o~ pyrocatechol
having the ~ormula (I): OH Rl
~ -o-C-oR3
in which
R is hydrogen or lower alkyl (Cl to C~);
R2 is unsubstituted or substituted (by halo~en (Cl, Br, I),
methoxy or ethoxy) lower alkyl (Cl to C3) or benzyl;
R3 is alkyl (Cl to C4), cycloalkyl (C3 to C7), ~-chloroethyl,
alkoxyalkyl (methoxyethyl, ethoxyethyl), alkenyl (up to C4),
alkynyl (up to C4), aoyl (acetyl); and moreover Rl and R2 to-
gether wlth the carbon atom whose substituents they are and
, .,
~ ''' ' .

o.z. 29,484
1(~3~i61Z
also Rl and R3 together with the carbon or oxygen atom whose
substituents they are, ~orm a ~ive-membered or six-membered ring
(cyclopentyl, cyclohexyl, tetrahydro~uranyl, tetrahydropyranyl)
are obtained in a simple manner and excellent yields when pyro-
catechol is reacted with pre~erably the amount required for ether-
ification of one hydroxyl group of pyrocatechol, or up to about
a 50% excess or deficiency o~ this amount, of a vinyl ether o~
the formula: 3
R-OR
where R is vinyl or vinyl bearing lower alkyl (up to C3) as a
substituent and R3 has the above meanings, with or without the
addition o~ a catalytically-acting substance such as an acid-
reacting substance, e.g. a mineral acid, acid salt, organic acid,
d~-haloether, organic or inorganic acid chloride, an ion exchanger
or a Lewis acid, ~or example AlCl~, FeCl3, BF3 and the like, in
a temperature range o~ ~rom -5C to 120C and pre~erably at 40
to 50C and/or with the addition of a solvent or diluent which
is inert to the reactants, ~or example an ether (diethyl ether,
tetrahydro~uran, dioxane), a hydrocarbon t~or example n-hexane,
benzene, toluene or xylene), halohydrocarbon (CH2Cl2, CHC13 or
20 cCl 4 ) .
The new compounds are important intermediates for the production
of active ingredients for plant protection ~gents and pharmaceutical
and veterinary produots.
I~ pyrocatechol is reacted wlth vinyl methyl ether, the
reaction may be illustrated by the following equation:
; ~ +HC-O-CH3 cata~st ~ CH
OCH3
-2-
': ,: ' ' -

O.Z. 29,4841036612
The abovementioned compounds are preferably used as catalysts.
The products according to the invention may also be prepared
by reaction of preferably equimolar amounts or an excess or de-
ficiency of up to about 50~ of an l-haloester of the formula: -
Rl .
Hal-C-OR3 ,
where Hal is Cl, Br or I and the radicals R1, R2 and R~ have the
above meanings, with a salt of pyrocatechol or with pyrocatechol ;
in the presence of an organic or inorganic base (for example an
alcoholate, alkali metal hydroxide, alkaline earth metal hydroxide
or suitable amIne~ or a substance having an alkaline reactionJ such
as an alkali or alkaline earth metal carbonate.
The followln~ equation illustrates the reaction:
~ + C1-C-OR -HCl ~ O-C-OR
The radicals R1, R2 and R3 have the above meanings. It is
preferred to dilute the reactants with a solvent, for example
from 5 to 80% by weight of an ether (diethyl ether, tetrahydro-
furan) or an aromatic hydro¢arbon (benzeneJ toluene, xylene).
The vinyl ethers and l-haloethers used for the reaction are
known from the llterature and are also readily prepared industrially
(cf. for example W. Reppe et al., Ann., 601, (1956), 98.
Depending on the excess of vinyl ether or l-haloether used in
20 the abovementioned processes there are formed corresponding amounts
of new bisethers of the formula (II). ~ -

O . Z . 29J 484
103661Z
' o 3
~2
R
(II).
-C -R
R2
me radicals R1, R2 and R3 have the above meanings.
The abovementioned bisethers may be prepared in quantitative
yields preferably by reaction o~ pyrocatechol with at least twice
the molar amount of a vinyl ether.
The catalysts and reaction conditions as regards temperature
and solvents are analogous to those given for the production of
compounds of formula (I).
Another process for the production of compounds of the formula
(I) consists in reacting a bisether of the formula (II) with pyro-
catechol according to the following equation:
o-l-oR3 OH OH
l ~ ~ cata~st)2 ~ o-C-oR3
o -C - oR3 R2
R2
(II) (I)
The radicals R1, R2 and R3J the catalysts and the reaction
conditions are the same as in the production of compounds of the
formula (I) from vinyl ethers.
The new pyrocatechol derivatives of the formulae (I) and (II)
are obtained in the form of colorless oils which after stabilization :
with organic or inorganic bases can be distilled in vacuo without -
-4- ;
~"''' ''
~':
~ .
! . ' . :. . .. ,. ~, . :

O.Z. 29,484
~036~ 2
decomposition. Compounds ~ ich may be prepared by the process
of the invention are listed below:
Formula (I):
-C-OR
Rl R2 R3 bp C; n25 :
D
H H CH3 bp(o,4 mm) 89 to 93
H H C2H5 bp(o 1 mm): 9 to 100
H CH3 CH3 P(.5 mm): 85 to 9o :
H CH3 C2H5P(l mm) 78 to 81 :.
CH3 n~C3H7bp(l mm): 96 to 98
H CH3 3 7bp(l mm): 89 to 94
H CH~; i-C4Hg P(0.2 mm) 9 9
H 3 ~3 bp(o 2 mm): 128 to 135
H CH3 -(~ bp(4 mm): 132 to 136
CH3 COCH3 nD5: 1.50'15
CH3 COC2H5 nD25: 1.4905
H CH3 -CH2-CH=CH2 5
~ ~ .
.... .

1~3661Z o.z. 29~484
Rl R2 R3 bp C; n25
H CH3 -CH2-C=CH
H CH3 CH3
H CH3 -CH2-CH2-OCH3
H CH3 2 2 2 5
HCH2Cl -CH3 nD5: 1.5135
HCH2Cl -C2H5 nD5: 1.5146
HCH2Cl -CH2-CH2Cl nD5: 1.4975
HCH2Cl COCH3 nD5: 1.5012
HCH2Br CH3 nD5: 1.5340
H CH2I 3
C2 5 CH3 bp(l 5 mm): 105 to 113
2 5 C2H5 bp(o 5 mm): lOO to 103
C2 5 CH2-C=CH
H CH2-CH2Cl CH3 ~ 5: 1.5023
CH2-CHcl-cH3 3
H CH2-CHBr-CH3 3
H CH2-CHCl-C2H5 CH3 ~ .
H n-C3H7 3 ~
-6- ~ :
~, ~

O.Z. 29,484
103661Z
Rl R2 R3 bp C; n25 - :
- .
H i-C3H7 3
H CH=CH2 3
H C--CH CH3
H CH2-C--CH 3
H CH2- ~ 3
3 3 CH3 bp (0.3 mm): 95 to 100
3 3 2 5
CH3 CH2Cl CH3 nD5: 1.5024
CH3 CH2Cl 2 5
CH3 CH2Br 3
CH3 CH2Br 2 5
3 2 5 3
3 3 7 CH~
CH3 i-C3H7 3
C2H5 C2H5 3
CH3
O OH 3
~ ~ R1 bp (0.5 mm) : 115 to 118
Formula (II) o-C-oR3
[~< F~l ' '.
o-c-oR3
R2 ':,
, .
: : .
' '

O.Z. 29,484
103661Z
Rl R2 R3 bp C
.
H H CH~ bp(o 4 mm): 105 to 109
H CH~ CH3 bp(o,5 mm): 99 to 105
H CH3 C2H5 P(0.3 mm) 97
H CH3 i-C4Hg bp(o 3 mm): 124 to 128
The new compounds are o~ great importance as precursors ~or
plant protection agents and pharmaceutical products.
~ or example by reaction of compounds o~ ~ormula (I) with
methyl isocyanate, active substances may be prepared which have
a good insecticidal action both on biting and sucking insects and
outstanding effectiveness against red spiders and ticks. At the
same tlme they have only slight phytotoxicity. The action is rapid
and prolonged. For this reason the active substances may be used
successfully in plant protection ~or cont~aling in~urious sucking
! lo and biting insects and Diptera and for combatting mites (Acarina)
both in this and the veterinary ~'ield. In this context emphasis
, may be placed on the excellent ef~ectiveness of the active sub-
stances against strains of red spiders which are resistant to
phosphoric esters. ~;
The following examples illustrate the invention.
.. . ..
, EXAMPLÆ l
!l o-(l-methoxv)-ethoxy~hen~l-N-meth~l carbamate:
34 parts by weight o~ o-(l-methoxy)-ethoxyphenol is dissolved
in 100 parts by weight of toluene. 12 parts by weight o~ methyl
,
isocyanate is poured in all at once. 2 drops of triethylamine are
added and the whole is le~t to stand overnight. The whole is then
-8- - ~;
, ~ :;: ': '
.:
`
: - . - ., .. , .. . :, . ,, . ,~ .

lQ3661Z o. z . 29, l~84
concentrated and to the oily residue there is added 100 parts
by weight of a mixture of equal parts of toluene and ligroin.
33 parts by weight of colorless crystals are precipitated upon
cooling. After recrystallization these crystals melt at 97 to
99C. ' ' - '
EXAMPLE 2
o-(1-ethox~)-ethoxyphen~l-N-meth~l_carbamate_
33.4 parts by weight of pyrocatecholmono-N-methyl carbamate
is suspended in 100 parts by weight of toluene. 3 drops of con-
centrated hydrochloric acid are added and then 15 parts by weight
of vinyl ethyl ether is dripped in over a period of ten minutes.
The whole is stirred for one hour at 80C. After cooling the
product is washed with 50 parts by weight of 3% sodium bicarbonate
solution and dried over sodium sulfate, and the solvent is re-
moved. A colorless oil remains which is taken up in 100 parts by
weight of a mixture of equal parts of toluene and ligroin. 31 parts
by weight of carbamate crystallizes out in the deep freezer. After
recrystallization the melting point is 62 to 63C.
The substances set out in the ~ollowing Table may be obtained
in a similar manner: 0-C0
¦ CH~
~ -o-C-R5
R7 R4 R5 R6 mp C
H CH~ H i-C3H7 40 to 45
C2H5 H CH3 88 to 90 -
H C2H5 ~2H5 52 to 54
3 7 H CH3

O.Z. 29,484
1~;)3661Z
R7 R4 R5 R6 mp. C
3 7 C2H5
H n-C4Hg H CH3
H n-C4Hg H C2H5
H i-C4Hg H CH3
n C4 11 H CH3
CH3 CH3 CH3 80 to 82
CH3 CH3 C2H5
H C2H5 CH3 CH3
CH3 CH3 H CH3
Other new active substances areCHas follows:
O-CON R7
~3 o\6~5 ~ ~
7 R4 R5 R6 mp. C (n25)
.
l H H CH2Cl C2H5 (1-5125)
H H CH2Cl COCH3 (1.5119)
CH3 H CH2Cl C2H5 (1.5205)
CH3 H CH2Br C~ (1.5310)
H H CH2Br CH3 70 to 72
H CH2I CH3 (1.5465)
CH H CH2 3
-
,~ -10- ' :'
,:

O.Z. 29,484
1~}3661Z ~:
R7 R4 R5 R6 mp C (n25)
H H CH2-CH2Cl CH3 65 to 66
CH3 H CH2-CH2C1 3 :-
H H CHCl-CH3 3
H H CHBrCH3 CH30
H H CH2-CH2Br CH3
H H CH20cH3 3
CH3 H CH2-0CH3 3
H H CH2-CH2-oCH3 CH3 (1.5184)
H H CH(OCH3)-CH3 3
H H COCH3 3
CH3 CH2Cl CH3 106 to 108
CH3 CH3 CH2Cl CH3
H CH3 CH2Br 3
3 CH3 CH2Br 3
H H CH2-SCH3 3
.
EXAMPLE 3
(a) o-(l-methoxyethox~-phenol: .
110 parts by weight o~ pyrocatechol is suspended in 100 .:
parts by weight of' toluene. At +5C 64 parts by weight of vinyl
methyl ether which has a temperature of` -40C is poured in all at
once and then 1 drop of' concentrated hydrochloric ac~d is added.
The whole is heated to about 120c while stirring, whereupon the
reaction commences and the temperature o~ the contents o~ the
~lask rises to about 65C. External cooling with ice-water may
--11- .

~ O.Z. 29J48l~
1036612
be applied if necessary. me whole is kept ~or half an hour at
65C and then 5 parts by weight of 2-normal caustic soda solution
is added. The whole is cooled, and dried by means o~ sodium
sulfate, and the solvent is evaporated in a rotary evaporator.
The product is distilled in vacuo. The yield is 155 parts by
weight. The boiling point is 85 to 90C at 0.5 mm.
Analysis: CgH120~ (168)
calculated: C 64.1 H 7.2
found: C 64.4 I~ 7.0
(b) pyrocatechol-bis- L(l-methoxy)-ethyl]-ether:
.
The reaction described under (a) is repeated but with twice
the amount (128 parts by weight) o~ vinyl methyl ether. 122 parts
by weight of a colorless oil is obtained having a boiling point
o~ 99 to 105 C at 0.5 mm. Analysis: C12H1804 (226)
calculated: C 6~.7 H 8.0 -
found: C ~3.~ H 8.1.
(c) o-(l-methox~ethox~)-phenol:
0.5 parts o~ SOCl2 is added to 113 parts by weight o~ pyro-
catechol-bis-~1-methoxy)-ethyl]-ether and 55 parts by weight o~
pyrocatechol at 40C and the whole is stirred at this temperature
for hal~ an hour. It is then allowed to cool and 2 parts by
20 volume of 25% by weight aqUeoUs caustio soda solution ls added.
The product is separated and dried over sodium sulfate and the
solvent is evaporated. There remains 168 parts o~ the abovemen-
tioned compound having a boiling point o~ 85 to 90C at 0.5 mm.
EXAMPLE 4
(a) o-(l-ethox~ethoxy~-phenol:
220 parts by weight o~ pyrocatechol is suspended in 200 parts
by weight of toluene. A~ter 2 drops of concentrated hydrochloric `
acid have been added 150 parts by weight o~ ethyl vinyl ether is
-12-

o~z~ 29J481~ .
10366~Z
dripped in while stirring. The internal temperature is prevented
from rising above 65C by external cooling with ice. A11 of the
pyrocatechol has dissolved upon completion of the reaction. 5
parts by weight of 2-normal caustic soda solution is added, the
whole is allowed to cool~ and dried over sodium sulfate, the
solvent is removed and the product is distilled in vacuo. The
` yield is almost quantitative; boiling point 78 to 81C at 1 mm;
i nD25= 1.5032
Analysis: C1oH1403 (182)
; 10 calculated: C 66.o H 7.7
found: C 66.3 H 7.9 -
(b) Pyrocatechol-bis- [(1-ethoxy)-ethyl~-ether:
The method of (a) is employed, except that 300 parts by weight
of ethyl vinyl ether is used instead of 150 parts by weight. 248
parts by weight of a colorless oil is obtained having a boiling
~, polnt of 97 to 102C at 0.3 mm.
Analysis: C14H2204 (254)
calculated: C 66.2 H 8.6
found: C 66.4 H 8.7. ;-
(c) o-(1-ethox~ethox~)-phenol:
127 parts by weight of pyrocatechol- [(1-ethoxy)-ethyl]-ether
and 55 parts by weight of pyrocatechol are reacted and processed
as described in Example 3(c). The yield is 179 parts of the phenol
compound, The boiling point is 79 to 80C at 1 mm.
EXAMPLE 5
o-(methoxymethox~)-phenol:
110 parts by weight of pyrocatechol is dissolved in 400 parts -
by weight of benzene. 101 parts by weight of triethylamine and
, ~: ' '
:
... . . ., . - . - - . - ~
. - . . ,, . ., ~
: - ~ :: - , - : -
.

` ` O.Z. 29,484
IV36612
81 parts by weight of chloromethyl methyl ether are dripped in
simultaneously at ambient temperature in such a manner that the
reaction medium has a weakly basic reaction. The whole is then
heated for another hour under re~lux; it is allowed to cool and
the hydrochloride is suction filtered, washed with water, dried
over sodium sulfate, concentrated and distilled in vacuo.
The yield is 120 parts by weight and the boiling point is 89C at
,,~
0.4 mm; nD'= 1.5150.
Analysis: CgHloO3 (154)
10 calculated: C 62.~ H 6.5 .
found: C 62.0 H 6.5 ~. :
-14- . :