CA1233181A - Ring-substituted derivatives of pyrogallol - Google Patents
Ring-substituted derivatives of pyrogallolInfo
- Publication number
- CA1233181A CA1233181A CA000427476A CA427476A CA1233181A CA 1233181 A CA1233181 A CA 1233181A CA 000427476 A CA000427476 A CA 000427476A CA 427476 A CA427476 A CA 427476A CA 1233181 A CA1233181 A CA 1233181A
- Authority
- CA
- Canada
- Prior art keywords
- hydrogen
- benzodioxol
- dimethyl
- nitro
- hydroxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/24—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms
- A01N43/26—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms five-membered rings
- A01N43/28—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms five-membered rings with two hetero atoms in positions 1,3
- A01N43/30—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms five-membered rings with two hetero atoms in positions 1,3 with two oxygen atoms in positions 1,3, condensed with a carbocyclic ring
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
- A01N43/38—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/84—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/64—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- G—PHYSICS
- G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
- G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
- G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
- G03F7/004—Photosensitive materials
- G03F7/027—Non-macromolecular photopolymerisable compounds having carbon-to-carbon double bonds, e.g. ethylenic compounds
- G03F7/028—Non-macromolecular photopolymerisable compounds having carbon-to-carbon double bonds, e.g. ethylenic compounds with photosensitivity-increasing substances, e.g. photoinitiators
- G03F7/031—Organic compounds not covered by group G03F7/029
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Plant Pathology (AREA)
- Agronomy & Crop Science (AREA)
- Environmental Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Dentistry (AREA)
- Pest Control & Pesticides (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- General Physics & Mathematics (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
ABSTRACT
Pyrogallol derivatives of general formula:
wherein R1 and R2 may be the same or different and re-present hydrogen or lower alkyl, R represents hydrogen or a group 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
Pyrogallol derivatives of general formula:
wherein R1 and R2 may be the same or different and re-present hydrogen or lower alkyl, R represents hydrogen or a group 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
Description
~ 2 ~
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 - C - (C~2)n~R5;
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~
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 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: `.
'''''
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 - C - (C~2)n~R5;
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~
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 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 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~
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 ~ ~
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 ~
-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:
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~ !
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 ~
-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~
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 , ;
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 ~ ~ `
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 ~ ;
.. 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;
, _~~
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 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~
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 ~ ~
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 ~
-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:
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~ !
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 ~
-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~
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 , ;
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 ~ ~ `
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 ~ ;
.. 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;
, _~~
Claims (39)
1. New pyrogallol derivatives of general formula:
(I) wherein R1 and R2 may be the same or different and represent hydrogen or lower alkyl, R represents hydrogen or a group 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 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 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.
(I) wherein R1 and R2 may be the same or different and represent hydrogen or lower alkyl, R represents hydrogen or a group 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 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 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.
2. New pyrogallol derivatives according to claim 1 and of general formula:
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.
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.
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.
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:
(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.
(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.
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.
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:
(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.
(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.
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.
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 CHOH. CH2OH
and .
and .
38. A process for preparing pyrogallol ethers of the general formula (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:
wherein X, Y, Z, R1 and R2 are as defined above, or a phenolate thereof, with a compound of the general formula 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 halogenation and/or nitration agents.
wherein X, Y, Z, R1 and R2 are as defined above, or a phenolate thereof, with a compound of the general formula 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 halogenation and/or nitration agents.
39 . A process for preparing pyrogallol derivatives of general formula:
(I) wherein R1 and R2 may be the same or different and represent hydrogen or lower alkyl, R represents hydrogen or a group 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 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;
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:
(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 b) when R in formula (I) represents said group:
reacting a pyrogallol derivative of formula:
wherein X, Y, Z, R1 and R2 are as defined above, or a phenolate thereof, with a compound of the general formula 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.
(I) wherein R1 and R2 may be the same or different and represent hydrogen or lower alkyl, R represents hydrogen or a group 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 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;
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:
(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 b) when R in formula (I) represents said group:
reacting a pyrogallol derivative of formula:
wherein X, Y, Z, R1 and R2 are as defined above, or a phenolate thereof, with a compound of the general formula 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.
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ATA1888/82 | 1982-05-13 | ||
| AT188882A AT375654B (en) | 1982-05-13 | 1982-05-13 | METHOD FOR PRODUCING NEW PYROGALLOL [THERS AND THEIR SALTS |
| AT467182A AT375360B (en) | 1982-12-23 | 1982-12-23 | METHOD FOR PRODUCING NEW 1,3-BENZODIOXOL DERIVATIVES AND THEIR SALTS |
| ATA4671/82 | 1982-12-23 | ||
| AT129883A AT378191B (en) | 1983-04-12 | 1983-04-12 | METHOD FOR PRODUCING NEW PYROGALLOLAETHER DERIVATIVES |
| ATA1298/83 | 1983-04-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1233181A true CA1233181A (en) | 1988-02-23 |
Family
ID=27147336
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000427476A Expired CA1233181A (en) | 1982-05-13 | 1983-05-04 | Ring-substituted derivatives of pyrogallol |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0095454A3 (en) |
| JP (1) | JPS58206581A (en) |
| AU (1) | AU566107B2 (en) |
| CA (1) | CA1233181A (en) |
| DK (1) | DK210483A (en) |
| NO (1) | NO831680L (en) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4472427A (en) * | 1980-12-23 | 1984-09-18 | Merck & Co., Inc. | (Aralkylamino-2-OR-propoxy)heterocyclic compounds |
| US5541204A (en) * | 1994-12-02 | 1996-07-30 | Bristol-Myers Squibb Company | Aryloxypropanolamine β 3 adrenergic agonists |
| SG99290A1 (en) * | 1996-04-09 | 2003-10-27 | Nps Pharma Inc | Calcilytic compounds |
| US6818660B2 (en) | 1996-04-09 | 2004-11-16 | Nps Pharmaceuticals, Inc. | Calcilytic compounds |
| TW483881B (en) | 1996-12-03 | 2002-04-21 | Nps Pharma Inc | Calcilytic compounds |
| US7202261B2 (en) | 1996-12-03 | 2007-04-10 | Nps Pharmaceuticals, Inc. | Calcilytic compounds |
| IT1304513B1 (en) * | 1998-12-30 | 2001-03-19 | Endura Spa | PROCESS FOR THE SYNTHESIS OF 5- (ALPHA-HYDROXIALKYL) BENZO (1,3) DIOXINS. |
| SE9902987D0 (en) | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
| FR2798126B1 (en) * | 1999-09-08 | 2001-10-19 | Sanofi Synthelabo | HETEROARYLOXYPROPANOLAMINES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
| FR2802533B1 (en) * | 1999-12-17 | 2002-02-15 | Sanofi Synthelabo | PHENOXYPROPANOLAMINES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
| FR2802529B1 (en) * | 1999-12-17 | 2004-07-30 | Sanofi Synthelabo | PHENOXYPROPANOLAMINES, PROCESS FOR PREPARING SAME AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME |
| JP4782342B2 (en) * | 1999-12-17 | 2011-09-28 | サノフィ−アベンティス | Phenoxypropanolamines, processes for their production and pharmaceutical compositions containing them |
| FR2802531B1 (en) * | 1999-12-17 | 2002-02-15 | Sanofi Synthelabo | PHENOXYPROPANOLAMINES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
| CO5300399A1 (en) | 2000-02-25 | 2003-07-31 | Astrazeneca Ab | HETEROCICLIOCS CONTAINING NITROGEN, PROCESS FOR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
| US7005439B2 (en) | 2000-06-20 | 2006-02-28 | Astrazeneca Ab | Compounds |
| AR028948A1 (en) | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | NEW COMPOUNDS |
| GB0104050D0 (en) | 2001-02-19 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| AR035230A1 (en) | 2001-03-19 | 2004-05-05 | Astrazeneca Ab | BENCIMIDAZOL COMPOUNDS, PROCESS FOR PREPARATION, PHARMACEUTICAL COMPOSITION, PROCESS FOR THE PREPARATION OF SUCH PHARMACEUTICAL COMPOSITION, AND USES OF THESE COMPOUNDS FOR THE PREPARATION OF MEDICINES |
| GB0107228D0 (en) | 2001-03-22 | 2001-05-16 | Astrazeneca Ab | Chemical compounds |
| SE0101038D0 (en) | 2001-03-23 | 2001-03-23 | Astrazeneca Ab | Novel compounds |
| SE0103818D0 (en) | 2001-11-15 | 2001-11-15 | Astrazeneca Ab | Chemical compounds |
| SE0301369D0 (en) | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Chemical compounds |
| TW200738634A (en) | 2005-08-02 | 2007-10-16 | Astrazeneca Ab | New salt |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3726924A (en) * | 1971-03-26 | 1973-04-10 | Hoffmann La Roche | Method for the preparation of tris (dimethylamino) methane |
| USRE27822E (en) * | 1971-07-06 | 1973-11-27 | Substituted phenoxy-z-hydroxy- j-isopropylamino-propanes | |
| DE2816474A1 (en) * | 1978-04-15 | 1979-10-25 | Bayer Ag | DICHLORBENZODIOXOL DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS SYNERGIS IN INSECTICIDES AND ACARICIDES |
-
1983
- 1983-05-02 EP EP83890068A patent/EP0095454A3/en not_active Withdrawn
- 1983-05-04 CA CA000427476A patent/CA1233181A/en not_active Expired
- 1983-05-10 AU AU14409/83A patent/AU566107B2/en not_active Ceased
- 1983-05-11 NO NO831680A patent/NO831680L/en unknown
- 1983-05-11 DK DK210483A patent/DK210483A/en not_active Application Discontinuation
- 1983-05-12 JP JP58081827A patent/JPS58206581A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AU1440983A (en) | 1983-11-17 |
| JPS58206581A (en) | 1983-12-01 |
| NO831680L (en) | 1983-11-14 |
| EP0095454A3 (en) | 1985-04-03 |
| AU566107B2 (en) | 1987-10-08 |
| DK210483D0 (en) | 1983-05-11 |
| EP0095454A2 (en) | 1983-11-30 |
| DK210483A (en) | 1983-11-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1233181A (en) | Ring-substituted derivatives of pyrogallol | |
| Tauer et al. | Photochemical and thermal reactions of aromatic Schiff bases | |
| Cole et al. | An improved method for the synthesis of 2, 2-disubstituted and 2-monosubstituted 1, 3-benzodioxoles | |
| EP0375670B1 (en) | Process for preparing 3-polyfluoroalkylisoxazolylamines | |
| Badadhe et al. | Synthesis and characterization of some novel isoxazolines and pyrazolines as potent antimicrobial agents | |
| CA1237726A (en) | 2-amino-1-(1,3-dioxolan-4-yl)-ethanol compounds, their preparation and use | |
| US4954659A (en) | 1,4-bis (dihydroxyphenyl) butane and analogs | |
| US4212808A (en) | 2-Oxiranyl-1,4-benzodioxans | |
| US4762648A (en) | Monofunctional and bisfunctional anthraquinone-(oxy-2,3-oxidopropanes), processes for their preparation, and their use as drugs | |
| Buu-Hoë et al. | Carbazole aldehydes | |
| Durden et al. | The Reaction of Azidoörganic Compounds with Acetylenes. | |
| OHISHI et al. | Reactions of salicylaldehydes with bromonitromethane | |
| US2353687A (en) | Cyanoaldehydes and process of producing them | |
| US6686466B2 (en) | Photochromic oxazine compounds and methods for their manufacture | |
| JP5408820B2 (en) | 5,6,7,8-Tetra-substituted-1,4-dialkoxy-2,3-dicyano-naphthalene derivatives | |
| JPS62158269A (en) | Pyrethroid, manufacture, pesticide and precursor for manufacturing same | |
| US4020071A (en) | Derivatives of 1-phenoxy-3-amino-propan-2-ol | |
| Somayajulu et al. | Search for physiologically active compounds: Part VIII. Synthesis of benzoxazoles from o-aminophenols and aromatic aldehydes | |
| AU2002354049A1 (en) | Photochromic oxazine compounds and methods for their manufacture | |
| JPH0419991B2 (en) | ||
| US3092653A (en) | 2-(substituted-benzyl)-1, 3-propane-dinitriles | |
| Roy et al. | A Simple and New Synthetic Method for the Preparation of 2-Pheynl-6-substituted Quinolines | |
| US2530831A (en) | Alkylene-bridged 5, 6-dihydroxyquinolines | |
| KR101916106B1 (en) | Synthetic method for 2,5-diaryloxazole compounds and anti-inflammatory pharmaceutical compounds containing the 2,5-diaryloxazole compounds | |
| He et al. | Synthesis and Characterization of Novel Stilbene Derivatives with 1, 3, 4‐Oxadiazole Unit |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |