GB2039474A - Process for preparing organothio-aldoximes - Google Patents
Process for preparing organothio-aldoximes Download PDFInfo
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- GB2039474A GB2039474A GB7901755A GB7901755A GB2039474A GB 2039474 A GB2039474 A GB 2039474A GB 7901755 A GB7901755 A GB 7901755A GB 7901755 A GB7901755 A GB 7901755A GB 2039474 A GB2039474 A GB 2039474A
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Abstract
A process for preparing 1- organothio-aldoxime compounds by halogenating the corresponding aldoxime in an aqueous solvent containing from 5 to 75 per cent by weight of a linear or cyclic polyhydric alcohol containing two or more hydroxyl groups and from 2 to 20 carbon atoms, and reacting the resulting 1-haloaldoxime with the sodium salt of a mercaptan. Some of the compound prepared in accordance with the process of the inventions are valuable intermediates in the preparation of other compounds that exhibit outstanding insecticidal, nematocidal and miticidal activity.
Description
SPECIFICATION
A process for preparing organothio- aldoxime compounds
This invention relates to an improved process for preparing 1-organothio-aldoxime compounds. More particularly, this invention is directed to a process for preparing 1 - organothio - aldoxime compounds by halogenating the corresponding aldoxime in an aqueous solvent containing from 5 to 75 per cent by weight of a linear or cyclic polyhydric alcohol containing two or more hydroxyl groups and from 2to 20 carbon atoms, and reacting the resulting 1-haloaldoxime with the sodium salt of a mercaptan.
1-Organothio-aldoxime compounds and their preparation by the chlorination of an aldoxime followed by reaction with a sodium mercaptide are well known. United States Patents Nos. 3,658,869 and 3,535,361 disclose a two-step preparation of organothio-aldoxime compounds by the chlorination of an aldoxime in an aqueous medium followed by the reaction of the resultantchloroacetaldoxime with a thiol. The main drawback of such prior art processes is the low yield of the desired product.
United States patent No. 3,752,841 discloses an improvement of the basic process in which the reaction medium is dimethylformamide or an aqueous mixture containing at least ten weight percent dimethyl-formamide. This process also suffers from a number of inherent disadvantages. The separation problems of the 1 -hydrocarbylthioaldoxime compounds are complicated by the use of the dimethylformamide since these compounds are very soluble in dimethylformamide. This makes it necessary to use costly, elaborate and cumbersome purification procedures, such as distillation and/or solvent extraction to isolate the final product.
It is, therefore, the object of this invention to provide a more effective process for preparing 1-organothioaldoxime compounds in enhanced yields.
According to the present invention there is provided an improved process for preparing a compound of the general formula:
wherein:
R1 and R2 are each individually an alkyl, alkoxyalkyl, cycloalkyl, phenyl or phenylalkyl group, all of which may be either unsubstituted or substituted with one or more halo, cyano, nitro or dialkylamino substituents, in which an aldoxime of the formula
R1CH= NOH is reacted with a halogen to form the corresponding 1-haloaldoxime and the 1-haloaldoxime is reacted with the sodium mercaptide salt of a compound of the formula R2SH, the improvement which comprises conducting the reaction in an aqueous solution containing from 5 to 75 per cent of a linear or cyclic polyhydric alcohol containing from 2 to 20 carbon atoms.
The halogenation step to form the 1-haloaldoxime reactant is conveniently performed by reacting the halogen and the aldoxime in an aqueous reaction medium containing from 5 to 75 weight percent of a linear or cyclic polyhydric alcohol. The formation of by-products is minimized by this process and the resulting products can be purified without resorting to elaborate and costly purification techniques.
Useful polyhydric alcohols are those containing from 2 to 20 carbon atoms. Examples of useful polyhydric alcohols are ethylene glycol, glycerol, erythritol, arabitol and sorbitol. The concentration of polyhydric alcohols in the reaction solvent may vary from 5 to 75 per cent by weight, based on the total weight of water employed. Preferred polyhydric alcohol concentrations are from 10 to 50 per cent by weight.
In general aldoxime reactants that are useful in the conduct of the process of this invention are well known to those skilled in the art. The aldoxime may be either an unsubstituted or substituted alkyl, cycloalkyl, alkoxyalkyl aryl or aralkyl compound. Examples ofthese aldoxime reactants are alkanaldoximes such as acetaldoxime, propionaldoxime, isobutyraldoxime and n-valeraldoxime. Also useful are the cyclic aldoximes and aromatic aldoximes, i.e. those compounds in which R1 is a cyclic group such as cyclohexane, cyclopentane and cycloheptane; an alkoxyalkyl group such as methoxymethyl, ethoxymethyl and proproxymethyl; or an aromatic group such as benzene, p-methylbenzene, p-ethylzenzene, benzyl and phenethyl.As previously noted these radicals may be suitable substituted with non-reactive functional groups, e.g., cyano, halo, nitro or alkyl groups.
The quantity of aldoxime employed is from 5 to 75 per cent by weight, based on the total weight of the solvent. The preferred amount is from 10 to 25 weight per cent. Greater amounts of solvent can of course be used, but these amounts merely dilute the components in the reaction mixture with no particular advantage being obtained.
The aldoxime compounds utilized as reactants in the process of this invention can be conveniently prepared according to conventional methods. For example, these compounds can be conveniently prepared by reacting an appropriate aldehyde with a hydroxylamine salt, optionally in the presence of an alkali metal hydroxide or carbonate. Another method involves reacting the corresponding aldehyde in a water medium with sodium nitrite, sodium bisulfite and sulfur dioxide.
In general, the aldoxime reactant will be reacted with a stoichiometric quantity of the halogen; however, more than or less than the stoichiometric amount of the halogen may also be employed. In the preferred embodiments of this invention the quantity of halogen may vary from the stoichiometric amount by from plus or minus one per cent.
The 1-haioalkoxime intermediate of the halogenation step may be isolated and purified for use at some latertime or it may be reacted with the mercaptide salt without purification or isolation. If the 1-haloaldoxime intermediate is employed in an in situ process, i.e. without isolation and/or purification, the stoichiometric amount of by-product hyd rogen chloride must be neutralized at some later point during the reaction.
The mercaptide salts utilized as reactants in the process of this invention, as well as their method of preparation, are well known to those skilled in the synthetic arts. The mercaptide salt reactant can be conveniently prepared by treating the corresponding mercaptan with an inorganic base.
The base employed should be of sufficient basicity and quantity to form a salt of the mercaptan. In addition an additional quantity of base may be added at the juncture in an amount sufficiently to neutralize the halogen halide produced in the second step of the process. The additional quantity of base may also be added after the addition of mercaptide salt to the reaction mixture.
Useful mercaptan (thiols) include the alkyl mercaptans such as methyl mercaptan, ethyl mercaptan, propyl mercaptan, isopropyl mercaptan, hexyl mercaptan, isobutyl mercaptan, pentyl mercaptan and decyl mercaptan. Other useful mercaptans are those in which R2 is a cyclic group such as cycloheptane, cyclohexane, cyclopentane or cyclobutane; those in which R2 is an alkoxyalkyl group such as a methoxymethyl, propoxymethyl or methoxyethyl group; or those in which R2 is an aromatic group such as benzene, 2-methylbenzene, 3-alkoxybenzene, a benzyl or a phenethyl group. As previously noted these radicals may be suitably substituted with non-reactive functional groups such as a halogen, cyano, alkyl or nitro group.
Suitable organic bases include the alkali metal alkoxides such as sodium methoxide and sodium ethoxide.
Useful inorganic bases include the alkali metal and the alkaline earth metal carbonates such as lithium, sodium, potassium, calcium and barium carbonate; the alkali metal bicarbonates such as sodium bicarbonate and potassium bicarbonate; the alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide. Inorganic bases are preferred for use in the process of this invention.
The mercaptide salt reactant may be generated outside the presence of the aldoxime reactant and used at some latter date. Alternatively, the mercaptide salt reactant may be generated in-situ, i.e. in presence of the aldoxime reactant.
In general, the 1-haloaldoxime reactant is reacted with a stoichiometric quantity of the mercaptide salt, although, it should be understood that the quantity of mercaptide salt employed can vary from stoichiometric to as much as a 50 per cent excess. In the preferred embodiments of this reaction the quantity of mercaptide salt employed will vary from stoichiometricto plus 10 percent.
The reaction temperature for the halogenation and the mercaptide addition steps is not critical and can be varied over a wide range. The reactions can be conducted at a temperature in the range of from -20 C to 40"C. Preferred reaction temperatures are from -lOCto 15"C; with particularly preferred reaction temperatures being from 00C to - 1 0,C. At temperatures below -20 C. the rate of reaction becomes
markedly slower, while at temperatures above 40"C.
product degradation and side reaction may occur.
Reaction pressures are not critical. The process of this invention can be conducted at either subatmospheric, atmospheric or superatmospheric pressures.
For convenience, the reaction is usually conducted at atmospheric or autogenous pressure.
The process of this invention is carried out over a period of time sufficient to produce the desired 1-organoaldoxime compound in an adequate yield.
In general, residence times can vary from a few minutes to 24 hours or longer. In most instances, when employing preferred reaction conditions, reaction times will be found to vary from 2 hours to 3 hours. Reaction time is influenced to a significant degree by the reactants; the reaction temperature; the concentration and choice of base; the choice and concentration of reaction solvent and by other factors known to those skilled in the art.
The process of this invention can be conducted in a batch, semi-continuous or continuous fashion. The reaction can be conducted in a single reaction zone or in a plurality of reaction zones, in series or in parallel or it may be conducted intermittently or continuously in an elongated tubular zone or series of such zones. The materials of construction employed should be inert to the reactants during the reaction and the fabrication of the equipment should be able to withstand the reaction temperatures and pressure.
The reaction zone can be fitted with one or more internal and/or external heat exchanger(s) in order to control undue temperature fluctuations, orto prevent any possible "runaway" reaction temperatures.
In preferred embodiments of the process, agitation means to vary the degree of mixing the reactions mixture can be employed. Mixing by vibration, shaking, stirring, rotation, oscillation, and ultrasonic vibration are all examples of the type of agitation means contemplated. Such means are available and well known to those skilled in the art.
The reactants and reagents may be initially introduced into the reaction zone batchwise or it may be continuously or intermittently introduced in such zone during the course of the process. Means to introduce and/or adjust the quantity of reactants introduced, either intermittently or continuously into the reaction zone during the course of the reaction can be conveniently utilized in the process especially to maintain the desired molar ratio of the reaction solvent, reactants and reagents.
Various embodiments of the present invention will now be described in the following Examples.
EXAMPLE I
Procedure: Acetaldoxime (309., 0.5 mole) was dissolved in 200 g. of a solvent mixture containing 175
g. of water and 25 g. of ethylene glycol, and the solution was cooled to -5 to -10 C. Over a period of
20-30 minutes, 30 g. of chlorine was introduced to the solution with good agitation. During chlorination, the reaction temperature was maintained at -5
to -10 C. An additional 6 g. of chlorine was added in
10 minutes. The mixture was stirred for 10-15 minutes at -1 lOOC A sodium methyl mercaptide sol- ution was prepared by dissolving methyl mercaptan
(25 g., 0.52 mole) in a caustic solution containing 40
g. of sodium hydroxide in 100 g. of water.The mer
captide solution was fed directly into the acethyd
roxamoyl chloride solution at -100C. over a 15-20
minute period. The reaction mixture was stirred for an additional 15 minutes and then neutralized to pH 7.5 with a 50-percent caustic solution. The crystalline methyl hydroxythioacetimidate was recovered at -10 C by filtration. The methyl hydroxythioacetimidate was reslurred in hexane, filtered and dried to obtain 47 gram of methylhydroxythioacetimidate mp 87-89"C. This represented a 90% yield.
EXAMPLE II
Procedure: Hydroxylamine hydrochloride (35 g., 0.5 mole) was dissolved in an aqueous mixture consisting of 140 g. of water and 25 g. of ethylene glycol.
The mixture was kept at 10-20"C. while adding dropwise a solution of acetaldehyde (22 g., 0.5 mole) in 22 g. of water and caustic solution containing 20 g.
of sodium hydroxide (0.5 mole) in 40 g. of water simultaneously. Afterthe addition was completed, the reaction mixture was stirred at 10-25"C. for one hour longer. The reaction mixture was then cooled to -5 to - 1 00C. and 36 g. of chlorine was introduced over a period of 30-40 minutes. The reaction mixture was stirred for 15 minutes longer at -10"C. while a sodium methyl mercaptide solution was prepared by dissolving methyl mercaptan (25 g., 0.52 mole) in a caustic solution containing 40 g. of sodium hydroxide in 100 g. of water. The mercaptide solution was fed directly into the acethydroxamoyl chloride solution at - 10 C over a 15-20 minute period.The reaction mixture was stirred for an additional 15 minutes and then neutralized to pH 7.5 with a 50-percent caustic solution. The crystalline methyl hydroxythioacetimidate was recovered at - 10 C by filtration. The wet product, after being sucked as dry as possible on the Buchnerfunnel, was re-slurried in hexane. Methyl hydroxythioacetimidate, afterfiltration and drying, was obtained in 82 per cent yield based on acrtaldehyde having a melting point of 88-90"C.
The reactions of Examples Ill to XV were conducted utilizing the procedure of Example I. In these examples, 0.50 moles of acetaldoxime; 0.50 moles of chlorine; 1.00 moles of sodium hydroxide and 0.52 moles of methyl mercaptan were the reactants, except as noted in TABLE I. The three reaction solvents employed were ethylene glycol (ETG) and water; glycerol (GLC) and water and sorbitol (SBL) and water.
TABLEI
Reaction Solvent % Yield Wgt.% Wgt.% Reaction Reaction b of Melting Ex polyol H2O Temperature Time (min) Oxime Point C.
Ill 75% ETGC 25 -5 to -10 70 78 87-89 IV 50%ETGC 50 -5to -10 70 84 85-87 V 25%ETGC 75 -5 to -10 70 87 87-89 VI 12%ETGC 88 -5to -10 70 90 87-89 VII 5%ETGC 95 -5 to -10 70 84 87-89 VIII 12%ETGC 88 -2to+ 2 70 86 87-89 IX 12% ETGC 88 10 70 77 88-89 X 12% ETGC 88 20 70 69 88-89 XI 12% ETGC 88 -2to+ 2 120 81 88-89 Xlla 12% ETGC 88 -5 70 86 86-88 XIII 25% SBLd 75 -5 to -10 70 86 88-90 XIV 25% GCLe 75 -5 to -10 70 90 88-90 XV r 43% SBLd 57 -5to -10 70 89 88-91 a .70 moles of methyl mercaptan b The reaction time is for the chlorination step; the second step required about one hour c ETG is an abbreviation for ethylene glycol d SBL is an abbreviation for sorbitol e GLC is an abbreviation for glycerol
To demonstrate more particularly the increased efficiency of the process of this invention in comparison with known processes, the experimental results of representative examples of this invention were compared with the experimental results from two examples of known processes. The comparison data is set forth in TABLE I below. The known processes were conducted using water as the reaction solvent as described in Examples XVI and XVII below:
EXAMPLEXVI
Procedure: Acetaldoxime (30 9., 0.5 mole) was dissolved in 200 g. of water and the solution cooled to -5 to -10"C. Over a period of 20 to 30 minutes, 30 g.
of chlorine was introduced into the solution with agitation. During the chlorine addition, the reaction temperature was maintained at -5 to -100C.An additional 6 grams of chlorine was added in 10 minutes. The mixture was stirred for 10-15 minutes at -10 C. A sodium methyl mercaptide solution was prepared by dissolving methyl mercaptan (259, 0.52 mole) in a caustic solution containing 40 g. of sodium hydroxide in 100 g. of water. The mercaptide solution was fed directly into the reaction mixture
over a 15 to 20 minute time period while maintaining
the temperature at - 10 C. The reaction mixture was
stirred for an additional 15 minutes and then neutral
ized to a pH 7.5 by addition of 50% sodium hydroxide
solution.Crystaline methyl hydroxythioacetimidate
was recovered at -10'C by filtration. The product
was re-slurried in hexane, filtered and dried to obtain
43 grams (83% yield) of methyl hydroxythioacetimi
date, mp 87-88"C.
EXAMPLE XWI Procedure: Acetaldoxime (30 g, 0.5 moles) was dis
solved in 1259. of water and the solution was cooled
to -10 to 0 C. Chlorine (35.5g,0.5 mole) was intro
duced over a period of 15 minutes at a pH of 5-6. The
reaction mixture was then added over a period of 10
minutes at -10"C. to an aqueous solution of sodium
methyl mercaptide, prepared by adding methyl mer
captan (259,0.52 moles) to sodium hydroxide g., 0.37 moie) in water (250 g.) at 0 C. The solid precipi
tate was formed and the resulting mixture was
highly acidic.The product was filtered, washed with
a little ice-water and dried to give 29 9. (56% yield) of
crystalline methyl hydroxythioacetamidate, m.p.
91 -93'C.
The data presented in TABLE I hereinabove clearly
illustrated the greatly increased efficiency of the
peracid oxidation process of this invention in com
parison with known processes. For example, the
known processes of EXAMPLES XVI and XVII which
were conducted without a polyhydric alcohol solvent
had yields of 83 and 56 per cent respectively. These
results are to be contrasted with EXAMPLES I, XIV
and XV which employ the process of this invention.
Note that the aldoxime product of EXAMPLES I, XIV
and XV was produced in an 90,90 /O and 88% yield,
respectively, and thus, for all practical purposes
quantitative. This represents a significant increase in
yield of the 2-organothioaldoxime compound.
The aldoxime compounds prepared in accordance
with the process of this invention have wide utility
and are valuable for a number of useful purposes.
Some of the compound prepared in accordance with
the process of the inventions are valuable inter
mediates in the preparation of other compounds that
exhibit outstanding insecticidal, nematocidal and
miticidal activity. Thus, for example,
O-(methylcarbamoyl) thioacetylhydroxamate, an
outstanding pesticide, may be conveniently pre
pared utilizing compounds prepared in accordance
with this invention as an intermediate. It should be
pointed out, however, that other aldoxime com
pounds prepared by the process of this invention are
not limited to use as intermediates in the preparation
of pesticidal compounds, but in addition are
extremely useful for other purposes which are
known to those skilled in the art.
Claims (11)
1. A process for preparing a compound of the
general formula: l
wherein:
R, and R2 are each individually an alkyl, cycloalkyl, phenyl orphenylalkyl group, all of which may be either unsubstituted or substituted with one or more alkyl, halo, alkoxy, cyano, nitro or dialkylamino substituents; which process comprises reacting an alkoxime of the formula R CH= NOH wherein R, is as defined above with a halogen to form the corresponding 1-haloaldoxime, and reacting the 1-haloaldoxime with the salt of a compound of the formula R2SH, wherein R2 is as defined above, wherein the reaction is conducted in an aqueous solution containing from 5 to 75 percent by weight of a linear or cyclic polyhydric alcohol containing from 2 to 20 carbon atoms.
2. A process as claimed in claim 1 wherein the polyhydric alcohol is ethylene glycol, glycerol, sorbitol, erythritol or arabitol.
3. A process as claimed in claim 1 or claim 2 wherein the aqueous solution contains from 10 to 50 per cent by weight of the polyhydric alcohol, based on the total weight of water.
4. A process as claimed in claim 3 wherein the aqueous solution contains from 10 to 35 per cent by weight of the polyhydric alcohol, based on the total weight of water.
5. A process as claimed in any one of the preceding claims which is conducted at a temperature of from -10'Cto 15"C.
6. A process as claimed in claim 5 which is conducted at a temperature of from - 10 C to 0 C.
7. A process as claimed in any one of the preceding claims wherein R1 and R2 are individually a cyanoalkyl or nitroalkyl group containing from one to eight carbon atoms.
8. A process as claimed in any one of claims 1 to 6 wherein R1 and R2 are each individually a methyl, ethyl or propyl group.
9. A process as claimed in claim 1 substantially as hereinbefore described.
10. A process as claimed in claim 1 substantially as hereinbefore described in any one of Examples I to XV.
11. A 1 -organothio-aldoxime compound when prepared by a process as claimed in any one of the preceding claims.
Priority Applications (1)
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GB7901755A GB2039474B (en) | 1979-01-17 | 1979-01-17 | Process for preparing organo thioaldoximes |
Applications Claiming Priority (1)
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GB7901755A GB2039474B (en) | 1979-01-17 | 1979-01-17 | Process for preparing organo thioaldoximes |
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GB2039474A true GB2039474A (en) | 1980-08-13 |
GB2039474B GB2039474B (en) | 1983-05-25 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995024383A1 (en) * | 1994-03-10 | 1995-09-14 | Bayer Aktiengesellschaft | Oxime derivatives and their use as pesticides |
-
1979
- 1979-01-17 GB GB7901755A patent/GB2039474B/en not_active Expired
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995024383A1 (en) * | 1994-03-10 | 1995-09-14 | Bayer Aktiengesellschaft | Oxime derivatives and their use as pesticides |
US6177463B1 (en) | 1994-03-10 | 2001-01-23 | Bayer Aktiengesellschaft | Oxime derivatives and their use as pesticides |
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GB2039474B (en) | 1983-05-25 |
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