CA1140590A - Process for the production of haloacylamides - Google Patents
Process for the production of haloacylamidesInfo
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- CA1140590A CA1140590A CA000294001A CA294001A CA1140590A CA 1140590 A CA1140590 A CA 1140590A CA 000294001 A CA000294001 A CA 000294001A CA 294001 A CA294001 A CA 294001A CA 1140590 A CA1140590 A CA 1140590A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
Abstract
Abstract of the Disclosure The disclosure herein concerns a new process for pro-ducing haloacylamides, particularly haloacetanilides typified by 2',6'-diethyl-N-(methoxymethyl)-2-chloroacetanilide (common name alachlor), by the reaction of the appropriate haloacyl amides one of which substituents has a reactive halogen atom with the appropriate alcohol or thioalcohol.
Description
V5~0 The invention herein relates to the field of chemical processes for the preparation of haloacylamides, particularly haloacetanilides, useful in the agronomic arts, e.g., as pesti-cides and plant growth regulatorsO
Description of the Prior Art Haloacylamides and haloacetanilides of the type de-scribed herein have been prepared by a varie~y of means ~nown to the prior art. In one prior art process, described in U.S.
Patent No. 2,863,752 ~e 26,961) N-substituted-2-haloacetanilides are prepared ~y reacting a primary or secondary amine with the acid chloride of haloacetic acid typically in the presence of caustic soda to neutralize the by-product hydrogen halide. A
similar process is described in German OLS 1,903,198 wherein the , intermediates and final products are characterized by the N-sub-stituent loweralkoxyethyl wherein the ethyl radical may have one or two methyl groups attached thereto.
In yet another prior art process described i.n U.S. Pat.
3,574,746, N-substituted-N-cycloalkenyl-2-haloacetamides are pre-pared by the haloacetylation of the corresponding N-substituted-cyclo-alkylimine in the presence of an acid acceptor.
Still another prior ar-t process for producing 2-halo-acetanilides is described in U. S. Patent Numbers 3,442,945 and 3j547,620 whereln the appropriate intermediate compound, an N-halomethyl-2-haloacetanilide, is reacted with tne appropriate alcohol preferably in the presence o~ an acid binding agent. An analogous process is described in Canadian Patent No. 867,769 wherein fluoroacylamlno-trichlorQmethyl-chlorometha~e is reacted with a thio compound of the formula Me-S-R where Me is H or alkali metal; when the thio compound is used in the free form it is expedient to use an acid-binding agent; when the thio com-pounds are used in the form of their salts, it is not necessary to add an acid binding agent.
The processes of each of the above '752, '945 and '620 patents are also described in U.S. Patent 3,875,228 as useful in the preparation of 2-haloacetamides ~also described as acylamines) exemplified by N-chloroacetyl-N-substituted (hydrogen, lower al-kyl, alkoxymethyl, allyloxymethyl or methoxyethyl)-amino-indanes.
;~ As relevant to the present invention involving the alcoholysis of the N-haloalkyl-N-substituted 2-haloacylamide or
Description of the Prior Art Haloacylamides and haloacetanilides of the type de-scribed herein have been prepared by a varie~y of means ~nown to the prior art. In one prior art process, described in U.S.
Patent No. 2,863,752 ~e 26,961) N-substituted-2-haloacetanilides are prepared ~y reacting a primary or secondary amine with the acid chloride of haloacetic acid typically in the presence of caustic soda to neutralize the by-product hydrogen halide. A
similar process is described in German OLS 1,903,198 wherein the , intermediates and final products are characterized by the N-sub-stituent loweralkoxyethyl wherein the ethyl radical may have one or two methyl groups attached thereto.
In yet another prior art process described i.n U.S. Pat.
3,574,746, N-substituted-N-cycloalkenyl-2-haloacetamides are pre-pared by the haloacetylation of the corresponding N-substituted-cyclo-alkylimine in the presence of an acid acceptor.
Still another prior ar-t process for producing 2-halo-acetanilides is described in U. S. Patent Numbers 3,442,945 and 3j547,620 whereln the appropriate intermediate compound, an N-halomethyl-2-haloacetanilide, is reacted with tne appropriate alcohol preferably in the presence o~ an acid binding agent. An analogous process is described in Canadian Patent No. 867,769 wherein fluoroacylamlno-trichlorQmethyl-chlorometha~e is reacted with a thio compound of the formula Me-S-R where Me is H or alkali metal; when the thio compound is used in the free form it is expedient to use an acid-binding agent; when the thio com-pounds are used in the form of their salts, it is not necessary to add an acid binding agent.
The processes of each of the above '752, '945 and '620 patents are also described in U.S. Patent 3,875,228 as useful in the preparation of 2-haloacetamides ~also described as acylamines) exemplified by N-chloroacetyl-N-substituted (hydrogen, lower al-kyl, alkoxymethyl, allyloxymethyl or methoxyethyl)-amino-indanes.
;~ As relevant to the present invention involving the alcoholysis of the N-haloalkyl-N-substituted 2-haloacylamide or
2-haloacetanilide intermediate, the prior art (see, e.g., the above '945, '620 and '228 patents) describes the preparation of the 2-haloacetanilide intermediate by the haloacetylation of the appropriate phenylazomethine. See also U.S. Patent 3,637,847.
In another process described in the Journal of the Chemical Society, Volume 1, pages 2087-88 ~1974) by O. O. Orazi et al, N-halo-N-substituted amides and imides are methylenated at the nitrogen-halogen bond ~lsing diazomethane to produce the corresponding N-halomethyl-W-substituted-amide or imide followed by condensation with nucleophiles. One species of this process involves the reaction of N-chloro-N-methyl-2-chloroacetamide with diazomethane to produce the corresponding N-chloromethyl-N-methyl-2-chloroacetamidel which can then be reacted with a nucleophile.
In the above-mentioned '746 patent, Examples 47 and 54, respectively, disclose N-chloromethyl and N-bromomethyl-~-substituted-cycloalkenyl-~-haloacetamides which are representa-tive of this class of compounds which can serve as intermediates in the process of the present invention Still otner known pro-;
In another process described in the Journal of the Chemical Society, Volume 1, pages 2087-88 ~1974) by O. O. Orazi et al, N-halo-N-substituted amides and imides are methylenated at the nitrogen-halogen bond ~lsing diazomethane to produce the corresponding N-halomethyl-W-substituted-amide or imide followed by condensation with nucleophiles. One species of this process involves the reaction of N-chloro-N-methyl-2-chloroacetamide with diazomethane to produce the corresponding N-chloromethyl-N-methyl-2-chloroacetamidel which can then be reacted with a nucleophile.
In the above-mentioned '746 patent, Examples 47 and 54, respectively, disclose N-chloromethyl and N-bromomethyl-~-substituted-cycloalkenyl-~-haloacetamides which are representa-tive of this class of compounds which can serve as intermediates in the process of the present invention Still otner known pro-;
-3-: ' :
35~C~
cesses for producing some intermediates used in this invention involve the N-haloalkylation of the appropriate aniline followed by N-haloacylation, For example, N-2-chloroethyl or N-2-chloro-l-methylethyl 2-haloacetanilides may be prepared by reacting the corresponding aniline with 2-chloroethyl-p-toluenesulfonate and 2-chloro-1-methylethyl-p-toluenesulfonate, respectively, followed by chloroacetylation. Still another process for preparing the N-haloalkyl intermediate involves reacting the appropriate halo-al~ane, e.g., l-chloro-2-bromoethane, with the appropriate aniline followed by chloroacetylation.
In the process for producing N-substituted-2-haloacet-anilides by alcoholysis of the corresponding N-haloalkyl-2-halo-acetanilide intermediate compound~ hydrogen halide is generated as a by-product which adversely a~fects not only the yield of desired product, but also adversely affects the natural environ-ment. Hence, as indicated in the above '945, '620 and '228 patents, it is necessary that this alcoholysis be conducted in the presence of an acid-binding agent. Examples of acid-binding agents which have been used in the prior art include inorganic and organic bases such as the alkali metal and alkaline earth metal hydroxides, and carbonates, e.g., sodium and potassium hydroxide, sodium carbonate, etc., tertiary amines, e.g., tri-methyl- and triethylamines, pyridine and pyridine bases, ammonia, qua~ernary ammonium hydroxides and alcoholates; metal alcoholates, e.g., sodium and potassium methylates, ethylates, etc. Both the hydrogen halide and the acid-binding agent can promote adverse side reactions which are undesirable, hence, constitute a dis-advantage in prior art processes.
~ significant disadvantage commonly encountered in the above-mentioned prior art processes is that ~he acid-binding ag2nt reacts with the by-product hydrogen halide to form insoluble pre-_~ _ , ~
~14~
cipitates which must be separated from the reaction mixture and disposed of. Separation of the desired product from waste by-products requently requires and/or includes stripping of any solvent used, aqueous washing, steam stripping of hydrogen halide, dehydration, filtration and/or stabilization of product. Other purification procedures include fractional distillation at sub-- or super atmospheric pressure, solvent extraction, film distilla-~ion, recrystallization, etc. For example, it is disclosed in Example 4 of each of the above '945 and '625 patents that in the production of N-(buto~ymethyl)-2'-t-butyl-6'-methyl-2-chloroacet-anilide (common name "terbuchlor"), t~e acid-binding agent, i.e., triethylamine, forms a voluminous precipitate of fine needles of triethylamine hydrochloride which must be removed by aqueous washing, solvent stripping and filtration. The same problem is also described in the above-mentioned '746 patent (see Column 6, lines 18-33).
As another example, when a~monia is used as the acid-; binding agent in the production of 2',6'-diethyl-N-(methoxymethyl)~
2-chloroacetanilide (common name "alachlor" ànd active ingredient in the commercial herbicide Lasso~, registered trademark of Mon-santo Company), ammonium chloride is formed as a solid by-product in large ~uantity and must be disposed of.
In some instances, during or after the alcoholysis of the N-haloalkyl intermediate, the bulk of the generated hydrogen halide by-product can be removed by conventional distillation.
However, the hydrogen halide itself is a gaseous pollutant in the environment. Moreover, in some cases distillation of the reactan-t alcohol and by-product hydrogen halide results in the production of an alkyl halide and water and water is detrimental to yield or product. Further, a certain percentage of the hydrogen halide ~ remains in the reaction mixture and must be removed by an acid-i.:
~ ~ binding agent, thus forminy solid waste products as mentioned ?
, ~
earlier. For example, in prior work on the alachlor process by another worker in the laboratories of applicants' assignee herein, efforts were made to remove by-product HCl with excess methanol by conventional vacuum distillation. However, these efforts in-volved prolonged exposure, i.e., ~-2 hours, of the ~-chloromethyl intermediate and final product (alachlor) to the adverse action of HCl, water and other by-products and resulted in greatly dimin-ished yields of alachlor. It was then concluded that an acid-binding agent should be used during or after the distillation stage, hence encountering the attendant disadvantages mentioned above.
In view of energy conservation and environmental con-siderations bearing on the disposal of process wastes it has be-come exceedingly crucial to ~lnd new processes which eliminate or minimize the adverse impact of all kinds of wastes, i.e., solids, liquids and/or gases from chemical processing. In some instances deleterious by-products can be reprocessed for recycling of com-ponent parts. In other situations, by-products may be purified or converted to other useful products. However, each of the foregoing treatments require additional capital investment and reprocessing costs and energy consumption. Accordingly, it is much more desirable to avoid the creation of environmentally adverse products as far as possible.
Still another problem in connection with known prior art processes for the production of 2-haloacetanilides is that they are batch processes with attendant disadvantages, particu-larly on a commercial scale.
Therefore, it is an obiect of this invention to pro-vide an improved process for produc~ng 2-haloacylamides or 2-; 30 haloacetanilides which overcomes dlsadvanta~es of prior art ~ ~ processes. In particular it is an object of this inven~ion to :
, ,.
provide the advantages of a process whicil requires no acid-binding agent and produces substantially no solid wastes thereby eliminating some raw material, e~uipment and separation costs and solid waste disposal problems inimical to the environment.
Still other objects of this invention relate to a process which is continuous, simple and inexpensive in operation, conserves energy, reduces environmental pollution and yet produces yields and purities as great or greater than prior art processes.
Summary of the Invention The present invention relates to a continuous process for the preparation of N,N-disubstituted-haloacylamides, particularly compounds of Formula I
y ~ C ~ R
: R - N ~ R4\
: I , ~ C ~ yl R6 : 20 \ 5/
~ \ R ~
; b wherein R is hydrogen, Cl 18 alkyl, alkenyl, alkynyl, alkoxy, polyalkoxy, alkoxyalkyl, polyalkoxyalkyl, C5 7 cyclo-alkyl, alkylcycloalkyl, cycloalkenyl, C6 l~ aryl, aralkyl, or alkaryl or said R members substituted with radicals which are nonreactive with hydrogen, e.g. alkyl, halogen, hydroxy, alkoxy, nitro or cyano;
R4 and R5 are independently hydrogen, fluorine, Cl 6 alkyl, haloalkyl, alkoxy or alkoxyalkyl;
R is hydrogen, Cl_lO alkyl, alkenyl, alkynyl, alkoxyalkyl, oxoalkyl, C3 7 cycloalkyl, .
lower alkylcycloalkyl or cycloalkenyl~ C6 12 aryl : or aralkyl; -N(R8)2 wherein R8 is hydrogen, Cl_16 alkyl, alkenyl, or alkynyl; or said R6 members substituted with alkyl, alkylthio, halogen, hydroxy, alkoxy, nitro or cyano;
~ ' .
. R7 is Cl 5 mono~ or dihaloalkyl;
Y and Y are oxygen or sulfur; and b is an integer from 1-4 inclusive, ``:
which comprises performing at least one sequence o~ reaction/
separation operations comprising:
(A) reacting a compound of Formula II
' R- ~ R \
,~' I CtX
~ : ~ R5~
: b with a compound of Formula III
III R (Y )H
i R R4 R5 R6 R7, y, yl/ and b are as defined above and X is halogen in the absence of ` added acid-binders and : (B) directing an effluent stream of the reaction ~ mixture from Step tA) to a separation zone from ~, !
. ` .
~ ~ .
~ , which is removed a complex mixture oE by-product HX with said compound of Formula III and a product stream com~rising predominantly said compound of Formula I.
A subgenus of compounds of particular interest which may be prepared by the process of this invention includes haloacetanilides of Formula IV
IV ~ ~ C ~ Y - R
(R )~ b wherein Rl and R2 are independently hydrogen, halogen, Cl 6 alkyl, haloalkyl, alkoxy or alkoxyalkyl;
R3 is hydrogen, halogen, Cl 6 alkyl, haloalkyl, alkoxy, alkoxyalkyl, alkylthio, CM, NO2 or CF3 or R3 may be combined with Rl or R2 to form an alkylene chain of up to 4 carbon atoms;
R4 and R5 are independently hydrogen, fluorine, Cl 6 ~: ~ alkyl, haloalkyl, alkoxy or alkoxyalkyl R6, R7, y, yl~ and b are as defined above, and a is an integer from 0-3 inclusive.
Preferred haloacetanilides include those wherein Rl, R2 and R6 are Cl 6 alkyl, R4 and R5 are hydrogen or Cl 6 alkyl, R7 is monohaloalkyl, Y and yl are oxygen, a is zero and b is 1 or 2.
In the most preferred embodiment, ~he process of this invention .is used to prepare alachlor by the reaction of 2',6'-diethyl-N-(chloromethyl)-2-chloroacetanilide and methanol as _g _ v described in Example 1 below.
In preferred embodiments the above reaction/separation process sequence is repeated a plurality of times to assure complete conversion of said compound of Formula II to said compound of Formula I. In the most preferred embodiment the process is efficiently carried out in two stages or reaction/separation sequences which comprise:
(A) reacting in a first reaction zone a compound of Formula II with a compoùnd of Formula III;
tB) directing an effluent stream of the reaction mixture of Step (A) to a first separation zone from which is rapidly removed most of by-product HX as a complex with said compound of Formula III
and a product stream comprising predominantly a compound of Formula I and unreacted compound of Formula II;
(~) directing said product stream from said first separation zone to a second reactlon zone into : which is also introduced an additional quantit~
of said compound of Formula III to react with said unreacted compound of Formula II;
: (D) directing an effluent stream of the reaction mixture of Step (C) to a second separation zone from which is rapidl~ removed substantially all of the remaining by-product HX as a complex with said compound of Formula III and a product stream . comprised of said compound of Formula I and trace impurities.
Significant features of the process of this invention include: (1) the elimination of an added base as used in the prior art as an acid-binding agent for liberated hydrogen ,:
..~
r ~ ~
.: ;
halide; and concomitantly (2) elimination of recovery systems for the neutralization by-product of (1) nence, elimination from the environment of the by-product itself and (3) separation, preferably immediately and usually within ~0.5 minute of equilibration of the reaction mixture, of by-product hydrogen halide as a complex with the compound of Formula III in the product separation operation(s) of the process.
In preferred embodiments of the invention, the molar ratio of the compound of Formula III relative to the compound of ~ormula II in Step A is greater than 1:1 and usually within the range of about 2-100:1 and, in the case of the alachlor process, within the range of about 2-10:1 and preferably of 4-5:1.
The reaction temperatures in Step (A) will depend upon the particular reactants and/or solvents or diluents involved.
In general, these temperatures will be temperatures at which mixtures of the alcohols of Formula III and/or solvents or diluents from complexes, e.g., azeotropic mixtures, with by-product hydrogen halide without significant degradation of the reactant compound of Formula II or desired product of Formula I
due to reaction with hydrogen halide. In general, a temperature within the range of from about -25 to 125C or higher depending upon the melting/boiling points of the reactants is used.
In those embodiments of the invention involving a plurality of reaction/separation sequences, or stages, the hydrogen halide concentration is greatly reduced in successive reaction zones, hence the respective reaction temperatures are generally somewhat elevated over the temperatures used in Step (A) in order to drive the reaction of the unreacted compound of Formula II to : -11-.
~ OS90 completion with additional alcohol. Accordingly, temperatures in the second and any subsequent reaction zone are generally within the range of from about -25 to 175C or higher i necessary, Suitably the temperatures and pressures within the separation zone(s) are, respectively, within the ranges of from about 50C to 175C and 1.0 to 300 mm Hg absolute, depending upon the boillng point of the particular compound of Formula III.
Detailed Description of the Invention Exam~_e 1 This example describes the use of the process of this invention in the preparation of alachlor. This process is efficiently carried out in a reaction/separation sequence of two stages as follows:
- Stage 1~ Molten (45-55C) 2',6'-diethyl-N-chloromethyl-2-chloroacetanilide is fed to an in-line mixer at a rate of 102.8 lbs/hr (46.67 kg/hr) and mixed with substantially anhydrous methanol which is fed to said mixer at a rate of 60.0 lbs/hr (27.24 kg/hr). The mixture is pumped through a thermostatted pipe reactor maintained at 40-45C of sufficient length to give a residence time of at least thirty (30) minutes. The reaction produces a yield of ~ 92~ 2l,6'-diethyl-N-(methox~methyl)-2-chloroacetanilide (alachlor) and hydrogen chloride based on the N-chloromethyl intermediate. The generated HCl is dissolved in excess methanol. The reactor effluent is directed to a falling film evaporator operated at 100C and 30 mm Hg absolute. A com-plex is removed and fed to a methanol recovery system.
Stage 2. The product stream from the evaporator in Stage 1 comprising predominantly alachlor and unreacted 2'~6'-diethyl-N-~chloromethyl)-2-chloroacetanilide is red to a second .~
, . . .
9~
in-line mixer into which is also fed an additional quantity of methanol at a rate of 60 lbs/hr (27~24 kg/hr). The mixture is then fed to a second reaction zone also comprising a thermo-statted pipe reactor maintained at 60-65C to give a residence time of thirty (30) minutes. The effluent ~rom this reactor is fed to a second falling film evaporator, operated at 100C and 30 mm ~g absolute, from which is removed a complex of methanol and substantially all of the remaining HCl. The methanol/HCl ; complex from this second stage evaporator is mixed with the methanol/HCl complex from the evaporator in Stage 1 and fed to ~ a methanol recovery system from which anhydrous methanol is ; recovered and recycled to Stage 1.
The product stream from the evaporator in Stage 2 com-prises alachlor in essentially quantitative yield and greater than 95% purity togethex with minor amounts of impurities. This alachlor can be used effectively as a herbicide as produced.
As will be apparent from the foregoing example, the reaction/separation process sequence o Stage 1 by itself pro-duces alachlor of high yield. Hence, under optimum conditions of reactant purities and concentrations, temperatures, residence times in the reactor and separation zones, etc., at least one reaction/separation process sequence corresponding to said Stage 1 operation would suffice to produce a commercial grade of alachlor or other compounds within the scope of the above Formula Example 2 This example describes the preparation of 2-chloro-2',6'-diethyl-N-(etho~ymethyl) acetanilide.
About 5.5 g (0.02 mole) of 2-chloro-2',6'-diethyl-N-tchloromethyl) acetanilide was dissolved in 25 ml of ethanol and allowed to stand in a ~5C ~ath fo~ 30 minutes. Excess ethanol ,.
~ 13-"~
v was removed rapidly on a rGtary vacuum evaporator at 50C
and 10 mm Hg. Twenty-five (25) ml of fresh ethanol was added to the residual oil and the mixture held at 65C for 30 minutes. Again excess ethanol was removed using a rotary evaporator. About 5.80 g of a pale amber oil was obtained which assayed (by gas chromatography) 92.8% of the desired product and 1.7% 2-chloro-2',6' diethylacetanilide (by-product). Yield of product was 94.5%.
Example 3 Following the same procedure, operating conditions and quantities of reactants described in Example 2, but substituting isopropanol for ethanol, 5.92 gms of product, a light amber oil assaying 90.2% 2', 6'-diethyl-N-(isopropoxymethyl)-2-chloroacetanilide ~89.4% yield) and 1.8% of the secondary amide by-product 2', 6'-diethyl-2-chloroacetanilide was obtained.
Example 4 Following the same procedure described in Examples 2 and 3, but substituting l-propanol as the reactant alcohol, 5.66 gms of lemon-yellow oil was recovered which assayed 92.8% (87.9% yield) of 2', 6'-diethyl-N-(n-propoxymethyl)-2-chloroacetanilide and 1.2% of the corresponding secondary amide by-product.
Example 5 The same procedure described in Examples 2-4 was used in this example, but using isobutanol as the reactant alcohol, 6.20 gm of an oil product was recovered which assayed 96.4%
(97% yield) of 2',,6'-diethyl-N-(isobutoxymethyl)-2-chloroacet-anilide and 3% of the correspondin~ secondary amide by-product.
Example 6 Repeating the process of Examples 2-5, but using 2-chloro-ethanol as reactant alcohol, 6.96 gms of light-amber oil was recovered which assayed 86.0% (94.0~ yield) of 2'j6'-diethyl-N-:~4~ 0 (chloroethoxymethyl)-2-chloroacetaniliae.
Example 17 Following the same procedure described in Examples 2-6, but substituting n-butanol as the reactant alcohol, 6.18 gms of pale lemon-yellow oil was recovered which assayed 98.8~
(99% yield) of 2',6'-diethyl-N-(n-butoxymethyl)-2-chloroacetani-; lide (i.e., butachlor) and 1% of the corresponding secondary amine by-product.
In the abo~e examples, NMR analysis indicated that the respective products were consistent with chemical structure thereof.
In further elaboration of the advantages provided by the present invention and the unobvious nature thereof, the ollowing discussion and additional experimental data in Examples 12 is presented.
The reaction between compounds like those identified by Formula II and Formula III above is a reversible second-order reaction. Equation 1 below, exemplified by the reaction in ;~ Example 1, illustrates the reaction:
C2H5 ,, C2H5 0 (1) ~ C-CH2Cl ~ N ' CCH2Cl +HCl CH2Cl CH20CH3 (a) (b) (cl (d) Because the reaction is reversible, an equilibrium con-dition is established; this equilibrium is affected by and directly related to various factors, e.g., alcohol concentration and~or by-product hydxogen halide concentration. For example, in Equation (1) as alcohol (b) concentration, hence reactants ratio, (b):(a), increases(to a given practical maximum) the equation is shited to the right b~cause of additional con~ersion of starting material ,L~S~O
(a) thus producing more product (c) and hydrogen halide by-product (d).
Another way to shift the eguilibrium of Equation (1) to the right is to remove the hydrogen halide (d),which can be done by adding an acid-binderr e~g., tertiary amines such as triethylamine, as in V. S. Patents 3,547,620, 3,442,945 and Canadian Patent No~ 867,679 mentioned above. However, the use of acid-binding materials intxoduces other disadvantages as described above.
The foregoing Canadian '769 patent suggests that when the thio compound starting material is in the form of an alkali metal sal~ the acid-binding material is unnecessary; the apparent reason for this is that said salts themselves provide the basic medium, favorable to the particular reaction described in that patent. In contrast, when the starting thio compound is used in the free form, it is necessary to use an acid-binder to bind the hydrogen chloride by-product.
Although the process disclosed in the above '620 and '945 patents is described as being preferably conducted in the presence of an acid-binding agent (as exemplified in all of the specific working embodiments), an inference arises that the same process may be performed wi~hout the addition of an acid-binder. ~owever, as mentioned earlier (in section entitled "Description of the Prior Art") efforts to perform the process disclosed in the '945 and '620 patents to obtain the preferred product alachlor without an acid-binding agent to remove by-product hydrogen halide resulted in greatly diminished yields of alachlor~
In order to further determine the comparative results ~ 30 of practicing the process disclosed in the '945 and '620 patents ; ~ without an acid-binding agent vis-a-vis the process of the present ~ -16-5~0 invention, applicants herein conducted the processes described in Examples ~-12 below. In each of these examples, the N-chloro-methyl-2-chloroacetanilide starting material was prepared by the reaction of the corresponding substituted N-methyleneaniline ana haloacetyl halide as described in the '945 and '620 patents.
Example 8 This example describes the preparation of 2-chloro-2',-6'-diethyl-N-tmethoxymethyl) acetanilide ~alachlor) as taught in Example 5 of said U. S. Patent Nos.3,547,620 and 3,442,945.
One-hundred g of 2-chloro-2',6'-diethyl-N-(chloromethyl) acetanilide assaying 96,0% (0.350 mole) dissolved ln about 70 g of benzene was added to 65.8 g (2.054 molas) of methanol. On addition an exothermic reaction occurred. The reaction mixture was refluxed ~at 63C) and an excess (about 63.3 g) of triethyl-amina was added dropwise over 1-1/2 hours. During this addition the temperature rose to about 70C where it was maintained for about ten minutes after completion of the triethylamine addition.
After cooling to 30C, the reaction mixture was washed with two 170 ml portions o water. The product, in a heavy, oily layer was stripped of solvent and dehydrated by vacuum distillation to ; a terminal pot temperature of about 70C at 1 mm hg. The residual amber oil weighed 96.15 g and assayed 90.4~ product and 4.9% 2-chloro-2',6'-diethylacetanilide ~by-product) by gas chromatogra-phy. There was no unreacted starting material in the product.
The yield of product was 92.0~.
Example 9 This example describes the preparation of alachlor as taught in Example 5 of said '620 and '945 patents, but without the use of an acid-binding agent.
One-hundred g o~ 2-chloro-2',6'-diethyl-N-(chloromethyl) ~4~
acetanilide assaying 96.~ (0.350 mole) dissolved in about 70 g.
of benzene was added to 66.0 g. of methanol (2.059 moles). On addition, an exothermic reaction occurred ana the reaction mixture was further heated to reflux (at 63C) or one hour. No acid-binding agent was added. After refluxing, excess methanol and solvent were remo~ed by vacuum distillation to a ~inal pot temper-ature of 70C at 1 mm Hg. About 96.83 g. of a pale lemon-yellow oil was obtained which contained (by gas chromatographic analysis) 83.7% product, 7.5% by-product 2-chloro-2',6'-diethyl acetanilide and 5.5% unreacted start1ng material. The yield of product was 85.8%.
As will be noted, omission of an acid-binding agent in this example resulted in a reduction in yield of 6.2%. In this process, the reaction was not shited completely to the right. As a result, the by~product HC1 reduced conversions and the unreacted starting material was found as a con~aminant în the product.
Example 10 This example describes the preparation of alachlor as taught in Example 5 of said '620 and '945 patents, but w1thout the use of an acid-binding agent and under optimized temperature condi-tions.
One-hundred g. of 2-chloro-2',6'-diethyl-N-(chloromethyl) acetanilide assaying 96.0% (0.350 mole) dissolved in about 70 g.
of benzene was added to 66 g. (2.059 moles) of methanol. An exothermic reaction occurred which raised the reaction mixture temperature to 45C where it was maintained for one hour. No acid-binding agent was added. Excess methanol and solvent were stripped off under vacuum distillation to a final pot temperature of about 80C at 1 mm Hg. About 96.20 g. of oil was recovered which assayed (by gas chromatography) 85.3% product, 6.2% by~
produc~, 2-chloro-2',6'~diethyl acetanilide and about 4.6~ un-_l g_ )590 reacted starting material. The yield of product was 87.4~.
By optimizing reaction conditions in the absence of an acid-binding agent, an increase in product quality (2.7%) and yield (1.6~ was reali~ed, but the basic problem, i.e., incomplete reaction, has still not been solved.
Example 11 This example describes the preparation of alachlor by the process of the present in~ention according to the embodi-ment using a single stage reactor; the starting materials used 1~ herein were the same as those used in Examples 8~
Ten g. of 2-chloro-2',6'-diethyl-N-(chloromethyl) acetanilide assaying 9~.0~ (0.035 mole) was added to about 6.0 0.1873 mole) of methanol. An exothermic reaction occurred raising the reaction mixture temperature to about 45C where it was maintained for thirty minutes. Excess methanol was removed rapidly on a vacuum rotary evaporator to a final pot temperatu~e of 70C at 1 mm Hg. About 9.80 g. of pale lemon yellow oil was ; recoverad assaying 91.0~ product, 1.7% by-pro~uct 2-chloro-2',6'-diethylacetanilide, and 2.4% unreacted starting material by gas chromatography. The yield of product was 94.4~.
Thus, using only a single stage, the quality and yield of the desired product is substantially improved over that of the prior art despite the fact that tha reaction was not complete (2.4% starting material in product). Comparison with Examples 8, 9 and iO shows an obvious improvement, although no acid-binding agent was used.
Example 1~
~ This example describes the preparation of alachlor in the absence of an added acid-binding agent according to the pre-ferred process of the present invention using a multiple stage -~ --19--1~jLL~ 59C~
reactor.
Ten g. of 2-chloro-2',6'-diethyl-N-(chloromethyl) acetanilide assaying 96.0% (.035Q mole) was dissol~ed in 6.0 g.
(0.1873 mole) of methanol. An exothermic reaction occurred raising the temperature to 45C where it was maintained for one-half hour. Excess methanol was remov~d rapidly on a rotary vacuum evaporat~r to a final pot temperature of 45C at 1 mm Hg.
A second addition of fresh methanol, 6.0 ~ (0.1873 mole) was added, the reaction mixture warmed to 65C and held for one-half hour. Excess methanol was removed as before and about 9.80 g. of pale lemon-yellow oil was recovered assaying 95.8% product, 1.4%
2-chloro-~',6'-diethylacetanilide and no unreacted starting material~ The yield of product was 99.4%.
A summaxy of the comparative results of the processes d scribed in Examples 8-l~ is shown in the following table. In this table, the "Starting Material" is unreacted 2l,6'-diethyl-N-~chloromethyl)-2-chloroacetanilide and the "By-Product" refers to 2',6'-diethyl-2-chloroacetanilide, the major acetanilide by-; product in the processes of each of these examples. It will be understood that minor amounts of acetanilide and other by-products are produced in addition to the large quantities of hydrogen hal-~ ide generated and, in the case of Example B, triethylamine hydro - chloride neutralization by-product produced. Product yield percentages herein are based on the 2',6'-diethyl-N-(chloromethyl)-2-chloroacetanilide starting materlal.
~2Q-:
S9~
~ABLE
~ ' Exam- Pro- Ala- Start-ple ce~s chlor Ala- By- ing Ma-No. Type Yield(%) chlor Product terial __ _ _ _ , 8 Ex. 5 U.S. Pats. 92.0 90.S 4.9 0 3,442,g45 &
3,s47,620;
base added 9 Ditto, except 85.8 83.7 7.5 5.5 base omitted 10 Same as Ex. 9 87.4 85.8 6.2 4.6 with optimized conditions 11 Present process, 94.4 91.0 1.7 2.4 l-stage 12 Ditto, plural 99.4 95.8 1.4 0 stages ,.~
An analysis of the data in the above table will show as ;; 20 the salient features and distinct advantages of the process of this invantion, i.e., Examples 11 and 12, vis-a-vis the process , ~
of the prior art exemplified in Examples 8-Io;(l~ substantial increases in yield of alachlor; (2) improvement in alachlor puri-ty; (3) markPdly decreased yields by-product; (4) increased con-version of starting material when operating without added base;
and (~) absence of solid neutralization product which is present in large quantities in the base-added process of Example 8 -- rep-resenting the best previously known technology for producing alachlor. These technical adva~tages are additive to the economi cal and ecological advantages mentioned earlier.
In practicing the present invention, no solvent is re-quired; however, in many cases a solvent or diluent may be used to moderate the reaction and/or aid in the solution, dispersion and/or recovery of reactants, by-products and products. Suitable ¢
- solvents or diluents include those which are inert under the re~uired conditions of reaction, such as petroleum ether, CC14, ;
5~3~
aliphatic and aromatic hydrocarbons, e.g., hexane, benzene, toluene, xylenes, etc., and halogenated hydrocarbons, e.g., mono-chlorobenzene.
An advantage of the process according to this invention is that the reactant of Formula III may be readily separated from its complex with by-product hydrogen halide, purified and recycled to one or more reaction stages of the process. In like manner, the hydrogen halide itself may be readily recovered for use in many useful commercial operations, e.g., pickling of metals, oxychlorinations, electrolysis to elemental chlorine and hydrogen, etc., or otherwise disposed of without detriment to the environment.
In one suitable raw material recovery/recycle system, exemplified with respect to the methanol/~Cl complex formed in the alachlor process described in the above Examples 1, 11 and 12, the methanol/HCl complex from the separation stage(s) is fed to a distillation system from which purified methanol is obtained.
With further respect to the present process, while the use of technical grade reactants, i.e~, the compounds of Formulae II and III, is suitable, it will be appreciated that the higher the purity of these reactants, the higher the quality of compounds of Formula I will be produced. Although in some instances the Formula III compounds, e.g., methanol~ containing minor amounts of water can be used, it is much more preferable to use anhydrous compounds, because water may cause hydrolysis of the Formula II reactants resulting in deteriorated product of Formula I. However, it will be understood that in the special case where R6 is hydrogen water itself can be used as the compound of Formula III to produce some compounds of Formula I by hydroly-sis of the N-haloalkyl intermediate. For example, it has been disclosed in the prior art that 2'-tert-butyl-6'-ethyl-N-(chloro-methyl~-2-chloroacetanilide is hydrolyzed with water in the :~
V5~0 presence of an acid binding agent to produce the corresponding N-hydroxymethyl compound which is useful as a herbicide tsee~
e.g., Example 1 in British Patent No. 1,088,397). Accordingly, it will be appreciated that in some embodiments of the present process the presence of some water may be detrimental to product yield but not in other embodiments, depending upon the reactivity of water with other reactants and final products as will be understood by those skilled in the art. In like manner, since hydrogen halide adversely impacts on product quality, it is preferred to use reactants substantially free of hydrogen halides such as HCl.
Representative compounds produced according to the process of this invention include those in which the groups of the above formulae have the following identities:
R - hydrogen~ Cl_l8 alkyls, e.g., methyl, ethyl, propyls, butyls, pentyls, hexyls, heptyls, octyls, nonyls, decyls, undecyls, dodecyls, pentadecyls, octadecyls, etc.; alkenyls, e.g., vinyl, allyl, crotyl, methallyl, butenyls, pentyls, hexenyls, heptenyls, octenyls, nonenyls, decenyls, etc., alkynyls, e.g., ethynyl, propynyls, butynyls, pentynyls, hexynyls, etc.; the alkoxy, polyalkoxy, alkoxyalkyl and polyalkoxyalkyl analogs of the foregoing alkyl groups; cycloalkyls and cycloalkylalkyls having up to 7 cyclic carbons, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, etc.; cycloalkenyls and cycloalkadienyls having up to 7 cyclic carbons, e.g., cyclo-pentenes, cyclohexenes and cycloheptenes having mono- and di-unsaturation; C6 18 aryl and aralkyl and alkaryl groups, e.g., phenyl, tolyls, xylyls, benzyl, naphthyl, etc., and said R members substituted with radicals which are non-reactive , with hydrogen, e.g., alkyls, alkoxys, halogen, nitro or cyano, ., . -, , ~ .
~;~4(;~5g~
when the substituent is a halogen atom, it must not be on the a-carbon atom in which position it is reactive with hydrogen.
Rl, R , R and R - hydrogen, fluorine, the Cl 6 alkyls o~ R, haloalkyls, e.g., chloromethyl, chloroethyl, bromomethyl, bromoethyl, iodomethyl, iodoethyl, trifluoro-methyl, chloropropyl, bromopropyl, iodopropyl, chlorobutyl, iodobutyl and di- and trihalo analogs thereof; alkoxys, e.g., methoxy, ethoxy, propoxys, butoxys, pentoxys and hexoxys and corresponding polyalkoxys and alkoxyalkyls, e.g., methoxymethoxy, methoxyethoxy, ethoxymethoxy, ethoxyethoxy, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, isobutoxymethyl, tert-butoxymethyl, pentoxymethyl, hexoxymethyl, etc.
Rl and R2 may also be chlorine, bromine or iodine.
R3 may be hydrogen, the halo, alkyl, haloalkyl, alkoxy and alkoxyalkyl groups of Rl, R2, R4 and R5, methylthio, ethyl-thio, propylthio, CN, NO2l CF3 or R3 may be combined with l or R2 to form an alkylene chain of up to 4 carbon atoms, thus forming acylated 5-amino-tetralins and acylated 4-aminoindanes typified in the above-mentioned U.S. Patent No.
` 3,875,228.
R6 may be hydrogen, the Cl 10 alkyl, alkenyl, alkynyl, and alkoxyalkyl groups of R; oxoalkyl groups corresponding to the above alkyl groups, e.g., 2-oxobutyl, 3-oxopentyl, 4-oxohexyl, etc., the C3 7 cycloalkyl, cycloalkenyl and alkylcycloalkyl groups of R; the C6 12 aryl and aralkyl groups of R; amino and mono- and di-substituted amino containing the above Cl 6 alkyl, alkenyl or alkynyl groups; and the above R6 members which may be substituted with substituents such as alkyl, halogen, hydroxy, alkoxy, nitro, cyano or alkylthio.
5~
R7 is Cl 5 haloalkyl, preferably Cl 2 monohaloalkyls, such as chloromethyl, chloroethyl, bromomethyl, bromoethyl, iodo-methyl, iodoethylr fluoromethyl and fluoroethyl; dihaloalkyls such as l,l-dichloromethyl, l,l-dibromomethyl, l,l-diodomethyl, etc., may also be present.
X is halo, expecially chlorine or bromine.
The process of the present invention is particularly amenab~e to use in the preparation of the above defined N-sub-stituted-2-haloacetanilides wherein R1, R2 and R6 are Cl 6 alkyl, R7 is monohalomethyl, Y and yl are oxygen, a is zero and b is 1 or 2, preferably 1.
Compounds of Formula I prepared acaording to this in-vention are known compounds. Representative compounds of Formula I are disclosed in the prior art described in the foregoing section entitled "Description of the Prior Art" and other prior art not cited herein. Hence, the inventors herein lay no claim to the compounds, per se, of Formula I.
It will be appreciated by those skilled in this art that the preferred 2-haloacetanilides are a subgenus of N,N-di-substituted-2-haloacylamides. Accordingly, the process of this invention may be modiied in a manner within the skill of this art as the nature and concentration of reactants, reaction and separation conditions of temperature, pressure, residence times, etc., to produce other compounds within a broad genesis of said N,N-disubstituted-2-haloacylamides.
`' `
''', .
35~C~
cesses for producing some intermediates used in this invention involve the N-haloalkylation of the appropriate aniline followed by N-haloacylation, For example, N-2-chloroethyl or N-2-chloro-l-methylethyl 2-haloacetanilides may be prepared by reacting the corresponding aniline with 2-chloroethyl-p-toluenesulfonate and 2-chloro-1-methylethyl-p-toluenesulfonate, respectively, followed by chloroacetylation. Still another process for preparing the N-haloalkyl intermediate involves reacting the appropriate halo-al~ane, e.g., l-chloro-2-bromoethane, with the appropriate aniline followed by chloroacetylation.
In the process for producing N-substituted-2-haloacet-anilides by alcoholysis of the corresponding N-haloalkyl-2-halo-acetanilide intermediate compound~ hydrogen halide is generated as a by-product which adversely a~fects not only the yield of desired product, but also adversely affects the natural environ-ment. Hence, as indicated in the above '945, '620 and '228 patents, it is necessary that this alcoholysis be conducted in the presence of an acid-binding agent. Examples of acid-binding agents which have been used in the prior art include inorganic and organic bases such as the alkali metal and alkaline earth metal hydroxides, and carbonates, e.g., sodium and potassium hydroxide, sodium carbonate, etc., tertiary amines, e.g., tri-methyl- and triethylamines, pyridine and pyridine bases, ammonia, qua~ernary ammonium hydroxides and alcoholates; metal alcoholates, e.g., sodium and potassium methylates, ethylates, etc. Both the hydrogen halide and the acid-binding agent can promote adverse side reactions which are undesirable, hence, constitute a dis-advantage in prior art processes.
~ significant disadvantage commonly encountered in the above-mentioned prior art processes is that ~he acid-binding ag2nt reacts with the by-product hydrogen halide to form insoluble pre-_~ _ , ~
~14~
cipitates which must be separated from the reaction mixture and disposed of. Separation of the desired product from waste by-products requently requires and/or includes stripping of any solvent used, aqueous washing, steam stripping of hydrogen halide, dehydration, filtration and/or stabilization of product. Other purification procedures include fractional distillation at sub-- or super atmospheric pressure, solvent extraction, film distilla-~ion, recrystallization, etc. For example, it is disclosed in Example 4 of each of the above '945 and '625 patents that in the production of N-(buto~ymethyl)-2'-t-butyl-6'-methyl-2-chloroacet-anilide (common name "terbuchlor"), t~e acid-binding agent, i.e., triethylamine, forms a voluminous precipitate of fine needles of triethylamine hydrochloride which must be removed by aqueous washing, solvent stripping and filtration. The same problem is also described in the above-mentioned '746 patent (see Column 6, lines 18-33).
As another example, when a~monia is used as the acid-; binding agent in the production of 2',6'-diethyl-N-(methoxymethyl)~
2-chloroacetanilide (common name "alachlor" ànd active ingredient in the commercial herbicide Lasso~, registered trademark of Mon-santo Company), ammonium chloride is formed as a solid by-product in large ~uantity and must be disposed of.
In some instances, during or after the alcoholysis of the N-haloalkyl intermediate, the bulk of the generated hydrogen halide by-product can be removed by conventional distillation.
However, the hydrogen halide itself is a gaseous pollutant in the environment. Moreover, in some cases distillation of the reactan-t alcohol and by-product hydrogen halide results in the production of an alkyl halide and water and water is detrimental to yield or product. Further, a certain percentage of the hydrogen halide ~ remains in the reaction mixture and must be removed by an acid-i.:
~ ~ binding agent, thus forminy solid waste products as mentioned ?
, ~
earlier. For example, in prior work on the alachlor process by another worker in the laboratories of applicants' assignee herein, efforts were made to remove by-product HCl with excess methanol by conventional vacuum distillation. However, these efforts in-volved prolonged exposure, i.e., ~-2 hours, of the ~-chloromethyl intermediate and final product (alachlor) to the adverse action of HCl, water and other by-products and resulted in greatly dimin-ished yields of alachlor. It was then concluded that an acid-binding agent should be used during or after the distillation stage, hence encountering the attendant disadvantages mentioned above.
In view of energy conservation and environmental con-siderations bearing on the disposal of process wastes it has be-come exceedingly crucial to ~lnd new processes which eliminate or minimize the adverse impact of all kinds of wastes, i.e., solids, liquids and/or gases from chemical processing. In some instances deleterious by-products can be reprocessed for recycling of com-ponent parts. In other situations, by-products may be purified or converted to other useful products. However, each of the foregoing treatments require additional capital investment and reprocessing costs and energy consumption. Accordingly, it is much more desirable to avoid the creation of environmentally adverse products as far as possible.
Still another problem in connection with known prior art processes for the production of 2-haloacetanilides is that they are batch processes with attendant disadvantages, particu-larly on a commercial scale.
Therefore, it is an obiect of this invention to pro-vide an improved process for produc~ng 2-haloacylamides or 2-; 30 haloacetanilides which overcomes dlsadvanta~es of prior art ~ ~ processes. In particular it is an object of this inven~ion to :
, ,.
provide the advantages of a process whicil requires no acid-binding agent and produces substantially no solid wastes thereby eliminating some raw material, e~uipment and separation costs and solid waste disposal problems inimical to the environment.
Still other objects of this invention relate to a process which is continuous, simple and inexpensive in operation, conserves energy, reduces environmental pollution and yet produces yields and purities as great or greater than prior art processes.
Summary of the Invention The present invention relates to a continuous process for the preparation of N,N-disubstituted-haloacylamides, particularly compounds of Formula I
y ~ C ~ R
: R - N ~ R4\
: I , ~ C ~ yl R6 : 20 \ 5/
~ \ R ~
; b wherein R is hydrogen, Cl 18 alkyl, alkenyl, alkynyl, alkoxy, polyalkoxy, alkoxyalkyl, polyalkoxyalkyl, C5 7 cyclo-alkyl, alkylcycloalkyl, cycloalkenyl, C6 l~ aryl, aralkyl, or alkaryl or said R members substituted with radicals which are nonreactive with hydrogen, e.g. alkyl, halogen, hydroxy, alkoxy, nitro or cyano;
R4 and R5 are independently hydrogen, fluorine, Cl 6 alkyl, haloalkyl, alkoxy or alkoxyalkyl;
R is hydrogen, Cl_lO alkyl, alkenyl, alkynyl, alkoxyalkyl, oxoalkyl, C3 7 cycloalkyl, .
lower alkylcycloalkyl or cycloalkenyl~ C6 12 aryl : or aralkyl; -N(R8)2 wherein R8 is hydrogen, Cl_16 alkyl, alkenyl, or alkynyl; or said R6 members substituted with alkyl, alkylthio, halogen, hydroxy, alkoxy, nitro or cyano;
~ ' .
. R7 is Cl 5 mono~ or dihaloalkyl;
Y and Y are oxygen or sulfur; and b is an integer from 1-4 inclusive, ``:
which comprises performing at least one sequence o~ reaction/
separation operations comprising:
(A) reacting a compound of Formula II
' R- ~ R \
,~' I CtX
~ : ~ R5~
: b with a compound of Formula III
III R (Y )H
i R R4 R5 R6 R7, y, yl/ and b are as defined above and X is halogen in the absence of ` added acid-binders and : (B) directing an effluent stream of the reaction ~ mixture from Step tA) to a separation zone from ~, !
. ` .
~ ~ .
~ , which is removed a complex mixture oE by-product HX with said compound of Formula III and a product stream com~rising predominantly said compound of Formula I.
A subgenus of compounds of particular interest which may be prepared by the process of this invention includes haloacetanilides of Formula IV
IV ~ ~ C ~ Y - R
(R )~ b wherein Rl and R2 are independently hydrogen, halogen, Cl 6 alkyl, haloalkyl, alkoxy or alkoxyalkyl;
R3 is hydrogen, halogen, Cl 6 alkyl, haloalkyl, alkoxy, alkoxyalkyl, alkylthio, CM, NO2 or CF3 or R3 may be combined with Rl or R2 to form an alkylene chain of up to 4 carbon atoms;
R4 and R5 are independently hydrogen, fluorine, Cl 6 ~: ~ alkyl, haloalkyl, alkoxy or alkoxyalkyl R6, R7, y, yl~ and b are as defined above, and a is an integer from 0-3 inclusive.
Preferred haloacetanilides include those wherein Rl, R2 and R6 are Cl 6 alkyl, R4 and R5 are hydrogen or Cl 6 alkyl, R7 is monohaloalkyl, Y and yl are oxygen, a is zero and b is 1 or 2.
In the most preferred embodiment, ~he process of this invention .is used to prepare alachlor by the reaction of 2',6'-diethyl-N-(chloromethyl)-2-chloroacetanilide and methanol as _g _ v described in Example 1 below.
In preferred embodiments the above reaction/separation process sequence is repeated a plurality of times to assure complete conversion of said compound of Formula II to said compound of Formula I. In the most preferred embodiment the process is efficiently carried out in two stages or reaction/separation sequences which comprise:
(A) reacting in a first reaction zone a compound of Formula II with a compoùnd of Formula III;
tB) directing an effluent stream of the reaction mixture of Step (A) to a first separation zone from which is rapidly removed most of by-product HX as a complex with said compound of Formula III
and a product stream comprising predominantly a compound of Formula I and unreacted compound of Formula II;
(~) directing said product stream from said first separation zone to a second reactlon zone into : which is also introduced an additional quantit~
of said compound of Formula III to react with said unreacted compound of Formula II;
: (D) directing an effluent stream of the reaction mixture of Step (C) to a second separation zone from which is rapidl~ removed substantially all of the remaining by-product HX as a complex with said compound of Formula III and a product stream . comprised of said compound of Formula I and trace impurities.
Significant features of the process of this invention include: (1) the elimination of an added base as used in the prior art as an acid-binding agent for liberated hydrogen ,:
..~
r ~ ~
.: ;
halide; and concomitantly (2) elimination of recovery systems for the neutralization by-product of (1) nence, elimination from the environment of the by-product itself and (3) separation, preferably immediately and usually within ~0.5 minute of equilibration of the reaction mixture, of by-product hydrogen halide as a complex with the compound of Formula III in the product separation operation(s) of the process.
In preferred embodiments of the invention, the molar ratio of the compound of Formula III relative to the compound of ~ormula II in Step A is greater than 1:1 and usually within the range of about 2-100:1 and, in the case of the alachlor process, within the range of about 2-10:1 and preferably of 4-5:1.
The reaction temperatures in Step (A) will depend upon the particular reactants and/or solvents or diluents involved.
In general, these temperatures will be temperatures at which mixtures of the alcohols of Formula III and/or solvents or diluents from complexes, e.g., azeotropic mixtures, with by-product hydrogen halide without significant degradation of the reactant compound of Formula II or desired product of Formula I
due to reaction with hydrogen halide. In general, a temperature within the range of from about -25 to 125C or higher depending upon the melting/boiling points of the reactants is used.
In those embodiments of the invention involving a plurality of reaction/separation sequences, or stages, the hydrogen halide concentration is greatly reduced in successive reaction zones, hence the respective reaction temperatures are generally somewhat elevated over the temperatures used in Step (A) in order to drive the reaction of the unreacted compound of Formula II to : -11-.
~ OS90 completion with additional alcohol. Accordingly, temperatures in the second and any subsequent reaction zone are generally within the range of from about -25 to 175C or higher i necessary, Suitably the temperatures and pressures within the separation zone(s) are, respectively, within the ranges of from about 50C to 175C and 1.0 to 300 mm Hg absolute, depending upon the boillng point of the particular compound of Formula III.
Detailed Description of the Invention Exam~_e 1 This example describes the use of the process of this invention in the preparation of alachlor. This process is efficiently carried out in a reaction/separation sequence of two stages as follows:
- Stage 1~ Molten (45-55C) 2',6'-diethyl-N-chloromethyl-2-chloroacetanilide is fed to an in-line mixer at a rate of 102.8 lbs/hr (46.67 kg/hr) and mixed with substantially anhydrous methanol which is fed to said mixer at a rate of 60.0 lbs/hr (27.24 kg/hr). The mixture is pumped through a thermostatted pipe reactor maintained at 40-45C of sufficient length to give a residence time of at least thirty (30) minutes. The reaction produces a yield of ~ 92~ 2l,6'-diethyl-N-(methox~methyl)-2-chloroacetanilide (alachlor) and hydrogen chloride based on the N-chloromethyl intermediate. The generated HCl is dissolved in excess methanol. The reactor effluent is directed to a falling film evaporator operated at 100C and 30 mm Hg absolute. A com-plex is removed and fed to a methanol recovery system.
Stage 2. The product stream from the evaporator in Stage 1 comprising predominantly alachlor and unreacted 2'~6'-diethyl-N-~chloromethyl)-2-chloroacetanilide is red to a second .~
, . . .
9~
in-line mixer into which is also fed an additional quantity of methanol at a rate of 60 lbs/hr (27~24 kg/hr). The mixture is then fed to a second reaction zone also comprising a thermo-statted pipe reactor maintained at 60-65C to give a residence time of thirty (30) minutes. The effluent ~rom this reactor is fed to a second falling film evaporator, operated at 100C and 30 mm ~g absolute, from which is removed a complex of methanol and substantially all of the remaining HCl. The methanol/HCl ; complex from this second stage evaporator is mixed with the methanol/HCl complex from the evaporator in Stage 1 and fed to ~ a methanol recovery system from which anhydrous methanol is ; recovered and recycled to Stage 1.
The product stream from the evaporator in Stage 2 com-prises alachlor in essentially quantitative yield and greater than 95% purity togethex with minor amounts of impurities. This alachlor can be used effectively as a herbicide as produced.
As will be apparent from the foregoing example, the reaction/separation process sequence o Stage 1 by itself pro-duces alachlor of high yield. Hence, under optimum conditions of reactant purities and concentrations, temperatures, residence times in the reactor and separation zones, etc., at least one reaction/separation process sequence corresponding to said Stage 1 operation would suffice to produce a commercial grade of alachlor or other compounds within the scope of the above Formula Example 2 This example describes the preparation of 2-chloro-2',6'-diethyl-N-(etho~ymethyl) acetanilide.
About 5.5 g (0.02 mole) of 2-chloro-2',6'-diethyl-N-tchloromethyl) acetanilide was dissolved in 25 ml of ethanol and allowed to stand in a ~5C ~ath fo~ 30 minutes. Excess ethanol ,.
~ 13-"~
v was removed rapidly on a rGtary vacuum evaporator at 50C
and 10 mm Hg. Twenty-five (25) ml of fresh ethanol was added to the residual oil and the mixture held at 65C for 30 minutes. Again excess ethanol was removed using a rotary evaporator. About 5.80 g of a pale amber oil was obtained which assayed (by gas chromatography) 92.8% of the desired product and 1.7% 2-chloro-2',6' diethylacetanilide (by-product). Yield of product was 94.5%.
Example 3 Following the same procedure, operating conditions and quantities of reactants described in Example 2, but substituting isopropanol for ethanol, 5.92 gms of product, a light amber oil assaying 90.2% 2', 6'-diethyl-N-(isopropoxymethyl)-2-chloroacetanilide ~89.4% yield) and 1.8% of the secondary amide by-product 2', 6'-diethyl-2-chloroacetanilide was obtained.
Example 4 Following the same procedure described in Examples 2 and 3, but substituting l-propanol as the reactant alcohol, 5.66 gms of lemon-yellow oil was recovered which assayed 92.8% (87.9% yield) of 2', 6'-diethyl-N-(n-propoxymethyl)-2-chloroacetanilide and 1.2% of the corresponding secondary amide by-product.
Example 5 The same procedure described in Examples 2-4 was used in this example, but using isobutanol as the reactant alcohol, 6.20 gm of an oil product was recovered which assayed 96.4%
(97% yield) of 2',,6'-diethyl-N-(isobutoxymethyl)-2-chloroacet-anilide and 3% of the correspondin~ secondary amide by-product.
Example 6 Repeating the process of Examples 2-5, but using 2-chloro-ethanol as reactant alcohol, 6.96 gms of light-amber oil was recovered which assayed 86.0% (94.0~ yield) of 2'j6'-diethyl-N-:~4~ 0 (chloroethoxymethyl)-2-chloroacetaniliae.
Example 17 Following the same procedure described in Examples 2-6, but substituting n-butanol as the reactant alcohol, 6.18 gms of pale lemon-yellow oil was recovered which assayed 98.8~
(99% yield) of 2',6'-diethyl-N-(n-butoxymethyl)-2-chloroacetani-; lide (i.e., butachlor) and 1% of the corresponding secondary amine by-product.
In the abo~e examples, NMR analysis indicated that the respective products were consistent with chemical structure thereof.
In further elaboration of the advantages provided by the present invention and the unobvious nature thereof, the ollowing discussion and additional experimental data in Examples 12 is presented.
The reaction between compounds like those identified by Formula II and Formula III above is a reversible second-order reaction. Equation 1 below, exemplified by the reaction in ;~ Example 1, illustrates the reaction:
C2H5 ,, C2H5 0 (1) ~ C-CH2Cl ~ N ' CCH2Cl +HCl CH2Cl CH20CH3 (a) (b) (cl (d) Because the reaction is reversible, an equilibrium con-dition is established; this equilibrium is affected by and directly related to various factors, e.g., alcohol concentration and~or by-product hydxogen halide concentration. For example, in Equation (1) as alcohol (b) concentration, hence reactants ratio, (b):(a), increases(to a given practical maximum) the equation is shited to the right b~cause of additional con~ersion of starting material ,L~S~O
(a) thus producing more product (c) and hydrogen halide by-product (d).
Another way to shift the eguilibrium of Equation (1) to the right is to remove the hydrogen halide (d),which can be done by adding an acid-binderr e~g., tertiary amines such as triethylamine, as in V. S. Patents 3,547,620, 3,442,945 and Canadian Patent No~ 867,679 mentioned above. However, the use of acid-binding materials intxoduces other disadvantages as described above.
The foregoing Canadian '769 patent suggests that when the thio compound starting material is in the form of an alkali metal sal~ the acid-binding material is unnecessary; the apparent reason for this is that said salts themselves provide the basic medium, favorable to the particular reaction described in that patent. In contrast, when the starting thio compound is used in the free form, it is necessary to use an acid-binder to bind the hydrogen chloride by-product.
Although the process disclosed in the above '620 and '945 patents is described as being preferably conducted in the presence of an acid-binding agent (as exemplified in all of the specific working embodiments), an inference arises that the same process may be performed wi~hout the addition of an acid-binder. ~owever, as mentioned earlier (in section entitled "Description of the Prior Art") efforts to perform the process disclosed in the '945 and '620 patents to obtain the preferred product alachlor without an acid-binding agent to remove by-product hydrogen halide resulted in greatly diminished yields of alachlor~
In order to further determine the comparative results ~ 30 of practicing the process disclosed in the '945 and '620 patents ; ~ without an acid-binding agent vis-a-vis the process of the present ~ -16-5~0 invention, applicants herein conducted the processes described in Examples ~-12 below. In each of these examples, the N-chloro-methyl-2-chloroacetanilide starting material was prepared by the reaction of the corresponding substituted N-methyleneaniline ana haloacetyl halide as described in the '945 and '620 patents.
Example 8 This example describes the preparation of 2-chloro-2',-6'-diethyl-N-tmethoxymethyl) acetanilide ~alachlor) as taught in Example 5 of said U. S. Patent Nos.3,547,620 and 3,442,945.
One-hundred g of 2-chloro-2',6'-diethyl-N-(chloromethyl) acetanilide assaying 96,0% (0.350 mole) dissolved ln about 70 g of benzene was added to 65.8 g (2.054 molas) of methanol. On addition an exothermic reaction occurred. The reaction mixture was refluxed ~at 63C) and an excess (about 63.3 g) of triethyl-amina was added dropwise over 1-1/2 hours. During this addition the temperature rose to about 70C where it was maintained for about ten minutes after completion of the triethylamine addition.
After cooling to 30C, the reaction mixture was washed with two 170 ml portions o water. The product, in a heavy, oily layer was stripped of solvent and dehydrated by vacuum distillation to ; a terminal pot temperature of about 70C at 1 mm hg. The residual amber oil weighed 96.15 g and assayed 90.4~ product and 4.9% 2-chloro-2',6'-diethylacetanilide ~by-product) by gas chromatogra-phy. There was no unreacted starting material in the product.
The yield of product was 92.0~.
Example 9 This example describes the preparation of alachlor as taught in Example 5 of said '620 and '945 patents, but without the use of an acid-binding agent.
One-hundred g o~ 2-chloro-2',6'-diethyl-N-(chloromethyl) ~4~
acetanilide assaying 96.~ (0.350 mole) dissolved in about 70 g.
of benzene was added to 66.0 g. of methanol (2.059 moles). On addition, an exothermic reaction occurred ana the reaction mixture was further heated to reflux (at 63C) or one hour. No acid-binding agent was added. After refluxing, excess methanol and solvent were remo~ed by vacuum distillation to a ~inal pot temper-ature of 70C at 1 mm Hg. About 96.83 g. of a pale lemon-yellow oil was obtained which contained (by gas chromatographic analysis) 83.7% product, 7.5% by-product 2-chloro-2',6'-diethyl acetanilide and 5.5% unreacted start1ng material. The yield of product was 85.8%.
As will be noted, omission of an acid-binding agent in this example resulted in a reduction in yield of 6.2%. In this process, the reaction was not shited completely to the right. As a result, the by~product HC1 reduced conversions and the unreacted starting material was found as a con~aminant în the product.
Example 10 This example describes the preparation of alachlor as taught in Example 5 of said '620 and '945 patents, but w1thout the use of an acid-binding agent and under optimized temperature condi-tions.
One-hundred g. of 2-chloro-2',6'-diethyl-N-(chloromethyl) acetanilide assaying 96.0% (0.350 mole) dissolved in about 70 g.
of benzene was added to 66 g. (2.059 moles) of methanol. An exothermic reaction occurred which raised the reaction mixture temperature to 45C where it was maintained for one hour. No acid-binding agent was added. Excess methanol and solvent were stripped off under vacuum distillation to a final pot temperature of about 80C at 1 mm Hg. About 96.20 g. of oil was recovered which assayed (by gas chromatography) 85.3% product, 6.2% by~
produc~, 2-chloro-2',6'~diethyl acetanilide and about 4.6~ un-_l g_ )590 reacted starting material. The yield of product was 87.4~.
By optimizing reaction conditions in the absence of an acid-binding agent, an increase in product quality (2.7%) and yield (1.6~ was reali~ed, but the basic problem, i.e., incomplete reaction, has still not been solved.
Example 11 This example describes the preparation of alachlor by the process of the present in~ention according to the embodi-ment using a single stage reactor; the starting materials used 1~ herein were the same as those used in Examples 8~
Ten g. of 2-chloro-2',6'-diethyl-N-(chloromethyl) acetanilide assaying 9~.0~ (0.035 mole) was added to about 6.0 0.1873 mole) of methanol. An exothermic reaction occurred raising the reaction mixture temperature to about 45C where it was maintained for thirty minutes. Excess methanol was removed rapidly on a vacuum rotary evaporator to a final pot temperatu~e of 70C at 1 mm Hg. About 9.80 g. of pale lemon yellow oil was ; recoverad assaying 91.0~ product, 1.7% by-pro~uct 2-chloro-2',6'-diethylacetanilide, and 2.4% unreacted starting material by gas chromatography. The yield of product was 94.4~.
Thus, using only a single stage, the quality and yield of the desired product is substantially improved over that of the prior art despite the fact that tha reaction was not complete (2.4% starting material in product). Comparison with Examples 8, 9 and iO shows an obvious improvement, although no acid-binding agent was used.
Example 1~
~ This example describes the preparation of alachlor in the absence of an added acid-binding agent according to the pre-ferred process of the present invention using a multiple stage -~ --19--1~jLL~ 59C~
reactor.
Ten g. of 2-chloro-2',6'-diethyl-N-(chloromethyl) acetanilide assaying 96.0% (.035Q mole) was dissol~ed in 6.0 g.
(0.1873 mole) of methanol. An exothermic reaction occurred raising the temperature to 45C where it was maintained for one-half hour. Excess methanol was remov~d rapidly on a rotary vacuum evaporat~r to a final pot temperature of 45C at 1 mm Hg.
A second addition of fresh methanol, 6.0 ~ (0.1873 mole) was added, the reaction mixture warmed to 65C and held for one-half hour. Excess methanol was removed as before and about 9.80 g. of pale lemon-yellow oil was recovered assaying 95.8% product, 1.4%
2-chloro-~',6'-diethylacetanilide and no unreacted starting material~ The yield of product was 99.4%.
A summaxy of the comparative results of the processes d scribed in Examples 8-l~ is shown in the following table. In this table, the "Starting Material" is unreacted 2l,6'-diethyl-N-~chloromethyl)-2-chloroacetanilide and the "By-Product" refers to 2',6'-diethyl-2-chloroacetanilide, the major acetanilide by-; product in the processes of each of these examples. It will be understood that minor amounts of acetanilide and other by-products are produced in addition to the large quantities of hydrogen hal-~ ide generated and, in the case of Example B, triethylamine hydro - chloride neutralization by-product produced. Product yield percentages herein are based on the 2',6'-diethyl-N-(chloromethyl)-2-chloroacetanilide starting materlal.
~2Q-:
S9~
~ABLE
~ ' Exam- Pro- Ala- Start-ple ce~s chlor Ala- By- ing Ma-No. Type Yield(%) chlor Product terial __ _ _ _ , 8 Ex. 5 U.S. Pats. 92.0 90.S 4.9 0 3,442,g45 &
3,s47,620;
base added 9 Ditto, except 85.8 83.7 7.5 5.5 base omitted 10 Same as Ex. 9 87.4 85.8 6.2 4.6 with optimized conditions 11 Present process, 94.4 91.0 1.7 2.4 l-stage 12 Ditto, plural 99.4 95.8 1.4 0 stages ,.~
An analysis of the data in the above table will show as ;; 20 the salient features and distinct advantages of the process of this invantion, i.e., Examples 11 and 12, vis-a-vis the process , ~
of the prior art exemplified in Examples 8-Io;(l~ substantial increases in yield of alachlor; (2) improvement in alachlor puri-ty; (3) markPdly decreased yields by-product; (4) increased con-version of starting material when operating without added base;
and (~) absence of solid neutralization product which is present in large quantities in the base-added process of Example 8 -- rep-resenting the best previously known technology for producing alachlor. These technical adva~tages are additive to the economi cal and ecological advantages mentioned earlier.
In practicing the present invention, no solvent is re-quired; however, in many cases a solvent or diluent may be used to moderate the reaction and/or aid in the solution, dispersion and/or recovery of reactants, by-products and products. Suitable ¢
- solvents or diluents include those which are inert under the re~uired conditions of reaction, such as petroleum ether, CC14, ;
5~3~
aliphatic and aromatic hydrocarbons, e.g., hexane, benzene, toluene, xylenes, etc., and halogenated hydrocarbons, e.g., mono-chlorobenzene.
An advantage of the process according to this invention is that the reactant of Formula III may be readily separated from its complex with by-product hydrogen halide, purified and recycled to one or more reaction stages of the process. In like manner, the hydrogen halide itself may be readily recovered for use in many useful commercial operations, e.g., pickling of metals, oxychlorinations, electrolysis to elemental chlorine and hydrogen, etc., or otherwise disposed of without detriment to the environment.
In one suitable raw material recovery/recycle system, exemplified with respect to the methanol/~Cl complex formed in the alachlor process described in the above Examples 1, 11 and 12, the methanol/HCl complex from the separation stage(s) is fed to a distillation system from which purified methanol is obtained.
With further respect to the present process, while the use of technical grade reactants, i.e~, the compounds of Formulae II and III, is suitable, it will be appreciated that the higher the purity of these reactants, the higher the quality of compounds of Formula I will be produced. Although in some instances the Formula III compounds, e.g., methanol~ containing minor amounts of water can be used, it is much more preferable to use anhydrous compounds, because water may cause hydrolysis of the Formula II reactants resulting in deteriorated product of Formula I. However, it will be understood that in the special case where R6 is hydrogen water itself can be used as the compound of Formula III to produce some compounds of Formula I by hydroly-sis of the N-haloalkyl intermediate. For example, it has been disclosed in the prior art that 2'-tert-butyl-6'-ethyl-N-(chloro-methyl~-2-chloroacetanilide is hydrolyzed with water in the :~
V5~0 presence of an acid binding agent to produce the corresponding N-hydroxymethyl compound which is useful as a herbicide tsee~
e.g., Example 1 in British Patent No. 1,088,397). Accordingly, it will be appreciated that in some embodiments of the present process the presence of some water may be detrimental to product yield but not in other embodiments, depending upon the reactivity of water with other reactants and final products as will be understood by those skilled in the art. In like manner, since hydrogen halide adversely impacts on product quality, it is preferred to use reactants substantially free of hydrogen halides such as HCl.
Representative compounds produced according to the process of this invention include those in which the groups of the above formulae have the following identities:
R - hydrogen~ Cl_l8 alkyls, e.g., methyl, ethyl, propyls, butyls, pentyls, hexyls, heptyls, octyls, nonyls, decyls, undecyls, dodecyls, pentadecyls, octadecyls, etc.; alkenyls, e.g., vinyl, allyl, crotyl, methallyl, butenyls, pentyls, hexenyls, heptenyls, octenyls, nonenyls, decenyls, etc., alkynyls, e.g., ethynyl, propynyls, butynyls, pentynyls, hexynyls, etc.; the alkoxy, polyalkoxy, alkoxyalkyl and polyalkoxyalkyl analogs of the foregoing alkyl groups; cycloalkyls and cycloalkylalkyls having up to 7 cyclic carbons, e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, etc.; cycloalkenyls and cycloalkadienyls having up to 7 cyclic carbons, e.g., cyclo-pentenes, cyclohexenes and cycloheptenes having mono- and di-unsaturation; C6 18 aryl and aralkyl and alkaryl groups, e.g., phenyl, tolyls, xylyls, benzyl, naphthyl, etc., and said R members substituted with radicals which are non-reactive , with hydrogen, e.g., alkyls, alkoxys, halogen, nitro or cyano, ., . -, , ~ .
~;~4(;~5g~
when the substituent is a halogen atom, it must not be on the a-carbon atom in which position it is reactive with hydrogen.
Rl, R , R and R - hydrogen, fluorine, the Cl 6 alkyls o~ R, haloalkyls, e.g., chloromethyl, chloroethyl, bromomethyl, bromoethyl, iodomethyl, iodoethyl, trifluoro-methyl, chloropropyl, bromopropyl, iodopropyl, chlorobutyl, iodobutyl and di- and trihalo analogs thereof; alkoxys, e.g., methoxy, ethoxy, propoxys, butoxys, pentoxys and hexoxys and corresponding polyalkoxys and alkoxyalkyls, e.g., methoxymethoxy, methoxyethoxy, ethoxymethoxy, ethoxyethoxy, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, propoxymethyl, isopropoxymethyl, butoxymethyl, isobutoxymethyl, tert-butoxymethyl, pentoxymethyl, hexoxymethyl, etc.
Rl and R2 may also be chlorine, bromine or iodine.
R3 may be hydrogen, the halo, alkyl, haloalkyl, alkoxy and alkoxyalkyl groups of Rl, R2, R4 and R5, methylthio, ethyl-thio, propylthio, CN, NO2l CF3 or R3 may be combined with l or R2 to form an alkylene chain of up to 4 carbon atoms, thus forming acylated 5-amino-tetralins and acylated 4-aminoindanes typified in the above-mentioned U.S. Patent No.
` 3,875,228.
R6 may be hydrogen, the Cl 10 alkyl, alkenyl, alkynyl, and alkoxyalkyl groups of R; oxoalkyl groups corresponding to the above alkyl groups, e.g., 2-oxobutyl, 3-oxopentyl, 4-oxohexyl, etc., the C3 7 cycloalkyl, cycloalkenyl and alkylcycloalkyl groups of R; the C6 12 aryl and aralkyl groups of R; amino and mono- and di-substituted amino containing the above Cl 6 alkyl, alkenyl or alkynyl groups; and the above R6 members which may be substituted with substituents such as alkyl, halogen, hydroxy, alkoxy, nitro, cyano or alkylthio.
5~
R7 is Cl 5 haloalkyl, preferably Cl 2 monohaloalkyls, such as chloromethyl, chloroethyl, bromomethyl, bromoethyl, iodo-methyl, iodoethylr fluoromethyl and fluoroethyl; dihaloalkyls such as l,l-dichloromethyl, l,l-dibromomethyl, l,l-diodomethyl, etc., may also be present.
X is halo, expecially chlorine or bromine.
The process of the present invention is particularly amenab~e to use in the preparation of the above defined N-sub-stituted-2-haloacetanilides wherein R1, R2 and R6 are Cl 6 alkyl, R7 is monohalomethyl, Y and yl are oxygen, a is zero and b is 1 or 2, preferably 1.
Compounds of Formula I prepared acaording to this in-vention are known compounds. Representative compounds of Formula I are disclosed in the prior art described in the foregoing section entitled "Description of the Prior Art" and other prior art not cited herein. Hence, the inventors herein lay no claim to the compounds, per se, of Formula I.
It will be appreciated by those skilled in this art that the preferred 2-haloacetanilides are a subgenus of N,N-di-substituted-2-haloacylamides. Accordingly, the process of this invention may be modiied in a manner within the skill of this art as the nature and concentration of reactants, reaction and separation conditions of temperature, pressure, residence times, etc., to produce other compounds within a broad genesis of said N,N-disubstituted-2-haloacylamides.
`' `
''', .
Claims (23)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. Process for the preparation and recovery of compounds of Formula I
I wherein R is hydrogen, C1-18 alkyl, alkenyl, alkynyl, alkoxy, polyalkoxy, alkoxyalkyl, polyalkoxyalkyl, C5-7 cyclo-alkyl, cycloalkylalkyl, cycloalkenyl, C6-18 aryl, aralkyl, or alkaryl or said R members substituted with radicals which are nonreactive with hydrogen, R4 and R5 are independently hydroyen, fluorine, C1-6 alkyl, haloalkyl, alkoxy or alkoxyalkyl;
R6 is hydrogen, C1-10 alkyl, alkenyl, alkynyl, alkoxyalkyl, oxoalkyl, C3-7 cycloalkyl, lower alkylcycloalkyl or cycloalkenyl, C6-12 aryl or aralkyl, -N(R8)2 wherein R8 is hydrogen, C1-6 alkyl, alkenyl, or alkynyl; or said R6 members substituted with alkyl, alkylthio, halogen, hydroxy, alkoxy, nitro or cyano;
R7 is C1-5 mono- or dihaloalkyl;
Y and Y1 are oxygen or sulfur and b is an integer from 1-4 inclusive, which comprises performing at least one sequence of reaction/
separation operations comprising:
(A) reacting a compound of Formula II
with a compound of Formula III
III R6(Y1)H
wherein R, R4, R5, R6, R7, Y, Y1, and b are as defined above and X is halogen in the absence of added acid-binders, and (B) directing an effluent stream of the reaction mixture from Step (A) to a separation zone from which is rapidly removed a complex mixture of by-product HX
with said compound of Formula III and a product stream comprising predominantly said compound of Formula I.
I wherein R is hydrogen, C1-18 alkyl, alkenyl, alkynyl, alkoxy, polyalkoxy, alkoxyalkyl, polyalkoxyalkyl, C5-7 cyclo-alkyl, cycloalkylalkyl, cycloalkenyl, C6-18 aryl, aralkyl, or alkaryl or said R members substituted with radicals which are nonreactive with hydrogen, R4 and R5 are independently hydroyen, fluorine, C1-6 alkyl, haloalkyl, alkoxy or alkoxyalkyl;
R6 is hydrogen, C1-10 alkyl, alkenyl, alkynyl, alkoxyalkyl, oxoalkyl, C3-7 cycloalkyl, lower alkylcycloalkyl or cycloalkenyl, C6-12 aryl or aralkyl, -N(R8)2 wherein R8 is hydrogen, C1-6 alkyl, alkenyl, or alkynyl; or said R6 members substituted with alkyl, alkylthio, halogen, hydroxy, alkoxy, nitro or cyano;
R7 is C1-5 mono- or dihaloalkyl;
Y and Y1 are oxygen or sulfur and b is an integer from 1-4 inclusive, which comprises performing at least one sequence of reaction/
separation operations comprising:
(A) reacting a compound of Formula II
with a compound of Formula III
III R6(Y1)H
wherein R, R4, R5, R6, R7, Y, Y1, and b are as defined above and X is halogen in the absence of added acid-binders, and (B) directing an effluent stream of the reaction mixture from Step (A) to a separation zone from which is rapidly removed a complex mixture of by-product HX
with said compound of Formula III and a product stream comprising predominantly said compound of Formula I.
2. Process according to Claim 1 wherein said reaction/separation process sequence is repeated a plurality of times to assure complete conversion of said compound of Formula II to said compound of Formula I.
3. Process according to Claim 2 in which said reaction/separation process is carried out in a sequence of two stages which comprises:
(A) reacting in a first reaction zone a compound of Formula II with a compound of Formula III;
(B) directing an effluent stream of the reaction mixture of Step (A) to a first separation zone from which is rapidly removed most of by-product HX as a complex with said compound of Formula III
and a product stream comprising predominantly a compound of Formula I and unreacted compound of Formula II;
(C) directing said product stream from said first separation zone to a second reaction zone into which is also introduced an additional quantity of said compound of Formula III to react with said unreacted compound of Formula II;
(D) directing an effluent stream of the reaction mixture of Step (C) to a second separation zone from which is rapidly removed substantially all of the remaining by-product HX as a complex with said compound of Formula III and a product stream comprised of said compound of Formula I and trace impurities.
(A) reacting in a first reaction zone a compound of Formula II with a compound of Formula III;
(B) directing an effluent stream of the reaction mixture of Step (A) to a first separation zone from which is rapidly removed most of by-product HX as a complex with said compound of Formula III
and a product stream comprising predominantly a compound of Formula I and unreacted compound of Formula II;
(C) directing said product stream from said first separation zone to a second reaction zone into which is also introduced an additional quantity of said compound of Formula III to react with said unreacted compound of Formula II;
(D) directing an effluent stream of the reaction mixture of Step (C) to a second separation zone from which is rapidly removed substantially all of the remaining by-product HX as a complex with said compound of Formula III and a product stream comprised of said compound of Formula I and trace impurities.
4. Process according to Claim 3 wherein Step (A) is conducted at a temperature within the range of from about -25 to 125°C.
5. Process according to Claim 3 wherein Step (C) is conducted at temperatures within the range of from about -25 to 175°C.
6. Process according to Claim 3 wherein Steps (B) and (D) are conducted at temperatures and pressures sufficient to separate a complex of the compound of Formula III and hydrogen halide from the effluent streams of Steps (A) and (C).
7. Process according to Claim 3 wherein the compound of Formula III is used in an amount corresponding to a molar ratio of > 1:1 relative to the compound of Formula II.
8. Process according to Claim 7 wherein said molar ratio is within the range of about 2-100:1.
9. Process according to Claim 3 wherein said complex of HX with compound of Formula III from Step (D) is fed to a recovery system from which said compound of Formula III is re-moved from said hydrogen halide, purified and recycled to Steps (A) and/or (C).
10. Process according to Claim 3 wherein temperatures in Steps (B) and (D) are within the range of about 50°C. to 175°C. and pressures are within the range of about 1.0 to 300 mm Hg absolute.
11. Process for the preparation and recovery of haloacetanilides of the formula IV:
IV
wherein R1 and R2 are independently hydrogen, halogen, C1-6 alkyl, haloalkyl, alkoxy or alkoxyalkyl;
R3 is hydrogen, halogen, C1-6 alkyl, haloalkyl, alkoxy, alkoxyalkyl, alkylthio, CN, NO2 or CF3 or R3 may be combined with R1 or R2 to form an alkylene chain of up to 4 carbon atoms;
R4 and R5 are independently hydrogen, fluorine, C1-6 alkyl, haloalkyl, alkoxy or alkoxyalkyl, R6 is hydrogen, C1-10 alkyl, alkenyl, alkynyl, alkoxyalkyl, oxoalkyl, C3-7 cycloalkyl, lower alkylcycloalkyl or cycloalkenyl, C6-12 aryl or aralkyl, -N(R8)2 wherein R8 is hydrogen, C1-6 alkyl, alkenyl, or alkynyl; or said R6 members substituted with alkyl, alkylthio, halogen, hydroxy, alkoxy, nitro or cyano;
R7 is C1-5 mono- or dihaloalkyl;
Y and Y1 are oxygen or sulfur;
a is an integer from 0-3 inclusive; and b is an integer from 1-4 inclusive;
which comprises performing at least one sequence of reaction/
separation operations comprising:
(A) reacting a compound of Formula II
II
with a compound of Formula III
R6(Y1)H III
wherein R, R4, R5, R6, R7, Y, Y1, and b are as defined above and X is halogen in the absence of added acid-binders, and (B) directing an effluent stream of the reaction mixture from Step (A) to a separation zone from which is rapidly removed a complex mixture of by-product HX with said compound of Formula III and a product stream com-prising predominantly said compound of Formula IV.
IV
wherein R1 and R2 are independently hydrogen, halogen, C1-6 alkyl, haloalkyl, alkoxy or alkoxyalkyl;
R3 is hydrogen, halogen, C1-6 alkyl, haloalkyl, alkoxy, alkoxyalkyl, alkylthio, CN, NO2 or CF3 or R3 may be combined with R1 or R2 to form an alkylene chain of up to 4 carbon atoms;
R4 and R5 are independently hydrogen, fluorine, C1-6 alkyl, haloalkyl, alkoxy or alkoxyalkyl, R6 is hydrogen, C1-10 alkyl, alkenyl, alkynyl, alkoxyalkyl, oxoalkyl, C3-7 cycloalkyl, lower alkylcycloalkyl or cycloalkenyl, C6-12 aryl or aralkyl, -N(R8)2 wherein R8 is hydrogen, C1-6 alkyl, alkenyl, or alkynyl; or said R6 members substituted with alkyl, alkylthio, halogen, hydroxy, alkoxy, nitro or cyano;
R7 is C1-5 mono- or dihaloalkyl;
Y and Y1 are oxygen or sulfur;
a is an integer from 0-3 inclusive; and b is an integer from 1-4 inclusive;
which comprises performing at least one sequence of reaction/
separation operations comprising:
(A) reacting a compound of Formula II
II
with a compound of Formula III
R6(Y1)H III
wherein R, R4, R5, R6, R7, Y, Y1, and b are as defined above and X is halogen in the absence of added acid-binders, and (B) directing an effluent stream of the reaction mixture from Step (A) to a separation zone from which is rapidly removed a complex mixture of by-product HX with said compound of Formula III and a product stream com-prising predominantly said compound of Formula IV.
12. Process according to Claim 11 wherein in said haloacetanilides R1, R2 and R6 are C1-6 alkyl, R4 and R5 are hydrogen or C1-6 alkyl, R7 is C1-2 monohaloalkyl, Y and Y1 are oxygen, a is zero and b is 1 or 2.
13. Process according to Claim 12 wherein in said haloacetanilides R1 and R2 are ethyl, R4 and R5 are hydrogen, R6 is C1-6 alkyl, R7 is 2-chloromethyl and b is 1.
14. Process according to Claim 13 wherein R6 is methyl.
15. Process according to Claim 13 wherein R6 is ethyl.
16. Process according to Claim 13 wherein R6 is a propyl isomer.
17. Process according to Claim 13 wherein R6 is a butyl isomer.
18. Process according to Claim 17 wherein said butyl isomer is n-butyl.
19. Process for the preparation and recovery of alachlor which comprises performing at least one sequence of reaction/separation operations comprising:
(A) reacting methanol with 2',6'-diethyl-N-chloro-methyl)-2-chloroacetanilide at a molar ratio of about 2-100:1 at temperatures within the range of from about 25°-65°C for a period of from about 15-30 minutes in the absence of added acid binders, and (B) directing an effluent stream of the reaction mixture from Step (A) to a separation zone from which is rapidly removed a complex mixture of HC1 and methanol and a product stream comprising predominantly alachlor.
(A) reacting methanol with 2',6'-diethyl-N-chloro-methyl)-2-chloroacetanilide at a molar ratio of about 2-100:1 at temperatures within the range of from about 25°-65°C for a period of from about 15-30 minutes in the absence of added acid binders, and (B) directing an effluent stream of the reaction mixture from Step (A) to a separation zone from which is rapidly removed a complex mixture of HC1 and methanol and a product stream comprising predominantly alachlor.
20. Process according to Claim 19 wherein said reac-tion/separation sequence is repeated a plurality of times to assure substantially complete conversion of 2',6'-diethyl-N-(chloromethyl)-2-chloroacetanilide to alachlor.
21. Process according to Claim 20 which comprises:
(A) reacting in a first reaction zone maintained at about 25-65°C methanol with 2',6'-diethyl-N-(chloromethyl)-2-chloroacetanilide at a molar feed ratio of about 2-10:1 in the absence of added acid binders for a period of from about 15 to 30 minutes;
(B) directing an effluent stream of the reaction mixture of Step (A) to a flash distillation zone maintained at temperatures and pressures within the ranges of about 50-100°C and 30-300 mm Hg absolute from which is removed a complex mixture of methanol and most of by-product HC1 and a product stream comprising predominantly alachlor and unreacted 2',6i-diethyl-N (chloromethyl)-2-chloroacetanilide;
(C) directing said product stream from said first separation zone to a second reaction zone main-tained at about 25-65°C into which is also intro-duced an additional quantity of methanol to react with said unreacted 2',6'-diethyl-N-(chloromethyl)-2-chloroacetanilide in an amount corresponding to the amount used in first reaction zone for a period of from about 15 to 30 minutes;
(D) directing an effluent stream of the reaction mixture of Step (C) to a second flash distillation zone maintained at temperatures and pressures within the ranges of about 50-100°C and 30-300 mm Hg absolute from which is removed a complex mix-ture comprising methanol and substantially all of the remaining by-product HC1 and a product stream comprised of alachlor and trace impurities.
(A) reacting in a first reaction zone maintained at about 25-65°C methanol with 2',6'-diethyl-N-(chloromethyl)-2-chloroacetanilide at a molar feed ratio of about 2-10:1 in the absence of added acid binders for a period of from about 15 to 30 minutes;
(B) directing an effluent stream of the reaction mixture of Step (A) to a flash distillation zone maintained at temperatures and pressures within the ranges of about 50-100°C and 30-300 mm Hg absolute from which is removed a complex mixture of methanol and most of by-product HC1 and a product stream comprising predominantly alachlor and unreacted 2',6i-diethyl-N (chloromethyl)-2-chloroacetanilide;
(C) directing said product stream from said first separation zone to a second reaction zone main-tained at about 25-65°C into which is also intro-duced an additional quantity of methanol to react with said unreacted 2',6'-diethyl-N-(chloromethyl)-2-chloroacetanilide in an amount corresponding to the amount used in first reaction zone for a period of from about 15 to 30 minutes;
(D) directing an effluent stream of the reaction mixture of Step (C) to a second flash distillation zone maintained at temperatures and pressures within the ranges of about 50-100°C and 30-300 mm Hg absolute from which is removed a complex mix-ture comprising methanol and substantially all of the remaining by-product HC1 and a product stream comprised of alachlor and trace impurities.
22. Process according to Claim 21 wherein said complex of methanol and HC1 from Steps (B) and (D) are combined and fed to a methanol recovery system from which HC1 is removed and re-covered methanol is purified and recycled to Steps (A) and/or (C).
23. Process according to Claim 22 wherein the residence time of said reaction mixture in said flash distillation zones of Steps (B) and (D) is <0.5 minute.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75527976A | 1976-12-29 | 1976-12-29 | |
| US755,279 | 1976-12-29 | ||
| US84454277A | 1977-10-26 | 1977-10-26 | |
| US844,542 | 1977-10-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1140590A true CA1140590A (en) | 1983-02-01 |
Family
ID=27116061
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000294001A Expired CA1140590A (en) | 1976-12-29 | 1977-12-28 | Process for the production of haloacylamides |
Country Status (30)
| Country | Link |
|---|---|
| JP (1) | JPS53101312A (en) |
| AR (1) | AR228123A1 (en) |
| AT (1) | AT359996B (en) |
| AU (1) | AU515013B2 (en) |
| BG (1) | BG31363A3 (en) |
| BR (2) | BR7708771A (en) |
| CA (1) | CA1140590A (en) |
| CH (1) | CH638489A5 (en) |
| DD (1) | DD134085A5 (en) |
| DE (1) | DE2758418A1 (en) |
| DK (1) | DK149196C (en) |
| ES (1) | ES465723A1 (en) |
| FR (1) | FR2376126A1 (en) |
| GB (1) | GB1587851A (en) |
| GR (1) | GR66096B (en) |
| IE (1) | IE46287B1 (en) |
| IL (1) | IL53711A0 (en) |
| IT (1) | IT1090371B (en) |
| LU (1) | LU78777A1 (en) |
| MX (1) | MX6258E (en) |
| MY (1) | MY8400362A (en) |
| NL (1) | NL7714405A (en) |
| NO (1) | NO147303C (en) |
| NZ (1) | NZ186106A (en) |
| PL (1) | PL121520B1 (en) |
| PT (1) | PT67465B (en) |
| RO (1) | RO83713B (en) |
| SE (1) | SE441182B (en) |
| TR (1) | TR19809A (en) |
| YU (1) | YU41581B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU177876B (en) * | 1979-04-24 | 1982-01-28 | Nitrokemia Ipartelepek | Process for preparing 2,6-dialkyl-n-/alkoxy-methyl/-chloro-acetanilide derivatives |
| US4311858A (en) * | 1980-12-01 | 1982-01-19 | Monsanto Company | Process for producing N-(halomethyl) acyl-amides |
| DE3569523D1 (en) * | 1984-09-03 | 1989-05-24 | Ciba Geigy Ag | N- (SUBSTITUTED ALKYL) DICHLOROACETAMIDE DERIVATIVES |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA867769A (en) * | 1971-04-06 | Farbenfabriken Bayer Aktiengesellschaft | Fluoracylamino-trichloromethyl-methane derivatives | |
| US2863752A (en) * | 1953-10-30 | 1958-12-09 | Monsanto Chemicals | Herbicides |
| US3287106A (en) * | 1963-11-15 | 1966-11-22 | Monsanto Co | Method for inhibiting the growth of grass type weeds |
| US3442945A (en) * | 1967-05-22 | 1969-05-06 | Monsanto Co | Phytotoxic alpha-halo-acetanilides |
| US3574746A (en) * | 1967-06-05 | 1971-04-13 | Monsanto Co | N-(cycloalken-1-yl) alpha-haloacetamides |
| DE1903198A1 (en) * | 1969-01-23 | 1970-08-06 | Basf Ag | Substituted anilides |
| US3547620A (en) * | 1969-01-23 | 1970-12-15 | Monsanto Co | N-(oxamethyl)alpha-halo-acetanilide herbicides |
| US3637847A (en) * | 1969-09-03 | 1972-01-25 | Monsanto Co | N-haloalkyl-anilides |
| BE795197A (en) * | 1972-02-11 | 1973-08-09 | Ciba Geigy | BICYCLIC HYDROCARBON ACYLAMINES ACTING ON PLANT GROWTH |
-
1976
- 1976-12-29 ES ES465723A patent/ES465723A1/en not_active Expired
-
1977
- 1977-12-16 MX MX776727U patent/MX6258E/en unknown
- 1977-12-22 NZ NZ186106A patent/NZ186106A/en unknown
- 1977-12-23 AU AU32015/77A patent/AU515013B2/en not_active Expired
- 1977-12-27 NL NL7714405A patent/NL7714405A/en not_active Application Discontinuation
- 1977-12-28 PT PT67465A patent/PT67465B/en unknown
- 1977-12-28 IT IT31350/77A patent/IT1090371B/en active
- 1977-12-28 AT AT935977A patent/AT359996B/en not_active IP Right Cessation
- 1977-12-28 BG BG7738247A patent/BG31363A3/en unknown
- 1977-12-28 DE DE19772758418 patent/DE2758418A1/en active Granted
- 1977-12-28 CH CH1612577A patent/CH638489A5/en not_active IP Right Cessation
- 1977-12-28 IL IL53711A patent/IL53711A0/en not_active IP Right Cessation
- 1977-12-28 FR FR7739526A patent/FR2376126A1/en active Granted
- 1977-12-28 DK DK582177A patent/DK149196C/en active
- 1977-12-28 BR BR7708771A patent/BR7708771A/en unknown
- 1977-12-28 RO RO92701A patent/RO83713B/en unknown
- 1977-12-28 AR AR270542A patent/AR228123A1/en active
- 1977-12-28 YU YU3142/77A patent/YU41581B/en unknown
- 1977-12-28 CA CA000294001A patent/CA1140590A/en not_active Expired
- 1977-12-28 JP JP15750477A patent/JPS53101312A/en active Granted
- 1977-12-28 DD DD77202986A patent/DD134085A5/en unknown
- 1977-12-28 BR BR7708711A patent/BR7708711A/en unknown
- 1977-12-28 LU LU78777A patent/LU78777A1/xx unknown
- 1977-12-28 GR GR55054A patent/GR66096B/el unknown
- 1977-12-28 NO NO774478A patent/NO147303C/en unknown
- 1977-12-28 GB GB53977/77A patent/GB1587851A/en not_active Expired
- 1977-12-29 IE IE2631/77A patent/IE46287B1/en not_active IP Right Cessation
- 1977-12-29 SE SE7714872A patent/SE441182B/en not_active IP Right Cessation
- 1977-12-29 PL PL1977203537A patent/PL121520B1/en not_active IP Right Cessation
-
1979
- 1979-12-28 TR TR19809A patent/TR19809A/en unknown
-
1984
- 1984-12-30 MY MY362/84A patent/MY8400362A/en unknown
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