Note: Descriptions are shown in the official language in which they were submitted.
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
AG-1141
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-
;
-3-
: ' :
AG-1141
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-
_~ _
AG-1141
, ~
~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
?
AG-1141
, ~
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,
.
7-
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
'
C-R7
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
R C-R7
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 ~ ~
--1 0--
.: ;
590
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-
.
AG 1141
~ 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
.~
AG-1141
, . . .
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-
-14-
AG-1141
:~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
-15-
AG-1141
,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-
AG-1141
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)
-17-
AG-1141
~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_
AG-1141
)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--
AG-1141
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-
:
AG-1141
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,
;
-21-
AG-1141
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
:~
22-
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,
., . -
-23-
,
,
~ .
~;~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.
-24-
AG-1141
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.
`' `
''',
.
-25-
