Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
6~
5 l523~/ZFOJCI~
rrocess for the prepa-ra-tlon of N-alkylaniline6
The pre6ent invention relates to a process for the preparation of
N-alkylanilines of the formula I
~Rl
H-C ~ (I)
.=.~ 4
~2
wherein
Rl and R2 are each independently Cl-C6alkyl, Cl-C6alkoxy or
hydroaen
R3 i6 Cl-C6alkyl, C3-C6cycloalkyl, Cl-C4alko~cy, Cl-C4alkoxy- Cl-
C4alkyl, phenyl or hydrogen,
R4 is Cl-C6alkyl, Cl-C4alkoxy, furfuryl, tetrahydrofurfuryl or
hydrogen, and R3 and R4 to~ether with the carbon atom to which
they are attached can form a 4- to 7-membered isocyclic rin~
which 18 unsub~tituted or ~ubstituted by one or two Cs-C4alkyl
groups or a pyran or a tetrahydropyran rin~,
and to a catalyst for carryina out said procen~.
N-alkylanilines of the formula I are valuable lntermediates for the
preparation of pesticidal actlve compounds. Thus, N-alkylanilines of
the formula I can be converted by means of haloacetyl halides, 6uch
a~ chloroacetyl chloride or bromoacetyl bromide, into the corre~pon-
dina acetanilides havln~ a pestlcidal action. Acetanilides of this
type snd their preparation and use are described, for example, in
l Z7~ L8
-- 2 --
U.S. Pat. Nos. 2,863,752, 3,345,151, 3,268,584, 3,952,056 and
3,937,730, in French Pat. No. 1,339,001 und in German Pat. No.
2,305,495 and German Auslegeschrift 2,328,340.
It is known to prepare N-alkylanllines by reacting anilines with
alkyl halides, alkyl tosylates or alkyl phosphates. When this method
is used, however, considerable amounts of N,N-dialkylaniline6 are
always formed in addition to the desired N-monoalkylanilines.
Therefore, because its selec~ivity is too low, this proces6 i6
unsuitable for indu~trial preparation of compounds of the formula I.
Moreover, this process present6 ecological problems since the waste
waters alway6 contain large amounts of hydrogen halide, toluene-
sulfonic acid or phosphoric acid, or salts of these acide.
It has also already been proposed to react anilines in the presence
of catalysts with alcohol~ to give N-alkylanilines (cf. Kirk-Othmer,
Encyclopaedia of Chemical Technology, 2nd edition, volume 2,
412-13). Catalysts used in this process were, in addltion to
aluminium oxide, aluminium silicate, a ml~ture of phosphorlc acid
and bentonite, and mineral acids, such a~ hydrochloric acid or
sulfuric acid, also hydrogen transfer catalysts. ~or e~ample,
according to a process de~cribed in ~.S. Patent No. 2,580,284,
aniline i8 reacted, in the presence of a copper-containin~ alumlna
catalyst and in the presence of hydrogen, with methanol to give
N-methylaniline in a yield of 96 % of theory. Furthermore, ethanol
can be reacted in the presence of Raney nickel to give N-ethylani-
line in a yield of 80 to 83 % of theory (cf. J. Org. Chem. 21,
474-(1956) and J. Amer. Chem. Soc. 77, 4052-54 (1955)), When Rnilin~
and methanol aro roact~d in the pro~nco of coppor chromito nnd
hydrogen, N-methylaniline i~ formed in vistually quantitative yield
as the sole reaction (cf. Japanese Published Specification
No. 73/49,727; C.A. 79, (1973) 136.769w and German Published
Specification No. 2,061,709).
-- 3 --
As the above discussion of the state of the art shows, the reaction
of anilines which are unsubstituted at the ortho-position of the
benzene rin~ with alcohols in the prefience of hydro~en and hydro~en
transfer catalysts results in N-alkylanilines in excellent yleld.
However, it is not possible to obtain a good yield by these proces-
ses by reactin~ o-mono- or o,o-disubstituted anilines with alcohols,
and especially with alkoxyalkanols, to ~ive the correspondin~
N-alkylanillnes~
4,~Y3, ~G8
In accordance with U.S. Pat. No. ~r~ra~- the monoalkylation of
2,6-dialkylanilines with alcohols can be carried out in the presence
of a copper-containin~ catalyst containin~ a small amount of
palladium or platinum in the temperature ran8e from 200 to 350C.
With primary alcohols this alkylation results in a moderate to ~ood
yield, whereas with secondary alcohols conversion, selectivity and
yield are unsatisfactory.
Accordin~ly, the obJect of the present invention is to provide a
process by which anilines and their o-mono- or o,o-disubstituted
derivatives csn be reacted with primary and secondary alcohols to
~ive the corresponding N-alkylanilines in ~ood yields.
It has now been found that N-alkylanilines of the formula I
~ NH-C ~ (I)
~R2
wherein Rl and R2 ~r~ a~3 do~ined for formula I, can be prepared in
e~cellent yield by reactin~ an aniline of the formula II
~Rl
~ --NH2 (II)
~R2
-- 4 --
wherein R1 and R2 are as defined for formula I, with an alcohol of
the formula III
H0-C ~ (III)
wherein R3 and R4 are as defined for formula I, in the presence of
hydrogen and a catalyst, which reaction is carried out in the
temperature ran~e from 150 to 300C and under a pressure of 0,5 to
6 bar, in the presence of a cataly6t consistln~ of silica ~el as
carrier and 0.2 to 10 % of platinum and 0.05 to 3 % of a co~pound of
a metal of the ~roups la andlor IIa of the Periodic ~able, said
catalyst additionally containin~ at least one compound of an element
of the ~roups Ib, IVa, IVb, Vb, VIIb and VIII in an amount such that
the atomic ratio of platinum to the ~um of these elements is
1 to 6.
In partlcular, the present invention relates to a process for the
preparation of N-alkylanilines of the formula I, wherein R1 is
C1-C3alkyl or hydro~en, R2 is C1-C3alkyl or C1-C2alkoxy, R3 is
C1-C3alkoxymethyl, R4 i~ methyl or hydro~en, and wherein R3 and R4
to~ether wlth the carbon atom to which they are attached form a
cycloalkyl, 2-methylcyclohexyl or 2,6-dimethylcyclohexyl radical.
The pre6ent invention also relates in particular to a process for
the preparation of N-alkylanilines of the formula I, wherein R4 is
C1-C6alkyl, C1-C4-alkoxy, furfuryl or tetrahydrofurfuryl.
The pre~ent lnventlon rolatoD furthor in partlcular ~o a proces~ for
the preparation of N-alkylanillnes of the formula I, wherein R3 and
R4 to~ether wlth the carbon atom to which they are attached form a
pyran or a tetrahydropyran rin~.
21489-6882
Most particularly, the presen~ invention relates to a
process for the preparation of 2-methyl-6-ethyl-~ (1-methyl-2-
methoxyethyl)-aniline and 2,6-diethyl-N-2-propoxyethylaniline.
The preferred temperature range for ~he process of the
present invention is normally from 175 to 225C, the preferred
pressure range is from 1 to 4 bar.
The hourly rate of addition of aniline of the Formula II
is conveniently 0.5 to 10 moles, preferably 1 ~o 5 moles, per
litre of catalyst.
The molar ratio of the alcohol of the Formula III to the
aniline of the Formula II is normally 0.1 to 10, preferably 1.1 to
2.1.
The addltion of hydrogen is conveniently 0.5 to 10
moles, preferably 0.8 to 1.2 moles, per mole of the aniline of the
Formula II employed.
The present invention also provides a catalyst
consisting of silica gel as carrier and 0.2 to 10% of platinium
and 0.05 to 3% of a compound of a metal of the groups Ia and~or
IIa of the Periodic Table, said catalyst additionally containing
at least one compound of an element of the groups Ib, IVa, IVb,
Vb, VIIb and VIII in an amount such that the atomlc ratio of
platinium to the sum of the~e elements i~ 1 to 6, with the proviso
that the catalyst does not contain, at the same time, a compound
of germanium and a compound of tin.
Suitable carriers for the catalysts of the present
invention are æilica gels with the following properties,
~J
1~27~6~L~
5a 21489-6882
specific surface area 300-700 m2/g
pore volume 0.25-1.0 ml/g
average pore radius 1-8 nm
bulk density V.25-0.9 g~ml
water content 1-5%
iron, aluminium and
titanium content, total max 750 ppm
The sillca gels employed may be commercially available
products providing they meet the requirements of this
speciflcatlon. Further, commercially available products with too
high an iron, aluminlum and titanium content can be converted into
carriers suitable for the present invention by washing out with
dllute acids, e.g. 10~ aqueous hydrochloric acid. In the productc
resulting in thls
C'
~ Z'~66~8
-- 6 --
reaction the total content of iron, aluminiu~ and titanium should be
below 750 ppm, preferably below 500 ppm, with the content of each
one of the metal6 indicatsd preferably bein~ below ~00 ppm.
Particularly suitable i~ a silica ~el with the following properties:
specific surface area 400-600 m2/~
pore volume 0.35-0.75 ml/g
avera~e pore radius 2-4 nm
bulk den~ity 0.65-0.75 ~/ml
water content 1.5-2.5 %
iron, aluminium and
titanium content~ max. 500 ppm
The silica ~el employed a~ carrier i8 stabili6ed, after an optional
washing with dilute acid, by keepin~ lt at a temperature above 500C
for several hours.
To prepare the catalyst, a suitable platinium compound, e.g.
hexachloroplatinic acid, and at least one water-soluble compound of
the elements of ~roups Ib, IVa, IVb, Vb, VIIb and VIII of the
Periodic Table, as promoter, i8 applied in solution to the pre-
calcined silica ~el as carrier such that the solution i~ absorbed by
the carrier (impre~nation). In most ca~es a suitable solvent is
water.
Products which are unstable in water, e.g. germanium tetrachloride,
are di~solved in sn inert organic ~olvent, e.g. methylene chloride.
After applicntlon of theue product~, thn ro~ultant mixture is dried
in vacuo at 80 to 150C, whereupon at lnast one compound of the
elements of ~roups Ia and Ila of the Periodic Table, as second
promoter, i6 applied in the same manner. Suitable compounds are e.~.
the hydroxides or chlorides. The application of the two promoter
types can also be made in reverse order.
lZ~76~
-- 7 --
The catalyst i8 subsequently dried again and then calcined by
keeping it in the temperature ranse of 400~ for several hours. The
crude catalyst so obtained is put, after coolin~, into the reactor
and activated at the beginning of an experiment.
The catalyst of the present invention is novel and likewise consti-
tutes an ob~ect of the invention.
The activ~tion of the crude catalyst is effected in the reactor in a
stream of sas under atmospheric pressure for several hours at 1~0C,
durins which activation the composition of the gas ls ~radually
changed from nitro~en to hydrosen. The ultimately obtalned catalyst
consi6ts of silica gel, platinlum and of at least one compound of
the elements of ~roups Ib, IVa, IVb, Vb, VIIb and VIII of the
Periodic Table and of at least one compound of the elements of
groups Ia and IIa of the Periodic Table and can be employed in the
proce6s of the present invention.
Among the novel ca~alysts in the presence of which the process of
the pre6ent invention for the preparation of compounds of the
formula I can be carried out, the followins compositions are
preferred:
a) - 0.5-6 % of platinum,
- 0.1-2 % of at least one compound selected from the elements
con6i6tinS of lithium, sodlum, pota6sium, rubidium, cesium,
beryllium, masnefiium, calclum, strontium or barium,
- at lea6t on4 compound Del~cted from tho olomont~ ~on8iBting of
copper, germanium, tln, load, titanium, niobium, manganese and
ruthenium, with the atomic ratio of platinum to the sum of
the6e element6 being 2.5 to 3.5.
b) - 0.5-6 % of platinum,
- 0.1-2 % of at lea6t one compound selected from the elQments
consi6ting of lithium, sodium, potassium, rubidium, cesium,
beryllium, magne6ium, calcium, strontium or barium,
~Z766~
-- 8 --
- a rhenium compound, with the atomic ratio of platinum to
rhenium bein~ 0.5 to 1.5.
Amon~ the novel catalyst6, the followin~ composition i5 most
preferred:
- 3-5 % of platinum,
- 0.1-2 % of a calcium compound,
- a tin(II) compound in the atomic ratio of platinum:tin =
2.5 to 3.5.
A catalyst which has been deactivated after prolon~ed operation can
be reactivated, after a re~eneration of ~everal hours at 450 to
600C in a stream of air, by a method of activation analo~ous to the
one described above, and reused.
The process of the present invention is convenlently carried out
continuously in a fixed-bed reactor or a trickle-bed apparatus. The
mixture flowin~ throu~h the reactor can either be in pure ~aseou6
form or can form a ~as and l~quid phase.
The two educts can either be introduced separately into the reactor
or as a mixture prepared in the desired ratio. It is advanta~Qous to
add the educts in fluid state, to which end they muDt, i necossary,
be heated. Dependln~ on the reaction conditions, the educts may,
before entry into the reactor, be further heated and also evapo-
rated.
The resultant reactlon mlxture can be nnnly~ed by ~a~ chromato-
graphy. The preparatlve ~ep~ration thoroof csn bo effected by
conventional methods of separation. The hydrogen and the unreacted
educts can be reused when carryin~ out the process lndustrially.
By the process of the present invention, aniline and its o-mono- and
o,o-disubstituted derivatives can be alkylated with alcohol~ in very
~ood yield. Moreover, the proceGs of the preGent invention Also
~l 27~61~3
makes it possible to carry out the alkylation with ~econdary
alcohols in equally 600d yield. As a result, the intermediates of
the formula I with high conversion and excellent 6electivity can be
prepared usin~ inexpensive, readily acces3ible alcohols. Because of
the 6hort reaction times, the process can easily be carried out
continuously and i6 therefore very suitable for an industrial
preparation of intermediates of the formula I. The activity of the
catalyst decreases markedly only after about one day of continuous
operation. Continuous operation of the reaction can be maintained by
cyclic repetition of the operational steps comprisin6 activation,
reaction, re~eneration, then reactivation, reaction etc. When
carryin6 out the reaction on an industrial scale, uniform continuous
production can be ensured by two or more parallel reactors with
appropriately di6placed operational steps.
Compared with those proces6es in which the alkylation 18 carried out
with alkyl halides or alkyl to~ylates, the process also offers
sub~tantial advantages from an ecolo6ical point of view, since the
hi6h-loading of the waste water with salts, whirh arises in the ca~e
of the former processes, does not occur.
The proce~s of the present invention is illustrated in more detail
by the following Examples:
xample 1: Preparation of 2-methvl-6-ethyl-N-(1-methyl-2-
methoxyethvl~aniline
9.5 g of an avera~o pore sizo nllica ~al havln~ the Eollowing
char~cteriotic~:
surface area (BET) 468 m~/g
pore volume 0.62 ml/6
avera~e pore radiu~ 2.65 nm
content of calcium <10 ppm
magnesium <10 ppm
iron 115 ppm
1~76618
- 10 -
potassium <20 ppm
sodium ~50 ppm
aluminium 155 ppm
titanium 180 ppm
are impre6nated with 7.5 ml of an aqueous solution consi6tin~ of
2.5 6 of he~achloroplatinic acid~H20 ~5.1 mmol) and 0.38 g of
tin(II) chloride-2H20 (1.7 mmol), thoroushly mixed and dried for
2 hours at 90C in vacuo. The resultant mi~ture is additionally
impre~nated with 6 ml of an aqueou6 solution consistin~ of 0.37 ~
of calcium chloride-dihydrate (2.5 mmol) and mixed. After renewed
dryins at 90C in vacuo, the mixture iB calcined by keeping it at
350C for 5 hours, thus affordin6 15 ml of the catalyst to be
activated.
4.6 ml of thi6 crude catalyst are activated in a microreactor with a
50 ml/min 6tream of hydro6en/nitrogen ~a~ at 140C for 1~ hour~,
while increasinS the hydro6en content linearly from 0 to 100 %
durins the first hour. Subsequently, the stream of hydro~en i6
ad~usted to 3.75 mllmin (9.2 mmol/h) and the temperature in the
reactor is raised to 200C. Then at a rate of 3 mllh a mixture of
135.2 g (1 mol~ of 2-methyl-6-ethylaniline and 180.2 ~ (2 mol~ of
1-methoxypropanol-2 is pumped into the reactor, evaporated and
pa6sed in saseou6 form over the layer of cataly0t, which corresporlds
to a rate of addition of 2 mol of 2-methyl-6-ethylaniline per hour
and per litre of catalyst. For a reaction time of 15 hours the
followin6 results are obtained:
total conversion, based on 2-methyl-6-ethylanilino, (CA): 65.4 %
~electivity, bssed on 2-methyl-6-ethylatlilin0, (SA): 93,7 %
The addition of hydro~en and educt is then replacad by a 50 ml/min
stream of nitro~en/air, while increa~in6 the proportion of air
linearly from 0 to 100 % and the temperature from 190 to 450C over
1~ hours. The catalyst iB kept under these conditions for 3 hours
and then cooled in a stream of nitrogen to 140C and, as de~cribed
above, activated with hydrosen.
12~66~8
Subsequently, the above-described cycle is commenced, the duration
of which is ~4 hours. The activity of the catalyst increases after
the first cycles compared with the first passa~e.
Only after several weeks' operation do the results show a marked
decrease in selectivity.
In accordance with the process of the present inVentioD~ further
E~amples are carried out with the same catalyst. The results are
~iven in the followin~ Table:
1 ;~7661~
r _ _
1 * ¢ ~ D r r o ~ ~ r~ r~ ~ o
v v~
~ ~ ~ ooo~ ~ ~ ~ ~ ~ C7~ ~ ~ cr~
C~ ~ O~ OD
c~l c
_~ rl
<I) ~ LO ~ ~ ~ O t~l
O ~ ~
'~ g C, 8 ~ ~ g ` g
C~
~: Cl
~o C
o
o V
~ ~ ~ ~J ~ ~ ~ ~`I
JJ _~ ~ V
, ' ' , ~ ..,, l , , , ,
S 5 ~ Y ~o
v ~ ~ ~ o o c~
~ o o l l o o o o o c:
~1 N N N N N 1~1 N N N N NN N
O ~
~ l l l l l l l l l l l l l
'33 l-i
O ~ (.1 1~ ~ 5~ N r~
N 5 ~ N ~ C.~ t.l !~ CI N 1~ N N
1 ~ C~ V C~ C;l O O O C.
JJ
~ ~ rl I I 11. 1 1 1,
~a o ~
al PLI ~ P l ~ ~ 31 3 3~ q 1 I q N p 3 ~ N
_~ O ~ ~ O
U~
E~
1 2 7f~6i8
.... .. _ . _
¢ ,, o ~ ~ o ~ o~
~- ~ C~ I~ ô _ ~ _
o
r~
_~ ~O oo ~ U~ O
C U ~
~ o o o o o o U~ o o o o
~ o o o o ~ ~o, ~ '`, ~ 2 ~. ~
CQ~ C~
~:5 C O ErC
rao~ r~
O ~ ~ C~ l C`l C~ O
C~ C~ t.O
~_ ~
E ~15 C ~ o
. .... ~ . . _I
t C~
~ ~ N
P~ ~ N ~ JJ ; ~ 0~
I ~ N _ N I N
1 :CC,~ 5 C~ 1 5 N NC O ~.1 ~'J ,t l JJ
~ t~ ~v _ 5 v ~ I JJ
N'7 ~ r') '1~ 0 ~ O V C ''J ~ C
al ~ V 5 ~ ~ ~ ~ o ~o" ~ o
P~ ~ O ~ D O O N 3 t.) C) ~ 1'1
~1 N N N ~ _' _' N N ~ t~ U
O ~ ~
ol I ~ I I I I I 'I' I I `~
~1 X ~ O ~
a
o ~ X ~ I ~ ~ ~ ~ ~ rl
O ¦ 1. ~ P4 ~ r--l o ~ O 1~
~ ICa ~L U ~ ~ ~
~1 ~n _I l l ~~ rC
~J J,) ;~ ~ X~ ~ ~rl O O
, ~ o td e
~_ ~ ~ ~ U ~
a~ o ~ O 1~ X o~ o ~ , _ C
D . _ _ _ ~IC
C ~C ~C
