CA1066296A - Process for preparation of pyrryl-2-acetonitriles - Google Patents

Abstract

Abstract of the Disclosure Pyrryl-2-acetonitriles corresponding to the formula wherein R1 stands for hydrogen or an alkyl group having 1-4 carbon atoms prepared from dialkyl (pyrryl-2-methyl)-amine corresponding to the formula

Description

1~6~Z~6 ~, .. . .......... , . . . ..
.~ Background. of _e Invention It has been known to prepare pyrryl-2-acetonitriles, for example, pyrryl-2-acetonitrile and N-methylpyrryl-2-acètonitrile, by reacting trimethyl-(pyrryl-2-methyl)-ammonium-iod.ide or tri-methyl-(N~methylpyrryl-2-methyl)-ammonium-iod.ide, respecti~ely, wlth sod.ium cyanid.e. Trimethyl-(pyrryl-2-methyl)-ammonium-iodide ~5 and. trimethyl-(N-methylpyrryl-2-methyl)-ammonium-iodide are formed in known manner by add.ing methyl-iod.ld.e to an.alcoholic solution . : '" , ' ~
~ ~'~

"' ~ ~ n~' ~

'~ :

, ~ ' ~ ' . of dimethyl-(pyrryl-2-methyl)-amine or dimethyl-(N-methylpyrryl-

2-methyl)-amine, respectively, see J. Amer. Chem. Soc. 73, l~921 (1951) and J. Amer. Chem. Soc. 75, l~8~ (1953) The above mentioned. processes have particularly the d.is-advantage that the ammonium salts prepared. from the Mannich bases by reaction with alkyl iodides in absolute alcohol must be isolated prior to their further reaction to the correspond.ing nitriles.
Furthermore, the isolated ammonium compounds d.ecompose easilyJ
~Ihereby the yield of pyrrylacetonitriles is adversely affected.
To overcome the above difficulties, Orth et al in U. S.

3,52~,952 cond.ucted the d.isplacement in a water-immiscible solvent.
On the scale d.isclosed. in the examples, the procedure of Orth et :.~ . ..
al apparently is satisfactory since the add.ition of the alkali .~. cyanide to the quaternary salt at room temperature d.oes not produce reaction. However, upon heating the reaction mixture to 80C, the reaction starts and is completed by maintaining the . temperature for two hours. Since the reaction ls exothermic, such proced.ures are not practical for large scale operatlons because upon heating the entire reaction mass to the initiation temperature severe evolution of gas occurs and the exotherm cannot . be controlled easily. As a result, foaming occurs and. extremely expensive pressure equipment is required to maintain and. control the reaction. According to the process of the present invention, a mode of operation has been found. which overcomes these dis-2~ ad.vantages. There is provid.ed. an extremely efficacious andpractical process for the prod.uction of pyrryl-2-acetonitriles. .
. .' The Invention ....................... ..... ...

.. . m e present invention provides improvement in a process for the preparation of pyrryl-2-acetonltriles corresponding to 30. the formula s -6G'~

C~12-CN

R
: .
.
wherein Rl is hydrogen or an alkyl group having 1-4 carbon atoms, -~ -by reacting a dialkyl-~pyrryl-2-methyl)-amine corresponding to .;
the formula ~ ~ _C~I -N ~ 2 wherein Rl is hydrogen or an alkyl having 1-4 carbon atoms and R~ and R3 are independently selected from alkyl groups having 1-4 carbon atoms with an alkylating agent selected from an alkyl sulfate to produce the corresponding trialkyl-(pyrryl-2-methyl)-ammonium sulfate salt and reaction of said salt with aqueous alkali metal cyanide in the presence of a water-immiscible solvent in which the pyrryl-2-acetonitrile is soluble, the improvement com-prising carrying out the displacement reaction using 125 to about .
140 percent of the stoichiometric amount of said alkali metal cyanide based on said dialkyl-(pyrryl-2-methyl)-amine at a tem-perature of from about 75 to about 100C, said solvent being present in an amount of from about 1.5 to about 10 parts per part -of said dialkyl-(pyrryl-2-methyl)-amine.
,~
In general, the process of the present invention ::
contemplates two reaction stages, quaternization and displacement.
The reactants employed can be similar to those used in U.S.
3,523,952. Of course the pro~ess by which the reactants are employed will vary from the procedure outlined in the 3,523,952 patent as further discussed hereinbelow.

, ~ . ' .

, ", ;

10~;6Z96 As mentioned in U, S. 3,523,952, the process involves treating a Mannich baseg such as a dialkyl-(pyrryl-2-methyl)-amine, with an alkylating agent und.er cond.itions to fa~ilitate the quaternization reaction and. obtain substantially quantitative yield.s of the corresponding quaternary salt. In the displacement step, the quaternary salt formed is then treated with an alkali .
cyanide whereby the amine is d.isplaced ~ith the nitrile forming ..
the desired. pyrryl-2 acetonitrile. Accord.ing to the present invention, the process of the displacement reaction is conducted.
by controlling the rate of feed. of the quaternary salt to the hot aqueous alkali cyanide in the presence of the water-i.~miscible solvent so that the evolution of gas during the displacement.is controlled. and. gradual and. accomplished. without excessive fo~ming, rapid increase in pressure or temperature from the reaction ~hich is exothermic in nature. Also, the controlled. feed. in the dis- .
placement reaction allows substantial decrease in the ~nount of alkali cyanide employed without d.ecreasing the yield of the desired pyrryl-2-acetonitrile. Such ad.vantages can be obtained ln the process of this invention using prior:art alkylating agent.
such as dimethyl sulfate. Further ad.vantage, according to the . process o~ the pr0sent invention, can be realized. using other dialkyl sulfate alkylating agents, such as higher molecular weight dialkyl sulfatesO Typically, dialkyl sulfates having alkyl groups containing f~om 2 to about 4 carbon atoms, e.g., d.ipropyl sulfate, 25 dibutyl sulfate, and preferably d.iethyl sul~ate are instances of .. . alkylating agents. For.example, the use of d.iethyl sulfate is pre~erable bec~use it is much less hazardous by being sub.stantially . ..
non-toxic and on displacement forms less volatile dimethyl ethyl amine, reducing the tendency to foam d.uring the displacement 3o reaction. Such considerations allow th~ d.isplacement reaction _ 4 _ . - . . . - cr r~
. . ,~, 101~6296 to be cond.ucted by either feeding the quaternary salt to the aqueous alkali cyanide or the reverse, The technique of the above procedures accomplishes prod.uction of pyrrole-2-acetonitriles wi:th a high ratio of this desired. material as compared. to other isomers, such as nuclear-substituted. cyanid.es, e.g,, 1,2-dimethyl-. -cyanopyrrole. -~ ecause the quaternization step is essentially quantitative ,only equiva~ent or stoichiometric amounts of the ~annich base, e.g., the d.ialkyl-(pyrryl-2-methyl)-amine~ and. alkylating agent are required.. The d.ialkyl groups on the amino rad.ical can be an alkyl group having 1-4 carbon atoms such as methyl, ethyl, propyl or butyl or their isomers, as defined for R2.and. R3 hereinabove.
The alkylating agents employed. should. be suitable for formation of quaternary salt with the d.ialkyl-(pyrryl-2-methyl)-amine. Suitable alkylating agents are alkyl sulfates, such as d.imethyl sulfate, diethyl sulfate and. the like. Some of the foregoing alkylating agents are ex~remely toxic such as, for example, dimethyl sulfate. Accord.inglyJ higher molecular weight alkyl sulfates such as diethyl sulfate are preferred Because of the exothermic nature of the alkylating reactior. , . the reaction mixture is cooled. during the quaternization step. r~
Any suitable means conventional in the art.can be employed., as is well understood by skilled practitioners in the art. Preferably the reaction mixture is maintained at about ambient cond.itions, about 25C as conventionally described.
Preferably, the reaction is cond.ucted in aqueous.sus~ensionwith stirring to insure intimate contact of reactants. The reactic proceed for a t~me sufficient to allow the reactants to substanti-ally complete the reaction. After the ad.ditlon of the alkylating 3 agent, the reaction mixture can be held with stirring to assure . 1066Z96 completion of the reaction. Completion of the react~on can be .
checked by analysis of the reaction mixture for unreacted. Ma~lich base, e.g., dialkyl-(pyrryl-2-methyl?-amine For convenience, if the reaction contains one phase then it can be assumed that the 5 reaction was complete. . ~ - .
The displacement step is carried out by the controlled reaction of the quaternary salt with aaueous alkali cyanide solution of water-immiscible solvent. Any suitable alkali cyanide can be employed, such as sodium or potassium cyanid.eg preferably sodium cyanide. The amount of alkali cyanide snould be sufficient to react with the quaternary salt produced.. It has been found that an excess of alkali cyanide is required to obtain ad.equate .
yields. Previously, over 100 percent excess has been employed..
Eowever, it has been found that from about 10 to about 80 percent . .
e~cess is sufficient to obtaln good. yields by the process of the present invention.
More preferably a 25 to 40 percent excess of alkali cyanide can be used.. Stated in other words, the amount of alkali cyanide employed. can be within the range of 110 to about 180 20 weight percent of the stolchiometric amount based on the Mannich .
base, i.e.~ the dialkyl-(pyrryl-2-methyl)-amine. Preferably, an .( amount of alkali metal cyanid.e of from about 125 to about 140 . ..
weight percent of the stoichiometric amount based on the Mannich baæe, i.e., the d.ialkyl-(pyrryl-2-methyl)-amine can be used. As indicated hereinabove, when dimethyl sulfate is employed as the alkylating agent it is preferred. to feed the quaternary salt to the alkali metai cyanide for the reasons stated.. On the other.
hand, the use of d.iethyl sulfate as the alkylating agent allows .
one to use either mod.e of feeding, e.g., either the quaternary salt to the alkali metal cyanide or tha alkali metal cyanide to , .. _. . ... .,. . ~

. 1066%96 the quaternary salt. ~atever mode of ad.dition is selected, the feed rate is controlled. to prevent the exothermic reaction from becoming uncontrollable The feed rate should be sufficient to .
p~ovide ad.equate yield of the desired pyrryl-2-acetonitriles, but not so low as to require unreasonably long cycle times. It should . be noted. that for d.ifferent size reaction vessels having varying heat transfer surface to volume ratios the feed. rate will vary.
For different sur~ace to volume ratios a higher or lower feed rate or an external heat exchanger can be used. Thus, depending on the size of the reaction vessel the feed. rate is preferably su~ficient to assure good. reaction rates but not cause foaming .
or impractical cycle times. Typically, the aqueous phase produced ;
in the quaternization reaction can be fed to the aqueous alkali cyanide solution a~ the ra.te of about 3.5 to about 10 parts by weight per minute. Such rates can also be employed ir. feeding the aqueous al~ali cyanide to the aqueous quaternary salt mîxture in the presence of the water-immiscible solvent.
The water-immiscible solvent can be any liquid which is substantially inert to the reactants and. has sufficient solvent power for dissolving the prod.uct pyrryl-2-acetonitriles. Ex~mples of such solvents are benzene and its homologs and halogenated .
al~anes, such as, for example, benzene, toluene, xylene,.chlori-nated hydrocarbons having a boiling point above the reaction . temperature, e.g., ethylene chloride, trichloroethylene, perchloro- .
ethylene, methyl chloroform, and the like. Such solvents are conventional and described in U. S. 2,52~,9529 supra. The amount of solvent employed should be only that amount suffic.ient to maintain an easily stirred reaction mixture. For convenience, the amount of solvent employed is stated in terms of the amount 3o ¦¦or s~ar g Mannicb base employed. The ef~ect o~ the amount o~

. 1C~66Z9~

solvent being too low is ~o depress the yield. of pyrryl-2-aceto-nitriles produced. Thus, it is preferred to employ at least about 1.5 parts of solvent per part of Mannich base, i.e., per part of dialkyl-(pyrryl-2-methyl)-~mine. Preferably, from about 1;5 to about 10 parts of sol~ent per part of Mannich base can--be ..
. used. However, to reduce the size of reaction equipment and.
increase reactor prod.uctivity an intermediate range is preferred For example, from about 3 to about 5 parts of.solvent per part of Mannich base has been found to give acceptable yield.s without unduly increasing capital investment or decreasing productivity of a given reaction vessel.
The reaction temp~rature of the displacement reaction depends somewhat upon the solvent selected and the stage of reaction. The reaction begins about 80C and the temperature is controlled, preferably between about 76 to about 95C by refluxing. The temperature being initially at the upper portion . ..
and gradually decreasing slightly as the low boiling by-product amine forms Further, it is preferred. that the controlled.
addition o~ the quaternary salt or the aqueous alkall cyanide, depending on the reactants selected, take place over a time . sufficient to allow adequate venting, heat transfer and. yield...... .~.
In general, cycle times of from about 2 to about 8 hours or more, d.epending upon the scale ~ operation ænd. the temperatures employed, can be used In general, the overall procedure ~lith the preparation of the pyrryl-2-acetonitrile compound.s of this invention can be described. as follows. To a suitable reaction vessel is charged.
the Mannich base ar.d ~rater. The react,or agitator and cooling medium on the reactor are started. Then, the alkylating agent is added. over a period sufficient to maintain the reaction ~ 66%~6 temperature at about 25C.with coclingJ e.g., from about 30 to about 60 minutes. The reaction conditions are maintained for a period sufficient to allow completion of the reaction, for example, about 90 to about 120 minutes, after which the reaction mixture is checked to see whether a clear water-soluble; one phase solution is obtained. If this is the case, the procedure is continued:. If not, agitation is continued. until a clear water-. soluble, one phase solution is obtained. In a separate reactor3are added. toluene and water. The agitator is activated and solid sodium cyanide-is added to the reactor. Caution should be observed in adding the sodium cyanid.e because of its toxicity.
The reactor is heated to reflux at about 90-C. The reaction ~:
mixture from the first reactor is then ad.ded to the second reactor at a rate sufficient to obtain good reaction without foaming or pressure build-up from displacement of alkylamine, for example.
about one gallon per minute and. reflux is maintained. ~or about 30 minutes. Alternately, the toluene can be add.ed to the first reactor and the alkali metal cyanide and. water solution then fed to the reaction mixture in the first reactor. The contents are then heated to reaction temperature. This alternate mod.e o~
. add.ition is preferably used. when the alkylating agent is a higher .
molecular weight d.ialkyl sulfate, such as diethyl sulfate, which forms a quaternary salt from which dimethyl ethylamine is displaced and which is less volatile. After this period, the phases are allowed to separate and the bottom aqueous phase is removed. The organic phase is transferred. to product recovery operations.
To lllustrate the improvement of the present process over the prior art, Example I of U. S. 3,523,952 was repeated on a half mole scale. To a 2-liter, 3-necked ~lask, equipped with .
reflux condenser, thermometer, stirrer and dropping funnel was ¦added 69 g (0.5 mole) of dimethyl-(N-methylpyrrole-2-methyl)-amine ..
¦and 75 ml of water. The flask was cooled in an ice bath to ¦maintain a temperature between 15 and 30C. To the flask was ¦added 47.5 ml (0.51 mole) of dimethyl sulfate. The addition took ¦30 minutes and. the reaction mixture was allowed to stir at room ¦temperature for 1-1/2 hours. Then, 250 ml of toluene was added ¦and. the mixture stirred. A sample was taken, analyzed by submitted ~ :
¦gas chromatography and showed. no Mannich base or d.imethyl sulfate. .
¦Next, the solution of 55 grams (1.12 moles) of sodium cyanide in 10 ¦100 ml of water was ad.ded to the reaction flask. Scale d.own of . ..
¦Example I of U. S. ~,523,952 would call for only 25 ml of water, . ¦but the cyanide was not soluble in that amount. This mixture .
¦was heated. and started sustaining reaction at 85C without ¦external heat. General reflux with slow gas evolution occurred.
¦after 20 minutes, the temperature dropped. to 80 and heat was ¦applied.After 1-1/2 hours gas evolution had.ceased. After heating it at 8~-85C for 2 hours, the reaction mixture was cooled. and the toluene layer separated.. The aqueous layer was extracted.
l wlth 250 ml of toluene. Filtration was required during each 20 ¦ separation because of the rag layer produced... The rag layer was ; ...
.~ also separated. after the second time and the toluene solutions .. . were stored for separate analysis. The toluene l.ayer was dried. .
over magnesium sulfate, filtered. and the toluene stripped on a rotary evaporator. Gas chromatographic analysis of the stripped.
solvent showed it to be clear of prod.uct. The liquid resid.ue weighed 57 g. The liquid. was ~lashed through a vigreux column with a trace boiling at 57C. The main fraction boiling point is 67-74C and welghed 47 g. ~is was a crude yleld. of 78~.
However, the product contained 2 isomers, one was the desired 3 ~ N-methylpyrryl-2-acetonitrile, and a second prod.uct of 1,2-dimethyl _ :

5-cyano pyrrole in a molar ratio of ~8:12. .
,/ - 10 - ' . .. . ...

10fi6296 It should be noted that Example I of U. S. 3,52~,952 ind.icates no by-products of the reaction but indicates that the reaction product boiling at 72-76C was N-methylpyrryl-2-aceto-nitrile and corresponded to a yield. of 8~. Such pure yield.s could. not be d.up;icated.
In an attempt to improve the yield over the first experi-. ment, a similar procedure was followed on a .~23 mole scale usingthe same reactants. The ma~or d.ifference was that the quaternary salt was heated to reflux and. then the aqueous sod.ium cyanide was ad.d.ed. to the reaction mixture. After work-up as above, the yield.
of product was lowered to 62~ and the molar ratio of the pyrryl-2-acetonitrile to the nuclear-substituted. nitrile was also 81:19, .
respectively.
The reaction was then scaled. up to 4 molar scale and. run i5 according to procedures oL the first experiment. To a $-liter flask was ad.d.ed. 552 g (4 moles) of dlmechyl-N-methylpyrrole-2-methylamine and 550 ml o~ water. This mixture was cooled in ice water bath with stirring while 504 g (4 moles) of dimethyl sulfate was added. me temperature was maintained between 15 and 20C. .-Addition of dimethyl sulfate took place over two hours. Stirring . was continued. for one hour after ad.d.ition was complete. Then, . . 1700 ml of toluene was added. and a solution of 392 g (8 moles) .
o~ sodium cyanide d.issolved. in 750 ml of water. The mixture was heated slowly to 85C.- At this point, reaction initiated and.
25 became so vigorous that material foamed. into the cond.ensers and .
even into the large d.ry ice trap. It was necessary to cool it ~. .
with CO2 fire extinguisher. Some material was lost through ~oints : .
. in the apparatus. It was necessary to alternately warm the . reaction flask and then remove the heating mantle to control the reaction. Contents of the traps were poured back into the ~lask ' ~ ' ' ' .

__ , . ..... ..

1~66Z96 -and alternate heating and. cooling continued for 1-1/2 hours.
After the exothermic reaction was finished. and the stirrer was shut off, there were three phases~ two liquid. and one solid, : :
which was presumed to be sodium sulfate. The reaction mixture was cooled. and ailowed. to stand under nitrogen overnight. Then, the liquid was transferred to a separatory funnel and. the organic ..
layer separated.. The rag layer was filtered. While water was add.ed to d.issolve the salt, another 1700 ml of toluene was added..
This was heated to 75C where general reflux occurred and stirred for one hour. The toluene layer was separated and the combined.
organic layers were dried over magnesium sulfateJ filtered and the solvent removed on a rotary evaporator. The stripped toluene .
was checked by gas chromatograph and contained no product. The .! resldue weighed 422 g and contained. 3~ solvent. The crude product ~15 yield was 82~ of which the molar ratio of the N-methylpyrryl-2-acetonitr.ile to 1,2-dimethyl-5-cyanopyrrole was 76:20~ . .
In contrast to this.experience, the present invention provides an easily controllable reaction procedure with high ratios of the d.esired. pyrryl-2-acetonitrile. The following examples illustrate the invention but should not be considered as limiting thereof. A11 parts are by weight.

.E~AMPLE 1 To a suitable reactor was ad.ded. 111 pa.rts of the Mannich ase d~methyl-(N-methylpyr-ryl-2-methyl)-amine and 120 parts of 2~ ater. The stirrer was activated and cooling started on the eaction vessel while 100~ theory of d.imethyl sulfate was slowly dded to the reactor. The te~perature was maintained. at about 5C during the ad.dition which took 30 minutes. After add.ition, .
he stirring was continued for another 30 minutes. A one-phase 3o queous solution was obtained. ~ .

~ . , ., .. ,. , . ., . , .. ... . . . . . .. .. . .. .. . .. ....... .. . . .. _ . . ... . .
r~

~ ;629~i In another reactor there was mixed 346 parts of toluene ¦and 160 parts of water with stirring To this was added 71 parts ¦of sod.ium cyanide, representing about 180~ of theory based. on ¦the Mannich base. While continuing the stirring, the cyanid.e ¦solution was heated. to reflux, about 88C and. held. at reflux for ¦about 30 minutes. Then the aqueous solution from the first reactor was added. to the refluxing cyanid.e over a period. of abou-t ¦60 minutes. After completing add.ition, the reacti~n mixture ¦continued. to reflu~ for another 90 minutes. During addition and. .
Ifor some time d.uring the continued reflux a gas was evolved. which ¦on an analysis was determined. to be triethylamine After refluxing was completed, the reaction mixture was cooled. to about ¦ 40C and allowed. to stand while the phases separated.. The aqueous . ¦ phase was removed and the organic phase was analyzed by vapor :
l phase chromatograph with the following results:

Mole 1. Starting Mannich base 0 2. 1,2-Dimethyl-5-cyanopyrrole 607 ¦ 3. N-methylpyrrole-2-acetonitrile70.0 ¦ ~. Ratio of ~ to ~ 10~4 . 5. Heavy end.s 23.3 In a further series of runs variables including reflux temperature, time of addition, amount of solvent, amount of alkali cyanid.e and the type of alkylating agentJ were stud.ied to d.eter-mine their result on the production of pyrryl-2-acetonitriles by the process of the present invention. Tables I and. II show the results of thesé runs.

.As in Example 1, the procedure is carried out in two stages, quaternization of the Mannich base, which for illustration ' ~

~.,,.. ,.. , ... , , , '.... . . .. . ... p. .~

. 1[366296 employs dimethyl-(N-methylpyrryl-2-methyl)-amine, and displacement .
In the quaternization step equimolar amounts of Mannich base and alkylating agent were usually employed.. This is the theoretical amount. TablesI and II use dimethyl sulfate and d.iethyl sulfate, respectively, as the alkylating agents. From NMR analysis, the :
quaternization steps all gave theoretical yield with these alkylating agents. Efficacy of these alkylating agents can be compared. from runs under similar displacement conditions, see for comparison Examples 2 and 13 In Table I, the quaternization step was cond.ucted. using 30 minutes ad.d.ition time, 30 minutes holding, both at 25C, and .
the Mannich base was 100~ pure. Example 7 used twice the amount of alkylating agent.
The amount of alkali cyanide is expressed as the theoretical amount or a percent of theory. That is, 100~ means . the stoichiometric amount was used. Thus, with 15, 30 or 80 percent excess alkali cyanide, it is expressed. as 115, 130 or 180 percent of theory. . .
In Table II, the alkylating agent used. was d.iethylsulfate.
Various addition and holding times did not appear to affect the quaternization yield by NMR analysis. In Example 9, the yield was low because o~ samples taken during the reaction.
For both Tables I and II the arrows used ind.icate the same value as that immediately preceding the arrow.

- ~6~Z~

l . . U~ , .
I . ~ o ~1 oco ~'`!
l ~ . . C~J . ~ ~oO~
I , . .
I
I
1 ~o L~ o o~ ~1 I . ~
l , . .' H . ¦ 1~\ O H LO
H E~ ~ -1 ~) CU .
l ~ ~ ., I O ¢
l ~ r'l . :. .
¢ H ¦ H O C~J ~CO
E~ ~ ~1 ~ O 0~ l I 1~ ~i ~ . ' ., I ~ ~ . . ';
i ~ ¢ . ..
1 ~ ~ oo~ ~
~1 ~; 1~ O I a) .' ~1 i~ Lt~ O C- ~ ~ . . :~
I ~~ _ cr . ~
~; ~ --i N L~ O
I O ¢ O O O O~ ' l ~ CU O O t~ . I + ' ~ -1 0 ~ `
I E-l ~ .~ 1 ,1 o ~ u ~ .
I ~ ~ ~0 "
1 ~4 . ~ ~1 ~
I ~ ~: , ~ ~ .' I ~ ~ O ~ O
I I h~ 0 ~
~:) h o l H ~ C d 0 C
I C~ I ~
h C) C~J ~ O
I ~ ~
h~ S~ m I ~ 0 I ~ ~ .~ 0 ~ C~
I 0 h c) O .bD o m ~ ~ ~ :~ ~ .
I ~ 0 o ~ ~ ~ a~
I o ~ ~ O a) ~ c~
' '~ ~ ~ ~B
I ~ 0 E~ rl R ~ O ~ O :~ ~
I o s ~ ~1 ¦iZS N c) ~ R X~ B 5 I ~ 1 O O q-~
Ia~ 0 ~ ~
I ~~ V ~ ~ V . ~ ~ ~rl I ~ 1 o ~ ,J q) ~
. 1 x ~ .
I . ;~
. , , ,, .

rl ..~

:~ r . 1~)66Z96 I . ` o . . ~oo~
, . ~ o .....
¦ . ~1 ~D.=tO~
I .
I .
I O ~ ~D O~ O
~ ~ CU .

¦ a ) .
1 ~3 ~1 ~ ~oc~
¦ 1~; ~ ' C~l L~ , I H ~1 .
i E~ ~ .
I ~ O 00 I ¢ ~i o + ) $ ~ ~D o.~D a~ .
l l H H O C~l O oO ~D ~J ~ N
I ~ t~ a~
I ~ ~ a) .
'~; O ,- 5:: .
O U~~ O ~D
v~ * Lt~ ~ bD
I .~ ¢ ~ + I+~Lf~DO ~
I ::~ lr~ Ir~ OIr~ r-l O rl _ ~ a~ ~o o o a~ C~l 1 a~ o o l ¢ . OU~OL~D 0~ ~ ~ 5 ~ ~i ~ a~ o c~o c~ + ~ I 1 0~D t-oa~ ~ ~ a) l O ~1 ~1 ~I Q ~ O ~ O ~
l E-l ~ , ~ CJ\~ d l ~ U~ + ~
~i ~ G~ CQ

H . q~
~ .-1 h ~ ~ O H ~q ., . I ~ 0~ O
H ~ h U H h O U~
. ~ P.~ ~ ~
P o a~ ..
~1 ~d ~ O ~ c~
~ ., ~ I
E~ ~ C~ CU ~ ~ r-l h a> ~
' I I ~ ~ O a~ u~ o L~l O bD~ ~
h ~ m .
o ~ +
p~
~ ~ ~ co ~ U~ ~ C) O
g) ~5 C) o ~ o æ
O ~d ~¢ ~ >, O
~ a~ :~ 04 o ~ ~ ~0 ~rl 0 E-l ~- ~ ~ ~ O h D ~ O O al ~ ~
0 ~3 ~ h h ~ ~ b.D
~; N ~ ~ O .~ ~:1 X . ~ S~ C~J E3 ~ ~ ~ S:~ a) O ~ ~ rl ~ 3 ~ a) o ~3 ~3 ~, o q~
~ æP; r r-l h ~ c~ 3 ~ ~ ~ ~ ~rl ~ ~
. ~ ~ ~ a) ~x~--~ ~1 ~ ~ ~ ~1 x ~ g ~ ~ a: ¢¢~ .
. . . ~ ~l N ~ ~ D *

: 16 ~66;~96 From the foregoing examples, it can be seen that it is preferred to use from about 115 to about 180 weight percent of :
the theoretical anount of alkali cyanid.e, based on the Mannich base, and. more preferably from about.125 to about 140 weight percent of the theoretical amoùnt of alkali cyanid.e, on the same ..
. basis. ~-Further illustrating the process of the present invention, a preferred. procedure for preparation of pyrryl-2-acetonitriles~ .:: ;
particularly N-methylpyrryl-2-acetonitriles, results from the addition to a suitable reactor of 80 parts of dimethyl-(N-methyl-pyrryl-2-methyl)-amine and. 87 parts of water. With stirring and cooling to maintain the temperature at 25C, there is then added ~ .
90 parts of d.iethyl sulfate to the reactor over a period of 60 .
~ minutes. After completing the add.ition the reactor contents are :.
stirred at 25C for an additional 90 minutes. During this time, there is prepared in a separate reactor a mixture of 252 parts . o~ toluene, 75 parts of water and. 37 parts of sodium cyanide.
These materials are mixed. with stirring at 25C and then heated to reflux at about 90C for 30 minutes. Then, over a period of ~0 about 60 minutes the aqueous phase from the L irst reactor which . contains only one clear water soluble phase is transferred to the alkali cyanide mixture over a period of 60 minutes during which the temperature grad.ually decreases to about 77C and. the reaction mixture in the second reactor is refluxed. for an additional period o~ about 90 minutes. Then the stirrer is shut off and the reactor contents cooled. to about 40C over a period of about 35 minutes during ~hich the organic and. aque~us phases separate. The aqueous phase is trans~erred to another reactor - .. ..
.. ~or waste treatment or discarded.. The organic phase containing .
3o product N-methylpyrryl-2-acetonitrile is trans~erred. to recovery operations, for example, distillation to remove toluene and.
purify the prod.uct further from small amounts of other isomers prod.uced. during the process.
Using the above process several ad.d.itional experiments were cond.ucted to illustrate the process of the invention. Table III shows the results of Examples 1l~-24 which were run as closely as possible to the procedure of the preceding paragraph. It should be noted that in Examples 15 and. 16 the yield was somewhat lower because of reaction temperature control during the add.ition of the quaternary salt. On the other hand, in Examples 22-24, the higher yield resulted from better control of displacement .- reaction temperature~
. ..................... , -. .' . .. .
.~ .

. 1~:i6296 .
. .
. '`
., ~ ~ O ~D ~ I ~
a3 ~ o ~ o~ i ~ ~ O Lr ~ ~ ~ ' ' . ~ ~ D ~ W ~ ~D ' ~ ~
. ~ ' bD ' ' ":
. ,, U~ ~ CO C~l ~ ~ ~ o~ ~ o ~ :> ...
~3 o~ J ~ ~ o ~o ~ ~ ~ ¢
........... ..
o ~ ~ ~ ,1 ~ ~ ~ CU Lt~ U~ ~
., E~ a~ ~ ~
. . .
~; ~ . ` . ~
H O ~
~' O r~ D '' ,:
.~ OOOC~JOOOOOOO ..
H . . :
. ~
H ~ O H a:~ CO r l C~l ~t ) ~1 ~D In .
~; ~; ............................................ .
O ~ r J ,~ N ~C\J ~,,,~ ~
e~ . :
l F~ ~ N~l ~ ~ ~ O ll~ 0 t-- a~
N~ Z; t~ ~:i-1~\ 1~ ~ ll~ ~ IS~
53 ~;~ ~; ~
. !~ ~ ~, . .
.,~ CC 5~~I ~ ~ ~ O ~ ~ U~ . ~
11 ~ N 1~ 1~ N 11~ U~
--l r~ ~ ~1 .I ~I N `
E-l ~ O O O O O O 0- O O ., .
C~; . .
' ~ ~ ~ .
- ~Z ~ . ~ ~ ~ O ~ C~ ~ ~ ~ ~ ~ ~ ' t~ ¢ H ~ CU 11~ N 0 ~ - a~ O ~
O _ ~0 t-~O t~ 0 O ~ . . . .
~1 ~1 . ' -., .
' '' '~ . ~ 0 ~ Lr ~ 'U~ 0 ~ ' ~ ~D ~ ~ ..
~; ~ ~ ~ ....
¢ tl ~ o o o~ ~ 0 o~ aD ~ ~ ~ o~ ~
~ ~ ~ ~ ~ ~:
~ ~ ~ ~
l ~ ~ ~ ~ ~ o ~ o~ o o . ~
HH ~ h t~ ~ ~ ~ ~ L~ ~ O ~rl .- . :, H ~ : h O
~1 ~ ~ o o o o ~ P, O

. ~ so ~ u~ ;: ~i ~CU
. ~ a~ Iq . , . . r~ l a~ a~ i~ ~ oo ~ ~ ~ ~ C) a) I ~ u~ ~ h . . . . ~l~S::~
0 ~'. . '' ' ' ' ' ' ~ ~ 'S~ ~ .
, ,~ ~1 O ~ _I Q ~
, ~, ~ o~ E'l . . Z. ~ J 1 N ~ ~
. . , .
. ~.
. 19 -. . . . .
, . .
_ .... ,~. . ...... ,,, .... . . , . ... .,.. ,., . .... . _

Claims (5)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. In a process for the production of pyrryl-2-aceto-nitriles of the formula wherein R1 is an alkyl group having 1-4 carbon atoms by reacting a dialkyl-(pyrryl-2-methyl)-amine corresponding to the formula wherein R1 is defined as above and R2 and R3 are independently selected from the same or different alkyl groups having 1 to about 4 carbon atoms with an alkylating agent to form the corresponding quaternary salt and displacing an amine on said salt with aqueous alkali metal cyanide in the presence of a water-immiscible solvent in which the product pyrryl-2-acetonitrile is soluble, the improve-ment comprising said alkylating agent being a dialkylsulfate and carrying out the displacement reaction by adding the aqueous phase containing the quaternary salt to the aqueous alkali metal cyanide in the presence of said solvent at a rate of about 3.5 to about 10 parts by weight per minute using 125 to about 1.0 percent by weight of the stoichiometric amount of said alkali metal cyanide based on said dialkyl-(pyrryl-2-methyl)-amine at a temperature of from about 75 to about 100°C, said solvent being present in an amount of from about 1.5 to about 10 parts per part of said dialkyl-(pyrryl-2-methyl)-amine whereby said improvement provides a molar ratio of said pyrryl-2-acetonitrile to by-product 1,2-dialkyl-5-cyanopyrrole which averages about 9.3.

2. The process of claim 1 wherein said alkylating agent is selected from the group consisting of dimethyl sulfate and diethyl sulfate.

3. The process of claim 1 wherein said alkylating agent is dimethyl sulfate.

4. The process of claim 1 wherein said alkylating agent is diethyl sulfate.

5. The process of claim 4 wherein said solvent is present at from about 3 to about 5 parts per part of said dialkyl-(pyrryl-2-methyl)-amine.