CA2133374A1 - 2,4,5-trihalocinnamonitriles and process for their preparation - Google Patents
2,4,5-trihalocinnamonitriles and process for their preparationInfo
- Publication number
- CA2133374A1 CA2133374A1 CA 2133374 CA2133374A CA2133374A1 CA 2133374 A1 CA2133374 A1 CA 2133374A1 CA 2133374 CA2133374 CA 2133374 CA 2133374 A CA2133374 A CA 2133374A CA 2133374 A1 CA2133374 A1 CA 2133374A1
- Authority
- CA
- Canada
- Prior art keywords
- palladium
- compound
- employed
- chloro
- fluoro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/35—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups
Abstract
Abstract 2,4,5-Trihalocinnamonitriles and process for their preparation 2,4,Trihalocinnamonitriles of the formula I
(I) wherein R1 is hydrogen, straight-chain or branched C1-C12 alkyl, fluoro, chloro or phenyl, the phenyl radical being unsubstituted or substituted, if desired, with C1-C4 alkyl or C1-C2 alkoxy, and X, Y and Z are identical or different and are fluoro, chloro or bromo.
Furthermore, a process for the preparation of the com-pounds of the formula I by reacting a compound of the formula (II) (II) in which R1 is as defined above with a compound of the formula III
(I) wherein R1 is hydrogen, straight-chain or branched C1-C12 alkyl, fluoro, chloro or phenyl, the phenyl radical being unsubstituted or substituted, if desired, with C1-C4 alkyl or C1-C2 alkoxy, and X, Y and Z are identical or different and are fluoro, chloro or bromo.
Furthermore, a process for the preparation of the com-pounds of the formula I by reacting a compound of the formula (II) (II) in which R1 is as defined above with a compound of the formula III
Description
';` 2~3337l.~
HO15:CHST ~RTï}SNG~SSi3L~SC}~F~ 0~: 93~F300 Dr. ~/b~
Descrip~Gion 2, 4, 5-l'rihalocinsla~onitrile~ and proc~s ~or their prepa~ation 5 The pre~eslt is:lvention relate~ to halogonated ci~a:mo-nitril~3 and to proc~t3eE~ for the~ prep;ar~tion.
The abovemerlkloned compou~d~ are of importance in indu~
'cry a~ termediate~ in the ps0para1:ion of ac:ti~re ingre-dien o or pharD:Iaceuticals, herbicids~ and ~ungi~id~O
10 The com}?ousld~ who~e preparatiOD. iB noYel can be prepar~d by the con~rentioD.al route, via the c:inna~nia ~Yt~r~ or the cinnamalcl~3hyda~, only with graat di~ ulty, ~ince th~a actual starting ~ tanc2s slec~ ary fox thi~ ~oute are 'c~ae corre~pondi~g 1 rihalobe~zald~}lyd~s (c~ thi~
15 r2spect Hou~e~-Weyl, ~srol~ne 135, p. 362, 1348).
A ~rariant ~ynthe~is, ther~fore~ the arylation o acrylonitril~. Thi~ rsaation, which ib catalyzod by palladium compound~, has bsen lcnown in pr~noiple ~i~ce the work by R. P~. H~ck; comprehe~ xe~ws o~ thi~
20 work can be found in l7Palladiu;n Reage~t~ in Ors~ani~
Synthe~s~", Acad~ic Pre~R N.Y~ (1985~ a~d in Organic Reaction~ 27, 345-390 (1982). T~e ole~ ompo~erlt~
emlployed are pref e~ably aarylic oster~ and ole~ins, wherea~ the reactio~ with a~rylonitrile i8 only attempted 25 in a few example~. ~or instance, R. F. ~Iec3~ et al. is~ J.
Or~. Ch~n. 43, 2g45 ~1978) de~ribe exp~rimen~c~ to ~y~the~ize p-aminocin~amo~itril~ from bromoaniline or iodoaniline~ o:nly the l~ttex gi-~ing a yleld o~ 53~6 w~ile the :t~romo compo~nd gaYe no target pxodu~t. The prepara-3û tion of p-Ponnyl~innamoni'crile i~ de~cribed in ~. Organo-met. C~hem. 258 ~- 9133~, 101 wher~, how~er, it i~ al~o indi::at~d that th~ react~ity of aryl bromide~ containing no stab~ti'csuen'cs capable o~ conjugation i~ limlted.
. ~ ."," ," ~...., "..,,~, . ;,.,~,.,., "s~ ~,, ,,,, ~,.,~ .,.~ ..,..~ " ""1, 2~33~7l~
Becau~e s:~f the general importanc!2 and the wide range of applicatio~ of thi~ cla~ of a~l~b~;ta~ca~3, it i~ a worth-while ob~ ~ct to pro~r~ de s:lo~el compound~3 rom thi~ group o ~ub~tax~cs~, ln orde~r rlot only to Elupplemen th~
5 ~p~ctrum of th~i~ po~ible u~ but al~o to enrlch and exterld i'c by ~a ine ad~u~arlt o~ the mat~rial prop~r-tie~. In addition, these n~-rel com~po~snd~ op~n up further route~ to th~ pxepar~tio:n o ollow-on productsg who~3 i%lportanc . h . ~ already b~e:~ meD.tion~d ~bove .
10 Thi~ ob~eat i8 achieved by 2,4,5-trihalocir~monitrilee o~ the for~ula I
N
R 1 ~:
wherein Rl iB hydroge~ tra~ ght-chai.~ or brancha~l Cl-Cl2 :~
alkyl, f luoro, chloro or phenyl, the phenyl radiaal being u~ t~ tuted or ~ tttuted, if de~ired, with Cl-C~ alkyl or Cl-C2 alkoxy~ and ~.
X, Y a~d Z are ideIltical or differe~t and are fluoro, chloro or bromo.
P~ c~rtai~ degree o i~pox anc~ 1~ at'cached to the aom~
20 pound~ e~f ~he ~ormula (I) ih which Rl ~ a hydroge~ or slethyl arld 2~, Y aDd Z are :E~ uoro or c~loro .
Al~o of intere~t are the compouIld~ of the fo~snul~
which X, Y ~d Z ar~ fluoro, in particular wh~n Rl 18 hydrog~n or methyl.
25 In addition, emphalsis ~hould b~ gi-rerl to the compou~ds of thQ :Eormula I i~ which X and Y are chloro all~ Z 1~ $1uoro or Y a~d Z are fluoro and X i~ ~hls~ro, in parti~ular wher Rl i hydros~en or methyl.
:; 2 ~ 3 3 3 14 The~ haloge~Lat@d ci~n~onitrile~ ~a~ be prepared ad~a~-tageoll~ly by reacting acrylonitrll~ c~r ~ tituted a~rylo~i'cril~3s of the $ormula ~XI) ~ ~g in which R1 i6 a;3 alr~ady de~ed with a compousld o the 5 ~ormula III
A
r ~x in which X, Y and Z ~r~ as deflTl~d aboY~ and A iB iodo, hrcmo or ~hlo:ro, in the pr-3senc~e o~ a palladium cataly~t, a ba~e a3~, if de~lrsd, a 301v~ t and/or a ~tabllizing ligand and/or an a~nonlu~ ~al at tesnperaturef) of 10 û0-200~C.
In ge~ral it i~ po~ible to emE~loy thoes aryl halide~
(III) in which, independently o~ the pattern o~ ti'cu-tion o~ ~he radical3 ~, Y and Z, A i~ arl lodine atom. If the radical~ X, Y and Z are~ o~ly luorine or chlorine 15 ato~s~ then aryl :bro3ni~s~ are pref.erably employed. In the ca~e o~ the preferrod ~ub~titutios~ patt~rn, where Y = z = fluoro and X ~ chlo~o, . A may ad~a~tag20ul31y likewi~e be chlors:.
. ..
The rea~cio3l i~ senerally carried out in ~olutiorl. Inert 20 organic IElOï~re~ltY which are 3uitabl~ may b~ alipha'cic or aromatic hydrocarborls~ chloro or dichlorobon~ne, ~thar~
su~h 8 tetr~h~rdrofuran, dioxa~e, di- tri- or te~tragly~
an E3oïe, ~itriles ~uch as as:etonitrll~ obutyrollitrile or benzonil;rile~ or alcc~hols ~uch as but~nol or 2-ethyl-hexanol. ~ow~er, preferen~ i8 ~ n ko u~ng polaraprotic ~olvent~ ~uch as ~ thyl or diethyl ~ul~oxide, N,N-dialkylamid~ of aliphati~ carboxyli~ acids, or ~ .. ... ;.. :.,.. ,.... .- - .. ~;
~",' ,'.' . '.', ~"' "''''","-''' ';`'~' " ' ' ' "'' '.
- ~ - 2~33~ -alkylat~d lactam~. Pa:rticularly ~uit3ble Bolverlt~ ara N,N-dimethylacetamide, N,N-dim~'c~l:Eo~namide a~d N-m0thylpyrrolidone.
8i3~1C3 hydroge~ hal~ de i~ gl~re~ o durirlg the xeaction, 5 it i advantageou~ to trap lt l:y adding a ba~e. Suitable ba~e~ ar~ ter'ciary æ~ e~3, suc:h as triall~yl~ls~e~ haviRg C2-C6 alkyl radic~ r cyclit: ~econd~ry amine~ 3uch a~3 piperidine, piperaziale or morp~oli~ 3, and th& alkali metal or alkaline earth met~l ~3al'cs si~ aliphati6 or 10 aromat~c carboxylic acid~ or of carbonlc acid, such a Rodium ace~atQ, pota~3sium ace'cate or calcium acetat0 ;ar;ld sodiu~n carbo~ate or pot~ssium carbonate.
The reactio~ i~3 accel~rate~ both homoge~eouElly by so1uble palladium compound~ ~d by hetaroge~ou~ pall~dium cata-lyst~
Solubl~ p~lladium compou~ds which are suitable arepalladium acetate, palladium chlor~d~ or palladium bromide and th~ tetrachloro- a~d tetra~romopalladate~
which are readily acces~ibls ther~rom a~ alkali ~et~l or ammoniu~ ~alt~. Other ~ighly ~uita~bl0 catalyst precur~or~
are the complex0~ of palladium chlorld~ with acokoni-trile, benzonitrile or triphanylpho~phi~e, or the com-plexes of ~ero-valent palladil~m ~uch a~ tetraki~-(triphenylpho~phi~e)palladium.
I~ order to ~tabilize the active ~ataly~t i~ th~ r~actlo~
BolUtiOn it may bs advantag00u~ to add complaxing agent~.
Compou~ds suitable ~or thi~ purpo~e ar~ ~itrile~, ni~rogen-co~taining lagan~ ~uch a~ 2,2'-bipyridyl or o-phenanthroline, or pho3phit~. Pref~r~nce is gl~en to ~mploying pho~phinos and guaternary ammonium ~alt~, whlch alo~e or i~ co~bination bring ~bout the stabill~atio~ a~d activatio~ of the pall~d~um ~ataly~t.
Particuli~rly ~uitable mo~od~tat~ monopho~phine~ ar~
triarylphoaphi~, dialkylarylpho~phi~e~, : - 5 - ~ ~3337 diarylpho~phin~, diaryla.lkylpho~phi~oa a~d trialkylphv~phi~e~, the al~yl group~ co~ta~i~g 1 to 12 carbon atom~ a~d th~ aryl group~ being phe~yl or ~aphthyl grQUp~, either of ~hich ~y be eub~ituted ~ith C1 C~
alkyl, Cl-C3 alkoxy or S03Na.
Ex~mple~ are ~riphen~lphoRphi~e, tri-o- and tri-p-tolyl-pho~phina, ~ri(methoxyphenyl~phosphine, tri(m-sul~o~ato-phe~yl)pho~phi~ tricyclohexylphoaphine~ trii~opropyl-pho~phi~e ~nd dii~opropylphenylpho~phi~e. ~mo~g the monodentat~ pho~ph~nea, tr~phe~ylpho~ph~ne, tri~o-tolyl-pho~phin2 and tricyclohexylpho~phi~e are amployed wlth particular pr~ere~ce.
:
It ~ay be ad~antageou~ to ~mploy chelati~g b~spho phi~ea, alone or a~ a mixture w th the ~onophosph~ , i~ which ca~e bi~5di~h~ylpho~phino~ethan~ or bie(diphenyl-pho~phi~o)propane i~ pre~erably ~m~loyed.
The additio~ of ammonium brom~del~ or ~mmo~lum chloride~
has a highly adYantagsous e~ect o~ the progres~ of the catalyzed reactio~. Owlng to th~ir very ready ~olubllity and their high ~tability in the re~action m~xture, quater-nary ammonium ~alt~ are preferred and may be added to the cataly~t system in qua~tities of from 1 to 100 mol%, b~ed on the aryl halide to be r2acted. Thoae w~i~h hav~
pro~en particularl~ ~uitabl~ ar~ tetraethyl-, tetrabutyl-, tetrahe~yl-, ~e~hyltrioctyl-, b~z~
triethyl- a~d be~zyltributylammonium chl~r~da a~d the corr~sponding bromide~.
The active ~taly~t i~ preferably formed fr~m the co~po-ne~t~ in the r~action ~olutio~, or dir~ctly be~oroha~d in a 3epar~e ~olutlon; ne~ther ~olatio~ ~or a complex preparation pro~dur~ i~ nece~ary. The ~uastity of palladi~m employed i8 from 0.01 to 5 mol%, preferably from 0.2 to 1.0 ~o~%, b~ed o~ the ~ryl hallde~
Heteroge~ous palladium cataly~t~ are metalli~ palladi~m, . - 6 - 2~333~
palladium black o:c palladium fixed o~ a s~upport ~aterial.
2~y in~rt ~301ids ca~ be ~nploy~d aL~ eupport ~ aterial~.
Examples ~r~ active charcoal, alumi~um oxideR, sillc:on oxides, magn~ium oxide, alumo~illcate~, pota~Rium 5 caxbonate, barium ~ul~ate and ~alcium carborlake. Particu-larly ~u1ta~le l3upport materials are actiYe ~harcoal, aluminu~ oxide, ~ilicon d~oxide and tit~x~ium d~ oxide .
The im~lementatior~ of th~3 proc~ permit~s a ra~ge o~
variant~9 the mo~ imple varian~c bea~g that in which all 10 o ~chc ~c~mponerlts ax~ placed togeth~r i~ ths r~actio~
~lask arld th~ ~ixtur~ !brought to he re~auir~d tempera-tu:re i~or a ~ufficient ime.
Where the acrylo~itrile deri~ati~e~ are of particular polymerizability, an ispro~ame~t in ~e eelecti~ity ca~
be achieved by meteri~g i~ the~e derivati~e~ during ~he r~action. I~ the ca~e of batche~ which are di~tinctly larger tha~ i~ conventio~al in th~ laboratory, ~.t i~
neceBsary for reaæonR 0~ ~afety to control the reaction ~uch that controlled diesipat~on of the heat of r~action i~ po~sibla. Thi~ Gan be carrled out, ~or ~xample, by u~ing a liguid organic baae which i~ matered i~ under the reaction condition~, ~imultaneou~ly ~ d~ired with the cataly~t pre~ur~or.
Te~perature~ o~ 80-200C are nece~ary for the reactio~;
aryl bromide~ reaot at 80-160C, pre~erably 120-140C, while aryl chloside~ reguire tem~erature~ of 120-200C, prefer~bly 140-180C.
The time~ requised ~or a high co~ver~io~ range ~etween 1 and 16 hour~.
Exa~ple 1 2,4-Dichloro-5-fluoro~innamo~itrlla 24.4 g (0.1 mol) of 1-bromo-2,4-di~hlo~o-5~1uorobenzene, 12.7 g ~0.1 mol) o~ sodium ~arbo~ate ~ground ~ dried) a~d - 7 - 2~3~37~
10.6 g (0~2 mol) of acrylonitr~l~ ar~ pla~ed i~ a rç3a~-tion f la~k togeth~r wi 'ch 4 0 ~1 o di:methylaceta:mid~ . A
~olution o~ 0 . 22~ g (1. O mm~ pall~dium ~aet~te arld 1t)o5 53~ ~0~05 mol) of tetraethyl~mnoaiu~n bromid~ in 30 ml 5 o~ dime'chylac:etamida i~ propared ~e~paratelyO Thie ~olu-tiorl iB the~ add~d to the su~pen~io~ of ~he othor compo-nen~, wit~ thorough ~tirrl~g, a~d thc mixtur~ i~ h~ated to 135C. Quantitatl~ on~rer0iox~ ~ ach~ evad ov~r tlle ~OU~ 3 h.
10 Th~ rea~tion t301utio~ :LB :EirEt :~il ered and the~ poured int~ 500 ml o~ cold wat~3r. The targ~3t product ~3eparatos out a~ a ligh brow:cl ~olid, wi~ h i~ collec~ed on a f il~ce:r ancl dried . T~ crud~ product i~ re~ryRtalliz~d f rom cyclohexane .
The prima3:y ~roduct comprise~ 36% ci~ i~om~r and 64%
tran~ ~eomerO t:rysti~lllzatlo~ yields ~ractio~ 12.7 g (56% oi~ theory3;
af ter concen'crating the ~olven'c fraction 2: 9 . O g (41% o$ kheory) crysta:l lizes .
In ~raction 1 the traIts isomer h2l8 concentrated to 94%~
The 3na~s spectrum ron~ or both i~OmerB tha nominal molar maR3 (ba~ed on th~ 35Cl i~otrope) o ~i = 215.
E ~qR ~pec t:ca:
H ~C N
F~H Ib el Gl Ha = 5 78~5 95 PP~ Jab = 17 E~z ~Ib o 7 . 63/7 .79 ppm i '. ' ''''',~ ' . .'~ ' . ~ J'~ ,~ `. `1 ,' ' - 8 - 2~3337~
NC H~
~a = 5O60/5~73 ppm J~ - 12.5 ~z Hb - 7.85/7.96 ppm Example 2 ~ ~
2,4-Dichloro-5-1uorocl~namonitrile ~ ~:
, The co~pound oan ~l~o ba prepared u~ing a phosphi~e-~tabilized cataly~t ~y~tem.
12.2 g (0.05 mol) o~ 1-bromo-2,4-dichloro-5-~luoro-benzene, 5.0 g (0.06 mol) o~ ~odium acetate and 5.~ g (0.1 mol) of a~rylonltr~le are pl~ed in a re~tio~ la~k together w~th 15 ml o~ DMAc.
' :
~10 mg (0.5 mmol) of palladium are di~ol~ed in 10 ml of di~ethylacetamide, and 264 mg ~1.0 mmol) of triphe~yl-phosphine a~d 200 mg (0.5 ~mol) of bis(diphe~yl-pho~phino)ethane ~DIP~OS) are added. After bri~ ~tirring at room temperature the Pd(IX)-pho~phine co~plex i~
ormed.
Thi~ ~olution is added ~o the mix ure of tho ~tarti~g ~ubetan~e~, a~d the entir~ batch i~ h~ated to 140C.
After 8 h a con~eraion of 95% ha~ been aahievedD To wo~
20 up ~he rea~tion mixture it 1~ diluted with methyl t~butyl ether, the psoduat ~ extract~d br shaki~y with w~ter, and the orga~ic pha~e i~ co~centrat~d. The ~rude product which ~Q~ain~ i~ recry~tallized fro~ cyclohex~no. A yl~ld of 10.0 g (76% o~ theo~y) wa~ a~hi~Yed.
25 A de~o~rated ~r the GC and }~ pe~tra, the produc~
i~ ide~'cical wi'ch th~ sub~tance ~ro3D. Exam~;31e 1 with regard to the dl0tributio~ o~ Ci8 a~d trans i~omer~ ar~d ;~
the purity. 213 3 3 7 ~ ~
Example 3 2,4,5-Trifluorocin~amonitrile 10.6 g (O.OS mol) of 2,4,X-~ri~luorobro~obsnzene/ 5.0 g ~0.06 ~ol) of ~odiu~ a~etate and 5.4 g (0.01 ~ol3 of acrylon~rll~ are pla~d i~ a reaction ~las~ together with 20 ml of dime~hylac0tamide.
A cataly~ ~olutio~ prepared from 22 mg (Ool ~mol~ o~
pallad~um acetats, 524 mg (0.2 mmol) o~ triphenyl-pho phine and 400 mg (0.1 mmol) o bi~diphanyl pho~phino~ethane (= DIP~OS) i~ 30 ~1 of di~ethylacetamide i~ prepared ~epar t~ly.
A~ter ~he catalyst compo~e~t~ have d~olved a~d the yellow palladium complex has ~ormed, this ~olution i~
added to the abov~ bakch and th~ batch ~ h~ated to 140C
with thorough stirring.
A conver~io~ of 86% i~ achieved over a pariod of 7 h. The sole product i0 the desired 2~4,5-trifluorocinnamo-nitrile, which i~ obtained a~ a~ approximately 40:60 mixtur~ of the ci~ and tranB ieomerB ~
The product i~ isolated ~rom th~ reac lon ~olution by first diluti~g it with dichloro~thanQ a~d the~ carryi~g out ext~aatio~ with wat~r. The ~olutio~ i~ C~2Cl2 is co~centrated ~d finally the concentx~te is distilled.
The boili~g poi~t o th~ target product is 65C at 9 1 mbar m p. ~ 94-g7C.
. .
The ma~s ~pectrum co~firm~ ~or both isomer~ th~ molar ma~ o~ ~ - 183. ThR ~ ~MR Bpectru~ co~firms the stru~
tur~. ~ v . '~ ''' ' .
H~ CN
3337~ -~Hb ~a - 5.R6/6.94 ppm ~ ~ 17 ~%
~b - 7030/7.49 ~pm ~1~1 b F~a = 5 . 54/5 . 66 pp~n ;r,~", ~ 12 . 5 ~z Hb = 6.95/7.09 p~m Example 4 2,4-Dichloro-5-fluoro(a-~thyl)~Lnnamonitrlle 24.4 g (0.1 mol) of 1-bromo-2,4-d~.~hloro-5-fluorobenzene, 10 12.7 ~ (0.12 mol) o~ eodium c~rbonat~ a~d 13.4 g (9.2 ~ol) of ~et~acrylonitrile are pl~ced i~ a raa~tion fla~k tog2ther with 40 ml o~ dimethylacetamide. A ~olu-tion of 0.224 g ~1.0 mmol) o~ palla~iu~ acetate 2~d 1005 g (0.05 ~ol) o~ etra~thylammonium bro~ide ln 30 ml of dimethylac~ta~ide i~ prepared ~aparately. Thia e~lu-tion i8 added to th~ suop~ion of ths other ~ompone~t~
wi~h thorou~h ~tirring, and the r~action m~xtur~ i~ th~n ~sated t~ 135C. Qua~t~tat~v~ convar~io~ i~ found by GC
after 2 h.
The reac~io~ mixture i~ worked up by diluting it with met~yl t-butyl ether, extractin~ the produ~t by ~ha~ing with w~ter, a~d di~tllli~ the organia pha~e. Af~r re~oval o the soIvent by di~t~ tion there rsmai~e a 213~37~
crude product which ia di~tilled i~ ~racuo; b~p.l _ 105C.
The iEiolaked ~UbB anca compxi~e~ three ieomer~ whic:h, ba~ed on the ma~ pectn~m, all ha~e a mol~cular maes : .
M = 229 (ba~ed o~ the 35Cl i~o ope). The ~I N~ pectrum S CO~f1rmB t~e followin~ ~stru~turo~:
I o~ner A, 68%:
a ~ C N
~ ~Hb el~cl Ha z 2 . 20 ppm (doublet) Hb = 7.70/7878 ppm .' ' 10 I~omer 13, 29%
NC~fCII~
~H b Cl ~1 ~a = 2 . 04 pp~n (doublat) ~Ib = 7.14/7,26 ppm IE;Omer C, 2%
~eH2o ~H~
HO15:CHST ~RTï}SNG~SSi3L~SC}~F~ 0~: 93~F300 Dr. ~/b~
Descrip~Gion 2, 4, 5-l'rihalocinsla~onitrile~ and proc~s ~or their prepa~ation 5 The pre~eslt is:lvention relate~ to halogonated ci~a:mo-nitril~3 and to proc~t3eE~ for the~ prep;ar~tion.
The abovemerlkloned compou~d~ are of importance in indu~
'cry a~ termediate~ in the ps0para1:ion of ac:ti~re ingre-dien o or pharD:Iaceuticals, herbicids~ and ~ungi~id~O
10 The com}?ousld~ who~e preparatiOD. iB noYel can be prepar~d by the con~rentioD.al route, via the c:inna~nia ~Yt~r~ or the cinnamalcl~3hyda~, only with graat di~ ulty, ~ince th~a actual starting ~ tanc2s slec~ ary fox thi~ ~oute are 'c~ae corre~pondi~g 1 rihalobe~zald~}lyd~s (c~ thi~
15 r2spect Hou~e~-Weyl, ~srol~ne 135, p. 362, 1348).
A ~rariant ~ynthe~is, ther~fore~ the arylation o acrylonitril~. Thi~ rsaation, which ib catalyzod by palladium compound~, has bsen lcnown in pr~noiple ~i~ce the work by R. P~. H~ck; comprehe~ xe~ws o~ thi~
20 work can be found in l7Palladiu;n Reage~t~ in Ors~ani~
Synthe~s~", Acad~ic Pre~R N.Y~ (1985~ a~d in Organic Reaction~ 27, 345-390 (1982). T~e ole~ ompo~erlt~
emlployed are pref e~ably aarylic oster~ and ole~ins, wherea~ the reactio~ with a~rylonitrile i8 only attempted 25 in a few example~. ~or instance, R. F. ~Iec3~ et al. is~ J.
Or~. Ch~n. 43, 2g45 ~1978) de~ribe exp~rimen~c~ to ~y~the~ize p-aminocin~amo~itril~ from bromoaniline or iodoaniline~ o:nly the l~ttex gi-~ing a yleld o~ 53~6 w~ile the :t~romo compo~nd gaYe no target pxodu~t. The prepara-3û tion of p-Ponnyl~innamoni'crile i~ de~cribed in ~. Organo-met. C~hem. 258 ~- 9133~, 101 wher~, how~er, it i~ al~o indi::at~d that th~ react~ity of aryl bromide~ containing no stab~ti'csuen'cs capable o~ conjugation i~ limlted.
. ~ ."," ," ~...., "..,,~, . ;,.,~,.,., "s~ ~,, ,,,, ~,.,~ .,.~ ..,..~ " ""1, 2~33~7l~
Becau~e s:~f the general importanc!2 and the wide range of applicatio~ of thi~ cla~ of a~l~b~;ta~ca~3, it i~ a worth-while ob~ ~ct to pro~r~ de s:lo~el compound~3 rom thi~ group o ~ub~tax~cs~, ln orde~r rlot only to Elupplemen th~
5 ~p~ctrum of th~i~ po~ible u~ but al~o to enrlch and exterld i'c by ~a ine ad~u~arlt o~ the mat~rial prop~r-tie~. In addition, these n~-rel com~po~snd~ op~n up further route~ to th~ pxepar~tio:n o ollow-on productsg who~3 i%lportanc . h . ~ already b~e:~ meD.tion~d ~bove .
10 Thi~ ob~eat i8 achieved by 2,4,5-trihalocir~monitrilee o~ the for~ula I
N
R 1 ~:
wherein Rl iB hydroge~ tra~ ght-chai.~ or brancha~l Cl-Cl2 :~
alkyl, f luoro, chloro or phenyl, the phenyl radiaal being u~ t~ tuted or ~ tttuted, if de~ired, with Cl-C~ alkyl or Cl-C2 alkoxy~ and ~.
X, Y a~d Z are ideIltical or differe~t and are fluoro, chloro or bromo.
P~ c~rtai~ degree o i~pox anc~ 1~ at'cached to the aom~
20 pound~ e~f ~he ~ormula (I) ih which Rl ~ a hydroge~ or slethyl arld 2~, Y aDd Z are :E~ uoro or c~loro .
Al~o of intere~t are the compouIld~ of the fo~snul~
which X, Y ~d Z ar~ fluoro, in particular wh~n Rl 18 hydrog~n or methyl.
25 In addition, emphalsis ~hould b~ gi-rerl to the compou~ds of thQ :Eormula I i~ which X and Y are chloro all~ Z 1~ $1uoro or Y a~d Z are fluoro and X i~ ~hls~ro, in parti~ular wher Rl i hydros~en or methyl.
:; 2 ~ 3 3 3 14 The~ haloge~Lat@d ci~n~onitrile~ ~a~ be prepared ad~a~-tageoll~ly by reacting acrylonitrll~ c~r ~ tituted a~rylo~i'cril~3s of the $ormula ~XI) ~ ~g in which R1 i6 a;3 alr~ady de~ed with a compousld o the 5 ~ormula III
A
r ~x in which X, Y and Z ~r~ as deflTl~d aboY~ and A iB iodo, hrcmo or ~hlo:ro, in the pr-3senc~e o~ a palladium cataly~t, a ba~e a3~, if de~lrsd, a 301v~ t and/or a ~tabllizing ligand and/or an a~nonlu~ ~al at tesnperaturef) of 10 û0-200~C.
In ge~ral it i~ po~ible to emE~loy thoes aryl halide~
(III) in which, independently o~ the pattern o~ ti'cu-tion o~ ~he radical3 ~, Y and Z, A i~ arl lodine atom. If the radical~ X, Y and Z are~ o~ly luorine or chlorine 15 ato~s~ then aryl :bro3ni~s~ are pref.erably employed. In the ca~e o~ the preferrod ~ub~titutios~ patt~rn, where Y = z = fluoro and X ~ chlo~o, . A may ad~a~tag20ul31y likewi~e be chlors:.
. ..
The rea~cio3l i~ senerally carried out in ~olutiorl. Inert 20 organic IElOï~re~ltY which are 3uitabl~ may b~ alipha'cic or aromatic hydrocarborls~ chloro or dichlorobon~ne, ~thar~
su~h 8 tetr~h~rdrofuran, dioxa~e, di- tri- or te~tragly~
an E3oïe, ~itriles ~uch as as:etonitrll~ obutyrollitrile or benzonil;rile~ or alcc~hols ~uch as but~nol or 2-ethyl-hexanol. ~ow~er, preferen~ i8 ~ n ko u~ng polaraprotic ~olvent~ ~uch as ~ thyl or diethyl ~ul~oxide, N,N-dialkylamid~ of aliphati~ carboxyli~ acids, or ~ .. ... ;.. :.,.. ,.... .- - .. ~;
~",' ,'.' . '.', ~"' "''''","-''' ';`'~' " ' ' ' "'' '.
- ~ - 2~33~ -alkylat~d lactam~. Pa:rticularly ~uit3ble Bolverlt~ ara N,N-dimethylacetamide, N,N-dim~'c~l:Eo~namide a~d N-m0thylpyrrolidone.
8i3~1C3 hydroge~ hal~ de i~ gl~re~ o durirlg the xeaction, 5 it i advantageou~ to trap lt l:y adding a ba~e. Suitable ba~e~ ar~ ter'ciary æ~ e~3, suc:h as triall~yl~ls~e~ haviRg C2-C6 alkyl radic~ r cyclit: ~econd~ry amine~ 3uch a~3 piperidine, piperaziale or morp~oli~ 3, and th& alkali metal or alkaline earth met~l ~3al'cs si~ aliphati6 or 10 aromat~c carboxylic acid~ or of carbonlc acid, such a Rodium ace~atQ, pota~3sium ace'cate or calcium acetat0 ;ar;ld sodiu~n carbo~ate or pot~ssium carbonate.
The reactio~ i~3 accel~rate~ both homoge~eouElly by so1uble palladium compound~ ~d by hetaroge~ou~ pall~dium cata-lyst~
Solubl~ p~lladium compou~ds which are suitable arepalladium acetate, palladium chlor~d~ or palladium bromide and th~ tetrachloro- a~d tetra~romopalladate~
which are readily acces~ibls ther~rom a~ alkali ~et~l or ammoniu~ ~alt~. Other ~ighly ~uita~bl0 catalyst precur~or~
are the complex0~ of palladium chlorld~ with acokoni-trile, benzonitrile or triphanylpho~phi~e, or the com-plexes of ~ero-valent palladil~m ~uch a~ tetraki~-(triphenylpho~phi~e)palladium.
I~ order to ~tabilize the active ~ataly~t i~ th~ r~actlo~
BolUtiOn it may bs advantag00u~ to add complaxing agent~.
Compou~ds suitable ~or thi~ purpo~e ar~ ~itrile~, ni~rogen-co~taining lagan~ ~uch a~ 2,2'-bipyridyl or o-phenanthroline, or pho3phit~. Pref~r~nce is gl~en to ~mploying pho~phinos and guaternary ammonium ~alt~, whlch alo~e or i~ co~bination bring ~bout the stabill~atio~ a~d activatio~ of the pall~d~um ~ataly~t.
Particuli~rly ~uitable mo~od~tat~ monopho~phine~ ar~
triarylphoaphi~, dialkylarylpho~phi~e~, : - 5 - ~ ~3337 diarylpho~phin~, diaryla.lkylpho~phi~oa a~d trialkylphv~phi~e~, the al~yl group~ co~ta~i~g 1 to 12 carbon atom~ a~d th~ aryl group~ being phe~yl or ~aphthyl grQUp~, either of ~hich ~y be eub~ituted ~ith C1 C~
alkyl, Cl-C3 alkoxy or S03Na.
Ex~mple~ are ~riphen~lphoRphi~e, tri-o- and tri-p-tolyl-pho~phina, ~ri(methoxyphenyl~phosphine, tri(m-sul~o~ato-phe~yl)pho~phi~ tricyclohexylphoaphine~ trii~opropyl-pho~phi~e ~nd dii~opropylphenylpho~phi~e. ~mo~g the monodentat~ pho~ph~nea, tr~phe~ylpho~ph~ne, tri~o-tolyl-pho~phin2 and tricyclohexylpho~phi~e are amployed wlth particular pr~ere~ce.
:
It ~ay be ad~antageou~ to ~mploy chelati~g b~spho phi~ea, alone or a~ a mixture w th the ~onophosph~ , i~ which ca~e bi~5di~h~ylpho~phino~ethan~ or bie(diphenyl-pho~phi~o)propane i~ pre~erably ~m~loyed.
The additio~ of ammonium brom~del~ or ~mmo~lum chloride~
has a highly adYantagsous e~ect o~ the progres~ of the catalyzed reactio~. Owlng to th~ir very ready ~olubllity and their high ~tability in the re~action m~xture, quater-nary ammonium ~alt~ are preferred and may be added to the cataly~t system in qua~tities of from 1 to 100 mol%, b~ed on the aryl halide to be r2acted. Thoae w~i~h hav~
pro~en particularl~ ~uitabl~ ar~ tetraethyl-, tetrabutyl-, tetrahe~yl-, ~e~hyltrioctyl-, b~z~
triethyl- a~d be~zyltributylammonium chl~r~da a~d the corr~sponding bromide~.
The active ~taly~t i~ preferably formed fr~m the co~po-ne~t~ in the r~action ~olutio~, or dir~ctly be~oroha~d in a 3epar~e ~olutlon; ne~ther ~olatio~ ~or a complex preparation pro~dur~ i~ nece~ary. The ~uastity of palladi~m employed i8 from 0.01 to 5 mol%, preferably from 0.2 to 1.0 ~o~%, b~ed o~ the ~ryl hallde~
Heteroge~ous palladium cataly~t~ are metalli~ palladi~m, . - 6 - 2~333~
palladium black o:c palladium fixed o~ a s~upport ~aterial.
2~y in~rt ~301ids ca~ be ~nploy~d aL~ eupport ~ aterial~.
Examples ~r~ active charcoal, alumi~um oxideR, sillc:on oxides, magn~ium oxide, alumo~illcate~, pota~Rium 5 caxbonate, barium ~ul~ate and ~alcium carborlake. Particu-larly ~u1ta~le l3upport materials are actiYe ~harcoal, aluminu~ oxide, ~ilicon d~oxide and tit~x~ium d~ oxide .
The im~lementatior~ of th~3 proc~ permit~s a ra~ge o~
variant~9 the mo~ imple varian~c bea~g that in which all 10 o ~chc ~c~mponerlts ax~ placed togeth~r i~ ths r~actio~
~lask arld th~ ~ixtur~ !brought to he re~auir~d tempera-tu:re i~or a ~ufficient ime.
Where the acrylo~itrile deri~ati~e~ are of particular polymerizability, an ispro~ame~t in ~e eelecti~ity ca~
be achieved by meteri~g i~ the~e derivati~e~ during ~he r~action. I~ the ca~e of batche~ which are di~tinctly larger tha~ i~ conventio~al in th~ laboratory, ~.t i~
neceBsary for reaæonR 0~ ~afety to control the reaction ~uch that controlled diesipat~on of the heat of r~action i~ po~sibla. Thi~ Gan be carrled out, ~or ~xample, by u~ing a liguid organic baae which i~ matered i~ under the reaction condition~, ~imultaneou~ly ~ d~ired with the cataly~t pre~ur~or.
Te~perature~ o~ 80-200C are nece~ary for the reactio~;
aryl bromide~ reaot at 80-160C, pre~erably 120-140C, while aryl chloside~ reguire tem~erature~ of 120-200C, prefer~bly 140-180C.
The time~ requised ~or a high co~ver~io~ range ~etween 1 and 16 hour~.
Exa~ple 1 2,4-Dichloro-5-fluoro~innamo~itrlla 24.4 g (0.1 mol) of 1-bromo-2,4-di~hlo~o-5~1uorobenzene, 12.7 g ~0.1 mol) o~ sodium ~arbo~ate ~ground ~ dried) a~d - 7 - 2~3~37~
10.6 g (0~2 mol) of acrylonitr~l~ ar~ pla~ed i~ a rç3a~-tion f la~k togeth~r wi 'ch 4 0 ~1 o di:methylaceta:mid~ . A
~olution o~ 0 . 22~ g (1. O mm~ pall~dium ~aet~te arld 1t)o5 53~ ~0~05 mol) of tetraethyl~mnoaiu~n bromid~ in 30 ml 5 o~ dime'chylac:etamida i~ propared ~e~paratelyO Thie ~olu-tiorl iB the~ add~d to the su~pen~io~ of ~he othor compo-nen~, wit~ thorough ~tirrl~g, a~d thc mixtur~ i~ h~ated to 135C. Quantitatl~ on~rer0iox~ ~ ach~ evad ov~r tlle ~OU~ 3 h.
10 Th~ rea~tion t301utio~ :LB :EirEt :~il ered and the~ poured int~ 500 ml o~ cold wat~3r. The targ~3t product ~3eparatos out a~ a ligh brow:cl ~olid, wi~ h i~ collec~ed on a f il~ce:r ancl dried . T~ crud~ product i~ re~ryRtalliz~d f rom cyclohexane .
The prima3:y ~roduct comprise~ 36% ci~ i~om~r and 64%
tran~ ~eomerO t:rysti~lllzatlo~ yields ~ractio~ 12.7 g (56% oi~ theory3;
af ter concen'crating the ~olven'c fraction 2: 9 . O g (41% o$ kheory) crysta:l lizes .
In ~raction 1 the traIts isomer h2l8 concentrated to 94%~
The 3na~s spectrum ron~ or both i~OmerB tha nominal molar maR3 (ba~ed on th~ 35Cl i~otrope) o ~i = 215.
E ~qR ~pec t:ca:
H ~C N
F~H Ib el Gl Ha = 5 78~5 95 PP~ Jab = 17 E~z ~Ib o 7 . 63/7 .79 ppm i '. ' ''''',~ ' . .'~ ' . ~ J'~ ,~ `. `1 ,' ' - 8 - 2~3337~
NC H~
~a = 5O60/5~73 ppm J~ - 12.5 ~z Hb - 7.85/7.96 ppm Example 2 ~ ~
2,4-Dichloro-5-1uorocl~namonitrile ~ ~:
, The co~pound oan ~l~o ba prepared u~ing a phosphi~e-~tabilized cataly~t ~y~tem.
12.2 g (0.05 mol) o~ 1-bromo-2,4-dichloro-5-~luoro-benzene, 5.0 g (0.06 mol) o~ ~odium acetate and 5.~ g (0.1 mol) of a~rylonltr~le are pl~ed in a re~tio~ la~k together w~th 15 ml o~ DMAc.
' :
~10 mg (0.5 mmol) of palladium are di~ol~ed in 10 ml of di~ethylacetamide, and 264 mg ~1.0 mmol) of triphe~yl-phosphine a~d 200 mg (0.5 ~mol) of bis(diphe~yl-pho~phino)ethane ~DIP~OS) are added. After bri~ ~tirring at room temperature the Pd(IX)-pho~phine co~plex i~
ormed.
Thi~ ~olution is added ~o the mix ure of tho ~tarti~g ~ubetan~e~, a~d the entir~ batch i~ h~ated to 140C.
After 8 h a con~eraion of 95% ha~ been aahievedD To wo~
20 up ~he rea~tion mixture it 1~ diluted with methyl t~butyl ether, the psoduat ~ extract~d br shaki~y with w~ter, and the orga~ic pha~e i~ co~centrat~d. The ~rude product which ~Q~ain~ i~ recry~tallized fro~ cyclohex~no. A yl~ld of 10.0 g (76% o~ theo~y) wa~ a~hi~Yed.
25 A de~o~rated ~r the GC and }~ pe~tra, the produc~
i~ ide~'cical wi'ch th~ sub~tance ~ro3D. Exam~;31e 1 with regard to the dl0tributio~ o~ Ci8 a~d trans i~omer~ ar~d ;~
the purity. 213 3 3 7 ~ ~
Example 3 2,4,5-Trifluorocin~amonitrile 10.6 g (O.OS mol) of 2,4,X-~ri~luorobro~obsnzene/ 5.0 g ~0.06 ~ol) of ~odiu~ a~etate and 5.4 g (0.01 ~ol3 of acrylon~rll~ are pla~d i~ a reaction ~las~ together with 20 ml of dime~hylac0tamide.
A cataly~ ~olutio~ prepared from 22 mg (Ool ~mol~ o~
pallad~um acetats, 524 mg (0.2 mmol) o~ triphenyl-pho phine and 400 mg (0.1 mmol) o bi~diphanyl pho~phino~ethane (= DIP~OS) i~ 30 ~1 of di~ethylacetamide i~ prepared ~epar t~ly.
A~ter ~he catalyst compo~e~t~ have d~olved a~d the yellow palladium complex has ~ormed, this ~olution i~
added to the abov~ bakch and th~ batch ~ h~ated to 140C
with thorough stirring.
A conver~io~ of 86% i~ achieved over a pariod of 7 h. The sole product i0 the desired 2~4,5-trifluorocinnamo-nitrile, which i~ obtained a~ a~ approximately 40:60 mixtur~ of the ci~ and tranB ieomerB ~
The product i~ isolated ~rom th~ reac lon ~olution by first diluti~g it with dichloro~thanQ a~d the~ carryi~g out ext~aatio~ with wat~r. The ~olutio~ i~ C~2Cl2 is co~centrated ~d finally the concentx~te is distilled.
The boili~g poi~t o th~ target product is 65C at 9 1 mbar m p. ~ 94-g7C.
. .
The ma~s ~pectrum co~firm~ ~or both isomer~ th~ molar ma~ o~ ~ - 183. ThR ~ ~MR Bpectru~ co~firms the stru~
tur~. ~ v . '~ ''' ' .
H~ CN
3337~ -~Hb ~a - 5.R6/6.94 ppm ~ ~ 17 ~%
~b - 7030/7.49 ~pm ~1~1 b F~a = 5 . 54/5 . 66 pp~n ;r,~", ~ 12 . 5 ~z Hb = 6.95/7.09 p~m Example 4 2,4-Dichloro-5-fluoro(a-~thyl)~Lnnamonitrlle 24.4 g (0.1 mol) of 1-bromo-2,4-d~.~hloro-5-fluorobenzene, 10 12.7 ~ (0.12 mol) o~ eodium c~rbonat~ a~d 13.4 g (9.2 ~ol) of ~et~acrylonitrile are pl~ced i~ a raa~tion fla~k tog2ther with 40 ml o~ dimethylacetamide. A ~olu-tion of 0.224 g ~1.0 mmol) o~ palla~iu~ acetate 2~d 1005 g (0.05 ~ol) o~ etra~thylammonium bro~ide ln 30 ml of dimethylac~ta~ide i~ prepared ~aparately. Thia e~lu-tion i8 added to th~ suop~ion of ths other ~ompone~t~
wi~h thorou~h ~tirring, and the r~action m~xtur~ i~ th~n ~sated t~ 135C. Qua~t~tat~v~ convar~io~ i~ found by GC
after 2 h.
The reac~io~ mixture i~ worked up by diluting it with met~yl t-butyl ether, extractin~ the produ~t by ~ha~ing with w~ter, a~d di~tllli~ the organia pha~e. Af~r re~oval o the soIvent by di~t~ tion there rsmai~e a 213~37~
crude product which ia di~tilled i~ ~racuo; b~p.l _ 105C.
The iEiolaked ~UbB anca compxi~e~ three ieomer~ whic:h, ba~ed on the ma~ pectn~m, all ha~e a mol~cular maes : .
M = 229 (ba~ed o~ the 35Cl i~o ope). The ~I N~ pectrum S CO~f1rmB t~e followin~ ~stru~turo~:
I o~ner A, 68%:
a ~ C N
~ ~Hb el~cl Ha z 2 . 20 ppm (doublet) Hb = 7.70/7878 ppm .' ' 10 I~omer 13, 29%
NC~fCII~
~H b Cl ~1 ~a = 2 . 04 pp~n (doublat) ~Ib = 7.14/7,26 ppm IE;Omer C, 2%
~eH2o ~H~
3 Hb ~ 1~ \ I
Ha = 5.74/6-~ PP~
Hb = 3 . 64 ppm ~;
Ha = 5.74/6-~ PP~
Hb = 3 . 64 ppm ~;
Claims (16)
1. A 2,4,5-trihalocinnamonitrile of the formula I
(I) wherein R1 is hydrogen, straight-chain or branched C1-C12 alkyl, fluoro, chloro or phenyl, the phenyl radical being unsubstituted or substituted, if desired, with C1-C4 alkyl or C1-C2 alkoxy, and X, Y and Z are identical or different and are fluoro, chloro or bromo.
(I) wherein R1 is hydrogen, straight-chain or branched C1-C12 alkyl, fluoro, chloro or phenyl, the phenyl radical being unsubstituted or substituted, if desired, with C1-C4 alkyl or C1-C2 alkoxy, and X, Y and Z are identical or different and are fluoro, chloro or bromo.
2. A compound as claimed in claim 1, wherein R1 is hydrogen or methyl and X, Y and Z are fluoro or chloro.
3. A compound as claimed in claim 1 or 2, wherein X, Y
and Z are fluoro.
and Z are fluoro.
4. A compound as claimed in claim 1 or 2, wherein X and Y are chloro and Z is fluoro.
5. A compound as claimed in claim 1 or 2, wherein Y and Z are fluoro and X is chloro.
6. A process for the preparation of a compound as claimed in claim 1, which comprises reacting a compound of the formula (II) (II) in which R1 is as defined above with a compound of the formula III
(III) in which X, Y and Z are as defined above and A is iodo, bromo or chloro, in the presence of a palladi-um catalyst, a base and, if desired, a solvent and/or stabilizing liquid and/or ammonium salt, at temperatures of 80-200°C.
(III) in which X, Y and Z are as defined above and A is iodo, bromo or chloro, in the presence of a palladi-um catalyst, a base and, if desired, a solvent and/or stabilizing liquid and/or ammonium salt, at temperatures of 80-200°C.
7. The process as claimed in claim 6, wherein A is bromo or iodo, especially iodo.
8. The process as claimed in claim 6 or 7, wherein the solvent employed is an aliphatic hydrocarbon, aro-matic hydrocarbon, chlorobenzene, dichlorobenzene, tetrahydrofuran, dioxane, diglyme, triglyme or tetraglyme, anisole, acetonitrile, isobutyronitrile, benzoitrile, butanol or 2-ethylhexanol, in particu-lar dimethyl sulfoxide, diethyl sulfoxide, the N,N-dialkylamide of an aliphatic carboxylic acid, an alkylated lactam, preferably N,N-dimethylacetamide, N,N-dimethylformamide or N-methylpyrrolidone.
9. The process as claimed in at least one of claims 6 to 8, wherein the base employed is a tertiary amine and/or an alkali metal or alkaline earth metal salt of an aliphatic or aromatic carboxylic acid or of carbonic acid, in particular a C2-C6 alkylamine, a cyclic secondary amine, preferably piperidine, piperazine or morpholine, sodium acetate, potassium acetate, calcium acetate and/or sodium carbonate or potassium carbonate.
10. The process as claimed in at least one of claims 6 to 9, wherein the palladium catalyst employed is a soluble palladium compound, especially palladium acetate, palladium chloride, palladium bromide, tetrachloropalladate, tetrabromopalladate, a complex of palladium dichloride with acetonitrile, benzo-nitrile or triphenylphosphine, or tetrakis(tri-phenylphosphine)palladium.
11. The process as claimed in at least one of claims 6 to 9, wherein the palladium catalyst employed is a heterogenous palladium catalyst, especially palladi-um black or palladium on a support material.
12. The process as claimed in claim 11, wherein the support material employed is active charcoal, alumi-num oxide, silicon oxide, magnesium oxide, a titani-um oxide, an alumosilicate, potassium carbonate, barium sulfate or calcium carbonate, especially active charcoal, aluminum oxide, silicon oxide or titanium dioxide.
13. The process as claimed in at least one of claims 6 to 10, wherein the stabilizing ligand employed is a nitrile, amine, phosphine or phosphite, in particu-lar an arylphosphine or alkylphosphine, preferably triphenylphosphine, tri-o-tolylphosphine or tri-cyclohexylphosphine.
14. The process as claimed in at least one of claims 6 to 13, wherein the ammonium salt employed is a quaternary ammonium bromide or ammonium chloride, especially tetraethyl-, tetrabutyl-, tetrahexyl-, methyltrioctyl-, benzyltriethyl- and/or benzyltri-butylammonium chloride or a corresponding bromide.
15. The process as claimed in at least one of claims 1 to 14, wherein from 1 to 100 mol% of ammonium salt, based on the aryl halide, are employed.
16. The process as claimed in at least one of claims 1 to 15, wherein from 0.01 to 5 mol%, in particular from 0.2 to 1 mol%, of palladium catalyst, based on the aryl halide, are employed.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19934333711 DE4333711A1 (en) | 1993-10-02 | 1993-10-02 | 2,4,5-trihalocinnamic acid nitriles and process for their preparation |
| DEP4333711.2 | 1993-10-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2133374A1 true CA2133374A1 (en) | 1995-04-03 |
Family
ID=6499320
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2133374 Abandoned CA2133374A1 (en) | 1993-10-02 | 1994-09-30 | 2,4,5-trihalocinnamonitriles and process for their preparation |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0647620A1 (en) |
| JP (1) | JPH07179413A (en) |
| CA (1) | CA2133374A1 (en) |
| DE (1) | DE4333711A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2997696B1 (en) * | 2012-11-08 | 2014-12-05 | Servier Lab | NOVEL PROCESS FOR THE SYNTHESIS OF (2E) -3- (3,4-DIMETHOXYPHENYL) PROP-2-ENENITRILE, AND APPLICATION TO THE SYNTHESIS OF IVABRADINE AND ITS SALTS OF ADDITION TO A PHARMACEUTICALLY ACCEPTABLE ACID |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3737983A1 (en) * | 1987-11-09 | 1989-08-03 | Bayer Ag | 3-CYANO-4-PHENYL-PYRROL DERIVATIVES |
| DE4107398A1 (en) * | 1991-03-08 | 1992-11-05 | Bayer Ag | METHOD FOR PRODUCING 4-CYANO-PYRROL COMPOSITIONS SUBSTITUTED IN 3-POSITION |
-
1993
- 1993-10-02 DE DE19934333711 patent/DE4333711A1/en not_active Withdrawn
-
1994
- 1994-09-22 EP EP94114936A patent/EP0647620A1/en not_active Withdrawn
- 1994-09-30 CA CA 2133374 patent/CA2133374A1/en not_active Abandoned
- 1994-09-30 JP JP23755194A patent/JPH07179413A/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07179413A (en) | 1995-07-18 |
| DE4333711A1 (en) | 1995-04-06 |
| EP0647620A1 (en) | 1995-04-12 |
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