Ruthenium-Catalysed Selective N-Monoalkylation of la with 2 Under. Various Reaction .... a short silica gel column (ethyl acetate), washed with brine and dried.
SYNTHEㄲ C COMMUNICAㄲ ONS, 3l(24) , 379--3797 (200l)
RUTHENIUMCATALYSED SELECTIVE jV-MONOALKYLATION OF
ANILINES
WITH
AMMONIUM
TETRAALKYLHALIDES
Chan sik Cho,* Joon Seok Kim, Hun Sco’ Kim, Tae-Je。 ng Kim, and San鷺 Chul Shim*
DepartmentofIndustrial Chemistry, College of Engineering, Kyungpook NationalUhiversity, Taegu 702-70l, South Korea
ABSTRACI’
Anihnesreactwithan arrayoftetraalkylammonium halides in
thePresence of a catalvtic amount of a ruthenium catalyst together withSnorZHZO indioxaneat 180oCto afford selectively jpmonoalkyfanilines in good yields.
h has been welldocumented thatN-alkylation of primaryand sec0n-
daryaminescan be achieved by various alkylating agentssuchas alkyl halides, aldehydes,and ketones.In Contrast to the classical methods, recently, homogeneous tra n도I[1On metalcatalysedN-alkylations utilising alcohols ’ and aminesZas alkylating substrates have als0been attemPted.
In thecourseo「ourcontintling studies on transition metalcatalysed synthesis o「N-heterocyclic compounds,we recently developedand reporteda
*Correspondingauthors 379 1
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CHO
ET
AL.
rutheniumfatalysed synthetic approachfortheformation ofindoles3가 and quin이ines. 5 S lt wa ’ suggestedthatal-reaction5 Proceededvia an initial a llll ne redistribution reaction (or amine exchangereactionbetweena nl linesand trialkylamines, and theaddition0ftin (ll) chloride dihydrate ，胛a s essent*al for the effectiveheteroannulat
lon.During a continuation to fook
fortheactual roleofSnC12· ZHZO, we accidently foundthatanilines react with tetraalkylammoniumhalidesto give selectively N-monoalkylanilines under therutheniumtincatalytic system. The results ofsevera ’ aitemPtedrutheni um-catalysed N-alkylaiions 。f aniline (la) withtetrabutylammonium bromide (2) aresummarisedinTablel (Equation1).TyPically, la was reacted with2 indioxaneinthepresence Of a rUthenium precursor (lmol% basedon Ia)ai 180OC for20h under argon . When the reaction was performedintheabseneeof Sn02· ZHZO, although thereactivity toward N-alkylati0ll was increased, theselectivity of 꾜＊monO-
alkylation toN,N-dialkylation was deereased comparedwiththeresult in the presenceof SnorZHZO (runs1 and 2). Under the treatment of equi풀 molar amounts o「la and Z,the selectivity was increased with the increase in the amount of sn02· ZHZO emPloyed (runs3 and 4). However, the exeessuse ofSnC12·ZHZO stoppedthereaction almostcomPletely (run 5).
Table 1. Ruthcnium-CatalysedSelective N·Monoalkylationof la with 2 Under Various ReactiorlConditionsa
50 75 53 68 2 51 35 42 46 20 24
현一
른a
令乙
-
RuornHZO/ l. sdPPec
l
Ru, (C이12 RuornHZO/ 3PPh3
츱j
댜 ‘
4
Ru, (C이 "
勺‘
今」
R써（C이12 R써（C이ㅁ Rus (C이I2
1
0
CP*RuC12(c이d
1
cP*Ruo (C이 （PEt) ,d
1
1
9
RuH玄PPh〕 ） 4
1
8
RuCI코PPhp〕
4a
5 0 - - 2 2 - 2
3a
I B幻
Of la
’
(mmol)
Z (mm이〕 Ruthcnium Catalyst
2
/b 쫴／
Conv.(o/ o)
54 95 98 79 20 55 35 60 74 29 37
Run
Yield(% )b
Sn02- ZHZO
aReactionconditlons: la (2 mm이） ,rutheniumcatalyst （以02 mmol) ,dioxane(I0mL) ,
I80oc, 20h,underargon bdetemllnedby GLC basedon la. cdppe= l,2-b1 (diphenyIphosphino) ’s ethan.
c5M이 dcp*= ns-
ANILINES
WITH
TETRAALKYLAMMON!
UM
Iㅓ ALIDES
379〕
Among catalyst Precursors exammed,as shown in Table l,the RuClr 〃H2이PPh3 and Rus (Co) .2 systems arethecholces forthepreference for the effective jValkylation (runs6】 ll).
cat. Ru
ROL’ ,HZ
+ Bu4NBr
l a: R
R叡， HBu+ ROL, ， 。 。 ， ,l」
SnCl2 ’2H20 -
-
-,
diOXafle
180 。 C, 20 h 2
=
H
寸．R = 4- Me
b: R = 2-Me
e: R = 4- OMe
c: R
r: R
=
3- Me
= 4- Cl
From thereaction of anilines 1 with an arrayof tetraalkylammonium halidesexcePtfor tetramethylammoniumchlorideunder the controned reaction conditions above,the corresponding N-alkylanihnes were formed ingood yields, and severa1 representative resuhsaresummarisedinTable2.
Table 2. Ruthenium-Catalysed SelectivejvMon。 alkylationof Anilineswith TetraalkylammoniumHaldiesa
Conv.(0/ o) R4X
4
