Three-component cyclocondensations. A convenient access to fused imidazolium and dihydropyrimidinium salts via the reaction of methyl chlorothioimidates with azines and isocyanides

Article abstract of DOI:10.1016/S0040-4039(00)77603-9

A mixture of methyl chlorothioimidate, isocyanide and pyrinidine react in a sequence of N-imidoylpyridinium formation then cycloaddition step, to give 1-amonoimidazo [1,5-a] pyridazine, pyrimidine and pyrazine allows the preparation of corresponding fused 1 -amino-3-(methylthio) imidazolium chlorides.

Full text of DOI:10.1016/S0040-4039(00)77603-9

TetrahedmnLette~.Vol.34,No,14.pl~2319-2322,1993
PrintedinGreatBritain
0040-4039/93$6.00+.00
PergamonPreas
Three-Component Cyclocondensations. A Convenient Access
to Fused Imidazolium and Dihydropyrimidinium Salts
via the Reaction of Methyl Chlorothioimidates
with Azines and Isocyanides.
Evelyne Marchand and Georges Morel*
Laboratoire de PhysicochimieStructuraleassoci~au CNRS, Campusde Beaulieu, 35042 Rennes,
France.
Abstrnct.A mixtureofmethylcklorothioiraidale,isocyanideandpyridinereactinasequence
ofN-imidoylpyridialwlnformation thencycloe__~_':ionstep,togiveIqunino~:_dn_.~[l.5-a]
pyr/d/n/amandeventuallypyr/d/no[I~2-c]dihydropyrimieh~isunsalts.Similarly,theuseof
pyri,~,i~e,pyrin6dineandpyrazineallowsthepreparmionofcorrespondingfusedI-amino-J-
(methylthio)i~:_,l,,yol~'nchlorides.
Into chlorosulfi~s are readily obtained from isocyanides and aryl or alkylsulfenyl chlorides and
these attractive products have recently been used in various ways in the field of heterocycficchcn~ 15. In
pa~ti'¢ular, we have reported that action of methyl chlorothioimidates 1, on benzaldimdnes affords N-
imidoylbenzylideniminhnnspecies as unstable intenmdiates which are trapped by ~ocyanides to give 4-Rmino-
2"-ttne~l~'h~j" ~ d h m sm~ ~/~ u~esameway, me~yi"a~ I~Y," ~hbr~'h~
~
amerCe-
with thio-DMF to furnish transient N.(thiocarbonyl) forwamidinium chlorides. [1 + 4] cycloaddition to
isocyanides in sire yields a large number of useful 4,5-diaminothiazolium salts 4. The efficiencyof these three-
¢on!vonem.vr~e~es prompts ~s W exam~e ~e ~>e~a~om" o~ o~er ac~ve com~enbs nnb~ ~m~ar
C'J~7~k.~'~~'~ymfi~k~ ~. ~ ~y"~t"~'~__~f~, ~
is expected (scheme l).
-wt~/~i~ ~,~i~,.my'rl)yr~iinm~
£~r~-h~a.~
-~
We have found that representative imidoyl chlorides 1 and pyridines undergo slow
at 2~ |r~) for several ~lays.Thus, wc~navcob~nc~ a mixture ot cyc~oe~ta~s• an&$ or 6~h~erv~)cof ~hese
sa~s s~Tng)y pr~po~m'am, ~¢p~n~ng upon ~e na~,v oF~¢ va~ous e~c~s, as hea~beh )n ~w ~ab)¢.The
ra~o ol~.~ sharg"t,v"tacreascs w'aen ster~mg compounds 1 and 2 are N-substimtcdtby ~¢ "tsopmpylgroup {~or
The first step of the reaction proceeds most probably asa quaternization at the nitrogen ring. The
resulting cationic species 3, in small equilibrium concenlradon 6, are trapped by nucleophilic isocyanides via
two competitive process. One way is the [1 + 4] cycl~_d_d_itionmute and subsequent tautomerism to produce 1-
amino-3-(methylthio) imidazo [1,5-a] pyridinium chlorides 4. Another way leads to 1-amino-2-imlno~-
(methylthio) pyridino [1,2-c] dihydropyrimidiniumchlorides 5, according to a [1 + 1 + 4] mechanism 7.
A third product can also be obtained in noticeable quantities, especially with the ethyl group as RI
and R4 substituents (entries 1-4), and identified as the 6-chloro-4,5-diimino-6-(methylthio)-l,6-dihydro-2-
pyrimidinethione 6.
2319