Abstract
It has been found that a Mannich-type reaction catalyzed by an
intramolecular phenolic hydroxy group involves simply heating a
hydroxybenzaldehyde with a secondary amine and a dialkyl phosphite
in alcohol, produced highly substituted α-aminomethylphosphonates.
The corresponding reaction can hardly be detected if the hydoxy
group of the benzaldehyde is absent or blocked, or the hydroxybenzaldehyde
is replaced by 2′-hydroxyacetophenone.
Key words
Mannich-type reaction - autocatalysis - α-amino
phosphonates - secondary amine - hydroxybenzaldehyde
References
<A NAME="RF10302SS-1">1 </A>
Fields EK.
J.
Am. Chem. Soc.
1952,
74:
1528
<A NAME="RF10302SS-2">2 </A>
Moedritzer K.
Irani RR.
J. Org. Chem.
1966,
31:
1603
<A NAME="RF10302SS-3">3 </A>
Dai Q.
Chen R.-Y.
Chem. J. Chin. Univ.
1997,
18:
64
<A NAME="RF10302SS-4">4 </A>
Tyka R.
Hagele G.
Synthesis
1984,
218
<A NAME="RF10302SS-5">5 </A>
Qian C.
Huang T.
J. Org. Chem.
1998,
63:
4125
<A NAME="RF10302SS-6">6 </A>
Heydari A.
Karimian A.
Ipaktschi J.
Tetrahedron
Lett.
1998,
39:
6729
7a </A>
Wang Q.
Mu S.-H.
Yang R.-F.
Wang H.
Chin. Pharmacol.
Bull.
2002,
18:
468
7b </A>
Shan L.-M.
PhD. Dissertation
Beijing
Institute of Pharmacology and Toxicoloy;
China:
2002.
7c </A>
Yang R, and
Wang H. inventors; Chinese Patent Application CN01137268.0.
7d </A>
Wang H, and
Yang R. inventors; Chinese Patent Application CN01137273.7.
7e </A>
Wang H, and
Yang R. inventors; Chinese Patent Application CN01137274.5.
<A NAME="RF10302SS-8">8 </A>
Schreiber SL.
Science
2000,
287:
1964
<A NAME="RF10302SS-9">9 </A>
Experiments were performed in which
2′-hydroxy-acetophenone and benzaldehydes without a phenolic hydroxy
group were used in place of the corresponding benzaldehydes with
a phenolic hydroxy group, and were respectively treated with diethyl
phosphite and the corresponding secondary amines or their hydrochloride
salts in the presence or absence of 1 equivalent of acetic acid
in the same way and under the same conditions as stated in the general
procedure.
<A NAME="RF10302SS-10">10 </A>
Anilines such as p -bromoaniline, p -hydroxyaniline and 2,3-dimethyl-2-butylamine
were reacted with piperonal and diethyl phosphite producing the
corresponding phosphonates in excellent yields.
<A NAME="RF10302SS-11">11 </A>
Takahashi H.
Yoshika M.
Imai N.
Onimura K.
Kobayashi S.
Synthesis
1994,
763
<A NAME="RF10302SS-12">12 </A>
Burckhalter JH.
Leib RI.
J. Org. Chem.
1961,
26:
4078
<A NAME="RF10302SS-13">13 </A>
Monti SA.
Johnson WO.
Tetrahedron
1970,
26:
3685
