<P>In the reaction of compound 7 with ethylenediamine
(
13) according to Scheme 4, it was reported
that 1-tosyl-1,4,7-triazacyclononane (
9)
was obtained in 78% isolated yield. However, after being
alerted by other laboratories, we repeated the same reaction under
identical experimental conditions and did not obtain compound
9 as the product of the reaction. While
the compound obtained was isomeric with
9 according
to its mass spectrum, its 1H NMR spectrum was similar but not identical
to that of
9, a known compound which could
be obtained by an alternate route and independently synthesized
according to Scheme 2.
¹ More significantly,
the 13C NMR spectrum of the obtained product has four aromatic and
five aliphatic carbon signals and is distinctly different from that
of 1-tosyl-1,4,7-triazacyclononane (
9)
which has eight carbon signals. The product is assigned to have
the structure 1-(2′-aminoethyl)-4-tosylpiperazine (
23) (revised Scheme 4). The formation of
a six-membered ring is consistent with the reaction of
7 with
N,
N-dimethylethylenediamine (
10) in giving 1-methyl-4-tosylpiperazine
(
11) as we had reported in Scheme 3.</P>
Revised Scheme 4: Reaction of 7 with 13
<P>We also re-examined the coupling of
7 with
1,4,7-triazaheptane (
19) using potassium
carbonate in refluxing acetonitrile (Scheme 7). The product obtained
was found not to be 1-tosyl-1,4,7,10-tetraazacyclododecane (
20), a known compound independently synthesized
by an alternate route.
² While the product was
isomeric with
20 according to its mass
spectrum, its
¹H and
¹³C
NMR spectra were different from those of
20.
The product is consistent with a piperazine structure
24, with four aromatic and six aliphatic
carbon signals in its
¹³C NMR spectrum
(revised Scheme 7).</P>
Revised Scheme 7: Reaction of 7 with 19
<P>In conclusion, ethylenediamine (
13)
and 1,4,7-triazaheptane (
19) did react
with
7 but did not give the corresponding
tacn
9 or cyclen
20.</P><P></P><P>
1-(2′-Aminoethyl)-4-tosylpiperazine
(23)
</P><P>Compound
7 (5.83 g, 10.0 mmol), K
2CO
3 (8.00
g, 58.0 mmol), ethylenediamine (0.60 g, 10.0 mmol) and anhydrous
MeCN (50 mL) were added to a round-bottom flask. The mixture was
heated to reflux under an N2 atmosphere for 12 h. The mixture was
cooled to r.t. and filtered. The filtrate was concentrated and the
residue was purified by flash chromatography (SiO
2, CH
2Cl
2-MeOH-Et
3N = 2:1:0.05
as eluent) to give 23 as a pale yellow oil (2.0 g, 78%).</P><P>
¹H NMR (400 MHz, CDCl
3): δ = 7.63
(d,
J = 7.4
Hz, 2 H), 7.32 (d,
J = 7.4
Hz, 2 H), 3.01 (br, 4 H), 2.73 (t,
J = 6.0
Hz, 2 H), 2.52 (br t, 4 H), 2.43-2.40 (m, 5 H).</P><P>
¹³C NMR (100 MHz, CDCl
3): δ = 143.7,
132.4, 129.6, 127.8, 60.2, 52.2, 46.0, 38.4, 21.5.</P><P>LRMS (ESI):
m/
z = 284 ([M
+ + H],
100).</P><P>HRMS (ESI): calcd for C
13H
22N
3O
2S
(M
+ + H); 284.1433; found: 284.1423.</P><P>
1-(1′,4′-Diazahexyl)-4-tosylpiperazine
(24)
</P><P>1,4,7-Triazaheptane (
19, 0.40 g, 4.00
mmol), compound
7 (2.30 g, 4.00 mmol),
K
2CO3 (6.00 g, 40.0 mmol) and anhydrous MeCN (20 mL)
were added to a round-bottom flask. The mixture was heated to reflux
under an N
2 atmosphere for 18 h. The mixture was cooled to
r.t. and filtered. The filtrate was concentrated and the residue
was purified by chromatography (SiO
2, CH
2Cl
2-MeOH = 2:1
as eluent) to give a light yellow oil (1.2 g, 83%).</P><P>
¹H NMR (400 MHz, CDCl
3): δ = 7.58
(d,
J = 8.0
Hz, 2 H), 7.27 (d,
J = 8.0
Hz, 2H), 2.95 (br, 4 H), 2.70 (t,
J = 6.0
Hz, 2 H), 2.59 (p,
J = 6.0
Hz, 2 H), 2.47 (br t, 4 H), 2.43 (t,
J = 6.0
Hz, 2H), 2.37 (s, 3 H).</P><P>
¹³C NMR (100 MHz, CDCl
3): δ = 143.7,
132.4, 129.6, 127.8, 57.4, 52.3, 52.2, 46.1, 46.0, 41.4, 21.5.</P><P>LRMS (ESI):
m/
z = 327 ([M
+ + H],
100), 349 ([M
+ + Na],
29).</P><P>HRMS (ESI): calcd for C
15H
27N
4O
2S [M
+ + H]:
327.1855; found: 327.1856.</P><P></P><P>
Acknowledgment
</P><P>We gratefully acknowledge the help of Dr. Kin-Fai Chan for repeating
the experiments.</P><P></P><P>
References
</P><P>(1) (a) Flassbeck, C.; Wieghardt, K.
Z.
Anorg. Allg. Chem. 1992,
608, 60. (b) Romakh, V. B.; Therrien,
B.; Labat, G.; Stoekli-Evans, H.; Shul"pin, G. B.; Suss-Fink,
G.
Inorg. Chim. Acta 2006,
359, 3297. (c) Romakh, V. B.; Therrien,
B.; Karmazin-Brelot, L; Labat, G.; Stoekli-Evans, H.; Shul"pin,
G. B.; Suss-Fink, G.
Inorg. Chim. Acta 2006,
359, 1619.
(d) Bambirra, S.; Leusen, D. V.; Cornelis G. J.; Tazelaar, A. M.;
Hessen, B.
Organometallics 2007,
26, 1014.</P><P>(2) Compound
20 could be obtained by
mono-tosylation of commercially available
2.
See: (a) Ohashi, M.; Konkol, M.; Del Rosal, I.; Poteau, R.; Maron,
L.; Okuda, J.
J. Am. Chem. Soc.,
2008,
130, 6920.
(b) Leivers, M.; Breslow, R.
Bioorg. Chem.,
2001,
29, 345.</P>
