An improved synthesis of 1,4,7-triazacyclononanes (tacns) and 1,4,7,10-tetraazacyclododecanes (cyclens) (Synthesis (2009) (2341)

Full text of DOI:10.1055/s-0030-1258316

ADDENDA AND ERRATA
3941
Erratum
An Improved Synthesis of 1,4,7-Triazacyclononanes (tacns) and
1
,4,7,10-Tetraazacyclododecanes (cyclens)
Jianying Huang, Zhongyuan Zhou, Tak Hang Chan* Synthesis 2009, 2341.
2
In the reaction of compound 7 with ethylenediamine (13) nate route. While the product was isomeric with 20 ac-
1
13
according to Scheme 4, it was reported that 1-tosyl-1,4,7- cording to its mass spectrum, its H and C NMR spectra
triazacyclononane (9) was obtained in 78% isolated yield. were different from those of 20. The product is consistent
However, after being alerted by other laboratories, we re- with a piperazine structure 24, with four aromatic and six
13
peated the same reaction under identical experimental aliphatic carbon signals in its C NMR spectrum (revised
conditions and did not obtain compound 9 as the product Scheme 7).
of the reaction. While the compound obtained was iso-
1
meric with 9 according to its mass spectrum, its H NMR
K2CO3
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
N
N
NH2
+
H2N
N
NH2
H
TsO
N
OTs
H
Ts
MeCN
reflux
N
19
7
24
1
13
Ts
2
. More significantly, the C NMR spectrum of the ob-
tained product has four aromatic and five aliphatic carbon
signals and is distinctly different from that of 1-tosyl-
Ts
H
1
,4,7-triazacyclononane (9) which has eight carbon sig-
N
N
N
nals. 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 re-
ported in Scheme 3.
N
H
H
2
0
Revised Scheme 7: Reaction of 7 with 19
In conclusion, ethylenediamine (13) and 1,4,7-triazahep-
tane (19) did react with 7 but did not give the correspond-
ing tacn 9 or cyclen 20.
NH2
K2CO3
N
+
TsO
N
OTs
H2N
NH2
Ts
MeCN
reflux
N
2
3
7
13
Ts
1-(2¢-Aminoethyl)-4-tosylpiperazine (23)
Compound 7 (5.83 g, 10.0 mmol), K CO (8.00 g, 58.0 mmol), eth-
2
3
ylenediamine (0.60 g, 10.0 mmol) and anhydrous MeCN (50 mL)
H
were added to a round-bottom flask. The mixture was heated to re-
flux under an N atmosphere for 12 h. The mixture was cooled to r.t.
N
2
N
and filtered. The filtrate was concentrated and the residue was puri-
fied by flash chromatography (SiO , CH Cl –MeOH–Et N =
9
N
H
2
2
2
3
Ts
2
:1:0.05 as eluent) to give 23 as a pale yellow oil (2.0 g, 78%).
Revised Scheme 4: Reaction of 7 with 13
1
H NMR (400 MHz, CDCl ): d = 7.63 (d, J = 7.4 Hz, 2 H), 7.32 (d,
3
J = 7.4 Hz, 2 H), 3.01 (br, 4 H), 2.73 (t, J = 6.0 Hz, 2 H), 2.52 (br t,
We also re-examined the coupling of 7 with 1,4,7-triaza-
heptane (19) using potassium carbonate in refluxing ace-
tonitrile (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 alter-
4
H), 2.43-2.40 (m, 5 H).
1
3
C NMR (100 MHz, CDCl ): d = 143.7, 132.4, 129.6, 127.8, 60.2,
3
5
2.2, 46.0, 38.4, 21.5.
+
LRMS (ESI): m/z = 284 ([M + H], 100).
+
HRMS (ESI): calcd for C H N O S (M + H); 284.1433; found:
1
3
22
3
2
2
84.1423.
SYNTHESIS 2010, No. 22, pp 3941–3942
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DOI: 10.1055/s-0030-1258316; Art ID: r12210ss
©
Georg Thieme Verlag Stuttgart · New York
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ADDENDA AND ERRATA
1
-(1¢,4¢-Diazahexyl)-4-tosylpiperazine (24)
Acknowledgment
1
4
,4,7-Triazaheptane (19, 0.40 g, 4.00 mmol), compound 7 (2.30 g,
We gratefully acknowledge the help of Dr. Kin-Fai Chan for repeat-
ing the experiments.
.00 mmol), K CO (6.00 g, 40.0 mmol) and anhydrous MeCN (20
2
3
mL) were added to a round-bottom flask. The mixture was heated
to reflux under an N atmosphere for 18 h. The mixture was cooled
2
to r.t. and filtered. The filtrate was concentrated and the residue was
purified by chromatography (SiO , CH Cl –MeOH = 2:1 as eluent)
to give a light yellow oil (1.2 g, 83%).
References
2
2
2
(
1) (a) Flassbeck, C.; Wieghardt, K. Z. Anorg. Allg. Chem. 1992,
08, 60. (b) Romakh, V. B.; Therrien, B.; Labat, G.; Stoekli-Evans,
H.; Shul'pin, G. B.; Suss-Fink, G. Inorg. Chim. Acta 2006, 359,
297. (c) Romakh, V. B.; Therrien, B.; Karmazin-Brelot, L; Labat,
6
1
H NMR (400 MHz, CDCl ): d = 7.58 (d, J = 8.0 Hz, 2 H), 7.27 (d,
3
J = 8.0 Hz, 2H), 2.95 (br, 4 H), 2.70 (t, J = 6.0 Hz, 2 H), 2.59 (p,
3
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).
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.
1
3
C NMR (100 MHz, CDCl ): d = 143.7, 132.4, 129.6, 127.8, 57.4,
3
5
2.3, 52.2, 46.1, 46.0, 41.4, 21.5.
(2) Compound 20 could be obtained by mono-tosylation of com-
+
+
LRMS (ESI): m/z = 327 ([M + H], 100), 349 ([M + Na], 29).
mercially 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.
+
HRMS (ESI): calcd for C H N O S [M + H]: 327.1855; found:
1
5 27 4 2
3
27.1856.
Synthesis 2010, No. 22, 3941–3942 © Thieme Stuttgart · New York