Prabhakaran et al.
[Amino-(3-benzylureido)-methylene]-carbamic Acid
Ethyl Ester 1b. To a 1:1 mixture of TFA and DCM (10 mL)
was added 1a (300 mg, 1.0 mmol) at room temperature. After
being stirred for 30 min, the reaction mixture was stripped
off the volatiles under reduced pressure, and the waxy residue
was dissolved in DCM (5 mL). Triethylamine (0.43 mL, 3.1
mmol, 3 equiv) was added to the above reaction mixture,
followed by the addition of ethylchloroformate (0.1 mL, 1.0
mmol, 1 equiv). After being stirred overnight, the reaction
mixture was diluted with DCM (10 mL) and washed succes-
sively with saturated bicarbonate solution and water, and the
organic layer was separated and dried over anhydrous Na2-
SO4. Evaporation of DCM under reduced pressure, followed
by purification of the crude product by column chromatography
(50% petroleum ether/ ethyl acetate, Rf 0.5), gave 1b as
colorless solid (61%) that could be crystallized by diffusion of
pet. ether into a solution of the compound in ethyl acetate.
mp 139-140 °C; IR (CHCl3) ν (cm-1): 3384, 3288, 3018, 2401,
2361, 1672, 1626, 1547, 1370, 1288, 1231, 1140; 1H NMR (500
MHz, CDCl3): δ 10.67-8.80 (br, 3H), 7.34-7.25 (m, 5H), 6.41
(bs, 1H), 4.39 (d, J ) 5.5 Hz, 2H), 3.99 (bs, 2H), 1.18 (bs, 3H);
13C (125 MHz, CDCl3): 161.7, 160.4, 157.1, 138.1, 128.7, 127.4,
Summary
Fixing multiple cooperative binding sites in an ideal
spatial arrangement on a structurally rigid backbone,
constrained by intramolecular hydrogen bonding, is a
novel way for facilitating the hydrogen bond-directed
synthesis of molecular dimers. In this article, we have
demonstrated the ability of the self-assembling constructs
1 and 2, both of them based on the amidinourea motif,
to form molecular dimers, whose structural preorgani-
zation has been solely effected by intramolecular hydro-
gen bonding. It is interesting to note that the molecular
dimers 1.1a-d and 2.2a,b undergo further self-assembly,
affording supramolecular hydrogen-bonded networks.28
The ease with which the amidinourea motif can be
manipulated to yield a diverse set of molecular dimers
and their high propensity for crystallization14 are note-
worthy. With these observations realized, experiments
are underway to extend this strategy for the preorgani-
zation of much larger linear hydrogen-bonding arrays.29
Such studies should allow us to further delineate the
contributions of cooperative forces on the molecular
assembly process such that the construction of organic
assemblies akin to those of nanoscale biological com-
plexes may be realized.
61.3, 43.7, 14.3; ESI mass: 265.20 (M+ + 1), 529.39 (2M+
+
1); Anal. Calcd for C12H16N4O3: C, 54.54; H, 6.10; N, 21.20.
Found: C, 54.38; H, 6.22; N, 21.28.
N-[Amino-3-benzylureido)-methylene]-4-methylben-
zenesulfonamide 2a. 2a was synthesized from 1a (300 mg,
1.0 mmol, 1 equiv), following the same procedure for synthesis
of compound 1b, and using p-toluenesulfonyl chloride (196 mg,
1.0 mmol, 1 equiv). Purification was effected by column
chromatography (60% petroleum ether/ethyl acetate, Rf 0.7)
to yield 2a as a white solid (60%) that could be crystallized
from chilled ethyl acetate. mp: 180-181 °C; IR (Nujol) ν
(cm-1): 3377, 3271, 3229, 2924, 2854, 1711, 1633, 1582, 1549,
Experimental Section
General Procedure: [Amino-(3-benzylureido)-meth-
ylene]-carbamic Acid tert-Butyl Ester 1a. A mixture of
N,N′-di-boc-guanidine (1.3 g, 5 mmol, 1 equiv) and benzyl-
amine (1.6 mL, 15 mmol, 3 equiv) in dry THF (10 mL) was
refluxed with stirring for 12 h. The solvent was evaporated
under reduced pressure, and the residue was subjected to
purification by column chromatography (50% pet. ether/ethyl
acetate, Rf 0.7) to yield a colorless sticky compound that was
crystallized from chilled chloroform to yield 1a (65%). mp 110
°C; IR (CHCl3) ν (cm-1): 3396, 3269, 3013, 2980, 2934, 1647,
1547, 1508, 1454, 1302, 1244, 1148; 1H NMR (500 MHz,
CDCl3): δ 8.65 (br, 3H), 7.33-7.26 (m, 5H), 6.25 (bs, 1H), 4.36
(d, J ) 5.5 Hz, 2H), 1.47 (s, 9H); 13C NMR (125 MHz, CDCl3):
158.3, 138.6, 128.5, 127.2, 82.0, 43.7, 28.0; ESI mass: 293.04
(M+ + 1), 586.02 (2M+ + 2); Anal. Calcd for C14H20N4O3: C,
57.52; H, 6.90; N, 19.16. Found: C, 57.28; H, 7.10; N, 19.32.
1
1456, 1261, 1224, 1155, 1142; H NMR (500 MHz, CDCl3): δ
9.62 (s, 1H), 9.53 (s, 1H), 7.81 (s, 1H), 7.74 (bs, 1H), 7.61 (d, J
) 7.9 Hz, 2H), 7.26-7.23 (m, 5H), 7.17 (d, J ) 7.9 Hz, 2H),
4.32 (d, J ) 5.7 Hz, 2H), 2.42 (s, 3H); 13C (125 MHz, CDCl3):
δ 156.8, 154.7, 142.8, 138.8, 137.6, 129.2, 128.3, 127.4, 127.1,
125.8, 43.5, 21.3; ESI mass: 347.09 (M+ + 1), 693.17 (2M+
+
1); Anal. Calcd for C16H18N4O3S: C, 55.49; H, 5.24; N, 16.18;
S, 9.25. Found: C, 55.43; H, 5.33; N, 16.04; S, 8.94.
Acknowledgment. P.P. is thankful to CSIR, New
Delhi, for a senior research fellowship. We gratefully
acknowledge the constant encouragement of Dr. S.
Sivaram, Director, NCL, and Dr. K. N. Ganesh, Head
of the Division, NCL.
(27) (a) Cheng, R. P.; Gellman, S. H.; DeGrado, W. F. Chem. Rev.
2001, 101, 3219-3232. (b) Venkatraman, J.; Shankaramma, S. C.;
Balaram, P. Chem. Rev. 2001, 101, 3131-3152. (c) Nowick, J. S.;
Brower, J. O. J. Am. Chem. Soc. 2003, 125, 876-877.
(28) Crystallographic data for 1a-d and 2a,b have been deposited
with the Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC 281678 (1a), CCDC 281679 (1b), CCDC 281680
(1c), CCDC 281681 (1d), CCDC 281682 (2a), and CCDC 281683 (2b).
Copies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK.
(29) Self-complementary self-assembling modules with larger (more
than six) linear hydrogen-bonding arrays have been reported. See: (a)
Mayer, M. F.; Nakashima, S.; Zimmerman, S. C. Org. Lett. 2005, 7,
3005-3008. (b) Reference 6i.
Supporting Information Available: Experimental pro-
1
cedures, H, 13C, and DEPT 135 NMR spectra and ESI mass
spectra of 1a-e and 2a,b (PDF), and crystallographic data of
1a-d and 2a,b (CIF). This material is available free of charge
JO051768A
10072 J. Org. Chem., Vol. 70, No. 24, 2005