Synthesis and crystal structure of 1,2-bis(phthalimidomethyl)-1,2-dicarba-closo-dodecaborane(12): a precursor to polyamines

Inorganic Chemistry Communications 4 (2001) 447±449

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Synthesis and crystal structure of 1,2-bis(phthalimidomethyl)-1,2-dicarba-closo-dodecaborane(12): a precursor to polyamines Yinghuai Zhu a

a,b,1

, Hongming Zhang b, John A. Maguire

b,*

, Narayan S. Hosmane

a,*

Department of Chemistry and Biochemistry, The Michael Faraday Laboratories, Northern Illinois University, DeKalb, IL 60115, USA b Department of Chemistry, Southern Methodist University, Dallas, TX 75275, USA

Abstract The reaction of 1 equivalent of the dilithium salt of the [closo-1,2-C2 B10 H10 Š2 dianion with two equivalents of N-(bromomethyl)phthalimide, in a mixture of anhydrous benzene and diethyl ether, produced a new bis-C…cage† -substituted o-carborane, 1,2bis(phthalimidomethyl)-1,2-dicarba-closo-dodecaborane(12) (1) in 65% yield. Ó 2001 Elsevier Science B.V. All rights reserved. Keywords: Phthalimidomethyl; bis-Substituted; Dicarbadodecaborane; Polyamine; BNCT

In recent years, an important area of our research has been the study of half-sandwich and full-sandwich metallacarboranes in the C2 B9 - and C2 B4 -cage systems with constrained geometries in which a C…cage† -alkylamino moiety is bonded to the metal that is coordinated to the open C2 B3 -face of the carborane ligand [1]. The most popular precursors to these constrained geometry ligands, such as 1-(phthalimidomethyl or ethyl)-1,2-dicarba-closo-dodecaborane, have been synthesized in high yields and, subsequently, converted into the corresponding aminoalkylcarborane derivatives [2,3]. A parallel interest in making such aminoalkyl derivatives is to synthesize carboranylpolyamines as boron delivery agents for tumor cells [4,5]. A number of reports have shown that a variety of functionalized carborane derivatives can be used in the treatment of cancer by boron neutron capture therapy (BNCT) [6±10]. One of the goals of our research is to prepare compounds in which a selected boron species is bracketed by appropriately spaced amino groups, which could be taken up directly by the native polyamine transporters and, hence, o€er a new system of boron drug delivery to the tumor cells. A key synthon for such species would be a bis-substituted

*

Corresponding author. Tel.: +1-815-753-3556; fax: +1-815-7534802. E-mail address: [email protected] (N.S. Hosmane). 1 On leave from Nankai University, People's Republic of China.

phthalimidomethylcarborane that could be transformed into the desired dialkylaminocarborane derivative. Herein, we report the synthesis, spectroscopic and crystallographic characterization of such a polyamine precursor, 1,2-bis(phthalimidomethyl)-1,2-dicarbacloso-dodecaborane(12) (1). The reaction of the dilithium salt of the [closo-1,22 C2 B10 H10 Š dianion with N-(bromomethyl)phthalimide, in a 1:2 molar ratio, in a 2:1 solvent mixture of anhydrous benzene and diethyl ether, followed by extraction and puri®cation, produced a new bis-C…cage† -substituted o-carborane, 1,2-bis(phthalimidomethyl)-1,2-dicarbacloso-dodecaborane(12) (1), in 65% yield [11]. Although the elemental analyses, IR spectrum, and the 1 H and 11 B NMR spectra [12] were consistent with the formation of the expected di-substituted carborane derivative (1), its exact molecular geometry could not be unambiguously determined from these data. Therefore, the X-ray diffraction analysis on the crystalline sample of the product was undertaken [13], which con®rmed that the coupling reaction was a straight forward process and yielded the hitherto unknown bis-C…cage† -phthalimidomethyl substituted o-carborane, as shown in Scheme 1. The crystal structure of the title compound (Fig. 1) shows it to be a closed polyhedral carborane cage with a distorted icosahedral geometry, typical of the C2 B10 ocarboranes [2,3b,14]. The major in¯uence of the phthalimidomethyl moieties attached to the cage carbons is to  The elongate the C(1)±C(2) bond to 1.700(2) A.

1387-7003/01/$ - see front matter Ó 2001 Elsevier Science B.V. All rights reserved. PII: S 1 3 8 7 - 7 0 0 3 ( 0 1 ) 0 0 2 4 4 - 1

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Y. Zhu et al. / Inorganic Chemistry Communications 4 (2001) 447±449

Li2+ 2 t-BuLi n-hexane

::-

-78oC - 2BuH O Br

2

N

-78oC - 2LiBr

C H

O

N H

C

H O

O H

O H

N C H

O

(1) Scheme 1. Synthesis of compound 1.

 and C(1)±C(31) and C(2)±C(21) distances are 1.529(3) A  1.528(3) A, respectively, which are slightly less than the  Otherwise, the usual C±C r-bond distances of 1.54 A. bond distances and angles in the cage and the exopolyhedral phthalimidomethyl groups are well within their expected values and those reported for similar compounds [2,3,14,15]. It is of interest to note that Hawthorne and co-workers [15] found a Ccage ±Ccage  for methyl/dichlorophenylbond length of 1.706(5) A substituted o-carborane, 1-(10 -closo-20 -CH3 -10 ; 20 C2 B10 H10 -2,3-Cl3 C6 H3 †. The similarity between that distance and the value found in Fig. 1 indicates that the long C(1)±C(2) bond is most likely due to a combination of the strong electron withdrawing nature of the phthalimide moieties and their steric bulk. Since compound 1 is made with the parent orthocarborane precursor, it is anticipated that similar experimental conditions could result in the di-substituted derivatives of both meta- and para-carboranes, allowing their reactivity to be further explored. Such an endeavor is currently in progress in our laboratory.

Supplementary materials Summary of crystallographic data, tables of positional and thermal parameters, bond distances, and bond angles (10 pages) are available from the authors on request.

Acknowledgements This work was supported by grants from the National Science Foundation (CHE-9988045), the Robert A. Welch Foundation (N-1322 to JAM), the donors of the Petroleum Research Fund, administered by the American Chemical Society, and Northern Illinois University.

References Fig. 1. Perspective view of 1 with the thermal ellipsoids drawn at the 40% probability level and showing the atom numbering scheme. Pertinent parameters include C(1)±C(2) 1.700 (2), C(2)±B(12) 1.698 (3), C(2)±B(6) 1.731 (3), C(2)±B(3) 1.719 (3), B(3)±B(8) 1.781 (3), B(7)±B(9) 1.774 (4), B(7)±B(10) 1.778 (4), B(7)±B(11) 1.788 (5), B(8)±B(9) 1.774 (4), C(1)±C(31) 1.529 (3), C(2)±C(21) 1.528 (3), C(21)±N(22) 1.450 (2), N(22)±C(28) 1.406 (2), N(22)±C(23) 1.398 (3), C(28)±O(1) 1.208 (2), C(23)±O(2) 1.211 (2) C(24)±C(25) 1.394 (3), C(25)±(26) 1.389 (4),  C(26)±C(27) 1.385 (4), C(28)±C(30) 1.484 (3), C(29)±C(30) 1.387 (3) A,

C(21)±C(2)±C(1) 119.9 (2), N(22)±C(21)±C(2) 114.2 (2), C(23)±N(22)± C(28) 111.5 (2), C(23)±N(22)±C(21) 124.4 (2), C(28)±N(22)±C(21) 123.9 (2), O(2)±C(23)±N(22) 124.6 (2), O(2)±C(23)±C(29) 129.4 (2), N(22)±C(23)±C(29) 106.0 (2), O(1)±C(28)±N(22) 124.1 (2). The full listing of bond distances and angles can be found in Supplementary materials.

[1] [a] G.T. Johnson, A. Ratanasuwan, N.S. Hosmane, Chemistry of half-sandwich metallacarboranes of early transition metals. Potential precursors for Ziegler-Natta catalysts, in: Paper presented at the Seventh Boron USA Workshop (BUSA-VII), University of Pittsburgh, Pittsburgh, PA, June 7±10, 2000, Abstract, #41; [b] Y. Zhu, K. Vyakaranam, J.A. Maguire, W. Quintana, F. Teixidor, C. Vi~ nas, N.S. Hosmane, Inorg. Chem. Commun. submitted for publication. [2] J.G. Wilson, A.K.M. Anisuzzaman, F. Alam, A.H. Soloway, Inorg. Chem. 31 (1992) 1955±1958. [3] [a] K. Vyakaranam, S. Li, C. Zheng, N.S. Hosmane, Inorg. Chem. Commun. 4 (2001) 180±182; [b] Y. Wu, P.J. Carroll, S.O. Kang, W. Quintana, Inorg. Chem. 36 (1997) 4753±4761.

Y. Zhuet al. / Inorganic Chemistry Communications 4 (2001) 447±449 [4] J. Cai, A.H. Soloway, R.F. Barth, D.M. Adams, J.R. Hariharan, I.M. Wyzlic, K. Radcli€e, J. Med. Chem. 40 (1997) 3887±3896. [5] [a] H. Ghaneolhosseini, W. Tjarks, S. Sj oberg, Tetrahedron 54 (1998) 3877±3884; [b] J.-C. Zhuo, J. Cai, A.H. Soloway, R.F. Barth, D.M. Adams, W. Ji, W. Tjarks, J. Med. Chem. 42 (1999) 1282±1292. [6] R.F. Barth, A.H. Soloway, R.G. Fairchild, Cancer Res. 50 (1990) 1061±1070. [7] A.H. Soloway, D.N. Butler, J. Med. Chem. 9 (1966) 411±412. [8] M.A. Davis, A.H. Soloway, J. Med. Chem. 10 (1967) 730±732. [9] E.A. Mizusawa, M.R. Thompson, M.F. Hawthorne, Inorg. Chem. 24 (1985) 1911±1916. [10] R.L. Sneath Jr., J.E. Wright, A.H. Soloway, S.M. O'Keefe, A.S. Dey, W.D. Smolnycki, J. Med. Chem. 19 (1976) 1290±1294. [11] A 19.4 mmol (2.8 g) sample of 1,2-dicarba- closo-dodecaborane(12) in 2:1 mixture of anhydrous benzene and diethyl ether (50 ml) was allowed to react with 41.3 mmol (16.5 ml of 2.5 M solution in hexane) of n-BuLi at 0°C with constant stirring over period of 1 h to form the corresponding dilithio derivative of o2 carborane, Li‡ 2 ‰C2 B10 H10 Š . The resulting solution was slowly allowed to react further with diethyl ether solution (100 ml) of N(bromomethyl)phthalimide (10.0 g, 41.5 mmol) with constant stirring for 30 min at 0°C and then at room temperature for an additional 30 min. At this point the mixture was re¯uxed for 2 h and after cooling it was hydrolyzed with 50 ml of de-ionized water. The ether layer was separated and the aqueous layer was extracted with an additional quantity of ether. The combined extracts were dried over anhydrous MgSO4 and concentrated in vacuo to yield a crude solid product. This solid was later re-crystallized from its toluene solution to isolate a pure crystalline solid, identi®ed as 1,2bis(phthalimidomethyl)-1,2-dicarba-closo-dodecaborane(12) (1), in 65% yield (5.8 g, 12.54 mmol, soluble in polar and slightly soluble in nonpolar organic solvents; m.p. 228±230°C). Elemental Anal. Calcd for 1: C, 51.94; H, 4.79; N, 6.06. Found: C, 51.82; H, 4.88; N, 5.88.

449

[12] The spectroscopic data for 1: 1 H NMR (CDCl3 , relative to external Me4 Si) d 0.30±3.08 [br, ill-de®ned peak, BH], 5.0 [s (br), 4 H, CH2 ], 7.75±7.98 [m (br), 8 H, aromatic H]; 11 B NMR …CDCl3 , relative to external BF3 :OEt2 † d 3.47 [br, ill-de®ned peak, basal BH], 5.72 [br, ill-de®ned peak, basal BH], 10.47 [br, ill-de®ned peak, apical BH]; IR (cm 1 , KBr pellet) 2995 (w,s) [m (C±H)], 2610 (s,s), 2567 (s,s) [m (B±H)], 1774 (s,s), 1714 (vs,s) [m (C@O) stretch], 1611 (s,s), 1470 (m,s), 1415 (s,s), 1394 (s,s), 1356 (s,s), 1128 (s,s), 1030 (m,s), 965 (m,s), 715 (s,s), 525 (m,s). [13] Crystal data for 1: ‰C20 H22 B10 N2 O4 Š, fw ˆ 462:50, monoclinic,  b ˆ 97:283…7†° P 21 =c;a ˆ 21:664…2†, b ˆ 14:622…2†, c ˆ 7:639…1† A, 3 , Z ˆ 4, Dcalcd ˆ 1:280 Mg=m3 , l ˆ 0:080 mm 1 . V ˆ 2400:3…5† A Of 4564 data collected on a Siemens R3m/V di€ractometer (MoKa, 2h ˆ 3:50±56:0°, at 228(2) K), 4217 re¯ections were independent and 3830 re¯ections were observed and were used for re®nement ‰I > 2:0r…I†Š. Data were corrected for Lorentz, polarization, but not for absorption e€ects (G.M. Sheldrick, Structure Determination Software Programs; Siemens X-ray Analytical Instrument Corp., Madison, WI, 1991). The structure was solved by direct methods and re®ned by full-matrix least-squares techniques using SH E L X L 97 (G.M. Sheldrick, SH E L X L , Version 5.1, Bruker Analytical X-ray Systems, Madison, WI, 1997). All non-H atoms were re®ned anisotropically. Cage-H atoms were located in the di€erence Fourier maps, and methyl and methylene H atoms were calculated. The ®nal re®nement of 1 converged at R ˆ 0:0452, wRz ˆ 0:1128, and GOF ˆ 1:032 for observed re¯ections. [14] [a] J.A. Potenza, W.N. Lipscomb, Inorg. Chem. 3 (1964) 1673± 1679; [b] D. Voet, W.N. Lipscomb, Inorg. Chem. 3 (1964) 1679±1683; [c] W. Jiang, C.B. Knobler, M.F. Hawthorne, Inorg. Chem. 35 (1996) 3056±3058. [15] T.J. Henly, C.B. Knobler, M.F. Hawthorne, Organometallics 11 (1992) 2313±2316.