N-[3-(tert-Butyl­dimethyl­siloxymeth­yl)-5-nitro­phen­yl]acetamide

Gul S Khan; George R Clark; David Barker

doi:10.1107/S1600536808030717

. 2008 Sep 27;64(Pt 10):o2031. doi: 10.1107/S1600536808030717

N-[3-(tert-Butyldimethylsiloxymethyl)-5-nitrophenyl]acetamide

Gul S Khan ^a, George R Clark ^a,^*, David Barker ^a

PMCID: PMC2959232 PMID: 21201225

Abstract

The title compound, C₁₅H₂₄N₂O₄Si, was prepared by the reaction of (3-acetamido-5-nitrobenzyl)methanol with tert-butyldimethylsilyl chloride and is a key intermediate in the synthesis of novel nonsymmetrical DNA minor groove-binding agents. There are two independent molecules in the structure, which differ primarily in the rotation about the C—O bond next to the Si atom. Two strong N—H⋯O hydrogen bonds align the molecules into a wide ribbon extending approximately parallel to the b axis.

Related literature

For literature related to protecting groups, see: Jarowicki & Kocienski (1998 ▶); Kocienski (2004 ▶); Schelhaas & Waldmann (1996 ▶); Wetter & Oertle (1985 ▶); Wuts & Green (2006 ▶). For literature related to benzamides as minor groove binders, see: Barker et al. (2008 ▶); Gong & Yan (1997 ▶). For related literature, see: Crouch (2004 ▶); Desiraju & Steiner (1999 ▶); Nelson & Crouch (1996 ▶).

Experimental

Crystal data

C₁₅H₂₄N₂O₄Si
M _r = 324.45
Triclinic,
a = 9.5037 (3) Å
b = 10.0713 (3) Å
c = 18.1985 (5) Å
α = 89.885 (1)°
β = 86.009 (1)°
γ = 88.888 (1)°
V = 1737.31 (9) Å³
Z = 4
Mo Kα radiation
μ = 0.15 mm⁻¹
T = 90 (2) K
0.34 × 0.22 × 0.20 mm

Data collection

Siemens SMART CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1997 ▶) T _min = 0.878, T _max = 0.977
15951 measured reflections
6570 independent reflections
4732 reflections with I > 2σ(I)
R _int = 0.042

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.117
S = 1.05
6570 reflections
409 parameters
H-atom parameters constrained
Δρ_max = 0.41 e Å⁻³
Δρ_min = −0.31 e Å⁻³

Data collection: SMART (Bruker, 1995 ▶); cell refinement: SAINT (Bruker, 1995 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 ▶); software used to prepare material for publication: SHELXTL (Sheldrick, 2008 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808030717/fb2117sup1.cif

e-64-o2031-sup1.cif^{(26.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808030717/fb2117Isup2.hkl

e-64-o2031-Isup2.hkl^{(315KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1A—H1A⋯O1B	0.86	2.13	2.982 (2)	172
N1B—H1B⋯O1Aⁱ	0.86	2.14	2.991 (2)	173

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors acknowledge financial support from the Higher Education Commission of Pakistan and The University of Auckland, New Zealand.

supplementary crystallographic information

Comment

Due to the nucleophilic nature of benzylic hydroxyl groups these are usually protected during multi-step organic synthesis (Barker et al., 2008). Large numbers of protecting groups are reported including a variety of silyl ethers. Among the silyl ethers, the tert-butyldimethylsilyl ether is widely used due to it stability towards oxidative, reductive, and mild acidic and basic conditions (Jarowicki & Kocienski, 1998; Kocienski, 2004; Schelhaas & Waldmann, 1996; Wetter & Oertle, 1985; Wuts & Green, 2006). It can however be easily deprotected to give the parent hydroxyl group efficiently using different fluoride reagents without affecting other functionalities (Crouch, 2004; Nelson & Crouch, 1996). The asymmetric unit contains two independent molecules which differ primarily in the rotation about the C7 - O4 bond. (Torsion angles C1-C7-O4-Si equal to -152.75, -110.21° for molecules A and B respectively). Two strong N-H···O hydrogen bonds (Desiraju & Steiner, 1999; Tab. 1) align the molecules into wide ribbons extending approximately parallel to the b axis. There are four very close intramolecular contacts (C4A-O1A 2.886 (3), C4B-O1B 2.894 (3), C6A-O4A 2.740 (3) and C6B-O4B 2.785 Å).

Experimental

To a solution of (3-acetamido-5-nitrobenzyl)methanol (alternatively 3-acetamido-5-nitrobenzyl alcohol) (150 mg, 0.714 mmol) in dry dimethylformamide (1 ml) under an atmosphere of nitrogen, was added tert-butyldimethylsilyl chloride (129 mg. 0.856 mmol) and imidazole (146 mg, 2.14 mmol) and the mixture stirred at room temperature, under an atmosphere of nitrogen for 2 h. Water (10 ml) was added, and the aqueous solution extracted with dichloromethane (2 × 10 ml). The combined organic extracts were washed with water (20 ml) and brine (20 ml), dried (MgSO₄), filtered and the solvent removed in vacuo to afford the crude product, which was purified by flash chromatography (19:1 dichloromethane-methanol) to afford the title compound (214 mg, 93%) as a pale yellow solid, which was recrystallized from ethyl acetate and n-hexane to give a white crystal suitable for single-crystal analysis. (mp 416–417 K). ν_max (NaCl)/cm^-1 3315, 2929, 1666, 1532. δH (400 MHz, CDCl₃) 0.13 (6H, s, OSi(CH₃)₂), 0.96 (9H, s, OSiC(CH₃)₂), 2.24 (3H, s, NHCOCH₃), 4.79 (2H, s, ArCH₂O), 7.56 (1H, s, NH), 7.91 (1H, s, Ar—H), 7.93 (1H, s, Ar—H) and 8.24 (1H, s, Ar—H). δC (100 MHz, CDCl₃) -5.4 (CH₃, OSi(CH₃)₂), 18.4 (quat. OSiC(CH₃)₃), 24.6 (CH₃, NHCOCH₃), 25.9 (CH₃, OSiC(CH₃)₃), 63.8 (CH₂, ArCH₂O), 112.9 (CH, Ar—C), 116.2 (CH, Ar—C), 122.4 (CH, Ar—C), 138.8 (quat. Ar—C), 144.6 (quat. Ar—C), 148.6 (quat. Ar—C) and 168.6 (C=O). m/z (CI⁺) 325 (MH⁺, 43%), 295 (M⁺—CH₂O, 100) 267 (M⁺-NHCOCH₃, 35), 221 (M⁺—C₂H₄N₂O₃, 32). Found MH⁺ 325.15862, C₁₅H₂₅N₂O₄Si requires 325.15836.