(S)-Methyl 2-{(S)-2-[bis­(4-meth­oxy­phen­yl)methyl­idene­amino]-3-hy­droxy­propanamido}-3-methyl­butano­ate

Charles M Keyari; Robin Polt; Gary S Nichol

doi:10.1107/S1600536810049032

. 2010 Dec 4;67(Pt 1):o13–o14. doi: 10.1107/S1600536810049032

(S)-Methyl 2-{(S)-2-[bis(4-methoxyphenyl)methylideneamino]-3-hydroxypropanamido}-3-methylbutanoate

Charles M Keyari ^a, Robin Polt ^a, Gary S Nichol ^a,^*

PMCID: PMC3050411 PMID: 21522640

Abstract

The title compound, C₂₄H₃₀N₂O₆, a Schiff base, adopts an extended conformation in which the methoxy groups are essentially coplanar with the aromatic ring to which they are bonded (mean planes fitted through the non-H atoms of each methoxyphenyl group have r.m.s. deviations of 0.078 and 0.044 Å) and the angle between mean planes fitted through the aromatic rings is 87.57 (10)°. An intramolecular N—H⋯N hydrogen bond keeps the imine and amide groups essentially coplanar. A mean plane fitted through these groups has an r.m.s. deviation of 0.0545 Å. Additional O—H⋯O hydrogen bonding parallel with the a axis links the molecules into a hydrogen-bonded chain in the crystal. C—H⋯O and C—H⋯π interactions are found within the crystal packing. The compound has been assigned the S,S configuration on the basis of the chemical synthesis, which used pure homotopic l-amino acids, and we have no reason to believe that the compound has epimerized.

Related literature

For background to our interest in developing new synthetic methods towards the synthesis of glycopeptide analogues and related compounds, see: Dhanasekaran et al. (2005 ▶); Dhanasekaran & Polt (2005 ▶); Egleton et al. (2005 ▶); Lowery et al. (2007 ▶); Polt et al. (2005 ▶); Keyari & Polt (2010 ▶). For a related structure, see: Wijayaratne et al. (1993 ▶).

Experimental

Crystal data

C₂₄H₃₀N₂O₆
M _r = 442.50
Triclinic,
a = 5.847 (5) Å
b = 8.981 (7) Å
c = 11.630 (9) Å
α = 80.456 (11)°
β = 83.922 (11)°
γ = 76.971 (12)°
V = 585.2 (8) Å³
Z = 1
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 150 K
0.60 × 0.20 × 0.10 mm

Data collection

Bruker SMART 1000 CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.948, T _max = 0.991
3801 measured reflections
1965 independent reflections
1484 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.037
wR(F ²) = 0.107
S = 1.09
1965 reflections
301 parameters
5 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: SMART (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXTL, publCIF (Westrip, 2010 ▶) and local programs.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810049032/bh2325sup1.cif

e-67-00o13-sup1.cif^{(22.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810049032/bh2325Isup2.hkl

e-67-00o13-Isup2.hkl^{(96.6KB, hkl)}

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

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

Cg1 is the centroid of the C18–C23 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1O⋯O2ⁱ	0.84 (1)	1.87 (2)	2.705 (5)	170 (6)
N1—H1N⋯N2	0.84 (1)	2.21 (4)	2.641 (5)	112 (4)
C6—H6B⋯O1ⁱⁱ	0.98	2.49	3.353 (6)	146
C17—H17C⋯O3ⁱⁱⁱ	0.98	2.53	3.410 (6)	149
C20—H20⋯O3ⁱ	0.95	2.46	3.222 (6)	137
C16—H16⋯Cg1^iv	0.95	2.52	3.460 (6)	169

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) .

Acknowledgments

This material is based upon work supported in part by the National Science Foundation (NSF) grant CHE-0607917, and by the Office of Naval Research grant 14–05-1–0807. The X-ray diffractometer was purchased with funds from NSF grant CHE-9610374.

supplementary crystallographic information

Comment

We have been interested for some time in developing new synthetic methods towards the synthesis of glycopeptide analogues and related compounds (Dhanasekaran et al., 2005; Dhanasekaran & Polt, 2005; Egleton et al., 2005; Lowery et al., 2007; Polt et al., 2005). The crystal structure of a dipeptide Schiff base, (I), was determined as part of our work, and is presented here. In solution such Schiff bases are normally present in equilibrium with an oxazolidine tautomer and we have previously reported the structure of a related compound which crystallized as the oxazolidine form (Wijayaratne et al., 1993).

The molecular structure of (I) is shown in Figure 1. The compound adopts an extended conformation and the molecular geometry is largely unexceptional. This conformation is given added stability by an intramolecular N—H···N hydrogen bond. O—H···O hydrogen bonding parallel with the a axis, as shown in Figure 2, connects the molecules into a hydrogen bonded chain. Weak C—H···O and C—H···π interactions are found within the crystal packing, although there is no evidence of face-face aromatic stacking.

Experimental

L-Valine methyl ester HCl salt (1.02 g, 6.11 mmol, 2.0 equiv.), benzyl N-[9-(fluorenylmethoxycarbonyl)]-L-serinate (1.0 g, 3.06 mmol, 1.0 equiv.), N-hydroxybenzotriazole (0.94 g, 6.11 mmol, 2.0 equiv.), O-benzotriazole-N,N,N',N-tetramethyluroniumhexafluorophosphate (2.32 g, 6.11 mmol, 2.0 equiv.) and 5.5 ml diisopropylethylamine (30.6 mmol, 10.0 equiv.) were stirred overnight in 15 cm³ of dichloromethane. The reaction mixture was then washed and concentrated and crystallization from ethyl acetate and hexanes provided white crystals. The crystals were then reacted with 20% piperidine in dichloromethane (15 ml) for 1 h. This was then concentrated and 1 N HCl in methanol was added with stirring at room temperature for 15 min. The solvent was stripped off and bis(4-methoxy)-diarylketimine (0.57 g, 2.36 mmol, 1.0 equiv.) was added to the HCl methyl ester salt and dried over P₂O₅ overnight in vacuo. Dry acetonitrile (10 ml) was added and stirring started at room temperature and reacted for at least 16 hrs. The crystalline product (I) was obtained by recrystallization from ethyl acetate and hexanes. Yield 0.23 g (0.52 mmol, 21% over 3 steps); mp = 120–122°C. FABMS: C₂₄H₃₀N₂O₆, m/z [M + H]⁺443.2. For a more detailed description of the overall synthetic procedure see Keyari & Polt (2010).