Crystal structure of γ-ethyl-l-glutamate N-carboxy anhydride

In the crystal of the title compound, molecules are linked by N—H⋯O hydrogen bonds between the imino group and the carbonyl O atom in the ethyl ester group, forming a tape structure along the c-axis direction. The oxazolidine rings of adjacent tapes are arranged into a layer parallel to the ac plane, which is a favourable arrangement for the polymerization of the title compound in the solid state.


Chemical context
N-Carboxy anhydrides (NCAs) of amino acids are extensively used as monomers in the preparation of high molecular weight polypeptides (Kricheldorf, 2006). Amino acid NCAs are easily soluble but the resulting polypeptides are not soluble in general organic solvents. Only a few amino acid ester NCAs such as -benzyl-l-glutamate NCA and -benzyl-l-aspartate NCA can be polymerized in solutions, because the resulting polypeptides are soluble in them. Thus, the polymerization of these amino acid ester NCAs has been investigated by many researchers. We found that every amino acid NCA crystal is polymerized in the solid state in hexane by the initiation of amines, and have studied the solid-state polymerization of amino acid NCAs with reference to the crystal structures (Kanazawa, 1992;Kanazawa & Magoshi, 2003;Kanazawa et al., 2006).
The title compound, -ethyl-l-glutamate NCA (ELG NCA) is polymerized both in dioxane solution and in the solid state in hexane, using butylamine as initiator. However, ELG NCA is very reactive in the solid state in hexane using the same initiator. Therefore, it is important to determine the crystal structure in order to consider the difference in the reactivity of ELG NCA in solution and in the solid state.

Supramolecular features
In the crystal, ELG NCA molecules are linked by N1-H1Á Á ÁO4 hydrogen bonds along the c axis (Table 1 and Fig. 2). The five-membered oxazolidine rings are packed in a layer and the -CH 2 CH 2 COOCH 2 CH 3 groups are packed in another layer; these two different layers are stacked alternately. This sandwich structure is one of the important requirements for high reactivity in the solid state, because the five-membered rings can react with each other in the layer.

Database survey
A search of the Cambridge Structural Database (Version 5.35, May 2014; Groom & Allen, 2014) revealed the presence of 20 hits for 4-methyloxazolidine-2,5-dione derivatives. A number of these compounds involve amino acid sides chains (amino acid NCAs). These include two polymorphs of a compound involving l-aspartate, namely N-carboxy--benzyl-l-aspartate anhydride (SOHRIQ: Kanazawa, 1998; no coordinates were deposited) and (SOHRIQ01: Kanazawa & Magoshi, 2003). Two other compounds involving l-glutamate have also been reported. They are very similar to the title compound and are polymorphs of N-carboxy--benzyl-l-glutamate anhydride (ANCBGL; Kanazawa et al., 1978) and (WIPDUV; Kanazawa et al., 2006). For the latter, unfortunately no coordinates have been deposited. The structural overlay of the title compound and ANCBGL indicates that the N-carboxy-l-glutamate anhydride moieties have very similar conformations (Fig. 3).

Figure 2
A crystal packing diagram of the title compound, viewed approximately along the a axis, showing the hydrogen bonds as dashed lines (see Table 1 for details).

Figure 3
A view of the structural overlay of the title compound (blue) and ANCBGL (red; Kanazawa et al., 1978).

Figure 1
The molecular structure of the title compound showing atom labels and 50% probability displacement ellipsoids for non-H atoms.

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 2. The N-bound H atom was found in a difference Fourier map and its position was refined with U iso (H) = 1.5U eq (N). C-bound H atoms were positioned geometrically (C-H = 0.96-0.98 Å ) and treated as riding with U iso (H) = 1.2U eq (C).