Crystal structure of O-benzyl-l-tyrosine N-carboxy anhydride

In the title compound, known also as (S)-4-[4-(benzyloxy)benzyl]oxazolidine-2,5-dione, the benzyloxy and benzyl rings are almost coplanar, making a dihedral angle of 0.078 (10)°, and are inclined to the oxazolidine ring by 59.16 (11) and 58.42 (11)°, respectively.


Chemical context
N-Carboxy anhydrides (NCAs) of amino acids are extensively used as monomers for 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 (BLG NCA) and -benzyl-l-aspartate NCA (BLA NCA) are polymerized in solutions, because the resulting polypeptides are soluble in them. On the other hand, we found that every amino acid NCA crystal is polymerized in the solid state in hexane by the initiation of amines. We studied the polymerization of BLA NCA (Kanazawa & Sato, 1996) and -benzyl-dl-aspartate NCA (BDLA NCA) initiated by a primary amine in the solution and solid states, and we determined the crystal structure of BLA NCA (Kanazawa & Magoshi, 2003) and BDLA NCA (Kanazawa & Inada, 2017) to consider their high reactivity in the solid state. In addition, we prepared single crystals of the title compound, O-benzyl-l-tyrosine (OBLT NCA) in hexane-ethyl acetate mixture. The polymerization of OBLT NCA is initiated by butyl amine initiator in dioxane or acetonitrile solutions. However, the polymerization rate was extremely slow, because the resultant polymer has a poor solubility in these solvents. On the other hand, the polymerization of OBLT NCA initiated by butyl amine was very reactive in the solid state in hexane. High molecular weight poly(OBLT) was obtained only in the solid-state polymerization. High molecular weight poly(OBLT) is valuable, because poly(l-tyrosine) is obtained by the hydration of benzyl groups of the polymer. Therefore, it is important to determine the crystal structure to consider the difference in the reactivity in solution and in the solid state.

Supramolecular features
In the crystal, molecules are linked via N1-H1Á Á ÁO3 i and C-HÁ Á ÁO3 ii hydrogen bonds, forming ribbons propagating along the b-axis direction (Table 1 and Fig. 2). The ribbons are linked by C-HÁ Á Á interactions, forming a three-dimensional supramolecular structure (Table 1 and Fig. 3). The fivemembered oxazolidine rings are packed in a layer and the -CH 2 C 6 H 4 OCH 2 C 6 H 5 side chains are packed in another layer; the two different layers stack 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.
Cg is the centroid of the C12-C17 benzyloxy ring.

Figure 2
A partial view along the a axis of the crystal packing of the title compound. The hydrogen bonds are shown as dashed lines (see Table 1). For clarity, only H atoms H1 and H3 (grey balls) have been included.

Figure 1
The molecular structure of the title compound, showing the atom labelling and 50% probability displacement ellipsoids.
hydrogen bonds are formed between the imino group and the carbonyl O atom in position 2 of the oxazolidine ring in the title compound and in ZATWEW. On the other hand, they are formed between the imino group and the carbonyl O atom at position 5 of the oxazolidine ring in KIXSUF and RESSUD.

Synthesis and crystallization
Reagent-grade O-benzyl-l-tyrosine (OBLT) (Product Code B3210; Tokyo Kasei Co. Ltd.) was used as received. The title compound was synthesized by the reaction of OBLT with triphosgene in tetrahydrofuran, as reported previously for the synthesis of BLA NCA (Kanazawa & Magoshi, 2003). The reaction product was recrystallized slowly in a mixture of ethyl acetate and hexane (1:50 v/v), avoiding moisture contamination, and gave colourless needle-shaped crystals.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The N-bound H atom was located in a difference-Fourier map and refined with a distance restraint of N-H = 0.88 (4) Å , with U iso (H) = 1.14U eq (N). Cbound H atoms were positioned geometrically and treated as riding: C-H = 0.95-1.00 Å with U iso (H) = 1.2U eq (C).

Figure 3
A view along the a axis of the crystal packing of the title compound. The hydrogen bonds and C-HÁ Á Á interactions are shown as dashed lines (see Table 1). For clarity, only H atoms H1 and H3 and H6 (grey balls) have been included.

Computing details
Data collection: RAPID-AUTO (Rigaku, 2009); cell refinement: RAPID-AUTO (Rigaku, 2009); data reduction: RAPID-AUTO (Rigaku, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: CrystalStructure (Rigaku, 2009) and Mercury (Macrae et al., 2008); software used to prepare material for publication: CrystalStructure (Rigaku, 2009). Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2sigma(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.