N-Carboxy-L-aspartic anhydride benzyl ester

The structure of the title compound, benzyl (1,2,3,4-tetra­hydro-2,5-dioxo-1,3-oxazol-4-yl)­acetate, C₁₂H₁₁NO₅, has been determined in an attempt to explain the polymerization observed in the solid state. The mol­ecules are linked by intermolecular hydrogen bonds between the imino group of the five-membered ring and an adjacent carbonyl O atom, along the c axis. Intramolecular hydrogen bonds are also formed, between the imino group and the carbonyl O atom of the ester group. The five-membered rings are arranged in a layer, sandwiched by layers incorporating the benzyl groups. This structure is thought to be preferable for the polymerization of the compound in the solid state, because the five-membered rings can react with each other in the layer.

S1. Comment

N-Carboxy anhydrides (NCAs) of amino acids are crystalline compounds and are usually polymerized in solution to prepare polypeptides (Bamford et al., 1956). Purified amino acid NCA crystals are sensitive to moisture and are polymerized or decomposed by water. When butylamine is added to amino acid NCA crystals immersed in a liquid such as hexane, decane, etc., which cannot dissolve the crystals, polymerization takes place in the solid state. Bamford et al. Is this the correct replacement for `The authors'? studied this solid-state polymerization and found that polymerizability is extremely dependent on the kind of amino acid NCA used.

The crystal structures of amino acid NCAs were not studied for a long time after the very early report by Leuchs (1906). One of the present authors has reported the crystal structures of glycine NCA (Kanazawa et al., 1976a) and L-alanine NCA (Kanazawa et al., 1976b) and discussed their polymerizability with reference to the crystal structure (Kanazawa & Kawai, 1980). In addition, the crystal structures of Ag-benzyl-L-glutamate NCA (Kanazawa et al., 1978a), L-leucine NCA (Kanazawa et al., 1978b), L-valine NCA (Kanazawa et al., 1984), DL-Valine NCA (Takenaka et al., 1994), DL-phenylalanine NCA (Kanazawa et al., 1997) and L-phenylalanine NCA (Kanazawa, 2000) have been determined.

The polymerization of L-leucine NCA, which was the most reactive in the solid state among the NCAs studied, has been studied in detail (Kanazawa et al., 1982; Kanazawa, 1992a,b). The reactivity of amino acid NCAs in the solid state is largely dependent on the purity of the crystals. The measurement of the molecular weight of the resulting polypeptides is very important in order to study the solid-state polymerization of amino acid NCAs in more detail. However, the usual polypeptides, such as poly(L-alanine), poly(L-valine) and poly(L-leucine), do not dissolve in the usual organic compounds, but do dissolve in strong acids, such as dichloroacetic acid and trifuluoroacetic acid. On the other hand, polypeptides prepared by the polymerization of NCAs of benzyl esters of amino acids, such as glutamic or aspartic acids, can be dissolved in common organic solvents, such as dioxane and N,N-dimethylformamide.

The polymerization of the title compound, (I), is much more reactive in the solid state than in solution; the polymer conversion in the solid-state polymerization of (I) initiated by butylamine was 18% in 2 h at 303 K, while the conversion of the polymerization in solution in acetonitrile was about 5% under similar conditions to the solid-state reaction. As the purified compound, (I) (BLA NCA) is very sensitive to moisture and crystallizes as very thin plates, so many crystallization and data-collection attempts were carried out to determine its crystal structure. Here, we present the crystal and molecular structure of (I). \sch

The molecular structure of (I) and the atom-numbering scheme are given in Fig. 1. In the structure of (I), intermolecular N1—H1···O1(3/2 − x, 1 − y, z − 1/2) hydrogen bonds are formed, with bond lengths and angles of N1···O1 2.922 (4) Å, H1···O1 2.11 (4) Å and N1—H1···O1 155 (3)°. In addition, intramolecular N1—H1···O4 hydrogen bonds are formed, with bond lengths and angles of N1···O4 2.852 (3) Å, H1···O4 2.44 (2) Å and N1—H1···O4 109 (2)°.

From Fig. 2, it can be seen that the five-membered NCA rings are packed in a layer and the benzyl ester groups are packed in another layer; these two layers are aligned alternately. The resulting sandwich structure is one of the important requirements for high reactivity in the solid state (Kanazawa, 1992a, 1998). In the crystal of DL-phenylalanine NCA, the sandwich structure was composed of D and L molecules (Kanazawa et al., 1997), and its crystal was also reactive in the solid state.

S2. Experimental

The synthesis of β-benzyl-L-aspartate (BLA) was carried out by the reaction of L-aspartic acid with benzyl alcohol in the manner described previously by Kanazawa (1992a). The title compound was obtained by the reaction of BLA with trichloromethyl chloroformate or triphosgen in tetrahydrofuran, similar to other NCAs (Kanazawa, 1992a). The reaction product, (I), was recrystallized in a mixture of ethyl acetate and hexane (Ratio?), avoiding contamination by moisture.

S3. Refinement

As the absolute structure, which was known from the chirality of the starting materials, could not be determined reliably from the Flack parameter (Flack, 1983), the Friedel pairs were merged. Systematically absent reflections indicated the space group to be P2₁2₁2₁. H atoms were refined isotropically.

Computing details

Data collection: PROCESS (Rigaku, 1996); cell refinement: PROCESS; data reduction: TEXSAN, Version 1.11 (Molecular Structure Corporation & Rigaku Corporation, 2000); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: TEXSAN, Version 1.10 (Molecular Structure Corporation & Rigaku Corporation, 1999); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: TEXSAN, Version 1.11.

Figures

	Fig. 1. The molecular structure of (I), showing 50% probability displacement ellipsoids and the numbering of the atoms. H atoms are drawn as small circles of arbitrary radii.
	Fig. 2. A stereo packing diagram for (I). Note the hydrogen bonds are indicated by thin solid lines.

Benzyl (1,2,3,4-tetrahydro-2,5-dioxo-1,3-oxazol-4-yl)acetate

Crystal data

C12H11NO5	Dx = 1.432 Mg m^−3 Dm = not measured Mg m^−3 Dm measured by ?
Mr = 249.22	Melting point: not measured K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 120 reflections
a = 7.995 (3) Å	θ = 5.0–32.7°
b = 26.611 (5) Å	µ = 0.11 mm^−1
c = 5.4348 (7) Å	T = 288 K
V = 1156.3 (5) Å^3	Plate, colourless
Z = 4	0.20 × 0.15 × 0.10 mm
F(000) = 520.0

Data collection

Rigaku RAXIS-IV imaging plate area-detector diffractometer	Rint = 0.053
Detector resolution: 10.00 pixels mm^-1	θmax = 31.4°
ω scans	h = 0→11
2319 measured reflections	k = 0→38
2115 independent reflections	l = 0→7
1128 reflections with F^2 > 2σ(F^2)

Refinement

Refinement on F^2	w = 1/[σ^2(Fo) + 0.00065|Fo|^2]
R[F^2 > 2σ(F^2)] = 0.054	(Δ/σ)max < 0.001
wR(F^2) = 0.076	Δρmax = 0.22 e Å^−3
S = 1.08	Δρmin = −0.21 e Å^−3
2113 reflections	Extinction correction: Zachariasen (1967) type 2 Gaussian isotropic
209 parameters	Extinction coefficient: 0.052 (5)
All H-atom parameters refined

Special details

Refinement. Refinement using reflections with F² > 0.0 σ(F²). The Weighted R-factor (wR), goodness of fit (S) and R-factor (gt) are based on F, with F set to zero for negative F. The threshold expression of F² > 2.0 σ (F²) is used only for calculating R-factor (gt).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.6900 (3)	0.53721 (8)	0.1669 (5)	0.0762 (8)
O2	0.4759 (3)	0.50459 (7)	0.3913 (4)	0.0637 (6)
O3	0.2625 (3)	0.45642 (9)	0.5189 (4)	0.0781 (8)
O4	0.5482 (4)	0.37125 (8)	−0.2088 (4)	0.0757 (8)
O5	0.5484 (3)	0.30393 (7)	0.0375 (4)	0.0609 (6)
N1	0.5589 (4)	0.46359 (9)	0.0571 (5)	0.0570 (7)
C1	0.5889 (4)	0.5045 (1)	0.1942 (6)	0.0593 (8)
C2	0.3698 (5)	0.4639 (1)	0.3730 (6)	0.0569 (8)
C3	0.4178 (4)	0.4346 (1)	0.1447 (5)	0.0503 (7)
C4	0.4599 (5)	0.3799 (1)	0.2099 (6)	0.0505 (7)
C5	0.5216 (4)	0.3525 (1)	−0.0141 (6)	0.0516 (7)
C6	0.6326 (5)	0.2749 (1)	−0.1586 (8)	0.0655 (10)
C7	0.5702 (4)	0.2215 (1)	−0.1467 (6)	0.0536 (7)
C8	0.6115 (5)	0.1902 (1)	0.0457 (7)	0.0632 (9)
C9	0.5525 (6)	0.1407 (1)	0.0483 (8)	0.076 (1)
C10	0.4573 (5)	0.1230 (1)	−0.1432 (9)	0.078 (1)
C11	0.4193 (6)	0.1536 (1)	−0.3329 (8)	0.076 (1)
C12	0.4741 (5)	0.2031 (1)	−0.3368 (6)	0.0631 (9)
H1	0.612 (4)	0.457 (1)	−0.079 (6)	0.058 (8)*
H2	0.324 (4)	0.4363 (10)	0.045 (5)	0.050 (8)*
H3	0.535 (4)	0.380 (1)	0.350 (7)	0.059 (8)*
H4	0.363 (4)	0.365 (1)	0.272 (7)	0.066 (9)*
H5	0.758 (6)	0.278 (1)	−0.124 (9)	0.106 (9)*
H6	0.590 (4)	0.292 (1)	−0.327 (6)	0.059 (8)*
H7	0.672 (4)	0.2032 (10)	0.169 (6)	0.052 (8)*
H8	0.582 (5)	0.122 (1)	0.196 (9)	0.105 (9)*
H9	0.415 (5)	0.086 (1)	−0.131 (7)	0.097 (9)*
H10	0.359 (5)	0.143 (1)	−0.470 (7)	0.069 (9)*
H11	0.451 (4)	0.222 (1)	−0.460 (6)	0.057 (8)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.073 (2)	0.057 (1)	0.100 (2)	−0.010 (1)	−0.019 (2)	−0.007 (1)
O2	0.068 (1)	0.059 (1)	0.063 (1)	0.006 (1)	−0.006 (1)	−0.021 (1)
O3	0.081 (2)	0.084 (1)	0.070 (1)	0.015 (1)	0.023 (1)	−0.006 (1)
O4	0.120 (2)	0.059 (1)	0.0485 (10)	0.006 (1)	0.010 (2)	−0.0014 (10)
O5	0.078 (2)	0.0472 (9)	0.058 (1)	0.003 (1)	0.011 (1)	−0.0055 (9)
N1	0.061 (2)	0.050 (1)	0.059 (1)	−0.006 (1)	0.008 (2)	−0.007 (1)
C1	0.059 (2)	0.051 (1)	0.068 (2)	0.010 (1)	−0.013 (1)	−0.007 (1)
C2	0.063 (2)	0.053 (1)	0.056 (1)	0.015 (1)	−0.006 (1)	−0.006 (1)
C3	0.052 (1)	0.051 (1)	0.048 (1)	0.000 (1)	−0.007 (1)	−0.002 (1)
C4	0.060 (2)	0.048 (1)	0.044 (1)	0.002 (1)	0.001 (1)	−0.003 (1)
C5	0.057 (2)	0.047 (1)	0.050 (1)	−0.002 (1)	0.001 (1)	−0.007 (1)
C6	0.073 (2)	0.051 (1)	0.072 (2)	−0.004 (2)	0.028 (2)	−0.008 (1)
C7	0.055 (2)	0.048 (1)	0.057 (1)	0.007 (1)	0.016 (1)	−0.008 (1)
C8	0.059 (2)	0.071 (2)	0.060 (2)	0.012 (2)	0.001 (2)	−0.002 (2)
C9	0.087 (3)	0.065 (2)	0.076 (2)	0.016 (2)	0.023 (2)	0.020 (2)
C10	0.083 (3)	0.056 (2)	0.096 (2)	−0.009 (2)	0.029 (2)	−0.002 (2)
C11	0.077 (3)	0.073 (2)	0.076 (2)	−0.017 (2)	0.014 (2)	−0.018 (2)
C12	0.071 (2)	0.062 (2)	0.056 (2)	0.003 (2)	0.000 (2)	0.001 (1)

Geometric parameters (Å, º)

O1—C1	1.197 (4)	C4—H4	0.94 (4)
O2—C1	1.402 (4)	C6—C7	1.507 (5)
O2—C2	1.379 (4)	C6—H5	1.02 (5)
O3—C2	1.185 (4)	C6—H6	1.08 (3)
O4—C5	1.189 (4)	C7—C8	1.378 (5)
O5—C5	1.339 (4)	C7—C12	1.378 (5)
O5—C6	1.478 (4)	C8—C9	1.399 (6)
N1—C1	1.341 (4)	C8—H7	0.89 (3)
N1—C3	1.447 (4)	C9—C10	1.373 (7)
N1—H1	0.87 (3)	C9—H8	0.98 (5)
C2—C3	1.515 (4)	C10—C11	1.349 (7)
C3—C4	1.535 (4)	C10—H9	1.04 (4)
C3—H2	0.93 (3)	C11—C12	1.387 (5)
C4—C5	1.504 (4)	C11—H10	0.93 (4)
C4—H3	0.97 (4)	C12—H11	0.86 (3)
C1—O2—C2	109.9 (2)	O5—C5—C4	110.6 (3)
C5—O5—C6	115.2 (3)	O5—C6—H5	105 (2)
C1—N1—C3	112.9 (3)	O5—C6—H6	104 (1)
C1—N1—H1	123 (2)	C7—C6—H5	112 (2)
C3—N1—H1	123 (2)	C7—C6—H6	109 (1)
O1—C1—O2	121.9 (3)	H5—C6—H6	115 (3)
O1—C1—N1	130.0 (4)	C6—C7—C8	121.6 (4)
O2—C1—N1	108.1 (3)	C6—C7—C12	119.2 (3)
O2—C2—O3	121.9 (3)	C8—C7—C12	119.2 (3)
O2—C2—C3	107.9 (3)	C7—C8—C9	119.8 (4)
O3—C2—C3	130.2 (3)	C7—C8—H7	117 (1)
N1—C3—C2	101.1 (3)	C9—C8—H7	122 (1)
N1—C3—C4	114.2 (3)	C8—C9—C10	120.2 (4)
N1—C3—H2	114 (1)	C8—C9—H8	114 (2)
C2—C3—C4	110.7 (3)	C10—C9—H8	125 (2)
C2—C3—H2	104 (1)	C9—C10—C11	119.8 (4)
C4—C3—H2	110 (1)	C9—C10—H9	117 (2)
C3—C4—C5	110.2 (3)	C11—C10—H9	122 (2)
C3—C4—H3	108 (1)	C10—C11—C12	120.9 (4)
C3—C4—H4	108 (1)	C10—C11—H10	123 (2)
C5—C4—H3	115 (2)	C12—C11—H10	115 (2)
C5—C4—H4	110 (2)	C7—C12—C11	120.2 (4)
H3—C4—H4	103 (2)	C7—C12—H11	119 (2)
O4—C5—O5	124.3 (3)	C11—C12—H11	120 (2)
O4—C5—C4	125.1 (3)
O1—C1—O2—C2	177.6 (3)	C1—O2—C2—C3	0.1 (3)
O1—C1—N1—C3	−176.3 (3)	C1—N1—C3—C2	−2.9 (3)
O2—C1—N1—C3	3.1 (4)	C1—N1—C3—C4	−121.8 (3)
O2—C2—C3—N1	1.6 (3)	C2—C3—C4—C5	−175.1 (3)
O2—C2—C3—C4	122.9 (3)	C4—C5—O5—C6	−171.4 (3)
O3—C2—O2—C1	−179.4 (3)	C5—O5—C6—C7	−148.5 (3)
O3—C2—C3—N1	−179.0 (3)	C6—C7—C8—C9	−179.3 (3)
O3—C2—C3—C4	−57.6 (5)	C6—C7—C12—C11	178.1 (3)
O4—C5—O5—C6	6.4 (6)	C7—C8—C9—C10	1.8 (6)
O4—C5—C4—C3	6.2 (6)	C7—C12—C11—C10	0.7 (6)
O5—C5—C4—C3	−176.0 (3)	C8—C7—C12—C11	0.3 (5)
O5—C6—C7—C8	−69.4 (4)	C8—C9—C10—C11	−0.8 (7)
O5—C6—C7—C12	112.8 (4)	C9—C8—C7—C12	−1.5 (5)
N1—C1—O2—C2	−1.9 (3)	C9—C10—C11—C12	−0.5 (7)
N1—C3—C4—C5	−61.8 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O4	0.87 (3)	2.44 (2)	2.852 (3)	109 (2)
N1—H1···O1^i	0.86 (3)	2.11 (4)	2.920 (3)	155 (3)

Symmetry code: (i) −x+3/2, −y+1, z−1/2.