N-Carboxy-DL-leucine anhydride

The structure of 4-iso­butyl-1,3-oxazolidine-2,5-dione, C₇H₁₁NO₃, has been determined to explain the polymerization of a series of amino acid N-carboxy anhydrides in the solid state. A dimer structure is formed between the L- and D-enantiomers around a crystallographic centre of symmetry via N—H...O hydrogen bonds. The five-membered rings are arranged in a layer, sandwiched between two layers of iso­propyl groups. This structure should be conducive to the polymerization of the compound in the solid state.

Key indicators

• Single-crystal X-ray study
• T = 288 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.048
• wR factor = 0.159
• Data-to-parameter ratio = 12.0

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT029_ALERT_3_A _diffrn_measured_fraction_theta_full Low .....       0.92

Alert level C
REFLT03_ALERT_3_C  Reflection count < 95% complete
           From the CIF: _diffrn_reflns_theta_max           25.00
           From the CIF: _diffrn_reflns_theta_full           0.00
           From the CIF: _reflns_number_total               1347
           TEST2: Reflns within _diffrn_reflns_theta_max
           Count of symmetry unique reflns         1462
           Completeness (_total/calc)             92.13%
PLAT022_ALERT_3_C Ratio Unique / Expected Reflections too Low ..       0.92
PLAT128_ALERT_4_C Non-standard setting of Space group P21/c   ..       P21/a
PLAT242_ALERT_2_C Check Low    U(eq) as Compared to Neighbors ..           C5
PLAT432_ALERT_2_C Short Inter X...Y Contact:O1      .. C2      =       2.99 Ang.

   1 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   5 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   2 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion

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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 generally sensitive to moisture and are polymerized or decomposed by water. When butylamine is added to amino acid NCA crystals suspended in an inert solvent such as hexane or decane, polymerization takes place in the solid state. We have studied this solid-state polymerization and found that the polymerizability is quite different in each amino acid NCA.

The crystal structures of amino acid NCAs were not studied for many years after the very early initial report by Leuchs (1906). We have reported the crystal structures of glycine NCA (Kanazawa et al., 1976a) and L-alanine NCA (Kanazawa et al., 1976b), and found that the polymerizability depended on the crystal structure (Kanazawa & Kawai, 1980). In addition, the crystal structures of γ-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), L-phenylalanine NCA (Kanazawa, 2000) and β-benzyl-L-aspartate NCA (Kanazawa & Magoshi, 2003) have also been determined.

We found that the polymerization of L-leucine NCA was the most reactive in the solid state among the amino acid NCAs examined, and the solution polymerization of L-alanine NCA in acetonitrile seemed to be more reactive than its solid state polymerization (Kanazawa et al., 1982; Kanazawa, 1992). However, we recently found that a partial polymerization initiated by moisture is not avoidable for highly purified amino acid NCA crystals under normal experimental conditions. Thus, a normal solution polymerization is affected by the partially polymerized amino acid NCAs dissolved in the solution, and the reactivity may be reported artificially high. In fact, many amino acid NCAs have been observed to be more reactive in the solid state than in the solution state when the experiments are carried out under cool conditions to avoid moisture.

As the title compound (DL-leucine NCA), (I), is a racemate, it polymerizes slowly in solution. However, we found that the solid state polymerization of compound (I) was much more reactive than its solution polymerization; polymer conversion was 100% in the solid state but only 10% in acetonitrile solution at 313 K under the same conditions (Kanazawa & Hayakawa, 2000). Therefore, it is important 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 shown in Fig. 1. In the crystal structure of (I), L– and D-enantiomers form dimeric pairs around a centre of symmetry. They are linked by N1—H1···O1ⁱ hydrogen bonds [N1···O1ⁱ 2.903 (2) Å, H1···O1ⁱ 2.08 Å, and N1—H1···O1ⁱ 173°; symmetry code: (i) 1 − x, 2 − y, 1 − z].

As seen in Fig. 2, the five-membered NCA rings in (I) are packed in a layer, with the isobutyl groups packed in another layer which alternates with the first. This sandwich structure is one of the important requirements for high reactivity in the solid state (Kanazawa, 1992, 1998), because the five-membered rings can react with each other within the layer. This structure seems to give a higher reactivity in the solid state than with the solution reaction. Although the hydrogen-bonded dimer structure is not formed in the crystal of DL-phenylalanine NCA (Kanazawa et al., 1997), the sandwich structure composed of D and L molecules is found and the crystal is also reactive in the solid state. Therefore, the DL dimer structure in the crystal of (I) is not considered to be an important requirement for high reactivity in the solid state.

S2. Experimental

Compound (I) was obtained by the reaction of DL-leucine with trichloromethyl chroloformate or triphosgen in tetrahydrofuran, as reported previously for other NCAs (Kanazawa, 1992). The reaction product was recrystallized in a mixture of ethyl acetate and hexane (Ratio?), avoiding contamination by moisture.

S3. Refinement

As compound (I) crystallizes as thin plates and is very unstable, many crystallization and data-collection attempts were carried out. As the crystal degraded rapidly, only a limited number of ocillation photographs were taken, which cover 120° rotation of the crystal. Thus, the completeness of the reflections up to 2θ_max = 50° is relatively low (92%). H atoms were located from a difference Fourier map and their positional parameters were allowed to ride on the parent atoms, with N—H distances of 0.83 Å and C—H distances in the range 0.94–0.98 Å Is this added text OK?; their isotropic displacement parameters were freely refined.

Computing details

Data collection: PROCESS (Rigaku, 1996); cell refinement: PROCESS; data reduction: PROCESS; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003).

Figures

	Fig. 1. The molecular structure of (I), showing 50% probability displacement ellipsoids with the atom-numbering scheme.
	Fig. 2. Packing diagram for (I) viewed along the b axis. Hydrogen bonds are shown by dashed lines.

4-isobutyl-1,3-oxazolidine-2,5-dione

Crystal data

C7H11NO3	F(000) = 336
Mr = 157.17	Dx = 1.261 Mg m^−3
Monoclinic, P21/a	Mo Kα radiation, λ = 0.71070 Å
Hall symbol: -P 2yab	Cell parameters from 3 reflections
a = 9.8780 (9) Å	θ = 2.7–25.0°
b = 5.640 (2) Å	µ = 0.10 mm^−1
c = 15.448 (2) Å	T = 288 K
β = 105.844 (3)°	Plate, colourless
V = 827.9 (3) Å^3	0.55 × 0.40 × 0.15 mm
Z = 4

Data collection

Rigaku R-AXIS IV diffractometer	1347 independent reflections
Radiation source: fine-focus sealed tube	1162 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.048
Detector resolution: 10 pixels mm^-1	θmax = 25.0°, θmin = 2.7°
ω scans	h = −11→11
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	k = −6→6
Tmin = 0.938, Tmax = 0.99	l = −18→17
3732 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.048	Only H-atom displacement parameters refined
wR(F^2) = 0.159	w = 1/[σ^2(Fo^2) + (0.1091P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.17	(Δ/σ)max < 0.001
1347 reflections	Δρmax = 0.15 e Å^−3
112 parameters	Δρmin = −0.26 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.099 (17)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
O1	0.60790 (14)	1.2638 (2)	0.49473 (9)	0.0683 (5)
O2	0.81780 (13)	1.2334 (2)	0.59985 (8)	0.0592 (4)
O3	1.00525 (14)	1.0851 (3)	0.70271 (10)	0.0743 (5)
N1	0.65918 (15)	0.9542 (3)	0.59640 (9)	0.0552 (5)
H1	0.5840	0.8830	0.5740	0.064 (6)*
C1	0.68312 (19)	1.1532 (3)	0.55696 (11)	0.0536 (5)
C2	0.88426 (18)	1.0672 (3)	0.66228 (11)	0.0560 (5)
C3	0.77737 (17)	0.8814 (3)	0.66966 (10)	0.0526 (5)
H2	0.8093	0.7266	0.6595	0.054 (4)*
C4	0.74324 (18)	0.8905 (3)	0.76091 (11)	0.0566 (5)
H3	0.7181	1.0506	0.7703	0.054 (4)*
H4	0.6621	0.7925	0.7566	0.065 (5)*
C5	0.8605 (2)	0.8073 (4)	0.84246 (12)	0.0655 (6)
H5	0.9466	0.8951	0.8442	0.076 (6)*
C6	0.8906 (3)	0.5446 (5)	0.83784 (18)	0.0978 (9)
H9	0.9635	0.4948	0.8878	0.108 (8)*
H10	0.8074	0.4567	0.8347	0.115 (10)*
H11	0.9189	0.5114	0.7836	0.137 (11)*
C7	0.8178 (3)	0.8673 (6)	0.92822 (14)	0.1005 (9)
H6	0.7966	1.0321	0.9311	0.145 (13)*
H7	0.8873	0.8236	0.9812	0.136 (11)*
H8	0.7318	0.7806	0.9279	0.108 (9)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0673 (9)	0.0715 (9)	0.0619 (8)	0.0029 (6)	0.0104 (6)	0.0200 (7)
O2	0.0606 (8)	0.0532 (8)	0.0617 (8)	−0.0035 (5)	0.0129 (6)	0.0099 (5)
O3	0.0574 (9)	0.0798 (10)	0.0779 (10)	−0.0092 (6)	0.0051 (7)	0.0120 (7)
N1	0.0532 (8)	0.0575 (9)	0.0519 (8)	−0.0066 (6)	0.0089 (6)	0.0054 (7)
C1	0.0567 (10)	0.0551 (10)	0.0485 (10)	−0.0004 (7)	0.0134 (8)	0.0029 (7)
C2	0.0596 (11)	0.0536 (10)	0.0530 (10)	−0.0009 (7)	0.0124 (8)	0.0023 (8)
C3	0.0592 (10)	0.0457 (9)	0.0497 (10)	0.0000 (7)	0.0097 (8)	0.0012 (7)
C4	0.0654 (11)	0.0505 (10)	0.0534 (10)	−0.0017 (7)	0.0152 (8)	0.0028 (7)
C5	0.0705 (12)	0.0670 (12)	0.0547 (11)	−0.0089 (9)	0.0096 (9)	0.0087 (8)
C6	0.111 (2)	0.0754 (15)	0.0915 (19)	0.0146 (15)	0.0005 (15)	0.0211 (13)
C7	0.128 (2)	0.118 (2)	0.0532 (13)	−0.0048 (17)	0.0210 (14)	0.0073 (13)

Geometric parameters (Å, º)

O1—C1	1.215 (2)	C4—H3	0.96
O2—C2	1.376 (2)	C4—H4	0.96
O2—C1	1.390 (2)	C5—C6	1.517 (4)
O3—C2	1.192 (2)	C5—C7	1.534 (3)
N1—C1	1.329 (2)	C5—H5	0.98
N1—C3	1.446 (2)	C6—H9	0.94
N1—H1	0.83	C6—H10	0.95
C2—C3	1.514 (2)	C6—H11	0.97
C3—C4	1.537 (2)	C7—H6	0.96
C3—H2	0.96	C7—H7	0.95
C4—C5	1.534 (2)	C7—H8	0.98
C2—O2—C1	108.88 (13)	C3—C4—H4	107.8
C1—N1—C3	113.08 (14)	H3—C4—H4	107.9
C1—N1—H1	117.9	C6—C5—C4	111.97 (17)
C3—N1—H1	128.8	C6—C5—C7	111.11 (19)
O1—C1—N1	130.53 (18)	C4—C5—C7	108.54 (18)
O1—C1—O2	120.59 (16)	C6—C5—H5	108.4
N1—C1—O2	108.87 (14)	C4—C5—H5	108.8
O3—C2—O2	121.86 (16)	C7—C5—H5	107.9
O3—C2—C3	129.73 (16)	C5—C6—H9	111.6
O2—C2—C3	108.37 (14)	C5—C6—H10	109.5
N1—C3—C2	100.09 (12)	H9—C6—H10	110.0
N1—C3—C4	112.08 (14)	C5—C6—H11	109.6
C2—C3—C4	112.20 (13)	H9—C6—H11	108.3
N1—C3—H2	111.3	H10—C6—H11	107.8
C2—C3—H2	110.6	C5—C7—H6	111.7
C4—C3—H2	110.3	C5—C7—H7	112.6
C5—C4—C3	115.96 (15)	H6—C7—H7	109.2
C5—C4—H3	109.4	C5—C7—H8	109.2
C3—C4—H3	107.5	H6—C7—H8	106.5
C5—C4—H4	108.0	H7—C7—H8	107.3
C3—N1—C1—O1	−179.47 (17)	O3—C2—C3—N1	−174.62 (19)
C3—N1—C1—O2	−0.43 (19)	O2—C2—C3—N1	7.75 (16)
C2—O2—C1—O1	−175.06 (14)	O3—C2—C3—C4	66.4 (2)
C2—O2—C1—N1	5.79 (18)	O2—C2—C3—C4	−111.27 (15)
C1—O2—C2—O3	173.56 (17)	N1—C3—C4—C5	177.77 (14)
C1—O2—C2—C3	−8.58 (17)	C2—C3—C4—C5	−70.54 (19)
C1—N1—C3—C2	−4.43 (17)	C3—C4—C5—C6	−66.3 (2)
C1—N1—C3—C4	114.67 (16)	C3—C4—C5—C7	170.64 (17)