X-rayStructureAnalysisOnline2015,VOL.31
2015©TheJapanSocietyforAnalyticalChemistry
17
Crystal Structure of L-Isoleucine N-Carboxy Anhydride
Aya INADA,* Hitoshi KANAZAWA,*† and Hidehiro UEKUSA**
*Faculty of Symbiotic Systems Science, Fukushima University, 1 Kanayagawa, Fukushima 960-1296, Japan
**Chemistry and Materials Science, Tokyo Institute of Technology,
Ookayama-2, Meguro-ku, Tokyo, 152-8551, Japan
The title compound, (4S)-4-[(2S)-butan-2-yl]-1,3-oxazolidine-2,5-dione, C7H11NO3 was synthesized and the crystal
structurewasdeterminedbythesingle-crystalX-raydiffractionmethodat123K.Itcrystallizesinanorthorhombicspace
group,P212121,withunit-cellparameters:a=6.4713(3)Å,b=6.7196(3)Å,c=17.9369(7)Å,andZ=4.Theoxazolidine
ringinthiscompoundisplanarwithamaximumdeviationof0.037(4)Å.
(Received November 30, 2014; Accepted December 22, 2014; Published on web February 10, 2015)
Amino acid N-carboxy anhydrides (amino acid NCAs) have
been used as monomers to prepare high molecular weight
polypeptides for about 80 years.1 In general, they are
polymerized by initiators, such as amines and other bases.
Amino acid NCAs, such as L-alanine NCA and L-valine NCA,
are easily soluble in usual polar organic solvents, such as
tetrahydrofuran, ethyl acetate and 1,4-dioxane, etc., but the
resulting poly(L-alanine) and poly(L-valine) are not soluble in
these solvents. Thus, the solution polymerization of these
NCAsisimpossible.Alternatively,thesolutionpolymerization
of amino acid ester NCAs, such as g-benzyl-L-glutamate NCA
and b-benzyl-L-aspartate NCA has been extensively studied
becausetheseresultingpolymersaresolubleintheusualpolar
organic solvents.2,3 On the other hand, we found that when
aminoacidNCAcrystalsaredippedinhexane(inwhichNCAs
are not soluble) and an initiator (butyl amine) is added to the
mixture,polymerizationtakesplaceattheNCAcrystalsurface
and proceeds in the crystal in the solid-state. This solid-state
polymerizationisusefulforeveryaminoacidNCA.Wefound
that the solid-state polymerization of amino acid NCAs was
influencedbythecrystalstructureoftheNCAs.4–9Recently,the
characteristics of the topochemical reaction were observed in
the solid-state polymerization of g-methyl-L-glutamate NCA
(MLG NCA), and the crystal structure was determined.10 In
MLG NCA crystal, the molecules are linked by N–H·O
hydrogen bonds between the oxazolidine NH and the carbonyl
Oatominthemethylestergroup,formingatapestructurealong
the a axis. This molecular arrangement seems to be favorable
forthecrystalline-statetopochemicalpolymerization.Likethe
Fig. 1 Chemicalstructureofthetitlecompound.
†Towhomcorrespondenceshouldbeaddressed.
E-mail:[email protected]
MLG NCA crystal, the title compound is also very reactive in
the solid state. Thus, it is necessary to determine the crystal
structuretounderstandthereactivity.
The title compound given in Fig. 1 was prepared by the
reactionof L-isoleucinewithtriphosgen,andcrystallizedinthe
mixtureofethylacetateandhexane.L-Isoleucine([a]20
D =+40.0
~ +41.5˚) was the product of Wako Pure Chemical Industries,
Ltd.,Japan.
All measurements of X-ray crystallography were carried out
using a Rigaku R-AXIS RAPID imaging plate area detector
with graphite-monochromated Cu-Ka radiation at 123 K. The
structure was solved by direct methods and refined full-matrix
least-squaresmethodsonF2.Hydrogenatomsoncarbonatoms
Table 1
Crystal and experimental data
Chemical formula: C7H11NO3
Formula weight = 157.17
T = 123(2)K
Crystal system: Orthorhombic
Space group: P212121
a = 6.4713(3)Å
b = 6.7196(3)Å
c = 17.9369(7)Å
V = 779.98(6)Å
Z=4
Dcalc = 1.338 g/cm3
Radiation: Cu Ka (l = 1.54186 Å)
m(Cu Ka) = 0.88 mm–1
F(0 0 0) = 336
Crystal size = 0.30 ¥ 0.05 ¥ 0.05 mm3
No. of reflections collected = 8122
No. of independent reflections = 1409
q range for data collection: 4.93 to 68.03˚
Data/Restraints/Parameters = 1409/0/105
Goodness-of-fit on F2 = 1.09
R indices [I > 2s(I)]: R1 = 0.0484, wR2 = 0.1207
R indices (all data): R1 = 0.0560, wR2 = 0.1332
(D/s)max = 0.006
(Dr)max = 0.23 eÅ–3
(Dr)min = –0.28 eÅ–3
Measurement: RIGAKU R-AXIS RAPID
Programs system: CrystalStructure 4.0
Structure solution: SHELXL-97
Structure determination: Direct methods (SIR92)
CCDC deposition number: 1035650
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X-rayStructureAnalysisOnline2015,VOL.31
Fig. 2 ORTEP structure of L-isoleucine NCA, showing 50%
probabilityellipsoids.
Table 2
Selected bond lengths (Å), bond angles (˚)
C1-O1
C2-C3
C3-C4
C4-C6
O2-C1
O3-C2
C1-N1-C3
C2-C3-C4
C5-C4-C3
C6-C4-C3
O1-C1-O2
O3-C2-O2
N1-C1O2
N1-C3-C4
1.202(3)
1.508(4)
1.544(4)
1.518(4)
1.398(3)
1.200(3)
112.9(3)
112.9(2)
111.1(2)
111.7(2)
120.3(3)
120.8(3)
108.4(3)
112.7(2)
C1-N1
C3-N1
C4-C5
C6-C7
O2-C2
1.341(4)
1.452(3)
1.526(3)
1.530(4)
1.382(3)
C2-O2-C1
C4-C6-C7
C6-C4-C5
O1-C1-N1
O2-C2-C3
O3-C2-C3
N1-C3-C2
109.0(2)
112.5(2)
112.7(2)
131.3(3)
108.89(19)
130.3(3)
100.2(2)
Fig. 3 CrystalstructureofL-isoleucineNCA.
Table 3
Hydrogen-bond geometry (Å, ˚)
D-H·A
N1-H1·O1
i
D-H
H·A
D·A
D-H·A
0.98(3)
1.86(4)
2.831(3)
172(3)
Symmetry code: (i) 1/2+x, –1/2–y, 1–z.
arrangementalongthea-axisseemspreferablefortheformation
oftheb-sheetstructurepolypeptide.Adetailedinvestigationof
werelocatedatthecalculatedpositionsandtreatedbyariding thepolymerizationwillbedescribedinthefuture.
atommodel.TheNHhydrogenatomwasfoundinadifference
Fourier map, and its position and isotropic thermal parameters
wererefined.Theabsolutestructurecouldnotbedeterminedby References
X-ray analysis due to the lack of enough anomalous scattering
(Flackparameter=0.1(4)).Thus,theabsoluteconfigurationof 1. C. H. Bamford, A. Elliot, and W. E. Hanby, “Synthetic
thecompoundhasbeenassignedbasedonthestartingmolecule
Polypeptides”, Ed. E. Hutchnson, 1956, New York,
and synthesis. Crystal data and details of data collection are
AcademicPress,7.
giveninTable1.
2. H.Sekiguchi,Pure Appl. Chem.,1981,53,1689.
The molecular structure, drawn by ORTEP with atom- 3. H.R.Kricheldorf,Angew. Chem.,2006,45,5752.
numbering,isgiveninFig.2.Selectedbondlengthsandangles 4. H.KanazawaandT.Kawai,J. Polym. Sci. Chem. Ed.,1980,
aregiveninTable2.Theoxazolidineringinthiscompoundis
18,629.
planarwithamaximumdeviationof0.037(4)Å.Thisfeatureis 5. H.Kanazawa,Polymer,1992,33,2557.
common among other amino acid NCAs.9,10 Other geometric 6. H.Kanazawa,Gendai Kagaku,1992,No. 259,28.
7. H.Kanazawa,Mol. Cryst. Liq. Cryst.,1998,313,205.
parametersofthismoleculeareintheexpectedrange.
The crystal structure is shown in Fig. 3. In the crystal, 8. H. Kanazawa,A. Inada, and N. Kawana, Macromolecular
Symposia,2006,242,104.
L-isoleucine NCA molecules are linked by N1–H1·O1i
hydrogen bonds, forming a tape structure along the a-axis 9. H. Kanazawa and J. Magoshi, Acta Cryst., 2003, C59,
direction.Thehydrogen-bondgeometryisgiveninTable3.
O159.
Weobservedthat L-isoleucineNCApolymerizedandformed 10. H. Kanazawa, A. Inada, A. Sakon, and H. Uekusa, Acta
Crys.,2015,E71,48.
the b-sheet structure poly(L-isoleucine). The molecular