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(S)-2-Aza­niumyl-2-methyl-3-phenyl­propano­ate monohydrate

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aSchool of Science, Tokai University, 4-1-1 Kitakaname, Hiratuka, Kanagawa 259-1292, Japan
*Correspondence e-mail: fujii@wing.ncc.u-tokai.ac.jp

Edited by S. Bernès, Benemérita Universidad Autónoma de Puebla, México (Received 25 August 2016; accepted 26 September 2016; online 7 October 2016)

The title compound, C10H13NO2·H2O, crystallizes in a zwitterionic form as a monohydrate, involving the propyl­benzene group with a trans conformation. It is a non-natural amino acid, and has attracted attention as an inhibitor of phenyl­alanine hy­droxy­lase. In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds, forming C(5) chains along the c-axis direction. Two chains are linked by another N—H⋯O hydrogen bond, forming an R33(11) ring motif. Further O—H⋯O hydrogen bonds link these motifs via the water mol­ecules, to form a three-dimensional framework.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

Solid-phase synthesis is now the accepted method to synthesize peptides, in which protected natural or non-natural amino acids are widely used; for example, 2-methyl­phenyl­alanine (MePhe), a non-natural amino acid. At first, it attracted attention as a substrate analogue and an inhibitor of phenyl­alanine hy­droxy­lase (EC 1.14.16.1: phenyl­alanine 4-monooxygenase), related to phenyl­ketonuria (PKU), a genetic disorder (Greengard et al., 1976[Greengard, O., Yoss, M. S. & Del Valle, J. A. (1976). Science, 192, 1007-1008.]; Binek et al., 1981[Binek, P. A., Johnson, T. C. & Kelly, C. J. (1981). J. Neurochem. 36, 1476-1484.]). Despite the biological and pharmaceutical inter­est, only a few crystal structures for 2-methyl-substituted phenyl­alanine derivatives have been reported, for example (R)-α-MePheOMe·HCl·H2O (QABCAX; Crisma et al., 1997[Crisma, M., Valle, G., Polese, A., Formaggio, F., Toniolo, C. & Kamphuis, J. (1997). Z. Kristallogr. New Cryst. Struct. 212, 113-114.]), (RS)-α-MeTyr (DMTYRS; Gaudestad et al., 1976[Gaudestad, O., Mostad, A. & Romming, C. (1976). Acta Chem. Scand. Ser. B, 30, 501-504.]) or (S)-α-MeDOPA·1.5H2O (COSGUM; Neuman et al., 1984[Neuman, A., Gillier, H., Avenel, D. & Perret, G. (1984). Acta Cryst. C40, 2124-2126.]).

In the title compound (Fig. 1[link], CAS No. 23239–35-2 for the non-hydrated mol­ecule), the mol­ecule has a conformation like a cross, in which the propyl­benzene group has a trans conformation [torsion angle C10—C2—C3—C4: τ = 167.9 (2)°]. A similar conformation is found in other 2-methyl-substituted amino acids, for example, isoVal monohydrate, CISNUP [τ = 177.0 (3)°; Butcher et al., 2013[Butcher, R. J., Brewer, G., Burton, A. S. & Dworkin, J. P. (2013). Acta Cryst. E69, o1829-o1830.]] and DMTYRS [τ = −176.58 (1)°], while the cis conformation is observed in other cases, as in QABCAX. This slightly distorted conformation is also comparable to that found in the crystal structures of phenyl­alanine derivatives, for example in L-Phe monohydrate (GOFWOP; Williams et al., 2013[Williams, P. A., Hughes, C. E., Buanz, A. B. M., Gaisford, S. & Harris, K. D. M. (2013). J. Phys. Chem. C, 117, 12136-12145.]).

[Figure 1]
Figure 1
A view of the mol­ecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level. The dashed line indicates the inter­molecular O—H⋯O hydrogen bond (see Table 1[link], entry 3).

In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds, forming C(5) chains along the c-axis direction (Table 1[link], entry 1). Two chains are linked by another N—H⋯O hydrogen bond, forming R33(11) rings, approximately parallel to the bc plane (Fig. 2[link]). Further O—H⋯O and N—H⋯O hydrogen bonds link the layers of R rings via the water mol­ecules, forming a three-dimensional framework (Table 1[link] and Fig. 3[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1C⋯O2i 0.93 (3) 1.83 (3) 2.7642 (18) 175 (3)
N1—H1B⋯O1ii 0.91 (2) 1.99 (2) 2.8581 (18) 160.6 (19)
O3—H11A⋯O2 0.87 (2) 2.06 (2) 2.897 (2) 160 (3)
O3—H11B⋯O1iii 0.91 (2) 1.92 (2) 2.825 (2) 178 (4)
N1—H1A⋯O3iv 0.96 (3) 2.40 (3) 3.050 (2) 124.9 (18)
Symmetry codes: (i) x, y, z+1; (ii) [-x+{\script{3\over 2}}, -y, z+{\script{1\over 2}}]; (iii) x-1, y, z; (iv) x+1, y, z+1.
[Figure 2]
Figure 2
A view of the crystal packing of the title compound. Dashed lines indicate the N—H⋯O and O—H⋯O hydrogen bonds (see Table 1[link]).
[Figure 3]
Figure 3
A view along the c axis of the crystal packing of the title compound. Dashed lines indicate the O—H⋯O and N—H⋯O hydrogen bonds (see Table 1[link]).

The methyl groups are surrounded by the hydro­philic planes and are arranged in a columnar structure (Fig. 3[link]), similar to that of 2-MeAsp (NUPVUR; Fujii, 2015[Fujii, I. (2015). Acta Cryst. E71, o731-o732.]). The hydro­philic layers present a honeycomb arrangement, and are well separated from the hydro­phobic layers along the b-axis direction (Fig. 3[link]).

Synthesis and crystallization

The title compound was purchased from Nagase–Sangyo Co. Ltd. The absolute configuration could not be established by anomalous-dispersion effects. The S enanti­omer has been chosen by referring to the sign of the known polarity in the synthetic procedure (Yamada et al., 1969[Yamada, S.-I., Achiwa, K., Terashima, S., Mizuno, H., Takamura, N. & Legrand, M. (1969). Chem. Pharm. Bull. 17, 2608-2613.]). Rod-like colourless crystals of the title compound were obtained by vapour-phase diffusion of an aqueous ethanol–chloro­form solvent mixture at room temperature.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link].

Table 2
Experimental details

Crystal data
Chemical formula C10H13NO2·H2O
Mr 197.23
Crystal system, space group Orthorhombic, P212121
Temperature (K) 297
a, b, c (Å) 6.1146 (9), 28.3272 (10), 5.9614 (8)
V3) 1032.6 (2)
Z 4
Radiation type Cu Kα
μ (mm−1) 0.77
Crystal size (mm) 0.4 × 0.2 × 0.2
 
Data collection
Diffractometer Enraf–Nonius CAD-4-turbo
Absorption correction ψ scan (North et al., 1968[North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351-359.])
Tmin, Tmax 0.750, 0.860
No. of measured, independent and observed [I > 2σ(I)] reflections 1490, 1448, 1384
Rint 0.071
(sin θ/λ)max−1) 0.623
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.029, 0.082, 1.08
No. of reflections 1448
No. of parameters 149
No. of restraints 2
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.16, −0.18
Computer programs: CAD-4 Software (Enraf–Nonius, 1994[Enraf-Nonius (1994). CAD-4 Software. Enraf-Nonius, Delft, The Netherlands.]), XCAD4 (Harms & Wocadlo, 1995[Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]), ORTEP-3 for Windows and WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]), Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Structural data


Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1994); cell refinement: CAD-4 Software (Enraf–Nonius, 1994); data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: WinGX (Farrugia, 2012) and publCIF (Westrip, 2010).

(S)-2-Azaniumyl-2-methyl-3-phenylpropanoate monohydrate top
Crystal data top
C10H13NO2·H2OF(000) = 424
Mr = 197.23Dx = 1.269 Mg m3
Orthorhombic, P212121Cu Kα radiation, λ = 1.54184 Å
Hall symbol: P 2ac 2abCell parameters from 25 reflections
a = 6.1146 (9) Åθ = 28–35°
b = 28.3272 (10) ŵ = 0.77 mm1
c = 5.9614 (8) ÅT = 297 K
V = 1032.6 (2) Å3Rod, colorless
Z = 40.4 × 0.2 × 0.2 mm
Data collection top
Enraf–Nonius CAD-4-turbo
diffractometer
1384 reflections with I > 2σ(I)
Radiation source: Enraf–Nonius FR590Rint = 0.071
Graphite monochromatorθmax = 73.9°, θmin = 3.1°
non–profiled ω/2θ scansh = 17
Absorption correction: ψ scan
(North et al., 1968)
k = 035
Tmin = 0.750, Tmax = 0.860l = 70
1490 measured reflections3 standard reflections every 60 min
1448 independent reflections intensity decay: 1%
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.029 w = 1/[σ2(Fo2) + (0.0485P)2 + 0.1286P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.082(Δ/σ)max < 0.001
S = 1.08Δρmax = 0.16 e Å3
1448 reflectionsΔρmin = 0.18 e Å3
149 parametersExtinction correction: SHELXL2014 (Sheldrick, 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
2 restraintsExtinction coefficient: 0.0047 (9)
0 constraints
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C100.2812 (3)0.03959 (6)0.5984 (3)0.0381 (4)
H10A0.32350.00720.57980.057*
H10B0.17250.04760.48860.057*
H10C0.2220.04410.74610.057*
N10.6435 (2)0.05862 (5)0.7456 (2)0.0301 (3)
O30.0250 (3)0.09096 (7)0.0372 (3)0.0624 (4)
C10.5807 (3)0.06044 (5)0.3360 (2)0.0280 (3)
C20.4804 (3)0.07123 (5)0.5680 (2)0.0271 (3)
C30.4175 (3)0.12352 (5)0.5933 (3)0.0343 (4)
H3A0.33050.13270.46440.041*
H3B0.32610.12690.72540.041*
C40.6074 (3)0.15712 (5)0.6137 (3)0.0380 (4)
C50.7560 (4)0.16373 (6)0.4415 (4)0.0473 (5)
H50.73820.14730.30770.057*
C60.9312 (4)0.19445 (7)0.4654 (5)0.0618 (6)
H61.03150.19790.34940.074*
C70.9564 (5)0.21965 (8)0.6600 (5)0.0756 (8)
H71.07240.24070.67550.091*
C80.8094 (6)0.21368 (8)0.8318 (5)0.0786 (8)
H80.82640.23070.96390.094*
C90.6365 (4)0.18263 (7)0.8105 (4)0.0565 (6)
H90.53890.17880.92870.068*
O10.75798 (19)0.03832 (4)0.3320 (2)0.0377 (3)
O20.4743 (2)0.07410 (5)0.16925 (18)0.0402 (3)
H1A0.778 (4)0.0757 (8)0.733 (4)0.054 (6)*
H1B0.683 (4)0.0279 (8)0.739 (3)0.043 (5)*
H1C0.579 (5)0.0644 (7)0.885 (4)0.055 (6)*
H11A0.158 (4)0.0929 (12)0.091 (6)0.111 (12)*
H11B0.058 (6)0.0735 (11)0.131 (6)0.124 (14)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C100.0367 (8)0.0508 (8)0.0267 (7)0.0065 (8)0.0027 (7)0.0004 (7)
N10.0343 (7)0.0354 (7)0.0207 (6)0.0039 (6)0.0012 (6)0.0007 (5)
O30.0504 (9)0.0922 (12)0.0447 (8)0.0064 (9)0.0081 (8)0.0098 (8)
C10.0313 (7)0.0329 (7)0.0199 (6)0.0011 (6)0.0032 (7)0.0014 (5)
C20.0288 (8)0.0352 (7)0.0173 (6)0.0033 (6)0.0005 (6)0.0003 (5)
C30.0356 (8)0.0386 (7)0.0286 (7)0.0082 (7)0.0030 (7)0.0002 (6)
C40.0464 (9)0.0305 (7)0.0371 (8)0.0069 (7)0.0009 (8)0.0029 (6)
C50.0531 (11)0.0382 (8)0.0507 (10)0.0007 (8)0.0072 (11)0.0034 (8)
C60.0539 (12)0.0495 (10)0.0819 (16)0.0035 (10)0.0101 (14)0.0158 (10)
C70.0731 (16)0.0520 (11)0.102 (2)0.0188 (12)0.0224 (19)0.0098 (13)
C80.108 (2)0.0584 (12)0.0692 (15)0.0206 (15)0.0236 (19)0.0094 (12)
C90.0775 (15)0.0477 (9)0.0443 (10)0.0044 (11)0.0012 (13)0.0067 (8)
O10.0375 (6)0.0449 (6)0.0306 (5)0.0102 (5)0.0062 (6)0.0029 (5)
O20.0383 (7)0.0628 (7)0.0194 (5)0.0065 (6)0.0007 (5)0.0011 (5)
Geometric parameters (Å, º) top
C10—C21.523 (2)C3—C41.506 (3)
C10—H10A0.96C3—H3A0.97
C10—H10B0.96C3—H3B0.97
C10—H10C0.96C4—C51.383 (3)
N1—C21.4983 (19)C4—C91.389 (2)
N1—H1A0.96 (3)C5—C61.388 (3)
N1—H1B0.91 (2)C5—H50.93
N1—H1C0.93 (3)C6—C71.371 (4)
O3—H11A0.87 (2)C6—H60.93
O3—H11B0.91 (2)C7—C81.373 (4)
C1—O21.2497 (19)C7—H70.93
C1—O11.252 (2)C8—C91.381 (4)
C1—C21.5435 (19)C8—H80.93
C2—C31.538 (2)C9—H90.93
C2—C10—H10A109.5C4—C3—H3A108.5
C2—C10—H10B109.5C2—C3—H3A108.5
H10A—C10—H10B109.5C4—C3—H3B108.5
C2—C10—H10C109.5C2—C3—H3B108.5
H10A—C10—H10C109.5H3A—C3—H3B107.5
H10B—C10—H10C109.5C5—C4—C9118.15 (19)
C2—N1—H1A113.3 (14)C5—C4—C3122.14 (15)
C2—N1—H1B112.2 (14)C9—C4—C3119.71 (17)
H1A—N1—H1B104.6 (19)C4—C5—C6121.1 (2)
C2—N1—H1C107.7 (16)C4—C5—H5119.5
H1A—N1—H1C110 (2)C6—C5—H5119.5
H1B—N1—H1C108.8 (19)C7—C6—C5120.0 (2)
H11A—O3—H11B109 (3)C7—C6—H6120
O2—C1—O1126.21 (14)C5—C6—H6120
O2—C1—C2116.37 (13)C6—C7—C8119.5 (2)
O1—C1—C2117.41 (13)C6—C7—H7120.2
N1—C2—C10107.93 (12)C8—C7—H7120.2
N1—C2—C3109.06 (12)C7—C8—C9120.7 (2)
C10—C2—C3110.82 (14)C7—C8—H8119.6
N1—C2—C1108.74 (12)C9—C8—H8119.6
C10—C2—C1107.95 (12)C8—C9—C4120.5 (2)
C3—C2—C1112.22 (12)C8—C9—H9119.8
C4—C3—C2115.10 (14)C4—C9—H9119.8
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1C···O2i0.93 (3)1.83 (3)2.7642 (18)175 (3)
N1—H1B···O1ii0.91 (2)1.99 (2)2.8581 (18)160.6 (19)
O3—H11A···O20.87 (2)2.06 (2)2.897 (2)160 (3)
O3—H11B···O1iii0.91 (2)1.92 (2)2.825 (2)178 (4)
C10—H10C···O3i0.962.53.378 (2)153
N1—H1A···O3iv0.96 (3)2.40 (3)3.050 (2)124.9 (18)
Symmetry codes: (i) x, y, z+1; (ii) x+3/2, y, z+1/2; (iii) x1, y, z; (iv) x+1, y, z+1.
 

Acknowledgements

The author thanks Tokai University for a research grant, which partially supported this work.

References

First citationBinek, P. A., Johnson, T. C. & Kelly, C. J. (1981). J. Neurochem. 36, 1476–1484.  CrossRef CAS PubMed Web of Science Google Scholar
First citationButcher, R. J., Brewer, G., Burton, A. S. & Dworkin, J. P. (2013). Acta Cryst. E69, o1829–o1830.  CSD CrossRef CAS IUCr Journals Google Scholar
First citationCrisma, M., Valle, G., Polese, A., Formaggio, F., Toniolo, C. & Kamphuis, J. (1997). Z. Kristallogr. New Cryst. Struct. 212, 113–114.  CAS Google Scholar
First citationEnraf–Nonius (1994). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands.  Google Scholar
First citationFarrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationFujii, I. (2015). Acta Cryst. E71, o731–o732.  Web of Science CSD CrossRef IUCr Journals Google Scholar
First citationGaudestad, O., Mostad, A. & Romming, C. (1976). Acta Chem. Scand. Ser. B, 30, 501–504.  CrossRef Web of Science Google Scholar
First citationGreengard, O., Yoss, M. S. & Del Valle, J. A. (1976). Science, 192, 1007–1008.  CrossRef CAS PubMed Web of Science Google Scholar
First citationHarms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.  Google Scholar
First citationMacrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
First citationNeuman, A., Gillier, H., Avenel, D. & Perret, G. (1984). Acta Cryst. C40, 2124–2126.  CSD CrossRef CAS Web of Science IUCr Journals Google Scholar
First citationNorth, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.  CrossRef IUCr Journals Web of Science Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationWestrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationWilliams, P. A., Hughes, C. E., Buanz, A. B. M., Gaisford, S. & Harris, K. D. M. (2013). J. Phys. Chem. C, 117, 12136–12145.  Web of Science CSD CrossRef CAS Google Scholar
First citationYamada, S.-I., Achiwa, K., Terashima, S., Mizuno, H., Takamura, N. & Legrand, M. (1969). Chem. Pharm. Bull. 17, 2608–2613.  CAS Google Scholar

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