Dimethyl [(5-ethoxy­carbonyl-4-methyl-1,3-thia­zol-2-ylamino)­phenyl­meth­yl]­phospho­nate

In the structure of the title compound, C₁₆H₂₁N₂O₅PS, the P atom adopts a slightly distorted tetra­hedral configuration. The crystal packing is stabilized by intra­molecular C—H...N and C—H...O and inter­molecular N—H...O hydrogen-bonding inter­actions.

Key indicators

• Single-crystal X-ray study
• T = 291 K
• Mean [sigma](C-C) = 0.004 Å
• R factor = 0.045
• wR factor = 0.136
• Data-to-parameter ratio = 15.7

checkCIF/PLATON results

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Alert level C
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical .          ?
PLAT154_ALERT_1_C The su's on the Cell Angles are Equal  (x 10000)        100 Deg.
PLAT180_ALERT_3_C Check Cell Rounding: # of Values Ending with 0 =          3
PLAT230_ALERT_2_C Hirshfeld Test Diff for    O5     -   C14     ..       5.61 su
PLAT322_ALERT_2_C Check Hybridisation of  S1     in Main Residue .          ?

Alert level G
PLAT793_ALERT_1_G Check the Absolute Configuration of C9     = ...          S

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

   3 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
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S1. Comment

Among many known heterocyclic compounds, the analogues containing a thiazole ring have received much attention since they possess significant biological and pharmacological activity (Vicini et al., 2006). Aminophosphonic acids and their derivatives represent an important class of organophosphorus compounds that continue to attract considerable attention due to their biological importance and extensive application in organic chemistry (Lu & Chen, 2000). The bioactivity of substituted aminophosphonates is described by Song & Jiang (2004). We report here the crystal structure of the title compound (Fig. 1)

The bond lengths of N2—C10 and C10—S1 are longer than those observed in free thiazole [1.286 and 1.728 Å] (Garbarczyk et al., 1999) and the N1—C9 bond is a little longer than the neighbouring N1—C10 bond. The bond angles O1—P1—O3, O1—P1—O2 and O1—P1—C9 are larger than of O3—P1—O2, O2—P1—C9 and O3—P1—C9, indicating the phosphorus atom adopts a slightly distorted tetrahedral configuration.

Some weak intramolecular C—H···N and C—H···O hydrogen-bonding interactions exist in the crystal structure. In additon, the crystal is also stabilized by intermolecular N1—H1···O1 hydrogen-bonding interactions that form dimers (Fig. 2).

Related literature

A similar synthetic method is described by Srikant & Asit (2007) and the bioactivity of substituted aminophosphonates is described by Song & Jiang (2004).

For related literature, see: Józef et al. (1999); Kenneth & Jason (2005); Lu & Chen (2000); Paola et al. (2006).

S2. Experimental

2-amino-5-carbethoxy-4-methylthiazole was prepared according to the literature method (Boy & Guernonenneth, 2005) in 75% yield. The mixture of benzaldehyde (5 mmol) and Mg(ClO₄)₂ (5mol%) was stirred magnetically for 11–15 min, then 2-amino-5-carbethoxy-4-methylthiazole (5 mmol) and dimethylphosphonate(5 mmol) were added and the reaction mixture was stirred at room temperature for 6 h (Bhagat & Chakraborti, 2007). The mixture was extracted with ethanol (3 times 10 ml), the combined ethanol extracts were dried (over MgSO₄) and concentrated in vacuo to afford a white solid (1.15 g, 61%) which on passing through a column of silica gel elution with acetone-peroleum ether (v/v 1/4) afford the title compound. The precipitate was recrystallized from ethanol-acetone (v/v 1/5) to give crystals suitable for X-ray diffraction.

S3. Refinement

All H-atoms were refined using a riding model with d(C—H) = 0.93 Å, U_iso=1.2U_eq(C) for aromatic 0.98 Å, U_iso = 1.2U_eq(C) for CH, 0.96 Å, U_iso = 1.5U_eq(C) for CH₃ atoms and d(N—H) = 0.86 Å, U_iso=1.2U_eq(N) for NH.

Computing details

Data collection: SMART (Bruker, 2000); cell refinement: SAINT (Bruker, 2000); data reduction: SAINT (Bruker, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXTL (Bruker, 1997).

Figures

	Fig. 1. The molecular structure of (I), showing 50% probability displacement ellipsolids and the atom-labelling scheme.
	Fig. 2. The crystal structure of (I), showing the formation of N—H···O hydrogen bonds (dashed lines)·H atoms not involved in hydrogen bonding have been omitted.

Dimethyl [(5-ethoxycarbonyl-4-methyl-1,3-thiazol-2-ylamino)phenylmethyl]phosphonate

Crystal data

C16H21N2O5PS	Z = 2
Mr = 384.38	F(000) = 404
Triclinic, P1	Dx = 1.374 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.1821 (4) Å	Cell parameters from 4630 reflections
b = 9.9884 (5) Å	θ = 2.5–19.2°
c = 11.9142 (6) Å	µ = 0.29 mm^−1
α = 98.249 (1)°	T = 291 K
β = 103.299 (1)°	Block, colorless
γ = 95.618 (1)°	0.20 × 0.20 × 0.10 mm
V = 929.08 (8) Å^3

Data collection

Bruker SMART APEX CCD area-detector diffractometer	3610 independent reflections
Radiation source: fine-focus sealed tube	3081 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.032
φ and ω scans	θmax = 26.0°, θmin = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 2000)	h = −10→9
Tmin = 0.945, Tmax = 0.972	k = −12→12
8937 measured reflections	l = −14→14

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.045	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.136	H-atom parameters constrained
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0776P)^2 + 0.2203P] where P = (Fo^2 + 2Fc^2)/3
3610 reflections	(Δ/σ)max = 0.001
230 parameters	Δρmax = 0.41 e Å^−3
0 restraints	Δρmin = −0.21 e Å^−3

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
C1	−0.0145 (4)	0.9080 (3)	1.2151 (2)	0.0730 (8)
H1A	−0.0472	0.8278	1.2449	0.110*
H1B	−0.0555	0.9849	1.2524	0.110*
H1C	0.1069	0.9248	1.2310	0.110*
C2	−0.4101 (3)	0.6895 (3)	0.8875 (3)	0.0758 (8)
H2A	−0.4252	0.5992	0.8430	0.114*
H2B	−0.4895	0.7421	0.8476	0.114*
H2C	−0.4288	0.6842	0.9635	0.114*
C3	0.2526 (3)	0.7897 (2)	1.05538 (19)	0.0411 (5)
C4	0.2955 (3)	0.6954 (2)	1.1295 (2)	0.0550 (6)
H4	0.2265	0.6122	1.1172	0.066*
C5	0.4383 (4)	0.7241 (3)	1.2204 (3)	0.0643 (7)
H5	0.4645	0.6614	1.2702	0.077*
C6	0.5427 (4)	0.8459 (3)	1.2378 (3)	0.0658 (7)
H6	0.6408	0.8644	1.2983	0.079*
C7	0.5023 (3)	0.9404 (3)	1.1659 (2)	0.0634 (7)
H7	0.5726	1.0229	1.1783	0.076*
C8	0.3567 (3)	0.9126 (2)	1.0750 (2)	0.0504 (6)
H8	0.3290	0.9769	1.0271	0.060*
C9	0.0939 (3)	0.7586 (2)	0.95480 (19)	0.0400 (5)
H9	0.0913	0.8335	0.9097	0.048*
C10	0.1302 (3)	0.6288 (2)	0.77337 (18)	0.0388 (5)
C11	0.1807 (3)	0.6978 (2)	0.6147 (2)	0.0490 (5)
C12	0.2079 (3)	0.5648 (2)	0.5898 (2)	0.0479 (5)
C13	0.1884 (4)	0.8039 (3)	0.5388 (3)	0.0727 (8)
H13A	0.2253	0.7672	0.4712	0.109*
H13B	0.2669	0.8820	0.5821	0.109*
H13C	0.0780	0.8306	0.5142	0.109*
C14	0.2556 (3)	0.4942 (3)	0.4884 (2)	0.0563 (6)
C15	0.3114 (4)	0.2811 (4)	0.3995 (2)	0.0750 (9)
H15A	0.4186	0.3233	0.3906	0.090*
H15B	0.2266	0.2748	0.3265	0.090*
C16	0.3282 (5)	0.1417 (4)	0.4301 (3)	0.0942 (11)
H16A	0.4169	0.1487	0.5001	0.141*
H16B	0.3553	0.0842	0.3671	0.141*
H16C	0.2232	0.1031	0.4427	0.141*
N1	0.0889 (3)	0.63109 (17)	0.87592 (16)	0.0444 (4)
H1	0.0584	0.5550	0.8961	0.053*
N2	0.1400 (2)	0.73480 (18)	0.72011 (16)	0.0454 (4)
O1	−0.1179 (2)	0.62813 (15)	1.06639 (15)	0.0521 (4)
O2	−0.0859 (2)	0.88752 (15)	1.09062 (14)	0.0501 (4)
O3	−0.2396 (2)	0.75427 (18)	0.90029 (15)	0.0559 (4)
O4	0.2876 (3)	0.5468 (2)	0.40968 (18)	0.0840 (7)
O5	0.2613 (2)	0.36168 (19)	0.49423 (15)	0.0622 (5)
P1	−0.09523 (7)	0.74679 (5)	1.00991 (5)	0.03896 (18)
S1	0.17583 (8)	0.47814 (5)	0.70125 (5)	0.04578 (19)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.079 (2)	0.0800 (19)	0.0519 (16)	0.0194 (16)	0.0123 (14)	−0.0131 (14)
C2	0.0435 (15)	0.089 (2)	0.087 (2)	0.0010 (14)	0.0043 (14)	0.0139 (17)
C3	0.0396 (12)	0.0400 (10)	0.0473 (12)	0.0088 (9)	0.0171 (9)	0.0071 (9)
C4	0.0541 (14)	0.0451 (12)	0.0663 (16)	0.0076 (10)	0.0115 (12)	0.0156 (11)
C5	0.0588 (16)	0.0698 (16)	0.0649 (17)	0.0145 (13)	0.0064 (13)	0.0241 (14)
C6	0.0490 (15)	0.0834 (19)	0.0589 (16)	0.0050 (13)	0.0054 (12)	0.0079 (14)
C7	0.0562 (16)	0.0632 (15)	0.0633 (16)	−0.0104 (12)	0.0127 (13)	0.0018 (13)
C8	0.0544 (14)	0.0452 (12)	0.0544 (14)	0.0048 (10)	0.0194 (11)	0.0092 (10)
C9	0.0465 (12)	0.0351 (10)	0.0420 (11)	0.0084 (9)	0.0164 (9)	0.0075 (8)
C10	0.0351 (11)	0.0412 (10)	0.0385 (11)	0.0041 (8)	0.0094 (8)	0.0021 (9)
C11	0.0456 (13)	0.0573 (13)	0.0438 (12)	0.0000 (10)	0.0112 (10)	0.0118 (10)
C12	0.0453 (13)	0.0590 (13)	0.0395 (12)	0.0027 (10)	0.0139 (10)	0.0065 (10)
C13	0.093 (2)	0.0731 (18)	0.0582 (17)	0.0049 (16)	0.0270 (15)	0.0216 (14)
C14	0.0462 (14)	0.0843 (18)	0.0375 (12)	0.0042 (12)	0.0150 (10)	0.0035 (12)
C15	0.0663 (18)	0.106 (2)	0.0492 (15)	0.0159 (16)	0.0226 (13)	−0.0144 (15)
C16	0.106 (3)	0.089 (2)	0.084 (2)	0.024 (2)	0.032 (2)	−0.0177 (19)
N1	0.0615 (12)	0.0335 (8)	0.0432 (10)	0.0060 (8)	0.0241 (9)	0.0046 (7)
N2	0.0490 (11)	0.0443 (9)	0.0446 (10)	0.0051 (8)	0.0146 (8)	0.0086 (8)
O1	0.0597 (10)	0.0444 (8)	0.0590 (10)	0.0086 (7)	0.0246 (8)	0.0143 (7)
O2	0.0605 (10)	0.0429 (8)	0.0476 (9)	0.0134 (7)	0.0172 (8)	0.0001 (7)
O3	0.0460 (9)	0.0653 (10)	0.0525 (10)	0.0048 (8)	0.0055 (8)	0.0101 (8)
O4	0.1037 (18)	0.1013 (16)	0.0567 (12)	0.0095 (13)	0.0412 (12)	0.0140 (11)
O5	0.0703 (12)	0.0710 (12)	0.0466 (10)	0.0112 (9)	0.0260 (9)	−0.0058 (8)
P1	0.0423 (3)	0.0363 (3)	0.0398 (3)	0.0079 (2)	0.0128 (2)	0.0050 (2)
S1	0.0526 (4)	0.0450 (3)	0.0425 (3)	0.0096 (2)	0.0189 (3)	0.0030 (2)

Geometric parameters (Å, º)

C1—O2	1.440 (3)	C10—N1	1.338 (3)
C1—H1A	0.9600	C10—S1	1.740 (2)
C1—H1B	0.9600	C11—C12	1.370 (3)
C1—H1C	0.9600	C11—N2	1.382 (3)
C2—O3	1.444 (3)	C11—C13	1.494 (3)
C2—H2A	0.9600	C12—C14	1.462 (3)
C2—H2B	0.9600	C12—S1	1.740 (2)
C2—H2C	0.9600	C13—H13A	0.9600
C3—C8	1.381 (3)	C13—H13B	0.9600
C3—C4	1.397 (3)	C13—H13C	0.9600
C3—C9	1.522 (3)	C14—O4	1.204 (3)
C4—C5	1.372 (4)	C14—O5	1.340 (3)
C4—H4	0.9300	C15—O5	1.451 (3)
C5—C6	1.376 (4)	C15—C16	1.501 (5)
C5—H5	0.9300	C15—H15A	0.9700
C6—C7	1.378 (4)	C15—H15B	0.9700
C6—H6	0.9300	C16—H16A	0.9600
C7—C8	1.387 (4)	C16—H16B	0.9600
C7—H7	0.9300	C16—H16C	0.9600
C8—H8	0.9300	N1—H1	0.8600
C9—N1	1.462 (3)	O1—P1	1.4612 (15)
C9—P1	1.815 (2)	O2—P1	1.5697 (15)
C9—H9	0.9800	O3—P1	1.5625 (17)
C10—N2	1.315 (3)
O2—C1—H1A	109.5	C12—C11—C13	126.5 (2)
O2—C1—H1B	109.5	N2—C11—C13	117.8 (2)
H1A—C1—H1B	109.5	C11—C12—C14	129.6 (2)
O2—C1—H1C	109.5	C11—C12—S1	109.96 (17)
H1A—C1—H1C	109.5	C14—C12—S1	120.46 (19)
H1B—C1—H1C	109.5	C11—C13—H13A	109.5
O3—C2—H2A	109.5	C11—C13—H13B	109.5
O3—C2—H2B	109.5	H13A—C13—H13B	109.5
H2A—C2—H2B	109.5	C11—C13—H13C	109.5
O3—C2—H2C	109.5	H13A—C13—H13C	109.5
H2A—C2—H2C	109.5	H13B—C13—H13C	109.5
H2B—C2—H2C	109.5	O4—C14—O5	123.6 (2)
C8—C3—C4	118.8 (2)	O4—C14—C12	125.2 (3)
C8—C3—C9	120.25 (19)	O5—C14—C12	111.1 (2)
C4—C3—C9	120.9 (2)	O5—C15—C16	107.4 (3)
C5—C4—C3	120.7 (2)	O5—C15—H15A	110.2
C5—C4—H4	119.6	C16—C15—H15A	110.2
C3—C4—H4	119.6	O5—C15—H15B	110.2
C4—C5—C6	119.9 (2)	C16—C15—H15B	110.2
C4—C5—H5	120.0	H15A—C15—H15B	108.5
C6—C5—H5	120.0	C15—C16—H16A	109.5
C5—C6—C7	120.2 (3)	C15—C16—H16B	109.5
C5—C6—H6	119.9	H16A—C16—H16B	109.5
C7—C6—H6	119.9	C15—C16—H16C	109.5
C6—C7—C8	120.0 (2)	H16A—C16—H16C	109.5
C6—C7—H7	120.0	H16B—C16—H16C	109.5
C8—C7—H7	120.0	C10—N1—C9	122.15 (17)
C3—C8—C7	120.3 (2)	C10—N1—H1	118.9
C3—C8—H8	119.8	C9—N1—H1	118.9
C7—C8—H8	119.8	C10—N2—C11	110.26 (18)
N1—C9—C3	112.70 (17)	C1—O2—P1	121.86 (17)
N1—C9—P1	108.02 (14)	C2—O3—P1	120.73 (17)
C3—C9—P1	110.69 (14)	C14—O5—C15	116.3 (2)
N1—C9—H9	108.4	O1—P1—O3	115.59 (10)
C3—C9—H9	108.4	O1—P1—O2	114.25 (9)
P1—C9—H9	108.4	O3—P1—O2	102.76 (9)
N2—C10—N1	124.56 (19)	O1—P1—C9	113.98 (9)
N2—C10—S1	115.39 (16)	O3—P1—C9	103.11 (10)
N1—C10—S1	120.05 (15)	O2—P1—C9	105.80 (10)
C12—C11—N2	115.7 (2)	C12—S1—C10	88.65 (10)
C8—C3—C4—C5	0.1 (4)	N1—C10—N2—C11	−178.3 (2)
C9—C3—C4—C5	−179.7 (2)	S1—C10—N2—C11	1.8 (2)
C3—C4—C5—C6	−1.3 (4)	C12—C11—N2—C10	−2.3 (3)
C4—C5—C6—C7	1.5 (5)	C13—C11—N2—C10	176.9 (2)
C5—C6—C7—C8	−0.5 (4)	O4—C14—O5—C15	0.8 (4)
C4—C3—C8—C7	0.9 (4)	C12—C14—O5—C15	−178.5 (2)
C9—C3—C8—C7	−179.3 (2)	C16—C15—O5—C14	173.8 (2)
C6—C7—C8—C3	−0.7 (4)	C2—O3—P1—O1	26.7 (2)
C8—C3—C9—N1	124.9 (2)	C2—O3—P1—O2	−98.4 (2)
C4—C3—C9—N1	−55.3 (3)	C2—O3—P1—C9	151.7 (2)
C8—C3—C9—P1	−114.0 (2)	C1—O2—P1—O1	32.1 (2)
C4—C3—C9—P1	65.8 (2)	C1—O2—P1—O3	158.1 (2)
N2—C11—C12—C14	−178.7 (2)	C1—O2—P1—C9	−94.1 (2)
C13—C11—C12—C14	2.2 (4)	N1—C9—P1—O1	55.35 (17)
N2—C11—C12—S1	1.7 (3)	C3—C9—P1—O1	−68.48 (16)
C13—C11—C12—S1	−177.3 (2)	N1—C9—P1—O3	−70.74 (15)
C11—C12—C14—O4	3.9 (4)	C3—C9—P1—O3	165.43 (14)
S1—C12—C14—O4	−176.6 (2)	N1—C9—P1—O2	−178.29 (13)
C11—C12—C14—O5	−176.8 (2)	C3—C9—P1—O2	57.88 (15)
S1—C12—C14—O5	2.7 (3)	C11—C12—S1—C10	−0.55 (18)
N2—C10—N1—C9	−16.7 (3)	C14—C12—S1—C10	179.8 (2)
S1—C10—N1—C9	163.21 (16)	N2—C10—S1—C12	−0.75 (17)
C3—C9—N1—C10	−100.6 (2)	N1—C10—S1—C12	179.34 (19)
P1—C9—N1—C10	136.84 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1^i	0.86	2.02	2.791 (2)	148
C13—H13A···O4	0.96	2.36	3.077 (4)	131
C9—H9···N2	0.98	2.47	2.886 (3)	105

Symmetry code: (i) −x, −y+1, −z+2.