4-[(2,4-Dimethyl-1,3-oxazol-5-yl)meth­yl]-4-hydr­oxy-2-methyl­isoquinoline-1,3(2H,4H)-dione

In the title isoquinolinedione derivative, C₁₆H₁₆N₂O₄, the piperidine ring in the tetra­hydro­isoquinoline unit adopts a half-boat conformation. The essentially planar oxazole ring [maximum deviation = 0.004 (2) Å] is inclined at a dihedral angle of 36.00 (8)° to the tetra­hydro­isoquinoline unit. In the crystal structure, pairs of inter­molecular C—H...O and O—H...N inter­actions link the mol­ecules into chains incorporating R₂²(9) ring motifs. Two neighbouring chains are further inter­connected by inter­molecular C—H...O inter­actions into chains two mol­ecules wide along the a axis.

Key indicators

• Single-crystal X-ray study
• T = 100 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.050
• wR factor = 0.135
• Data-to-parameter ratio = 12.2

checkCIF/PLATON results

No syntax errors found



Alert level C
SHFSU01_ALERT_2_C  Test not performed. _refine_ls_shift/su_max and
            _refine_ls_shift/esd_max not present.
            Absolute value of the parameter shift to su ratio given   0.001
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) .....          2
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600         13
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600         12

Alert level G
PLAT720_ALERT_4_G Number of Unusual/Non-Standard Labels ..........          1
PLAT793_ALERT_4_G The Model has Chirality at C9      (Verify) ....          R

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

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   3 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

A series of isoquinoline-1,3,4-trione derivatives were identified as novel and potent inhibitors of caspase-3 through structural modification of the original compounds from high-throughput screening (Chen et al., 2006). Moreover, the series of isoquinoline-1,3,4-triones were found to be fast-acting post-emergence herbicides, producing symptoms of desiccation (Mitchell et al., 2000). These redox-active compounds are very potent stimulators of the light-dependent consumption of oxygen at photosystem in isolated chloroplasts (Mitchell et al., 1995). Isoquinoline-1,3,4-trione derivatives have a variety of biological activities and are synthetic precursors for many naturally occuring alkaloids (Hall et al., 1994; Malamas & Hohman, 1994). The crystal structure of the related Z-2-methyl-3'-phenyl-spiro[isoquinoline-4,2'-oxirane]-1,3-dione has been reported (Wang et al., 2000).

In the title isoquinoline-1,3-dione compound (Fig. 1), the piperidine ring (C1/N1/C2/C3/C8/C9) in the 1,2,3,4-tetrahydroisoquinolin moiety adopts a half-boat conformation (Cremer & Pople, 1975) with puckering parameters of Q = 0.3114 (19) Å, θ = 71.4 (3)° and ϕ = 114.9 (4)°. The oxazole ring (C11/C12/N2/C13/O4) is essentially planar with maximum deviation of -0.004 (2) Å at atom C13. The oxazole ring is inclined at a dihedral angle of 36.00 (8)° with the mean plane through 1,2,3,4-tetrahydroisoquinolin moiety. Bond lengths (Allen et al., 1987) and angles are normal and comparable to those related isoquinoline-1,3-dione structures (Wang et al., 2000; Subbiah Pandi et al., 2002).

In the crystal structure (Fig. 2), intermolecular O3—H1O3···N2 and C16—H16A···O1 hydrogen bonds (Table 1) link the molecules into one-dimensional chains along a axis incorporating R²₂(9) ring motifs (Bernstein et al., 1995). Two neighbouring chains are further interconnected by intermolecular C16—H16B···O1 hydrogen bonds into two-molecule-wide chains along the same axis.

Related literature

For general background to and applications of the title isoquinoline compound, see: Chen et al. (2006); Hall et al. (1994); Malamas & Hohman (1994); Mitchell et al. (1995, 2000). For ring conformations, see: Cremer & Pople (1975). For hydrogen-bond motifs, see: Bernstein et al. (1995). For related structures, see: Subbiah Pandi et al. (2002); Wang et al. (2000). For bond-length data, see: Allen et al. (1987). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986).

S2. Experimental

The title compound was obtained in the reaction between 1,3,4(2H)-isoquinolinetrione and 2,4,5-trimethyloxazole. The compound was purified by flash column chromatography in ethyl acetate and petroleum ether. X-ray quality single crystals of the title compound were obtained from slow evaporation of a chloroform solution. M.p. 434–436 K.

S3. Refinement

All the H atoms were located from difference Fourier map [range of C—H = 0.91 (2) - 1.01 (3) Å] and allowed to refine freely.

Computing details

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures

	Fig. 1. The structure of the title compound, showing the atom numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. The crystal structure of the title compound, showing two-molecule-wide chain along the a axis. H atoms not involved in intermolecular interactions (dashed lines) have been omitted for clarity.

4-[(2,4-Dimethyl-1,3-oxazol-5-yl)methyl]-4-hydroxy-2-methylisoquinoline- 1,3(2H,4H)-dione

Crystal data

C16H16N2O4	Z = 2
Mr = 300.31	F(000) = 316
Triclinic, P1	Dx = 1.421 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.3866 (5) Å	Cell parameters from 1833 reflections
b = 8.8044 (5) Å	θ = 4.4–32.7°
c = 10.6734 (7) Å	µ = 0.10 mm^−1
α = 103.997 (3)°	T = 100 K
β = 90.025 (3)°	Block, colourless
γ = 112.663 (2)°	0.24 × 0.19 × 0.08 mm
V = 701.80 (7) Å^3

Data collection

Bruker SMART APEXII CCD area-detector diffractometer	3198 independent reflections
Radiation source: fine-focus sealed tube	2401 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.034
ϕ and ω scans	θmax = 27.5°, θmin = 2.7°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −10→10
Tmin = 0.976, Tmax = 0.992	k = −11→11
6623 measured reflections	l = −13→13

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)] = 0.050	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.135	All H-atom parameters refined
S = 1.04	w = 1/[σ^2(Fo^2) + (0.0731P)^2 + 0.0844P] where P = (Fo^2 + 2Fc^2)/3
3198 reflections	(Δ/σ)max < 0.001
263 parameters	Δρmax = 0.40 e Å^−3
0 restraints	Δρmin = −0.28 e Å^−3

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1)K.

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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	1.23014 (16)	0.40877 (16)	0.32581 (13)	0.0234 (3)
O2	0.76462 (17)	0.27268 (17)	0.04028 (14)	0.0269 (3)
O3	1.13932 (17)	0.07862 (17)	0.33591 (13)	0.0224 (3)
O4	0.78937 (15)	0.36205 (15)	0.40053 (12)	0.0185 (3)
N1	0.99911 (18)	0.34315 (18)	0.18332 (15)	0.0175 (3)
N2	0.50707 (18)	0.22071 (19)	0.33559 (15)	0.0186 (3)
C1	1.0928 (2)	0.3023 (2)	0.26656 (17)	0.0175 (4)
C2	0.8503 (2)	0.2243 (2)	0.10092 (18)	0.0187 (4)
C3	0.8116 (2)	0.0419 (2)	0.08846 (17)	0.0175 (4)
C4	0.6900 (2)	−0.0817 (2)	−0.01212 (19)	0.0217 (4)
C5	0.6559 (2)	−0.2517 (3)	−0.0275 (2)	0.0249 (4)
C6	0.7436 (3)	−0.3003 (2)	0.0555 (2)	0.0249 (4)
C7	0.8637 (2)	−0.1782 (2)	0.15593 (19)	0.0209 (4)
C8	0.8972 (2)	−0.0063 (2)	0.17380 (17)	0.0171 (4)
C9	1.0118 (2)	0.1260 (2)	0.29105 (18)	0.0175 (4)
C10	0.8979 (2)	0.1419 (3)	0.40732 (18)	0.0191 (4)
C11	0.7513 (2)	0.1891 (2)	0.38373 (17)	0.0172 (4)
C12	0.5796 (2)	0.1033 (2)	0.34423 (17)	0.0180 (4)
C13	0.6360 (2)	0.3692 (2)	0.36869 (17)	0.0179 (4)
C14	1.0594 (3)	0.5246 (2)	0.1865 (2)	0.0238 (4)
C15	0.4717 (3)	−0.0836 (2)	0.3101 (2)	0.0238 (4)
C16	0.6387 (2)	0.5395 (2)	0.3724 (2)	0.0216 (4)
H1O3	1.243 (4)	0.142 (3)	0.321 (3)	0.054 (8)*
H4A	0.637 (3)	−0.043 (3)	−0.065 (2)	0.033 (6)*
H5A	0.574 (3)	−0.336 (3)	−0.097 (2)	0.031 (6)*
H6A	0.722 (3)	−0.420 (3)	0.045 (2)	0.029 (6)*
H7A	0.924 (3)	−0.208 (2)	0.217 (2)	0.019 (5)*
H10A	0.855 (3)	0.032 (3)	0.430 (2)	0.024 (5)*
H10B	0.979 (3)	0.226 (3)	0.484 (2)	0.024 (5)*
H14A	1.064 (3)	0.595 (3)	0.277 (3)	0.045 (7)*
H14B	0.985 (3)	0.538 (3)	0.127 (3)	0.048 (7)*
H14C	1.175 (4)	0.565 (3)	0.154 (3)	0.052 (8)*
H15A	0.436 (3)	−0.124 (3)	0.215 (3)	0.037 (6)*
H15B	0.530 (3)	−0.148 (3)	0.337 (2)	0.040 (7)*
H15C	0.360 (3)	−0.114 (3)	0.349 (3)	0.047 (7)*
H16A	0.526 (3)	0.529 (3)	0.344 (2)	0.037 (6)*
H16B	0.682 (3)	0.622 (3)	0.461 (3)	0.039 (6)*
H16C	0.718 (4)	0.594 (3)	0.314 (3)	0.053 (8)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0134 (6)	0.0238 (7)	0.0300 (8)	0.0053 (5)	−0.0010 (5)	0.0053 (6)
O2	0.0215 (7)	0.0300 (8)	0.0333 (8)	0.0113 (6)	−0.0025 (6)	0.0136 (6)
O3	0.0105 (6)	0.0283 (7)	0.0340 (8)	0.0096 (6)	0.0033 (5)	0.0151 (6)
O4	0.0104 (6)	0.0223 (7)	0.0219 (7)	0.0072 (5)	0.0009 (5)	0.0026 (5)
N1	0.0133 (7)	0.0185 (7)	0.0224 (8)	0.0073 (6)	0.0023 (6)	0.0070 (6)
N2	0.0116 (7)	0.0221 (8)	0.0226 (8)	0.0077 (6)	0.0020 (6)	0.0052 (6)
C1	0.0132 (8)	0.0217 (9)	0.0203 (9)	0.0095 (7)	0.0049 (7)	0.0063 (7)
C2	0.0126 (8)	0.0260 (9)	0.0204 (9)	0.0092 (7)	0.0053 (7)	0.0088 (7)
C3	0.0113 (8)	0.0210 (9)	0.0203 (9)	0.0062 (7)	0.0045 (7)	0.0057 (7)
C4	0.0157 (9)	0.0290 (10)	0.0205 (9)	0.0086 (8)	0.0036 (7)	0.0073 (8)
C5	0.0167 (9)	0.0267 (10)	0.0240 (10)	0.0045 (8)	0.0035 (8)	0.0004 (8)
C6	0.0225 (10)	0.0201 (10)	0.0315 (11)	0.0087 (8)	0.0095 (8)	0.0055 (8)
C7	0.0167 (9)	0.0220 (9)	0.0271 (10)	0.0098 (8)	0.0055 (7)	0.0086 (8)
C8	0.0115 (8)	0.0212 (9)	0.0203 (9)	0.0075 (7)	0.0058 (7)	0.0070 (7)
C9	0.0112 (8)	0.0249 (9)	0.0210 (9)	0.0102 (7)	0.0026 (7)	0.0090 (7)
C10	0.0122 (8)	0.0270 (10)	0.0199 (9)	0.0086 (7)	0.0022 (7)	0.0079 (8)
C11	0.0133 (8)	0.0224 (9)	0.0162 (9)	0.0075 (7)	0.0033 (7)	0.0047 (7)
C12	0.0143 (8)	0.0236 (9)	0.0174 (9)	0.0087 (7)	0.0025 (7)	0.0055 (7)
C13	0.0108 (8)	0.0256 (10)	0.0169 (9)	0.0080 (7)	0.0009 (6)	0.0036 (7)
C14	0.0230 (10)	0.0190 (9)	0.0302 (11)	0.0084 (8)	0.0015 (8)	0.0077 (8)
C15	0.0157 (9)	0.0219 (10)	0.0333 (12)	0.0055 (8)	0.0027 (8)	0.0099 (8)
C16	0.0139 (9)	0.0216 (9)	0.0285 (11)	0.0067 (7)	0.0011 (8)	0.0059 (8)

Geometric parameters (Å, º)

O1—C1	1.219 (2)	C6—H6A	0.98 (2)
O2—C2	1.219 (2)	C7—C8	1.392 (2)
O3—C9	1.4096 (19)	C7—H7A	0.97 (2)
O3—H1O3	0.87 (3)	C8—C9	1.510 (2)
O4—C13	1.3590 (19)	C9—C10	1.579 (3)
O4—C11	1.395 (2)	C10—C11	1.481 (2)
N1—C1	1.381 (2)	C10—H10A	0.99 (2)
N1—C2	1.405 (2)	C10—H10B	1.00 (2)
N1—C14	1.469 (2)	C11—C12	1.352 (2)
N2—C13	1.300 (2)	C12—C15	1.491 (3)
N2—C12	1.407 (2)	C13—C16	1.481 (3)
C1—C9	1.524 (2)	C14—H14A	1.01 (3)
C2—C3	1.482 (2)	C14—H14B	0.94 (3)
C3—C8	1.395 (2)	C14—H14C	0.99 (3)
C3—C4	1.398 (3)	C15—H15A	1.00 (3)
C4—C5	1.379 (3)	C15—H15B	0.97 (2)
C4—H4A	0.91 (2)	C15—H15C	0.99 (3)
C5—C6	1.391 (3)	C16—H16A	0.95 (2)
C5—H5A	0.96 (2)	C16—H16B	1.01 (3)
C6—C7	1.388 (3)	C16—H16C	0.98 (3)
C9—O3—H1O3	111.7 (18)	C1—C9—C10	106.39 (14)
C13—O4—C11	105.09 (13)	C11—C10—C9	115.98 (15)
C1—N1—C2	124.28 (14)	C11—C10—H10A	110.1 (12)
C1—N1—C14	116.33 (15)	C9—C10—H10A	106.9 (13)
C2—N1—C14	119.36 (14)	C11—C10—H10B	111.0 (12)
C13—N2—C12	105.17 (14)	C9—C10—H10B	106.8 (12)
O1—C1—N1	120.67 (16)	H10A—C10—H10B	105.3 (17)
O1—C1—C9	121.09 (15)	C12—C11—O4	107.30 (14)
N1—C1—C9	118.01 (15)	C12—C11—C10	135.61 (17)
O2—C2—N1	120.21 (16)	O4—C11—C10	117.05 (15)
O2—C2—C3	123.36 (17)	C11—C12—N2	108.95 (15)
N1—C2—C3	116.36 (14)	C11—C12—C15	129.76 (17)
C8—C3—C4	120.28 (16)	N2—C12—C15	121.29 (15)
C8—C3—C2	120.80 (16)	N2—C13—O4	113.49 (15)
C4—C3—C2	118.91 (16)	N2—C13—C16	129.41 (16)
C5—C4—C3	119.75 (18)	O4—C13—C16	117.08 (15)
C5—C4—H4A	123.9 (14)	N1—C14—H14A	110.5 (14)
C3—C4—H4A	116.4 (14)	N1—C14—H14B	109.2 (15)
C4—C5—C6	120.24 (18)	H14A—C14—H14B	112 (2)
C4—C5—H5A	119.7 (13)	N1—C14—H14C	110.9 (15)
C6—C5—H5A	120.0 (13)	H14A—C14—H14C	110 (2)
C7—C6—C5	120.25 (18)	H14B—C14—H14C	104 (2)
C7—C6—H6A	118.6 (13)	C12—C15—H15A	108.7 (13)
C5—C6—H6A	121.1 (13)	C12—C15—H15B	112.9 (14)
C6—C7—C8	120.05 (18)	H15A—C15—H15B	111 (2)
C6—C7—H7A	122.2 (12)	C12—C15—H15C	113.7 (15)
C8—C7—H7A	117.7 (12)	H15A—C15—H15C	104 (2)
C7—C8—C3	119.42 (17)	H15B—C15—H15C	106 (2)
C7—C8—C9	120.71 (16)	C13—C16—H16A	110.0 (14)
C3—C8—C9	119.63 (15)	C13—C16—H16B	112.3 (13)
O3—C9—C8	112.25 (14)	H16A—C16—H16B	111 (2)
O3—C9—C1	111.38 (14)	C13—C16—H16C	112.0 (16)
C8—C9—C1	111.91 (14)	H16A—C16—H16C	106 (2)
O3—C9—C10	105.32 (14)	H16B—C16—H16C	105 (2)
C8—C9—C10	109.17 (14)
C2—N1—C1—O1	172.69 (16)	C3—C8—C9—C1	−29.7 (2)
C14—N1—C1—O1	−9.2 (3)	C7—C8—C9—C10	−86.56 (19)
C2—N1—C1—C9	−12.7 (2)	C3—C8—C9—C10	87.76 (19)
C14—N1—C1—C9	165.40 (16)	O1—C1—C9—O3	−27.0 (2)
C1—N1—C2—O2	172.40 (17)	N1—C1—C9—O3	158.35 (15)
C14—N1—C2—O2	−5.6 (3)	O1—C1—C9—C8	−153.60 (16)
C1—N1—C2—C3	−10.5 (2)	N1—C1—C9—C8	31.8 (2)
C14—N1—C2—C3	171.54 (16)	O1—C1—C9—C10	87.24 (19)
O2—C2—C3—C8	−170.30 (17)	N1—C1—C9—C10	−87.39 (18)
N1—C2—C3—C8	12.7 (2)	O3—C9—C10—C11	−179.26 (15)
O2—C2—C3—C4	11.0 (3)	C8—C9—C10—C11	−58.5 (2)
N1—C2—C3—C4	−166.05 (16)	C1—C9—C10—C11	62.40 (19)
C8—C3—C4—C5	−0.6 (3)	C13—O4—C11—C12	−0.42 (18)
C2—C3—C4—C5	178.13 (17)	C13—O4—C11—C10	177.85 (15)
C3—C4—C5—C6	−0.8 (3)	C9—C10—C11—C12	95.1 (3)
C4—C5—C6—C7	1.1 (3)	C9—C10—C11—O4	−82.6 (2)
C5—C6—C7—C8	−0.1 (3)	O4—C11—C12—N2	0.00 (19)
C6—C7—C8—C3	−1.3 (3)	C10—C11—C12—N2	−177.81 (19)
C6—C7—C8—C9	173.05 (17)	O4—C11—C12—C15	178.81 (18)
C4—C3—C8—C7	1.6 (3)	C10—C11—C12—C15	1.0 (4)
C2—C3—C8—C7	−177.07 (16)	C13—N2—C12—C11	0.4 (2)
C4—C3—C8—C9	−172.78 (16)	C13—N2—C12—C15	−178.48 (17)
C2—C3—C8—C9	8.5 (3)	C12—N2—C13—O4	−0.7 (2)
C7—C8—C9—O3	29.8 (2)	C12—N2—C13—C16	177.28 (19)
C3—C8—C9—O3	−155.84 (15)	C11—O4—C13—N2	0.75 (19)
C7—C8—C9—C1	155.93 (16)	C11—O4—C13—C16	−177.54 (16)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H1O3···N2^i	0.87 (3)	2.04 (3)	2.847 (2)	153 (3)
C16—H16A···O1^ii	0.96 (3)	2.28 (3)	3.162 (2)	153 (2)
C16—H16B···O1^iii	1.01 (3)	2.50 (3)	3.270 (2)	132.9 (19)

Symmetry codes: (i) x+1, y, z; (ii) x−1, y, z; (iii) −x+2, −y+1, −z+1.