Ethyl 4-methyl-1,3-dioxo-1,2,3,4-tetra­hydro­isoquinoline-4-carboxyl­ate

Li, X.-Y.; Wu, J.-L.

doi:10.1107/S1600536812008136

organic compounds

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ISSN: 2056-9890

Volume 68| Part 3| March 2012| Page o891

doi:10.1107/S1600536812008136

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Ethyl 4-methyl-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate

Xing-Yao Li ^a and Jin-Long Wu ^a ^*

^aLaboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China
^*Correspondence e-mail: wyz@zju.edu.cn

(Received 18 February 2012; accepted 23 February 2012; online 29 February 2012)

In the title compound, C₁₃H₁₃NO₄, the fused-ring system is nearly planar, with an r.m.s. deviation of 0.0408 Å. In the crystal, molecules are linked into centrosymmetric dimers by a pair of N—H⋯O hydrogen bonds. The ethyl group is disordered over two positions in a ratio of 0.758 (6):0.242 (6).

Related literature

For pharmaceutical usage of derivatives of isoquinoline-1,3(2H,4H)-dione, see: Lu et al. (2010 ); Tsou et al. (2008 , 2009 ); Billamboz et al. (2011 ).

Experimental

Crystal data

C₁₃H₁₃NO₄
M_r = 247.24
Triclinic, $[P \overline 1]$
a = 6.4585 (9) Å
b = 8.1999 (7) Å
c = 12.5763 (11) Å
α = 78.876 (7)°
β = 77.228 (9)°
γ = 72.354 (9)°
V = 613.28 (11) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 293 K
0.38 × 0.23 × 0.09 mm

Data collection

Agilent Xcalibur Atlas Gemini ultra diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010 ) T_min = 0.963, T_max = 0.991
3820 measured reflections
2243 independent reflections
1659 reflections with I > 2σ(I)
R_int = 0.021

Refinement

R[F² > 2σ(F²)] = 0.049
wR(F²) = 0.135
S = 1.06
2243 reflections
170 parameters
5 restraints
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1ⁱ	0.86	2.05	2.903 (3)	172
Symmetry code: (i) -x, -y, -z+1.

Data collection: CrysAlis PRO (Agilent, 2010); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009 ); software used to prepare material for publication: OLEX2.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812008136/xu5472sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812008136/xu5472Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812008136/xu5472Isup3.cml

checkCIF report

Comment top

Derivatives of isoquinoline-1,3(2H,4H)-dione are important compounds in pharmaceutical chemistry and have great research values, such as inhibitors of the cyclic-dependent kinase 4 (CDK4) (Tsou et al., 2008, 2009; Lu et al.., 2010); inhibitors of HIV-1 integrase (Billamboz et al., 2011). In our research of synthesis of cyclonitrones, we have obtained the title compound as a minor product from ethyl 2-(2-(1,3-dioxolan-2-yl)phenyl)-2-cyanopropanoate hydrolysed by hydrogen peroxide. The structure of the title compound has been characterized by spectroscopic methods and further confirmation by X-ray analysis. We report here its crystal structure. In the molecule of the title compound (Fig. 1), there is one benzene ring fused by carbonyl amide closing six-membered heterocyclic ring, the two rings are almost coplanar with only 1.02 (10)° dihedral angle. One sterogenic center but the crystallizes as a racemate as indicated by the centrosymmetric space group. In the crystal structure, molecules are linked by two N—H···O hydrogen bonds into dimers that are located on centres of inversion.

Related literature top

For pharmaceutical usage of derivatives of isoquinoline-1,3(2H,4H)-dione, see: Lu et al. (2010); Tsou et al. (2008, 2009); Billamboz et al. (2011).

Experimental top

At room temperature, to a solution of ethyl 2-(2-(1,3-dioxolan-2-yl) phenyl)-2-cyanopropanoate (344 mg, 1.25 mmol) in DMSO (3.0 ml) was added K₂CO₃ (89 mg, 0.64 eq), after then H₂O₂ (0.55 mL, 30%, 4 eq) was added as three portions in 2 hours. The mixture was then stirred for another 1h and quenched with brine (20 mL). The resulting mixture was subjected to extraction with ethyl acetate (2 x 30 mL). The combined organic phase was washed with brine (2 x 20 mL), dried over Na₂SO₄, concentrated in vacuo, and the residue was subjected to flash chromatography (silica gel, 25% ethyl acetate in hexane) to give ethyl 2-(2-(1,3-dioxolan-2-yl)phenyl)-3-amino-2-methyl-3-oxopropanoate (264 mg, 72%) as a colorless solid and the title compound, ethyl 4-methyl-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate (50 mg, 16%) as colorless needles (m.p. 440-441.5 K). Single crystals suitable for X-ray diffraction of the title compound were grown at ambient temperature in dichloromethane.

Computing details top

Data collection: CrysAlis PRO (Agilent, 2010); cell refinement: CrysAlis PRO (Agilent, 2010); data reduction: CrysAlis PRO (Agilent, 2010); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures top

	Fig. 1. The molecular structure of the title compound with displacement ellipsoids are drawn at 30% probability level. H atoms are presented as a small spheres of arbitrary radius.
	Fig. 2. Centrosymmetric dimers of the title compound linked by two N—H···O hydrogen bonds (dotted lines). Symmetry code: (i) -x, -y, -z+1.

Ethyl 4-methyl-1,3-dioxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate top

Crystal data top

C₁₃H₁₃NO₄	Z = 2
M_r = 247.24	F(000) = 260
Triclinic, P1	D_x = 1.339 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.4585 (9) Å	Cell parameters from 1387 reflections
b = 8.1999 (7) Å	θ = 3.3–29.2°
c = 12.5763 (11) Å	µ = 0.10 mm⁻¹
α = 78.876 (7)°	T = 293 K
β = 77.228 (9)°	Platelet, colorless
γ = 72.354 (9)°	0.38 × 0.23 × 0.09 mm
V = 613.28 (11) Å³

Data collection top

Agilent Xcalibur Atlas Gemini ultra diffractometer	2243 independent reflections
Radiation source: fine-focus sealed tube	1659 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.021
Detector resolution: 10.3592 pixels mm^-1	θ_max = 25.4°, θ_min = 3.3°
ω scans	h = −7→6
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010)	k = −9→9
T_min = 0.963, T_max = 0.991	l = −14→15
3820 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.135	H-atom parameters constrained
S = 1.06	w = 1/[σ²(F_o²) + (0.061P)² + 0.1013P] where P = (F_o² + 2F_c²)/3
2243 reflections	(Δ/σ)_max < 0.001
170 parameters	Δρ_max = 0.18 e Å⁻³
5 restraints	Δρ_min = −0.25 e Å⁻³

Crystal data top

C₁₃H₁₃NO₄	γ = 72.354 (9)°
M_r = 247.24	V = 613.28 (11) Å³
Triclinic, P1	Z = 2
a = 6.4585 (9) Å	Mo Kα radiation
b = 8.1999 (7) Å	µ = 0.10 mm⁻¹
c = 12.5763 (11) Å	T = 293 K
α = 78.876 (7)°	0.38 × 0.23 × 0.09 mm
β = 77.228 (9)°

Data collection top

Agilent Xcalibur Atlas Gemini ultra diffractometer	2243 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2010)	1659 reflections with I > 2σ(I)
T_min = 0.963, T_max = 0.991	R_int = 0.021
3820 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.049	5 restraints
wR(F²) = 0.135	H-atom parameters constrained
S = 1.06	Δρ_max = 0.18 e Å⁻³
2243 reflections	Δρ_min = −0.25 e Å⁻³
170 parameters

Special details top

Experimental. ¹H NMR (400 MHz, CDCl₃): 8.37 (br s, 1H), 8.26 (d, J = 8.0 Hz, 1H), 7.68 (t, J = 8.0 Hz, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 4.23-4.05 (m, 2H), 1.89 (s, 3H), 1.12 (t, J = 7.2 Hz, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): 171.1, 169.1, 163.6, 140.1, 134.8, 128.9, 128.6, 125.9, 123.5, 62.6, 55.0, 25.1, 13.7 ppm.

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 (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
O1	0.2337 (3)	−0.13049 (17)	0.54786 (12)	0.0529 (4)
O2	−0.1215 (2)	0.40108 (18)	0.63638 (13)	0.0527 (4)
O3	0.1682 (3)	0.4585 (2)	0.83716 (14)	0.0734 (6)
O4	−0.0080 (3)	0.2543 (2)	0.86413 (12)	0.0610 (5)
N1	0.0689 (3)	0.13902 (19)	0.58943 (13)	0.0379 (4)
H1	−0.0268	0.1471	0.5494	0.046*
C1	0.5645 (4)	−0.1829 (3)	0.67306 (17)	0.0453 (5)
H1A	0.5636	−0.2759	0.6411	0.054*
C2	0.7280 (4)	−0.1987 (3)	0.7311 (2)	0.0559 (6)
H2	0.8373	−0.3023	0.7390	0.067*
C3	0.7288 (4)	−0.0596 (3)	0.7776 (2)	0.0578 (6)
H3	0.8405	−0.0696	0.8161	0.069*
C4	0.5663 (4)	0.0937 (3)	0.76769 (18)	0.0477 (6)
H4	0.5684	0.1858	0.8001	0.057*
C5	0.3988 (3)	0.1116 (2)	0.70940 (15)	0.0333 (4)
C6	0.4003 (3)	−0.0284 (2)	0.66182 (14)	0.0333 (4)
C7	0.2317 (3)	−0.0136 (2)	0.59585 (15)	0.0353 (5)
C8	0.0413 (3)	0.2804 (2)	0.63970 (15)	0.0338 (4)
C9	0.2282 (3)	0.2843 (2)	0.69348 (14)	0.0325 (4)
C10	0.3389 (4)	0.4169 (3)	0.61867 (18)	0.0478 (5)
H10A	0.4522	0.4298	0.6520	0.072*
H10B	0.2307	0.5261	0.6088	0.072*
H10C	0.4030	0.3776	0.5485	0.072*
C11	0.1267 (3)	0.3452 (3)	0.80564 (17)	0.0420 (5)
C12	−0.1109 (6)	0.3031 (5)	0.9735 (2)	0.0928 (10)
H12A	0.0009	0.2758	1.0194	0.111*	0.758 (6)
H12B	−0.1798	0.4266	0.9674	0.111*	0.758 (6)
H12C	−0.0798	0.2026	1.0286	0.111*	0.242 (6)
H12D	−0.0493	0.3888	0.9884	0.111*	0.242 (6)
C13	−0.2713 (9)	0.2137 (8)	1.0226 (3)	0.1076 (18)	0.758 (6)
H13A	−0.3858	0.2455	0.9791	0.161*	0.758 (6)
H13B	−0.3334	0.2432	1.0954	0.161*	0.758 (6)
H13C	−0.2036	0.0915	1.0268	0.161*	0.758 (6)
C13A	−0.340 (2)	0.371 (2)	0.9802 (11)	0.1076 (18)	0.242 (6)
H13D	−0.3722	0.4842	0.9389	0.161*	0.242 (6)
H13E	−0.4090	0.3774	1.0558	0.161*	0.242 (6)
H13F	−0.3969	0.2969	0.9504	0.161*	0.242 (6)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0628 (10)	0.0400 (8)	0.0648 (10)	−0.0090 (7)	−0.0201 (8)	−0.0254 (7)
O2	0.0404 (9)	0.0454 (9)	0.0740 (10)	0.0051 (7)	−0.0223 (7)	−0.0247 (8)
O3	0.0921 (14)	0.0731 (11)	0.0728 (11)	−0.0273 (10)	−0.0124 (10)	−0.0462 (10)
O4	0.0681 (11)	0.0740 (11)	0.0415 (8)	−0.0234 (9)	0.0101 (7)	−0.0258 (8)
N1	0.0375 (10)	0.0385 (9)	0.0429 (9)	−0.0059 (7)	−0.0146 (7)	−0.0159 (7)
C1	0.0484 (13)	0.0332 (11)	0.0496 (12)	−0.0030 (9)	−0.0069 (10)	−0.0094 (9)
C2	0.0492 (14)	0.0422 (12)	0.0656 (15)	0.0057 (10)	−0.0151 (11)	−0.0057 (11)
C3	0.0463 (14)	0.0610 (15)	0.0650 (15)	−0.0035 (12)	−0.0275 (11)	−0.0035 (12)
C4	0.0460 (13)	0.0464 (12)	0.0569 (13)	−0.0082 (10)	−0.0224 (10)	−0.0133 (10)
C5	0.0323 (10)	0.0331 (10)	0.0342 (10)	−0.0069 (8)	−0.0043 (8)	−0.0089 (8)
C6	0.0351 (11)	0.0307 (10)	0.0323 (10)	−0.0078 (8)	−0.0024 (8)	−0.0062 (8)
C7	0.0385 (11)	0.0320 (10)	0.0371 (10)	−0.0104 (9)	−0.0027 (8)	−0.0114 (8)
C8	0.0323 (11)	0.0333 (10)	0.0367 (10)	−0.0072 (8)	−0.0050 (8)	−0.0112 (8)
C9	0.0329 (10)	0.0293 (9)	0.0380 (10)	−0.0073 (8)	−0.0070 (8)	−0.0116 (8)
C10	0.0494 (13)	0.0361 (11)	0.0607 (13)	−0.0152 (10)	−0.0107 (10)	−0.0058 (10)
C11	0.0405 (12)	0.0409 (11)	0.0459 (12)	−0.0019 (10)	−0.0133 (9)	−0.0168 (10)
C12	0.094 (2)	0.134 (3)	0.0461 (15)	−0.029 (2)	0.0168 (14)	−0.0391 (17)
C13	0.125 (4)	0.143 (5)	0.059 (3)	−0.068 (4)	0.035 (2)	−0.030 (3)
C13A	0.125 (4)	0.143 (5)	0.059 (3)	−0.068 (4)	0.035 (2)	−0.030 (3)

Geometric parameters (Å, º) top

O1—C7	1.223 (2)	C6—C7	1.473 (3)
O2—C8	1.208 (2)	C8—C9	1.519 (3)
O3—C11	1.197 (2)	C9—C11	1.527 (3)
O4—C11	1.324 (3)	C9—C10	1.535 (3)
O4—C12	1.463 (3)	C10—H10A	0.9600
N1—C7	1.371 (2)	C10—H10B	0.9600
N1—C8	1.372 (2)	C10—H10C	0.9600
N1—H1	0.8600	C12—C13A	1.406 (13)
C1—C2	1.373 (3)	C12—C13	1.412 (5)
C1—C6	1.390 (3)	C12—H12A	0.9700
C1—H1A	0.9300	C12—H12B	0.9700
C2—C3	1.380 (3)	C12—H12C	0.9700
C2—H2	0.9300	C12—H12D	0.9700
C3—C4	1.376 (3)	C13—H13A	0.9600
C3—H3	0.9300	C13—H13B	0.9600
C4—C5	1.394 (3)	C13—H13C	0.9600
C4—H4	0.9300	C13A—H13D	0.9600
C5—C6	1.390 (2)	C13A—H13E	0.9600
C5—C9	1.517 (2)	C13A—H13F	0.9600

C11—O4—C12	115.2 (2)	C9—C10—H10C	109.5
C7—N1—C8	127.34 (15)	H10A—C10—H10C	109.5
C7—N1—H1	116.3	H10B—C10—H10C	109.5
C8—N1—H1	116.3	O3—C11—O4	124.5 (2)
C2—C1—C6	120.26 (19)	O3—C11—C9	123.9 (2)
C2—C1—H1A	119.9	O4—C11—C9	111.54 (16)
C6—C1—H1A	119.9	C13A—C12—C13	54.0 (7)
C1—C2—C3	119.5 (2)	C13A—C12—O4	110.5 (6)
C1—C2—H2	120.3	C13—C12—O4	110.2 (3)
C3—C2—H2	120.3	C13A—C12—H12A	139.8
C4—C3—C2	120.8 (2)	C13—C12—H12A	109.6
C4—C3—H3	119.6	O4—C12—H12A	109.6
C2—C3—H3	119.6	C13A—C12—H12B	58.6
C3—C4—C5	120.40 (19)	C13—C12—H12B	109.6
C3—C4—H4	119.8	O4—C12—H12B	109.6
C5—C4—H4	119.8	H12A—C12—H12B	108.1
C6—C5—C4	118.45 (18)	C13A—C12—H12C	109.5
C6—C5—C9	121.52 (16)	C13—C12—H12C	58.8
C4—C5—C9	119.93 (16)	O4—C12—H12C	109.5
C1—C6—C5	120.58 (18)	H12A—C12—H12C	54.2
C1—C6—C7	118.94 (17)	H12B—C12—H12C	140.7
C5—C6—C7	120.46 (16)	C13A—C12—H12D	109.5
O1—C7—N1	120.24 (17)	C13—C12—H12D	140.2
O1—C7—C6	122.58 (17)	O4—C12—H12D	109.5
N1—C7—C6	117.17 (15)	H12A—C12—H12D	56.7
O2—C8—N1	120.90 (17)	H12B—C12—H12D	54.3
O2—C8—C9	121.31 (15)	H12C—C12—H12D	108.1
N1—C8—C9	117.70 (15)	C12—C13—H13A	109.5
C5—C9—C8	114.29 (15)	C12—C13—H13B	109.5
C5—C9—C11	108.88 (15)	C12—C13—H13C	109.5
C8—C9—C11	107.75 (15)	C12—C13A—H13D	109.5
C5—C9—C10	109.59 (16)	C12—C13A—H13E	109.5
C8—C9—C10	106.40 (15)	H13D—C13A—H13E	109.5
C11—C9—C10	109.85 (16)	C12—C13A—H13F	109.5
C9—C10—H10A	109.5	H13D—C13A—H13F	109.5
C9—C10—H10B	109.5	H13E—C13A—H13F	109.5
H10A—C10—H10B	109.5

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1ⁱ	0.86	2.05	2.903 (3)	172

Symmetry code: (i) −x, −y, −z+1.

Experimental details

Crystal data
Chemical formula	C₁₃H₁₃NO₄
M_r	247.24
Crystal system, space group	Triclinic, P1
Temperature (K)	293
a, b, c (Å)	6.4585 (9), 8.1999 (7), 12.5763 (11)
α, β, γ (°)	78.876 (7), 77.228 (9), 72.354 (9)
V (Å³)	613.28 (11)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.38 × 0.23 × 0.09

Data collection
Diffractometer	Agilent Xcalibur Atlas Gemini ultra diffractometer
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2010)
T_min, T_max	0.963, 0.991
No. of measured, independent and observed [I > 2σ(I)] reflections	3820, 2243, 1659
R_int	0.021
(sin θ/λ)_max (Å⁻¹)	0.602

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.135, 1.06
No. of reflections	2243
No. of parameters	170
No. of restraints	5
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.25

Computer programs: CrysAlis PRO (Agilent, 2010), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1ⁱ	0.86	2.05	2.903 (3)	172

Symmetry code: (i) −x, −y, −z+1.

Acknowledgements

This work was supported by a research grant from the Zhejiang Provincial Natural Science Foundation of China (grant No. Y207295). We thank Mr J. Gu for his valuable help and Mr J. Liu for his assistance in data collection.

References

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