4-[(1,3-Dioxo-2,3-dihydro-1H-isoindol-2-yl)meth­yl]phthalonitrile

In the title compound, C₁₇H₉N₃O₂, the phthalonitrile group and the isoindole-1,3-dione group lie in approximately orthogonal planes and exhibit a dihedral angle of 92.76 (8)°. Partial face-to-face overlap is observed between the two groups. In addition, the crystal packing is stabilized by C—H...O and C—H...N inter­actions.

Key indicators

• Single-crystal X-ray study
• T = 298 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.037
• wR factor = 0.117
• Data-to-parameter ratio = 13.2

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT063_ALERT_3_C Crystal Probably too Large for Beam Size .......       0.70 mm
PLAT371_ALERT_2_C Long   C(sp2)-C(sp1) Bond  C1     -   C7     ...       1.44 Ang.
PLAT371_ALERT_2_C Long   C(sp2)-C(sp1) Bond  C2     -   C8     ...       1.43 Ang.

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

   0 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
   1 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion

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S1. Comment

The title compound, (I), is a precursor for the synthesis of amphiphilic phthalocyanine, which is utilized in the photodynamic therapy (PDT) of tumors (Huang et al., 2000). After phthalocyanine is formed, the phthalimide is easily converted to an amine, which is believed to have a better interaction with cell tissues. In the structure of a similar precursor (Zhu et al., 2005), the two groups are connected by a flexible butoxy chain. The difference between the earlier structure and (I) is that there is no O atom linked to the phthalocynine ring, and we are investigating if this O atom will or will not influence the yield of active ¹O₂ in PDT (Kobayashi et al., 2003).

The molecular structure of (I) is shown in Fig. 1. The cyano-group N1—C7 [1.130 (3) Å] and N2—C8 bonds [1.137 (3) Å] are short enough to indicate their triple-bond character, and agree with the values reported by Zhu et al. (2005). The C1—C7 [1.436 (3) Å] and C2—C8 [1.435 (3) Å] bond distances are comparable to the mean value of phthalonitrile, 1.443 (8) Å, reported by Allen et al. (1987). The benzene ring of the phthalonitrile group and the isoindole ring system are perpendicular to each other, with an angle of 92.76 (8)°.

In the crystal packing, the molecules are stacked along the short a axis with weak π–π interactions due to the partial overlap of the C1–C6 benzene rings and the isoindole ring systems, with perpendicular distances of 3.556 and 3.150 Å, respectively. In addition, the molecular packing is stabilized by C—H···O and C—H···N interactions (Table 1).

S2. Experimental

4-Methylphthalic anhydride (50 g, 308 mmol) and urea (18.5 g, 308 mmol) were mixed and heated to 433 K; the mixture melted then solidified. The solid was washed with water and vacuum dried at 353 K to give 4-methylphthalimide (yield 87%, 43.5 g; m.p. 470.8–471.4 K). All of the 4-methylphthalimide obtained was suspended in methanol (800 ml) and stirred for 5–7 days at room temperature while ammonia gas was pumped into the vessel. As the reaction progressed, the suspension dissolved and then a new suspension formed. After filtering and drying at 343 K, 4-methylphthalic diamide was obtained (yield 30%, 12 g; m.p. 455.4–455.6 K). 4-Methylphthalic diamide (10 g, 56.1 mmol) was suspended in pyridine (150 ml) and POCl₃ (13 ml, 142 mmol) was added dropwise at 276–278 K. The mixture was stirred at room temperature for 3 h and then poured into ice water; the precipitate was filtered off, washed with water and dried at 353 K, and 4-methylphthalonitrile was obtained (yield 60%, 4.6 g; m.p. 391.5–391.6 K). This was suspended in CCl₄ (70 ml), and then N-bromosuccimide (5.8 g, 32.6 mmol) and benzoyl peroxide (0.1–0.2 g) were added. The suspension was refluxed for 24 h, and then cooled to room temperature and filtered; the CCl₄ was evaporated and crude 4-bromomethylphthalonitrile (3.5 g) was obtained. The crude 4-bromomethylphthalonitrile (3.5 g, 15.8 mmol), phthalimide (2.4 g, 16.3 mmol) and K₂CO₃ (5 g, 36.2 mmol) were added to N,N-dimethylformamide (60 ml), and then stirred at 353 K for 12 h. The reaction mixture was poured into ice water (800 ml), and the precipitate was separated by centrification, washed with water and vacuum dried at 353 K, resulting in crude (I) (1.7 g). The crude (I) was washed with CH₃OH and recrystallized in tetrahydrofuran and CH₂Cl₂ repeatedly; colorless needle-shaped crystals of (I) were obtained (m.p. 550–551 K). MS (m/z, %): 287 (M⁺, 100); IR (KBr, cm⁻¹): 2229 (C—N), 3069 (Ar—H), 1706 (C–O), 1776, 1420 (–CH₂–), 1390, 1112 (N—H), 951 (C—H), 724; UV–vis: 227.41, 294.02 nm (CH₂Cl₂), 235.04, 284.18, 293.95 nm (THF); ¹H NMR (DMSO-d₆): δ 4.919 (s, 2H), 7.910 (br, 5H), 8.115 (d, 1H), 8.183 (s, 1H).

S3. Refinement

All H atoms were located in a difference Fourier map and refined isotropically. The C—H distances lie in the range 0.89 (2)–1.01 (3) Å.

Computing details

Data collection: RAPID-AUTO (Rigaku, 1998); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEX (McArdle, 1995); software used to prepare material for publication: SHELXL97.

Figures

Fig. 1. The structure of (I), showing the atomic numbering scheme. Displacement ellipsoids are drawn at the 40% probability level.

4-[4-(1,3-Dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]phthalonitrile

Crystal data

C17H9N3O2	F(000) = 592
Mr = 287.27	Dx = 1.407 Mg m^−3
Monoclinic, P21/c	Melting point: 550 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71069 Å
a = 4.9331 (3) Å	Cell parameters from 6576 reflections
b = 26.2490 (13) Å	θ = 6.1–54.9°
c = 10.4901 (6) Å	µ = 0.10 mm^−1
β = 93.0930 (13)°	T = 298 K
V = 1356.37 (13) Å^3	Needle, colourless
Z = 4	0.70 × 0.10 × 0.08 mm

Data collection

Rigaku R-AXIS RAPID diffractometer	1558 reflections with I > 2σ(I)
Radiation source: Rotating anode	Rint = 0.044
Graphite Monochromator monochromator	θmax = 27.5°, θmin = 1.6°
ω scans	h = 0→6
11806 measured reflections	k = 0→34
3107 independent 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)] = 0.037	Hydrogen site location: difference Fourier map
wR(F^2) = 0.117	All H-atom parameters refined
S = 1.00	w = 1/[σ^2(Fo^2) + (0.042P)^2] where P = (Fo^2 + 2Fc^2)/3
3107 reflections	(Δ/σ)max < 0.001
235 parameters	Δρmax = 0.14 e Å^−3
0 restraints	Δρmin = −0.23 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
O1	0.2424 (4)	0.45468 (6)	0.53538 (16)	0.0646 (5)
N3	0.6074 (4)	0.43376 (6)	0.67135 (16)	0.0426 (4)
O2	0.9408 (3)	0.43535 (6)	0.83339 (16)	0.0630 (5)
N2	−0.0776 (5)	0.31120 (8)	1.0056 (2)	0.0745 (7)
N1	0.1309 (5)	0.17509 (8)	0.8964 (2)	0.0818 (8)
H7	0.538 (5)	0.6111 (9)	0.953 (2)	0.073 (8)*
H9	0.093 (5)	0.5598 (8)	0.641 (2)	0.059 (7)*
H6	0.808 (5)	0.5375 (8)	0.950 (2)	0.059 (7)*
H8	0.187 (5)	0.6222 (10)	0.795 (2)	0.081 (8)*
H4	0.871 (5)	0.3810 (8)	0.612 (2)	0.054 (7)*
H5	0.583 (5)	0.3847 (9)	0.525 (3)	0.081 (9)*
H3	0.582 (4)	0.2153 (9)	0.675 (2)	0.057 (6)*
H2	0.771 (5)	0.2870 (8)	0.580 (2)	0.054 (6)*
H1	0.317 (4)	0.3757 (8)	0.7989 (19)	0.044 (6)*
C1	0.3429 (5)	0.25312 (8)	0.7931 (2)	0.0466 (6)
C2	0.2638 (4)	0.30184 (7)	0.83024 (19)	0.0421 (5)
C3	0.3708 (5)	0.34450 (8)	0.7736 (2)	0.0426 (5)
C4	0.5586 (4)	0.33982 (7)	0.6807 (2)	0.0406 (5)
C5	0.6381 (5)	0.29126 (9)	0.6455 (2)	0.0490 (6)
C6	0.5322 (5)	0.24848 (9)	0.7004 (2)	0.0537 (6)
C7	0.2260 (5)	0.20910 (9)	0.8501 (2)	0.0565 (6)
C8	0.0730 (5)	0.30722 (8)	0.9279 (2)	0.0511 (6)
C9	0.6713 (6)	0.38532 (8)	0.6138 (2)	0.0485 (6)
C10	0.4034 (4)	0.51094 (7)	0.70815 (19)	0.0416 (5)
C11	0.6141 (4)	0.50473 (7)	0.80021 (19)	0.0420 (5)
C12	0.6674 (5)	0.54112 (9)	0.8928 (2)	0.0551 (6)
C13	0.5050 (6)	0.58403 (9)	0.8901 (3)	0.0618 (7)
C14	0.2955 (5)	0.59030 (9)	0.7978 (3)	0.0577 (7)
C15	0.2404 (5)	0.55369 (8)	0.7046 (2)	0.0509 (6)
C16	0.3947 (5)	0.46518 (8)	0.6249 (2)	0.0450 (5)
C17	0.7488 (5)	0.45506 (8)	0.7767 (2)	0.0452 (5)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0690 (12)	0.0635 (10)	0.0591 (11)	0.0001 (9)	−0.0150 (10)	−0.0092 (8)
N3	0.0472 (10)	0.0382 (9)	0.0425 (10)	−0.0015 (9)	0.0045 (9)	−0.0008 (8)
O2	0.0583 (11)	0.0651 (10)	0.0642 (11)	0.0162 (9)	−0.0093 (9)	−0.0038 (9)
N2	0.0887 (17)	0.0611 (13)	0.0777 (16)	−0.0039 (12)	0.0414 (14)	0.0014 (11)
N1	0.105 (2)	0.0569 (13)	0.0849 (18)	−0.0153 (14)	0.0165 (15)	0.0083 (13)
C1	0.0510 (13)	0.0399 (12)	0.0490 (13)	−0.0011 (10)	0.0045 (11)	−0.0004 (10)
C2	0.0424 (12)	0.0428 (12)	0.0415 (13)	−0.0004 (10)	0.0053 (10)	0.0008 (9)
C3	0.0470 (13)	0.0386 (12)	0.0427 (13)	0.0048 (11)	0.0072 (10)	−0.0027 (10)
C4	0.0415 (12)	0.0402 (12)	0.0400 (12)	0.0000 (10)	0.0022 (10)	−0.0026 (9)
C5	0.0522 (14)	0.0462 (13)	0.0500 (14)	0.0037 (11)	0.0157 (12)	−0.0058 (11)
C6	0.0643 (16)	0.0392 (13)	0.0588 (16)	0.0045 (12)	0.0134 (13)	−0.0065 (11)
C7	0.0671 (17)	0.0448 (13)	0.0583 (15)	−0.0030 (13)	0.0086 (13)	0.0006 (12)
C8	0.0570 (15)	0.0434 (13)	0.0543 (15)	−0.0022 (11)	0.0148 (13)	0.0017 (11)
C9	0.0534 (16)	0.0426 (12)	0.0508 (15)	−0.0008 (12)	0.0140 (12)	−0.0033 (11)
C10	0.0431 (13)	0.0399 (11)	0.0422 (13)	−0.0052 (10)	0.0062 (10)	0.0025 (9)
C11	0.0436 (13)	0.0408 (11)	0.0419 (13)	−0.0042 (10)	0.0063 (11)	0.0001 (10)
C12	0.0558 (16)	0.0591 (16)	0.0497 (15)	−0.0042 (13)	−0.0038 (13)	−0.0066 (12)
C13	0.0754 (18)	0.0484 (14)	0.0617 (17)	−0.0015 (14)	0.0057 (15)	−0.0138 (13)
C14	0.0634 (17)	0.0422 (13)	0.0679 (17)	0.0046 (13)	0.0071 (14)	−0.0020 (12)
C15	0.0521 (14)	0.0475 (13)	0.0532 (15)	0.0026 (12)	0.0042 (12)	0.0059 (11)
C16	0.0466 (13)	0.0457 (12)	0.0429 (13)	−0.0063 (11)	0.0049 (11)	0.0035 (10)
C17	0.0445 (13)	0.0484 (12)	0.0432 (13)	−0.0016 (11)	0.0065 (11)	0.0032 (10)

Geometric parameters (Å, º)

O1—C16	1.202 (2)	C5—H2	0.98 (2)
N3—C17	1.391 (3)	C6—H3	0.95 (2)
N3—C16	1.401 (3)	C9—H4	0.99 (2)
N3—C9	1.450 (3)	C9—H5	1.01 (3)
O2—C17	1.207 (3)	C10—C15	1.380 (3)
N2—C8	1.137 (3)	C10—C11	1.390 (3)
N1—C7	1.130 (3)	C10—C16	1.484 (3)
C1—C6	1.390 (3)	C11—C12	1.377 (3)
C1—C2	1.398 (3)	C11—C17	1.490 (3)
C1—C7	1.436 (3)	C12—C13	1.382 (3)
C2—C3	1.386 (3)	C12—H6	0.89 (2)
C2—C8	1.435 (3)	C13—C14	1.387 (4)
C3—C4	1.386 (3)	C13—H7	0.98 (2)
C3—H1	0.91 (2)	C14—C15	1.388 (3)
C4—C5	1.390 (3)	C14—H8	0.99 (3)
C4—C9	1.507 (3)	C15—H9	0.97 (2)
C5—C6	1.378 (3)
C17—N3—C16	111.94 (17)	C4—C9—H5	105.4 (14)
C17—N3—C9	124.89 (19)	H4—C9—H5	111 (2)
C16—N3—C9	123.16 (19)	C15—C10—C11	121.8 (2)
C6—C1—C2	118.9 (2)	C15—C10—C16	130.1 (2)
C6—C1—C7	121.4 (2)	C11—C10—C16	108.11 (18)
C2—C1—C7	119.7 (2)	C12—C11—C10	121.0 (2)
C3—C2—C1	120.1 (2)	C12—C11—C17	130.8 (2)
C3—C2—C8	120.42 (19)	C10—C11—C17	108.11 (18)
C1—C2—C8	119.50 (19)	C11—C12—C13	117.6 (2)
C2—C3—C4	121.0 (2)	C11—C12—H6	120.6 (15)
C2—C3—H1	118.8 (13)	C13—C12—H6	121.8 (15)
C4—C3—H1	120.3 (13)	C12—C13—C14	121.4 (2)
C3—C4—C5	118.5 (2)	C12—C13—H7	120.2 (15)
C3—C4—C9	122.34 (19)	C14—C13—H7	118.4 (14)
C5—C4—C9	119.1 (2)	C13—C14—C15	121.3 (2)
C6—C5—C4	121.2 (2)	C13—C14—H8	120.0 (15)
C6—C5—H2	118.8 (13)	C15—C14—H8	118.6 (15)
C4—C5—H2	120.0 (13)	C10—C15—C14	116.9 (2)
C5—C6—C1	120.4 (2)	C10—C15—H9	124.3 (13)
C5—C6—H3	121.5 (13)	C14—C15—H9	118.7 (13)
C1—C6—H3	118.1 (13)	O1—C16—N3	124.1 (2)
N1—C7—C1	178.6 (3)	O1—C16—C10	130.0 (2)
N2—C8—C2	179.6 (3)	N3—C16—C10	105.91 (18)
N3—C9—C4	114.01 (18)	O2—C17—N3	124.4 (2)
N3—C9—H4	110.2 (13)	O2—C17—C11	129.6 (2)
C4—C9—H4	107.9 (13)	N3—C17—C11	105.92 (19)
N3—C9—H5	107.9 (14)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C3—H1···O2^i	0.91 (2)	2.47 (2)	3.275 (3)	148.4 (17)
C6—H3···N2^ii	0.95 (2)	2.60 (2)	3.280 (3)	128.6 (16)
C15—H9···O1^iii	0.97 (2)	2.44 (2)	3.378 (3)	160.7 (17)

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