Formyl­ation of an indole­nine: 2-(diformyl­methyl­idene)-3,3-dimethyl-2,3-dihydro-1H-indole

Helliwell, M.; Afgan, A.; Baradarani, M.M.; Joule, J.A.

doi:10.1107/S1600536806002261

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 62| Part 2| February 2006| Pages o737-o738

https://doi.org/10.1107/S1600536806002261

Formylation of an indolenine: 2-(diformylmethylidene)-3,3-dimethyl-2,3-dihydro-1H-indole

Madeleine Helliwell,^a Arash Afgan,^b Mehdi M. Baradarani ^b and John A. Joule ^a ^*

^aSchool of Chemistry, University of Manchester, Manchester M13 9PL, England, and ^bDepartment of Chemistry, Faculty of Science, University of Urmia, Urmia 57135, Iran
^*Correspondence e-mail: john.joule@manchester.ac.uk

(Received 18 January 2006; accepted 18 January 2006; online 25 January 2006)

Reaction of 2,3,3-trimethyl-3H-indole with dimethylformamide/POCl₃ and then aqueous NaOH produces 2-(diformylmethylidene)-2,3-dihydro-3,3-dimethylindole, C₁₃H₁₃NO₂. The crystal structure shows the molecule to be planar, with the exception of the two methyl groups, which lie above and below the plane.

Comment

Reaction of the 3,3-disubstituted 3H-indole, (1), with the Vilsmeier reagent (dimethylformamide and POCl₃) (Cheng et al., 1999 , 2002 ; Fischer et al., 1925 ; Jutz, 1976 ; Vilsmeier & Haack, 1927 ) gave compound (2), the product of N-formylation (Fritz, 1959 ). Further reaction of (2) with the Vilsmeier reagent and subsequent alkaline hydrolysis produced compound (4) (Fritz, 1959). Formation of this product presumably involves the intermediate N,C-diformyl derivative (3), from which the N-formyl group is then hydrolytically removed.

According to this previous work, we expected that the 2,3,3-trimethylindolenine, (5) (2,3,3-trimethyl-3H-indole), would react with the Vilsmeier reagent to form an N-formylated product. However, when (5) was subjected to the Vilsmeier conditions, at 323 K, followed by aqueous alkaline hydrolysis, a diformyl product was obtained in 56% yield. On the basis of the earlier work (Fritz, 1959), it appeared that (5) had been converted into (6). However, ¹H NMR analysis of the diformyl product showed the presence of an NH H atom, inconsistent with structure (6). In order to define the structure, crystals were grown and subjected to X-ray analysis, which showed the product to be the title compound, (7) (Fig. 1).

In the solid state, the molecule of (7) is planar, with the exception of the two methyl groups, which lie above and below the plane. The greatest deviation from the least-squares plane through atoms C1–C11/N1/O1/O2 is 0.052 (1) Å for C2.

Further examples of this interesting conversion, together with the utilization of such diformyl compounds for heterocyclic ring synthesis, will be described in a forthcoming paper.

Figure 1
A plot of (7), with displacement ellipsoids drawn at the 50% probability level.

Experimental

To dimethylformamide (10 ml) cooled in an ice bath, phosphorus oxychloride (6 ml, 66 mmol) was added dropwise with stirring over a period of 2 h at below 298 K. After the addition was complete, a solution of trimethylindolenine, (5) (12.6 mmol), in dimethylformamide (10 ml) was added dropwise. The cooling bath was removed and the reaction mixture was stirred at 323 K for 2 h. The resulting solution was added to ice-cooled water, the pH was adjusted to 8.0 by the addition of aqueous NaOH (35%) and the mixture was extracted with ethyl acetate (3 × 30 ml). The organic layer was washed with hot water and dried over Na₂SO₄. The solvent was evaporated and the resulting crude product was purified by column chromatography on silica gel, eluting with ethyl acetate–toluene (1:5 v/v), to give the pure diformyl compound, (7), as yellow crystals.

Crystal data

C₁₃H₁₃NO₂
M_r = 215.24
Monoclinic, P 2₁ /c
a = 12.1488 (13) Å
b = 12.2273 (13) Å
c = 7.3404 (8) Å
β = 99.329 (2)°
V = 1076.0 (2) Å³
Z = 4
D_x = 1.329 Mg m⁻³
Mo Kα radiation
Cell parameters from 1781 reflections
θ = 2.4–26.3°
μ = 0.09 mm⁻¹
T = 100 (2) K
Prism, yellow
0.65 × 0.50 × 0.50 mm

Data collection

Bruker SMART CCD area-detector diffractometer
φ and ω scans
Absorption correction: none
4520 measured reflections
2177 independent reflections
1729 reflections with I > 2σ(I)
R_int = 0.051
θ_max = 26.4°
h = −14 → 14
k = −15 → 10
l = −6 → 9

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.036
wR(F²) = 0.095
S = 0.99
2177 reflections
151 parameters
H atoms treated by a mixture of independent and constrained refinement
w = 1/[σ²(F_o²) + (0.0477P)²] where P = (F_o² + 2F_c²)/3
(Δ/σ)_max < 0.001
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯O1	0.858 (16)	2.075 (16)	2.7021 (15)	129.3 (13)
N1—H1N⋯O2ⁱ	0.858 (16)	2.157 (16)	2.8254 (15)	134.4 (14)
Symmetry code: (i) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

The H atom bonded to atom N1 was found by difference Fourier methods and refined isotropically. H atoms bonded to C atoms were included in calculated positions, using the riding method, with C—H distances of 0.95–0.98 Å and U_iso(H) = 1.2U_eq(C), or 1.5U_eq(C) for methyl groups. The methyl groups were allowed to rotate but not to tip.

Data collection: SMART (Bruker, 2001 ); cell refinement: SAINT (Bruker, 2002 ); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 2001); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks global, 7. DOI: https://doi.org/10.1107/S1600536806002261/bt6806sup1.cif

Structure factors: contains datablock 7. DOI: https://doi.org/10.1107/S1600536806002261/bt68067sup2.hkl

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SMART; data reduction: SAINT (Bruker, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 2001); software used to prepare material for publication: SHELXTL.

2-(Diformylmethylidene)-3,3-dimethyl-2,3-dihydro-1H-indole top

Crystal data top

C₁₃H₁₃NO₂	D_x = 1.329 Mg m⁻³
M_r = 215.24	Melting point = 118–120 K
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 12.1488 (13) Å	Cell parameters from 1781 reflections
b = 12.2273 (13) Å	θ = 2.4–26.3°
c = 7.3404 (8) Å	µ = 0.09 mm⁻¹
β = 99.329 (2)°	T = 100 K
V = 1076.0 (2) Å³	Prismatic, yellow
Z = 4	0.65 × 0.50 × 0.50 mm
F(000) = 456

Data collection top

Bruker SMART CCD area-detector diffractometer	1729 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.051
Graphite monochromator	θ_max = 26.4°, θ_min = 1.7°
φ and ω scans	h = −14→14
4520 measured reflections	k = −15→10
2177 independent reflections	l = −6→9

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)] = 0.036	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.095	H atoms treated by a mixture of independent and constrained refinement
S = 0.99	w = 1/[σ²(F_o²) + (0.0477P)²] where P = (F_o² + 2F_c²)/3
2177 reflections	(Δ/σ)_max < 0.001
151 parameters	Δρ_max = 0.26 e Å⁻³
0 restraints	Δρ_min = −0.16 e Å⁻³

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.41864 (8)	0.59632 (7)	0.17572 (13)	0.0248 (2)
O2	0.45038 (8)	0.30192 (7)	0.41990 (14)	0.0291 (3)
N1	0.64031 (10)	0.59216 (9)	0.16885 (15)	0.0175 (3)
H1N	0.5812 (14)	0.6311 (13)	0.141 (2)	0.034 (5)*
C1	0.63698 (10)	0.49488 (10)	0.25163 (16)	0.0164 (3)
C2	0.75649 (11)	0.44847 (10)	0.29030 (17)	0.0175 (3)
C3	0.82031 (11)	0.53649 (10)	0.20644 (16)	0.0173 (3)
C4	0.93209 (11)	0.54392 (10)	0.19213 (18)	0.0205 (3)
H4	0.9828	0.4877	0.2394	0.025*
C5	0.96879 (12)	0.63560 (11)	0.10687 (18)	0.0225 (3)
H5	1.0456	0.6425	0.0974	0.027*
C6	0.89476 (11)	0.71681 (11)	0.03570 (18)	0.0239 (3)
H6	0.9216	0.7781	−0.0235	0.029*
C7	0.78199 (11)	0.71067 (10)	0.04888 (17)	0.0218 (3)
H7	0.7310	0.7663	0.0004	0.026*
C8	0.74801 (11)	0.61946 (10)	0.13616 (16)	0.0169 (3)
C9	0.53856 (11)	0.44934 (10)	0.29297 (17)	0.0176 (3)
C10	0.43321 (11)	0.50492 (11)	0.24412 (17)	0.0209 (3)
H10	0.3687	0.4669	0.2672	0.025*
C11	0.53515 (12)	0.34386 (11)	0.37930 (18)	0.0226 (3)
H11	0.6029	0.3040	0.4067	0.027*
C12	0.79827 (11)	0.44121 (11)	0.49983 (17)	0.0220 (3)
H12A	0.8754	0.4147	0.5216	0.033*
H12B	0.7509	0.3905	0.5557	0.033*
H12C	0.7950	0.5138	0.5553	0.033*
C13	0.76813 (11)	0.33804 (10)	0.19465 (19)	0.0219 (3)
H13A	0.7362	0.3438	0.0636	0.033*
H13B	0.7284	0.2814	0.2527	0.033*
H13C	0.8472	0.3185	0.2068	0.033*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0231 (5)	0.0236 (5)	0.0268 (5)	0.0046 (4)	0.0010 (4)	0.0003 (4)
O2	0.0291 (6)	0.0220 (5)	0.0380 (6)	−0.0075 (5)	0.0104 (5)	−0.0016 (4)
N1	0.0162 (6)	0.0153 (6)	0.0208 (6)	0.0026 (5)	0.0029 (4)	0.0009 (5)
C1	0.0203 (7)	0.0135 (6)	0.0147 (6)	0.0009 (5)	0.0009 (5)	−0.0033 (5)
C2	0.0169 (7)	0.0152 (6)	0.0197 (7)	0.0005 (5)	0.0007 (5)	0.0000 (5)
C3	0.0205 (7)	0.0152 (6)	0.0157 (6)	−0.0007 (5)	0.0019 (5)	−0.0031 (5)
C4	0.0202 (7)	0.0197 (7)	0.0212 (7)	0.0024 (6)	0.0018 (5)	−0.0048 (6)
C5	0.0190 (7)	0.0254 (7)	0.0243 (7)	−0.0038 (6)	0.0073 (6)	−0.0050 (6)
C6	0.0294 (8)	0.0218 (7)	0.0222 (7)	−0.0052 (6)	0.0096 (6)	0.0006 (6)
C7	0.0258 (8)	0.0192 (7)	0.0208 (7)	0.0014 (6)	0.0049 (6)	0.0017 (5)
C8	0.0176 (7)	0.0173 (6)	0.0162 (6)	0.0008 (5)	0.0035 (5)	−0.0034 (5)
C9	0.0184 (7)	0.0166 (6)	0.0176 (6)	−0.0016 (5)	0.0018 (5)	−0.0037 (5)
C10	0.0196 (7)	0.0232 (7)	0.0199 (7)	−0.0026 (6)	0.0031 (5)	−0.0045 (6)
C11	0.0218 (7)	0.0199 (7)	0.0259 (7)	−0.0023 (6)	0.0027 (6)	−0.0038 (6)
C12	0.0217 (7)	0.0204 (7)	0.0227 (7)	−0.0005 (6)	−0.0003 (6)	0.0020 (6)
C13	0.0212 (7)	0.0162 (7)	0.0278 (7)	0.0016 (6)	0.0022 (6)	−0.0018 (6)

Geometric parameters (Å, º) top

O1—C10	1.2262 (16)	C5—H5	0.9500
O2—C11	1.2296 (16)	C6—C7	1.3910 (19)
N1—C1	1.3393 (16)	C6—H6	0.9500
N1—C8	1.4082 (17)	C7—C8	1.3822 (17)
N1—H1N	0.858 (16)	C7—H7	0.9500
C1—C9	1.3963 (18)	C9—C10	1.4420 (18)
C1—C2	1.5417 (18)	C9—C11	1.4406 (18)
C2—C3	1.5144 (18)	C10—H10	0.9500
C2—C13	1.5390 (17)	C11—H11	0.9500
C2—C12	1.5421 (17)	C12—H12A	0.9800
C3—C4	1.3818 (18)	C12—H12B	0.9800
C3—C8	1.3856 (17)	C12—H12C	0.9800
C4—C5	1.3920 (18)	C13—H13A	0.9800
C4—H4	0.9500	C13—H13B	0.9800
C5—C6	1.3840 (19)	C13—H13C	0.9800

C1—N1—C8	112.64 (11)	C6—C7—H7	121.7
C1—N1—H1N	121.0 (10)	C7—C8—C3	122.98 (12)
C8—N1—H1N	126.4 (10)	C7—C8—N1	128.74 (12)
N1—C1—C9	122.86 (12)	C3—C8—N1	108.27 (11)
N1—C1—C2	108.28 (11)	C1—C9—C10	120.99 (12)
C9—C1—C2	128.85 (11)	C1—C9—C11	122.64 (12)
C3—C2—C1	101.10 (10)	C10—C9—C11	116.33 (12)
C3—C2—C13	110.31 (10)	O1—C10—C9	126.49 (13)
C1—C2—C13	113.11 (10)	O1—C10—H10	116.8
C3—C2—C12	109.81 (10)	C9—C10—H10	116.8
C1—C2—C12	110.65 (10)	O2—C11—C9	124.41 (13)
C13—C2—C12	111.39 (10)	O2—C11—H11	117.8
C4—C3—C8	119.67 (12)	C9—C11—H11	117.8
C4—C3—C2	130.68 (12)	C2—C12—H12A	109.5
C8—C3—C2	109.65 (11)	C2—C12—H12B	109.5
C3—C4—C5	118.52 (12)	H12A—C12—H12B	109.5
C3—C4—H4	120.7	C2—C12—H12C	109.5
C5—C4—H4	120.7	H12A—C12—H12C	109.5
C6—C5—C4	120.76 (13)	H12B—C12—H12C	109.5
C6—C5—H5	119.6	C2—C13—H13A	109.5
C4—C5—H5	119.6	C2—C13—H13B	109.5
C5—C6—C7	121.47 (12)	H13A—C13—H13B	109.5
C5—C6—H6	119.3	C2—C13—H13C	109.5
C7—C6—H6	119.3	H13A—C13—H13C	109.5
C8—C7—C6	116.57 (12)	H13B—C13—H13C	109.5
C8—C7—H7	121.7

C8—N1—C1—C9	−178.12 (11)	C5—C6—C7—C8	−0.11 (19)
C8—N1—C1—C2	2.49 (14)	C6—C7—C8—C3	−0.71 (18)
N1—C1—C2—C3	−2.13 (12)	C6—C7—C8—N1	179.96 (12)
C9—C1—C2—C3	178.53 (12)	C4—C3—C8—C7	0.73 (18)
N1—C1—C2—C13	−120.06 (12)	C2—C3—C8—C7	−179.21 (11)
C9—C1—C2—C13	60.60 (17)	C4—C3—C8—N1	−179.82 (11)
N1—C1—C2—C12	114.17 (11)	C2—C3—C8—N1	0.24 (14)
C9—C1—C2—C12	−65.18 (16)	C1—N1—C8—C7	177.63 (12)
C1—C2—C3—C4	−178.83 (12)	C1—N1—C8—C3	−1.77 (14)
C13—C2—C3—C4	−58.89 (17)	N1—C1—C9—C10	1.32 (19)
C12—C2—C3—C4	64.25 (17)	C2—C1—C9—C10	−179.42 (11)
C1—C2—C3—C8	1.10 (12)	N1—C1—C9—C11	178.96 (11)
C13—C2—C3—C8	121.04 (11)	C2—C1—C9—C11	−1.8 (2)
C12—C2—C3—C8	−115.82 (11)	C1—C9—C10—O1	−4.9 (2)
C8—C3—C4—C5	0.09 (18)	C11—C9—C10—O1	177.36 (12)
C2—C3—C4—C5	−179.98 (12)	C1—C9—C11—O2	178.99 (12)
C3—C4—C5—C6	−0.88 (19)	C10—C9—C11—O2	−3.28 (19)
C4—C5—C6—C7	0.9 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O1	0.858 (16)	2.075 (16)	2.7021 (15)	129.3 (13)
N1—H1N···O2ⁱ	0.858 (16)	2.157 (16)	2.8254 (15)	134.4 (14)

Symmetry code: (i) −x+1, y+1/2, −z+1/2.

Acknowledgements

The authors are grateful to the University of Urmia for financial support of the preparative aspects of this work

References

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