Experimental and computational thermochemical study of oxindole

J. Chem. Thermodynamics 42 (2010) 1101–1106

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Experimental and computational thermochemical study of oxindole Margarida S. Miranda a,b, M. Agostinha R. Matos a,*, Victor M.F. Morais a,c, Joel F. Liebman d a

Centro de Investigação em Química, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre, 687, P-4169-007 Porto, Portugal Centro de Geologia da Universidade do Porto, Rua do Campo Alegre, 687, P-4169-007 Porto, Portugal c Instituto de Ciências Biomédicas Abel Salazar, ICBAS, Universidade do Porto, P-4099-003 Porto, Portugal d Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, MD 21250, USA b

a r t i c l e

i n f o

a b s t r a c t

Article history: Received 24 February 2010 Received in revised form 13 April 2010 Accepted 14 April 2010 Available online 21 April 2010

An experimental and computational thermochemical study was performed for oxindole. The standard (p ¼ 0:1 MPa) molar enthalpy of formation of solid oxindole was derived from the standard molar energy of combustion, in oxygen, at T = 298.15 K, measured by static bomb combustion calorimetry. The respective standard molar enthalpy of sublimation, at T = 298.15 K, was measured by Calvet microcalorimetry. The standard molar enthalpy of formation in the gas phase was derived as (66.8 ± 3.2) kJ  mol1. Density functional theory calculations with the B3LYP hybrid functional and the 6-31G* and 6-311G** sets have also been performed in order to obtain the most stable conformation of oxindole. A comparison has been made between the structure of oxindole and that of the related two-ring molecules: indoline and 2-indanone and the one-ring molecules: pyrrolidine and 2,3-dihydropyrrole. The G3(MP2)//B3LYP method and appropriate reactions were used to obtain estimates of the standard molar enthalpy of formation of oxindole in the gas phase, at T = 298.15 K. Computationally obtained estimates of the enthalpy of formation of oxindole are in very good agreement with the experimental gas phase value. The aromaticity of oxindole was evaluated through the analysis of the nucleus independent chemical shifts (NICS) obtained from the B3LYP/6-311G** wave functions. Ó 2010 Elsevier Ltd. All rights reserved.

Keywords: Oxindole Combustion calorimetry Microcalorimetry Calvet Enthalpy of formation Computational calculations G3(MP2)//B3LYP NICS

1. Introduction The oxindole (indolin-2-one) structure (see scheme 1) appears in the core of several natural products with a wide spectrum of biological activities [1–3].

O N H

(A) SCHEME 1. Molecular structure of oxindole (A).

Convolutamydines, arundaphine, donaxaridine, maremycins, paratunamide, celogentin K, TMC-95AD, neuroprotectin B, flustraminol A and B, 3-hydroxy welwitindolinones and pyrrolidinoindoline-type alkaloid, and CPC-1 are some examples of bioactive 3substituted-3-hydroxy-2-oxindole natural products which show potent anti-oxidant, anti-cancer, anti-HIV, neuroprotective among other biological properties [4]. * Corresponding author. Tel.: +351 22 0402 517; fax: +351 22 0402 522. E-mail addresses: [email protected] (M.S. Miranda), [email protected] (M. Agostinha R. Matos), [email protected] (V.M.F. Morais), [email protected] (J.F. Liebman). 0021-9614/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.jct.2010.04.006

A study of oxindole alkaloids such as isatinone A and B (chemical constituents of Isatis costata, which is an annual or biennial herb, found in northern parts of Pakistan) found that these compounds showed significant antifungal activity [5]. Pentacyclic oxindole alkaloids such as mitraphylline, isomitraphylline, pteropodine (uncarine C), isopteropodine (uncarine E), speciophylline (uncarine D), rhynchophylline, and isorhynchophylline have been associated with immunomodulatory and cytotoxic activities [6]. Oxindole is usually regarded as the lactam (A) of o-aminophenylacetic acid. However, the lactim (B) and the enol (C) formulae represent also possible structures (see scheme 2). OH

OH

N

(B)

(C)

N H

SCHEME 2. Molecular structure of the two possible enol forms of oxindole: (B) 3Hindole-2-ol and (C) 1H-indole-2-ol.

A 1H and 13C NMR study [7] of the protropic equilibria between forms (A), (B), and (C), in chloroform and methanol, has concluded that (A) is the dominant structure. A solid state X-ray diffraction study reported by Lipkowski et al. [8] for six indolinones confirmed that the lactam moiety forms a

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typical planar amide structure with no evidence for the presence of the enol forms. We have already performed studies of the energetics of other compounds containing the –C(@O)–NH– group in a 5-membered ring fused to a benzene ring, e.g. isatin [9]; saccharin [10]; 2-benzimidazolinone, 2-benzoxazolinone, and 3-indazolinone [11]; and 1,2,4,5-benzenetetracarboxylic diimide [12]. In the present work we report the standard molar enthalpy of formation of oxindole in the gaseous phase, at T = 298.15 K, obtained from the standard molar energy of combustion using a static bomb calorimeter and from the standard molar enthalpy of sublimation measured by Calvet microcalorimetry. Density functional theory calculations with the hybrid functional B3LYP and the 631G* and 6-311G** basis sets were also performed in order to compare the structure of the two-ring molecules: oxindole, indoline, and 2-indanone with that of the related one-ring molecules: 2,3dihydropyrrole and 3-cyclopentenone. Estimates of the standard molar enthalpy of formation of oxindole in the gaseous phase, at T = 298.15 K, were obtained from G3(MP2)//B3LYP calculations with appropriate reactions. Additionally, the aromaticity of oxindole was evaluated through the analysis of the calculated nucleus independent chemical shifts (NICS) and the gas-phase enthalpy of formation analyzed by use of two recent thermochemical approaches. 2. Experimental 2.1. Material and purity control Oxindole [59-48-3] was obtained commercially from Aldrich Chemical Co. with the assigned mass fraction purity of 0.9980 determined by gas chromatography and was further purified by repeated vacuum sublimation before the calorimetric measurements. The final purity of the compound was assessed by DSC analysis using the fractional fusion technique [13]. The DSC experiments were performed with a Setaram DSC 141 calorimeter. The samples were hermetically sealed in stainless steel crucibles and the heating rate was 1.67  102 K  s1. No phase transitions were observed between the temperature of 298.15 K and the melting temperature of the compound. The power scale of the calorimeter was calibrated with high purity indium (mass fraction >0.99999) and its temperature scale was calibrated by measuring the melting temperature of the following three high purity reference materials [14]: naphthalene, benzoic acid, and indium. The purity of the compound was also assessed through the carbon dioxide recovery ratio. The average ratios, together with the standard deviation of the mean, of the mass of carbon dioxide recovered to that calculated from the mass of sample was (100.06 ± 0.01). The specific density of oxindole was taken from reference [15] as q = 0.995 g  cm3. 2.2. Combustion calorimetry The energy of combustion of oxindole was measured using a static bomb calorimeter. Since the apparatus and the technique have been described [16,17], only a brief description will be given here. The energy equivalent of the calorimeter was determined from the combustion of benzoic acid BDH Thermochemical Standard, batch 69376/01, certified in Manchester University, having a massic energy of combustion of Dcu = (26435.1 ± 3.5) J  g1, under certificate conditions. Calibration experiments were carried out in oxygen at the pressure 3.04 MPa in the presence of 1.00 cm3 of water added to the bomb. One set of seven calibration experiments was performed leading to the value of the energy equivalent

of the calorimeter: ecal = (16005.0 ± 2.0) J  K1, where the uncertainty quoted is the standard deviation of the mean. The solid compound was burnt in pellet form. For all experiments, the sample was ignited at T = (298.150 ± 0.001) K in oxygen, at a pressure of 3.04 MPa, with a volume of water of 1.00 cm3 added to the bomb. The electrical energy for ignition DU(ign.) was determined from the change in potential difference across a capacitor when discharged through the platinum ignition wire. For the cotton thread fuse of empirical formula CH1.686O0.843, the specific energy of combustion is Dc u ¼ 16240 J  g1 [18], a value previously confirmed in our laboratory. The corrections for nitric acid formation DU(HNO3) were based on 59.7 kJ  mol1 [19], for the molar energy of formation of 0.1 mol  dm3 HNO3(aq) from N2(g), O2(g), and H2O(l). The mass of compound, m(compound), used in each experiment was determined from the total mass of carbon dioxide, m(CO2, total), produced after allowance for that formed from the cotton thread fuse. To calculate the standard massic energy of combustion, Dc u , corrections to the standard state were performed using the procedure given by Hubbard et al. [20]. An estimated pressure coefficient of specific energy: (@u/@p)T = 0.2 J  g1  MPa1 at T = 298.15 K, a typical value for most organic compounds, was assumed [21]. 2.3. Microcalorimetry The standard molar enthalpy of sublimation of oxindole was measured using the ‘‘vacuum sublimation” drop microcalorimetric method [22]. Samples, about 3 mg of the solid compound, contained in thin glass capillary tubes sealed at one end, were dropped from room temperature into the hot reaction vessel in the Calvet High-temperature Microcalorimeter (SETARAM HT 1000D) held at a convenient temperature 390 K and then removed from the hot zone by vacuum sublimation. Simultaneously, an empty capillary tube was dropped in the reference calorimetric cell. For these measurements, the microcalorimeter was calibrated in situ using the reported standard molar enthalpy of sublimation of naphthalene (72.600 ± 0.600) kJ  mol1 [23]. Accuracy tests were performed with benzoic acid. g;T Hm was corrected to The observed enthalpy Dcr;298:15K T = 298.15 K using equation (1):

DT298:15K Hm ðgÞ ¼

Z

T 298:15K

C p;m ðgÞdT;

ð1Þ

where T is the temperature of the hot reaction vessel and C p;m ðgÞ is the molar heat capacity of the compound in the gas phase. The molar heat capacity and its temperature dependence

C p;m ðgÞ=ðJ  mol

1

 K1 Þ ¼ 0:000326ðT=KÞ2 þ 0:650ðT=KÞ  40:443 ð2Þ

were derived from statistical thermodynamics using the vibrational frequencies obtained from the DFT calculations with the B3LYP functional and the 6-31G* basis set. The atomic weights of the elements were those recommended by the IUPAC commission [24]. 3. Computational details The geometry of the experimentally studied compound and of all auxiliary molecules were fully optimized using density functional theory (DFT) with the Becke 3-parameter hybrid exchange [25] and Lee–Yang–Parr [26] correlation density functional (B3LYP) and two basis sets. The optimum geometries obtained from the calculations with the smaller basis set, 6-31G* [27], were characterized as true minima through construction and diagonal-

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DTad is the adiabatic temperature raise (calculated using the program LABTERMO [33]) and DUign is the energy of ignition. The mean value for the standard massic energy of combustion, hDc u i, at T = 298.15 K, refers to the following combustion reaction:

ization of the Hessian matrices. We have further refined these optimum geometries by re-optimizing them using the same methodology with the Pople’s split-valence 6-311G** extended basis set [28]. In order to obtain more reliable energetic estimates we have also conducted calculations using the G3(MP2)//B3LYP method [29]. This method is a variation of the previous G3(MP2) [30] composite method with the B3LYP/6-31G* method in lieu of the much more expensive MP2(FU)/6-31G* calculations for obtaining the optimum geometries and the thermal corrections. The energies obtained at T = 0 K are corrected to enthalpies at T = 298.15 K by adding the vibrational, translational, rotational, and RT terms. Nucleus independent chemical shifts (NICS) values were calculated using B3LYP/6-311G** wave functions at the B3LYP/6-311G** geometries. The methodology used was developed by Schleyer and his co-workers as a means of providing useful aromaticity indices [31]. Two different values were calculated for each ring and each molecule: one at the geometrical centre of the ring (i.e., the point whose coordinates are the un-weighted mean of the homologous coordinates of the heavy atoms of the rings), denoted NICS(0), and 1.0 Å above the centre of the ring, denoted NICS(1.0). All calculations were performed with the Gaussian 03 series of programs [32].

C8 H7 NOðcrÞ þ

ð4Þ

Table 2 lists the derived standard molar energy and enthalpy of combustion, Dc U m ðcrÞ and Dc Hm ðcrÞ, and the standard molar enthalpy of formation of the oxindole in the solid phase, Df Hm ðcrÞ, at T = 298.15 K. In accordance with customary thermochemical practice [34], the uncertainties assigned to the standard molar enthalpies of combustion are, in each case, twice the overall standard deviation of the mean and include the uncertainties in calibration and in the values of auxiliary quantities used. To derive Df Hm ðcrÞ from Dc Hm ðcrÞ the standard molar enthalpies of formation of H2O(l) and CO2(g), at T = 298.15 K, were taken, respectively as, (285.830 ± 0.042) kJ  mol1 [35] and (393.51 ± 0.13) kJ  mol1 [35]. In Domalski’s thermochemical compendium [36] there are two citations to measurements on the enthalpies of combustion and of formation of solid oxindole. The values therein are (3976.1 and 172.4) kJ  mol1 taken from Berthelot and Andre [37] values determined in 1899 – these values are in stunning agreement with our value with samples of higher and defined purity and contemporary calorimetric methodologies. The standard molar enthalpy of sublimation of oxindole, at T = 298.15 K, was measured by Calvet microcalorimetry. The experimental results are reported in table 3 and correspond to the mean of seven independent microcalorimetric experiments with uncertainties of twice the standard deviation of the mean. From the values for the standard molar enthalpy of formation and sublimation of the solid compound, the value of the standard molar enthalpy in the gaseous phase, at T = 298.15 K, was derived. These results are summarized in table 4.

4. Experimental results The purity of the solid compound was assessed using differential scanning calorimetry (DSC). The temperature (observed at the onset of the calorimetric peaks) and enthalpy of fusion and the mole fraction purity were computed from the DSC thermograms as: 1 Tfus = (398.86 ± 0.17) K, Dlcr Hm ðT fus Þ ¼ ð18:74  0:24Þ kJ  mol and w = (99.93 ± 0.02). The uncertainties assigned to the results are twice the standard deviation of the mean of six independent runs. Results of all combustion experiments performed for oxindole are given in table 1. The symbols in this table have the same meaning as in reference [20]. As samples were ignited at T = 298.15 K,

DUðIBPÞ ¼ fecal þ cp ðH2 O; lÞDmðH2 OÞ þ ef gDT ad þ DUðignÞ;

37 7 1 O2 ðgÞ ! 8CO2 ðgÞ þ H2 OðlÞ þ N2 ðgÞ: 4 2 2

TABLE 2 Derived standard (p ¼ 0:1 MPa) molar values in the solid phase, at T = 298.15 K (kJmol-1).

ð3Þ

where DU(IBP) is the energy associated to the isothermal bomb process, Dm(H2O) is the deviation of the mass of water added to the calorimeter from 3119.6 g, cp(H2O, l) is the specific heat capacity of liquid water, ef is the energy of the bomb contents after ignition,

Compound

Dc U m

Dc Hm

Df Hm

Oxindole (cr)

(3980.1 ± 1.7)

(3982.0 ± 1.7)

(166.5 ± 2.0)

TABLE 1 Combustion experiments, at T = 298.15 K, of oxindole. Experiment no.

m(CO2, total)/g m(compound)/g m(fuse)/g DTad/K ef/(J  K1) Dm(H2O)/g –DU(IBP)/J DU(HNO3)/J DU(carbon)/J DU(ign.)/J DUP/J DU(fuse)/J Dc u =ðJ  g1 Þ % CO2

1

2

3

4

5

6

1.46254 0.55166 0.00236 1.03393 15.55 0.1 16563.35 31.21 0.00 1.21 11.35 38.33 29877.93 100.042

1.64732 0.62153 0.00238 1.16587 15.69 -0.1 18676.34 34.63 0.00 1.21 12.91 38.65 29910.30 100.043

1.51286 0.57064 0.00244 1.06980 15.64 -0.2 17136.79 32.72 0.00 1.20 11.76 39.63 29883.43 100.082

0.61921 0.00249 1.16081 15.73 -0.1 18595.34 35.52 0.00 1.20 12.85 40.44 29887.32 (100.06)

1.60052 0.60374 0.00252 1.13257 15.69 0.0 18143.36 35.34 0.00 1.19 12.49 40.92 29904.61 100.075

1.51864 0.57296 0.00222 1.07408 15.37 0.1 17206.41 31.46 0.00 1.20 11.82 36.05 29892.28 100.071

hDc u i ¼ ð29892:6  5:1Þ J  g1 ð0:017%Þ m(CO2, total) is the total mass of CO2 formed in the experiment; m(compound) is the mass of compound burnt in the experiment; m(fuse) is the mass of fuse (cotton) used in the experiment; DTad is the corrected temperature rise; ef is the energy equivalent of contents in the final state; Dm(H2O) is the deviation of the mass of water added to the calorimeter from 3119.6 g; DU(IBP) is the energy change for the isothermal combustion reaction under actual bomb conditions; DU(IBP) includes the ignition energy, DU(ignition); DU(HNO3) is the energy correction for the nitric acid formation; DU(carbon) is the energy correction for carbon formation; DUR is the energy correction to the standard state; DU(fuse) is the energy of combustion of the fuse (cotton); Dc u is the standard massic energy of combustion of the compound.

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M.S. Miranda et al. / J. Chem. Thermodynamics 42 (2010) 1101–1106

TABLE 3 Standard (p ¼ 0:1 MPa) molar enthalpy of sublimation of oxindole, at T = 298.15 K. Compound

No. of expts.

T/K

 Dg;T cr;298:15K Hm =ðkJ  mol

Oxindole (cr)

7

390

113.0 ± 2.5

1

DT298:15K Hm =ðkJ  mol

Þ

Compound

ðkJ  mol Oxindole

Dgcr Hm = Þ

(166.5 ± 2.0)

ðkJ  mol

1

Df Hm ðgÞ=ðkJ  mol Þ

99.7 ± 2.5

1

Dgcr Hm ð298:15 KÞ=ðkJ  mol

Þ

13.3

TABLE 4 Derived standard (p ¼ 0:1 MPa) molar enthalpy of formation in the gas phase, at T = 298.15 K.

Df Hm ðcrÞ= 1

1

2

5 N1

4

Computationala

(66.8 ± 3.2)

69.9 (equation (5)) 67.8 (equation (6))

3 2

3

O

7

5 N1

2

6

1

4 5

H

H

Experimental

Þ

99.7 ± 2.5

4 3

Þ

1

O

6

6

4 5

a

The G3(MP2)//B3LYP method was used to calculate the enthalpy of the reactions indicated in parenthesis.

3 N1

2

2

3 4

1

O

6

5

H6

FIGURE 1. Atom numbering scheme for oxindole, indoline, 2-indanone, 2,3dihydropyrrole, and 3-cyclopentenone.

5. Computational results and discussion The geometries of the two-ring molecules, oxindole and indoline, and the one-ring molecule, 2,3-dihydropyrrolidine have been fully optimized using the B3LYP hybrid density functional and the 6-31G* and 6-311G** extended basis sets. The most relevant geometrical parameters obtained using the larger basis set are shown in table 5 (see figure 1 for the numbering of the atoms). In this table, we also show the most relevant geometrical parameters of 2indanone and 3-cyclopentenone taken from a previous study on 1-, 2-indanone and 1,3-indandione [38] and the relevant bond lengths and angles for oxindole taken from a X-ray diffraction study [8]. The calculated geometrical parameters for oxindole (A) are in generally good agreement with the experimental values. The bond lengths obtained from our calculations differ at most by 0.04 Å from the experimental ones while for the bond angles differences of at most 2° are observed. The geometries of the two enol tautomers of oxindole (A) (see scheme 2), 3H-indole-2-ol (B) and 1H-indole-2-ol (C), were also fully optimized at the B3LYP/6-31G* level. The B3LYP/6-31G* electronic energy for the keto form (A) was 439.062326 hartree, for the enol form (B) 439.038870 hartree, and for the enol form (C)

439.032229 hartree. The two enol forms have higher energy than the keto form so we may conclude that oxindole exists, in the gas phase, essentially exclusively in the keto form as, was found for the solid phase in the aforementioned X-ray study [8]. We can conclude from the parameters shown in table 5 that the compounds containing only nitrogen as the heteroatom, indoline and 2,3-dihydropyrrole, are non-planar molecules with the dihedral angle H1,2,3,4 (HN–C–C–C) of 26.5° and 23.7°, respectively. This behaviour can be explained by the partial relief, in the nonplanar compounds, of strain due to the four H–H interactions. On the other hand, the absence of such destabilizing H–H interactions in oxindole allows this molecule to adopt a planar structure, with the N–H bond in the same plane of the bicyclic structure. This fact was also found experimentally in a X-ray diffraction study for various indolinones [7]. Even though this planar conformation, which has also been found previously for other similar systems: 1-indanone, 2-indanone, and 1,3-indandione and the monocyclic molecules 2-cyclopentenone and 3-cyclopentenone [38], could lead us to expect that conjugation involving the carbonyl group, the lone electron pair of the nitrogen atom and the p electron system of

TABLE 5 Most relevant B3LYP/6-311G** geometrical parameters.a Oxindole Calc. R1,2 R2,3 R3,4 R4,5 R1,5 R1,6 R2,7

H1,2,3 H2,3,4 H3,4,5 H4,5,1 H5,1,2 H6,1,2 H1,2,7 H7,2,3 H1,2,3,4 H6,1,2,3 H1,5,4,3 H2,3,4,5 a b

0.139 0.154 0.151 0.140 0.140 0.101 0.121 106.0 103.8 108.3 109.1 112.8 121.6 125.8 128.2 0.0 180.0 0.0 0.0

Indoline

2,3-Dihydropyrrole

2-Indanoneb

3-Cyclopentenoneb

Exp. [8] 0.1354 0.1511 0.1495 0.1387 0.1413 – 0.1234 108.0 103.2 108.6 108.7 111.5 – 125.3 126.7 – – – –

Bond lengths in nm and bond angles in degrees. From reference [38].

0.148 0.155 0.151 0.140 0.140 0.101 – 103.4 102.1 108.2 110.6 107.6 115.9 – – 26.5 160.1 0.1 16.9

0.148 0.155 0.152 0.134 0.141 0.101 – 103.7 101.8 108.7 113.3 105.9 114.4 – – 23.7 152.0 0.1 15.3

0.154 0.151 0.140 0.151 0.154 0.120 – 104.2 111.4 111.4 104.2 108.8 125.6 – – 0.0 180.0 0.0 0.0

0.154 0.151 0.133 0.151 0.154 0.120 – 103.4 112.6 112.6 103.4 108.1 126.0 – – 0.0 180.0 0.0 0.0

M.S. Miranda et al. / J. Chem. Thermodynamics 42 (2010) 1101–1106 TABLE 6 Nucleus independent chemical shifts (106). 6-Ring

5-Ring

NICS(0) Benzene Pyrrole Oxindole Indole 2-Indanone Isatin

NICS(1.0)

8.9

11.1

8.7 10.5 8.3 6.8

10.2 11.6 10.5 8.6

NICS(0)

NICS(1.0)

14.8 0.5 13.4 5.2 7.7

11.1 1.5 11.0 0.9 1.7

O +

O N H

N H

8C+7H+N+O

+

ence for the current species may thus be deduced to be ca. 260 kJ  mol1. This is a typical difference. We are encouraged, if not surprised. The second makes use of a recent model of aromaticity designed for heterocycles related to indane and indene [44] so we suggest the equation

Oxindole þ 2C2 H6 ! o-C6 H4 ðCH3 Þ2 þ CH3 CH2 CONHCH3 :

ð7Þ

While the necessary value for N-methylpropionamide is not available from experiment, the desired consensus value of 269 kJ  mol1 may be plausibly derived by assuming thermoneutrality for the reactions

the benzenoid ring, the presence of a sp3-hybridized carbon atom in the 5-membered ring is likely to prevent the circular electron delocalization to become effective around this ring. This fact would certainly be reflected in the aromatic character of such a ring and of the whole molecule. In order to ascertain this conjecture we have conducted nucleus independent chemical shifts (NICS) calculations for oxindole (A) and some related planar one-ring (benzene and pyrrole) and two-ring molecules (indole, 2-indanone, isatin), the results being reported in table 6. As can be seen from this table the aromaticity of the benzene ring of oxindole, 2-indanone, and indole is essentially the same and does not differ significantly from that of the benzene ring alone. On the other hand the 5-membered rings of oxindole and 2-indanone does not display significant aromatic character in contrast to the aromaticity observed for the pyrrole rings. In order to obtain a reliable estimate of the enthalpy of formation of oxindole, we have also conducted calculations using the G3(MP2)//B3LYP method [29] for all the molecules involved in the following gas phase reactions:

N H

1105

CH3 CONHCH3 ½ð45Þ þ CH3 CH2 COOCH3 ! CH3 CH2 CONHCH3 þ CH3 COOCH3 ;

ð8Þ

CH3 CONHCH3 ½ð45Þ þ CH3 CH2 COCH2 CH3 ! CH3 CH2 CONHCH3 þ CH3 COCH2 CH3 :

ð9Þ

Reaction (7) is so found to be exothermic by ca. 15 kJ  mol1. This value is very nearly the same as for indene and indane, and even the weakly destabilized phthalic anhydride [12], N-methylphthalimide [46], and isatin [9], all species in which any aromatic delocalization resides almost totally in the benzene rings, and very different from the more extensively delocalized indole and benzimidazole. We are pleased, if not surprised. We may conclude that the thermochemistry of oxindole is now well-understood in terms of calorimetry, calculation, and general chemical concepts. Acknowledgements

ð5Þ

Thanks are due to Fundação para a Ciência e a Tecnologia, F.C.T., Lisbon, Portugal, and to FEDER for financial support to Centro de Investigação em Química of the University of Porto (CIQ-UP). M.S. Miranda thanks the F.C.T. for the award of the postdoctoral scholarship (BPD/5594/2001) and for the financial support under the frame of the Ciência 2008 program.

ð6Þ

References

O

We have chosen these two reactions on the basis of the availability of experimental thermochemical data for the auxiliary compounds used. The enthalpy of reaction calculated at the G3(MP2)//B3LYP level was combined with the experimental standard molar enthalpies of formation of all the intervening species to obtain the standard molar enthalpy of formation of oxindole in the gas phase, at T = 298.15 K. The experimental gas-phase enthalpies of formation at T = 298.15 K 1 used are: indane, Df Hm ðgÞ ¼ ð60:3  1:7Þ kJ  mol [39]; indoline, 1 Df Hm ðgÞ ¼ ð120:0  2:9Þ kJ  mol [40]; 2-indanone, Df Hm ðgÞ ¼ 1 [38]; carbon atom, Df Hm ðgÞ ¼ 716:67 ð56:6  4:8Þ kJ  mol 1 1 kJ  mol [41]; hydrogen atom, Df Hm ðgÞ ¼ 218:00 kJ  mol [41]; 1 [41]; oxygen atom, nitrogen atom, Df Hm ðgÞ ¼ 472:68 kJ  mol 1 Df Hm ðgÞ ¼ 249:18 kJ  mol [41]. The G3(MP2)//B3LYP calculated enthalpies of formation are presented and compared with the experimental value in table 4. As can be seen from this table the computational estimates are in excellent agreement with the experimental value, both calculated estimates being within the experimental uncertainty. From the nearly equal enthalpies of formation of calorimetric experiments and quantum chemical calculations, we may now investigate two recent thermochemical models and modes of comparison. The first relates amides to their corresponding imine [11] and so oxindole is related to the unconventional tautomer of the parent heterocycle, namely the model is 3H-indole. A value of ca. 193 kJ  mol1 has been suggested for the gas-phase enthalpy of formation of this species [42,43] and so the amide–imine differ-

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JCT 10-68