Short communication
Photocycloaddition of 2-Morpholinopropenenitrile
to 8-Acetylquinoline
Dietrich Döpp and Andreas Jung
Fachbereich Chemie Universität Duisburg-Essen, D-45117 Essen, Germany * Corresponding author: E-mail: dietrich.doepp@uni-duisburg-essen.de
Received: 13-10-2008 Dedicated to Professor Blanko Stanovnik on the occasion of his 70'' birthday
Abstract
Upon broad-band UV-irradiation in benzene solution, the title compounds 2 and 5 form rel-(2R,2aR,8bS)-8b-acetyl-2-morpholino-1,2,2a,8b-tetrahydrocyclobuta[h]quinoline-2-carbonitrile (6) in a [2+2]- and rel-(5R,8R,10R)-8-acetyl-10-morpholino-5,8-ethano-5,8-dihydroquinoline-10-carbonitrile (7) in a [4+2]-photocycloaddition. The latter compound may be thermally cleaved into the starting materials 2 and 5 (AH^ = 130.5 ± 8 kJ mol-1 and AS^ = 46 ± 3 J mol-1 K-1) and hydrolyzed to the tricyclic diketone rel-(5R,8R)-8-acetyl-5,8-ethano-5,5-dihydroquinolin-10-one (8).
Keywords: Acylquinoline photochemistry, aminonitrile hydrolysis, biradical intermediate, captodative alkene, cyclore-versions, [2+2]- and [4+2]-photocycloadditions.
1. Introduction
Several light induced [2+2]-and [4+2]-cycloaddi-tions of a-cyanoenamines to suitable ring atoms of fused aromatic hydrocarbons and carbonyl derivatives thereof have been carried out successfully,1 especially to 1-aceto-naphthone (1) and analogous fused carbonyl compounds.2-4
When 1 was irradiated (X > 280 nm) in various solvents (cyclohexane, benzene, acetonitrile or methanol) in the presence of 2-morpholinopropenenitrile (2), a photo-Diels-Alder adduct 4 was readily formed, the structure of which was confirmed by a single crystal X-ray structural analysis.2 Analogous results were obtained with 1-napht-haldehyde and 1-naphthophenone.3 Later it was elucidated that a photoreversible [2+2]-photoaddition of 2 to the
Ac
-X
1,5
+
CN

hv
hv
Ac = COCH3
1,3,4: X = CH; 5,6,7: X = N
3,6
Ac
Cu^VHzO buffer
Vl
.N
o^Ac

Scheme 1
C1-C2 bond of 1 forming the tetrahydrocyclobu-ta[a]naphthalene 3 paralleled the [4+2]-photocycloaddi-tion generating 4 (see Scheme 1). While 3 proved to be photolabile and readily underwent cleavage to the starting materials 1 and 2 upon 313 nm irradiation in solution, the [4+2]-adduct was stable under the irradiation conditions and accumulated at the expense of 3.4 Similar results were also obtained with methyl naphthalene-1-carboxylate in place of 1.5
It had been surmised that the preferred geometry of the main product 4, bearing the morpholino group syn to the unaffected benzenoid ring, was facilitated by an attractive interaction between the benzenoid ring and the partially electron-depleted donor in an intermediate capto-dative6 biradical 9 assuming preferentially conformation 9A and eventually leading to product 4, while conformer 9B should rather show a repulsive and thus destabilizing interaction and return to the starting materials1 or cyclize to 3 (see Scheme 2).
compounds, a trend to a decrease in efficiency compared to compound 1 was observed requiring longer irradiation times and leading to lower yields.7 Among the compounds studied, 8-acetylquinoline (5) performed moderately well. It shows a UV absorption maximum at 280 nm in acetoni-trile solution (log e = 3.9) allowing the use of benzene as solvent (facilitating mutual complexation of both reac-tants prior to the first bond forming step) and the use of Duran glassware (short wavelength cut-off at 280 nm) for selective excitation.
Like for 1, upon irradiation of 5 in the presence of 2 to 26% conversion of 5, two products were isolated after two consecutive chromatographic operations, namely the tetrahydrocyclobuta[h]quinoline 6 (13%) and the 5,8-et-hano-5,8-dihydroquinoline 7 (33%, yields refer to consumed starting material).
These products were characterized predominantly by 1H and 13C NMR spectroscopy including 1H,1H and 1H,13C correlation. The syn orientation of the morpholino

[1-2]
(complex)
Ac = COCH3 Mo = 4-morpholinyl
Scheme 2
Thus, we wondered whether aza-substitution in the unaffected ring would in any way influence the efficiency of the photocycloadditions by decreasing the attractive interaction within 9A.
2. Results and Discussion
We decided to test various 8- and 5-acylquinolines in photoreactions with 2. Generally, with both classes of
9B
St. m.
group with respect to the heterocyclic ring in 7 and the anti orientation of that group with respect to the quinoline moiety in 6 were supported by comparison of the 1H chemical shifts of the alicyclic part of these compounds with those for compounds 34 and 42, respectively, as well as for further analogous systems,5,8,9 and by NOE intensity difference measurements. Saturation of the resonance of the axial ^-methylene protons of 6 intensified the signals of 2a-H, 3-H, and 4-H. Irradiation into the resonance of the equatorial ^-methylene protons increased the signal in-
Fig. 1. Numbering and NOE interactions in compounds 6 and 7.
tensity of 5-H and 4-H in compound 7, and saturation of the resonance of HA intensified the signal of 7-H in that compound (see Fig. 1 for numbering, geometries and interactions).
The mass spectra (70 eV EI mode, direct inlet system) of both 6 and 7 did not show the molecular ions due to the lability of these products. Since the UV absorption of 6 with its styrene-like chromophor is extending to longer wavelengths than that of the starting material 5, the latter cannot (even when present in large excess) serve sufficiently as an effective screen to protect 6 from photochemical cleavage back to the starting materials, while the main product 7 is protected by 5 under the conditions of the irradiation (26% conversion of 5) and accumulates at the expense of the initially formed 6. Complete cleavage of isolated 6 into 2 and 5 was effected in hexadeutero-benzene using broadband UV radiation and monitored by 1H NMR. There was no indication of direct conversion into the main product 7.
It should be pointed out that [4+2]-photocycloaddi-tions of alkenes to the quinoline skeleton have not been reported before, and such photocycloadditions to naphthalenes are rare compared to [2+2]-cycloadditions of that ring system.10
As typical for a photo-Diels-Alder adduct, compound 7 was thermally reverted in a unimolecular process (temperature, k, and t1/2 given: 323 K, 1.25 ■ 10-6 s-1, 154 h; 333 K, 6.4 ■ 10-6 s1, 30.1 h; 343 K, 2.26 ■ 10-5 s-1, 8.5 h) with AH^ = 130.5 ± 8 kJ mol-1 and a negative entropy of activation AS^ = -46 ± 3 J mol-1 K-1.
The nature of the excited state of 5 responsible for the reactions cannot be stated with certainty. Attempting oxygen quenching to reveal triplet state participation turned out to be an inappropriate approach due to the sensitivity of 2 towards oxygen: ^-cyanocarbonyl-morpholine is always formed. It was found, though, that the reaction of photoexcited 5 could be partly quenched using tetra-methyldiazetine ^,^-dioxide (in cyclohexane: Àmax = 260 nm, log e = 3.96; log e = 2.0 at 310 nm)11 in concentrations between 10-3 to 10-2 mol/L. The ratio of products (6:7), however, remained constant at 1.7 over that range, indicating that probably the same excited state [3(n,n*)] was involved in the formation of both products.
Since alkenes like 2 are suitable as ketene equivalents, the bridged diketone 8 could be prepared in good yield by mild hydrolysis12 of 7 in a buffered Cu(II) salt solution.
3. Conclusion
Substitution of C-8 of 1-acetonaphthone (1) by nitrogen as in 8-acetyl-quinoline (5) retards but does not suppress the [2+2]- and [4+2]-photocycloadditions of 2-morpholinopropene-nitrile (2) to the acylated ring. However, a tendency toward a higher yield of the minor pro-
duct, compared to the results obtained with 1, where only 2.6% or less of 3 had ever been isolated,4 was observed. Thus, another example of the rare [4+2]-photocycloaddi-tion of an alkene to a naphthalene-like system has been presented, and the product of that reaction shows normal behavior in cycloreversion.
4. Experimental Part
General: Melting points have been determined using a Reichert Thermovar hot-stage microscope. - IR spectra (from KBr disks) have been recorded on a Perkin-Elmer 283 instrument, UV spectra on a Perkin-Elmer 554 spectrophotometer. - NMR spectra: Unless stated otherwise, a Bruker WM 300 instrument (1H at 300 MHz, 13C at 75 MHz) has been used on solutions in CDCl3 with TMS as an internal standard. The 13C chemical shifts have been taken from the broadband 1H decoupled spectra and assigned on the basis of DEPT and 13C,1H correlations. - Mass spectra: A Varian MAT 311 spectrometer equipped with digitalized data processing operating in the EI mode at 70 eV ionization energy in connection with a direct inlet system (temperature given) has been used. - Preparative layer chromatography (plc) was conducted on 20 cm tall and 48 cm wide glass plates covered with a 1 mm thick slurry applied and air dried layer of silica gel Merck PF254. Sample quantities were adjusted to achieve complete separation. Zones were detected by indicator fluorescence, mechanically removed from the plates and eluted with acetone.
Starting materials: 1-(Quinolin-8-yl)ethanone (8-acetyl-quinoline) (5). Was prepared13 by oxidation of 1-(quino-lin-8-yl)ethanol (prepared from quinoline-8-carbaldehyde and methyl- magnesium iodide) using a finely powdered mixture of KMnO4 and CuSO4 ■ 5 H2O and purified by bulb-to-bulb distillation at 125 °C/0.05 mbar, m.p. 38-40 °C (ref.14 m.p. 45 °C), yield 55%. - 80 MHz 1H NMR: 8 = 8.90, dd, 1H, J = 1.9 and 4.2 Hz, 2-H), 8.12 (dd, 1H, J = 1.9 and 8.3 Hz, 4-H), 7.92-7.19 (several m, 5H), 2.37 (s, 3H, CH3). - 2-Morpholinopropenenitrile (2) was prepared according to Temin,15 colorless to yellowish crystals, m.p. 61-62 °C, ref.15 m.p. 62.5-63.5 °C. - UV (acetonitri-le): (log e) = 258 (3.83), 306 nm (2.46).
Irradiation of 5 in presence of 2: A solution of 1.01 g (5.8 mmol) of 5 and 1.73 g (12.5 mmol) of 2 in 130 mL of benzene was purged with a stream of argon 15 min prior and during the entire irradiation (10 h) with a Philips HPK 125W high pressure mercury lamp mounted in a water cooled Duran immersion well (X > 280 nm). The residue after concentration was passed over a 2 cm thick layer of dry silica gel Merck PF254 using toluene/ethyl acetate 2:1 (v/v), concentrated and subjected to plc using the same solvent for developing. Three zones were detected: zone
1, Rf 0.54, containing 739 mg (4.3 mmol) of starting material 5 (thus 26% of 5 had been converted), zone 2, Rf 0.23 (containing 256 mg), and zone 3, Rf 0.13 (containing 127 mg). All yields reported below refer to converted starting material 5.
re/-(2Ä,2aÄ,8bS)-8-Acetyl-2-morpholino-1,2,2a,8b-te-trahydrocyclobuta[Ä]quinoline-2-carbonitrile (6).
From zone 3, by crystallization from 2-propanol 60 mg (13%) of colorless crystals, m.p. 176-177 °C, were obtained. - IR: V = 2220 (weak, CN), 1710 (C=O) cm-1. -UV (acetonitrile): Àmax (log e) = 272 (3.9), 320 (2.95) nm. - 1H NMR: ABX 7.42 (5-H), = 7.18 (6-H), 8X = 8.41 (7-H), JAB = 7.7, JAX = 1.7, JBX = 4.9 Hz], ABX [5A = 6.66 (4-H), 5B = 5.83 (3-H), 5X = 3.44 (2a-H), JAB = 9.7, JAX = 1.0, JBX = 5.8 Hz], 3.74-3.71 (m, 4H, CHa^O-CH2), aAB [5a = 3.28 (anti 1-H), 5B = 2.89 (syn 1-H), |2JAB| = 12.2 Hz], 2.53 (m, 2H, ax. HC-N-CH), 2.05 (m, 2H, eq. HC-N-CH), 2.04 (s, 3H, CH3). - 13C NMR: 5 = 204.1 (C=O), 154.2 (C8-a), 149.5 (C-7), 135.1 (C-5), 129.9 (C-6), 127.8 (C-4a), 123.4 (C-4), 123.0 (C-3), 116.3 (CN), 66.4 (H2C-0-CH2), 63.0 (C-2), 49.7 (C-8b), 47.5 (C-2a), 47.0 (H2C-N-CH2), 41.4 (C-1), 25.9 (CH3). - MS (130 °C): m/z (%) = 264 (18), 239 (25) [M+ - HCN - COCH3], 181 (48), 172 (94), 171 (21) [M+ - 2], 156 (32), 154 (4^), 138 (100) [representing 2+], 128 (30). - Anal.: Calcd for C18H19N302 (309.43): C, 69.88; H, 6.19; N, 13.58. Found: C, 69.86; H, 6.16; N, 13.50.
re/-(5Ä,8Ä,10Ä)-8-Acetyl-10-morpholino-5,8-dihy-dro-5,8-ethanoquinoline-10-carbonitrile (7). From zone 2, 150 mg (32%) of colorless crystals were obtained by crystallization from 2-propanol, m.p. 153-153.5 °C. - IR: v = 2220 (CN), 1710 (C=0) cm-1. - UV (acetonitrile): Amax = 266 nm (log e = 3.6). - 1H NMR: ABX [5A = 7.45 (4-H), 5, = 7.11 (3-H), = 8.31 (2-H), JAB = 7.5, JAX = 1.6, JBX = 5.1 Hz], ABX [5a = 6.98 (7-H), 5B = 6.72 (6-H), 5X = 4.47 (5-H), JAB = 7.7, JAX = 1.0, JBX = 6.4 Hz], 3.60-3.44 (m, 4H, CH2-0-CH2), 2.73 (m, 2H, ax. CH-N-CH), 2.55 (m, 2H, eq. CH-N-CH), 2.54 (s, 3H, COCH3), AB [5A = 2.30 (anti 9-H), 5B = 2.00 (syn 9-H), |2JAB| = 12.9 Hz]. -13C NMR: 5 = 206.3 (C=0), 162.4 (C-Aa), 146.2 (C-2), 137.4 (C-4), 133.3 (C-3), 132.0 (C-7), 130.6 (C-4a), 121.2 (C-6), 118.4 (CN), 66.3 (C-10 and H2C-O-CH2 superimposed), 60.6 (C-8), 48.7 (H2C-N-CH22), 44.7 (2C-5), 41.3 (C-9), 29.1 (CH3). -MS (138 °C): m/z (%) = 282 (15) [M+
-	HCN], 239 (29), 181 (29), 172 (80), 171 (76) [M+ - 2], 170 (16), 156 (81), 154 (73), 138 (100) [representing 2+].
-	Anal.: Calcd for C18H19N3O2 (309.43): C, 69.88; H, 6.19; N, 13.58. Found C, 69.82, H, 6.18; N, 13.51.
re/-(5Ä,8Ä)-8-Acetyl-5,8-dihydro-5,8-ethanoquinoline-10-one (8). In accord with a procedure published by Büchi,12 91 mg (0.29 mmol) of 7 were stirred with a finely powdered mixture of 233 mg (0.52 mmol) of CuSO4 ■ 5H20 and 154 mg (0.48 mmol) of Na2HPO4 ■ 12H2O in a
mixture of 5 mL of acetone and 3 mL of water for 96 h at room temperature. The filtrate was extracted with ethyl acetate and the extract was concentrated to 62 mg of crude product, which after crystallization from hexane/ethyl acetate melted at 101-102 °C. - IR: v = 1720 (10-C=0), 1705 (acetyl C=0), 1415, 1350, 700 cm1. - 1H NMR: ABX [5a = 7.61 (4-H), 5B = 7.15 (3-H), 5X = 8.38 (2-H), JAB = 7.5, JAX = 1.6, JBX = 5.1 Hz], ABX [5A = 7.04 (7-H), 5g = 6.75 (6-H), 5X = 4.49 (5-H), JAB = 7.6, JAX = 1.5, JBX = 6.1 Hz], 2.59 (s, 3H, CH3), AB [5A = 2.46 (anti 9-H), 5B = 2.39 (syn 9-H), |2JAB| = 17.6 Hz]. ^ 13C NMR: 5 = 204.8 (C=0), 202.1 (C=0), 161.9 (C-8a), 147.0 (C-2), 136.4 (C-7), 132.5 (C-4a), 130.6 (C-4), 130.0 (C-6), 121.4 (C-3), 61.5 (C-8), 58.6 (C-5), 37.1 (C-9), 28.6 (CH3). - MS (70 °C): m/z (%) = 171 (14) [M+-42], 170 (82) [M+-43], 156 (27), 154 (15), 143 (18), 142 (100) [M+-COCH3- CO], 141 (13), 129 (10), 128 (24). - Anal.: Calcd for C13H11N02 (213.24): C, 73.23; H, 5.19; N, 6.56. Found C, 7^.14; H, 5.24; N, 6.65.
Thermolysis of compound 7. Solutions of 25 mg of 7 in the proper amount of hexadeuterobenzene were kept in 5 mm NMR tubes at 50, 60, and 70 °C, and scanned after suitable time intervals. The relative concentrations of 7 and starting material 5 were determined by 1H NMR integration. Plots of ln c(7) vs. time gave straight lines from which k [s-1] was extracted by linear regression analysis.
5. References
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2.	D. Döpp, C. Krüger, H. R. Memarian, and Y.-H. Tsay, An-gew. Chem. 1985, 97, 1059; Angew. Chem. Int. Ed. Engl. 1985, 24, 1048.
3.	D. Döpp, H. R. Memarian, C. Krüger, and E. Raabe, Chem. Ber. 1989, 122, 585.
4.	D. Döpp and H. R. Memarian, Chem. Ber. 1990, 123, 315.
5.	D. Döpp and B. Mlinaric, Bull. Soc. Chim. Belg. 1994, 103, 449.
6.	H. G. Viehe, Z. Janousek, R. Merényi, and L. Stella, Acc. Chem. Res. 1985, 18, 148; H. G. Viehe, R. Merényi, and Z. Janousek, Pure Appl. Chem. 1988, 60, 1635; R. Sustmann and H.-G. Korth, Adv. Phys. Org. Chem. 1990, 26, 131.
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8.	C. Kruse, doctoral thesis, Duisburg University, 2001.
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Povzetek
Fotokemijska 1-acetonaftona (1) in 8-acetilkinolina (5) na 2-morfolinopropenonitril (2) v benzenu je vodila [2+2]-ci-kloadukta, rel-(2R,2aR,8bS)-8b-acetil-2-morfolino-1,2,2a,8b-tetrahidrociklobuta-[h]kinolin-2-carbonitrila (6) in [4+2]-cikloadukta, rel-(5R,8R,10R)-8-acetil-10-morfolino-5,8-etano-5,8-dihidrokinolin-10-karbonitrila (7). Pod termičnimi pogoji poteče razcep cikloadukta 7 v izhodni spojini 2 in 5 (AH^ = 130.5 ± 8 kJ mol-1 and AS^ = 46 ± 3 J mol-1 K-1) pod hidrolitskimi podoji pa pretvorba v triciklični diketon, rel-(5R,8R)-8-acetil-5,8-etano-5,5-dihidrokinolin-10-on (8).