Synthesis of quinolin-2-ones by an intramolecular Knoevenagel condensation and by tandem Michael–Knoevenagel heterocyclization

The synthesis of 2-(N-R-amino)- and 2-(N-vinylcarbonylamino)acylbenzenes has been carried out and their heterocyclization into quinolin-2-ones under the action of sodium ethylate has been studied.

Compounds containing the quinolin-2-one fragment have already been studied systematically as subjects of medicobiological investigations for more than 50 years. Since then it was discovered that quinolin-2-ones as structural units, form part of the composition of a series of natural alkaloids [1]. The investigations led to a remarkable result, but only in practically the last 10–12 years, when new biological targets were discovered and test systems based on them were designed and in practice highly coeffective screening was embodied in the search for new medicinals. It was established that derivatives of quinolin-2-ones may display properties of nonsteroidal selective androgen modulators [2–4] and may show effective action against hepatitis B [5], act as inhibitors of acyl coenzyme A and cholesterol acyltransferase and increase the permeability of calcium activated K⁺ channels [6,7], display high antiproliferative activity [8–11] and the ability to bind to 5-HT₃ receptors [12], to receptors of antibiotics [13], and are inhibitors of various types of kinase [14–17], of farnesyl transferase [18], and affect erectile dysfunction [19]. The established broad spectrum of biological activity of quinolin-2-ones derivatives studied up to the present time, on the one hand, stimulated the search of new medicinals of various profile based on them, and on the other, made urgent the problem of synthesizing new representatives of this class with the prospect of developing for them characteristic forms of biological activity and the potential of using them for practical purposes.

For the synthesis of new derivatives of quinolin-2-ones, we turned to the Knoevenagel intramolecular condensation using as precursor the corresponding derivatives of ortho-aminoacylbenzenes. This route to the synthesis of quinolin-2-one, comprising the heterocyclization of 2-(acetylamino)acetophenone under the action of aqueous alcoholic alkaline solution, was used for the first time in [20]. However, many years passed before a series of quinolin-2-ones was synthesized in a similar manner [21,22]. In all probability, insufficient attention to this method of synthesis was linked with the difficulties of obtaining the starting ortho-aminoacylbenzenes.

This was confirmed, for example, by the fact that with the development of new approaches to the synthesis of ortho-aminoacylbenzenes, the intramolecular Knoevenagel condensation as a method of heterocyclization in quinolin-2-ones became used more intensively [5,15,18,19].

Previously, in a brief communication [23], we showed that by the Knoevenagel reaction it was possible to synthesize the corresponding quinolin-2-ones from ortho-amino ketones of the 1,4-benzodioxane series. The condensation occurs in alcohol at 20 °C in the presence of an equimolecular quantity of sodium ethylate. In the present work we have studied the behavior of a series of ortho-(R-acetylamino)acylbenzenes under the action of the same reagent to obtain functionalized quinolin-2-ones.

The starting ortho-(R³-acetylamino)acylbenzenes 20–49 were obtained by the acylation of ortho-acylanilines 1–19 with acid chlorides of substituted acetic acids. Most of the ortho-acylanilines 1–5, 7–14, 17–19 used were synthesized as described in [23–28], but 6-amino-7-butyroyl-1,4-benzodioxane (6), 6-amino-7-(2-iodo-benzoyl)-1,4-benzodioxane (15), and 2-amino-4,5-dimethoxyacetophenone (16), were obtained by the reduction of the corresponding nitro compounds (see EXPERIMENTAL).

1–3 R = H, 1 R¹ = t-Bu, R² = Me; 2 R¹ = H, R² = Et; 3 R¹ = Br, R² = Et; 4– 15 R + R¹ = OCH₂CH₂O, 4 R² = Me, 5 R² = Et, 6 R² = Pr, 7 R² = cyclo-Pr, 8 R² = Ph, 9 R² = p-MeC₆H₄, 10 R² = m-FC₆H₄, 11 R² = p-FC₆H₄, 12 R² = o-ClC₆H₄, 13 R2 = p-ClC₆H₄, 14 R² = o-BrC₆H₄, 15 R² = o-IC₆H₄; 16, 17 R = R¹ = OMe, 16 R² = Me; 17 R² = cyclo-Pr; 20– 23 R = H, 20 R¹ = t-Bu, R² = Me, R³ = o-MeOC₆H₄; 21 R¹ = H, R² = Et, R³ = Ph; 22 R¹ = Br, R² = Et, R³ = Ph; 23 R¹ = Br, R² = Et, R³ = o-MeOC₆H₄; 24– 45 R + R¹ = OCH₂CH₂O, 24 R² = Me, R³ = Ph; 25 R² = Me, R³ = o-MeOC₆H₄; 26 R² = Et, R³ = Ph; 27 R² = Pr, R³ = Me; 28 R² = Pr, R³ = Ph; 29 R² = Pr, R³ = o-MeOC₆H₄; 30 R² = cyclo-Pr, R³ = Ph; 31 R² = cyclo-Pr, R³ = p-NO₂C₆H₄; 32 R² = R³ = Ph; 33 R² = p-MeC₆H₄, R³ = p-ClC₆H₄O; 34 R² = p-MeC₆H₄, R³ = CH₂Br; 35 R² = p-MeC₆H₄, R³ = p-NO₂C₆H₄; 36 R² = m-FC₆H₄, R³ = Ph; 37 R² = p-FC₆H₄, R³ = CH₂Br; 38 R² = o-ClC₆H₄, R³ = p-NO₂C₆H₄; 39 R² = p-ClC₆H₄, R³ = Pr; 40 R² = p-ClC₆H₄, R³ = Ph; 41 R² = p-ClC₆H₄, R³ = o-MeOC₆H₄; 42 R² = p-ClC₆H₄, R³ = p-NO₂C₆H₄; 43 R² = o-BrC₆H₄, R³ = Ph; 44 R² = o-IC₆H₄, R³ = Ph; 45 R² = o-IC₆H₄, R³ = o-MeOC₆H₄; 46, 47 R = R¹ = OMe, 46 R² = Me, R³ = Ph; 47 R² = cyclo-Pr, R³ = Ph

All the R-acylaminobenzenes 20–49 had not been obtained previously, their yields and physicochemical characteristics are given in Tables 1–3.

Table 1 Characteristics of Compounds 20–49

Table 2 Mass Spectra of Compounds 20, 26, 32, 36, 40, 59, 64, 67

Table 3 ¹H NMR Spectra of Compounds 20–49

We found further, that if the reaction of ortho-arylacetylaminoacylbenzenes 20–26, 28–32, 35, 36, 38, 40–47 was carried out under the conditions described in [23] (equivalent quantity of sodium ethylate, in alcohol, 20 °C), the heterocyclization, irrespective of the nature of the substituents in the aromatic ring of the starting anilides, was effected practically regioselectively and the corresponding quinolin-2-ones 50–72 were formed in high yield (see Tables 2, 4–6). The substituents R, R¹, R², and R³ are identical with the substituents of these in the starting anilides respectively.

Table 4 Characteristics of Quinolin-2-ones 50–74, 79, 80, 83, 86–88

Table 5 ¹H NMR Spectra of Quinolin-2-ones 74, 79, 80, 83, 86–88

Table 6 IR Spectra of Compounds 51, 56, 59, 60, 61, 64, 65, 70, 80, 83

5-Phenacetylamino-substituted 6-acyl-1,4-benzodioxanes 48, 49 were cyclized in a similar manner under the same conditions.

In contrast to this, derivatives of alkyl (compounds 27, 39) or aryloxy (compound 33) substituted acetic acids did not react, but derivatives of β-bromopropionic (bromomethylacetic) acid 34, 37 were converted into the products of hydrogen bromide elimination (compounds 75, 76) and nucleophilic substitution of the halogen atom (compounds 77, 78), and not into quinolin-2-ones of type A.

It turned out that if the alkoxy derivatives 77, 78 were treated repeatedly with 2 equiv. sodium ethylate, and β-bromomethylacetylamines 34, 37 were reacted with 3 equiv. alcoholate and the reaction was carried out with heating, then in both cases alkoxy-substituted quinolin-2-ones 79, 80 were formed in high yield.

34, 77, 79 R = Me; 37, 78, 80 R = F

When transforming β-haloethylcarbonylamino-substituted acylbenzenes 34, 37 into alkoxy-substituted quinolin-2-ones 79, 80, two separate and subsequent processes are undergoing. 1) Conversion of the starting anilides 34, 37 into alkoxyethylcarbonylamino-1,4-benzodioxanes 77, 78, in all probability, occurs in an excess of alcoholate by way of both the direct substitution reaction of the halogen atom by an alkoxy group, and addition of ethanol to the α,β-vinyl group of compounds 75, 76, catalyzed by alcoholate, and 2) subsequent condensation into quinolin-2-ones 79, 80.

81, 82, 83 R = Cl

Indirect confirmation of the fact that the β-alkoxyethylcarbonyl fragment in compounds 77, 78 may be formed from the vinylcarbonyl substituent in the process of base-catalyzed addition of alcohol according to Michael, is the conversion of 6-acyl-7-vinylcarbonylamino-1,4-benzodioxanes 75, 76, 81 into the corresponding alkoxy-substituted quinolin-2-ones 79, 80, 83 under heterocyclization conditions.

It is seen from the scheme that the formation of quinolinones 79, 80, 83 may occur both through the stage of forming addition products of ethanol to the vinylcarbonyl group according to Michael 77, 78, 82 and through the stage of forming the cyclic ion II, obtained in the process of adding alcohol according to a pseudo-Michael reaction involving the carbonyl group in the ortho-position to the vinyl-containing substituent. It is interesting that if the reaction of vinylcarbonylamino-substituted acylbenzenes 75, 76, 81 is completed with the formation of the corresponding quinolinones, analogously substituted benzodioxane 84 containing a 2-chloro-benzoyl group in the ortho-position is mainly converted into the product of Michael addition 85. In this way, a partial cleavage of the amide bond is observed with the formation of 7-acyl-6-amino-1,4-benzodioxane 12.

The obtained result shows that alkoxy-substituted acylaminobenzenes, the immediate precursors of the corresponding quinolinones, may in reality be formed from the vinylcarbonyl fragments by a Michael reaction. Regarding the impossibility of compound 85 to give products of heterocyclization, it is evident that the heterocyclization stage to the corresponding quinolinone is inhibited due to steric factors.

On the whole, irrespective of the fact that whether products of addition according to Michael are formed or heterocyclization into the corresponding quinolin-2-ones is effected through anions of types I, II (see scheme on p. 1112), arising at the stage of adding ethylate anion to the double bond of the vinylcarbonyl group, the process of forming alkoxy-substituted quinolin-2-ones (of type 79, 80, 83) from ortho-acylanilides of acrylic acid (of type 75, 76, 81) under the action of sodium ethylate may be considered as a tandem heterocyclization.

It is interesting to note that if 3 equiv. alcoholate and heating are necessary for complete conversion of β-haloethylcarbonylamino-substituted benzodioxanes 34, 37 into the corresponding quinolin-2-ones 79, 80, then compounds 27, 33, and 39 were practically unchanged by the action of 1 equiv. sodium ethylate at 20 °C, but underwent complete conversion into the corresponding quinolin-2-ones 86–88 at a substrate–sodium ethylate ratio of 1:2 in boiling alcohol.

27, 86 R = Pr, R¹ = Me; 33, 87 R = p-MeC₆H₄, R¹ = p-ClC₆H₄O; 39, 88 R = p-ClC₆H₄, R¹ = Pr

According to the scheme of the intramolecular variant of the Knoevenagel condensation of N-acylamino-substituted acylbenzenes 20–49, 77, 78 studied by us, this conversion may be effected under the action of even catalytic quantities of alcoholate, moreover, this reaction may be initiated by released hydroxide anion [21,22].

Probably, since the positive charge on the carbon atom of the carbonyl group in the present case is lower than in the classical variant of the Knoevenagel condensation, the process is conducted significantly more slowly. In our case, it is therefore necessary to use a larger quantity of alcoholate to achieve complete conversion of the starting substrates into quinolin-2-ones. In reality, we have established that under the action of catalytic amounts of sodium ethylate chromatographically appreciable quantities of condensation products are formed only after 10–12 h.

The lower proton mobility of hydrogen atoms in the methylene component of the starting substrates 27, 33, 39, 77, 78 (in comparison with classical substrates) leads to the fact that their heterocyclization into the corresponding quinolin-2-ones succeeds not only because of the increase in alcoholate concentration, but also as a result of an increase in times of the reaction and heating.

It is important to emphasize that under conditions of heterocyclization not only is the Knoevenagel intermolecular condensation not observed but also there is no formation of the isomeric quinolones (quinolin-4-ones) from substrates for which this is possible (compounds 20–29, 46, 48).

Experimental

The IR spectra were recorded on a UR 20 instrument in nujol (compounds 51, 56, 60, 61, 64, 65, 70, 83) or hexachlorobutadiene (compounds 59, 80). The ¹H and ¹³ C NMR spectra were obtained on a Bruker Avance 400 instrument (at 400 MHz and 100 MHz respectively), internal standard was TMS. Mass spectra were recorded on a Finnigan SSQ 7000 (GC-MS type) instrument using a capillary column (30 m × 2 mm, stationary phase DB-1), carrier gas was helium (40 ml/min) with temperature programing from 50 to 300 °C (10 deg/min). Ionization energy was 70 eV. Elemental analysis was carried out on a Vario-II CHN analyzer. A check on the purity of compounds obtained and the separation of certain reaction mixtures was effected by TLC on Al₂O₃, activity grade II (according to Brockmann) in the systems ether–petroleum ether (40–70 °C), 1:3, or ether–CH2Cl2–petroleum ether (40–70 °C), 1:1:3 by volume.

1-(7-Nitro-2,3-dihydro-1,4-benzodioxin-6-yl)butan-1-one was obtained by the nitration of 1-(2,3-di-hydro-1,4-benzodioxin-6-yl)butan-1-one with acetyl nitrate in Ac₂O as described in [29]. Yield 84%; mp 90–91 °C (EtOH). ¹H NMR spectrum (CDCl₃), δ, ppm (J, Hz): 1.02 (3H, t, J = 6.7 CH₂CH₂CH₃); 1.79 (2H, m, CH₂CH₂CH₃); 2.78 (2H, t, J = 6.8, CH₂CH₂CH₃); 4.19 (4H, m, OCH₂CH₂O); 6.82 (1H, s, H-5); 7.71 (1H, s, H-8).

1-(7-Amino-2,3-dihydro-1,4-benzodioxin-6-yl)butan-1-one (6) was synthesized by the reduction of 1-(7-nitro-2,3-dihydro-1,4-benzodioxin-6-yl)butan-1-one by the procedure of [28]. Yield 77%; mp 65–66 °C (EtOH). ¹H NMR spectrum (CDCl₃), δ, ppm (J, Hz): 1.01 (3H, t, J = 6.8, CH₂CH₂CH₃); 1.71 (2H, m, CH₂CH₂CH₃); 2.79 (2H, t, J = 6.8, COCH₂CH₂CH₃); 4.18 (2H, m) and 4.28 (2H, m, OCH₂CH₂O); 5.88 (2H, br. s, NH₂); 6.11 (1H, s, H-5); 7.22 (1H, s, H-8). Found, %: C 64.78; H 6.69; N 6.12. C₁₂H₁₅NO₃. Calculated, %: C 65.14; H 6.83; N 6.33.

7-Nitro-2,3-dihydro-1,4-benzodioxin-6-yl 2-iodophenyl ketone was obtained by the nitration of (2,3-dihydro-1,4-benzodioxin-6-yl) 2-iodophenyl ketone by the procedure of [27]. Yield 86%; mp 167–168 °C (EtOH). ¹H NMR spectrum (CDCl₃), δ, ppm (J, Hz): 4.41 (4H, m, OCH₂CH₂O); 7.03 (1H, s, H Ar); 7.15 (1H, m, H Ar); 7.31 (2H, m, H Ar); 7.67 (1H, s, H-8); 8.04 (1H, d, J = 8.0, H Ar). Found, %: C 43.61; H 2.31; N 3.26. C₁₅H₁₀INO₅. Calculated, %: C 43.82; H 2.45; N 3.41.

7-Amino-2,3-dihydro-1,4-benzodioxin-6-yl 2-iodophenyl ketone (15) was synthesized analogously to compound 6 by the reduction of 2-iodophenyl 7-nitro-2,3-dihydro-1,4-benzodioxin-6-yl ketone, yield 79%, mp 168–169 °C (EtOH). ¹H NMR spectrum (DMSO-d₆), δ, ppm (J, Hz): 4.11 (2H, m) and 4.27 (2H, m, OCH₂CH₂O); 6.32 (1H, s, H-5); 6.65 (1H, s, H-8); 6.96 (2H, br. s, NH₂); 7.43 (1H, d, J = 8.1, H Ar); 7.52 (2H, m, H Ar); 7.63 (1H, d, J = 8.1, H Ar). Found, %: C 47.12; H 3.01; N 3.51. C₁₅H₁₂INO₃. Calculated, %: C 47.27; H 3.17; N 3.68.

4,5-Dimethoxy-2-nitroacetophenone was obtained by the nitration of 3,4-dimethoxyacetophenone, as described in [29]. Yield 64%; mp 121–122 °C (EtOH). ¹H NMR spectrum (CDCl₃), δ, ppm (J, Hz): 2.51 (3H, s, COCH₃); 3.90 (3H, s, OCH₃); 3.95 (3H, s, OCH₃); 7.21 (1H, s, H Ar); 7.62 (1H, s, H Ar).

2-Amino-4,5-dimethoxyacetophenone (16) was syhthesized analogously to compound 6 by the reduction of 4,5-dimethoxy-2-nitroacetophenone. Yield 55%. ¹H NMR spectrum (CDCl₃), δ, ppm: 2.48 (3H, s, COCH₃); 3.82 (3H, s, OCH₃); 3.87 (3H, s, OCH₃); 6.09 (1H, s, H Ar); 6.25 (2H, br. s, NH₂); 7.07 (1H, s, H Ar). Found, %: C 61.28; H 6.52; N 6.96. C₁₀H₁₃NO₃. Calculated, %: C 61.53; H 6.71; N 7.18.

( o -Acylamino)acylbenzenes 20-49 (General Method). The acid chloride of the corresponding acid (10 mmol) and 3 N NaOH solution (10 mmol) were added gradually and at the same time, with stirring to a solution of the corresponding ortho-aminoacylbenzene 1–19 in dioxane (25 ml). The reaction mixture was stirred for 30 min and poured into water (250 ml). The precipitated solid was filtered off, washed with water, air-dried, and recrystallized from a suitable solvent. The yields and physicochemical characteristics of the obtained anilides 20–49 are given in Tables 1 and 2.

Interaction of o -Acylaminoacylbenzenes 20–49 with Equimolecular Quantities of Sodium Ethylate (General Method). The corresponding acylanilide (2 mmol) was added to a solution of sodium ethylate, prepared from sodium (46 mg, 2 mmol) and ethanol (25 ml). The mixture was stirred at 20 °C for 2 h, poured into water (120 ml) and neutralized with 2 N HCl. The precipitated solid was filtered off, washed with alcohol, air-dried, and recrystallized from a suitable solvent. In the case of o-acylaminoacylbenzenes 20–26, 28–32, 35, 36, 38, and 40–49 the corresponding quinolin-2-ones 50–74 were obtained. Yields, physicochemical characteristics, and data of elemental analysis of the obtained heterocycles are given in Tables 3 and 4.

N -[7-(4-Methylbenzoyl)-2,3-dihydro-1,4-benzodioxin-6-yl]acrylamide (75) and 3-Ethoxy- N -[7-(4-methylbenzoyl)-2,3-dihydro-1,4-benzodioxin-6-yl]propionamide (77). A mixture (0.74 g) was obtained from 3-bromo-N-[7-(4-methylbenzoyl)-2,3-dihydro-1,4-benzodioxin-6-yl]propionamide (34) (0.81 g, 2 mmol), chromatography of which on preparative plates of Al₂O₃ gave the starting anilide 34 (0.36 g, 44%), compound 75 (0.21 g, 58%), and compound 77 (0.17 g, 42%). The yields of compounds 75 and 77 were calculated on the anilide consumed in the reaction. Compound 75: mp 116–117 °C. 1H NMR spectrum (CDCl₃), δ, ppm (J, Hz): 2.44 (3H, s, CH₃); 4.24 (2H, m) and 4.35 (2H, m, OCH₂CH₂O); 5.76 (1H, d, J = 10.1, COCH = CH ₂, H-cis); 6.30 (1H, dd, J = 10.1, J = 17.0, COCH = CH₂); 6.42 (1H, d, J = 17.0, COCH = CH ₂, H-trans); 7.14 (1H, s) and 8.36 (1H, s, H-5,8); 7.28 (2H, d, J = 7.9, H-3',5'); 7.57 (2H, d, J = 7.9, H-2',6'); 11.34 (1H, s, NH). Found, %: C 70.65; H 5.13; N 4.22. C₁₉H₁₇NO₄. Calculated, %: C 70.58; H 5.30; N 4.33. Compound 77: viscous oil. ¹H NMR spectrum (CDCl₃), δ, ppm (J, Hz): 1.19 (3H, t, J = 6.9, OCH₂CH₃); 2.43 (3H, s, CH₃); 2.66 (2H, t, J = 6.1, COCH₂CH₂O); 3.55 (2H, q, J = 6.9, CH₃CH₂O); 3.77 (2H, t, J = 6.1, COCH₂CH₂O); 4.23 (2H, m) and 4.32 (2H, m, OCH₂CH₂O); 7.08 (1H, s) and 8.22 (1H, s, H-5,8); 7.26 (2H, d, J = 8.2, H-3',5'); 7.56 (2H, d, J = 8.2, H-2',6'); 11.01 (1H, s, NH). Found, %: C 68.45; H 5.98; N 3.65. C₂₁H₂₃NO₅. Calculated, %: C 68.28; H 6.21; N 3.79.

N -[7-(4-Fluorobenzoyl)-2,3-dihydro-1,4-benzodioxin-6-yl]acrylamide (76) and 3-ethoxy- N -[7-(4-fluo-robenzoyl)-2,3-dihydro-1,4-benzodioxin-6-yl]propionamide (78) were obtained from 3-bromo-N-[7-(4-fluoro-benzoyl)-2,3-dihydro-1,4-benzodioxin-6-yl]propionamide (37) (0.82 g, 2 mmol) analogously to compound 75. From the mixture (0.79 g) of reaction products the starting compound 37 (0.43 g, 52%), compound 76 (0.18 g, 52%), and compound 78 (0.19 g, 48%) were separated chromatographically. The yields of compounds 76 and 78 were calculated on the anilide 37 consumed in the reaction. Compound 76: mp 141–142 °C. ¹H NMR spectrum, δ, ppm (J, Hz): 4.32 (4H, m, OCH₂CH₂O); 5.77 (1H, d, J = 10.1, COCH = CH ₂-cis); 6.29 (1H, dd, J = 10.1, J = 16.9, COCH = CH₂); 6.42 (1H, d, J = 16.9, COCH = CH ₂-trans); 7.08 (1H, s) and 8.36 (1H, s, H-5,8); 7.16 (2H, m, H Ar); 7.69 (2H, m, H Ar); 11.24 (1H, s, NH). Found, %: C 66.32; H 4.36; N 4.09. C₁₈H₁₄FNO₄. Calculated, %: C 66.05; H 4.31; N 4.28. Compound 78: viscous oil. ¹H NMR spectrum, δ, ppm (J, Hz): 1.18 (3H, t, J = 7.0, CH ₃CH₂O); 2.66 (2H, t, J = 6.1, COCH ₂CH₂O); 3.55 (2H, q, J = 7.0, CH₃CH ₂O); 3.77 (2H, t, J = 6.1, COCH₂CH ₂O); 4.28 (4H, m, OCH₂CH₂O); 7.02 (1H, s) and 8.21 (1H, s, H-5,8); 7.15 (2H, m, H Ar); 7.71 (2H, m, H Ar); 10.58 (1H, s, NH). Found, %: C 64.18; H 5.29; N 3.71. C₂₀H₂₀FNO₅. Calculated, %: C 64.34; H 5.40; N 3.75

Cyclization of ( o -Acylamino)acylbenzenes 27, 33, 39, 77, 78 was carried out by the general method using sodium ethylate (2 equiv.) in boiling ethanol for 5 h. The corresponding quinolin-2-ones 79, 80, 86–88 were obtained. Yields and physicochemical characteristics are given in Tables 4 and 5.

Cyclization of ( o -Acylamino)acylbenzenes 34 and 37. Analogously, but at a substrate–sodium ethylate ratio of 1:3, quinolinone 79 (0.31 g, 88%) was obtained from compound 34 (0.4 g, 1 mmol) and also the corresponding quinolin-2-ones 79 and 80 were obtained from compound 37 (0.41 g, 1 mmol).

Interaction of N -(7-Aroyl-2,3-dihydro-1,4-benzodioxin-6-yl)acrylamides 75, 76, 81, 84 with Sodium Ethylate. The corresponding anilide (1 mmol) was added to a solution of sodium ethylate prepared from sodium (46 mg, 2 mmol) and ethanol (10 ml). The mixture was refluxed for 2 h, the ethanol was evaporated, the residue was treated with water (30 ml), the resulting solid filtered off, and air-dried. (In the case of compound 84, after evaporation of the ethanol the reaction products were extracted with CHCl₃.) The corresponding quinolin-2-ones 79, 80, and 83 were obtained from vinylcarbonylaminobenzodioxanes 75, 76, and 81. From compound 84, after chromatography of the reaction mixture on Al₂O₃, N-[7-(2-chlorobenzoyl)-2,3-di-hydro-1,4-benzodioxin-6-yl]-3-ethoxypropionamide (85) (0.24 g, 72%) and 7-amino-2,3-dihydro-1,4-benzo- dioxin-6-yl 2-chlorophenyl ketone (12) (60 mg, 22%) were obtained. Compound 85: viscous oil. ¹H NMR spectrum, δ, ppm (J, Hz): 1.22 (3H, t, J = 7.2, OCH₂CH ₃); 2.74 (2H, t, J = 6.0, COCH ₂CH₂O); 3.58 (2H, q, J = 7.2, CH₃CH ₂O); 3.84 (2H, t, J = 6.0, COCH₂CH ₂O); 4.21 (2H, m) and 4.32 (2H, m, OCH₂CH₂O); 6.85 (1H, s, H Ar); 7.29-7.48 (4H, m, H Ar); 8.42 (1H, s, H Ar); 11.65 (1H, br. s, NH). Found, %: C 61.41; H 5.01; N 3.42. C₂₀H₂₀ClNO₅. Calculated, %: C 61.62; H 5.17; N 3.59.