Acta Chim. Slov. 2002, 49, 575–585. 575 SYNTHESIS AND REACTIVITY OF MANNICH BASES. XIV. BASE-CATALYZED CYCLOCONDENSATION OF P–AMINOKETONES TO 1,5-BENZODIAZEPINES AND 1,4-NAPHTHODIAZEPINES Gheorghe Roman Department of Chemistry, “Transi lvania” University, 29 Eroilor Blvd., Brașov, RO-2200, Romania Eugenia Comaniță Department of Organic Chemistry, “Gh. Asachi” Technical University, 71A D. Mangeron Blvd., Iași,RO-6600, Romania Bogdan Comaniță National Research Council, Institute for Chemical Process and Environmental Technology, Montreal Road Campus, K1A 0R6, Ottawa, Canada Received 03-04-2002 Abstract Several 2,3-dihydro-1,5-benzodiazepines and 2,3-dihydronaphtho[2,3-b]-1,4-diazepines were prepared via cyclocondensation of the corresponding ortho-arylenediamine with 3-dialkylaminopropiophenone hydrochlorides in ethanol in the presence of anhydrous sodium acetate. Introduction The discovery of diazepam followed by many other psychotropic agents sharing a 1,4-benzodiazepine skeleton has also promoted the studies on the isomeric 1,5-benzodiazepine ring system1 along with the synthetic approaches to mono- and diannelated 1,5-benzodiazepines.2 Due to their accessibility, easy functionalization and potential pharmacological proprieties, mainly 1,5-benzodiazepinone and 1,5-benzodiazepinedione derivatives have received significant attention. Peripheral cholecystokinin receptor agonists,3 CCK-B/gastrin receptor antagonists,4 arginine vasopressin antagonists,5 CNS depressants,6,7 antiamoebics8 and antiproliferative agents9 derived from 1,5-benzodiazepinones have been reported. Heterofused 1,5-benzodiazepinones have also been evaluated towards benzodiazepine receptor binding10 or HIV reverse transcriptase inhibition11 and found to possess anticonvulsant,12 analgesic or anti-inflammatory,13 antipsychotic14 or PAF-induced aggregation inhibitory15,16 activities. The synthesis of 1,5-benzodiazepine derivatives 1-3, hydrogenated in the heterocyclic Gh. Roman, E. Comaniță, B. Comaniță: Synthesis and reactivity of Mannich bases. XIV. Base-catalyzed… 576 Acta Chim. Slov. 2002, 49, 575–585. R1 N, R1 R2 R2 R1 R2 1 3 2 Figure 1 ring (Figure 1), has been less investigated. In particular, 2,4-disubstituted 2,3-dihydro-1H-1,5-benzodiazepines 2 (R1, R2=alkyl, (hetero)aryl) have been synthesized by cyclocondensation of ortho-phenylendiamine with ketones,17 chalcones18 or via a more recently described three-component one-pot procedure involving a coupling-isomerisation sequence of an electron poor (hetero)aryl halide and a terminal propargyl alcohol, subsequently followed by cyclocondensation with ortho-phenylendiamine.19 When 2,3-dihydro-1H-1,5-benzodiazepines substituted only at the position 4 (2, R1=alkyl, (hetero)aryl, R2=H) represent the preparative target, the cyclocondensation of ortho-arylenediamines with Mannich bases 4 (useful synthetic equivalents of the less stable 2-propen-1-ones 5) seems to be the most reasonable entry. A few older references describing this approach to 1,5-benzodiazepines are available20 along with a recent one.21 O Ar NR2 Ar O R R ^'^ H3C N N C6H5 7 N" "Ar H3C N Ar N H C6H5 8 NH2 Ar H2NT N 9 Figure 2 Antileukemic benzopyrano[4,3-b]-1,5-benzodiazepine22 6 (Figure 2), the heterofused 2,3-dihydropyrazolo[4,3-b]diazepines23 7 and 8 or 2,3-dihydropyrimidino[4,5-b]-1,4- 4 5 6 Gh. Roman, E. Comanita, B. Comanita: Synthesis and reactivity of Mannich bases. XIV. Base-catalyzed… Acta Chim. Slov. 2002, 49, 575-585. 577 .24 diazepines 9 (Figure 2) have also been obtained through similar cyclocondensations. The present paper aims at preparing several simple, but yet unknown 2,3-dihydro-1,5-benzodiazepines through anhydrous sodium acetate-catalyzed cyclocondensation of Mannich bases derived from acetophenones with ortho-phenylenediamine. Another series of 2,3-dihydronaphtho[2,3-b]-1 H-1,4-diazepines has been obtained by a similar procedure using 2,3-diaminonaphthalene instead of ortho-phenylenediamine. Results and discussion The reaction between ortho-arylenediamines 10 and Mannich bases 11 is depicted in Scheme 1: O + Ar N(CH3)2HCI lla-h AcONa anh. t HN(CH3)2HCI - H20 12a-j Compound Ar R R 12a 4-methoxyphenyl H H 12b 4-bromophenyl H H 12c 4-methylphenyl H H 12d 2-thienyl H H 12e 2-hydroxy-5-methylphenyl H H 12f 3-bromo-2-hydroxy-5-methylphenyl H H 12g 2-hydroxy-5-methylphenyl CH=CH-CH=CH 12h 3-bromo-2-hydroxy-5-methylphenyl CH=CH-CH=CH 12i 2-hydroxyphenyl CH=CH-CH=CH 12j 2-hydroxy-4-methylphenyl CH=CH-CH=CH Scheme 1. Base-catalyzed cyclocondensation of ortho-arylenediamines with ketonic Mannich bases hydrochlorides The earlier cyclocondensations of ortho-phenylenediamines with Mannich bases hydrochlorides carried out by Hideg et al20 or Werner et al22 were conducted in Gh. Roman, E. Comaniță, B. Comaniță: Synthesis and reactivity of Mannich bases. XIV. Base-catalyzed… 578 Acta Chim. Slov. 2002, 49, 575–585. refluxing apolar solvents (e.g. benzene, toluene, xylene) with water separation as an azeotrope. The work-up in this procedure sometimes comprised, after the filtration of the amine hydrochloride, the distillation in vacuo of the solvent prior to the separation of 1,5-benzodiazepine.22 The present work employs a modification that replaces the highly toxic aromatic hydrocarbons with ethanol as a solvent. This modification ensures a more facile isolation of the reaction product through a simple filtration; the by-products (water and the amine hydrochloride) as well as the unreacted reactants would be removed along with ethanol. Another difference from the earlier reported procedures refers to the use of anhydrous sodium acetate as a basic catalyst in the cyclocondensation of diamines 10 with Mannich base hydrochlorides 11, as it has been considered that the addition of a mild base will be beneficial for the condensation between the ketonic group in Mannich bases 11 and the amine group in ortho-arylenediamines. While this work was in progress, Insuasty et al. reported their own investigations on the reaction of ortho-phenylenediamine with 3-(dimethylamino)propiophenones.21 In their detailed studies, that were also conducted using ethanol as solvent but in the absence of any catalyst, two of the 2,3-dihydro-1,5-benzodiazepines described in this paper (12a and 12b) were presented. As the yields reported by Insuasty et al for these two compounds are very similar to those recorded by us, no advantage arises from the use of anhydrous sodium acetate as a catalyst in the investigated reaction. To produce the fused diazepines 12, the hydrochloride of the required Mannich base 11 and the diamine 10 were refluxed in ethanol in the presence of anhydrous sodium acetate. A preliminary study conducted for the reaction of 1-(3-bromo-2-hydroxy-5-methylphenyl)-3-dimethylamino-1-propanone hydrobromide 11f and 1,2-diaminobenzene 10a has established that a reaction period up to 30 minutes resulted in reasonable yields of benzodiazepines and that refluxing the reaction mixture for longer reaction times lowers the yields of the desired 2,3-dihydro-1,5-benzodiazepines. This is consistent with the findings of Insuasty et al21, which have shown that when Mannich bases hydrochlorides and ortho-phenylenediamine were refluxed for 3-4 hrs, complex reaction mixtures comprising derivatives of the initially formed 2,3-dihydro-1,5-benzodiazepines are produced. By applying the established reaction conditions, the Gh. Roman, E. Comaniță, B. Comaniță: Synthesis and reactivity of Mannich bases. XIV. Base-catalyzed… Acta Chim. Slov. 2002, 49, 575–585. 579 yields in compounds 12 are moderate, higher yields of fused diazepines being recorded only in the case of bromine-substituted or naphthalene-fused diazepines, probably due to their lower solubility in ethanol. As our interest in the chemistry of Mannich bases is mainly directed to ß-aminoketones 11 derived from ortho-hydroxyacetophenones,24-28 most of compounds 12 were acquired from this less investigated type of aminomethylated ketones. By using several 3-dialkylamino-1-(2-hydroxy-5-methyl)propiophenone hydrochlorides and 3-(dialkylamino)-1-(3-bromo-2-hydroxy-5-methyl)propiophenone hydrobromides, it has been found out that nor the different amino moieties (dimethylamino, 4-morpholinyl or 1-piperidinyl), neither the nature of the counter ion in these salts could lead to major improvement of the yields. Only symmetric ortho-arylenediamines have been used to generate fused diazepines 12 since the involvement of diamines possessing two non-equivalent amino groups would afford a mixture of regioisomeric cyclocondensation products, whose separation should be performed prior to their characterization. The characterization of compounds 12 by IR spectroscopy revealed the typical band for the N-H stretching vibration at 3300-3400 cm-1 together with a band at 1610-1640 cm-1 due to the >C=N- group. The structure of 2,3-dihydro-1,5-benzodiazepines and 2,3-dihydronaphtho[2,3-b]-1,4-diazepines was further assigned by 1H- and 13C-NMR spectroscopy. The representative signal in the 1H-NMR spectra of compounds 12 is the two triplets pattern given by the protons of the neighbouring methylene groups. The signal of the N-H proton mingled with the signals of the 2-CH2- group,21,30 whose intensity always corresponds for 2.8-2.9 protons. The peak due to N-H proton could be evidenced only in the case of compound 12d. The singlet, noticed in the far off-set (above 15 ppm) of the spectra of the cyclocondensation products of Mannich bases derived from ortho-hydroxyacetophenones, was attributed to the phenolic proton involved in an intramolecular hydrogen bond with the nitrogen atom. 13C-NMR spectra confirmed the structure of the cyclic reaction products. Conclusions Cyclocondensation of ketonic Mannich bases hydrochlorides with ortho-arylenediamines proceeds smoothly in ethanol in the presence of anhydrous sodium Gh. Roman, E. Comaniță, B. Comaniță: Synthesis and reactivity of Mannich bases. XIV. Base-catalyzed… 580 Acta Chim. Slov. 2002, 49, 575–585. acetate and leads to fused diazepines. The use of ethanol instead of aromatic hydrocarbons ensures milder reaction conditions, shorter reaction times and an easy separation of the cyclocondensation products from the reaction mixture. However, the yields of fused diazepines, obtained via a base-catalyzed cyclocondensation, are comparable with those reported when the reaction was carried out without any catalyst. Along with several 1,5-benzodiazepines, a series of naphtho-1,4-diazepines have been prepared starting from 2,3-diaminonaphthalene. The NMR analysis of fused diazepines derived from ortho-hydroxyacetophenones revealed the signal for the phenolic proton as a singlet located far in off-set as a result of an intramolecular hydrogen bonding. Experimental Melting points were determined using a Boetius hot-stage microscope and are uncorrected. Elemental analyses were performed on a Carlo Erba-1106 analyzer. IR spectra were registered on a SPECORD M80 instrument. 1H- and 13C-NMR spectra were recorded on a Varian Gemini 300 NMR spectrometer in CDCl3 (with TMS for 1H-and CDCl3 for 13C-NMR as the internal reference), except for 12j, whose 1H-NMR spectrum was taken in DMSO-d6. All commercially available reagents were used without further purification. The Mannich bases hydrochlorides 11 required in this study, namely 1-(4-methoxyphenyl)-3-dimethylamino-1-propanone hydrochloride 11a,31 1-(4-bromophenyl)-3-dimethylamino-1-propanone hydrochloride 11b,32 1-(4-methylphenyl)-3-dimethylamino-1-propanone hydrochloride 11c,33 3-dimethylamino-1-(2-thienyl)-1-propanone hydrochloride 11d,34 1-(2-hydroxy-5-methylphenyl)-3-dimethylamino-1-propanone hydrochloride 11e,25 and 1-(3-bromo-2-hydroxy-5-methylphenyl)-3-dimethylamino-1-propanone hydrobromide 11f,29 1-(2-hydroxyphenyl)-3-dimethylamino-1-propanone hydrochloride 11g,26 1-(2-hydroxy-4-methylphenyl)-3-dimethylamino-1-propanone hydrochloride 11h,26 were synthesized by described in the literature. General procedure for the preparation of 4-aryl-2,3-dihydro-1H-1,5-benzodiazepines 12a-f. A mixture of ortho-phenylenediamine (0.54 g, 5 mmol) and Mannich base hydrochloride 11a-f (5 mmol) in ethanol (10 mL) were treated with Gh. Roman, E. Comaniță, B. Comaniță: Synthesis and reactivity of Mannich bases. XIV. Base-catalyzed… Acta Chim. Slov. 2002, 49, 575–585. 581 anhydrous sodium acetate (1.25 g) and refluxed for 30 min, when the color changed from light yellow to deep yellow or reddish. The reaction mixture was cooled to room temperature and then kept in a freezer for several hours. The solids were collected by filtration and washed thoroughly with water to remove the inorganic salts. All 4-aryl-2,3-dihydro-1 H-1,5-benzodiazepines 12a-f were recrystallized from ethanol prior to analysis. 2,3-Dihydro-4-(4-methoxyphenyl)-lH-l,5-benzodiazepine (12a). This compound was prepared from ortho-phenylenediamine 10a and Mannich base 11a, yellow leaflets (0.7 g, 55%), m.p. 152-153 °C (m.p.21 155 oC). Anal. Calculated for C16H16N2O: C, 76.16; H, 6.39; N, 11.10. Found: C, 76.05; H, 6.44; N, 11.03. IR (KBr, cm-1): 1628 (vC=N), 3404 (vNH). 1H NMR: 5 7.95 (dd, 2H, J1,3=2.1 Hz, J1,2=6.8 Hz), 7.34 (dd, 1H, J1,3=1.8 Hz, J 1,2=7.6 Hz), 6.91-7.00 (m, 4H), 6.72 (dd, 1H, J 1,3=1.7 Hz, J 1,2=7.5 Hz), 3.84 (s, 3H), 3.83 (t, 2H, J=5.9 Hz), 2.97 (t, 2H, J=5.9 Hz). 13C NMR: 5 168.00, 161.49, 139.75, 138.33, 131.74, 129.44, 128.73, 126.14, 120.82, 119.82, 113.78, 55.39, 53.26, 31.06. 4-(4-Bromophenyl)-2,3-dihydro-lH-l,5-benzodiazepine (12b) This compound was prepared from ortho-phenylenediamine 10a and Mannich base lib, yellow microcrystals (0.74 g, 49%), m.p. 138-139 °C (m.p.21 140 oC). Anal. Calculated for C15H13BrN2: C, 59.82; H, 4.35; N, 9.30. Found: C, 59.98; H, 4.17; N, 9.09. IR (KBr, cm-1): 1622 (vc=n), 3410 (vNH). 1H NMR: 5 7.83 (d, 2H, J=8.6 Hz), 7.54 (d, 2H, J=8.6 Hz), 7.34 (dd, 1H, J 1,3=1.4 Hz, J 1,2=7.7 Hz), 6.88-7.07 (m, 2H), 6.71 (dd, 1H, J 1,3=1 Hz, J 1,2=7.8 Hz), 3.80 (t, 2H, J=5.7 Hz), 3.00 (t, 2H, J=5.6 Hz). 13C NMR: 5 166.26, 140.19, 138.57, 137.52, 131.51, 130.50, 128.47, 126.77, 124.51, 120.66, 119.50, 51.97, 31.95. 2,3-Dihydro-4-(4-methylphenyl)- lH-l,5-benzodiazepine (12c) This compound was prepared from ortho-phenylenediamine 10a and Mannich base lie, yellow leaflets (0.49 g, 41%), m.p. 125-126 °C. Anal. Calculated for C16H16N2: C, 81.32; H, 6.82; N, 11.85. Found: C, 81.13; H, 6.56; N, 11.94. IR (KBr, cm-1): 1632 (vc=n), 3405 (vNH). 1H NMR: 5 7.86 (d, 2H, J=7.9 Hz), 7.35-7.21 (m, 3H), 7.01-6.91 (m, 2H), 6.70 (dd, 1H, J 1,3=1 Hz, J 1,2=7.9 Hz), 3.82 (t, 2H, J=5.7 Hz), 2.98 (t, 2H, J=5.7 Hz), 2.39 (s, 3H). 13C NMR: 5 Gh. Roman, E. Comaniță, B. Comaniță: Synthesis and reactivity of Mannich bases. XIV. Base-catalyzed… 582 Acta Chim. Slov. 2002, 49, 575–585. 168.04, 140.17, 139.80, 138.44, 136.74, 129.74, 129.07, 126.84, 126.13, 120.65, 119.64, 52.99, 31.34, 21.29. 2,3-Dihydro-4-(2-thienyl)-lH-l,5-benzodiazepine (12d) This compound was prepared from ortho-phenylenediamine 10a and Mannich base lid, yellow leaflets (0.52 g, 45%), m.p. 109-110 °C. Anal. Calculated for d3H12N2S: C, 68.39; H, 5.30; N, 12.27. Found: C, 68.59; H, 5.17; N, 12.37. IR (KBr, cm"1): 1625 (vc=n), 3405 (vNH). 'H-NMR: 5 7.41 (d, 1H, J=5 Hz), 7.36-7.38 (m, 2H), 7.05 (dd, 1H, J=3.8 Hz, J=5 Hz), 6.96-7.01 (m, 1H), 6.87-6.92 (m, 1H), 6.67 (d, 1H, J=7.8 Hz), 3.85 (bs, 1H), 3.71 (t, 2H, J=5.5 Hz), 3.02 (t, 2H, J=5.5 Hz). 13C-NMR: 5 162.1, 147.79, 141.39, 136.85, 131.55, 130.42, 128.11, 127.68, 127.14, 120.62, 119.59, 50.52, 33.69. 2,3-Dihydro-4-(2-hydroxy-5-methylphenyl)-lH-l,5-benzodiazepine (12e) This compound was prepared from ortho-phenylenediamine 10a and Mannich base lie, orange crystals (0.77 g, 61%), m.p. 112-113 °C. Anal. Calculated for Ci6Hi6N20: C, 76.16; H, 6.39; N, 11.10. Found: C, 76.38; H, 6.48; N, 10.97. IR (KBr, cm"1): 1610 (vc=n), 3307 (vNH). 'H NMR: 5 15.55 (s, 1H), 7.34 (bs, 1H), 7.24-7.31 (m, 1H), 7.14 (d, 1H, J=8.4 Hz), 6.99-7.09 (m, 1H), 6.87-6.97 (m, 2H), 6.71 (d, 1H, J=7.9 Hz), 3.81 (t, 2H, J=5.3 Hz), 3.09 (t, 2H, J=5A Hz), 2.30 (s, 3H). 13C NMR: 5 171.58, 160.42, 140.63, 133.62, 133.57, 129.31, 127.87, 127.27, 126.69, 120.40, 119.45, 118.78, 118.10, 51.02, 30.90, 20.68. 4-(3-Bromo-2-hydroxy-5-methylphenyl)-2,3-dihydro-lH-l,5-benzodiazepine (12f) This compound was prepared from ortho-phenylenediamine 10a and Mannich base llf, orange-reddish crystals (1.23 g, 74%), m.p. 192-193 °C. Anal. Calculated for Ci6Hi5BrN20: C, 58.02; H, 4.56; N, 8.46. Found: C, 57.81; H, 4.68; N, 8.36. IR (KBr, cm"1): 1613 (Vc=n), 3321 (vNH). 'H NMR: 5 7.44 (d, 1H, J=1.6 Hz), 7.29 -7.34 (m, 2H), 7.03-7.07 (m, 1H), 6.85-6.89 (m, 1H), 6.71-6.73 (m, 1H), 3.74 (t, 2H, J=5A Hz), 3.15 (t, 2H, J=5.2 Hz), 2.28 (s, 3H). 13C NMR: 5 170.17, 158.45, 141.55, 136.72, 131.08, 129.56, 128.04, 127.30, 126.85, 120.18, 119.18, 112.54, 94.36, 48.86, 31.96, 20.49. Gh. Roman, E. Comanita, B. Comanita: Synthesis and reactivity of Mannich bases. XIV. Base-catalyzed… Acta Chim. Slov. 2002, 49, 575–585. 583 General procedure for the preparation of 4-aryl-2,3-dihydro-lH-naphtho[2,3-b]-1,4-diazepines 12g-j. 2,3-Diaminonaphthalene (1.1 g, 7 mmol) was dissolved in ethanol (35 mL) and then treated with the Mannich base hydrochloride lle-h (7 mmol) and anhydrous sodium acetate (1.75g). The reaction mixture was refluxed for 30 min. and afterwards cooled in a freezer. The solids were collected by filtration, washed with plenty of water and air-dried. Recrystallization from ethanol afforded 4-aryl-2,3-dihydronaphtho[2,3-b]-1 H-1,4-diazepinesl2g-j. 2,3-Dihydro-4-(2-hydroxy-5-methylphenyl)-lH-naphtho[2,3-b]-l,4-diazepine (12g) This compound was prepared from 2,3-diaminonaphthalene 10b and Mannich base lie, yellow-greenish crystals (1.16 g, 55%), m.p. 182-183 °C. Anal. Calculated for C20H18N2O: C, 79.44; H, 6.00; N, 9.26. Found: C, 79.63; H, 6.14; N, 9.05. IR (KBr, cm-1): 1639 (vc=n), 3404 (vNH). 1H NMR: 5 15.13 (s, 1H), 7.70-7.75 (m, 2H), 7.61 (d, 1H, J=8 Hz), 7.24-7.39 (m, 3H), 7.15-7.17 (m, 2H), 6.95 (d, 1H, J=8.4 Hz), 3.87 (t, 2H, J=6.1 Hz), 3.08 (t, 2H, J=6.1 Hz), 2.32 (s, 3H). 13C NMR: 5 173.15, 160.57, 139.44, 137.53, 134.10, 132.84, 129.78, 128.02, 127.69, 127.01, 126.18, 126.07, 125.64, 124.11, 118.51, 118.28, 115.58, 52.06, 29.44, 20.74. 4-(3-Bromo-2-hydroxy-5-methylphenyl)-2,3-dihydro-lH-naphtho[2,3-b]-l,4-diazepine (12h). This compound was prepared from 2,3-diaminonaphthalene 10b and Mannich base llf, brick-reddish crystals (2.16 g, 81%), m.p. 237-239 °C. Anal. Calculated for C20H17BrN2O: C, 63.00; H, 4.49; N, 7.35. Found: C, 63.17; H, 4.61; N, 7.22. IR (KBr, cm-1): 1644 (vc=n), 3358 (vNH). 1H NMR: 5 7.16-7.80 (m, 8H), 3.84 (t, 2H, J=5.8 Hz), 3.16 (t, 2H, J=6 Hz), 2.31 (s, 3H). 2,3-Dihydro-4-(2-hydroxyphenyl)-lH-naphtho[2,3-b]-l,4-diazepine (12i) This compound was prepared from 2,3-diaminonaphthalene 10b and Mannich base llg, greenish crystals (1.17 g, 58%), m.p. 176-177 °C. Anal. Calculated for C19H16N2O: C, 79.14; H, 5.59; N, 9.72. Found: C, 79.33; H, 5.68; N, 9.57. IR (KBr, cm-1): 1627 (vc=n), 3397 (vNH). 1H NMR: 5 15.44 (s, 1H), 7.72-7.75 (m, 2H), 7.60 (d, 2H, J=8 Hz), 7.30-7.39 (m, 3H), 7.13 (s, 1H), 7.05 (d, 1H, J=8.2 Hz), 6.87 (t, 1H, J=8 Hz), 3.84 (t, 2H, J=6 Gh. Roman, E. Comaniță, B. Comaniță: Synthesis and reactivity of Mannich bases. XIV. Base-catalyzed… 584 Acta Chim. Slov. 2002, 49, 575–585. Hz), 3.07 (t, 2H, J=6 Hz). 13C NMR: ? 173.13, 162.83, 139.47, 137.20, 133.17, 132.87, 129.71, 128.03, 127.68, 126.24, 126.17, 125.64, 124.11, 118.89, 118.53, 118.10, 115.54, 51.81, 29.60. 2,3-Dihydro-4-(2-hydroxy-4-methylphenyl)-lH-naphtho[2,3-b]-l,4-diazepine (12j) This compound was prepared from 2,3-diaminonaphthalene 10b and Mannich base llh, greenish crystals (1.31 g, 62%), m.p. 180-181 °C. Anal. Calculated for C20Hi8N2O: C, 79.44; H, 6.00; N, 9.26. Found: C, 79.34; H, 6.11; N, 9.36. IR (KBr, cm"1): 1632 (vc=n), 3407 (vNH). *H NMR: 5 15.42 (s, 1H), 7.70-7.75 (m, 2H), 7.61 (d, 1H, J=7.9 Hz), 7.48 (d, 1H, J=8.1 Hz), 7.24-7.38 (m, 2H), 7.14 (bs, 1H), 6.85 (bs, 1H), 6.68 (d, 1H, J=8.1 Hz), 3.84 (t, 2H, J=5.6 Hz), 3.06 (t, 2H, J=5.7 Hz), 2.35 (s, 3H). 13C NMR: 5 173.05, 162.91, 144.25, 139.47, 137.42, 132.78, 129.78, 127.89, 127.65, 126.12, 125.94, 125.63, 124.09, 119.35, 118.79, 116.47, 115.53, 52.03, 29.07, 21.56. References and Notes 1. 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Comaniță E; Roman Gh.; Popovici I.; Comaniță B., J. Serb. Chem. Soc. 2001, 66, 9–16. 27. Comaniță E.; Popovici I.; Roman, Gh.; Robertson, G.; Comaniță B., Heterocycles 1999, 51, 2139– 2146. 28. Roman Gh., Comaniță E., Comaniță B., Tetrahedron 2002, 58, 1617–1622. 29. Roman Gh.; Comaniță E.; Comaniță B., Rev. Chim. (Bucharest) 2002, 53, 361–366. 30. Orlov V. D.; Kolos N. N.; Abramov A. F., Chem. Heterocycl. Comp. (Engl. Transl.) 1984, 1370– 1374. 31. Casy A. F.; Parulkar A. P., Can. J. Chem. 1963, 47, 423–427. 32. Constable E. C.; Rees D. G. F., Polyhedron 1998, 17, 3281–3289. 33. Maxwell C. E., Org. Synth. Coll. Vol. III 1955, 305–306. 34. Meth-Cohn O.; Gronowitz S., Acta Chem. Scand. 1966, 20, 1577–1587. Povzetek Opisana je enostavna enostopenjska sinteza 4-substituiranih 2,3-dihidro-1H-1,5-benzodiazepinov in 2,3-dihidro-1H-nafto[2,3-b]-1,4-diazepinov. Avtorji so izhajali iz ß-dialkilaminopropiofenonov (Mannichovih baz) in orto-arilendiaminov, pretvorbe pa so potekale v etanolu pod refluksom v prisotnosti brezvodnega natrijevega acetata. Produkti, benzodiazepini 12a–f in naftodiazepini 12g–j, so bili v veèini primerov izolirani v zmernih izkoristkih (41–81%). Gh. Roman, E. Comaniță, B. Comaniță: Synthesis and reactivity of Mannich bases. XIV. Base-catalyzed