Introduction

β-Lactam antibiotics comprises penicillins, cephalosporins, cephamycins, monobactams, carbacephems, and carbapenems and are so named since they all contain the β-lactam (2-azetidinone) moiety [1]. These miracle antibacterial drugs have served an important and highly successful role in medicine and in pharmaceutical industry [2,3,4]. Ezetimibe has 2-azetidinone ring in its structure and is used clinically as a cholesterol absorption inhibitor [5]. In addition, 2-azetidinones possess various other biological activities [6,7,8] and are also used as synthon for the synthesis of several organic compounds [9,10,11]. Several synthetic methods have been reported for the preparation of the 2-azetidinone ring [12,13,14,15,16,17,18,19,20].

Sulfur-containing organic molecules are a very important motif; particularly, aryl sulfides and their derivatives are imperative molecules having biological, pharmaceutical, and material interest [21, 22]. Many synthetic methods have been developed for the synthesis of aryl sulfides [21,22,23,24]. The development of transition-metal-catalyzed synthesis of aryl sulfides using a thiol precursor is also reported [21, 25,26,27,28,29,30].

In the past few decades, synthesis of heterocyclic compounds containing nitrogen and sulfur has been of great interest for researchers, due to their potential use in the pharmaceutical and medicinal applications [31].

Some of β-lactam antibiotics such as penicillins, cephalosporins, and monobactams containing thioether group in their structure [1]. N-Thiolated β-lactams (β-lactam compounds have a sulfur substituent on the nitrogen center) have been synthesized which have been represented a broad family of bioactive molecules and the thiol-substituent was effective at biological activities [32, 33]. Also, series of N-sulfonyl monocyclic [34] and 3-thiolated β-lactams [35] have been prepared and evaluated for their in vitro antibacterial and antifungal activities against pathogenic strains.

Hence, according to the above facts, the novel 2-azetidinones having thioether moieties were synthesized using copper-catalyzed thioetherification of 2-azetidinones with thiol precursor.

Results and discussion

We started our studies by synthesis of cis 2-azetidinones containing aryl chloride substituents in N-1 or C-3 or C-4 position (Table 1). Previously application of Vilsmeier reagent in the preparation of 2-azetidinones via ketene-imine cycloaddition has been reported [36, 37].

Table 1 Synthesis of 2-azetidinones containing aryl chloride substituents
Full size table

Schiff base 1 on reaction with substituted acetic acid 2 in the presence of Vilsmeier reagent and triethylamine at room temperature afforded cis 2-azetidinones 3a–3f.

1H NMR spectra of compound 3a–3f displayed two signals about 5.2 and 5.5 ppm for H-4 and H-3, respectively, with the coupling constant about 4.7 Hz, this clearly indicated the cis stereochemistry for 2-azetidinones 3a–3f (the coupling constant H-3 and H-4 (J3,4 > 4.0 Hz) for the cis stereoisomer and (J3,4 ≤ 3.0 Hz) for the trans stereoisomer) [38, 39].

Compound 3a, treated with iodobenzene in the presence of CuI and S8 at 110 °C, afforded 2-azetidinone containing thioether 5a, which was characterized by spectral data and elemental analysis. To improve the yield and find the optimum condition for the synthesis of 2-azetidinone 5a, next, condition of reaction was investigated. All reactions were monitored by TLC (Table 2).

Table 2 Reaction condition in the synthesis of 2-azetidinone 5a
Full size table

According to Table 2, reaction of 2-azetidinone 3a and iodobenzene in the presence of CuI as a catalyst, Na2S2O3·5H2O as a sulfur source and K2CO3 as a base in dimethylformamide at 110–120 °C is the best condition with the highest yield. The reaction was not performed at room temperature.

With the optimized conditions in hand, the reactions of different 2-azetidinones 3 with various aryl or alkyl halides 4 were examined to explore the scopes of the reaction (Scheme 1). The results were shown in Table 3.

scheme 1
Table 3 Scope of the thioarylation or thioalkylation of halogenated-2-azetidinones
Full size table

The purity of the compounds was checked by TLC and elemental analysis. Spectral data (IR, 1H NMR, and 13C NMR) of all the compounds were in full agreement with the proposed structures. IR spectra of β-lactams 5a–5p showed sharp peaks at 1731–1765 cm−1 due to β-lactam carbonyl group. Also signal for aldehyde carbonyl group of products 5a, 5e, 5h, 5k, and 5o were observed at 1723–1732 cm−1. Their 1H NMR spectra showed well-separated doublet of doublet for H-4 and H-3 protons of cis β-lactams 5a–5p. The signals appeared at 9.85–10.08 ppm for the carbonyl of CHO group in compounds 5a, 5e, 5h, 5k, and 5o. Peaks at 161.8–164.4 ppm were attributed to the 2-azetidinone carbonyl and 190.2–192.4 ppm was referred to the aldehyde carbonyl confirmed by 13C NMR.

According to a reported mechanism for the thioarylation or thioalkylation using sodium thiosulfate as a thiol precursor [10, 30], it is suggested that the reaction performed via formation of aryl or alkyl thiosulfate and organo-copper intermediates (Scheme 2).

scheme 2

Conclusion

We have developed a protocol for the synthesis of new 2-azetidinones containing sulfide groups in N-1 or C-3 or C-4 position. Copper-catalyzed thioarylation or thioalkylation of halogenated-2-azetidinones using CuI as a catalyst, Na2S2O3·5H2O as a sulfur sources and K2CO3 as a base gave desired products in moderate to excellent yields. Purification of products was simple and proceeded without the use of column chromatography.

Experimental

All required chemicals were purchased from Merck, Fluka, or Acros chemical companies. The melting points were determined on an Electrothermal 9200 apparatus. IR spectra were measured on a Galaxy series FT-IR 5000 spectrometer. NMR spectra were recorded in DMSO-d6 using a Bruker spectrophotometer (1H NMR 300 MHz, 13C NMR 75 MHz) with tetramethylsilane as an internal standard and coupling constants were given in cycles per second (Hz). Elemental analyses were run on a Vario EL III elemental analyzer. Thin-layer chromatography was carried out on silica gel 254 analytical sheets obtained from Fluka. (Chloromethylene)dimethylammonium chloride (Vilsmeier reagent) 2 was obtained as a white solid by a reported procedure [40]. β-Lactams 3a–3f were prepared according to reported methods and spectral data for 3a, 3c, 3e, and 3f have been previously reported [41,42,43,44].

4-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-(naphthalen-2-yloxy)azetidin-2-one (3b, C26H20ClNO3)

White solid; m.p.: 181–184 °C; IR (KBr): \( \bar{\nu } \) = 1749 (CO, β-lactam) cm−1; 1H NMR (300 MHz): δ = 3.79 (OMe, s, 3H), 5.34 (H-4, d, 1H, J = 5.1 Hz), 5.66 (H-3, d, 1H, J = 5.1 Hz), 6.89–6.95 (ArH, m, 3H), 7.10–7.23 (ArH, d, 2H), 7.30–7.33 (ArH, d, 2H), 7.58–7.61 (ArH, m, 4H), 7.67–7.70 (ArH, m, 4H) ppm; 13C NMR (75 MHz): δ = 56.3 (OMe), 62.1 (C-4), 81.9 (C-3), 110.9, 114.1, 117.9, 120.9, 124.2, 126.0, 126.9, 127.9, 128.4, 129.0, 129.8, 130.9, 131.3, 132.5, 133.8, 135.7, 155.9, 156.6 (aromatic carbons), 162.4 (CO, β-lactam) ppm.

1-(4-Chlorophenyl)-3-(naphthalen-2-yloxy)-4-phenylazetidin-2-one (3d, C25H18ClNO2)

Cream color solid; m.p.: 233–237 °C; IR (KBr): \( \bar{\nu } \) = 1753 (CO, β-lactam) cm−1; 1H NMR (300 MHz): δ = 5.09 (H-4, d, 1H, J = 4.6 Hz), 5.44 (H-3, d, 1H, J = 4.6 Hz), 6.97–7.24 (ArH, d, 2H), 7.26–7.30 (ArH, m, 11H), 7.32–7.34 (ArH, m, 1H), 7.52–7.73 (ArH, m, 2H) ppm; 13C NMR (75 MHz): δ = 62.1 (C-4), 82.9 (C-3), 111.7, 121.2, 124.2, 126.9, 127.9, 128.3, 128.5, 128.7, 128.9, 129.0, 129.7, 130.6, 131.7, 133.9, 135.9, 138.1, 155.9 (aromatic carbons), 161.9 (CO, β-lactam) ppm.

General procedure for the synthesis of 2-azetidinones 5a–5p

A one-necked flask was charged with CuI (0.3 mmol), potassium carbonate (5 mmol), Na2S2O3·5H2O (1.5 mmol), alkyl/aryl halide (1.25 mmol), 2-azetidinones 3a–3f (1.25 mmol), and 5 cm3 DMF. The mixture was stirred at 110–120 °C overnight. The reaction mixture was cooled to room temperature. Water (10 cm3) was added to the reaction mixture, and organics were extracted with EtOAc (3 × 10 cm3). Evaporation of the solvent followed by purification by crystallization from 95% ethanol provided the corresponding products.

1-(4-Methoxyphenyl)-3-phenoxy-4-[4-(phenylthio)phenyl]azetidin-2-one (5a, C28H23NO3S)

White solid; m.p.: 171–174 °C; IR (KBr): \( \bar{\nu } \) = 1755 (CO, β-lactam) cm−1; 1H NMR (300 MHz): δ = 3.83 (s, 3H, OMe), 5.20 (d, 1H, J = 4.6 Hz, H-4), 5.62 (d, 1H, J = 4.6 Hz, H-3), 6.89–7.03 (m, 5H, ArH), 7.06–7.09 (m, 7H, ArH), 7.10–7.34 (m, 6H, ArH) ppm; 13C NMR (75 MHz): δ = 56.3 (OMe), 61.9 (C-4), 81.7 (C-3), 116.0, 120.4, 122.8, 127.6, 128.5, 128.9, 129.5, 130.8, 132.1, 134.1, 135.0, 135.7, 136.1, 146.1, 156.4, 157.8 (aromatic carbons), 162.1 (CO, β-lactam) ppm.

4-[[4-[1-(4-Methoxyphenyl)-4-oxo-3-phenoxyazetidin-2-yl]phenyl]thio]benzaldehyde (5b, C29H23NO4S)

White solid; m.p.: 173–175 °C; IR (KBr): \( \bar{\nu } \) = 1731 (CHO), 1754 (CO, β-lactam), 2715, 2804 (CH, aldehyde) cm−1; 1H NMR (300 MHz): δ = 3.70 (s, 3H, OMe), 5.22 (d, 1H, J = 4.9 Hz, H-4), 5.71 (d, 1H, J = 4.9 Hz, H-3), 6.92–7.03 (m, 5H, ArH), 7.11–7.18 (m, 8H, ArH), 7.22–7.33 (d, 2H, ArH), 7.45–7.66 (d, 2H, ArH), 9.90 (s, 1H, CHO) ppm; 13C NMR (75 MHz): δ = 56.6 (OMe), 62.0 (C-4), 83.8 (C-3), 114.3, 116.6, 120.5, 122.4, 128.0, 129.8, 130.1, 131.6, 131.6, 134.2, 142.7, 156.0, 157.8 (aromatic carbons), 163.3 (CO, β-lactam), 192.0 (CHO) ppm.

4-[4-(Hexylthio)phenyl]-1-(4-methoxyphenyl)-3-phenoxyazetidin-2-one (5c, C28H31NO3S)

White solid; m.p.: 178–180 °C; IR (KBr): \( \bar{\nu } \) = 1740 (CO, β-lactam) cm−1; 1H NMR (300 MHz): δ = 0.99 (t, 3H, J = 6.5 Hz, Me), 1.31–1.40 (m, 6H, 3CH2), 1.76–1.81 (m, 2H, SCH2CH2), 2.96 (t, 2H, J = 5.4 Hz, SCH2), 3.82 (s, 3H, OMe), 5.28 (d, 1H, J = 4.4 Hz, H-4), 5.60 (d, 1H, J = 4.4 Hz, H-3), 6.92–7.01 (m, 5H, ArH), 7.13–7.16 (d, 2H, ArH), 7.23–7.33 (m, 6H, ArH) ppm; 13C NMR (75 MHz): δ = 14.0 (Me), 22.9, 28.3, 29.0, 31.6 (CH2), 34.2 (SCH2), 55.9 (OMe), 61.8 (C-4), 84.2 (C-3), 113.9, 116.2, 121.1, 123.0, 129.2, 129.9, 130.9, 138.2, 146.1, 156.0, 158.1 (aromatic carbons), 162.5 (CO, β-lactam) ppm.

4-[4-(Hexylthio)phenyl]-1-(4-methoxyphenyl)-3-(naphthalen-2-yloxy)azetidin-2-one (5d, C32H33NO3S)

White solid; m.p.: 184–186 °C; IR (KBr): \( \bar{\nu } \) = 1747 (CO, β-lactam) cm−1; 1H NMR (300 MHz): δ = 0.97 (t, 3H, J = 6.0 Hz, Me), 1.29–1.43 (m, 6H, 3CH2), 1.74–1.83 (m, 2H, SCH2CH2), 2.92 (t, 2H, J = 6.1 Hz, SCH2), 3.80 (s, 3H, OMe), 5.36 (d, 1H, J = 4.8 Hz, H-4), 5.69 (d, 1H, J = 4.8 Hz, H-3), 6.86–7.10 (d, 2H, ArH), 7.12–7.30 (d, 2H, ArH), 7.32–7.36 (m, 7H, ArH), 7.54–7.61 (m, 2H, ArH), 7.66–7.80 (d, 2H, ArH) ppm; 13C NMR (75 MHz): δ = 13.7 (Me), 23.1, 27.9, 29.1, 32.0 (CH2), 34.9 (SCH2), 55.8 (OMe), 61.5 (C-4), 83.2 (C-3), 111.7, 114.4, 119.0, 120.9, 123.6, 127.3, 127.5, 127.9, 128.6, 129.1, 129.5, 131.1, 131.4, 132.0, 135.8, 138.6, 156.6, 156.8 (aromatic carbons), 161.8 (CO, β-lactam) ppm.

4-[[4-[1-(4-Methoxyphenyl)-3-(naphthalen-2-yloxy)-4-oxoazetidin-2-yl]phenyl]thio]benzaldehyde (5e, C33H25NO4S)

White solid; m.p.: 131–135 °C; IR (KBr): \( \bar{\nu } \) = 1723 (CHO), 1744 (CO, β-lactam), 2703, 2792 (CH, aldehyde) cm−1; 1H NMR (300 MHz): δ = 3.65 (s, 3H, OMe), 5.16 (d, 1H, J = 4.6 Hz, H-4), 5.48 (d, 1H, J = 4.6 Hz, H-3), 6.87–7.10 (d, 2H, ArH), 7.10–7.12 (m, 4H, ArH), 7.28–7.33 (m, 5H, ArH), 7.34–7.55 (m, 6H, ArH), 7.60–7.66 (m, 1H, ArH), 10.08 (s, 1H, CHO) ppm; 13C NMR (75 MHz): δ = 55.6 (OMe), 60.8 (C-4), 80.9 (C-3), 110.9, 113.9, 118.7, 120.7, 123.9, 126.9, 127.6, 128.2, 128.7, 129.4, 129.9, 130.0, 131.1, 131.6, 133.5, 134.0, 135.1, 135.3, 136.1, 143.0, 152.7, 156.8 (aromatic carbons), 164.0 (CO, β-lactam), 192.4 (CHO) ppm.

1-(4-Methoxyphenyl)-3-(naphthalen-2-yloxy)-4-[4-(phenylthio)phenyl]azetidin-2-one (5f, C32H25NO3S)

Crème-color solid; m.p.: 172–175 °C; IR (KBr): \( \bar{\nu } \) = 1758 (CO, β-lactam) cm−1; 1H NMR (300 MHz): δ = 3.72 (s, 3H, OMe), 5.31 (d, 1H, J = 4.7 Hz, H-4), 5.63 (d, 1H, J = 4.7 Hz, H-3), 6.90–7.09 (m, 9H, ArH), 7.11–7.33 (m, 8H, ArH), 7.50–7.70 (m, 3H, ArH) ppm; 13C NMR (75 MHz): δ = 55.7 (OMe), 61.6 (C-4), 81.8 (C-3), 111.7, 113.7, 118.1, 121.2, 123.5, 126.9, 127.0, 127.7, 127.9, 128.6, 129.3, 129.8, 131.2, 131.5, 133.8, 135.1, 135.3, 135.9, 136.2, 155.7, 156.2 (aromatic carbons), 162.2 (CO, β-lactam) ppm.

1-[4-(Hexylthio)phenyl]-3-phenoxy-4-phenylazetidin-2-one (5g, C27H29NO2S)

White solid; m.p.:193–196 °C; IR (KBr): \( \bar{\nu } \) = 1765 (CO, β-lactam) cm−1; 1H NMR (300 MHz): δ = 0.99 (t, 3H, J = 6.1 Hz, Me), 1.27–1.40 (m, 6H, 3CH2), 1.66–1.77 (m, 2H, SCH2CH2), 2.88 (t, 2H, J = 8.0 Hz, SCH2), 5.10 (d, 1H, J = 5.2 Hz, H-4), 5.54 (d, 1H, J = 5.2 Hz, H-3), 6.84–7.00 (m, 3H, ArH), 7.10–7.13 (d, 2H, ArH), 7.23–7.40 (m, 9H, ArH) ppm; 13C NMR (75 MHz): δ = 12.9 (Me), 22.8, 28.7, 29.1, 32.0 (CH2), 34.4 (SCH2), 64.0 (C-4), 83.8 (C-3), 116.4, 122.8, 124.6, 126.7, 127.9, 128.3, 129.4, 133.9, 134.7, 136.0, 147.2, 159.2 (aromatic carbons), 164.4 (CO, β-lactam) ppm.

4-[[4-(2-Oxo-3-phenoxy-4-phenylazetidin-1-yl)phenyl]thio]benzaldehyde (5h, C28H21NO3S)

Cream solid; m.p.: 245–249 °C; IR (KBr): \( \bar{\nu } \) = 1724 (CHO), 1757 (CO, β-lactam), 2709, 2811 (CH, aldehyde) cm−1; 1H NMR (300 MHz): δ = 5.24 (d, 1H, J = 5.0 Hz, H-4), 5.50 (d, 1H, J = 5.0 Hz, H-3), 6.94–7.07 (m, 5H, ArH), 7.22–7.38 (m, 11H, ArH), 7.61–7.63 (d, 2H, ArH), 9.89 (s, 1H, CHO) ppm; 13C NMR (75 MHz): δ = 60.8 (C-4), 83.6 (C-3), 113.7, 122.5, 122.6, 127.0, 127.9, 128.6, 129.4, 130.1, 131.1, 132.0, 133.3, 133.7, 134.6, 138.8, 143.3, 158.9 (aromatic carbons), 164.1 (CO, β-lactam), 190.2 (CHO) ppm.

3-Phenoxy-4-phenyl-1-[4-(phenylthio)phenyl]azetidin-2-one (5i, C27H21NO2S)

White solid; m.p.: 240–244 °C; IR (KBr): \( \bar{\nu } \) = 1746 (CO, β-lactam) cm−1; 1H NMR (300 MHz): δ = 5.26 (d, 1H, J = 4.9 Hz, H-4), 5.57 (d, 1H, J = 4.9 Hz, H-3), 6.91–7.24 (m, 8H, ArH), 7.25–7.38 (m, 11H, ArH) ppm; 13C NMR (75 MHz): δ = 62.3 (C-4), 82.2 (C-3), 109.3, 117.0, 122.8, 126.7, 127.8, 127.9, 128.6, 129.6, 129.9, 130.9, 131.6, 133.7, 134.5, 135.3, 138.0, 157.7, (aromatic carbons), 161.9 (CO, β-lactam) ppm.

1-[4-(Hexylthio)phenyl]-3-(naphthalen-2-yloxy)-4-phenylazetidin-2-one (5j, C31H31NO2S)

Cream solid; m.p.: 240–244 °C; IR (KBr): \( \bar{\nu } \) = 1753 (CO, β-lactam) cm−1; 1H NMR (300 MHz): δ = 0.98 (t, 3H, J = 6.0 Hz, Me), 1.26–1.40 (m, 6H, 3CH2), 1.62–1.72 (m, 2H, SCH2CH2), 2.90 (t, 2H, J = 7.9 Hz, SCH2), 5.26 (d, 1H, J = 4.5 Hz, H-4), 5.53 (d, 1H, J = 4.5 Hz, H-3), 7.04–7.20 (d, 2H, ArH), 7.22–7.35 (m, 10H, ArH), 7.50–7.72 (m, 4H, ArH) ppm; 13C NMR (75 MHz): δ = 15.3 (Me), 21.9, 27.9, 28.8, 31.7 (CH2), 35.2 (SCH2), 62.4 (C-4), 81.7 (C-3), 111.7, 115.7, 123.9, 124.4, 126.8, 127.3, 127.5, 128.1, 128.4, 128.9, 131.5, 135.5, 136.1, 154.9, (aromatic carbons), 160.6 (CO, β-lactam) ppm.

4-[[4-[3-(Naphthalen-2-yloxy)-2-oxo-4-phenylazetidin-1-yl]phenyl]thio]benzaldehyde (5k, C32H23NO3S)

Cream solid; m.p.: 300–303 °C; IR (KBr): \( \bar{\nu } \) = 1732 (CHO), 1759 (CO, β-lactam), 2706, 2801 (CH, aldehyde) cm−1; 1H NMR (300 MHz): δ = 5.35 (d, 1H, J = 4.7 Hz, H-4), 5.62 (d, 1H, J = 4.7 Hz, H-3), 6.98–7.21 (d, 2H, ArH), 7.22–7.34 (m, 12H, ArH), 7.36–7.68 (m, 5H, ArH), 9.85 (s, 1H, CHO) ppm; 13C NMR (75 MHz): δ = 61.5 (C-4), 84.2 (C-3), 107.5, 110.9, 122.2, 124.2, 126.4, 127.5, 127.6, 128.8, 129.1, 129.9, 130.8, 131.1, 131.5, 133.8, 134.2, 135.3, 138.0, 156.3 (aromatic carbons), 162.2 (CO, β-lactam), 191.3 (CHO) ppm.

3-(Naphthalen-2-yloxy)-4-phenyl-1-[4-(phenylthio)phenyl]azetidin-2-one (5l, C31H23NO2S)

Pale-yellow solid; m.p.: 233–235 °C; IR (KBr): \( \bar{\nu } \) = 1752 (CO, β-lactam) cm−1; 1H NMR (300 MHz): δ = 5.19 (d, 1H, J = 4.5 Hz, H-4), 5.47 (d, 1H, J = 4.5 Hz, H-3), 6.95–7.15 (m, 5H, ArH), 7.16–7.20 (m, 13H, ArH), 7.22–7.33 (m, 1H, ArH), 7.39–51 (m, 1H, ArH), 7.52–7.70 (m, 1H, ArH) ppm; 13C NMR (75 MHz): δ = 60.3 (C-4), 81.4 (C-3), 105.9, 107.7, 111.3, 121.9, 124.1, 126.7, 127.4, 127.6, 127.9, 128.3, 128.9, 129.4, 129.7, 131.6, 132.2, 133.6, 135.7, 138.9, 153.4, 157.1 (aromatic carbons), 164.3 (CO, β-lactam) ppm.

3-[4-(Hexylthio)phenoxy]-1-(4-methoxyphenyl)-4-phenylazetidin-2-one (5m, C28H31NO3S)

Cream solid; m.p.: 187–189 °C; IR (KBr): \( \bar{\nu } \) = 1741 (CO, β-lactam) cm−1; 1H NMR (300 MHz): δ = 1.00 (t, 3H, J = 6.9 Hz, Me), 1.28–1.40 (m, 6H, 3CH2), 1.66–1.77 (m, 2H, SCH2CH2), 2.88 (t, 2H, J = 8.0 Hz, SCH2), 3.81 (s, 3H, OMe), 5.31 (d, 1H, J = 4.4 Hz, H-4), 5.76 (d, 1H, J = 4.4 Hz, H-3), 6.90–6.95 (m, 4H, ArH), 7.14–7.33 (m, 9H, ArH) ppm; 13C NMR (75 MHz): δ = 14.6 (Me), 22.7, 28.5, 29.3, 31.4 (CH2), 34.5 (SCH2), 55.2 (OMe), 63.7 (C-4), 83.9 (C-3), 114.2, 119.1, 120.6, 126.7, 127.9, 128.6, 130.3, 131.4, 133.3, 134.5, 156.5, 157.9 (aromatic carbons), 162.6 (CO, β-lactam) ppm.

1-(4-Methoxyphenyl)-4-phenyl-3-[4-(phenylthio)phenoxy]azetidin-2-one (5n, C28H23NO3S)

Cream solid; m.p.: 164–168 °C; IR (KBr): \( \bar{\nu } \) = 1740 (CO, β-lactam) cm−1; 1H NMR (300 MHz): δ = 3.78 (s, 3H, OMe), 5.30 (d, 1H, J = 4.3 Hz, H-4), 5.74 (d, 1H, J = 4.3 Hz, H-3), 6.66–6.68 (d, 2H, ArH), 7.03–7.09 (m, 3H, ArH), 7.17–7.36 (m, 13H, ArH) ppm; 13C NMR (75 MHz): δ = 55.3 (OMe), 63.5 (C-4), 84.2 (C-3), 114.7, 116.2, 121.3, 126.3, 127.9, 128.0, 128.7, 129.6, 130.9, 131.4, 131.9, 133.3, 134.7, 136.1, 155.2, 158.3 (aromatic carbons), 162.6 (CO, β-lactam) ppm.

4-[[4-[[1-(4-Methoxyphenyl)-2-oxo-4-phenylazetidin-3-yl]oxy]phenyl]thio]benzaldehyde (5o, C29H23NO4S)

White solid; m.p.: 185–188 °C; IR (KBr): \( \bar{\nu } \) = 1728 (CHO), 1754 (CO, β-lactam), 2717, 2808 (CH, aldehyde) cm−1; 1H NMR (300 MHz): δ = 3.83 (s, 3H, OMe), 5.15 (d, 1H, J = 4.6 Hz, H-4), 5.51 (d, 1H, J = 4.6 Hz, H-3), 6.81–6.96 (d, 2H, ArH), 7.14–7.25 (d, 2H, ArH), 7.25–7.49 (m, 9H, ArH), 7.65–7.68 (d, 4H, ArH), 9.91 (s, 1H, CHO) ppm; 13C NMR (75 MHz): δ = 56.1 (OMe), 61.8 (C-4), 81.1 (C-3), 113.8, 115.9, 120.4, 126.8, 127.9, 128.2, 130.1, 130.8, 131.1, 132.0, 133.8, 134.2, 143.5, 150.9, 156.4, 158.4 (aromatic carbons), 162.3 (CO, β-lactam), 192.2 (CHO) ppm.

4-(4-Nitrophenyl)-3-phenoxy-1-[2-(phenylthio)pyridin-3-yl]azetidin-2-one (5p, C26H19N3O4S)

White solid; m.p.: 193–195 °C; IR (KBr): \( \bar{\nu } \) = 1324, 1528 (NO2), 1616 (C=N, pyridine ring), 1748 (CO) cm−1; 1H NMR (300 MHz): δ = 5.21 (d, 1H, J = 5.0 Hz, H-4), 5.47 (d, 1H, J = 5.0 Hz, H-3), 6.88–6.91 (m, 4H, ArH), 7.10 (d, 2H, ArH), 7.22–7.28 (m, 4H, ArH), 7.74–7.79 (m, 4H, ArH), 8.02–8.04 (m, 3H, ArH) ppm; 13C NMR (75 MHz): δ = 64.6 (C-4), 83.9 (C-3), 115.9, 118.1, 118.9, 122.0, 124.8, 125.1, 125.6, 127.3, 129.7, 131.0, 135.7, 136.4, 138.5, 142.1, 148.6, 152.4, 157.8 (aromatic carbons), 164.3 (CO, β-lactam) ppm.