Synthesis of Some New Mono- and Bis-Polycyclic Aromatic Spiro and Bis-Nonspiro-β-Lactams

Some new mono-and bis-polycyclic aromatic spiro-β-lactams and bis-non spiro-polycyclic aromatic β-lactams have been synthesized from imines derived from anthracene-9-carbaldehyde, 2-naphtaldehyde and a ketene derived from 9H-xanthene-9-carboxylic acid and phenoxyacetic acid by a [2+2] cycloaddition reaction. The cycloadducts were characterized by spectral data, including 1H-NMR, 13C-NMR, IR and elemental analyses. The configurations of some of these mono-spiro-β-lactams were established by X-ray crystal analysis.


Results and Discussion
Treatment of anthracene-9-carbaldehyde or 2-naphtaldehyde with different primary amines in refluxing ethanol afforded the polycyclic aromatic imines 1a-n [50][51][52][53]. These Schiff bases were then treated with 9H-xanthene-9-carboxylic acid in the presence of triethylamine and tosyl chloride to afford polycyclic aromatic spiro-β-lactams 2a-n as single diastereomers (Scheme 1). The reaction progress was monitored by TLC and the presence of a new compound was confirmed. In addition, the cycloadducts were characterized by spectral analysis. For 2a the IR spectrum showed the characteristic absorption of a β-lactam carbonyl at 1,747 cm −1 . The 1 H-NMR spectrum exhibited the methoxy protons as a singlet at 3.64 ppm, the β-lactam H-4 proton as a singlet at 6.29 and aromatic protons as a multiplet at 6. 39-8.82. The 13 C-NMR spectrum exhibited the C-3 (spiro carbon) at 64.3. The results for other polycyclic aromatic spiro-β-lactams 2a-n are shown in Table 1.  Then we decided to synthesize bis-spiro-and bis-nonspiro-polycyclic aromatic β-lactams 4a-d, 6b and 4e-h, 6a from bis-imines 3a-d and 5 [53] (Scheme 2). The structures of 4a-h and 5a-b are shown in Table 2. The cis-trans stereochemistry of 2-azetidinones 4e-h and 6a were deduced from the coupling constant of H-3 and H-4, which was calculated to be J 3,4 = 4-9 Hz for the cis and J 3,4 = 1-3 Hz for the trans stereoisomers.

General
All needed chemicals were purchased from the Merck, Fluka or Acros chemical companies. All reagents and solvents were dried prior to use according to standard methods [60]. IR spectra were run on a Shimadzu FT-IR 8300 spectrophotometer. 1 H-NMR and 13 C-NMR spectra were recorded in DMSO-d 6 or CDCl 3 using a Bruker Avance DPX instrument ( 1 H-NMR 250 MHz, 13 C-NMR 62.9 MHz). Chemical shifts were reported in parts per million (δ) downfield from TMS. All of the coupling constants (J) are in hertz. The mass spectra were recorded on a Shimadzu GC-MS QP 1000 EX instrument. Elemental analyses were run on a Thermo Finnigan Flash EA-1112 series. Melting points were determined in open capillaries with Buchi 510 melting point apparatus. Thin-layer chromatography was carried out on silica gel F254 analytical sheets obtained from Fluka. Column chromatography was performed on Merck Kiesel gel (230-270 mesh).

General Procedure for Preparation of Schiff Bases 1a-n
A mixture of an aromatic amine (1.00 mmol) and anthracene-9-carbaldehyde or 2-naphtaldehyde (1.00 mmol) was refluxed in ethanol (20 mL) for 1-5 hours. After cooling, the pure Schiff bases were separated as crystals. Some of these were recrystallized from ethanol.

General Procedure for Preparation of Bis-Schiff Bases 3a-d and 5
A mixture of anthracene-9-carbaldehyde (1.00 mmol) and bisamine (0.50 mmol) was refluxed in ethanol (20 mL) for (1-5) h. After cooling, the pure Schiff bases were separated as crystals. Some of these were recrystallized from ethanol.

General Procedure for the Synthesis of Polycyclic Aromatic Spiro-β-Lactams 2a-n
A mixture of Schiff base (1.00 mmol), triethylamine (5.00 mmol), 9H-xanthene-9-carboxylic acid (1.50 mmol) and tosyl chloride (1.50 mmol) in dry CH 2 Cl 2 (15 mL) was stirred at room temperature for 24 h. Then it was washed with HCl 1N (20 mL), saturated NaHCO 3 (20 mL) and brine (20 mL). The organic layer was dried (Na 2 SO 4 ), filtered and the solvent was evaporated to give the product as a crystal which was then purified by recrystallization from appropriate organic solvents.

General Procedure for the Synthesis of Bis-Polycyclic Aromatic Spiro and Nonspiro-β-Lactams 4a-h and 6a-b
A mixture of Schiff base (1.00 mmol), triethylamine (10.00 mmol), 9H-xanthen-9-carboxylic acid or phenoxyacetic acid (3.00 mmol) and tosyl chloride (3.00 mmol) in dry CH 2 Cl 2 (15 mL) was stirred at room temperature for 24 h. Then it was washed with HCl 1N (20 mL), saturated NaHCO 3 (20 mL) and brine (20 mL). The organic layer was dried (Na 2 SO 4 ), filtered and the solvent was evaporated to give the product as a crystal which was then purified by recrystallization from suitable organic solvents.

Conclusions
This article describes for the first time the synthesis and characterization of some examples of mono-and bis-spiro-and nonspiro-β-lactams bearing a polycyclic aromatic moiety by reaction of polycyclic aromatic imines and two ketenes derived from 9H-xanthene-9-carboxylic acid and phenoxyacetic acid. These ketenes were prepared in situ with triethylamine and p-toluenesulfonyl chloride.