Home Physical Sciences 4,15-Diamino[2.2]paracyclophane as a useful precursor for the synthesis of novel pseudo-geminal [2.2]paracyclophane compounds
Article Publicly Available

4,15-Diamino[2.2]paracyclophane as a useful precursor for the synthesis of novel pseudo-geminal [2.2]paracyclophane compounds

  • Kamal M. El-Shaieb EMAIL logo , Aboul-Fetouh E. Mourad and Alaa A. Hassan
Published/Copyright: October 7, 2015
Download Article (PDF)
Become an author with De Gruyter Brill
Author Information Explore this Subject
Zeitschrift für Naturforschung B
From the journal Zeitschrift für Naturforschung B Volume 70 Issue 11

Abstract

New reactions of 4,15-diamino[2.2]paracyclophane (1) are described. When 1 is reacted with acetyl, benzoyl, or phthaloyl chloride, respectively, the amides 2, 6, 7, and 9 are formed; the latter suffers loss of H2O to give the product 8. Bromination of 2 yields the pseudo-geminally substituted derivative 3 exclusively; the formation of its expected regioisomer 4 is not observed. Heating of 2 with POCl3 in ethanol furnishes the triply-bridged cyclophane 5. Condensation of 1 with some selected carbonyl compounds (phthalaldehyde, formic acid, cyclohexane-1,3-dione, and terephthalaldehyde) provides the products 17–20. Thiourea and isothiocyanate derivatives 21 and 22 were obtained on heating 1 in CS2. The structures of the products were assigned on the basis of their spectroscopic and analytical data. Rationalizations for the formation of 3, 5, 6, and 17 are presented.

Keywords: cyclization reactions; 4,15-diamino[2.2]paracyclophane; neighboring group effects; tris-bridged cyclophanes

1 Introduction

The chemistry of [2.2]paracyclophane is still a field of ongoing research [1–5]. For a long time, [2.2]paracyclophane and its derivatives were mostly studied because of their unusual geometry, transannular, and ring strain effects [6, 7]. Recently, the stereochemical properties of these systems, especially their planar chirality, have been in the focus of studies in this field [8]. Paracyclophanes [9] having substituted amino functions have also been shown to be useful as effective photoconductive components [10, 11]. We recently described a straightforward synthesis of 4,15-diamino[2.2]paracyclophane [12]. Its chemical behavior has been investigated [12, 13]. In addition, the diamine 1 also serves as an excellent electron-donating system in charge-transfer complexation [14], a behavior mainly due to the presence of transannular electronic interactions between the two benzene rings in the cyclophane moiety [15, 16].

Recently, we have succeeded to construct a variety of poorly investigated types of pseudo-geminally substituted cyclophanes [13, 14]. In the light of these promising findings, we turned our attention to 4,15-diamino[2.2]paracyclophane (1) to investigate its nucleophilic properties towards several electrophiles.

2 Results and discussion

Treatment of 1 with excess acetyl chloride gave, as expected, 4,15-bis(acetylamino)[2.2]paracyclophane (2). The 1H NMR spectrum of 2 displays an exchangeable (D2O) broad singlet at δ = 9.24 ppm representing the NH groups. In addition, the aromatic protons could be detected at δ = 6.48 (d, J = 7.7 Hz, 2H), 6.36–6.35 (dd, 1J = 1.4, 2J = 7.8 Hz, 2H), and 6.34 ppm (d, J = 1.4 Hz, 2H). The bridged methylene protons present themselves as three multiplets: at δ = 3.15–3.07 (2H), 2.98–2.86 (4H), and 2.76–2.65 ppm (2H). Furthermore, the methyl protons are detected as a singlet at δ = 2.03 ppm. This interpretation is confirmed by the 13C NMR spectrum which displays a peak at δ = 167.03 ppm typical for an amide carbonyl carbon atom. The aromatic carbon atoms are recorded in the expected region of δ = 138.78–125.96 ppm. The two distinct methylene and the methyl carbon atoms resonate at δ = 34.28, 31.87, and 23.30 ppm, respectively. The mass spectrum shows a molecular ion peak at m/z = 322, which is compatible with the molecular weight of the compound. The symmetry of the product 2 could be inferred from both simple 13C NMR spectrum (half number of carbon signals) and mass spectral data (showing a peak at [M/2]+). It is well known that bromination of N-acetylamine results in the formation of the p-bromo derivative as a major product together with a very small ratio of the o-bromo isomer. Interestingly, bromination of 2 in glacial acetic acid afforded a novel unexpected product, 4,15-bis(acetylamino)-5,16-dibromo[2.2]paracyclophane (3), instead of the less sterically hindered one 4 (Scheme 1).

Scheme 1: Reactions of 1. Reagents and conditions: (i) CH3COCl/pyridine; (ii) Br2/Fe/AcOH; (iii) POCl3/EtOH, refl.; (iv) PhCOCl/CH2Cl2; (v) phthaloyl chloride/CH3OH, refl.
Scheme 1:

Reactions of 1. Reagents and conditions: (i) CH3COCl/pyridine; (ii) Br2/Fe/AcOH; (iii) POCl3/EtOH, refl.; (iv) PhCOCl/CH2Cl2; (v) phthaloyl chloride/CH3OH, refl.

The structure of this product was deduced on the basis of its elemental and spectral analyses. The 1H NMR spectrum of 3 shows a broad band at δ = 8.10 ppm related to the NH groups. In addition, the paracyclophane ring protons appear as two doublets at δ = 6.60 (d, J = 7.8 Hz, 2H) and 6.55 ppm (d, J = 7.8 Hz, 2H), the coupling constants confirming the ortho coupling. The bridge methylene protons resonate as three sets of multiplets: one at δ = 3.40–3.45 ppm integrated for two protons, the second at 2.95–3.05 ppm (4H), and the third at 2.73–2.80 ppm (2H). In addition, a singlet was registered at δ = 2.03 ppm representing the two methyl groups. The two identical carbonyl carbon atoms were detected in the 13C NMR spectrum at δ = 167.60 ppm. The two distinct methylene and methyl carbon atoms resonate at δ = 35.09, 33.42, and 23.18 ppm, respectively. Furthermore, the mass spectrum gave a molecular ion peak at m/z = 482/480/478 (Br isotope ratio) which is in accordance with the molecular weight of the product; the fragmentation pattern of the molecular ion peak emphasizes the dibromo derivative. The formation of the product 3 can be rationalized as shown in Fig. 1.

Fig. 1: Rational pathway for the formation of the product 3.
Fig. 1:

Rational pathway for the formation of the product 3.

On heating 2 in POCl3/EtOH, the reaction product 5 was obtained. The 1H NMR spectrum of compound 5 shows, in addition to the aromatic carbon atoms in the expected positions, a quartet at δ = 4.05 ppm for –CH2–CH3 (J = 7.13 Hz) protons, while the –CH2–CH3 protons resonate in the 1H NMR spectrum as a triplet at δ = 1.04 ppm (J = 7.11 Hz). The protons of the methyl group attached to the double bond appear as a singlet at δ = 2.67 ppm. The carbonyl group of 5 could be detected in the IR spectrum at ν = 1735 cm–1, in addition to an absorption band at ν = 1631 cm–1. Furthermore, elemental analysis and mass spectrum are entirely consistent with the proposed structure. A suggested mechanism for the formation of compound 5 is shown in Fig. 2.

Fig. 2: Rational pathway for the formation of the product 5.
Fig. 2:

Rational pathway for the formation of the product 5.

On warming an equimolar ratio of 1 and benzoyl chloride, 4-amino-15-benzoylamino[2.2]paracyclophane (6) was obtained. Reacting 1 with excess benzoyl chloride provided 4,15-bis-benzoylamino[2.2]paracyclophane (7). The mass spectrum of 7 shows a molecular ion peak at m/z = 446, together with a peak at m/z = 223 [M/2]+ characteristic of a symmetrical paracyclophane.

Derivatives 8 and 9 were obtained on refluxing 1 with phthaloyl chloride in methanol (Scheme 1). The 1H NMR spectrum of 8 shows, in addition to the aromatic protons (see Experimental section), two multiplets at δ = 3.01–3.13 and 2.78–2.89 ppm related to the two ethano bridges. The 13C NMR spectrum exhibits a signal at δ = 167.30 ppm typical for the amide carbonyl group, whereas the (C=N) group resonated at δ = 156.20 ppm. The IR spectrum displays two bands at 1736 and 1669 cm–1 corresponding to both (CO) and (C=N) groups, respectively. Furthermore, the mass spectrum of 8 is in agreement with its molecular weight by giving a molecular ion peak at m/z = 350.

The 1H NMR, 13C NMR, IR, and mass spectra as well as elemental analysis provided a firm support for the structural proof of the second product 9 (see Experimental section).

We have found that on heating 1 with phthalaldehyde, the product 17 was obtained (Scheme 2). The structure of 17 was deduced from its spectral data and elemental analysis. The characteristic features of the 1H NMR spectrum were the appearance of one doublet and two multiplets at δ = 8.45 (d, J = 7.7, 1H), 7.88–7.92 (m, 1H), and 7.76–7.85 (m, 2H) for the aromatic protons of the isoindoline part, while the paracyclophane ring protons appeared as two doublets at δ = 6.78 (d, J = 1.3 Hz, 1H) and 6.67 ppm (d, J = 7.9 Hz, 1H) and two singlets at 6.97 (s, 1H) and 6.71 ppm (s, 2H), in addition to a doublet of doublets at δ = 6.58–6.61 (dd, 1J = 1.4, 2J = 7.9, 1H). However, the methylene protons of the isoindoline nucleus appeared as a singlet at 5.12 ppm. This peak was shifted to a lower field due to the strong inductive effect of the adjacent groups (nitrogen atom and aryl group). The bridged methylene protons appeared as three multiplets at 2.86–3.33 ppm. The IR spectrum revealed no absorption maxima for either NH or C=O groups, but instead the C=N absorption was observed at 1636 cm–1. On the other hand, both the mass spectrum and the elemental analysis confirm the molecular formula of the product 17 as C24H20N2.

Scheme 2: Reactions of diamine 1. Reagents and conditions: (vi) phthalaldehyde/CH3OH; (vii) HCO2H, refl.; (viii) cyclohexane-1,3-dione/CH3OH, refl.; (ix) terphthalaldehyde/CH3OH, refl.
Scheme 2:

Reactions of diamine 1. Reagents and conditions: (vi) phthalaldehyde/CH3OH; (vii) HCO2H, refl.; (viii) cyclohexane-1,3-dione/CH3OH, refl.; (ix) terphthalaldehyde/CH3OH, refl.

On refluxing 1 with formic acid, 4,15-bis(formylamino)[2.2]paracyclophane (18) was obtained in 81% yield (Scheme 2). The 1H NMR spectrum of this product showed a doublet at δ = 10.55 ppm with a coupling constant of 10.1 Hz, for the two formyl protons, which coupled with the neighboring NH protons. However, the two NH protons were present in the 1H NMR spectrum as a doublet at δ = 8.0 ppm (J = 10.9 Hz). The paracyclophane ring protons appear as one doublet at δ = 6.57 ppm (Jo = 7.85 Hz, 2H) and a doublet of doublets at δ = 6.45 ppm (Jm = 1.7, Jo = 7.8 Hz, 2H) as well as a doublet at δ = 6.37 ppm (Jm = 1.7 Hz, 2H). The bridge methylene protons appear as two multiplets at δ = 3.64–3.71 (m, 2H) and 2.83–3.09 (m, 6H) ppm. Furthermore, the symmetry of 18 resulted in a decrease in the number of signals in the 13C NMR spectrum, so that only half signals were observed for aromatic and aliphatic carbon atoms. The NH groups absorb in the IR spectrum at ν = 1698 cm–1. The mass spectrum displays a molecular ion peak at m/z = 294, which is in accordance with the molecular weight of the compound 18. The symmetry of the product could be confirmed by the presence of a mass peak at m/z = 147 which represents half of the molecular mass.

The structure of 20 is deduced from microanalytical and spectral data, where both the mass spectrum and the elemental analysis confirm the molecular formula of the product 20 as C48H40N4.

The thiourea derivative 21 was prepared by heating 1 with CS2 in alcoholic KOH (Scheme 3). The structure of the product 21 was assigned on the basis of the spectroscopic data as well as elemental analysis. The 1H NMR spectrum of 21 shows a broad singlet at δ = 9.46 ppm related to the two similar NH protons. The paracyclophane ring protons resonate as two doublets at δ = 6.49 (J = 1.7 Hz) and 6.46 (J = 7.8 Hz) and a doublet of doublets at δ = 6.37 (1J = 1.7, 2J = 7.8 Hz). The bridge methylene protons appear as four sets of multiplets at δ = 2.80–3.33 ppm. Furthermore, the 13C NMR spectrum exhibits a peak at 177.6 ppm corresponding to the (C=S) group. In addition, there are six aromatic carbon signals as well as two aliphatic carbons at 34.76 and 31.14 ppm. The presence of both NH and C=S groups was further confirmed by an IR spectrum, where the NH group was observed at ν = 3444 cm–1, and the C=S group absorbed at ν = 1595 cm–1. Both mass spectrum and elemental analysis confirm the molecular formula of the product 21 as C17H16N2S.

Scheme 3: Reaction of 1. Reagents and conditions: (x) CS2/KOH/EtOH, refl.; (xi) CS2/NH4OH.
Scheme 3:

Reaction of 1. Reagents and conditions: (x) CS2/KOH/EtOH, refl.; (xi) CS2/NH4OH.

On treatment of 1 with CS2 in ammonia solution, paracyclophane-4,15-diisothiocyanate (22) was formed. The product was characterized on the basis of its spectroscopic data and elemental analysis. The 1H NMR spectrum displays, as shown in the aforementioned symmetrically disubstituted [2.2]paracyclophane, the aromatic protons as two doublets at δ = 6.44 and 6.35 ppm with coupling constants of J = 7.9 and 1.7 Hz, respectively, as well as a doublet of doublets at 6.39 (1J = 1.7, 2J = 7.9 Hz). The methylene protons resonated as two multiplets at 2.87–3.55 ppm. The structure of 22 gets a further support by a 13C NMR spectrum which showed only six signals related to the aromatic carbons, in addition to two signals for the aliphatic carbons. The molecular ion peak of 22 was detected in a mass spectrum at m/z = 322 which is compatible with the sum formula of the compound.

3 Experimental section

Melting points were determined on Büchi 530 melting point apparatus and are uncorrected. 4,15-Diamino[2.2]paracyclophane (1) was prepared as reported in [12]. The NMR spectra were recorded on a Bruker AM 400 MHz spectrometer with TMS as an internal standard; the coupling constants (J) are given in Hz. The mass spectra (EI) were performed using a Finnigan MAT 8430 spectrometer. IR spectra were measured without solvents using a Bruker Tensor 27 instrument. All reagents were purchased from Alfa Aesar, Fluka, and Aldrich companies and were used without further purification.

3.1 4,15-Bis(acetylamino)[2.2]paracyclophane (2)

To a solution of 4,15-diamino[2.2]paracyclophane (1) (100 mg, 0.42 mmol) in dry CH2Cl2 (10 mL) three drops of pyridine were added and the reaction mixture was cooled to 0°C. A solution of acetyl chloride (66 mg, 0.84 mmol) in CH2Cl2 (5 mL) was added dropwise for 10 min with stirring. The mixture was stirred for 1 h; the formed precipitate was collected by filtration and washed with CH2Cl2 to give 2 as a white powder (130 mg, 96%), m.p. 159–160°C. – IR (film): ν = 3336, 3278 (NH), 1661 (CO) cm–1. – 1H NMR (400 MHz, CDCl3): δ = 2.03 (s, 6H, 2CH3), 2.65–2.76 (m, 2H), 2.86–2.98 (m, 4H), 3.07–3.15 (m, 2H), 6.34 (d, J = 1.4 Hz, 2H), 6.36 (dd, J = 1.4, 7.8 Hz, 2H), 6.48 (d, J = 7.7 Hz, 2H), 9.24 (br.s, 2H, 2NH) ppm. – 13C NMR (100 MHz, CDCl3): δ = 23.30 (CH3), 31.87, 34.28 (CH2), 125.96 (Ar-CH), 129.79, 133.28 (Ar-C), 134.8 (Ar-CH), 135.4 (Ar-C), 138.78, 167.03 (CO) ppm. – MS: m/z (%) = 322 (90) [M]+, 307 (10) [M–CH3]+, 279 (20) [M–COCH3]+, 220 (10), 161 (94) [M/2]+, 119 (100), 91 (30), 66 (18). – C20H22N2O2 (322.38): calcd. C 74.51, H 6.88, N 8.69; found C 74.37, H 6.84, N 8.60.

3.2 4,15-Bis(acetylamino)-5,12-dibromo[2.2]paracyclophane (3)

To a solution of 1 (80 mg, 0.336 mmol) dissolved in 10 mL of glacial acetic acid, 100 mg of iron powder was added. A solution of bromine (107 mg, 0.66 mmol) dissolved in 5 mL of glacial acetic acid was added dropwise with stirring. The reaction mixture was stirred at 0°C for 2 h. The mixture was poured onto 100 g ice water. The mixture was treated with NaHSO3 and NaHCO3. The product was obtained by extraction using CH2Cl2. The organic layer was washed with water and dried over anhydrous CaCl2. The solvent was evaporated and the residue was subjected to column chromatography using dry ethyl acetate as an eluent to afford 3 as a white powder (80 mg, 67%), m.p. > 300°C. – IR (film): ν = 3426, 33337 (NH), 1701 (CO) cm–1. – 1H NMR (400 MHz, CDCl3): δ = 2.03 (s, 6H, 2CH3), 2.72–2.80 (m, 2H), 2.95–3.05 (m, 4H), 3.40–3.45 (m, 2H), 6.55 (d, J = 7.78 Hz, 2H), 6.61 (d, J = 7.82 Hz, 2H), 8.10 (br.s, 2H, 2NH) ppm. – 13C NMR (100 MHz, CDCl3): δ = 23.18 (CH3), 33.42, 35.09 (CH2), 124.31, 132.84, 133.33 (Ar-CH), 134.74, 135.17, 135.34 (Ar-C), 167.67 (CO) ppm. – MS: m/z (%) = 482/480/478 (50/100/50) [M]+, 401/399 (10/18) [M–HBr]+, 277 (100), 241/239 (48/52) [M/2]+, 199 (60),160 (76), 152 (20), 130 (12), 118 (28), 91 (30), 77 (26). – C20H20Br2N2O2 (480.18): calcd. C 50.02, H 4.19, N 5.83; found C 49.89, H 4.12, N 5.68.

3.3 Reaction of bisacetylamino[2.2]paracyclophane (2) with POCl3

A solution of 2 (80 mg, 0.25 mmol) dissolved in 5 mL of EtOH was added to 15 mL of POCl3. The reaction mixture was heated under reflux conditions for 4 h; then it was cooled to room temperature and poured onto 100 g ice water. It was neutralized with a saturated solution of NaHCO3. The product was extracted with CH2Cl2 and dried over anhydrous CaCl2. The solvent was removed and the residue was separated on chromatographic plates using CH2Cl2–n-pentane (1:1) as eluent to afford compound 5 as a white powder (32 mg, 40%), m.p. 81–82°C. – IR: ν = 3073, 3021 (CH), 1735 (CO), 1629 (C=N) cm–1. – 1H NMR (400 MHz, CDCl3): δ = 1.04 (t, J = 7.1 Hz, 3H, CH3), 2.67 (s, 3H, CH3), 2.70–2.83 (m, 3H), 2.85–2.95 (m, 1H), 3.03–3.17 (m, 4H), 3.97–4.05 (q, J = 7.1 Hz, 2H, CH2), 5.91 (d, J = 1.7 Hz, 1H), 6.03–6.05 (dd, J = 1.7, 7.8 Hz, 1H), 6.34 (d, J = 7.8 Hz, 1H), 6.36–6.40 (m, 3H) ppm. – 13C NMR (100 MHz, CDCl3): δ = 14.06, 26.83 (2CH3), 30.38, 32.35, 35.49, 35.79 (4CH2), 62.67 (C=CH2), 127.08, 127.4, 127.5, 133.3, 133.6, 134.5, 136.35, 137.08, 138.51, 140.60, 141.53, 147.48, 148.61, 154.5 (CO) ppm. MS: m/z (%) = 334 (100) [M]+, 319 (10), 305 (12), 261 (20), 246 (16), 218 (4), 144 (38), 115 (12), 91 (6), 77 (10). – C21H22N2O2 (334.41): calcd. C 75.42, H 6.63, N 8.37; found C 75.27, H 6.55, N 8.21.

3.4 4-Amino-15-benzoylamino[2.2]paracyclophane (6)

4,15-Diamino[2.2]paracyclophane (1) (50 mg, 0.21 mmol) was dissolved in 10 mL of dry CH2Cl2, cooled to 0 °C, and then three drops of Et3N were added. Benzoyl chloride (29 mg, 0.21 mmol) dissolved in 5 mL of dry CH2Cl2 was added dropwise with stirring for 1/2 h. A white precipitate was formed. The precipitate was filtered off, washed with CH2Cl2, and recrystallized from EtOH affording 6 as a white powder (20 mg, 28%), m.p. > 300 °C. – IR: ν = 3442, 3418, 3217 (NH, NH2), 1703 (CO) cm–1. – 1H NMR (400 MHz, CDCl3): δ = 3.21–2.79 (m, 8H), 3.68 (br.s, 2H, NH2), 6.22 (d, J = 1.7 Hz, 1H), 6.29–6.32 (dd, 1H, J = 1.7, 7.6 Hz), 6.35 (d, J = 7.6 Hz), 6.36 (d, J = 1.8 Hz), 6.38–6.41 (dd, 1H, J = 1.8, 7.7 Hz), 6.42 (d, J = 7.7 Hz), 7.90–7.93 (m, 3H), 8.03 (d, J = 8.0 Hz, 2H), 9.59 (br.s, 1H, NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 31.5, 32.1, 34.79, 35.08 (2CH2-CH2), 125.58, 127.0, 128.3, 129.65 (Ar-CH), 130.1, 130.7 (Ar-C), 131.07, 131.4, 131.6 (Ar-CH), 132.2, 133.1, 133.4, 133.6, 135.1, 136.6, 138.89 (Ar-C), 167.5 (CO) ppm. – MS: m/z (%) = 342 (100) [M]+, 222 (40), 195 (20), 145 (34), 119 (80), 104 (60), 91 (26), 77 (14). – C23H22N2O (342.433): calcd. C 80.67, H 6.47, N 8.18; found C 80.42, H 6.40, N 8.07.

3.5 4,15-Bis(benzoylamino)[2.2]paracyclophane (7)

4,15-Diamino[2.2]paracyclophane (1) (50 mg, 0.21 mmol) was dissolved in 10 mL of dry CH2Cl2 and cooled to 0°C. Then three drops of Et3N were added. Benzoyl chloride (87 mg, 0.63 mmol) dissolved in 5 mL of dry CH2Cl2 was added dropwise at room temperature with stirring for 1/2 h. A white precipitate was formed. The precipitate was filtered off and washed with CH2Cl2 to furnish 7 as a white powder (80 mg, 86%), m.p. 228–230°C. – IR: ν = 3429, 3289 (NH), 1717 (CO) cm–1. – 1H NMR (400 MHz, CDCl3): δ = 2.77–2.88 (m, 2H), 2.91–3.04 (m, 4H), 3.16–3.29 (m, 2H), 6.44–6.48 (m, 4H), 6.66 (s, 2H), 7.25–8.15 (m, 10H, 2Ph), 8.41 (br.s, 2H, 2NH) ppm. – 13C NMR (100 MHz, CDCl3): δ = 34.82, 32.31 (CH2), 128.40, 128.44, 130.11, 131.08, 131.63 (Ar-CH), 133.37, 133.58, 134.65 (Ar-C), 135.35 (Ar-CH), 139.94 (Ar-C), 166.2 (2CO) ppm. – MS: m/z (%) = 446 (100) [M]+, 418 (10), 341 (22), 222 (56), 195 (18), 145 (36), 119 (8), 105 (78), 91 (6), 77 (44). – C30H26N2O2 (446.539): calcd. C 80.69, H 5.86, N 6.27; found C 80.51, H 5.85, N 6.19.

3.6 Reaction of diamine 1 with phthaloyl chloride

To a solution of 1 (100 mg, 0.42 mmol) in 20 mL of abs. CH3OH, three drops of Et3N were added. Then a solution of phthaloyl chloride (84.5 mg, 0.42 mmol) dissolved in 5 mL of abs. CH3OH was added dropwise at room temperature with stirring. The reaction mixture was heated under reflux conditions for 20 h; then it was cooled to room temperature and the solvent was removed. The residue was separated on chromatographic plates with CH2Cl2/Et2O (5:1) as an eluent yielding two different products. Compound 8 was isolated from the first zone as yellow crystals (50 mg, 34%), m.p. 119–120 °C. – IR: ν = 3038, 3033 (CH), 1736 (CO), 1620 (C=N) cm–1. – 1H NMR (400 MHz, CDCl3): δ = 2.78–2.89 (m, 2H), 3.00–3.13 (m, 6H), 6.15–6.18 (m, 2H), 6.43 (d, 1H, J = 8.5 Hz), 6.47–6.52 (m, 2H), 6.58 (d, 1H, J = 8.5 Hz), 7.66–7.75 (m, 2H), 7.89 (dd, 1H, J = 1.7, 6.9 Hz), 8.12 (dd, 1H, J = 1.6, 7.8 Hz) ppm. – 13C NMR (100 MHz, CDCl3): δ = 30.9, 31.8, 35.2, 35.4 (CH2), 122.9, 123.6, 127.5 (Ar-CH), 128.5, 130.4 (Ar-C), 132.5, 133.6 (Ar-CH), 133.9, 134.3, 134.5 (Ar-CH), 134.9 (Ar-C), 135.2, 137.7 (Ar-CH), 139.4 (Ar-C), 141.3 (Ar-C), 141.7 (Ar-C), 156.2 (C=N), 167.3 (CO) ppm. – MS: m/z (%) = 350 (100) [M]+, 321 (4), 306 (4), 246 (12), 232 (20), 204 (4), 175 (4), 152 (2), 130 (2), 102 (4), 84 (6), 77 (4). – C24H18N2O (350.412): calcd. C 82.26, H 5.17, N 7.99; found C 82.15, H 5.11, N 7.89.

The second zone afforded compound 9 as a white powder (50 mg, 32%), m.p. 268–270 °C. – IR: ν = 3425, 3380 (NH), 1701 (CO). 1H NMR (400 MHz, CDCl3): δ = 2.70–3.32 (m, 8H), 6.30–6.70 (m, 6H), 7.60–8.01 (m, 4H), 8.10 (br.s, 2H, 2NH) ppm. – 13C NMR (100 MHz, CDCl3): δ = 29.6, 34.2 (CH2), 125.7, 126.8, 133.7, 134.4 (Ar-CH), 134.7 (Ar-C), 135.2, 136.3 (Ar-CH), 136.8 (Ar-C), 137.5, 164.3 (CO) ppm. – MS: m/z (%) = 368 (30) [M]+, 350 (20) [M–H2O]+, 249 (18), 196 (8), 178 (6), 145 (4), 131 (8), 119 (100), 104 (14), 91 (20), 76 (8). – C24H20N2O2 (368.410): calcd. C 78.24, H 5.47, N 7.60; found C 78.09, H 5.49, N 7.47.

3.7 Reaction of 1 with phthalaldehyde

A solution of 1 (100 mg, 0.42 mmol) in 10 mL abs. EtOH was added to a solution of phthalaldehyde (56 mg, 0.42 mmol) in 10 mL abs. EtOH. The mixture was heated under reflux conditions for 18 h. The mixture was then cooled to room temperature, and the solvent was evaporated to yield the product 17 as white crystals (140 mg, 99%), m.p. 59–60 °C. – IR: ν = 3034, 3020, 1636 (C=N) cm–1. – 1H NMR (400 MHz, CDCl3): δ = 2.86–3.02 (m, 2H), 3.06–3.18 (m, 5H), 3.26–3.31 (m, 1H), 5.12 (s, 2H, CH2-N), 6.58–6.61 (dd, J = 1.4, 7.9, 1H), 6.67 (d, J = 7.9 Hz, 1H), 6.71 (s, 2H), 6.78 (d, J = 1.3 Hz, 1H), 6.97 (s, 1H), 7.76–7.85 (m, 2H), 7.88–7.92 (m, 1H), 8.45 (d, J = 7.7, 1H) ppm. – 13C NMR (100 MHz, CDCl3): δ = 30.45, 30.61, 34.68, 34.87 (CH2), 60.4 (N-CH2), 123.59, 123.7 (Ar-CH), 128.67 (Ar-C), 128.81, 133.35, 133.63, 134.45, 134.65, 134.93, 134.98, 135.7 (Ar-CH), 135.8, 136.7, 137.4, 142.1, 142.2, 142.49 (Ar-C), 157.26 (C=N) ppm. – MS: m/z (%) = 336 (100) [M]+, 232 (16), 217 (12), 168 (6), 104 (6), 91 (10), 77 (10). – C24H20N2 (336.42): calcd. C 85.68, H 5.99, N 8.33; found C 85.58, H 5.96, N 8.28.

3.8 4,15-Bis(formylamino)[2.2]paracyclophane (18)

A mixture of 1 (50 mg, 0.21 mmol) and formic acid (10 mL) was heated under reflux for 4 h, and then cooled to room temperature. The solvent was removed and the solid product 18 was obtained as buff crystals (50 mg, 81%), m.p. 150–151 °C. – IR: ν = 3443, 3205 (NH), 1698 (CO) cm–1. – 1H NMR (400 MHz, CDCl3): δ = 2.83–3.09 (m, 6H), 3.64–3.71 (m, 2H), 6.37 (d, J = 1.7, 2H), 6.45–6.47 (dd, J = 1.7, 7.8 Hz, 2H), 6.57 (d, J = 7.8 Hz, 2H), 8.30 (d, J = 10.9 Hz, 2H, 2NH), 10.55 (d, J = 10.1 Hz, 2H, 2CHO) ppm. – 13C NMR (100 MHz, CDCl3): δ = 34.8, 30.95 (CH2), 125.8, 129.6, 130.3 (Ar-CH), 135.8, 136.17, 141.30 (Ar-C), 165.90 (CO) ppm. – MS: m/z (%) = 294 (100) [M]+, 276 (22) [M–H2O]+, 265 (30) [M–CHO]+, 147 (68) [M/2]+, 119 (100), 104 (34), 91 (28), 77 (10). – C18H18N2O2 (294.34): calcd. C 73.44, H 6.16, N 9.52; found C 73.32, H 6.15, N 9.43.

3.9 4,15-Bis(3-oxocyclohex-1-en-1-yl)amino[2.2]paracyclophane (19)

A solution of 1 (50 mg, 0.21 mmol) in 10 mL of abs. EtOH was added to a solution of cyclohexane-1,3-dione (47 mg, 0.42 mmol) dissolved in 10 mL abs. EtOH. The mixture was heated under reflux for 72 h, and then cooled to room temperature. The solvent was evaporated and the residue was subjected to column chromatography using CH2Cl2 as an eluent. Product 19 was obtained as a white powder (76 mg, 85%), m. p. 199–200°C. – IR: ν = 3382, 3351 (NH), 1719 (C=O) cm–1. – 1H NMR (400 MHz, CDCl3): δ = 2.0–2.03 (m, 4H), 2.28–2.37 (m, 4H), 2.49–2.53 (m, 4H), 2.80–2.83 (m, 2H), 3.16–3.21 (m, 2H), 2.88–2.99 (m, 4H), 5.85 (t, J = 4.7 Hz, 2H), 6.20 (d, J = 1.7 Hz, 2H), 6.25–6.28 (dd, J = 1.8, 7.7 Hz, 2H), 6.43 (br.s, 2H, 2NH), 6.47 (d, J = 7.7 Hz, 2H) ppm. – 13C NMR (100 MHz, CDCl3): δ = 37.68, 35.08, 31.70, 24.42, 23.05 (CH2), 113.19, 124.27, 127.52 (Ar-CH), 130.74 (Ar-C), 135.18 (Ar-CH), 136.31, 139.78, 140.44 (Ar-C), 195.08 (C=O) ppm. – MS: m/z (%) = 426 (88) [M]+, 408 (18), 398 (14), 379 (10), 331 (10), 213 (64), 197 (100), 156 (86), 143 (26), 130 (22), 128 (14), 103 (12), 77 (14). – C28H30N2O2 (426.55): calcd. C 78.84, H 7.08, N 6.57; found C 78.73, H 6.98, N 6.51.

3.10 Reaction of 1 with terephthalaldehyde

A solution of 1 (50 mg, 0.21 mmol) in 10 mL of abs. EtOH was added to a solution of terephthalaldehyde (28 mg, 0.21 mmol) in 10 mL of abs. EtOH. The mixture was heated under reflux conditions for 5 h. A red precipitate was formed. The mixture was cooled to room temperature and the precipitate was filtered off to yield the product 20 as red crystals (120 mg, 85%), m.p. > 300°C. – IR: ν = 3023, 3000, 1616 (C=N) cm–1. – 1H NMR (400 MHz, CDCl3): δ = 2.90–3.58 (m, 16H), 6.25–6.70 (m, 12H), 6.80–7.20 (m, 8H), 8.0 (s, 2H), 8.37 (s, 2 H, 2 CH=N) ppm. – 13C NMR (100 MHz, CDCl3): δ = 37.22, 36.45, 36.30, 35.33 (CH2), 133.30, 132.97, 128.02 (Ar-C), 134.55, 134.20 (Ar-C), 134.11 (Ar-CH), 134.77, 134.90, 134.98, 135.17, 135.51, 136.07, 137.89, 138.22, 138.27 (Ar-CH), 138.84, 139.5, 143.64 (Ar-C), 151.25, 153.7 (C=N) ppm. – MS: m/z (%) = 672 (100) [M]+, 567 (10), 542 (10), 439 (12), 316 (22), 231 (20), 206 (18), 130 (16), 104 (34), 78 (22). – C48H40N4 (672.85): calcd. C 85.68, H 5.99, N 8.33; found C 85.45, H 5.94, N 8.17.

3.11 Synthesis of compound 21

A solution of 1 (119 mg, 0.5 mmol) in 20 mL of rectified spirit was added to a mixture of CS2 (190 mg, 2.5 mmol) and KOH (84 mg, 1.5 mmol) dissolved in 10 mL water. The mixture was heated under a reflux condition for 3 h; then it was cooled to room temperature. The mixture was acidified with AcOH. A white precipitate was formed which was collected by filtration to give 21 as white crystals (126 mg, 90%), m.p. 263–265 °C. – IR: ν = 3444, 3149 (NH), 1595 (CO) cm–1. – 1H NMR (400 MHz, CDCl3): δ = 2.81–2.85 (m, 2H), 2.93–2.98 (m, 2H), 3.06–3.14 (m, 2H), 3.29–3.33 (m, 2H), 6.37–6.40 (dd, J = 1.7, 7.9 Hz, 2H), 6.48 (d, J = 7.9 Hz, 2H), 6.49 (d, J = 1.7 Hz, 2H), 9.46 (br.s, 2H, 2NH) ppm. – 13C NMR (100 MHz, CDCl3): δ = 31.11, 34.70 (CH2), 132.0, 133.80, 136.30 (Ar-CH), 137.60, 141.30 (Ar-C), 177.60 (C=S) ppm. – MS: m/z (%) = 280 (100) [M]+, 265 (20), 246 (20), 232 (12), 161 (16), 119 (70), 91 (30), 77 (18). – C17H16N2S (280.38): calcd. C 72.82, H 5.75, N 9.99, S 11.43; found C 72.70, H 5.73, N 9.91, S 11.50.

3.12 [2.2]Paracyclophane-4,15-diisothiocyanate (22)

A solution of 1 (100 mg, 0.42 mmol) was added at room temperature to a mixture of CS2 (5 g, 65 mmol) and 10 mL NH4OH (25%) with stirring. The mixture was refluxed for 19 h; then it was cooled to room temperature and poured onto ice water (50 mL). The product was extracted using CH2Cl2. The solvent was concentrated and the residue was subjected to column chromatography using CH2Cl2/Et2O (1:1). The product was obtained after removing eluent and was identified as 22: white powder (24 mg, 43%), m.p. 129–130°C. – IR: ν = 3038, 2957, 2892 (CH), 2058 (N=C=S) cm–1. – 1H NMR (400 MHz, CDCl3): δ = 2.85–2.95 (m, 6H), 3.47–3.55 (m, 2H), 6.35 (d, J = 1.7 Hz, 2H), 6.38–6.40 (dd, J = 1.7, 7.9 Hz, 2H), 6.43 (d, J = 7.8 Hz, 2H) ppm. – 13C NMR (100 MHz, CDCl3): δ = 31.48, 34.62 (CH2), 130.67 (Ar-CH), 130.99 (Ar-C), 132.01, 135.08 (Ar-CH), 135.57, 141.30 (Ar-C) ppm. – MS: m/z (%) = 322 (16) [M]+, 299 (10), 258 (100), 192 (26), 161 (40), 128 (42), 96 (24), 64 (38). – C18H14N2S2 (322.45): calcd. C 67.04, H 4.37, N 8.69, S 19.89; found C 66.83, H 4.38, N 8.58, S 19.72.

Corresponding author: Kamal M. El-Shaieb, Faculty of Science, Chemistry Department, Minia University, El-Minia, Egypt, Fax: +2-086-2363011, E-mail:

Acknowledgments

Kamal M. El-Shaieb is indebted to Prof. H. Hopf for providing working facilities and valuable discussion, and to the Egyptian Government for donating a scholarship under the channel system.

References

[1] F. Vögtle, Cyclophane Chemistry, Wiley, New York, 1993.Search in Google Scholar

[2] F. Diederich, Cyclophanes, Royal Society of Chemistry, Cambridge, 1991.10.1039/9781788010924Search in Google Scholar

[3] K. M. El-Shaieb, H. Hopf, P. G. Jones, Arkivoc2009, 146.Search in Google Scholar

[4] F. F. Abdel-Latif, K. M. El-Shaieb, A. G. El-Deen, Z. Naturforsch.2011, 66b, 965.10.1515/znb-2011-0916Search in Google Scholar

[5] A. A. Aly, H. Hopf, P. G. Jones, I. Dix, Tetrahedron2006, 62, 4498.10.1016/j.tet.2006.02.047Search in Google Scholar

[6] H. Hopf, R. Gleiter, Modern Cyclophane Chemistry, Wiley-VCH, Weinheim, 2004, chapter 17, p. 435.10.1002/3527603964Search in Google Scholar

[7] L. Birsa, P. G. Jones, H. Hopf, Eur. J. Org. Chem.2005, 15, 3263.10.1002/ejoc.200500093Search in Google Scholar

[8] H. Hopf, W. Grahn, D. G. Barrett, A. Gerdes, J. Hilmer, J. Hucker, Y. Okamoto, Y. Kaida, Chem. Ber.1990, 123, 841.10.1002/cber.19901230432Search in Google Scholar

[9] A. A. Aly, A. A. Hassan, A. E. Mourad, Can. J. Chem.1993, 71, 1845.10.1139/v93-231Search in Google Scholar

[10] I. Held, A. Villinger, H. Zipse, Synthesis2005, 9, 1425.Search in Google Scholar

[11] T. V. Hansen, P. Wu, V. V. Fokin, J. Org. Chem.2005, 70, 7761.10.1021/jo050163bSearch in Google Scholar

[12] H. Zitt, I. Dix, H. Hopf, P. G. Jones, Eur. J. Org. Chem.2002, 2002, 2298.10.1002/1099-0690(200207)2002:14<2298::AID-EJOC2298>3.0.CO;2-ESearch in Google Scholar

[13] K. El-Shaieb, V. Narayanan, H. Hopf, I. Dix, A. Fischer, P. G. Jones, L. Ernst, K. Ibrom, Eur. J. Org. Chem.2003, 2003, 567.10.1002/ejoc.200390095Search in Google Scholar

[14] K. M. El-Shaieb, A.-E. Mourad, A. A. Aly, H. Hopf, Arkivoc2006, ii, 193.10.3998/ark.5550190.0007.222Search in Google Scholar

[15] D. J. Cram, R. H. Bauer, J. Am. Chem. Soc.1959, 81, 5971.10.1021/ja01531a031Search in Google Scholar

[16] L. A. Singer, D. J. Cram, J. Am. Chem. Soc.1963, 85, 1080.10.1021/ja00891a011Search in Google Scholar

Received: 2015-5-31
Accepted: 2015-7-17
Published Online: 2015-10-7
Published in Print: 2015-11-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. In this Issue
  3. Gd4(BO2)O5F – a gadolinium borate fluoride oxide comprising a linear BO2 moiety
  4. Hydrolysis of 8-(pinacolboranyl)quinoline: where is the 8-quinolylboronic acid?
  5. Synthesis of some novel 6′-(4-chlorophenyl)-3,4′-bipyridine-3′-carbonitriles: assessment of their antimicrobial and cytotoxic activity
  6. Synthesis of some 6-alkylureido-4-aryl-2(1H)-pyridones: further transformations and pharmacological activity
  7. Multicomponent green synthesis, spectroscopic and structural investigation of multi-substituted imidazoles. Part 1
  8. Sonochemical synthesis of 5-substituted 1H-tetrazoles catalyzed by ZrP2O7 nanoparticles and regioselective conversion into new 2,5-disubstituted tetrazoles
  9. Two new taxane-glycosides from the needles of Taxus canadensis
  10. Cytotoxic 24-nor-ursane-type triterpenoids from the twigs of Mostuea hirsuta
  11. 4,15-Diamino[2.2]paracyclophane as a useful precursor for the synthesis of novel pseudo-geminal [2.2]paracyclophane compounds
https://doi.org/10.1515/znb-2015-0093
Keywords for this article
cyclization reactions; 4,15-diamino[2.2]paracyclophane; neighboring group effects; tris-bridged cyclophanes

Articles in the same Issue

  1. Frontmatter
  2. In this Issue
  3. Gd4(BO2)O5F – a gadolinium borate fluoride oxide comprising a linear BO2 moiety
  4. Hydrolysis of 8-(pinacolboranyl)quinoline: where is the 8-quinolylboronic acid?
  5. Synthesis of some novel 6′-(4-chlorophenyl)-3,4′-bipyridine-3′-carbonitriles: assessment of their antimicrobial and cytotoxic activity
  6. Synthesis of some 6-alkylureido-4-aryl-2(1H)-pyridones: further transformations and pharmacological activity
  7. Multicomponent green synthesis, spectroscopic and structural investigation of multi-substituted imidazoles. Part 1
  8. Sonochemical synthesis of 5-substituted 1H-tetrazoles catalyzed by ZrP2O7 nanoparticles and regioselective conversion into new 2,5-disubstituted tetrazoles
  9. Two new taxane-glycosides from the needles of Taxus canadensis
  10. Cytotoxic 24-nor-ursane-type triterpenoids from the twigs of Mostuea hirsuta
  11. 4,15-Diamino[2.2]paracyclophane as a useful precursor for the synthesis of novel pseudo-geminal [2.2]paracyclophane compounds
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2026 De Gruyter Brill
Downloaded on 20.1.2026 from https://www.degruyterbrill.com/document/doi/10.1515/znb-2015-0093/html
Scroll to top button