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Journal of Chemistry
Volume 2019, Article ID 3424319, 7 pages
https://doi.org/10.1155/2019/3424319
Research Article

One-Pot Synthesis of Novel Dibenzoxanthenes, Diarylbutanes, and Calix[4]resorcinarenes via Consecutive Pyrrolidine Ring-Closure/Ring-Opening Reactions

Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russia

Correspondence should be addressed to Andrey V. Smolobochkin; ur.cpoi@nikhcoboloms

Received 17 December 2018; Revised 22 January 2019; Accepted 31 January 2019; Published 15 April 2019

Academic Editor: Sylvain Antoniotti

Copyright © 2019 Andrey V. Smolobochkin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Herein, we report the approach to the otherwise hardly accessible dibenzoxanthenes, diarylbutanes, and calix[4]resorcinarenes possessing urea moieties based on the reaction of N-(4,4-diethoxybutyl)ureas with electron-rich aromatics in strongly acidic media. Unlike the previously developed methods, the proposed approach benefits from one-pot procedure and allows to obtain the target compounds with much higher yields.

1. Introduction

Diarylmethane derivatives containing two phenolic moieties are of interest due to their wide spectrum biological activity. These compounds are known to inhibit C-C chemokine receptors [1], possess anti-inflammatory [2], antiproliferative [3], antimicrobial [4], anti-HIV [5], and anticancer activity [6]. Some compounds of this class exhibit antibacterial properties [7, 8]. Additionally, diarylmethane derivatives containing an urea fragment can be used to treat hyperparathyroidism [911], malaria [12], and atherosclerosis [13] and inhibit lysine-specific demethylase 1 (LSD1) [14], DNA topoisomerase [15], and epoxy hydrolase [16].

The most general approach to these compounds is the acidic media condensation of electron-rich aromatic nucleophiles with aldehydes [1719] or acetals [2022] (Scheme 1(A)). However, this method is inapplicable in case of acetals containing urea moiety, since these compounds are subject to intramolecular cyclization in acidic media [2326]. Earlier, we have developed the approach to diarylbutanes, dibenzoxanthenes, and calixarenes possessing urea fragment via acid-catalyzed ring opening of 2-(2-hydroxynaphthalene-1-yl)pyrrolidine-1-carboxamides 1 [27, 28] (Scheme 1(B)). Although the proposed approach benefits from mild reaction conditions and usage of inexpensive trifluoroacetic acid as catalyst, its certain disadvantage is the necessity of preliminary synthesis of intermediate 2-(2-hydroxynaphthalene-1-yl)pyrrolidines 1. At the same time, methods allowing “one-pot” synthesis of the target compounds is of a great importance nowadays due to both their effectiveness and atom economy [29], which are among main principles of green chemistry. Thus, herein we report the improved one-pot approach to the diarylbutane derivatives containing urea moieties starting from easily accessible N-(4,4-diethoxybutyl)ureas 2.

Scheme 1: Synthesis of diarylmethane derivatives.

2. Results and Discussion

We assumed that pyrrolidine ring opening in strongly acidic media is general for all 2-aryl substituted pyrrolidines. This assumption was supported both by our own observations [27] and synthesis of diphenylbutane derivative upon treatment of N-phenacyl-2-phenylpyrrolidine with triflic acid in benzene solution described by King et al. [30] (Scheme 1(C)). Based on this data, we proposed that carrying out the reaction of N-(4,4-diethoxybutyl)ureas with phenols in strongly acidic media would allow us to obtain appropriate diarylbutanes in one-pot procedure via consecutive pyrrolidine ring closure-ring opening processes. Thus, the need of preliminary synthesis of 2-(2-hydroxynaphthalene-1-yl)pyrrolidines would be eliminated.

First, we studied the reaction of ureas 2a,c with 2-naphthol 3. The reaction was carried out in chloroform solution in the presence of 3-fold excess of trifluoroacetic acid, since these conditions were found to be optimal for the ring opening in 2-(2-hydroxynaphthalene-1-yl)pyrrolidines 1 [27]. However, according to NMR data, in this case the yield of target dibenzoxanthenes 5a,c appeared to be rather low. The main products were previously described by us 2-naphthylpyrrolidine derivatives 1a,c [24] (Scheme 2). Next, we gradually increased the amount of trifluoroacetic acid used. Upon increasing the excess of trifluoroacetic acid up to 20-fold, the reaction led to the formation of target dibenzoxanthenes with about 80% yield (Table 1, Nos. 1 and 2). Naphthalene-2,7-diol 4 reacted under the same conditions with urea 2b with the formation of previously unknown 2,12-dihydroxydibenzoxanthene derivative 6b containing urea moiety (Table 1, No. 3).

Scheme 2: Synthesis of dibenzoxanthenes.
Table 1: Synthesis of the compounds 510.

Further, 4-bromoresorcinol and sesamol were involved into this reaction. The choice of the substrates was based on their known biological activity. For example, sesamol exhibits antioxidant properties [31, 32] and is a part of the antidepressant paroxetine structure [3335] and bromoresorcinol dimers are known for their antimicrobial activity [4]. The reaction of these compounds with ureas 2ac led to the diarylbutane derivatives and 8ac (Scheme 3, Table 1, Nos. 4–7). Hydroxycoumarine, which is part of the many biologically active compounds [3639], also successfully undergoes this reaction, leading to the formation of bis(4-hydroxy-2H-chromen-2-one) derivative (Table 1, No. 8).

Scheme 3: Synthesis of diarylbutanes.

The applicability of this approach to the synthesis of macrocyclic compounds has been demonstrated as well using 2-methylresorcinol as a model substrate. The reaction of this phenol with ureas 2a,d resulted in the appropriate calix[4]resorcinarenes 10а,d formation with up to 70% yield (Scheme 4, Table 1, No. 9, 10).

Scheme 4: Synthesis of calixarenes.

As seen from Table 1, using N-(4,4-diethoxybutyl)ureas 2 as a starting compounds instead of 2-(2-hydroxynaphthalene-1-yl)pyrrolidines allowed us to increase the yields of the target compounds by 16% in average. Taking into account the losses of the starting material during the preliminary synthesis of 2-(2-hydroxynaphthalene-1-yl)pyrrolidines, the overall gain in yield was more than 20% (Scheme 5).

Scheme 5: Synthesis of 2-arylpyrrolidines and polyphenols.

Taking into consideration previously published data [30, 40], we proposed the mechanism of this reaction depicted in Scheme 6. The first stage of the reaction is a protonation of ethoxy group and elimination of ethanol molecule. The oxonium cation A thus formed may further react with phenol molecule, leading to the 2-arylpyrrolidine derivative B as previously described [24]. Subsequent pyrrolidine ring opening in the presence of excess of trifluoroacetic acid followed by interaction with another phenol molecule via the mechanism similar to that of 2-(2-hydroxynaphthalene-1-yl)pyrrolidines [27] results in the formation of target compounds E.

Scheme 6: Proposed mechanism for the substituted ureas formation.

In principle, the other pathway is also possible. It includes the protonation of urea moiety of the oxonium cation A, leading to the dication F. The presence of significant positive charge on the nitrogen atom prevents its intramolecular cyclization, and its further reaction with phenol molecule leads to the acyclic intermediate H. Further reaction of this compound with another phenol molecule via the benzylic cation I also results in the formation of final compounds E.

The experimental data present at the moment does not allow us to unequivocally distinguish between these mechanisms. However, taking into account much higher rate of intramolecular cyclization of N-(4,4-diethoxybutyl)ureas 2 compared to their intermolecular interaction with phenols, as well as instability of dicationic species in non-superacidic media, the first pathway seems to be more probable. Additionally, no acyclic intermediates were present in mass-spectra of the reaction mixture, which may also indicate the preference of the first pathway over second one.

3. Conclusions

In conclusion, we have developed one-pot approach to the otherwise hardly accessible dibenzoxanthenes, diarylbutanes, and calix[4]resorcinarenes possessing urea moieties via the reaction of N-(4,4-diethoxybutyl)ureas with electron-rich aromatics in strongly acidic media. The reaction presumably proceeds via consecutive pyrrolidine ring closure-ring opening stages. The proposed approach, in contrast to the previously developed method, does not require an isolation of intermediates and allows to obtain target compounds with much higher yields.

4. Experimental

IR spectra were recorded on a UR-20 spectrometer in the 400–3600 cm −1 range in KBr. 1H NMR spectra were recorded on a Bruker MSL 400 spectrometer (400 MHz) with respect to the signals of residual protons of deuterated solvent (DMSO-d6). 13C NMR spectra were recorded on a Bruker Avance 600 (150 MHz) spectrometer relative to signals of residual protons of deuterated solvent (DMSO-d6). MALDI mass-spectra are obtained on a mass spectrometer UltraFlex III TOF/TOF (Bruker Daltonik GmbH, Bremen, Germany) in a linear mode. The laser is Nd : YAG, λ = 266 nm.

The data were processed with the FlexAnalysis 3.0 program (Bruker Daltonik GmbH, Bremen, Germany). Positively charged ions were fixed, and a metal target was used. 2,5-Dihydroxybenzoic acid (DHB) was used as a matrix. Elemental analysis is performed on a Carlo Erba device EA 1108. The melting points are determined in glass capillaries on a Stuart SMP 10 instrument.

2-(2-Hydroxynaphthalen-1-yl)pyrrolidine-1-carboxamides 1ad were obtained as described previously [24, 25].

4.1. General Method for the Synthesis of Dibenzoxanthenes 5a,b and 6c [27]

To a solution of 1.10 mmol naphthol 4 or 5 in 5 ml of dry chloroform, 0.55 mmol 2-(2-hydroxynaphthalen-1-yl)pyrrolidine-1-carboxamides 1 and 2 ml trifluoroacetic acid were added. The mixture was stirred at room temperature for 72 h. Solvent was evaporated in vacuum. Residue was washed with diethyl ether, filtered, and dried in vacuum (1 h, 0.01 Torr) to give the title compound.

4.2. General Method for the Synthesis of Dibenzoxanthenes 5a,c and 6b

To a mixture of 1.17 mmol of naphthol, 5 ml of chloroform and 0.59 mmol of acetal 2, and 2 ml of trifluoroacetic acid were added. The reaction mixture was stirred for 24 hours at room temperature, the solvent was removed in vacuum, and the residue was washed with diethyl ether and dried in vacuum.

4.2.1. 1-(3-(14H-Dibenzo[a,j]xanthen-14-yl)pro-pyl)-3-phenylurea (5a)

White crystals, m.p. 240°C–241°C, yield 87%. IR (cm−1, KBr): 1592, 1650, 2937, 3065, 3328. 1H NMR (δ ppm, DMSO-d6): 1.00–1.11 (m, 2Н, СН2), 1.89–1.99 (m, 2Н, СН2), 2.71–2.79 (m, 2Н, СН2), 5.72–5.77 (m, 1Н, CH), 5.81–8.84 (m, 1Н, NH), 6.82 (t, J = 7.1 Hz, 1Н, CНAr), 7.13 (t, 2Н, J = 8.2 Hz, CНAr), 7.23 (d, 2Н, J = 7.8 Hz, CНAr), 7.44 (d, 2Н, J = 8.9 Hz, CНAr), 7.49–7.54 (m, 2Н, CНAr), 7.65–7.71 (m, 2Н, CНAr), 7.91 (d, 2Н, J = 8.9 Hz, CНAr), 7.96–8.00 (m, 2Н, CНAr), 8.15 (br.s, 1Н, NH), 8.54–8.59 (m, 2Н, CНAr). 13С NMR (δ ppm, DMSO-d6): 26.3, 30.3, 33.9, 39.5, 117.0, 117.6, 118.0, 121.3, 123.6, 124.9, 127.4, 129.0, 129.1, 131.1, 131.5, 140.9, 149.9, 155.3. MALDI TOF, m/z: 481 [M+Na]+ [27].

4.2.2. 1-(3-(14H-Dibenzo[a,j]xanthen-14-yl)propyl)-3-hexylurea (5c)

White crystals, m.p. 183°C–184°C, yield 79%. %. IR (cm−1, KBr): 1592, 1625, 2857, 2927, 3069, 3417. 1H NMR (δ ppm, DMSO-d6): 0.83 (t, 3Н, J = 7.04 Hz, СН3), 0.91–1.02 (m, 2Н, СН2), 1.08–1.27 (m, 8Н, СН2), 1.84–1.93 (m, 2Н, СН2), 2.59–2.67 (m, 2Н, СН2), 2.76–2.83 (m, 2Н, СН2), 5.42–5.51 (m, 2Н, NH), 5.69–5.74 (m, 1Н, СН), 7.43 (d, 2Н, J = 8.9 Hz, СНAr), 7.47–7.54 (m, 2Н, СНAr), 7.64–7.70 (m, 2Н, СНAr), 7.91 (d, 2Н, J = 8.9 Hz, СНAr), 7.94–7.99 (m, 2Н, СНAr), 8.51–8.56 (m, 2Н, СНAr). 13С NMR (δ ppm, DMSO-d6): 14.3, 15.6, 22.5, 26.4, 26.5, 26.5, 30.3, 31.4, 33.9, 39.4, 117.0, 117.6, 123.5, 124.8, 127.3, 128.9, 129.1, 131.1, 131.5, 149.8, 158.2. MALDI TOF, m/z: 489 [M+Na]+ [27].

4.2.3. 1-(3-(2,12-Dihydroxy-14H-dibenzo[a,j]xanthen-14-yl)propyl)-3-(4-methoxyphenyl)urea (6b)

White crystals, m.p. 183–185°С, yield 65%. IR (cm−1, KBr): 1596, 2835, 3195, 3314. 1H NMR (δ ppm, DMSO-d6): 1.00–1.14 (m, 2H, СН2), 2.73–2.87 (m, 2H, СН2), 3.62–3.71 (m, 2H, СН2), 3.66 (s, 3H, СН3), 5.25 (t, J = 4.7 Hz, 1H, СН), 5.76 (t, J = 5.4 Hz, 1H, NН), 6.74 (d, J = 8.9 Hz, 2H, СНAr), 7.08 (d, J = 7.6 Hz, 2H, СНAr), 7.13–7.18 (m, 4H, СНAr), 7.57 (s, 2H, СНAr), 7.75 (d, J = 8.7 Hz, 2H, СНAr), 7.80 (d, J = 8.7 Hz, 2H, СНAr), 7.89 (s, 1H, NН), 9.86 (s, 2H, OН). 13С NMR (δ ppm, DMSO-d6): 14.52, 26.43, 30.65, 32.69, 55.56, 105.07, 114.21, 114.25, 114.96, 117.05, 119.92, 125.56, 128.67, 130.81, 133.18, 134.01, 150.28, 154.32, 155.67, 156.97. MALDI-TOF: 543 [M+Na]+. Anal. Calcd.: C32H28N2O5 (520), C, 73.83; H, 5.42; N, 5.38. Found: C, 73.98; H, 5.60; N, 5.48.

4.3. General Method for the Synthesis of Diarylbutanes , 8ac, 9a [27]

To a mixture of 0.30 mmol pyrrolidine-1-carboxamide 1 in 5 ml of dry chloroform, appropriate 0.90 mmol phenol and 2 ml trifluoroacetic acid were added. The mixture was stirred at room temperature for 72 h. Solvent was evaporated in vacuum. Residue was washed with diethyl ether, filtered, and dried in vacuum (1 h, 0.01 Torr) to give the title compound , 8ac, 9a.

4.4. General Method for the Synthesis of Diarylbutanes , 8ac, 9a

To a mixture of 1.82 mmol of phenol, 5 ml of chloroform, and 0.91 mmol of acetal 2, 2 ml of trifluoroacetic acid was added. The reaction mixture was stirred for 24 hours at room temperature, the solvent was removed in vacuum, and the residue was washed with diethyl ether and dried in vacuum.

4.4.1. 1-(4,4-Bis(5-bromo-2,4-dihydroxyphenyl)butyl)-3-phenylurea (7a)

White crystals, m.p. 132°C–133°C, yield 72%. IR (cm−1, KBr): 1597, 1652, 2868, 2937, 3402. 1H NMR (δ ppm, DMSO-d6): 1.27–1.37 (m, 2Н, СН2), 1.77–1.86 (m, 2Н, СН2), 3.02–3.10 (m, 2Н, СН2), 4.25 (t, 1Н, J = 7.9 Hz, CНAr), 6.08 (t, 1Н, J = 5.8 Hz, NH), 6.45 (s, 2Н, CНAr), 6.84–6.89 (m, 1Н, CНAr), 7.03 (s, 2Н, CНAr), 7.16–7.22 (m, 2Н, CНAr), 7.33–7.38 (m, 2Н, CНAr). 13С NMR (δ ppm, DMSO-d6): 29.0, 31.5, 36.1, 65.4, 98.2, 104.0, 118.1, 121.3, 124.4, 129.0, 131.7, 141.0, 152.7, 155.5, 155.6. MALDI TOF, m/z: 589 [M+Na]+ [27].

4.4.2. 1-(4,4-Bis(6-hydroxybenzo[d][1,3]dioxol-5-yl)butyl)-3-phenylurea ()

White crystals, m.p. 165–166°С, yield 95%. IR (cm−1, KBr): 1596, 2935, 3291, 3383. 1H NMR (δ ppm, DMSO-d6): 1.29–1.39 (m, 2H, СН2), 1.80–1.89 (m, 2H, СН2), 3.02–3.10 (m, 2H, СН2), 4.43 (t, J = 7.8 Hz, 1H, СН), 5.83 (d, J = 8.3 Hz, 4H, СН2), 6.07 (s, 1H, NН), 6.38 (s, 2H, СНAr), 6.69 (s, 2H, СНAr), 7.20 (t, J = 7.6 Hz, 2H, СНAr), 7.35 (d, J = 7.6 Hz, 2H, СНAr), 8.29 (s, 1H, NН), 8.90 (s, 2H, OН). 13С NMR (δ ppm, DMSO-d6): 15.65, 29.08, 31.73, 36.18, 98.01, 100.80, 108.05, 118.09, 121.36, 123.42, 129.05, 140.11, 141.06, 145.47, 149.56, 155.65. MALDI-TOF: 487 [M+Na]+, 503 [M+K]+. Anal. Calcd.: C25H24N2O7 (464), 64.65; H, 5.21; N, 6.03. Found: 64.79; H, 5.11; N, 5.98.

4.4.3. 1-(4,4-Bis(6-hydroxybenzo[d][1,3]dioxol-5-yl)butyl)-3-(4-methoxyphenyl)urea (8b)

White crystals, m.p. 130–131°С, yield 93%. IR (cm−1, KBr): 1595, 2818, 3212, 3337. 1H NMR (δ ppm, DMSO-d6): 1.29–1.37 (m, 2H, СН2), 1.79–1.86 (m, 2H, СН2), 2.98–3.08 (m, 2H, СН2), 3.68 (s, 3H, СН3), 4.42 (t, J = 7.8 Hz, 1H, СН), 5.83 (d, J = 9.5 Hz, 4H, СН2), 5.95 (s, 1H, NН), 6.37 (s, 2H, СНAr), 6.68 (s, 2H, СНAr), 6.79 (d, J = 9.1 Hz, 2H, СНAr), 7.24 (d, J = 9.1 Hz, 2H, СНAr), 8.08 (s, 2H, СНAr), 8.90 (s, 2H, OН). 13С NMR (δ ppm, DMSO-d6): 29.15, 31.73, 36.14, 55.61, 55.68, 98.00, 100.80, 108.07, 114.38, 119.89, 123.43, 134.20, 140.10, 145.46, 149.55, 154.34, 155.90. MALDI-TOF: 507 [M+Na]+. Anal. Calcd.: C26H26N2O8 (494), C, 63.15; H, 5.30; N, 5.67. Found: C, 63.27; H, 5.41; N, 5.85.

4.4.4. 1-(4,4-Bis(6-hydroxybenzo[d][1,3]dioxol-5-yl)butyl)-3-hexylurea (8c)

White crystals, m.p. 102–103°С, yield 59%. IR (cm−1, KBr): 1597, 2719, 3147, 3214, 3362. 1H NMR (δ ppm, DMSO-d6): 0.84 (t, J = 6.4 Hz, 3H, СН3), 1.21–1.27 (m, 8H, СН2), 1.31–1.35 (m, 2H, СН2), 1.72–1.85 (m, 2H, СН2), 2.93–2.99 (m, 2H, СН2), 4.42 (t, J = 7.8 Hz, 1H, СН), 5.83 (d, J = 10.8 Hz, 4H, СН2), 6.39 (s, 2H, СНAr), 6.67 (s, 2H, СНAr), 7.67 (s, 2H, OН). 13С NMR (δ ppm, DMSO-d6): 14.29, 22.53, 26.51, 29.31, 30.43, 31.50, 31.70, 36.14, 46.68, 55.21, 98.03, 100.76, 107.96, 119.74, 140.11, 149.54, 153.03, 158.70. MALDI-TOF: 495 [M+Na]+. Anal. Calcd.: C25H32N2O7 (472), C, 63.55; H, 6.83; N, 5.93. Found: C, 63.63; H, 6.99; N, 6.16.

4.4.5. 1-(4,4-Bis(4-hydroxy-2-oxo-2H-chromen-3-yl)butyl)-3-phenylurea (9a)

White crystals, m.p. 235–237°С, yield 42%. IR (cm−1, KBr): 1595, 2810, 3198, 3358, 3334. 1H NMR (δ ppm, DMSO-d6): 1.28–1.45 (m, 2H, СН2), 2.06–2.20 (m, 2H, СН2), 2.95–3.10 (m, 2H, СН2), 4.89 (t, J= 8.3 Hz, 1H, СН), 6.84 (t, J= 7.5 Hz, 1H, СНAr), 7.14–7.19 (m, 2H, СНAr), 7.25–7.30 (m, 3H, СНAr), 7.32 (d, J= 8.6 Hz, 1H, СНAr), 7.34–7.38 (m, 2H, СНAr), 7.53 (t, J= 6.9 Hz, 1H, СНAr), 7.64 (t, J= 7.6 Hz, 1H, NH), 7.82 (d, J= 8.0 Hz, 1H, СНAr), 7.91 (d, J= 6.7 Hz, 2H, СНAr), 8.27 (s, 1H, NH). 13С NMR (δ ppm, DMSO-d6): 27.57, 29.25, 32.16, 61.66, 116.84, 118.07, 123.68, 124.26, 124.39, 129.02, 131.79, 133.17, 141.05, 152.58, 155.60, 162.34, 165.10, 166.10. MALDI-TOF: 513 [M+H]+. Anal. Calcd.: C29H24N2O7 (512), C, 67.96; H, 4.72; N, 5.47. Found: C, 68.11; H, 4.90; N, 5.59.

4.5. General Method for the Synthesis of Calix[4]resorcinarenes 10a,d [27, 41]

To a mixture of 1.25 mmol pyrrolidine-1-carboxamide 1 and appropriate 0.16 g (1.25 mmol) 2-methylresorcinol in 5 ml dry chloroform, 2 ml trifluoroacetic acid was added. The mixture was stirred at room temperature for 72 h. Solvent was evaporated in vacuum. Residue was washed with diethyl ether and acetone, filtered, and dried in vacuum (1 h, 0.01 Torr) to give the title compound 10.

4.6. General Method for the Synthesis of Calix[4]resorcinarenes 10a,d

To a mixture of 0.16 g (1.25 mmol) of 2-methylresorcinol, 5 ml of chloroform, and 1.25 mmol of acetal 2, 2 ml of trifluoroacetic acid was added. The reaction mixture was stirred for 24 hours at room temperature, the solvent was removed in vacuum, and the residue was washed with diethyl ether and dried in vacuum.

4.6.1. 1,1′,1″,1‴-((14,16,34,36,54,56,74,76-Octahydroxy-15,35,55,75-tetramethyl-1,3,5,7(1,3)-tetrabenzenacyclooctaphane-2,4,6,8-tetrayl)tetrakis(propane-3,1-diyl))tetrakis(3-phenylurea) (10a)

White crystals, m.p. > 250°C, yield 70%. IR (cm−1, KBr): 1598, 1653, 2862, 2933, 3057, 3387. 1H NMR (δ ppm, DMSO-d6): 1.43–1.59 (m, 8Н, СН2), 2.00–2.18 (m, 8Н, СН2), 2.04 (s, 12Н, СН3), 2.23–2.32 (m, 8Н, СН2), 3.18–3.28 (m, 8Н, СН2), 4.40 (t, 4Н, J= 7.80 Hz, CН), 6.90–6.96 (m, 4Н, CНAr), 7.15 (s, 4Н, CНAr), 7.17–7.22 (m, 8Н, CНAr), 7.27–7.34 (m, 8Н, CНAr). 13С NMR (δ ppm, DMSO-d6): 8.5, 28.9, 31.4, 34.3, 39.4, 112.4, 119.2, 120.0, 122.2, 124.8, 128.5, 139.4, 149.5, 157.2. MALDI TOF, m/z: 1249 [M]+; 1250 [M+Н]+; 1272 [M+Na]+; 1288 [M+К]+ [27].

4.6.2. 1,1′,1″,1‴-((14,16,34,36,54,56,74,76-Octahydroxy-15,35,55,75-tetramethyl-1,3,5,7(1,3)-tetrabenzenacyclooctaphane-2,4,6,8-tetrayl)tetrakis(propane-3,1-diyl))tetrakis(3-cyclohexylurea) (10d)

White crystals, m.p. > 250°C, yield 62%. IR (cm−1, KBr): 1642, 2860, 3096, 3198. 1H NMR (δ ppm, DMSO-d6): 1.00–1.17 (m, 12Н, СН2), 1.19–1.36 (m, 12 Н, СН2), 1.47–1.55 (m, 4 Н, СН2), 1.58–1.67 (m, 8 Н, СН2), 1.69–1.80 (m, 8 Н, СН2), 1.95 (s, 12 Н, СН3), 2.17–2.29 (m, 4 Н, СН2), 2.96–3.10 (m, 4 Н, СН), 3.29–3.47 (m, 8 Н, СН2), 4.16–4.24 (m, 4 Н, СН), 5.68 (s, 4 Н, NH), 5.79 (s, 4 Н, NH), 7.23 (s, 4 Н, CНAr). 13С NMR (δ ppm, DMSO-d6): 10.46, 24.98, 25.78, 29.47, 30.78, 33.83, 34.51, 38.84, 48.15, 112.18, 121.45, 125.05, 149.58, 157.96. MALDI TOF, m/z: 1273 [M+Н]+; 1295 [M+Na]+ [41].

Data Availability

The NMR source data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Acknowledgments

The authors are grateful to the Assigned Spectral-Analytical Center of FRC Kazan Scientific Center of RAS for technical assistance in research.

Supplementary Materials

Copies of NMR spectra for all of the new compounds. (Supplementary Materials)

References

  1. M. Imai, T. Shiota, K.-i. Kataoka et al., “Small molecule inhibitors of the CCR2b receptor. Part 1: discovery and optimization of homopiperazine derivatives,” Bioorganic & Medicinal Chemistry Letters, vol. 14, no. 21, pp. 5407–5411, 2004. View at Publisher · View at Google Scholar · View at Scopus
  2. S. Cardinal, P.-A. Paquet-Côté, J. Azelmat, C. Bouchard, D. Grenier, and N. Voyer, “Synthesis and anti-inflammatory activity of isoquebecol,” Bioorganic & Medicinal Chemistry, vol. 25, no. 7, pp. 2043–2056, 2017. View at Publisher · View at Google Scholar · View at Scopus
  3. K. Pericherla, A. N. Shirazi, V. Kameshwara Rao et al., “Synthesis and antiproliferative activities of quebecol and its analogs,” Bioorganic & Medicinal Chemistry Letters, vol. 23, no. 19, pp. 5329–5331, 2013. View at Publisher · View at Google Scholar · View at Scopus
  4. E. Bouthenet, K.-B. Oh, S. Park, N. K. Nagi, H.-S. Lee, and S. E. Matthews, “Synthesis and antimicrobial activity of brominated resorcinol dimers,” Bioorganic & Medicinal Chemistry Letters, vol. 21, no. 23, pp. 7142–7145, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. S. K. Chauthe, S. B. Bharate, S. Sabde, D. Mitra, K. K. Bhutani, and I. P. Singh, “Biomimetic synthesis and anti-HIV activity of dimeric phloroglucinols,” Bioorganic & Medicinal Chemistry, vol. 18, no. 5, pp. 2029–2036, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. S. K. Chauthe, S. B. Bharate, G. Periyasamy et al., “One pot synthesis and anticancer activity of dimeric phloroglucinols,” Bioorganic & Medicinal Chemistry Letters, vol. 22, no. 6, pp. 2251–2256, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. K. Sumoto, N. Mibu, K. Yokomizo, and M. Uyeda, “Synthesis of 2,2-dihydroxybisphenols and antiviral activity of some bisphenol derivatives,” Chemical & Pharmaceutical Bulletin, vol. 50, no. 2, pp. 298–300, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. N. Mibu, K. Yokomizo, T. Miyata, and K. Sumoto, “Synthesis and antiviral activities of some heteroaryl-substituted triarylmethanes,” Journal of Heterocyclic Chemistry, vol. 47, no. 6, pp. 1434–1438, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. T. Temal, H. Jary, M. Auberval et al., “New potent calcimimetics: I. Discovery of a series of novel trisubstituted ureas,” Bioorganic & Medicinal Chemistry Letters, vol. 23, no. 8, pp. 2451–2454, 2013. View at Publisher · View at Google Scholar · View at Scopus
  10. P. Deprez, T. Temal, H. Jary et al., “New potent calcimimetics: II. Discovery of benzothiazole trisubstituted ureas,” Bioorganic & Medicinal Chemistry Letters, vol. 23, no. 8, pp. 2455–2459, 2013. View at Publisher · View at Google Scholar · View at Scopus
  11. P. M. Vevert, P. E. Harrington, T. J. Carlson et al., “Metabolism-guided discovery of a potent and orally bioavailable urea-based calcimimetic for the treatment of secondary hyperparathyroidism,” Bioorganic & Medicinal Chemistry Letters, vol. 23, no. 24, pp. 6625–6628, 2013. View at Publisher · View at Google Scholar · View at Scopus
  12. U. R. Mane, D. Mohanakrishnan, D. Sahal, P. R. Murumkar, R. Giridhar, and M. R. Yadav, “Synthesis and biological evaluation of some novel pyrido[1,2-a]pyrimidin-4-ones as antimalarial agents,” European Journal of Medicinal Chemistry, vol. 79, pp. 422–435, 2014. View at Publisher · View at Google Scholar · View at Scopus
  13. V. G. DeVries, J. D. Bloom, M. D. Dutia, A. S. Katocs, and E. E. Largis, “Potential antiatherosclerotic agents. 6. Hypocholesterolemic trisubstituted urea analogs,” Journal of Medicinal Chemistry, vol. 32, no. 10, pp. 2318–2325, 1989. View at Publisher · View at Google Scholar · View at Scopus
  14. S. L. Nowotarski, B. Pachaiyappan, S. L. Holshouser et al., “Structure-activity study for (bis)ureidopropyl- and (bis)thioureidopropyldiamine LSD1 inhibitors with 3-5-3 and 3-6-3 carbon backbone architectures,” Bioorganic & Medicinal Chemistry, vol. 23, no. 7, pp. 1601–1612, 2015. View at Publisher · View at Google Scholar · View at Scopus
  15. A. Esteves-Souza, K. Pissinate, M. d. Graça Nascimento, N. F. Grynberg, and A. Echevarria, “Synthesis, cytotoxicity, and DNA-topoisomerase inhibitory activity of new asymmetric ureas and thioureas,” Bioorganic & Medicinal Chemistry, vol. 14, no. 2, pp. 492–499, 2006. View at Publisher · View at Google Scholar · View at Scopus
  16. J. A. Kowalski, A. D. Swinamer, I. Muegge et al., “Rapid synthesis of an array of trisubstituted urea-based soluble epoxide hydrolase inhibitors facilitated by a novel solid-phase method,” Bioorganic & Medicinal Chemistry Letters, vol. 20, no. 12, pp. 3703–3707, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. S. G. K. Prakash, G. Fogassy, and G. A. Olah, “Microwave-assisted nafion-H catalyzed friedel-crafts type reaction of aromatic aldehydes with arenes: synthesis of triarylmethanes,” Catalysis Letters, vol. 138, no. 3-4, pp. 155–159, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. S. Udayakumar, S. Ajaikumar, and A. Pandurangan, “Electrophilic substitution reaction of phenols with aldehydes: enhance the yield of bisphenols by HPA and supported HPA,” Catalysis Communications, vol. 8, no. 3, pp. 366–374, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Barbero, S. Cadamuro, S. Dughera, C. Magistris, and P. Venturello, “A new practical synthesis of triaryl and trisindolylmethanes under solvent-free reaction conditions,” Organic & Biomolecular Chemistry, vol. 9, no. 24, p. 8393, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. Y. Torisawa, T. Nishi, and J.-i. Minamikawa, “Aldehyde bis-arylation by metal triflates including bismuth triflate powder,” Organic Process Research & Development, vol. 5, no. 1, pp. 84–88, 2001. View at Publisher · View at Google Scholar · View at Scopus
  21. Z. Hussain, D. Danner, A. Masutani et al., “Effect of long flexible chain reactive monomers on the operating voltage of optically isotropic blue phase liquid crystals,” Liquid Crystals, vol. 39, no. 2, pp. 221–230, 2012. View at Publisher · View at Google Scholar · View at Scopus
  22. T. Kolasa, D. E. Gunn, P. Bhatia et al., “Symmetrical bis(heteroarylmethoxyphenyl)alkylcarboxylic acids as inhibitors of leukotriene biosynthesis,” Journal of Medicinal Chemistry, vol. 43, no. 17, pp. 3322–3334, 2000. View at Publisher · View at Google Scholar · View at Scopus
  23. A. R. Burilov, A. S. Gazizov, M. S. Khakimov, N. I. Kharitonova, M. A. Pudovik, and A. I. Konovalov, “Reaction of 1-(2,2-dimethoxyethyl)-1-methyl-3-phenylurea with pyrogallol,” Russian Journal of General Chemistry, vol. 78, no. 12, pp. 2411-2412, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. A. S. Gazizov, A. V. Smolobochkin, A. R. Burilov, and M. A. Pudovik, “Interaction of 2-naphthol with γ-ureidoacetals. A new method for the synthesis of 2-arylpyrrolidines,” Chemistry of Heterocyclic Compounds, vol. 50, no. 5, pp. 707–714, 2014. View at Publisher · View at Google Scholar · View at Scopus
  25. A. S. Gazizov, A. V. Smolobochkin, J. K. Voronina, A. R. Burilov, and M. A. Pudovik, “Acid-catalyzed reaction of (4,4-diethoxybutyl)ureas with phenols as a novel approach to the synthesis of α-arylpyrrolidines,” Synthetic Communications, vol. 45, no. 10, pp. 1215–1221, 2015. View at Publisher · View at Google Scholar · View at Scopus
  26. A. V. Smolobochkin, A. S. Gazizov, J. K. Voronina, A. R. Burilov, and M. A. Pudovik, “Cyclization of 1-(4,4-diethoxybutyl)-3-arylureas: a case study,” Monatshefte für Chemie - Chemical Monthly, vol. 149, no. 3, pp. 535–541, 2018. View at Publisher · View at Google Scholar · View at Scopus
  27. А. S. Gazizov, А. V. V. Smolobochkin, J. K. Voronina, А. R. Burilov, and М. А. Pudovik, “Acid-catalyzed ring opening in 2-(2-hydroxynaphthalene-1-yl)-pyrrolidine-1-carboxamides: formation of dibenzoxanthenes, diarylmethanes, and calixarenes,” Tetrahedron, vol. 71, no. 3, pp. 445–450, 2015. View at Publisher · View at Google Scholar · View at Scopus
  28. A. V. Smolobochkin, A. S. Gazizov, A. R. Burilov, and M. A. Pudovik, “Synthesis of functionalized diarylbutane derivatives by the reaction of 2-methylresorcinol with γ-ureidoacetals,” Russian Journal of General Chemistry, vol. 85, no. 7, pp. 1779–1782, 2015. View at Publisher · View at Google Scholar · View at Scopus
  29. Y. Hayashi, “Pot economy and one-pot synthesis,” Chemical Science, vol. 7, no. 2, pp. 866–880, 2016. View at Publisher · View at Google Scholar · View at Scopus
  30. F. D. King and S. Caddick, “Triflic acid-mediated phenylation of N-acylaminoalkyl diethylacetals and N-acyl-2-phenyl cyclic amides,” Organic & Biomolecular Chemistry, vol. 9, no. 11, p. 4361, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. J. Y. Kim, D. S. Choi, and M. Y. Jung, “Antiphoto-oxidative activity of sesamol in methylene blue- and chlorophyll-sensitized photo-oxidation of oil,” Journal of Agricultural and Food Chemistry, vol. 51, no. 11, pp. 3460–3465, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. Y. Fukuda, M. Nagata, T. Osawa, and M. Namiki, “Contribution of lignan analogues to antioxidative activity of refined unroasted sesame seed oil,” Journal of the American Oil Chemists' Society, vol. 63, no. 8, pp. 1027–1031, 1986. View at Publisher · View at Google Scholar · View at Scopus
  33. A. J. Wagstaff, S. M. Cheer, A. J. Matheson, D. Ormrod, and K. L. Goa, “Paroxetine,” Drugs, vol. 62, no. 4, pp. 655–703, 2002. View at Publisher · View at Google Scholar · View at Scopus
  34. P. Lotke, “Paroxetine controlled release was effective and tolerable for treating menopausal hot flash symptoms in women,” Evidence-Based Medicine, vol. 9, no. 1, p. 23, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Fava, J. Amsterdam, J. Deltito, C. Salzman, M. Schwaller, and D. Dunner, “A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression,” Annals of Clinical Psychiatry, vol. 10, no. 4, pp. 145–150, 1998. View at Publisher · View at Google Scholar
  36. H.-J. Liang, F.-M. Suk, C.-K. Wang et al., “Osthole, a potential antidiabetic agent, alleviates hyperglycemia in db/db mice,” Chemico-Biological Interactions, vol. 181, no. 3, pp. 309–315, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. M.-Z. Zhang, R.-R. Zhang, J.-Q. Wang et al., “Microwave-assisted synthesis and antifungal activity of novel fused Osthole derivatives,” European Journal of Medicinal Chemistry, vol. 124, pp. 10–16, 2016. View at Publisher · View at Google Scholar · View at Scopus
  38. Z.-C. Wang, Y.-J. Qin, P.-F. Wang et al., “Sulfonamides containing coumarin moieties selectively and potently inhibit carbonic anhydrases II and IX: design, synthesis, inhibitory activity and 3D-QSAR analysis,” European Journal of Medicinal Chemistry, vol. 66, pp. 1–11, 2013. View at Publisher · View at Google Scholar · View at Scopus
  39. J. A. Kumar, G. Saidachary, G. Mallesham et al., “Synthesis, anticancer activity and photophysical properties of novel substituted 2-oxo-2H-chromenylpyrazolecarboxylates,” European Journal of Medicinal Chemistry, vol. 65, pp. 389–402, 2013. View at Publisher · View at Google Scholar · View at Scopus
  40. S. Sheshmani, “Catalytic application of two novel sandwich-type polyoxometalates in synthesis of 14-substituted-14H-dibenzo[a, j]xanthenes,” Journal of Chemical Sciences, vol. 125, no. 2, pp. 345–351, 2013. View at Publisher · View at Google Scholar · View at Scopus
  41. A. V. Smolobochkin, A. S. Gazizov, A. R. Burilov, and M. A. Pudovik, “Reaction of N-cyclohexyl-2-(2-hydroxynaphthalen-1-yl)pyrrolidine-1-carboxamide with resorcinol and its derivatives and synthesis of polyphenols,” Russian Chemical Bulletin, vol. 65, no. 5, pp. 1377–1379, 2016. View at Publisher · View at Google Scholar · View at Scopus