Synthesis 2019; 51(06): 1435-1444
DOI: 10.1055/s-0037-1610332
paper
© Georg Thieme Verlag Stuttgart · New York

Metal-Free Synthesis of Biaryl- and Teraryl-Cored Diarylmethanes by Ring Transformation of 2H-Pyran-2-ones

Chemistry Division, School of Advanced Science, VIT University, Chennai Campus, Chennai 600127, Tamil Nadu, India   Email: [email protected]
,
Priyanka B. Kole
› Author Affiliations
Further Information

Publication History

Received: 06 September 2018

Accepted after revision: 26 October 2018

Publication Date:
30 November 2018 (online)

 


Abstract

An efficient metal-free approach for the synthesis of functionalized biaryl-cored diarylmethanes is described by the ring transformation of 2H-pyran-2-ones using 4-phenylbutan-2-one as carbanion source. Moreover, 2H-pyran-2-ones were reacted with 1,3-diphenylacetone in the presence of base to achieve functionalized teraryl-cored diarylmethanes. All the ring transformation reactions were performed under mild reaction conditions to afford the biaryl- and teraryl-cored reaction products in high yields.


#

Functionalized diarylmethanes are important scaffolds found in various biologically active synthetic and naturally occurring compounds.[1] Diarylmethane-cored compounds are known to exhibit various biological activities such as antibreast cancer,[2] thyroid hormone and histamine H1-receptor antagonist,[3] [4] antiviral,[5] antiallergic,[6] and antidiabetic activities.[7] Molecules embedded with diarylmethane units are widely found in various biologically active compounds (Figure [1]). Beclobrate (1) has been introduced as potent cholesterol and triglyceride-lowering drug.[8] Trimethoprim (2) has been developed as effective antibiotic and used for the treatment of urinary tract infections.[9] In addition, naturally occurring compound avrainvilleol (3) is isolated from red algae and found to exhibit antioxidant activity.[10] Moreover, the alkaloid papaverine (4), isolated from Papaver somniferum L., exhibits diverse biological activities such as antiplasmodic activity,[11] cerebral vasodilator,[12] and non-selective phosphodiesterase inhibitory activity.[13] In addition, various tetronic acid derived chiral analogues of diarylmethanes have been found to show anti-HIV and anticancer activities.[14] Recently diarylmethane derivatives have been used as an important precursors in several dye preparations.[15]

Zoom Image
Figure 1 Structures of synthetic and natural products of biological importance with diarylmethane units

There are several methods available in literature for the synthesis of diarylmethanes, but most of them are associated with transition-metal-catalyzed coupling reactions such as Pd-catalyzed Suzuki type cross-coupling reactions of benzylic halides with arylboranes.[16] In 2015, Yoshikai and co-workers reported the synthesis of diarylmethanes by ortho­-CH benzylation of arylimines using Cobalt-Pyphos catalytic system.[17] In 2016, Zhang and co-workers described a one-pot synthesis of diarylmethanes from benzyl chlorides by a Ni-catalyzed reductive cross-coupling reactions.[18]

Furthermore, synthesis of allyldiarylmethanes was accomplished via 1,6-conjugate allylation of p-quinonemethides using B(C6F5)3 as catalyst.[19] In 2016, Hemelaere and co-workers developed the synthesis of diarylmethanes by Friedel–Crafts reaction of benzyl fluorides in the presence of TFA.[20] Furthermore, the synthesis of diarylmethanes was achieved through transition-metal-free cross-coupling reaction of benzylic bromides with arylboronic acids in the presence of Cs2CO3 using the solvent combination BTF/H2O (10:1).[21]

Most of the existing approaches are associated with some limitations such as the use of toxic transition-metal catalysts and harsh reaction conditions. Despite the availability of several existing approaches, there is still scope to develop a new approach that could overcome the problems associated with them and offers the flexibility of introducing a wide range of functional groups in the diarylmethane architecture.

Herein, we report a metal-free approach for the synthesis of functionalized biaryl-cored diarylmethanes 9 in high yields by the ring transformation of 6-aryl-2H-pyran-2-ones 8 using 4-phenylbutan-2-one (6) as a source of nucleophile. The parent precursors 5 were synthesized by the reaction of methyl 2-cyano-3,3-dimethylsulfanylacrylate with functionalized acetophenones in DMSO at room temperature under alkaline conditions.[22] Furthermore, the substrates 5 were reacted with secondary amines in methanol at reflux temperature to synthesize 6-aryl-4-amino-2H-pyran-2-ones 8.[22]

The ring transformation of 2H-pyran-2-ones has been used to synthesize various arenes,[23] heteroarenes,[24] and fused cyclic systems.[25] Recently, we have reported the ultrasound-assisted synthesis of functionalized 2-tetralones via ring transformation of 2H-pyran-2-ones.[26]

Our approach to prepare functionalized biaryl-cored diarylmethanes 9 was based on the ring transformation of 6-aryl-2H-pyran-2-ones 5 and 8 using 4-phenylbutan-2-one (6) as a carbanion source. Both substrates 5 and 8 have three electrophilic centers at C-2, C-4, and C-6. The presence of the electron-withdrawing substituent at C-3 position of pyran ring and the extended conjugation makes the latter position to be more reactive towards nucleophiles.

Initially, our studies were focused on the ring transformation of 3-cyano-4-methylsulfanyl-2H-pyran-2-ones (5a) with 4-phenylbutan-2-one (6). The ring transformation of substrate 5a with 6 was performed in DMF in the presence of KOH at room temperature (Table [1], entry 1). Unfortunately, the reaction suffered from several unwanted side reactions and ring transformed product 7a was obtained in 50% yield. When other substrates 5b and 5c were used in similar reactions and the desired products were observed in slightly improved yields (entries 2 and 3). Probably, the presence of SMe group at C-4 position of lactone ring in substrate 5 makes this position more susceptible for nucleophilic attack, which leads to various undesired side products.

Table 1 Ring Transformation of 6-Aryl-4-(methylthio)-2-oxo-2H-pyran-3-carbonitriles 5ac with 4-Phenylbutan-2-one (6)

Entry

Ar

Reaction time (h)

Yield (%) of 7

1

Ph

10

50

2

4-BrC6H4

12

52

3

4-MeOC6H4

10

57

Next, our efforts were directed to limit the reactivity of 2H-pyran-2-ones 5 at C-4 position towards the nucleophile. In order to limit the reactivity at C-4 position, the leaving group SMe in substrates 5 was replaced with tert-amino functionality by treating with cyclic amines and new substrates 6-phenyl-4-amino-2H-pyran-2-ones 8 were synthesized.[22] Further, to know the influence of amino functionality in the ring transformation reaction, the substrate 2-oxo-6-phenyl-4-(piperidin-1-yl)-2H-pyran-3-carbonitrile (8a) was treated with the same ketone 6 under similar reaction conditions and a significant improvement was observed in the yield of ring-transformed product 9a (Scheme [1]).

Zoom Image
Scheme 1

After that our efforts were directed towards the screening of different solvents using 8a as model substrate. Various polar and nonpolar solvents were employed for the ring transformation of model substrate 8a to the corresponding synthesis of diarylmethane derivative 9a using ketone 6 as source of carbanion and the results obtained are summarized in Table [2]. Initially, the ring transformation reaction of 8a was performed in polar and aprotic solvents DMF and DMSO, and the reaction product 9a was isolated in 85% and 82% yield, respectively (Table [2], entries 1 and 2). The yield of ring transformed product was slightly lowered when acetonitrile was used as solvent (entry 3). The yield was further reduced up to 69% yield in EtOAc (entry 4). Additionally, the ring transformation reaction was performed in polar and protic solvents but could not proceed (entries 5–7). The ring transformation reaction could proceed in dichloromethane but desired product 9a was obtained in moderate yield (entry 8). The course of reaction was investigated in aprotic and nonpolar solvents such as benzene and toluene. The ring transformed product was formed in toluene but was observed only in traces in benzene (entries 9 and 10). Finally, the reaction was performed in THF, diethyl ether, and 1,4-dioxane but the reaction did not proceed in any of these solvents (entries 11–13).

Table 2 Solvent Optimization for the Ring Transformation of 6-Phenyl-2H-pyran-2-one 8a to Diarylmethane Derivative 9a

Entry

Solvent

Reaction time (h)

9a Yield (%)

 1

DMF

10

85

 2

DMSO

10

82

 3

MeCN

10

79

 4

EtOAc

10

69

 5

AcOH

14

 6

MeOH

14

 7

EtOH

14

 8

CH2Cl2

12

58

 9

toluene

12

30

10

benzene

12

11

Et2O

12

12

THF

14

13

1,4-dioxane

14

After determining the optimal solvent, our aim was to screen the different bases for the same ring transformation reaction. Several bases were employed for the ring transformation of 8a to the desired product 9a and results are listed in Table [3]. Initially, the reaction was carried out with KOH in DMF and ring transformation product was obtained in 85% yield (Table [3], entry 1). Similarly, the reaction was tested with NaHCO3 under the same reaction condition and the product 9a was isolated in 75% yield (entry 2). Additionally, K2CO3 and Cs2CO3 were also used as base for same reaction and desired product 9a was achieved in 65% and 60% yield, respectively (entries 3 and 4). The course of reaction was quite similar with LiOH and the reaction product 9a was isolated in 63% yield (entry 5).

Table 3 Base Optimization for the Ring Transformation of 6-Phenyl-2H-pyran-2-one 8a to Diarylmethane Derivative 9a

Entry

Base

Reaction time (h)

9a Yield (%)

1

KOH

10

85

2

NaHCO3

12

75

3

K2CO3

15

65

4

Cs2CO3

15

60

5

LiOH

15

63

After the optimization studies, the presence of KOH as base and DMF as solvent at room temperature for 10 hours was found as the best reaction conditions for the ring transformation of 6-phenyl-2H-pyran-2-one 8a to 2-benzyl-3-methyl-5-(piperidin-1-yl)[1,1′-biphenyl]-4-carbonitrile (9a).

Table 4 Synthesis of Biaryl-Cored Diarylmethanes 9ak via Ring Transformation of 6-Aryl-2H-pyran-2-ones 8ak

Entry

Ar

R

Time (h)

9 Yield (%)

 1

Ph

H

piperidin-1-yl

10

85

 2

Ph

H

4-phenylpiperazin-1-yl

10

82

 3

4-ClC6H4

H

piperidin-1-yl

14

78

 4

4-BrC6H4

H

piperidin-1-yl

12

82

 5

4-BrC6H4

H

4-phenylpiperazin-1-yl

12

80

 6

4-MeC6H4

H

piperidin-1-yl

10

94

 7

4-MeOC6H4

H

piperidin-1-yl

10

90

 8

4-MeOC6H4

H

4-phenylpiperazin-1-yl

10

92

 9

2-naphthyl

H

piperidin-1-yl

10

88

10

Ph

Me

4-phenylpiperazin-1-yl

12

78

11

2-thienyl

H

piperidin-1-yl

10

83

After achieving the best reaction conditions, a series of biaryl-cored diarylmethanes 9ak were synthesized in 78–94% yields by the reaction of various 2H-pyran-2-ones 8ak with 4-phenyl-butan-2-one (6) in DMF in the presence of KOH for 10–14 hours at room temperature (Table [4], entries 1–11). The ring transformation reaction proceeded well with both electron-withdrawing and electron-donating groups on the aromatic ring of 6-aryl-2H-pyran-2-ones 8. Notably, the ring transformation products 9fh were obtained in slightly higher yields when the reactions were performed with the substrates 8fh (entries 6–8) having electron-donating groups compared to substrates with electron-withdrawing groups 8ce (entries 3–5). Furthermore, the ring transformation reaction proceeded well with substrate 8i having naphthyl group at C-6 position and the desired product 9i was isolated in 88% yield (entry 9). Additionally, the course of reaction was also investigated with the substrate 8j having methyl group at C-5 position and reaction proceeded well with up to 78% yield (entry 10). The course of reaction was also evaluated with the substrate 8k containing thiophene functionality at C-6 position and reaction worked well with up to 83% yield (entry 11).

In order to generalize this approach, the same synthetic protocol was applied to construct teraryl-cored diarylmethanes 11. To achieve the synthesis of teraryl-cored diarylmethanes 11, the similar substrates 6-aryl-2H-pyran-2-ones 8 were treated with 1,3-diphenylacetone (10) in DMF in the presence of KOH at room temperature and teraryl-cored diarylmethanes 11 were obtained 74–95% yields (Table [5], entries 1–11). Various functional groups were successfully tolerated during these ring transformations.

Table 5 Synthesis of Teraryl-Cored Diarylmethanes 11aj and 11l via Ring Transformation of 6-Aryl-2H-pyran-2-ones 8aj and 8l

Entry

Ar

R

Time (h)

11 Yield (%)

 1

Ph

H

piperidin-1-yl

10

88

 2

Ph

H

4-phenylpiperazin-1-yl

10

82

 3

4-ClC6H4

H

piperidin-1-yl

15

79

 4

4-BrC6H4

H

piperidin-1-yl

12

82

 5

4-BrC6H4

H

4-phenylpiperazin-1-yl

12

80

 6

4-MeC6H4

H

piperidin-1-yl

10

95

 7

4-MeOC6H4

H

piperidin-1-yl

10

92

 8

4-MeOC6H4

H

4-phenylpiperazin-1-yl

10

93

 9

2-naphthyl

H

piperidin-1-yl

10

90

10

Ph

Me

4-phenylpiperazin-1-yl

12

74

11

Ph

Me

piperidin-1-yl

12

79

It was observed that the course of reaction was quite similar with both electron-donating and -withdrawing cored substrates but ring transformation products were obtained in slightly higher yields in the case of substrates having electron-donating functionalities (Table [5], entries 6–8). Additionally, the reaction was found to be slightly slower when substrates 8j and 8l having methyl group at C-5 position were used and reaction products were obtained in 74% and 79% yield, respectively (entries 10 and 11). All the synthesized compounds were characterized by spectroscopic analysis.

Finally, the reaction of substrate 5a was performed with 1,3-diphenylacetone (10) under similar reaction conditions. Expectedly, the reaction suffered from some undesired side reactions probably due to the presence of good leaving SMe at C-4 position in substrate 5a, which makes this position more vulnerable towards the nucleophile. The ring transformation product 12a was isolated in 62% yield (Scheme [2]). Unfortunately, we could not isolate any side product from the reaction mixture. The isolated compound 12a was characterized as 3′-benzyl-5′-(methylthio)-[1,1′:2′,1′′-terphenyl]-4′-carbonitrile by its spectroscopic analysis.

Zoom Image
Scheme 2 The ring transformation of 2H-pyran-2-ones 5a with 1,3-diphenylacetone (10)

The possible mechanism for the ring transformation of 2H-pyran-2-ones 8 with 4-phenylbutan-2-one (6) to diarylmethanes 9 is described in Scheme [3].[27] Initially, the formation of bicyclic intermediate 13 takes place by the nucleophilic attack of anion generated from ketone 6 to the C-6 position of 2H-pyran-2-ones 8, followed by intramolecular cyclization involving the carbonyl functionality of 6 and C-3 of the pyranone ring. Furthermore, the bicyclic intermediate 13 transforms to final product 9 on decarboxylation followed by dehydration.

Zoom Image
Scheme 3 Proposed mechanism for the synthesis of diarylmethanes 9 by the ring transformation of 2H-pyran-2-ones 8 with 4-phenylbutan-2-one (6)

In conclusion, we have developed a facile metal-free synthetic methodology for the synthesis of functionalized biaryl-cored diarylmethanes 9 through carbanion-induced ring transformation of 6-aryl-2H-pyran-2-ones 8 in good yields. In addition, the same approach was employed to achieve the synthesis of teraryl-cored diarylmethanes 11. Our methodology for the synthesis of functionalized diarylmethanes is simple, economical and does not require any toxic transition metal. Further investigations about this ring transformation approach are currently in progress.

Melting points were measured with REMI DDMS 2545 melting point apparatus. IR spectra were recorded with a Thermo Scientific Nicolet Nexus 470FT-IR spectrophotometer and band positions are reported in reciprocal centimeters. Samples were subjected to ATR mode to record the IR data. 1H NMR and 13C NMR spectra were recorded on a Bruker AV-400 spectrometer using the solvents indicated at 400 and 100 MHz, respectively. Mass spectra (m/z) were recorded under the conditions of electron ionization (EI). All reactions were monitored by TLC that was performed on pre-coated sheets of silica gel 60 and column chromatography was performed with Al2O3 (neutral, 95%) (Avra synthesis Pvt. Ltd.). Hexane and EtOAc were used as eluting solvents and bought from Avra Synthesis Pvt. Ltd. DMF was bought from Avra Synthesis Pvt. Ltd and was used without further purification.


#

Diarylmethanes 7a–c; General Procedure

A mixture of 3-cyano-4-methylsulfanyl-2H-pyran-2-one 5 (1.0 mmol, 1.0 equiv), 4-phenylbutan-2-one (6; 0.18 mL, 1.2 mmol, 1.2 equiv), and powdered KOH (84 mg, 1.5 mmol, 1.5 equiv) in DMF (5 mL) was stirred at r.t. for 10–12 h. The course of reaction was monitored by TLC. On completion of the reaction, few ice pieces were added to the reaction mixture and neutralized with aq 2 M HCl. The mixture was extracted with EtOAc (3 × 10 mL), the combined organic layers were dried (anhyd Na2SO4), filtered, and concentrated under vacuum. The crude residue was purified by neutral alumina column chromatography using EtOAc–hexane (1:49) as an eluent and isolated products were characterized as diarylmethanes 7 by their spectroscopic analysis (Table [1]).


#

2-Benzyl-3-methyl-5-(methylthio)[1,1′-biphenyl]-4-carbonitrile (7a)

White solid; yield: 164 mg (0.5 mmol, 50%); mp 148–150 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2212 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3 H, CH3), 2.46 (s, 3 H, SCH3), 3.88 (s, 2 H, CH2), 6.81 (d, J = 7.2 Hz, 2 H, ArH), 6.98 (s, 1 H, ArH), 7.05–7.20 (m, 5 H, ArH), 7.22–7.28 (m, 3 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 15.9, 18.9, 35.8, 112.1, 116.6, 125.4, 126.1, 127.7, 127.9, 128.3, 128.5, 128.6, 133.8, 139.6, 140.6, 141.2, 143.3, 147.8.

GC-MS: m/z = 330 [M + 1]+.

Anal. Calcd for C22H19NS: C, 80.20; H, 5.81; N, 4.25; S, 9.73. Found: C, 79.75; H, 5.83; N, 4.20; S, 9.06.


#

2-Benzyl-4′-bromo-3-methyl-5-(methylthio)[1,1′-biphenyl]-4-carbonitrile (7b)

White solid; yield: 212 mg (0.52 mmol, 52%); mp 150–152 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2214 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 2.34 (s, 3 H, CH3), 2.46 (s, 3 H, SCH3), 3.86 (s, 2 H, CH2), 6.79 (d, J = 6.8 Hz, 2 H, ArH), 6.94 (s, 1 H, ArH), 6.97 (td, J 1 = 8.8 Hz, J 2 = 2.0 Hz, 2 H, ArH), 7.07–7.20 (m, 3 H, ArH), 7.38 (td, J 1 = 8.8 Hz, J 2 = 2.0 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 15.8, 18.9, 35.7, 112.4, 116.5, 122.2, 125.1, 126.3, 127.6, 128.7, 130.2, 131.5, 133.6, 139.3, 139.4, 141.5, 143.4, 146.5.

GC-MS: m/z = 409 [M + 1]+, 410 [M + 2]+.

Anal. Calcd for C22H18BrNS: C, 64.71; H, 4.44; N, 3.43; S, 7.85. Found: C, 64.69; H, 4.50; N, 3.39; S, 7.81.


#

2-Benzyl-4′-methoxy-3-methyl-5-(methylthio)[1,1′-biphenyl]-4-carbonitrile (7c)

White solid; yield: 204 mg (0.57 mmol, 57%); mp 144–146 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2214 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 2.32 (s, 3 H, CH3), 2.46 (s, 3 H, SCH3), 3.73 (s, 3 H, OCH3), 3.90 (s, 2 H, CH2), 6.78 (td, J 1 = 8.8 Hz, J 2 = 2.0 Hz, 2 H, ArH), 6.82 (d, J = 7.2 Hz, 2 H, ArH), 6.98 (s, 1 H, ArH), 7.03 (td, J 1 = 8.8 Hz, J 2 = 2.0 Hz, 2 H, ArH), 7.08–7.20 (m, 3 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 15.9, 18.9, 35.8, 55.3, 111.8, 113.7, 116.7, 125.6, 126.1, 127.7, 128.6, 129.7, 132.9, 133.9, 139.7, 141.1, 143.3, 147.5, 159.3.

GC-MS: m/z = 360 [M + 1]+.

Anal. Calcd for C23H21NOS: C, 76.85; H, 5.89; N, 3.90; S, 8.92. Found: C, 76.10; H, 5.84; N, 3.84; S, 8.58.


#

Biaryl-Cored Diarylmethanes 9a–k; General Procedure

A mixture of 2H-pyran-2-one 8 (1.0 mmol, 1.0 equiv), 4-phenylbutan-2-one (6; 0.18 mL, 1.2 mmol, 1.2 equiv), and powdered KOH (84 mg, 1.5 mmol, 1.5 equiv) in DMF (5 mL) was stirred at r.t. for 10–14 h. The course of reaction was monitored by TLC. On completion of the reaction, few ice pieces were added to the reaction mixture and neutralized with aq 2 M HCl. The reaction mixture was extracted with EtOAc (3 × 10 mL), the combined organic layers were dried (anhyd Na2SO4), filtered, and concentrated under vacuum. The crude residue was purified by neutral alumina column chromatography using EtOAc–hexane (1:49) as an eluent and isolated products were characterized as biaryl-cored diarylmethanes 9 by their spectroscopic analysis (Table [4]).


#

2-Benzyl-3-methyl-5-(piperidin-1-yl)[1,1′-biphenyl]-4-carbonitrile (9a)

White solid; yield: 311 mg, 0.85 mmol (85%); mp 114–116 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2215 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.46–1.54 (m, 2 H, CH2), 1.66–1.75 (m, 4 H, 2 × CH2), 2.30 (s, 3 H, CH3), 3.06 (t, J = 5.2 Hz, 4 H, 2 × NCH2), 3.84 (s, 2 H, CH2), 6.70 (s, 1 H, ArH), 6.82 (d, J = 7.6 Hz, 2 H, ArH), 7.03–7.18 (m, 5 H, ArH), 7.20–7.25 (m, 3 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 18.9, 24.1, 26.3, 35.7, 53.6, 107.5, 118.1, 118.4, 125.9, 127.5, 127.8, 128.2, 128.5, 128.6, 129.6, 140.3, 141.4, 143.4, 148.1, 155.6.

GC-MS: m/z = 367 [M + 1]+.

Anal. Calcd for C26H26N2: C, 85.21; H, 7.15; N, 7.64. Found: C, 85.04; H, 7.18; N, 7.52.


#

2-Benzyl-3-methyl-5-(4-phenylpiperazin-1-yl)[1,1′-biphenyl]-4-carbonitrile (9b)

White solid; yield: 363 mg (0.82 mmol, 82%); mp 180–182 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2210 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 2.32 (s, 3 H, CH3), 3.25–3.35 (m, 8 H, 4 × NCH2), 3.86 (s, 2 H, CH2), 6.76 (s, 1 H, ArH), 6.81 (t, J = 7.6 Hz, 3 H, ArH), 6.89 (d, J = 8.4 Hz, 2 H, ArH), 7.03–7.20 (m, 7 H, ArH), 7.21–7.26 (m, 3 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 19.0, 24.2, 35.7, 49.6, 51.9, 107.6, 116.4, 117.9, 118.3, 120.1, 126.0, 127.7, 127.8, 128.3, 128.5, 128.6, 129.2, 130.6, 140.1, 141.2, 143.8, 148.4, 151.2, 154.1.

GC-MS: m/z = 444 [M + 1]+.

Anal. Calcd for C31H29N3: C, 83.94; H, 6.59; N, 9.47. Found: C, 83.55; H, 6.58; N, 9.37.


#

2-Benzyl-4′-chloro-3-methyl-5-(piperidin-1-yl)[1,1′-biphenyl]-4-carbonitrile (9c)

White solid; yield: 312 mg (0.77 mmol, 78%); mp 141–143 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2218 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.46–1.57 (m, 2 H, CH2), 1.66–1.75 (m, 4 H, 2 × CH2), 2.30 (s, 3 H, CH3), 3.06 (t, J = 5.6 Hz, 4 H, 2 × NCH2), 3.81 (s, 2 H, CH2), 6.65 (s, 1 H, ArH), 6.80 (d, J = 7.2 Hz, 2 H, ArH), 7.01 (d, J = 8.4 Hz, 2 H, ArH), 7.04–7.21 (m, 5 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 18.9, 24.1, 26.2, 35.6, 53.5, 107.7, 117.9, 118.2, 126.0, 127.7, 128.4, 128.6, 129.4, 129.9, 133.7, 139.8, 140.0, 143.5, 146.9, 155.7.

GC-MS: m/z = 401 [M + 1]+, 402 [M + 2]+.

Anal. Calcd for C26H25ClN2: C, 77.89; H, 6.28; N, 6.99. Found: C, 77.39; H, 6.41; N, 6.43.


#

2-Benzyl-4′-bromo-3-methyl-5-(piperidin-1-yl)[1,1′-biphenyl]-4-carbonitrile (9d)

White solid; yield: 364 mg (0.82 mmol, 82%); mp 116–118 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2217 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.47–1.56 (m, 2 H, CH2), 1.66–1.73 (m, 4 H, 2 × CH2), 2.30 (s, 3 H, CH3), 3.06 (t, J = 4.8 Hz, 4 H, 2 × NCH2), 3.81 (s, 2 H, CH2), 6.65 (s, 1 H, ArH), 6.80 (d, J = 7.6 Hz, 2 H, ArH), 6.95 (d, J = 8.0 Hz, 2 H, ArH), 7.03–7.19 (m, 3 H, ArH), 7.34 (d, J = 8.0 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 18.9, 24.1, 26.2, 35.6, 53.5, 107.7, 117.9, 118.1, 121.9, 126.1, 127.7, 128.6, 129.4, 130.2, 131.3, 140.0, 140.2, 143.6, 146.8, 155.7.

GC-MS: m/z = 446 [M + 1]+, 447 [M + 2]+.

Anal. Calcd for C26H25BrN2: C, 70.11; H, 5.66; N, 6.29. Found: C, 70.03; H, 5.66; N, 6.11.


#

2-Benzyl-4′-bromo-3-methyl-5-(4-phenylpiperazin-1-yl)[1,1′-biphenyl]-4-carbonitrile (9e)

White solid; yield: 417 mg (0.79 mmol, 80%); mp 172–174 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2210 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 2.34 (s, 3 H, CH3), 3.25–3.36 (m, 8 H, 4 × NCH2), 3.84 (s, 2 H, CH2), 6.71 (s, 1 H, ArH), 6.79–6.85 (m, 3 H, ArH), 6.91 (d, J = 8.0 Hz, 2 H, ArH), 6.97 (td, J 1 = 8.4 Hz, J 2 = 1.6 Hz, 2 H, ArH), 7.06–7.25 (m, 5 H, ArH), 7.37 (td, J 1 = 8.4 Hz, J 2 = 1.6 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 18.9, 35.6, 49.6, 51.9, 107.8, 116.4, 117.7, 118.1, 120.1, 122.0, 126.1, 127.7, 128.6, 129.2, 130.2, 130.4, 131.4, 139.8, 140.0, 143.9, 147.1, 151.2, 154.2.

GC-MS: m/z = 523 [M + 1]+, 524 [M + 2]+.

Anal. Calcd for C31H28BrN3: C, 71.26; H, 5.40; N, 8.04. Found: C, 71.19; H, 5.47; N, 7.91.


#

2-Benzyl-3,4′-dimethyl-5-(piperidin-1-yl)[1,1′-biphenyl]-4-carbonitrile (9f)

White solid; yield: 357 mg (0.94 mmol, 94%); mp 162–164 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2215 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.45–1.56 (m, 2 H, CH2), 1.64–1.75 (m, 4 H, 2 × CH2), 2.26 (s, 3 H, CH3), 2.28 (s, 3 H, CH3), 3.05 (t, J = 5.2 Hz, 4 H, 2 × NCH2), 3.85 (s, 2 H, CH2), 6.70 (s, 1 H, ArH), 6.83 (d, J = 7.6 Hz, 2 H, ArH), 6.95–7.10 (m, 5 H, ArH), 7.14 (t, J = 7.6 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 18.9, 21.2, 24.2, 26.3, 35.7, 53.6, 107.3, 118.1, 118.4, 125.9, 127.8, 128.5, 128.9, 129.7, 137.3, 138.5, 140.4, 143.4, 148.1, 148.2, 155.6.

GC-MS: m/z = 381 [M + 1]+.

Anal. Calcd for C27H28N2: C, 85.22; H, 7.42; N, 7.36. Found: C, 84.71; H, 7.42; N, 7.16.


#

2-Benzyl-4′-methoxy-3-methyl-5-(piperidin-1-yl)[1,1′-biphenyl]-4-carbonitrile (9g)

White solid; yield: 356 mg (0.90 mmol, 90%); mp 172–174 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2213 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.45–1.58 (m, 2 H, CH2), 1.66–1.75 (m, 4 H, 2 × CH2), 2.28 (s, 3 H, CH3), 3.05 (t, J = 5.2 Hz, 4 H, 2 × NCH2), 3.71 (s, 3 H, OCH3), 3.86 (s, 2 H, CH2), 6.70 (s, 1 H, ArH), 6.75 (d, J = 8.0 Hz, 2 H, ArH), 6.83 (d, J = 7.2 Hz, 2 H, ArH), 7.02 (d, J = 8.0 Hz, 2 H, ArH), 7.04–7.10 (m, 1 H, ArH), 7.14 (t, J = 7.2 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 18.9, 24.2, 26.3, 35.7, 53.6, 55.3, 107.2, 113.6, 118.2, 118.5, 125.9, 127.8, 128.5, 129.7, 133.8, 140.4, 143.3, 147.9, 155.6, 159.1.

GC-MS: m/z = 397 [M + 1]+.

Anal. Calcd for C27H28N2O: C, 81.78; H, 7.12; N, 7.06. Found: C, 81.11; H, 7.14; N, 6.92.


#

2-Benzyl-4′-methoxy-3-methyl-5-(4-phenylpiperazin-1-yl)[1,1′-biphenyl]-4-carbonitrile (9h)

White solid; yield: 435 mg (0.92 mmol, 92%); mp 174–176 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2214 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 2.31 (s, 3 H, CH3), 3.25–3.36 (m, 8 H, 4 × NCH2), 3.72 (s, 3 H, OCH3), 3.89 (s, 2 H, CH2), 6.75–6.77 (m, 2 H, ArH), 6.78 (s, 1 H, ArH), 6.81–6.87 (m, 2 H, ArH), 6.88–6.95 (m, 2 H, ArH), 7.04 (d, J = 8.8 Hz, 2 H, ArH), 7.06–7.12 (m, 1 H, ArH), 7.13–7.24 (m, 5 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 19.0, 35.7, 49.6, 51.9, 55.3, 107.3, 113.7, 116.4, 118.5, 120.1, 126.0, 127.8, 128.5, 128.7, 129.2, 129.7, 130.8, 133.5, 140.2, 143.7, 148.1, 151.2, 154.1, 159.2.

GC-MS: m/z = 474 [M + 1]+.

Anal. Calcd for C32H31N3O: C, 81.15; H, 6.60; N, 8.87. Found: C, 81.02; H, 7.12; N, 8.71.


#

3-Benzyl-2-methyl-4-(naphthalen-2-yl)-6-(piperidin-1-yl)benzonitrile (9i)

White solid; yield: 366 mg (0.88 mmol, 88%); mp 162–164 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2213 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.44–1.55 (m, 2 H, CH2), 1.66–1.76 (m, 4 H, 2 × CH2), 2.33 (s, 3 H, CH3), 3.07 (t, J = 5.2 Hz, 4 H, 2 × NCH2), 3.87 (s, 2 H, CH2), 6.79 (s, 1 H, ArH), 6.82 (d, J = 6.8 Hz, 2 H, ArH), 7.07 (d, J = 6.8 Hz, 1 H, ArH), 7.13 (t, J = 7.6 Hz, 2 H, ArH), 7.21 (dd, J 1 = 8.4 Hz, J 2 = 1.6 Hz, 1 H, ArH), 7.35–7.41 (m, 2 H, ArH), 7.54 (s, 1 H, ArH), 7.58–7.65 (m, 1 H, ArH), 7.68 (d, J = 8.8 Hz, 1 H, ArH), 7.70–7.78 (m, 1 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 19.0, 24.2, 26.3, 35.8, 53.6, 107.6, 118.1, 118.6, 125.9, 126.3, 126.4, 126.8, 127.5, 127.6, 127.7, 127.8, 128.1, 128.5, 129.8, 132.5, 133.0, 138.9, 140.3, 143.5, 148.1, 155.7.

GC-MS: m/z = 417 [M + 1]+.

Anal. Calcd for C30H28N2: C, 86.50; H, 6.78; N, 6.72. Found: C, 86.17; H, 6.77; N, 6.60.


#

2-Benzyl-3,6-dimethyl-5-(4-phenylpiperazin-1-yl)[1,1′-biphenyl]-4-carbonitrile (9j)

White solid; yield: 356 mg (0.78 mmol, 78%); mp 140–142 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2215 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.89 (s, 3 H, CH3), 2.30 (s, 3 H, CH3), 3.18–3.55 (m, 8 H, 4 × NCH2), 3.69 (s, 2 H, CH2), 6.72 (d, J = 7.2 Hz, 2 H, ArH), 6.79 (t, J = 7.2 Hz, 1 H, ArH), 6.85–6.94 (m, 4 H, ArH), 7.01–7.15 (m, 3 H, ArH), 7.16–7.24 (m, 5 H, ArH).

13CNMR (100 MHz, CDCl3): δ = 16.9, 18.5, 36.6, 50.5, 50.6, 111.7, 116.6, 118.4, 119.9, 125.8, 127.3, 127.8, 128.2, 128.3, 128.5, 129.1, 133.5, 134.3, 139.8, 140.1, 140.2, 148.9, 151.5, 151.8.

GC-MS: m/z = 458 [M + 1]+.

Anal. Calcd for C32H31N3: C, 83.99; H, 6.83; N, 9.18. Found: C, 83.67; H, 6.87; N, 8.99.


#

3-Benzyl-2-methyl-6-(piperidin-1-yl)-4-(thiophen-2-yl)benzonitrile (9k)

White solid; yield: 308 mg (0.83 mmol (83%); mp 115–117 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2215 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.49–1.58 (m, 2 H, CH2), 1.67–1.76 (m, 4 H, 2 × CH2), 2.30 (s, 3 H, CH3), 3.07 (t, J = 5.2 Hz, 4 H, 2 × NCH2), 4.00 (s, 2 H, CH2), 6.78 (ds, J = 3.2 Hz, 1 H, ArH), 6.85–6.91 (m, 4 H, ArH), 7.11 (t, J = 7.2 Hz, 1 H, ArH), 7.14–7.25 (m, 3 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 19.0, 24.1, 26.2, 35.9, 53.5, 107.9, 117.9, 119.2, 126.0, 126.1, 126.9, 127.3, 127.8, 128.6, 130.2, 140.2, 140.4, 142.1, 143.7, 155.5.

GC-MS: m/z = 373 [M + 1]+.

Anal. Calcd for C24H24N2S: C, 77.38; H, 6.49; N, 7.52; S, 8.61. Found: C, 77.68; H, 6.44; N, 7.43; S, 8.50.


#

Teraryl-Cored Diarylmethanes 11a–j and 11l; General Procedure

A mixture of 2H-pyran-2-one 8 (1.0 mmol, 1.0 equiv), 1,3-diphenylacetone (10; 0.24 mL, 1.2 mmol, 1.2 equiv), and powdered KOH (84 mg, 1.5 mmol, 1.5 equiv) in DMF (5 mL) was stirred at r.t. for 10–15 h. The progress of the reaction was checked by TLC. On completion of the reaction, few ice pieces were added to the reaction mixture and neutralized with aq 2 M HCl. The reaction mixture was extracted with EtOAc (3 × 10 mL), the combined organic layers were dried (anhyd Na2SO4), filtered, and evaporated under vacuum. The crude residue was purified by neutral alumina column chromatography using EtOAc–hexane (1:49) as an eluent and compounds were characterized as teraryl-cored diarylmethanes 11 by their spectroscopic analysis (Table [5]).


#

3′-Benzyl-5′-(piperidin-1-yl)[1,1′:2′,1′′-terphenyl]-4′-carbonitrile (11a)

White solid; yield: 376 mg (0.88 mmol, 88%); mp 145–148 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2214 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.49–1.58 (m, 2 H, CH2), 1.69–1.78 (m, 4 H, 2 × CH2), 3.13 (t, J = 5.2 Hz, 4 H, 2 × NCH2), 4.06 (s, 2 H, CH2), 6.71–6.81 (m, 3 H, ArH), 6.86 (s, 1 H, ArH), 6.90–6.95 (m, 2 H, ArH), 6.96–7.10 (m, 9 H, ArH), 7.17–7.26 (m, 1 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 24.1, 26.2, 38.4, 53.6, 107.2, 118.9, 125.9, 126.8, 126.9, 127.6, 127.7, 128.1, 128.5, 129.4, 130.9, 135.0, 138.1, 138.2, 139.5, 141.1, 144.3, 147.1, 156.8.

GC-MS: m/z = 429 [M + 1]+.

Anal. Calcd for C31H28N2: C, 86.88; H, 6.59; N, 6.54. Found: C, 86.82; H, 6.69; N, 5.97.


#

3′-Benzyl-5′-(4-phenylpiperazin-1-yl)[1,1′:2′,1′′-terphenyl]-4′-carbonitrile (11b)

White solid; yield: 414 mg (0.82 mmol, 82%); mp 167–169 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2215 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 3.30–3.38 (m, 8 H, 4 × NCH2), 4.08 (s, 2 H, CH2), 6.72–6.84 (m, 5 H, ArH), 6.88–6.96 (m, 5 H, ArH), 6.99–7.07 (m, 9 H, ArH), 7.20 (t, J = 7.6 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 38.5, 49.6, 52.0, 107.3, 116.5, 117.9, 118.9, 120.1, 126.1, 126.9, 127.1, 127.7, 127.8, 128.2, 128.5, 129.2, 129.4, 130.8, 135.9, 137.9, 139.3, 140.8, 144.7, 147.4, 151.2, 155.3.

GC-MS: m/z = 506 [M + 1]+.

Anal. Calcd for C36H31N3: C, 85.51; H, 6.18; N, 8.31. Found: C, 85.02; H, 6.24; N, 8.13.


#

3′-Benzyl-4-chloro-5′-(piperidin-1-yl)[1,1′:2′,1′′-terphenyl]-4′-carbonitrile (11c)

White solid; yield: 365 mg (0.79 mmol, 79%); mp 158–160 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2215 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.49–1.57 (m, 2 H, CH2), 1.67–1.78 (m, 4 H, 2 × CH2), 3.12 (t, J = 5.2 Hz, 4 H, 2 × NCH2), 4.04 (s, 2 H, CH2), 6.70–6.78 (m, 4 H, ArH), 6.81 (s, 1 H, ArH), 6.85 (d, J = 8.4 Hz, 2 H, ArH), 6.97–7.10 (m, 8 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 24.1, 26.2, 38.4, 53.5, 107.4, 118.0, 118.7, 126.0, 127.0, 127.9, 128.1, 128.5, 128.7, 129.5, 130.7, 130.8, 134.9, 137.9, 139.3, 139.5, 144.6, 145.8, 156.8.

GC-MS: m/z = 464 [M + 1]+, 465 [M + 2]+.

Anal. Calcd for C31H27ClN2: C, 80.42; H, 5.88; N, 6.05. Found: C, 80.59; H, 5.96; N, 5.48.


#

3′-Benzyl-4-bromo-5′-(piperidin-1-yl)[1,1′:2′,1′′-terphenyl]-4′-carbonitrile (11d)

White solid; yield: 415 mg (0.82 mmol, 82%); mp 150–152 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2217 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.49–1.57 (m, 2 H, CH2), 1.68–1.77 (m, 4 H, 2 × CH2), 3.12 (t, J = 5.2 Hz, 4 H, 2 × NCH2), 4.04 (s, 2 H, CH2), 6.69–6.79 (m, 6 H, ArH), 6.80 (s, 1 H, ArH), 6.97–7.08 (m, 6 H, ArH), 7.16 (d, J = 8.4 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 24.1, 26.2, 38.4, 53.5, 107.5, 118.0, 118.7, 121.3, 126.0, 127.0, 127.9, 128.1, 128.5, 130.8, 131.0, 134.8, 137.9, 138.0, 139.3, 140.0, 144.6, 145.7, 156.8.

GC-MS: m/z = 508 [M + 1]+, 509 [M + 2]+.

Anal. Calcd for C31H27BrN2: C, 73.37; H, 5.36; N, 5.52. Found: C, 73.53; H, 5.44; N, 5.35.


#

3′-Benzyl-4-bromo-5′-(4-phenylpiperazin-1-yl)[1,1′:2′,1′′-terphenyl]-4′-carbonitrile (11e)

White solid; yield: 467 mg (0.80 mmol, 80%); mp 170–172 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2212 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 3.31–3.37 (m, 8 H, 4 × NCH2), 4.06 (s, 2 H, CH2), 6.70–6.83 (m, 7 H, ArH), 6.86 (s, 1 H, ArH), 6.89 (d, J = 8.0 Hz, 2 H, ArH), 6.99–7.09 (m, 6 H, ArH), 7.12–7.23 (m, 4 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 38.5, 49.6, 51.9, 107.6, 116.5, 117.8, 118.7, 120.2, 121.5, 126.1, 127.2, 128.0, 128.2, 128.5, 129.2, 130.7, 130.9, 131.0, 135.8, 137.7, 139.2, 139.7, 145.0, 146.0, 151.2, 155.4.

GC-MS: m/z = 585 [M + 1]+, 586 [M + 2]+.

Anal. Calcd for C36H30BrN3: C, 73.97; H, 5.17; N, 7.19. Found: C, 74.01; H, 5.36; N, 6.99.


#

3′-Benzyl-4-methyl-5′-(piperidin-1-yl)[1,1′:2′,1′′-terphenyl]-4′-carbonitrile (11f)

White solid; yield: 419 mg (0.95 mmol, 95%); mp 156–158 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2210 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.47–1.57 (m, 2 H, CH2), 1.68–1.77 (m, 4 H, 2 × CH2), 2.15 (s, 3 H, CH3), 3.12 (t, J = 5.2 Hz, 4 H, 2 × NCH2), 4.04 (s, 2 H, CH2), 6.76 (t, J = 8.4 Hz, 4 H, ArH), 6.80–6.87 (m, 5 H, ArH), 6.97–7.10 (m, 6 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 21.1, 24.1, 26.2, 38.4, 53.6, 106.9, 118.2, 119.0, 125.9, 126.7, 127.7, 128.1, 128.4, 128.5, 129.3, 130.9, 135.0, 136.6, 138.1, 138.4, 139.5, 144.3, 147.1, 156.8.

GC-MS: m/z = 443 [M + 1]+.

Anal. Calcd for C32H30N2: C, 86.84; H, 6.83; N, 6.33. Found: C, 86.77; H, 6.82; N, 6.24.


#

3′-Benzyl-4-methoxy-5′-(piperidin-1-yl)[1,1′:2′,1′′-terphenyl]-4′-carbonitrile (11g)

White solid; yield: 421 mg (0.92 mmol, 92%); mp 95–97 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2212 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.48–1.59 (m, 2 H, CH2), 1.68–1.77 (m, 4 H, 2 × CH2), 3.12 (t, J = 5.2 Hz, 4 H, 2 × NCH2), 3.63 (s, 3 H, OCH3), 4.04 (s, 2 H, CH2), 6.57 (d, J = 8.4 Hz, 2 H, ArH), 6.76 (t, J = 8.4 Hz, 4 H, ArH), 6.82–6.88 (m, 3 H, ArH), 6.98–7.10 (m, 6 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 24.2, 26.2, 38.5, 53.6, 55.1, 106.8, 113.1, 118.3, 119.0, 125.9, 126.8, 127.8, 128.1, 128.5, 130.6, 130.9, 133.4, 135.0, 138.4, 139.5, 144.3, 146.7, 156.8, 158.5.

GC-MS: m/z = 459 [M + 1]+.

Anal. Calcd for C32H30N2O: C, 83.81; H, 6.59; N, 6.11. Found: C, 83.08; H, 6.70; N, 6.07.


#

3′-Benzyl-4-methoxy-5′-(4-phenylpiperazin-1-yl)[1,1′:2′,1′′-terphenyl]-4′-carbonitrile (11h)

White solid; yield: 497 mg (0.93 mmol, 93%); mp 120–122 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2209 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 3.32–3.38 (m, 8 H, 4 × NCH2), 3.64 (s, 3 H, OCH3), 4.07 (s, 2 H, CH2), 6.58 (d, J = 8.8 Hz, 2 H, ArH), 6.77 (t, J = 7.6 Hz, 4 H, ArH), 6.80–6.94 (m, 6 H, ArH), 6.98–7.11 (m, 6 H, ArH), 7.21 (t, J = 8.8 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 38.5, 49.6, 52.0, 55.2, 106.9, 113.2, 116.5, 118.1, 118.9, 120.2, 126.0, 126.9, 127.9, 128.1, 128.5, 129.2, 130.6, 130.8, 133.2, 135.9, 138.2, 139.4, 144.7, 147.0, 151.2, 155.3, 158.6.

GC-MS: m/z = 536 [M + 1]+.

Anal. Calcd for C37H33N3O: C, 82.96; H, 6.21; N, 7.84. Found: C, 82.86; H, 6.25; N, 7.73.


#

2-Benzyl-6-(naphthalen-2-yl)-4-(piperidin-1-yl)[1,1′-biphenyl]-3-carbonitrile (11i)

White solid; yield: 430 mg (0.90 mmol, 90%); mp 182–184 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2214 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.63–1.71 (m, 2 H, CH2), 1.82–1.90 (m, 4 H, 2 × CH2), 3.28 (t, J = 5.2 Hz, 4 H, 2 × NCH2), 4.22 (s, 2 H, CH2), 6.90–6.96 (m, 4 H, ArH), 7.08–7.13 (m, 5 H, ArH), 7.14–7.23 (m, 3 H, ArH), 7.42–7.50 (m, 2 H, ArH), 7.56 (d, J = 8.4 Hz, 1 H, ArH), 7.64 (s, 1 H, ArH), 7.71–7.78 (m, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 24.2, 26.2, 38.4, 53.6, 107.3, 118.2, 119.3, 125.9, 126.1, 126.2, 126.8, 126.9, 127.4, 127.6, 127.8, 127.9, 128.1, 128.4, 128.5, 130.9, 132.1, 132.9, 135.1, 138.2, 138.8, 139.5, 144.5, 147.0, 156.9.

GC-MS: m/z = 479 [M + 1]+.

Anal. Calcd for C35H30N2: C, 87.83; H, 6.32; N, 5.85. Found: C, 83.69; H, 6.36; N, 5.58.


#

3′-Benzyl-6′-methyl-5′-(4-phenylpiperazin-1-yl)[1,1′:2′,1′′-terphenyl]-4′-carbonitrile (11j)

White solid; yield: 384 mg (0.74 mmol, 74%); mp 178–180 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2217 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.99 (s, 3 H, CH3), 3.22–3.60 (m, 8 H, 4 × NCH2), 3.98 (s, 2 H, CH2), 6.64 (dd, J 1 = 7.2 Hz, J 2 = 1.6 Hz, 2 H, ArH), 6.78 (dt, J 1 = 7.2 Hz, J 2 = 1.6 Hz, 5 H, ArH), 6.89–6.96 (m, 5 H, ArH), 6.95–7.09 (m, 6 H, ArH), 7.20 (t, J = 8.4 Hz, 2 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 17.2, 38.2, 50.5, 50.7, 111.4, 116.6, 118.5, 120.0, 126.0, 126.6, 127.4, 127.7, 128.1, 128.5, 129.1, 129.3, 130.3, 133.9, 138.6, 139.5, 139.6, 139.9, 141.4, 148.2, 151.8, 152.8.

GC-MS: m/z = 520 [M + 1]+.

Anal. Calcd for C37H33N3: C, 85.51; H, 6.40; N, 8.09. Found: C, 85.38; H, 6.70; N, 8.07.


#

3′-Benzyl-6′-methyl-5′-(piperidin-1-yl)[1,1′:2′,1′′-terphenyl]-4′-carbonitrile (11l)

White solid; yield: 349 mg (0.79 mmol, 79%); mp 156–158 °C; Rf = 0.5 (EtOAc–hexane 1:49).

IR (ATR): 2213 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 1.55–1.74 (m, 6 H, 3 × CH2), 1.94 (s, 3 H, CH3), 3.10–3.36 (m, 4 H, 2 × NCH2), 3.96 (s, 2 H, CH2), 6.63 (dd, J 1 = 7.6 Hz, J 2 = 2.0 Hz, 2 H, ArH), 6.74–6.80 (m, 4 H, ArH), 6.86–6.93 (m, 3 H, ArH), 6.94–7.10 (m, 6 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 16.9, 24.3, 26.9, 38.1, 52.0, 110.5, 118.8, 125.9, 126.4, 126.5, 127.3, 127.6, 128.0, 128.5, 129.4, 130.3, 133.8, 138.7, 138.8, 139.7, 140.2, 141.0, 148.0, 154.5.

GC-MS: m/z = 443 [M + 1]+.

Anal. Calcd for C32H30N2: C, 86.84; H, 6.83; N, 6.33. Found: C, 86.62; H, 6.87; N, 6.11.


#

3′-Benzyl-5′-(methylthio)[1,1′:2′,1′′-terphenyl]-4′-carbonitrile (12a)

A mixture of 4-(methylthio)-2-oxo-6-phenyl-2H-pyran-3-carbonitrile (5a; 243 mg, 1.0 mmol, 1.0 equiv), 1,3-diphenylacetone (10; 0.24 mL, 1.2 mmol, 1.2 equiv), and powdered KOH (84 mg, 1.5 mmol, 1.5 equiv) in DMF (5 mL) was stirred at r.t. for 12 h. The course of the reaction was monitored by TLC. On completion of the reaction, few ice pieces were added to the reaction mixture and neutralized with aq 2 M HCl. After that the reaction mixture was extracted with EtOAc (3 × 10 mL). The combined organic layers were dried (anhyd Na2SO4), filtered, and, concentrated under vacuum. The crude product was purified by neutral alumina column chromatography using EtOAc–hexane (1:49) as an eluent to afford 12a; white solid; yield: 242 mg (0.62 mmol, 62%); mp 144–146 °C; Rf = 0.4 (EtOAc–hexane 1:49).

IR (ATR): 2211 cm–1 (C≡N).

1H NMR (400 MHz, CDCl3): δ = 2.49 (s, 3 H, SCH3), 4.07 (s, 2 H, CH2), 6.72–6.77 (m, 4 H, ArH), 6.90–6.96 (m, 2 H, ArH), 6.98–7.09 (m, 9 H, ArH), 7.12 (s, 1 H, ArH).

13C NMR (100 MHz, CDCl3): δ = 14.7, 37.3, 110.7, 115.6, 124.4, 125.1, 126.1, 126.2, 126.7, 126.8, 127.1, 127.4, 128.3, 129.5, 136.5, 137.7, 137.8, 139.3, 142.2, 143.1, 145.6.

GC-MS: m/z = 392 [M + 1]+, 393 [M + 2]+.

Anal. Calcd for C27H21NS: C, 82.83; H, 5.41; N, 3.58; S, 8.19. Found: C, 82.21; H, 5.52; N, 3.42; S, 8.09.


#
#

Acknowledgment

Fateh V. Singh is thankful to the SAIF, VIT University, Vellore Campus for providing spectroscopic analysis. Priyanka B. Kole is grateful to VIT Chennai Campus for providing a fellowship.

Supporting Information

  • References

    • 1a Canel C, Moraes RM, Dayan FE, Ferreira D. Photochemistry 2000; 54: 115
    • 1b Tsutsui C, Yamada Y, Ando M, Toyama D, Wu J.-l, Wang L, Taketani S, Kataoka T. Bioorg. Med. Chem. Lett. 2009; 19: 4084
    • 2a Mondal S, Panda G. RSC Adv. 2014; 4: 28317
    • 2b Wood PM, Woo LW. L, Labrosse J.-R, Trusselle MN, Abbate S, Longhi G, Castiglioni E, Lebon F, Purohit A, Reed MJ, Potter BV. L. J. Med. Chem. 2008; 51: 4226
  • 3 Yoshihara HA. I, Apriletti JW, Baxter JD, Scanlan TS. Bioorg. Med. Chem. Lett. 2001; 11: 2821
  • 4 Kong X, Chen L, Jiao L, Lian F, Lu J, Zhu K, Du D, Liu J, Ding H, Zhang N, Shen J, Zheng M, Chen K, Liu X, Jiang H, Luo C. J. Med. Chem. 2014; 57: 9512 ; and the references cited therein
    • 5a Wai JS, Egbertson MS, Payne LS, Fisher TE, Embrey MW, Tran LO, Melamed MW, Langford HM, Guare JP, Zhuang L, Grey VE, Vacca JP, Holloway MK, Naylor-Olsen AM, Hazuda DJ, Felock PJ, Wolfe AL, Stillmock KA, Schleif WA, Gabryelski LJ, Young SD. J. Med. Chem. 2000; 43: 4924
    • 5b Zhuang L, Wai JS, Embrey MW, Fisher TE, Egbertson MS, Payne LS, Guare JP, Vacca JP, Hazuda DJ, Felock PJ, Wolfe AL, Moyer G, Schlelf WA, Gabryelski LJ, Leonard YM, Lynch JJ, Michelson SR, Young SD. J. Med. Chem. 2003; 46: 453
    • 5c Long Y.-Q, Jiang X.-H, Dayam R, Sanchez T, Shoemaker R, Sel S, Neamati N. J. Med. Chem. 2004; 47: 2561
    • 5d Cheltsov AV, Aoyagi M, Aleshin A, Yu C.-WE, Gilliland T, Zhai D, Bobkov AA, Reed JC, Liddington RC, Abagyan R. J. Med. Chem. 2010; 53: 3899
    • 6a Procopiou PA, Browning C, Buckley JM, Clark KL, Fechner L, Gore PM, Hancock AP, Hodgson ST, Holmes DS, Kranz M, Looker BE, Morriss KM. L, Parton DL, Russell LJ, Slack RJ, Sollis SL, Vile S, Watts CJ. J. Med. Chem. 2011; 54: 2183
    • 6b Procopiou PA, Ford AJ, Gore PM, Looker BE, Hodgson ST, Holmes DS, Vile S, Clark KL, Saunders KA, Slack RJ, Rowedder JE, Watts CJ. ACS Med. Chem. Lett. 2017; 8: 577
    • 7a Ohtake Y, Sato T, Kobayashi T, Nishimoto M, Taka N, Takano K, Yamamoto K, Ohmori M, Yamaguchi M, Takami K, Yeu S.-Y, Ahn K.-H, Matsuoka H, Morikawa K, Suzuki M, Hagita H, Ozawa K, Yamaguchi K, Kato M, Ikeda S. J. Med. Chem. 2012; 55: 7828
    • 7b Li Y, Shi Z, Chen L, Zheng S, Li S, Xu B, Liu Z, Liu J, Deng C, Ye F. J. Med. Chem. 2017; 60. 4173
  • 8 Mahesh S, Anand RV. Org. Biomol. Chem. 2017; 15: 8393
    • 9a Novelli A, Rosi E. J. Chemother. 2017; 29: 10
    • 9b Wang S, Yin Y, Wang J. Appl. Microbiol. Biotechnol. 2018; 102: 1997
    • 10a Takamatsu S, Hodges TW, Rajbhandari I, Gerwick WH, Hamann MT, Nagle DG. J. Nat. Prod. 2003; 66: 605
    • 10b Wegener A, Miller KA. J. Org. Chem. 2017; 82: 11655 ; and references cited therein
    • 11a Jablonicka V, Ziegler J, Vatehova Z, Liskova D, Heilmann I, Oblozinsky M, Heilmann M. J. Plant Physiol. 2018; 223: 1
    • 11b Yang X, Tsui GC. Org. Lett. 2018; 20: 1179
  • 12 Kern L, Xu R, Julien S, Suter DM, Preynat-Seauve O, Baquie M, Poncet A, Combescure C, Stoppini L, Thriel CV, Krause K.-H. Curr. Med. Chem. 2013; 20: 710
  • 13 Kito Y, Suzuki H, Edwards FR. J. Smooth Muscle Res. 2002; 38: 165
  • 14 Xu M.-M, Wang H.-Q, Wan Y, He G, Yan J, Zhang S, Wang S.-L, Shi F. Org. Chem. Front. 2017; 4: 358
  • 15 Liang F, Ji X, Zhang J, Cao S. Org. Chem. Front. 2016; 3: 1425
    • 16a Chowdhury S, Georghiou PE. Tetrahedron Lett. 1999; 40: 7599
    • 16b Nobre SM, Monteiro AL. Tetrahedron Lett. 2004; 45: 8225
    • 16c Liegault B, Renaud J.-L, Bruneau C. Chem. Soc. Rev. 2008; 37: 290
    • 16d Zhao G, Zhang K, Wang L, Li J, Zou D, Wu Y, Wu Y. Tetrahedron Lett. 2015; 56: 6700
  • 17 Xu W, Paira R, Yoshikai N. Org. Lett. 2015; 17: 4192
  • 18 Zhang J, Lu G, Sun H, Shen Q. Org. Lett. 2016; 18: 2860
  • 19 Mahesh S, Kant G, Anand RV. RSC Adv. 2016; 6: 80718
  • 20 Hemelaere R, Champagne PA, Desroches J, Paquin J.-F. J. Fluorine Chem. 2016; 190: 1
  • 21 Ueda M, Nakakoji D, Kuwahara Y, Nishimura K, Ryu I. Tetrahedron Lett. 2016; 57: 4142
    • 22a Goal A, Singh FV, Dixit M, Verma D, Raghunandan R, Maulik PR. Chem. Asian. J. 2007; 2: 239
    • 22b Singh FV, Chaurasia S, Joshi MD, Srivastava AK, Goel A. Bioorg. Med. Chem. Lett. 2007; 17: 2425
    • 22c Goal A, Ram VJ. Tetrahedron 2009; 65: 7865
    • 23a Singh FV, Kumar V, Goal A. Synlett 2007; 13: 2086
    • 23b Singh FV, Kumar V, Kumar B, Goal A. Tetrahedron 2007; 63: 10971
    • 23c Goal A, Singh FV, Kumar V, Reichert M, Gulder TA. M, Bringmann G. J. Org. Chem. 2007; 72: 7765
    • 23d Kumar A, Singh FV, Goal A. Tetrahedron Lett. 2007; 48: 8223
    • 23e Goel A, Kumar V, Hemberger Y, Singh FV, Nag P, Knauer M, Kant R, Raghunandan R, Maulik PR, Bringmann G. J. Org. Chem. 2016; 81: 10721
    • 24a Goal A, Singh FV, Sharon A, Maulik PR. Synlett 2005; 623
    • 24b Goal A, Singh FV, Verma D. Synlett 2005; 2027
    • 24c Goel A, Taneja G, Raghuvanshi A, Kant R, Maulik PR. Org. Biomol. Chem. 2013; 11: 5239
    • 25a Goel A, Singh SP, Kumar A, Kant R, Maulik PR. Org. Lett. 2009; 11: 5122
    • 25b Goel A, Kumar V, Chaurasia S, Rawat M, Prasad R, Anand RS. J. Org. Chem. 2010; 75: 3656
    • 25c Maurya HK, Tandon VK, Kumar B, Kumar A, Huch V, Ram V. J. Org. Biomol. Chem. 2012; 10: 605
    • 25d Goel A, Kumar V, Singh SP, Sharma A, Prakash S, Singh C, Anand RS. J. Mater. Chem. 2012; 22: 14880
    • 25e Goel A, Sharma A, Kathuria M, Bhattacharjee A, Verma A, Mishra PR, Nazir A, Mitra K. Org. Lett. 2014; 16: 756
    • 25f Goel A, Umar S, Nag P, Sharma A, Kumar L, Shamsuzzama Hossain Z, Gayen JR, Nazir A. Chem. Commun. 2015; 51: 5001
    • 25g Sharma A, Umar S, Kar P, Singh K, Sachdev M, Goel A. Analyst 2016; 141: 137
    • 25h Taneja G, Gupta CP, Mishra S, Srivastava R, Rahuja N, Rawat AK, Pandey J, Gupta AP, Jaiswal N, Jiaur GR, Tamrakar AK, Srivastava AK, Goel A. Med. Chem. Commun. 2017; 8: 329
  • 26 Shetgaonkar SE, Singh FV. Synthesis 2018; 50: 3540
    • 27a Goel A, Singh FV. Tetrahedron Lett. 2005; 46: 5585
    • 27b Goel A, Verma D, Singh FV. Tetrahedron Lett. 2005; 46: 8487
    • 27c Singh FV, Kumar A, Goel A. Tetrahedron Lett. 2006; 47: 7767
    • 27d Kumar V, Singh FV, Parihar A, Goel A. Tetrahedron Lett. 2009; 50: 680
    • 27e Goel A, Kumar V, Nag P, Bajpai V, Kumar B, Singh C, Prakash S, Anand RS. J. Org. Chem. 2011; 76: 7474

  • References

    • 1a Canel C, Moraes RM, Dayan FE, Ferreira D. Photochemistry 2000; 54: 115
    • 1b Tsutsui C, Yamada Y, Ando M, Toyama D, Wu J.-l, Wang L, Taketani S, Kataoka T. Bioorg. Med. Chem. Lett. 2009; 19: 4084
    • 2a Mondal S, Panda G. RSC Adv. 2014; 4: 28317
    • 2b Wood PM, Woo LW. L, Labrosse J.-R, Trusselle MN, Abbate S, Longhi G, Castiglioni E, Lebon F, Purohit A, Reed MJ, Potter BV. L. J. Med. Chem. 2008; 51: 4226
  • 3 Yoshihara HA. I, Apriletti JW, Baxter JD, Scanlan TS. Bioorg. Med. Chem. Lett. 2001; 11: 2821
  • 4 Kong X, Chen L, Jiao L, Lian F, Lu J, Zhu K, Du D, Liu J, Ding H, Zhang N, Shen J, Zheng M, Chen K, Liu X, Jiang H, Luo C. J. Med. Chem. 2014; 57: 9512 ; and the references cited therein
    • 5a Wai JS, Egbertson MS, Payne LS, Fisher TE, Embrey MW, Tran LO, Melamed MW, Langford HM, Guare JP, Zhuang L, Grey VE, Vacca JP, Holloway MK, Naylor-Olsen AM, Hazuda DJ, Felock PJ, Wolfe AL, Stillmock KA, Schleif WA, Gabryelski LJ, Young SD. J. Med. Chem. 2000; 43: 4924
    • 5b Zhuang L, Wai JS, Embrey MW, Fisher TE, Egbertson MS, Payne LS, Guare JP, Vacca JP, Hazuda DJ, Felock PJ, Wolfe AL, Moyer G, Schlelf WA, Gabryelski LJ, Leonard YM, Lynch JJ, Michelson SR, Young SD. J. Med. Chem. 2003; 46: 453
    • 5c Long Y.-Q, Jiang X.-H, Dayam R, Sanchez T, Shoemaker R, Sel S, Neamati N. J. Med. Chem. 2004; 47: 2561
    • 5d Cheltsov AV, Aoyagi M, Aleshin A, Yu C.-WE, Gilliland T, Zhai D, Bobkov AA, Reed JC, Liddington RC, Abagyan R. J. Med. Chem. 2010; 53: 3899
    • 6a Procopiou PA, Browning C, Buckley JM, Clark KL, Fechner L, Gore PM, Hancock AP, Hodgson ST, Holmes DS, Kranz M, Looker BE, Morriss KM. L, Parton DL, Russell LJ, Slack RJ, Sollis SL, Vile S, Watts CJ. J. Med. Chem. 2011; 54: 2183
    • 6b Procopiou PA, Ford AJ, Gore PM, Looker BE, Hodgson ST, Holmes DS, Vile S, Clark KL, Saunders KA, Slack RJ, Rowedder JE, Watts CJ. ACS Med. Chem. Lett. 2017; 8: 577
    • 7a Ohtake Y, Sato T, Kobayashi T, Nishimoto M, Taka N, Takano K, Yamamoto K, Ohmori M, Yamaguchi M, Takami K, Yeu S.-Y, Ahn K.-H, Matsuoka H, Morikawa K, Suzuki M, Hagita H, Ozawa K, Yamaguchi K, Kato M, Ikeda S. J. Med. Chem. 2012; 55: 7828
    • 7b Li Y, Shi Z, Chen L, Zheng S, Li S, Xu B, Liu Z, Liu J, Deng C, Ye F. J. Med. Chem. 2017; 60. 4173
  • 8 Mahesh S, Anand RV. Org. Biomol. Chem. 2017; 15: 8393
    • 9a Novelli A, Rosi E. J. Chemother. 2017; 29: 10
    • 9b Wang S, Yin Y, Wang J. Appl. Microbiol. Biotechnol. 2018; 102: 1997
    • 10a Takamatsu S, Hodges TW, Rajbhandari I, Gerwick WH, Hamann MT, Nagle DG. J. Nat. Prod. 2003; 66: 605
    • 10b Wegener A, Miller KA. J. Org. Chem. 2017; 82: 11655 ; and references cited therein
    • 11a Jablonicka V, Ziegler J, Vatehova Z, Liskova D, Heilmann I, Oblozinsky M, Heilmann M. J. Plant Physiol. 2018; 223: 1
    • 11b Yang X, Tsui GC. Org. Lett. 2018; 20: 1179
  • 12 Kern L, Xu R, Julien S, Suter DM, Preynat-Seauve O, Baquie M, Poncet A, Combescure C, Stoppini L, Thriel CV, Krause K.-H. Curr. Med. Chem. 2013; 20: 710
  • 13 Kito Y, Suzuki H, Edwards FR. J. Smooth Muscle Res. 2002; 38: 165
  • 14 Xu M.-M, Wang H.-Q, Wan Y, He G, Yan J, Zhang S, Wang S.-L, Shi F. Org. Chem. Front. 2017; 4: 358
  • 15 Liang F, Ji X, Zhang J, Cao S. Org. Chem. Front. 2016; 3: 1425
    • 16a Chowdhury S, Georghiou PE. Tetrahedron Lett. 1999; 40: 7599
    • 16b Nobre SM, Monteiro AL. Tetrahedron Lett. 2004; 45: 8225
    • 16c Liegault B, Renaud J.-L, Bruneau C. Chem. Soc. Rev. 2008; 37: 290
    • 16d Zhao G, Zhang K, Wang L, Li J, Zou D, Wu Y, Wu Y. Tetrahedron Lett. 2015; 56: 6700
  • 17 Xu W, Paira R, Yoshikai N. Org. Lett. 2015; 17: 4192
  • 18 Zhang J, Lu G, Sun H, Shen Q. Org. Lett. 2016; 18: 2860
  • 19 Mahesh S, Kant G, Anand RV. RSC Adv. 2016; 6: 80718
  • 20 Hemelaere R, Champagne PA, Desroches J, Paquin J.-F. J. Fluorine Chem. 2016; 190: 1
  • 21 Ueda M, Nakakoji D, Kuwahara Y, Nishimura K, Ryu I. Tetrahedron Lett. 2016; 57: 4142
    • 22a Goal A, Singh FV, Dixit M, Verma D, Raghunandan R, Maulik PR. Chem. Asian. J. 2007; 2: 239
    • 22b Singh FV, Chaurasia S, Joshi MD, Srivastava AK, Goel A. Bioorg. Med. Chem. Lett. 2007; 17: 2425
    • 22c Goal A, Ram VJ. Tetrahedron 2009; 65: 7865
    • 23a Singh FV, Kumar V, Goal A. Synlett 2007; 13: 2086
    • 23b Singh FV, Kumar V, Kumar B, Goal A. Tetrahedron 2007; 63: 10971
    • 23c Goal A, Singh FV, Kumar V, Reichert M, Gulder TA. M, Bringmann G. J. Org. Chem. 2007; 72: 7765
    • 23d Kumar A, Singh FV, Goal A. Tetrahedron Lett. 2007; 48: 8223
    • 23e Goel A, Kumar V, Hemberger Y, Singh FV, Nag P, Knauer M, Kant R, Raghunandan R, Maulik PR, Bringmann G. J. Org. Chem. 2016; 81: 10721
    • 24a Goal A, Singh FV, Sharon A, Maulik PR. Synlett 2005; 623
    • 24b Goal A, Singh FV, Verma D. Synlett 2005; 2027
    • 24c Goel A, Taneja G, Raghuvanshi A, Kant R, Maulik PR. Org. Biomol. Chem. 2013; 11: 5239
    • 25a Goel A, Singh SP, Kumar A, Kant R, Maulik PR. Org. Lett. 2009; 11: 5122
    • 25b Goel A, Kumar V, Chaurasia S, Rawat M, Prasad R, Anand RS. J. Org. Chem. 2010; 75: 3656
    • 25c Maurya HK, Tandon VK, Kumar B, Kumar A, Huch V, Ram V. J. Org. Biomol. Chem. 2012; 10: 605
    • 25d Goel A, Kumar V, Singh SP, Sharma A, Prakash S, Singh C, Anand RS. J. Mater. Chem. 2012; 22: 14880
    • 25e Goel A, Sharma A, Kathuria M, Bhattacharjee A, Verma A, Mishra PR, Nazir A, Mitra K. Org. Lett. 2014; 16: 756
    • 25f Goel A, Umar S, Nag P, Sharma A, Kumar L, Shamsuzzama Hossain Z, Gayen JR, Nazir A. Chem. Commun. 2015; 51: 5001
    • 25g Sharma A, Umar S, Kar P, Singh K, Sachdev M, Goel A. Analyst 2016; 141: 137
    • 25h Taneja G, Gupta CP, Mishra S, Srivastava R, Rahuja N, Rawat AK, Pandey J, Gupta AP, Jaiswal N, Jiaur GR, Tamrakar AK, Srivastava AK, Goel A. Med. Chem. Commun. 2017; 8: 329
  • 26 Shetgaonkar SE, Singh FV. Synthesis 2018; 50: 3540
    • 27a Goel A, Singh FV. Tetrahedron Lett. 2005; 46: 5585
    • 27b Goel A, Verma D, Singh FV. Tetrahedron Lett. 2005; 46: 8487
    • 27c Singh FV, Kumar A, Goel A. Tetrahedron Lett. 2006; 47: 7767
    • 27d Kumar V, Singh FV, Parihar A, Goel A. Tetrahedron Lett. 2009; 50: 680
    • 27e Goel A, Kumar V, Nag P, Bajpai V, Kumar B, Singh C, Prakash S, Anand RS. J. Org. Chem. 2011; 76: 7474

Zoom Image
Figure 1 Structures of synthetic and natural products of biological importance with diarylmethane units
Zoom Image
Scheme 1
Zoom Image
Scheme 2 The ring transformation of 2H-pyran-2-ones 5a with 1,3-diphenylacetone (10)
Zoom Image
Scheme 3 Proposed mechanism for the synthesis of diarylmethanes 9 by the ring transformation of 2H-pyran-2-ones 8 with 4-phenylbutan-2-one (6)