Pergamon

Solvent Effect in the “Fragment Condensation” Synthesis of Calix[4]arenes

and Temperature Dependent ‘H-NMR Studies of New Dihomomonoxacalixarenes

Giovanni Sartori*, Franca Bigi, Cecilia Porta, Raimondo Magi and Francesco Peri

Diporrmwnro di Chimlco Urxon~ca e Indusrrrale dell’Unwersird

l’rale de/k Sclenzr. I-4.3100 Parrno, Italy

Abstmcf: Rractmn of formaldehyde with ?.?‘-dlhydroxy-3.3’-di-rerr-butyldiphenylmethane (1) in basic media affords cahx[4]arenes 2 or dihomomonooxacalix[4]arenes 3 depending on the solvent (xylene or CKHCHCIZ). Temperature dependent ‘H-NMR studies of compounds 3 are repotted.

During our studies on the synthesis of new phenolic metacyclophanes we discovered a route toward a class

of calix[4]arenes bearing two aryl substituents on the diametrical methylene bridges (2).’ Compounds 2 were

synthetized in moderate yields (,1X-27%) by BF, Et20 promoted condensation of niphenylmethane 1 with

formaldehyde. Attempting to increase the yield of the macrocyclization process, we reacted compound 1 with

formaldehyde following the useful base induced synthesis of calix[4]arenes.2 Reactions were carried out in

refluxing xylene (mixture of isomers; bp=137- 140°C) or ClzCHCHC12 (bp=142-143T) because compound 1

undergoes thermal decomposition by prolonged heating at temperatures higher than 150°C. After the usual

work-up (see below) we recovered the expected calix[4]arenes 2 [(E) + (Z) mixture] in 20% yield from the

reaction in xylene but. very surprisingly, we found that the two isomeric dihomomonooxacalixarenes 3 were

produced when the same reaction was performed in C12CHCHCl: [25% total yield; 14% (Z), 11% (E)].3

Compounds 2 were described m a previous article.’ In this communication we report the synthesis and

temperature-dependent ‘H-NMR studies of the new dihomomonooxacalixarenes (E)-3 and (Z)-3.

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Synthesis of compounds 3.’ To a mixture of the aromatic substrate 1 (1.16 g, 0.003 mol) and sodium

hydroxide (0.12 g, 0.003 mol) in distilled HZ0 (10 ml), 0.35 ml of 36.5% aqueous formaldehyde solution (0.004

mol of HCHO) were added. The resulting mixture was stirred for 1 hour at 100°C in an open fla& the reaction,

which was clear at the beginning, became viscous as the water evaporated. Then 1,1,2,2-tetra~hloroetha (20

ml) was added to dissolve the residue, followed by NaOH (0.12 g, 0.003 mol), Hz0 (5 ml) and 0.35 ml of the

same aqueous formaldehyde solution. The content of the open flask was heated for 1 hour at 100°C to remove

water, then refluxed for 3 hours (-142°C). The solvent was distilled off and the products were purified by

cromathography on silica gel plates with hexane/CH& mixtures (80/20) giving the two isomers (E)-3 and (Z)-

3 in 25% total yield. We successively studied the temperature dependent ‘H-NMR spectra of compounds (E)-3

and (Z)-3 (Figure 1) in order to obtain information on their conformational mobility. The methine, methylene and

oxamethylene regions were analyzed as the more informative and diagnostic for configurational assignment and

conformational studies of compounds 3.4

Dihomomonooxacaltiarene (E)-3 (Fig. 1A). The methylene and methine resonances of (E)-3 are broad

singlets at 6 3.9 (ArCH&), 4.6 and 4.7 (CH2GCH2), and 5.7 (CHPh) at 300K according with the equilibration

between the two mirror image forms (E)-3a and (E)-3b. These signals resolve at 253K into three pairs of sharp

doublets at 6 3.55 and 4.17 (ArCH2Ar, J=13.8 Hz), 4.34 and 4.89 (CHaOCHa, J=lO.O Hz), 4.53 and 5.02

(CH2OCH2, J=lO.l Hz); moreover two sharp singlets appear at 6 5.46 and 6.05 (equatorial and axial CHPh)

indicating the frozen cone conformation. At high temperature (375K) the fast interconversion (E)-3as (E)-3b

is confirmed by the presence of a sharp singlet at 6 3.82 (ArCH&), a pair of doublets at 6 4.60 and 4.69

(CHZOCHZ, J=lO.O Hz) and a singlet at 6 5.72 (CHPh). The coalescence temperature of 283K for the me&tine

resonances corresponds to 13.1 Kcal/mol free energy of activation for the cone inversion. This value is 1.2

KcaJ/mol lower than that of compound (E)-2 (AG*=14.3 KcaJ/mol).

Dihomonwnooxacalixarene (2)3 (Fig. 1B). Compound (Z)-3 shows apparently temperature-independent

‘H-NMR spectra at 320 and 253K. At 320K a fast interconversion (Z)-3a% (Z)-3b occurs; instead at 253K

the frozen cone conformation (Z)-3a is quite prevalent, possibly due to the strong preference to assume the less

hindered conformation. We observed two pairs of sharp doublets at 6 3.63 and 4.30 (ArCHaAr, J=13.8 Hz), 4.44

and 4.98 (CHzOCHz, J=10.3 Hz), accompanied by a sharp singlet at 6 6.18 (axial CHPh). Expected signals for

conformer (Z)-3b (e.g. equatorial metbine signal at 6-5.3) are not evident; for this reason it was impossible to

estimate the coalescence temperature for (2).3. It is noteworthy the change of OH resonances by lowering the

temperature. The two sharp singlets at 6 8.61 and 9.17 observed at 300K, due to the two kinds of hydroxy

groups with different distance from CHzOCH2 bridge, are splitted into four broad peaks (6 8.3, 9.2, 9.7 and 9.9)

at 178K. A quite similar behavior was previously reported’ for the corresponding calix[4]arene (Z)-2, possibly

due to a frozen circular hydrogen bonding. To get information about the “inside” and “outside” forms of the

CHZOCHZ bridge, we examined the temperature dipendence of that bridge signals, according to the studies of D.

Gutsche.’ We observed a signal broadening at 215K that did not resolved into expected new sets of resonances

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by further lowering the temperature, suggesting that a “inside-outside” interconversion is still operating.

UC)-3b

253K

r 6.0 5.0 4.0 6.0 5.0 4.0

PPM PPM A B

Figure 1. Section of the 300 MHz ‘H-NMR variable temperature spectra of compounds (E)-3 and (29-3 ia CDCIs or CI~CDCDC~L (*) at the temperatures indicated.

Acknowledgements. This work was supported by the Ministero delI’LJniversid e delIa Ricerca Scientifica e

Tecnologica (M.U.R.S.T.) “Progetto Nazionale Sintesi e Reattivita Organica”. We thank the C. N. R. (Progetto

Strategic0 Tecnologie Chimiche Innovative: Sottoprogetto A). We are grateful to the Cenao Intcrdipattimentale

Misure (C.I.M.) for the use of NMR and Mass instruments.

References and notes

1) Sartori, G.; Maggi, R.; Bigi, F.; Arduini, A.; Pastorio, A.; Porta, C. J. Chem. Sot. Perkin Trans. I, 1994.

1657.

2) Gutsche, C. D.; lqbal, M. Org. Synth., 1988.68, 234.

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3) For previous synthesis and use of homooxacahxarenes see: a) Dhawan, B.; Gutsche, C. D. J. Org. Chem.,

1983.48, 1536; b) Arnaud-Neu, F.; Cremin, S.; Cunnigan, D.; Harris, S. J.; MC Ardle, P. ; MC Kervey, M.

A.; MC Marnts, M.; Schwing-Weill , M.J.; Ziat, K. J. Incl. Phenom., 1991, IO, 329; c) Asfari, Z.;

Harrowfield, J. M.; Ogden, M. I.; Vicens, J.; White, A. H. Angew. Chem. Int. Ed. Engf., 1991,30, 854; d)

ikrr, P.: Mussrabi, M; Vicens, J. Tetrahedron Let?., 1991, 48, 1536; e) Araki, K.; Hashimoto, N.; Otsuka,

H.; Shinkai, S. J. Org. Chem., 1993, 58, 5958; f) A&i, K.; Inada, K.; Otsuka, H.; Shinkai, S.

Tetrahedron, 1993,49,9465; g) De Iasi, G.; Masci, B. Tetrahedron Let?., 1993.34, 6635; h) Hampton, P.

D.; Bencze, Z.; Tong, W.; Daitch, C. E. J. Org. Chem., 1994,59,4838.

4) 27~8,29~~tetrahydroxy-7,13,19,25-tetra-tert-butyI-10,22-diphenyl-2J-dihomo-3-oxacalix[4]arne

(E)-3. Yield 0.14 g (1 l%), white solid; mp 186- 188°C; ‘H NMR (300 MHz), at 300K (ClXDCDCl~): 6

1.20 (s, 18H, 2 (CH&C), 1.23 (s, l8H, 2 (CH&C), 3.9 (br s, 2H, CHz), 4.6 (br s, 2H, OCHz), 4.7 (br s,

2H, OCHz), 5.7 (br s, 2H, 2 CH), 6.9-7.4 (m, 18H, Harom.), 8.7 (br s, 2H, 2 OH), 9.0 (br s, 2H, 2 OH); at

253K (CDCl,): 6 1.14 (s, 9H, (CH&C), 1.17 (s, 9H, (CH&C), 1.25 (s, 9H, (CH&C), 1.28 (s, 9H,

(CH&C). 3.55 (d, lH, ‘hCHzeq., J=13.8 Hz), 4.17 (d, lH, WCH,ax., J=13.8 Hz), 4.34 (d, lH, LAOCHaeq.,

J=lO.O Hz), 4.53 (d, lH, MOCHleq., J=lO.l Hz), 4.89 (d, lH, ‘/iOCHzax., J=lO.l Hz), 5.02 (d, lH,

t/lLCHrOCH2ax., J=lO.O Hz), 5.46 (s, lH, CHeq.), 6.05 (s, IH, CHax.), 6.9-7.4 (m, 18H, Harom.), 8.61 (s,

IH, OH), 8.85 (s, 2H, 2 OH), 9.39 (s, IH, OH); at 375K (C12CDCDC12): 6 1.21 (s, 18H, 2 (CH,),C), 1.22

6, 18H, 2 0X3)X). 3.82 (s, 2H, CH,), 4.60 (d, 2H, %?CH#CHr, J=lO.O Hz), 4.69 (d, 2H, ‘kCH2OCH2,

J=lO.O Hz), 5.72 (s, 2H, 2 CH), 6.97 (d, 2H, Harom., J=2.3 Hz), 7.12 (d, 2H, Harem., J=2.3 Hz), 7.1-7.2

(m, 12H, Harom.), 7.24 (d, 2H. Harom., J=2.3 Hz), 8.39 (s, 2H, 2 OH), 8.67 (s, 2H, 2 OH); MS (CI):

m/z=832 (M++l, 23%) 831 (M’, 100); FT-IR (KBr): 3260 cm-’ (OH).

2728,29,30-tetrahydroxy-7,13,19,25-tetra-&~-butyI-l0,22-diphenyl-2J-dihomo-3-oxacalix[4]arene

603. Yield 0.18 g (14%), white solid; mp 193-195°C; ‘H NMR (300 MHz), at 300K (ClrCDCDCl~): 6

1.15 (s, 18H 2 (CH,),C), 1.19 (s, 18H, 2 (CH3)3C), 3.63 (d, 1H. %zCH,eq., J=13.7 Hz), 4.25 (d, lH,

rhCH,ax., J=13.7 Hz), 4.43 (d, 2H, l/ICH20CH2eq., J=lO.l Hz), 4.93 (d, 2H, MCH20CH2ax., J=lO.l Hz),

6.08 (s, 2H, 2 CHax.), 6.92 (s, 2H, Harom.), 7.13 (s, 2H, Harom.), 7.1-7.4 (m, 14H, Harom.), 8.61 (s, 2H,

2 OH), 9.17 6, 2H 2 OH); at 253K (CDClj): 6 1.14 (s, 18H, 2 (CH,),C), 1.19 (s, 18H, 2 (CH&C!), 3.63

(d, H-I, %CH,eq., J=13.8 Hz), 4.30 (d, lH, MCH,ax., J=13.8 Hz), 4.44 (d, 2H, L/ICH20CH2eq., J=10.3

HZ), 4.98 (4 2H, MCHzOCHzax., J=10.3 Hz), 6.12 (s, 2H, 2 CHax.), 6.94 (d, 2H, Harom., J=1.9 Hz),

7.14 (d, 2H, Harom., J=2.0 Hz), 7.1-7.4 (m, 14H, Harom.), 8.75 (s, 2H, 2 OH), 9.34 (s, 2H, 2 OH); MS

63: m/z=832 (M’+l, 38%) 831 (M’, 100); FT-IR (KBr): 3252 cm-’ (OH).

All resonances were attributed by 2D-NMR (NOESY) experiments.

5) Gutsche, C. D.; Bauer, L. J. J. Am. Chem. Sot., 1985, 107,6052.

(Received in UK 3 August 1995; revised I 1 September 1995; uccepted 15 September 1995)