J. CHEM. SOC. FARADAY TRANS., 1994, 90(7), 947-951 Intramolecular Photodimerization of 2-Naphthoates:Successful Application of Hydrophobic Forces in the Preparation of Large-ring Compoundst Chen-Ho Tung,* Yi Li and Zhi-Qiang Yang The Laboratory of Photochemistry, Institute of Photographic Chemistry, Academia Sinica, Beijing 100101,China ~ ~~ ~~ ~~ ~~ ~ ~ The fluorescence spectra and photodimerization of polymethylene bis(2-naphthoate) (N -M, -N) in aqueous organic binary mixed solvents have been studied. Strong intramolecular excimer fluorescence was observed, suggesting that hydrophobic interactions force polymethylene chains to self-coil. Photoirradiation of these solu- tions resulted in intramolecular dimerization of 2-naphthoate groups to give ring-closure products.The quantum yields for the photodimeriration are significantly greater than those in organic solvents. This work provides an example of the application of hydrophobic interactions in expediting the formation of macrocyclic entities. The construction of macrocyclic compounds is a long-standing problem in synthetic organic A bifunctional molecule may undergo either intramolecular or intermolecular reactions. The intramolecular reaction gives macrocyclic ring-closure products, while the intermolecular reaction results in polymers. The rates of the latter type of reaction are dependent on the concentration of the substrate, while those of the former are not, since the effective concen- tration for the reaction is kept constant by the function of a molecular chain linking the two functional groups.Therefore, the cyclization can occur without competition only at low concentrations, as first described by Ziegler.' Reactivity in cyclization reactions may be interpreted on the basis of the activation energy and the probability of end-to-end encounters. According to transition-state theory, the activation energy for a cyclization reaction depends on the structure of the initial open-chain state and on that of the transition state, whose conformation can reasonably be expected to resemble that of the cyclic product. In general, the activation energy reflects the strain energy of the ring to be formed, which is markedly dependent on ring size.6 The probability of end-to-end encounters of a molecular chain will decrease as the chain becomes longer.' Thus, the forma- tion of a large ring from a flexible chain demands a for-midable price in terms of entropy.398 Traditionally, chemists use energetically highly favoured reactions between the ter- minal groups to synthesize large-ring compound^.^ The new approach is to use forces to reduce the entropy expense."*" It is well established that in aqueous organic binary mixed solvents hydrophobic interactions force molecules with long hydrocarbon chains to ~elf-coil.'~*'~ Self-coiling of a chain linking two terminal groups would increase the intramolecu- lar ring-closure probability and expedite the formation of macrocyclic entities.In the present work, we report a suc-cessful example of the utilization of hydrophobic forces to promote large-ring formation.We use 2-naphthoate as the terminal groups of polymethylene chains, since this group may undergo photodimerization to give a 'cubane-like' dimer as the unique product with a reasonable quantum yield.14 The molecules we studied have the following struc- tures and are abbreviated as N -M, -N. NPCO~(CH~),CO,NP N -M, -N (n = 2, 3, 5, 8, 10) where Np = 2-naphthoate. t Hydrophobic Effects on Photochemical and Photophysical Pro- cesses. Part 15. For Part 14*see ref. 1. Through the examination of excimer formation and photo- dimerization, we obtained evidence for the self-coiling of N -M, -N in aqueous organic mixed solvents and demon- strated that the intramolecular photodimerization of the ter- minal groups of N -M, -N is enhanced by self-coiling of the chains.Results and Discussion Intramolecular Excimer Formation of N -M, -N To establish that the self-coiling of polymethylene chains is driven by hydrophobic interactions we studied the emission spectra of N -M, -N in aqueous organic binary mixed sol- vents. Fig. 1 shows the fluorescence spectra of N -MI, -N (1 x lo-' mol dm-3) in ethylene glycol-water (EG-H,O) mixed solvents at ambient temperature, which is typical of , 300 340 380 420 460 500 540 A/nm Fig. 1 Fluorescence spectra of N -M,,-N and BN in EG-H,O. -M,, -N] = 1/2[BN] = 1 x lo-' mol dm-3. 1, BN in the mixed solvents with various ratios of water to EG; 2, N -MI, -N in EG; 3, N -M,, -N in EG-H,O with H,O :EG = 30 : 70.the other polymethylene 2-naphthoates in aqueous organic mixed solvents. The fluorescence spectrum of the model com- pound, butyl 2-naphthoate (BN) is also shown. In the mixed solvents with various EG :H,O ratios, BN exhibits struc- tured fluorescence characteristic of the naphthoate monomer with maxima at 340, 350 and 370 nm. The behaviour of N -M,, -N is quite different from that of BN. In ethylene glycol, N -M,, -N also shows only monomer emission. However, in the mixed solvents, an excimer fluorescence centred at ca. 400 nm is observed. For solvents with water : EG ratios >30 : 70, the excimer emission dominates the fluorescence spectrum of N -N,, -N.At concentra- tions <5 x mol dm-3, the ratio of the fluorescence intensities of excimer to monomer, lD/IM,is independent of concentration, suggesting that the excimer is intramolecular. Thus the excimer formation for N -M, -N in EG-H,O is attributed to the self-coiling of the polymethylene chain, which makes the two terminal chromophores approach each other. The excitation spectra for the excimer and monomer emission are identical, and the maxima correspond to that in the UV absorption spectrum, suggesting the absence of strong interaction between the naphthoate chromophores in the ground state. Thus, N -M, -N in EG-H,O tends to assume the self-coiling conformation and the two end groups are in proximity but do not associate with each other in the ground state.In other aqueous organic solvents, such as dimethyl sulfoxide-water (DMSO-H20) and 1,Cdioxane-water (DX-H,O), the behaviour of N -M, -N is analogous to that in EG-H,O. Effectsof Amylose on Excimer Formation of N -M, -N In order to ascertain the self-coiling of the polymethylene chain in aqueous organic solvents we studied the effect of amylose on the excimer formation of N -M, -N in EG-H,O. Amylose is a water-soluble polymer. The confor- mation of this polymer in solution and its interaction with polar and non-polar compounds have been extensively inves- tigated in connection with the biological significance of the amylose structure. In aqueous organic solvents, amylose molecules exist in the helical form and can incorporate long- chain substrates." In the absence of amylose, the excimer emission dominates the fluorescence spectrum of N -M,, -N in EG-H20 with H20 :EG = 30 :70 (Fig.2). Addition of amylose results in the enhancement of monomer emission and a reduction in the excimer fluorescence. In the presence of sufficient amylose the 'fluorescence spectrum is dominated by monomer emission. Obviously this is due to the fact that amylose forms an inclusion complex with N -M,, -N and prevents the two terminal naphthoate groups from approach- ing each other. Enhancement of Intramolecular Photodimerization of the 2-Naphthoate End Group of N -M, -N via Hydrophobic Interaction Photodimers of naphthalene derivatives have been known since Bradshaw and Hammond reported the intermolecular (4n+ 4n) photodimerization of 2-methoxynaphthalene.' Photoirradiation of alkyl 2-naphthoates results in a 'cubane- like' photodimer as the unique product (Scheme 1)in spite of the fact that six isomeric dimers are formally possible.'4 This selectivity originates from two restrictions.First, the photo- dimerization occurs only between the substituted rings. Sec- ondly, in the dimer the substituents are in the head-to-tail orientation. The photoirradiation of a bichromophoric com- pound, like N -M, -N, can lead either to intra- or inter- molecular reactions. The intramolecular reaction gives J. CHEM. SOC. FARADAY TRANS., 1994, VOL. 90 2 300 340 380 420 460 500 540 A/nm Fig. 2 Effect of amylose on the fluorescence spectra of N -MI, -N in EG-H,O (H,O :EG = 40:60)[N -MI, -N) = 1 x mol drn-j.[amylose]/mol dm-3: 1,O; 2, 5 x macrocyclic ring-closure products, while the intermolecular reaction results in polymers. In order to protect the cubane- like photodimer from decomposition we used II > 280 nm light as the light source. Irradiation of 5 x lo-' mol dm-3 N -M, -N in DX-H,O with H20 : DX = 60 :40 at ambient temperature led to the formation of intramolecular ring-closure photodimers only, as shown in Scheme 1. No 0-(CH2) 0 I o=c c=o 6/> 6/> 8 Scheme 1 J. CHEM. SOC. FARADAY TRANS., 1994, VOL. 90 polymerization products were detected. The yield of the intramolecular products was 100% based on the consump- tion of the starting materials.The assignment of the intramol- ecular reaction relies on the observation that the m/z values of the molecular ion in the mass spectra of the products are identical with those of the corresponding starting materials N -M,-N. Furthermore, in the ‘HNMR spectra of the products no protons assignable to naphthyl group were detected. The structure proposed for the cubane-like photo- Hd-0.-/ Hd’ “\3q;Hd” C/CH2 -0’ \\ \ a’ Hd dimer rests mainly on its ‘H NMR spectrum, which is in close agreement with that reported in the 1iterat~re.l~ The ‘H NMR spectra for the intramolecular photodimers of N -M,, -N, N -M, -N and N -M, -N are shown in Fig. 3 and the spectral details and assignments for the pro- ducts are given in Table 1.Note that the product molecules belong to the C, point group and the geminate protons for the methylene groups in the neighbourhood of the carboxyl groups are not magnetically equivalent. The difference Hd-0. ’ .c Hd” \ Hd’ (CH2)6‘d-0’ \Hd I z /’ I I J I I f I ’ //7 5 4 7.0 4.5 4.0 3.5 6 Hd-0. / ,c c& Hd” \GJkg; II I L II \ \ a’ -0’ \ Hd w 0 I7.0f, 4.5 4.0 3.5 6 Fig. 3 400MHz ‘HNMR spectra of the intramolecular photodimers of N -M, -N, N -M, -N and N -MI, -N in CDCl, 950 Table 1 'HNMR data of intramolecular photodimers of N -M, -N,N -M, -NandN-MI, -N 6 split JJHZ intensity assignment intramolecular photodimer of N -M, -N 6.78-7.17 m 8H Ar 4.90 m 2H Hd 4.61 d Jc,,a= 11.2 2H Ha 3 Ha, 4.34 dd Ja, = Jas 2H H,, Hc, = 11.2 Jb, c = 'b*, c = 9.9 4.20 m 2H Hd' 3.78 d Jc,b= 9.9 2H Hb, Hb' intramolecular photodimer of N -M, -N 7.00 m 8H Ar 4.55 d Jc,,a = 11.0 2H Ha 7 Ha, 4.41 dd Jar,c= Ja,cI = 11.0 2H Hc, H,y 'b,c = 7.1 = JW, c' 4.31 m 2H Hd 4.16 m 2H Hd' 3.86 d Jc?,b = 7.1 2H Hb, Hb, intramolecular photodimer of N -M -N 6.96-7.04 m 8H Ar 4.54 d Jcr.a= 11.9 2H Ha, Ha, 4.41 dd Jar,, = Ja,cI 2H H,, H,.= 11.9 Jb. c = 'b', c' = 7.9 4.25-4.19 m 4H Hd, Hd* 3.84 d Jc,b = 7.9 2H Hb, Hb' between the chemical shifts of the geminate protons decreases with increasing ring size. We have demonstrated experimentally that the yield of product in the photodimerization of N -M, -N is depen- dent on the square of the light intensity. This suggests that the formation of the cubane-like photodimer for N -M, -N is a two-photon process.A plausible proposal for this photodimerization is shown in Scheme 2. N -M, -N absorbs the first photon to give a [4 +4] cycloaddition product (1) which then rearranges thermally to 2, as described by Sasse and co-workers." Absorption of the second photon by 2 results in the cubane-like photodimer. Another possible pathway to form the cubane-like dimer from 1 is that the naphthyl group of the unreacted starting material N -M, -N plays the role of triplet sensitizer to induce conversion of 1 into the final product, since Yang has demonstrated that in the presence of a triplet sensitizer pho- toirradiation can bring about the conversion of the adduct of naphthalene and cyclohexa- 1,3-diene into a cubane-like dimer., The photodimerization of N -M, -N in organic sol- vents, both polar and non-polar, was also studied.Photoirra- diation of these solutions gave the same products as those in aqueous organic mixed solvents, but the quantum yields were much lower. Table 2 gives the conversions of N -M, -N in J. CHEM. SOC. FARADAY TRANS., 1994, VOL. 90 0 0 endo (1) cubane-like end4ope rearranged (2) Scheme 2 DX-H,O with H,O : DX = 60 : 40, cyclohexane and meth- anol after irradiation for 15 min with a 450 W Hanovia high- pressure mercury lamp in a merry-go-round apparatus. The conversions of all N -M, -N in cyclohexane and methanol are smaller than those in DX-H,O.For example, the conver- sion of N -M, -N in DX-H,O is ca. 10 times greater than that in cyclohexane. Obviously the high yields of the photo- dimerization of N -M, -N in aqueous organic mixed sol- vents are attributed to the self-coiling of the polymethylene chain, This demonstrates the potential application of hydro-phobic interactions to the synthesis of macrocyclic entities. Experimenta1 'H NMR spectra were recorded either at 100 MHz with a Varian FX-100 or at 400 MHz with a Varian XL-400 spec- trometer. MS spectra were run either on a Finigan 4021C spectrometer or on a VG ZAB spectrometer. UV spectra were measured with a Hitachi UV-340 spectrometer.Fluores- cence spectra were run either on a Hitachi EM 850 or a Hitachi MPF-4 spectrofluorimeter. Photoirradiation pro- ducts were separated by using a Varian VISTA 5500 liquid chromatograph with a Lichrosorb RP 18 column. Poly- methylene bis(2-naphthoates) (N -M, -N) were synthesized by esterification of 2-naphthoyl chloride with corresponding diols, as previously reported. 10~22Spectral-grade cyclohexane, methanol and 1,4-dioxane were used without further purifi- cation for fluorescence measurements. Amylose was a gift from the Shanghai Institute of Organic Chemistry, Academia Sinica. The average degree of polymerization was 350; the purity of straight chain species was > 95%. Fluorescence Measurements The samples were purged with nitrogen for at least 30 min before measurement. The excitation wavelength was 280 nm.Table 2 Conversions of N -M, -N in various solvents at ambient temperature after irradiation for 15 min with a 450 W Hanovia lamp ([N -M, -N] x 5 x lop5mol dm-') DX-H,O 65 40 37 33 cyclo hexane 7 12 17 9 methanol 1 2 3 2 J. CHEM. SOC. FARADAY TRANS., 1994, VOL. 90 951 The spectra were fully corrected for instrumental response. 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