Facile Synthesis of Methanofullerenes in an Aqueous Two-Phase System under Photoirradiation Conditions

Abstract

Methanofullerenes, such as [6,6]-phenyl-C₆₁-butyric acid methyl ester {[6,6]PC₆₁BM (1a)}, were synthesized in good yields from the corresponding tosylhydrazones in an aqueous two-phase (o-dichlorobenzene–H₂O) system under photoirradiation conditions. This simple and convenient procedure was adopted for the synthesis of thienyl analogues of PC₆₁BM and its C₇₀ analogue, PC₇₁BM.

Organic thin-film photovoltaics are a promising alternative to silicon-based solar cells owing to their considerable advantages, such as light weight, flexibility, and low fabrication cost. The power-conversion efficiency of organic photovoltaics is still lower than that of silicon-based solar cells; however, numerous studies have achieved improvements in the performance of organic photovoltaics during the past decade.[1] Following the report of a power-conversion efficiency of 2.5% by Sariciftci and coworkers for a polymer solar cell based on a bulk heterojunction of [6,6]-phenyl-C₆₁-butyric acid methyl ester {[6,6]PC₆₁BM (1a), Figure [1]}[2] and poly[2-methoxy-5-(3′,7′-dimethyloctyloxy)-1,4-phenylenevinylene] (MDMO-PPV),[3] improvement of the power-conversion efficiency sped up and has now reached more than 9%.[4] These achievements were based on the development of polymer donor materials, such as poly(3-hexylthiophene) (P3HT),[5] some other low-band-gap polymers,[6] and also the development of fullerene-based acceptor molecules.[7] [8] [9] In spite of these developments, [6,6]PC₆₁BM (1a) is still widely recognized as a standard acceptor molecule,[5] and numerous studies have continued to develop novel acceptor materials based on the modification of PCBM, including our previous work.[8b] [c] [d]

Syntheses of PC₆₁BM and its analogues are carried out following the procedure reported by Hummelen et al.[2] In their procedure[3] C₆₀ reacts with tosylhydrazone 3a in the presence of NaOMe in pyridine and o-dichlorobenzene (ODCB) to give derivative of [6,6]PC₆₁BM (1a, Scheme [1]). In general, this procedure is performed under severe anhydrous conditions and [6,6]PC₆₁BM (1a) is obtained in relatively low yield (ca. 40%) together with unreacted C₆₀ and higher adducts, such as bisadducts. This reaction is very sensitive to moisture; in our group, we have found the reproducibility of this method problematic and also found that the selectivity and yield of PC₆₁BM depends on the degree of anhydrous conditions.[10] To improve the selectivity for PC₆₁BM, excess amounts of C₆₀ are sometimes used to prevent the formation of higher adducts. Additionally, during this procedure, open-cage [5,6]PC₆₁BM (2a) is obtained first and then converted into the thermally stable closed-cage [6,6]PC₆₁BM (1a) under thermal or photoirradiation conditions.[2] [11] Recently, the synthesis of [6,6]PC₆₁BM derivatives via photoirradiation conditions has gained popularity,[7d,e,h,11] but the yields and selectivity of the PCBM are still low. Separation of PC₆₁BM from the reaction mixture and purification are laborious and costly; therefore, a cost-effective and convenient preparation of PC₆₁BM is desired for practical use.

During our research on the development of fullerene derivatives for acceptor molecules in photovoltaics,[8] we have also focused on efficient, convenient, and cost-effective synthetic methods for PCBM. Herein, we report a facile synthesis of [6,6]PC₆₁BM (1a) with a good yield using an aqueous two-phase system in the presence of quaternary ammonium hydroxide under photoirradiation conditions.

First, we reinvestigated the procedure to generate the diazo compound from the corresponding tosylhydrazone 3a. Hummelen et al. used the aprotic Bamford–Stevens conditions[12] in pyridine using NaOMe as a base. This aprotic conditions require severe anhydrous conditions; however, in general the diazo compound can also be prepared in protic solvents, such as alcohols, though these conditions are rarely used for the synthesis of fullerene derivatives owing to the poor solubility of the fullerenes.[13] In our preliminary experiment, a methanol solution of n-Bu₄NOH (TBAH) was used as a base and caused precipitation of C₆₀ from the ODCB solution, which would affect the proportion of the products. On the other hand, Jończyk et al. reported the reaction of cycloalkenes with in situ generated diazo compounds from tosylhydrazones in an aqueous basic two-phase system.[14] This result encouraged us to perform the synthesis of PCBM under similar conditions. In the ODCB–H₂O two-phase system, the reactants, tosylhydrazone and C₆₀ are soluble in ODCB, and H₂O, which is immiscible with ODCB would not cause precipitation of fullerene. Therefore, we expected an aqueous basic two-phase system would be effective to generate diazo compounds that can subsequently react with C₆₀ to obtain PC₆₁BM derivatives. Jończyk et al. used an excess amount of sodium hydroxide (50% aqueous solution) to generate diazocompounds;[14] however, theoretically only one equivalent of base is needed for the formation of the tosylhydrazone anion and the diazotization. In addition, an excess amount of hydroxide ions may result in hydroxylation of fullerenes,[15] thus the use of one equivalent of base should be adequate for this reaction.

Table 1 Reaction Optimization of the Synthesis of [5,6]PC₆₁BM (2a)

				LC yield (%)
Entry	3a (equiv)	TBAH (equiv)	Temp (°C)	4	2a	5a
1	0.8	0.8	110	36	49	14
2	1.0	1.0	110	24	49	19
3	1.2	1.2	110	16	48	26
4	1.5	1.5	110	8	42	36
5	1.0	1.0	70	41	47	11
6	1.0	1.0	90	26	52	20
7	1.0	1.0	110	28a	52a	18a

^a Isolated yields.

The optimization of the reaction is summarized in Table [1]. An ODCB solution of tosylhydrazone 3a was vigorously stirred with aqueous TBAH at room temperature for 0.5 hours, and then an ODCB solution of C₆₀ (4) was added and heated to reflux (Table [1], entries 1–4). The reactions were completed within two hours, and the yields of [5,6]PC₆₁BM (2a) reached 48–49% when 0.8–1.2 equivalents of tosylhydrazone 3a were used (Table [1], entries 1–3). The use of an excess amount of tosylhydrazone 3a decreased the yield of monoadduct 2a and increased the ratio of bisadduct 5a and higher adducts (Table [1], entry 4). During the reaction, tosylhydrazone 3a was consumed almost quantitatively, and the diazo compound was generated and reacted to C₆₀ (4) with high efficiency.[16] A lower reaction temperature did not result in completion of the reaction within two hours, and the yields were slightly decreased. However, at 90 °C the reaction was completed, and the yields were quite similar to those obtained at 110 °C (Table [1], entries 5 and 6). A higher selectivity for monoadducts over bisadducts was observed at 70 °C but the conditions of entry 7 (Table [1]) were selected as the optimized conditions owing to the high isolated yield and short reaction time.

Using these optimized reaction conditions, the obtained PC₆₁BM was open-cage [5,6]fulleroid with small amounts of closed-cage [6,6]methanofullerene. It is well-known that [5,6]fulleroid has a lower solubility than [6,6]methanofullerene and is thermodynamically unstable; therefore, [6,6]methanofullerene is used in photovoltaic devices. The conversion of [5,6]fulleroid to [6,6]methanofullerene could be performed under thermal heating or photoirradiation conditions.

The direct preparation of [6,6]methanofullerene from tosylhydrazone and C₆₀ was then examined. After treatment of tosylhydrazone with TBAH at room temperature for 0.5 hours, C₆₀ was added and the mixture was heated to reflux under irradiation of a 375 W incandescent lamp for two hours (Scheme [2]).[17] The obtained PC₆₁BM was predominantly [6,6]methanofullerene 1a and [5,6]fulleroid 2a was not detected by ¹H NMR spectroscopy or HPLC.

Table 2 Synthesis of Thienyl Analogues of [6,6]PC₆₁BM

			Yield (%)a
Entry	Ar		4	Monoadduct	Bisadducts
1	3b		26	2b 46b	5b 22b
2c	3b		22	1b 43 (32)d	6b 20
3	3c		30	1c 50 (33)d	6c 18
4	3d		30	1d 44 (42)d	6d 19

^a Isolated yield.

^b [5,6]-Isomers were obtained.

^c Irradiated with an incandescent lamp (375 W).

^d Yields reported by Matsumoto et al. using the Hummelen procedure.[8d]

To evaluate the versatility of this reaction, thienyl analogues of PC₆₁BM,[7c] ^, [8b] [c] [d] which are prominent acceptor candidates owing to their expected higher compatibility with P3HT, were examined, and the results are summarized in Table [2]. The thienyl analogues of PC₆₁BM 1b–d were synthesized from the corresponding tosylhydrazones 3b–d. Without photoirradiation, the benzothiophene derivative was obtained as the [5,6]fulleroid 2b (Table [2], entry 1), similar to the synthesis of PC₆₁BM. However, under photoirradiation conditions, [6,6]methanofullerene 1b was directly synthesized (Table [2], entry 2). On the other hand, thienothiophene derivatives 1c and 1d were directly converted into the [6,6]methanofullerene without photoirradiation, as reported by Matsumoto et al. (Table [2], entries 3 and 4).[8d]

Hummelen et al. also synthesized PC₇₁BM (8),[7h] the higher fullerene analogue of PC₆₁BM. C₇₀ (7) has a higher absorption coefficient in the visible region of the spectrum; therefore, C₇₀ derivatives are regarded as some of the most promising acceptor molecules for organic photovoltaics. PC₇₁BM (8) was synthesized using the optimized reaction conditions and irradiation with a 375 W incandescent lamp for two hours and was obtained in 49% isolated yield with 17% of bisadducts 9 and 20% of unreacted C₇₀ (7) (Scheme [3]). The obtained monoadducts 8 consisted of the three inseparable isomers (α-type and two kinds of β-type) in a ratio similar to that previously reported.[7h]

In conclusion, we have developed a facile synthetic method to obtain methanofullerenes, such as PC₆₁BM. This aqueous two-phase system with quaternary ammonium hydroxide under photoirradiation conditions gave reproducible results and avoids the need for laborious anhydrous conditions and excess amount of reagents. PC₆₁BM, PC₇₁BM, and some thienyl analogues could be obtained in good yields. Further exploration to improve the yield and selectivity for the monoadducts are now in progress, including the utilization of flow synthesis.[18]

Acknowledgment

This research was supported in part by Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency (JST) and JSPS KAKENHI Grant Number 23750232 and 22550176.

• References and Notes

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• 12b Bamford WR, Stevens TS. J. Chem. Soc. 1952; 4735
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• 16 When an excess amount of tosylhydrazone was used, higher adducts, such as trisadducts, were detected.
• 17 General Procedure for the Synthesis of Methanofullerenes under Photoirradiation Conditions Under Ar atmosphere, to a solution of tosylhydrazone (18.7 mg, 0.050 mmol) in ODCB (2.0 mL) was added a solution of TBAH (1.0 M in H₂O, 0.05 mL, 0.050 mmol) in H₂O (1.95 mL), and the mixture was stirred at r.t. for 0.5 h. A solution of C₆₀ (36.0 mg, 0.050 mmol) in ODCB was added to the mixture, and the mixture was stirred (800–1000 rpm by magnetic stirrer), heated in an oil bath, and irradiated with a 375 W incandescent lamp for 2 h. During the irradiation, the oil bath temperature was kept at 105–115 °C by adjusting the distance between the light source and the flask was approximately 15 cm. After the reaction, the layers were separated and the aqueous phase was extracted with toluene (2 × 5 mL). The combined organic phase was dried over MgSO₄, filtered, and concentrated to 1 mL under reduced pressure. The residue was purified by silica gel column chromatography [silica gel; 20 g, eluent; toluene for C₆₀ and monoadduct, toluene–CH₂Cl₂ (1:2) for bisadducts], and the obtained [6,6]PC₆₁BM (1a) was dissolved in a small amount of toluene and transferred to a 50 mL centrifuge tube. MeOH (ca. 30 mL) was added, and the mixture was immersed in an ultrasound bath for 1 min, the suspension was centrifuged (4000 rpm, 30 min), the supernatant was decanted, and the residue was treated with MeOH in the same manner. The product was dried in vacuo at 60 °C. [6,6]PC₆₁BM (1a, 23.5 mg, 0.026 mmol, 52%) was obtained as brown powder. Unreacted C₆₀ (7.8 mg, 0.011 mmol, 22%) and bisadducts (10.9 mg, 0.010 mmol, 20%) were isolated in the same manner. Analytical Data for 1a ¹H NMR (300 MHz, CDCl₃): δ = 7.92 (d, J = 8.7 Hz, 2 H), 7.60–7.44 (m, 3 H), 3.68 (s, 3 H), 2.94–2.88 (m, 2 H), 2.52 (t, J = 7.5 Hz, 2 H), 2.23–2.13 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 173.40, 148.79–136.71, 132.06, 128.43, 128.24, 79.87, 51.85, 51.64, 33.87, 33.67, 22.37. IR (KBr): 2921, 2849, 1735, 699, 573, 550, 526, 482, 453 cm^–1. MS (MALDI): m/z calcd for C₇₂H₁₄O₂: 910.1; found: 910.1 [M]^–.

A few pieces of research for the synthesis of methanofullerenes using flow synthesis have been reported:
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• References and Notes

• 1a Matsuo Y. Chem. Lett. 2012; 41: 754
  CrossrefSearch in Google Scholar
• 1b Brabec CJ, Gowrisanker S, Halls JJ. M, Laird D, Jia S, Williams SP. Adv. Mater. 2010; 22: 3839
  CrossrefSearch in Google Scholar
• 1c Dennler G, Schaber MC, Brabec CJ. Adv. Mater. 2009; 21: 1323
  CrossrefSearch in Google Scholar
• 1d Brabec CJ, Sariciftci NS, Hummelen JC. Adv. Funct. Mater. 2001; 11: 15
  CrossrefSearch in Google Scholar
• 2 Hummelen JC, Knight BW, LePeq F, Wudl F, Yao J, Wilkins CL. J. Org. Chem. 1995; 60: 532
  CrossrefSearch in Google Scholar
• 3 Shaheen SE, Brabec CJ, Sariciftci NS, Padinger F, Fromherz T, Hummelen JC. Appl. Phys. Lett. 2001; 78: 841
  CrossrefSearch in Google Scholar
• 4 Service RF. Science 2011; 332: 293
  CrossrefSearch in Google Scholar
• 5a Dang MT, Hirsch L, Wantz G, Wuest JD. Chem. Rev. 2013; 113: 3734
  CrossrefSearch in Google Scholar
• 5b Dang MT, Hirsch L, Wantz G. Adv. Mater. 2011; 23: 3597
  CrossrefSearch in Google Scholar
• 5c Troshin PA, Hoppe H, Renz J, Egginger M, Mayorova JY, Goryachev AE, Peregudov AS, Lyubovskaya RN, Gobsch G, Sariciftci NS, Razumov VF. Adv. Funct. Mater. 2009; 19: 779
  CrossrefSearch in Google Scholar
• 5d Li G, Shrotriya V, Yao Y, Yang Y. J. Appl. Phys. 2005; 98: 043704
  CrossrefSearch in Google Scholar
• 6a Gendron D, Morin P.-O, Berrouard P, Allard N, Aïch BR, Garon CN, Tao Y, Leclerc M. Macromolecules 2011; 44: 7188
  CrossrefSearch in Google Scholar
• 6b Su M.-S, Kuo C.-Y, Yuan M.-C, Jeng US, Su C.-J, Wei K.-H. Adv. Mater. 2011; 23: 3315
  CrossrefSearch in Google Scholar
• 6c Price SC, Stuart AC, Yang L, Zhou H, You W. J. Am. Chem. Soc. 2011; 133: 4625
  CrossrefSearch in Google Scholar
• 6d Piliego C, Holcombe TW, Douglas JD, Woo CH, Beaujuge PM, Fréchet JM. J. J. Am. Chem. Soc. 2010; 132: 7595
  CrossrefSearch in Google Scholar
• 7a Morinaka Y, Nobori M, Murata M, Wakamiya A, Sagawa T, Yoshikawa S, Murata Y. Chem. Commun. 2013; 49: 3670
  CrossrefSearch in Google Scholar
• 7b Bouwer RK. M, Hummelen JC. Chem. Eur. J. 2010; 16: 11250
  CrossrefSearch in Google Scholar
• 7c Zhao H, Guo X, Tian H, Li C, Xie Z, Geng Y, Wang F. J. Mater. Chem. 2010; 20: 3092
  CrossrefSearch in Google Scholar
• 7d Lenes M, Shelton SW, Sieval AB, Kronholm DF, Hummelen JC, Blom PW. M. Adv. Funct. Mater. 2009; 19: 3002
  CrossrefSearch in Google Scholar
• 7e Shu C, Xu W, Slebodnick C, Champion H, Fu W, Reid JE, Azurmendi H, Wang C, Harich K, Dorn HC, Gibson HW. Org. Lett. 2009; 11: 1753
  CrossrefSearch in Google Scholar
• 7f Lens M, Wetzelaer G.-JA. H, Kooistra FB, Veenstra SC, Hummelen JC, Blom PW. M. Adv. Mater. 2008; 20: 2116
  CrossrefSearch in Google Scholar
• 7g Kooistra FB, Knol J, Kastenberg F, Popescu LM, Verhees WJ. H, Kroon JM, Hummelen JC. Org. Lett. 2007; 9: 551
  CrossrefSearch in Google Scholar
• 7h Wienk MM, Kroon JM, Verhees WJ. H, Knol J, Hummelen JC, van Hal PA, Janssen RA. J. Angew. Chem. Int. Ed. 2003; 42: 3371
  CrossrefSearch in Google Scholar
• 8a Matsumoto F, Iwai T, Moriwaki K, Takao Y, Ito T, Mizuno T, Ohno T. J. Org. Chem. 2012; 77: 9038
  CrossrefSearch in Google Scholar
• 8b Moriwaki K, Matsumoto F, Takao Y, Shimizu D, Ohno T. Tetrahedron 2010; 66: 7316
  CrossrefSearch in Google Scholar
• 8c Matsumoto F, Moriwaki K, Takao Y, Ohno T. Synth. Met. 2010; 160: 961
  CrossrefSearch in Google Scholar
• 8d Matsumoto F, Moriwaki K, Takao Y, Ohno T. Beilstein J. Org. Chem. 2008; 4: 33
  Search in Google Scholar
• 9a Yoshimura K, Matsumoto K, Uetani Y, Sakumichi S, Hayase S, Kawatsura M, Itoh T. Tetrahedron 2012; 68: 3605
  CrossrefSearch in Google Scholar
• 9b Meng X, Zhang W, Tan Z, Du C, Li C, Bo Z, Li Y, Yang X, Zhen M, Jiang F, Zheng J, Wang T, Jiang L, Shu C, Wang C. Chem. Commun. 2012; 48: 425
  CrossrefSearch in Google Scholar
• 9c Li C.-Z, Chien S.-C, Yip H.-L, Chueh C.-C, Chen F.-C, Matsuo Y, Nakamura E, Jen AK.-Y. Chem. Commun. 2011; 47: 10082
  CrossrefSearch in Google Scholar
• 9d He Y, Chen HY, Hou J, Li Y. J. Am. Chem. Soc. 2010; 132: 1377
  Search in Google Scholar
• 9e Matsuo Y, Iwashita A, Abe Y, Li C.-Z, Matsuo K, Hashiguchi M, Nakamura E. J. Am. Chem. Soc. 2008; 130: 15429
  CrossrefSearch in Google Scholar
• 10 Authors supposed trace amount of H₂O caused poor reproducibility of the original Hummelen’s procedure² owing to degradation of NaOMe and precipitation of NaOH from reaction media.
• 11 Janssen RA. J, Hummelen JC, Wudl F. J. Am. Chem. Soc. 1995; 117: 544
  CrossrefSearch in Google Scholar
• 12a Shapiro RH. Org. React. 1976; 23: 405
  Search in Google Scholar
• 12b Bamford WR, Stevens TS. J. Chem. Soc. 1952; 4735
  Crossref
• 13a Ruoff RS, Tse DS, Malhotra R, Lorents DC. J. Phys. Chem. 1993; 97: 3379
  CrossrefSearch in Google Scholar
• 13b Scrivens WA, Tour JM. J. Chem. Soc., Chem. Commun. 1993; 1207
• 14 Jończyk A, Włostowska J, Mąkosza M. Tetrahedron 2001; 57: 2827
  CrossrefSearch in Google Scholar
• 15 Li J, Takeuchi A, Ozawa M, Li X, Saigo K, Kitazawa K. J. Chem. Soc., Chem. Commun. 1993; 1784
• 16 When an excess amount of tosylhydrazone was used, higher adducts, such as trisadducts, were detected.
• 17 General Procedure for the Synthesis of Methanofullerenes under Photoirradiation Conditions Under Ar atmosphere, to a solution of tosylhydrazone (18.7 mg, 0.050 mmol) in ODCB (2.0 mL) was added a solution of TBAH (1.0 M in H₂O, 0.05 mL, 0.050 mmol) in H₂O (1.95 mL), and the mixture was stirred at r.t. for 0.5 h. A solution of C₆₀ (36.0 mg, 0.050 mmol) in ODCB was added to the mixture, and the mixture was stirred (800–1000 rpm by magnetic stirrer), heated in an oil bath, and irradiated with a 375 W incandescent lamp for 2 h. During the irradiation, the oil bath temperature was kept at 105–115 °C by adjusting the distance between the light source and the flask was approximately 15 cm. After the reaction, the layers were separated and the aqueous phase was extracted with toluene (2 × 5 mL). The combined organic phase was dried over MgSO₄, filtered, and concentrated to 1 mL under reduced pressure. The residue was purified by silica gel column chromatography [silica gel; 20 g, eluent; toluene for C₆₀ and monoadduct, toluene–CH₂Cl₂ (1:2) for bisadducts], and the obtained [6,6]PC₆₁BM (1a) was dissolved in a small amount of toluene and transferred to a 50 mL centrifuge tube. MeOH (ca. 30 mL) was added, and the mixture was immersed in an ultrasound bath for 1 min, the suspension was centrifuged (4000 rpm, 30 min), the supernatant was decanted, and the residue was treated with MeOH in the same manner. The product was dried in vacuo at 60 °C. [6,6]PC₆₁BM (1a, 23.5 mg, 0.026 mmol, 52%) was obtained as brown powder. Unreacted C₆₀ (7.8 mg, 0.011 mmol, 22%) and bisadducts (10.9 mg, 0.010 mmol, 20%) were isolated in the same manner. Analytical Data for 1a ¹H NMR (300 MHz, CDCl₃): δ = 7.92 (d, J = 8.7 Hz, 2 H), 7.60–7.44 (m, 3 H), 3.68 (s, 3 H), 2.94–2.88 (m, 2 H), 2.52 (t, J = 7.5 Hz, 2 H), 2.23–2.13 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 173.40, 148.79–136.71, 132.06, 128.43, 128.24, 79.87, 51.85, 51.64, 33.87, 33.67, 22.37. IR (KBr): 2921, 2849, 1735, 699, 573, 550, 526, 482, 453 cm^–1. MS (MALDI): m/z calcd for C₇₂H₁₄O₂: 910.1; found: 910.1 [M]^–.

A few pieces of research for the synthesis of methanofullerenes using flow synthesis have been reported:
• 18a Seyler H, Wong WH, Holmes AB. J. Org. Chem. 2011; 76: 3551
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• 18b Rossi E, Carofiglio T, Venturi A, Ndobe A, Muccini M, Maggini M. Energy Environ. Sci. 2010; 4: 725
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