Chemical Papers 69 (3) 479–485 (2015) DOI: 10.1515/chempap-2015-0042 ORIGINAL PAPER Facile and direct synthesis of symmetrical acid anhydrides using a newly prepared powerful and efficient mixed reagent Hamed Rouhi-Saadabad, Batool Akhlaghinia* Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, 9177948974 Mashhad, Iran Received 31 March 2014; Revised 16 July 2014; Accepted 7 August 2014 An efficient mixed reagent for direct synthesis of symmetrical carboxylic anhydrides from car- boxylic acids has been prepared. Carboxylic acids are converted to anhydrides using triphenylphos- phine/trichloroisocyanuric acid under mild reaction conditions at room temperature. Short reaction time, excellent yields of products, low cost, availability of reagents, simple experimental procedure, and easy work-up of the products are the main advantages of the presented method. c 2014 Institute of Chemistry, Slovak Academy of Sciences Keywords: trichloroisocyanuric acid, triphenylphosphine, carboxylic acid, carboxylic anhydride, functional group transformation Introduction 1968; Jorba et al., 1990; Katritzky et al., 1992; Ke- shavamurthy et al., 1982; Kim et al., 2003; Kita et Among the most important classes of reagents, car- al., 1984, 1986; Mestres & Palomo, 1981; Newman & boxylic anhydrides are useful compounds either as Louge, 1971; Rinderknecht & Ma, 1964; Rinderknecht acylating agents or as intermediates in organic syn- & Guttenstein, 1967; Kocz et al., 1994; Sandler & thesis due to the high electrophilic character of their Karo, 1972), new and more convenient methods for carbonyl groups (Ogliaruso & Wolfe, 1991; Mariella & the synthesis of this class of compounds still pro- Brown, 1971; Shambhu & Digenis, 1974; Tamura et ceeds. Carboxylic anhydrides are usually prepared al., 1987a, 1987b; Holzapfel & Pettit, 1985; Fukuoka through a reaction of carboxylic acids with acylat- et al., 1987; Bryson & Roth,Author 1986). They are preferred ing or dehydratingcopy coupling agents, such as acid chlo- reactive acid derivatives for the preparation of amides, rides (Rambacher & Mäke, 1968), anhydrides (Sandler esters, and peptides (Ogliaruso & Wolfe, 1991; Tar- & Karo, 1972), mixed carboxylic–sulfonic anhydrides bel, 1969; Meienhofer & Gross, 1979). Mixed anhy- (Karimi Zarchi et al., 2010; Kazemi et al., 2004), drides are not suitable for many transacylation ap- triphenylphosphine (PPh3)/trichloroacetonitrile (Kim plications because the attack at the other acyl group & Jang, 2001), thionyl chloride (Fife & Zhang, 1986; leads to the formation of by-products; therefore, the Adduci & Ramirez, 1970; Kazemi & Kiasat, 2003; availability of symmetrical anhydrides is very impor- Kazemi et al., 2007), phosgene (Rinderknecht & Ma, tant in such reactions (Fife & Zhang, 1986). Although 1964; Rinderknecht & Guttenstein, 1967; Kocz et al., many reagents for the synthesis of carboxylic acid an- 1994), phosphorus pentoxide (Burton & Kaye, 1989; hydrides have been developed (Tamura et al., 1987b; Mestres & Palomo, 1981), isocyanate (Keshavamurthy Bryson & Roth, 1986; Fife & Zhang, 1986; Adduci et al., 1982), 1,3-dicyclohexylcarbodiimide (Chen & & Ramirez, 1970; Kazemi & Kiasat, 2003; Kazemi Benoiton, 1979; Hata et al., 1968), ketene (Kita et et al., 2007; Blankemeyer-Menge et al., 1990; Bur- al., 1986), ethoxyacetylene (Tamura et al., 1987b; ton & Kaye, 1989; Chen & Benoiton, 1979; Edman Bryson & Roth, 1986; Edman & Simmons, 1968; & Simmons, 1968; Eglinton et al., 1954; Hata et al., Eglinton et al., 1954; Kita et al., 1984, 1986; Mestres *Corresponding author, e-mail: [email protected] 480 H. Rouhi-Saadabad, B. Akhlaghinia/Chemical Papers 69 (3) 479–485 (2015) & Palomo, 1981; Newman & Louge, 1971), sulfated Experimental zirconia (Hu et al., 2011), triazine reagents (Kami´nski et al., 2004), 4,5-dichloro-2-[(4-nitrophenyl)sulphonyl] General pyridazin-3(2H )-one (Kim et al., 2003) as well as the reaction of carboxylate salts with powerful acy- The products were purified by column chromatog- lating agents, such as acid chlorides (Rambacher & raphy. Purity of the products was determined by TLC Mäke, 1968; Hajipour & Mazloumi, 2002), or acid an- on silica gel polygram STL G/UV 254 plates (60 hydrides (Sandler & Karo, 1972). Anhydrides have mesh; Merck, Germany). Melting points of the prod- been also prepared by the dehydration of carboxylic ucts were determined using an Electrothermal Type acids (Wallace & Copenhaver, 1941; Rammler & 9100 melting point apparatus (UK). FT-IR spectra Khorana, 1963; Liesen & Sukenik, 1987) or from were recorded on an Avatar 370 FT-IR Thermo Nico- acid chlorides (Serieys et al., 2008; Kim & Jang, let spectrometer (USA). NMR spectra for 13CNMR 2009). and 1H NMR were provided by Brucker Avance (Ger- However, many of these methods have major or many) 100 MHz and 400 MHz instruments in CDCl3 minor disadvantages, and the development of a new and using TMS as an internal standard. Chemical and efficient method for the synthesis of symmetrical shift is given in δ relative to TMS. Mass spectra were anhydrides is of current interest. recorded with a CH7A Varianmat Bremem instrument Trichloroisocyanuric acid (TCCA) in combination (Germany) at 70 eV; in m/z (rel. %). Silica gel in the with PPh3 has found widespread use in synthetic or- size of 40–73 m that used for column chromatography ganic chemistry (Sugimoto et al., 2012; Sugimoto & was purchased from Merck. All products are known Tanji, 2005; Hiegel et al., 1999). In continuation of compounds and they were characterized by IR spec- our search new methods of functional group trans- tral data and a comparison of their melting points formations (Iranpoor et al., 2004a, 2004b, 2004c, with those of authentic samples. Also, structures of 2005; Akhlaghinia, 2004, 2005a, 2005b; Akhlagh- some selected products were further confirmed by 1H inia & Pourali, 2004; Akhlaghinia & Samiei, 2009; NMR and 13C NMR spectroscopy and by mass spec- Akhlaghinia & Rouhi-Sadabad 2013; Rouhi-Sadabad trometry. & Akhlaghinia, 2014; Kiani et al., 2014), a direct, mild and efficient procedure for the synthesis of var- General procedure for potassium carboxylate ious symmetrical acid anhydrides from carboxylic (II) preparation acids using the prepared mixed reagent is reported here. Potassium hydroxide (112.2 mg, 2 mmol) was Table 1. Spectral data of selected prepared compounds Compound Spectral data −1 IIIa IR,ν ˜/cm : 3011 (CH-arom), 2843 (CH-aliph), 1789 and 1711 (C—O), 1607 (C—C) 1 H NMR (400 MHz, CDCl3), δ:8.13(d,4H,J = 8.0 Hz, H-arom), 7.01 (d, 4H, J = 8.0 Hz, H-arom), 3.93 (s, 6H, 2 × OCH3) 13 C NMR (100 MHz, CDCl3), δ: 164.6, 162.3, 132.9, 121.3, 114.2, 55.6 −1 IIIb IR,ν ˜/cm : 3023 (CH-arom), 2859 (CH-aliph), 1782 and 1713 (C—O), 1608 (C—C) 1 H NMR (100Author MHz, CDCl3), δ:7.75(s,4H,H-arom),7.26(s,2H,H-arom),2.40(s,12H,4 copy × CH3) + + MS, m/z (Ir/%): 282 (5) (M ) 149 (10) (M –(Me)2PhCO), 133 (100) ((Me)2PhCO), 105 (88) ((Me)2PhCO), 91 (30) (PhCH2) −1 IIIc IR,ν ˜/cm : 3059 (CH-arom), 2912 (CH-aliph), 1774 and 1713 (C—O), 1609 (C—C) 1 H NMR (400 MHz, CDCl3), δ:8.07(d,4H,J = 8.0 Hz, H-arom), 7.34 (d, 4H, J = 8.0 Hz, H-arom), 2.48 (s, 6H, 2 × CH3) 13 C NMR (100 MHz, CDCl 3), δ: 162.6, 145.6, 130.7, 129.6, 126.2, 21.9 −1 IIId IR,ν ˜/cm : 3064 (CH-arom), 1785 and 1724 (C—O), 1598 (C—C) 1 H NMR (400 MHz, CDCl3), δ:8.19(dt,4H,J =8.4Hz,J = 1.6 Hz, H-arom), 7.71 (tt, 2H, J =5.6Hz,J =1.6Hz, H-arom), 7.56 (td, 4H, J =7.2Hz,J =1.6Hz,H-arom) −1 IIIk IR,ν ˜/cm : 3023 (CH-arom), 2933 (CH-aliph), 1801 and 1736 (C—O), 1699 (C—C) 1 δ × — H NMR (400 MHz, CDCl3), : 7.38–7.20 (m, 20H, H-arom), 5.07 (s, 2H, 2 (Ph)2CH—C—O) 13 C NMR (100 MHz, CDCl3), δ: 167.6, 136.9, 128.8, 128.7, 127.7, 57.9 −1 IIIo IR,ν ˜/cm : 3066 and 3023 (CH-arom), 1768 and 1701 (C—O), 1631 (C—Cvinyl), 1450 (C—Carom) 1 H NMR (100 MHz, CDCl3), δ:7.75(d,2H,J = 16.0 Hz, PhCH—), 7.68–7.31 (m, 10H, H-arom), 6.52 (d, 2H, J = 16.0 Hz, PhCH—) + + MS, m/z (Ir/%): 278 (40) (M ) 149 (23) (M –PhCH—CHCO), 130 (100) (PhCH—CHCO), 103 (95) (PhCH—CH), 91 (75) (PhCH2), 77 (95) (Ph) H. Rouhi-Saadabad, B. Akhlaghinia/Chemical Papers 69 (3) 479–485 (2015) 481 Table 2. Conversion of benzoic acid to benzoic anhydride using the PPh3/TCCA/PhCOOK system under different reaction conditions a Entry Solvent PPh3/TCCA/PhCOOH/PhCOOK mole ratio Time/h Yield /% 1CH3CN 1:1:1:1 5 75 2CH3CN 1:1:1:1.5 3 80 3CH3CN 1:1:1:2 2 85 4CH3CN 1:1:1:2.5 2 85 5CH3CN 1:0.3:1:2.5 2 85 6CH3CN 1:0.3:1:2 2 80 7CH3CN 1:0.3:1:1 5 75 8CH3CN 1:0.3:0.5:1 4 70 b 9CH3CN 1:0.3:0.5:2 50 90 b 10 CH2Cl2 1:0.3:0.5:2 50 95 11 THF 1:0.3:0.5:2 1 90 12 EtOAc 1:0.3:0.5:2 70b 85 a) Yields refer to the isolated products; b) in min. added to a solution of carboxylic acid (2 mmol) in distilled water. The solution was stirred at room tem- perature for 30 min. Evaporation of the solvent gave crystals of potassium carboxylate salt. General procedure for benzoic anhydride (IIId) preparation Fig. 1. Direct synthesis of symmetric anhydrides (III )from ◦ → To a cold solution of TCCA (77.4 mg, 0.3 mmol) carboxylic acids (I ); i) PPh3, TCCA, CH2Cl2,0C r.t.; for substituent specification see Table 3.