Synthesis of Isonitriles from N-Substituted Formamides Using Triphenylphosphine and Iodine

Abstract

Treatment of N-substituted formamides with the reagent combination of triphenylphosphine and molecular iodine, in the presence of a tertiary amine, quickly produces the corresponding isocyanides in high yields under ambient conditions. The process employs readily available and low-cost reagents, a convenient synthetic procedure, and mild reaction conditions for the synthesis of various alkyl and aryl isocyanides.

Key words

isonitriles - formamides - dehydration - triphenylphosphine - iodine

Isonitriles are very important functionalities in organic synthesis due to the presence of an isocyano group with ambiphilic reactivity, which enables them to react with electrophiles, nucleophiles, and radicals.[1] The diverse range of transformations in which isocyanides participate have covered multicomponent reactions, metal-catalyzed isocyanide insertions and polymerizations.[2] Their important synthetic utility encompasses the synthesis of complex amides, polypeptides and glycopeptides of biological importance, the formation of substituted nitrogen-containing heterocycles, and the enantioselective construction of chiral heterocyclic compounds.[3]

Despite their wide range of utility in organic synthesis, the commercial supply of isonitriles is relatively limited, and only the simplest, unfunctionalized examples can be purchased. In most cases, access to isonitriles relies heavily on their preparation in the laboratory.[4] Therefore, more convenient methods for the preparation of isocyanides would provide a solution to this problem. Reliable preparative routes to these compounds mainly include the dehydration of formamides and the carbylamine reaction of amines;[5] the standard method involves the dehydration of formamides using acyl halides of group IV–VI elements in the presence of a base as the dehydrating agent.[5a] Among these dehydrating reagents, acyl halides of group IV elements, typically, phosgene and its related compounds, are particularly efficacious, but their application is limited due to their extreme toxicity and/or high costs.[6] At the same time, sulfonyl chlorides (which are acyl halides of group VI elements) with low toxicity, are also efficient dehydrating reagents in the presence of bases for the preparation of isocyanides from formamides, but these reagents are mainly used for the dehydration of N-alkyl-substituted formamides rather than the N-aryl-substituted counterparts.[7] Consequently, a system utilizing phosphoryl trichloride and an organic base is most commonly used.[3c] However, phosphoryl trichloride is a specific controlled hazardous substance under a series of legal regulations in China[8] and Japan.[9] For ordinary users in China, to obtain such reagents requires a purchase license for highly toxic chemicals issued by the local public security bureau. Therefore, efficient methods for the preparation of isocyanides employing readily accessible and cheap dehydrating reagents with low toxicity are attractive.[9] [10] In our previous research,[11] we found that N,N-dimethylformamide (DMF) was not suitable for the amidation of carboxylic acids promoted by trimethyl phosphite and iodine, whereas N-methyl-2-pyrrolidone (NMP) gave good results. During further examination of this observation, we found that the combination of triphenylphosphine and iodine was an efficient dehydrating system toward formamides, which could be used for the preparation of isocyanides under ambient conditions. This finding has led to the development of a practical method for convenient access to isonitriles by using inexpensive and readily available reagents of low toxicity.

We began our studies on the dehydration of formamides by using the combination of trimethyl phosphite and iodine (Table [1]). It was disclosed in previous research[11] that the in situ reaction of trialkyl phosphites and iodine formed alkyl iodophosphates, which were efficient activating reagents for the carboxyl group. However, the carboxyl­ activation did not occur in N,N-dimethylform­amide, whereas N-methyl-2-pyrrolidone and other common organic solvents gave good results.[11] We deduced that the deactivation of iodophosphates in N,N-dimethylformamide resulted from the reaction of the iodophosphate with the formamide. In addition, chlorophosphate compounds are known to be efficient reagents for the dehydration of formamides.[9] Thus, we hoped that the combination of trimethyl phosphite and iodine could be used as a dehydrating system for the preparation of isonitriles. When N-(4-methoxyphenyl)formamide (1a, R = OMe) or N-(4-bromophenyl)formamide (1b, R = Br) was employed as the substrate, the dehydration took place (Table [1], entries 1–4), but the conversions were incomplete, even with an excess of the dehydrating system (Table [1], entry 1). Improved results could not be obtained despite attempting several optimization experiments (Table [1], entries 2–6). We speculate that a possible reason behind this lack of reactivity lay in the fact that the alkyl iodophosphates were unstable in the present reaction system and were inclined to undergo rapid conversion into the inactive form(s), which led to incomplete conversion of the substrate. We then turned to the combination of triphenylphosphine and iodine as the reagents. Fortunately, this combination was very efficient (Table [1], entry 7). Interestingly, the dehydration of formamides promoted by triphenylphosphine and carbon tetrachloride (CCl₄) (halohydrocarbon solvent, 60 °C, 2.5 h) has been reported previously,[10c] but there are no related studies on the use of triphenylphosphine and iodine, although the latter is faster and more convenient (see below).

Table 1 Dehydration of Formamides Promoted by Phosphorus(III) Compounds^a

Entry	R	Conditionsb	Results
1c	4-MeO	1a/P(OMe)3/I2/Et3N = 1:4.5:4.5:13.5 (added in portions), ice-bath to r.t., 4 h	60%d
2	4-MeO	1a/P(OMe)3/I2/DIPA = 1:3:3:9 (added in portions), ice-bath to r.t., 4 h	partial conversione
3	4-MeO	1a/P(OEt)3/I2/DIPEA = 1:2:2:6, ice-bath to r.t., 2 h	partial conversione
4	4-Br	1b/P(OMe)3/I2/DIPEA = 1:2:2:6, ice-bath to 30 °C, 24 h	partial conversione
5	4-MeO	1a/P(OMe)3/I2/DMAP = 1:2:2:6, ice-bath to r.t., 2.5 h	no reactione
6	2-O2N	1c/P(OMe)3/I2/Et3N = 1:2:2:6, ice-bath to r.t., 12 h	no reactione
7c	4-MeO	1a/Ph3P/I2/Et3N = 1:1.5:1.5:3, r.t., 1 h	90%d

^a Formamide 1 (0.1 mmol) was used unless otherwise stated.

^b DIPA = diisopropylamine; DIPEA = N,N-diisopropylethylamine; DMAP = 4-(N,N-dimethylamino)pyridine.

^c Formamide 1a (1 mmol) was used.

^d Yield of isolated product.

^e Monitored by thin-layer chromatography (TLC).

Table 2 Optimization of the Reaction Conditions for the Dehydration of N-(4-Bromophenyl)formamide (1b)^a

Entry	Solvent	Base	Time	Yieldb
1	DMF	Et3N	5 h	trace
2c	THF	Et3N	5 h	80%
3c	CHCl3	Et3N	5 h	84%
4	toluene	Et3N	8 h	82%
5	DCE	Et3N	1 h	84%
6	CH2Cl2	Et3N	1 h	90%
7	CH2Cl2	DIPEA	1 h	87%
8	CH2Cl2	DIPA	1 h	69%
9	CH2Cl2	DBU	5 h	56%
10	CH2Cl2	DABCO	5 h	52%
11	CH2Cl2	DMAP	4 h	60%
12	CH2Cl2	KOH	5 h	no reaction
13	CH2Cl2	K2CO3	5 h	no reaction
14	CH2Cl2	Na2CO3	5 h	no reaction

^a Reaction conditions: 1b (1.0 mmol), Ph₃P (1.5 mmol), I₂ (1.5 mmol), base (3.0 mmol), solvent (3 mL), r.t. (unless otherwise stated).

^b Yield of isolated product.

^c Ph₃P (2.0 mmol), I₂ (2.0 mmol) and Et₃N (4.0 mmol) were employed.

We next examined the dehydration of N-(4-bromophenyl)formamide (1b) as a model system to optimize the reaction conditions. As shown in Table [2], the reactions in many of the common aprotic solvents, such as halohydrocarbons, ether and hydrocarbon, generated isonitrile 2b in good to excellent yields (Table [2], entries 2–6). However, when the dehydration was conducted in N,N-dimethylform­amide, only a trace amount of the product was observed (Table [2], entry 1). Among the tested solvents, dichloromethane gave the best performance (Table [2], entry 6). Therefore, dichloromethane was the solvent of choice for further investigations. Screening the base indicated that the dehydration reaction could be accomplished with common organic bases (Table [2], entries 6–11), but not with inorganic bases (Table [2], entries 12–14). Among the tested common organic bases, tertiary amines such as triethylamine and N,N-diisopropylethylamine proved to be superior (Table [2], entries 6 and 7 vs 8–11). Therefore, we established optimized conditions for the dehydration of formamides using the combination of triphenylphosphine and iodine for the preparation of isonitriles. The reaction was complete within one hour in dichloromethane using triphenylphosphine (1.5 equiv) and iodine (1.5 equiv) in the presence of triethylamine or N,N-diisopropylethylamine (3.0 equiv) at room temperature.

Under the optimized conditions, the substrate scope of our protocol was examined. The results, which are summarized in Scheme [1], demonstrate the generality of this method. A wide range of N-aryl- and N-alkyl-substituted formamides were quickly converted into the expected isonitriles in good to excellent yields. N-Aryl-substituted substrates containing an electron-withdrawing or an electron-donating group on the benzene ring gave good results. Various functional groups, such as ether, halo, nitro, ester, and alkoxycarbonylamino, were only slightly affected under these conditions. The positional isomers of substituted N-phenylformamides afforded the expected products in similar yields (Scheme [1], 2c vs 2i and 2j, and 2g vs 2h). Other o-mono and o,o-disubstituted N-phenylformamides also gave good results (2k and 2l), which indicated that steric effects adjacent to the formamido group did not significantly affect the progress of the reactions.

Scheme 1 Substrate scope for the preparation of isonitriles via the dehydration of formamides using the combination of triphenylphosphine and iodine. ^a Reagents and conditions: 1 (1 mmol), Ph₃P (1.5 mmol), I₂ (1.5 mmol), Et₃N (3 mmol), CH₂Cl₂ (3 mL), unless noted otherwise. The products were purified on silica gel. ^b Conditions as above, but with DIPEA (3 mmol) as the base instead of Et₃N

It should be noted that the dehydrations of both acid- and alkali-sensitive substrates produced the expected isonitriles in good yields, without the side-chain protecting groups being affected (2m and 2n). Due to the fact that most syntheses of isonitriles take place under alkaline conditions, related examples containing an alkali-sensitive group are rare.[9] [10a] Accordingly, Sureshbabu et al. reported that substrates containing an alkali-sensitive 9-fluorenylmethyloxycarbonylamino (FmocNH) moiety could be dehydrated using the Burgess reagent in dichloromethane at reflux temperature under neutral reaction conditions.[10a] They pointed out that the methods employing phosphorus(V) oxychloride/pyridine and triphenylphosphine/carbon tetrachloride did not produce satisfactory results. Compared with Sureshbabu’s method, our protocol did not require an expensive water-sensitive reagent, or a heating device, since our reactions were conducted at room temperature and used reagents that were stable toward moisture. Moreover, the combined cost of triphenylphosphine and iodine is less than 10% that of the Burgess reagent,[12] whereas the dehydrating ­efficiency of our approach was equivalent to that of Sureshbabu’s method. In addition, Kitano’s method for isonitrile synthesis gave good results with acid- and alkali-sensitive substrates using chlorophosphate compounds as the dehydrating reagent,[9] however, chlorophosphate compounds are not as stable as triphenylphosphine and iodine toward moisture, which is disadvantageous when storing reagents.

Gratifyingly, when analytical grade dichloromethane was employed (as received commercially), the reaction yields were of no significant difference. Moreover, purification of the products was very simple (column chromatography); even the purification of relatively highly polar 2m could be achieved easily using polar dichloromethane as the eluent. Removal of the triphenylphosphine oxide by-product from reactions which employ triphenylphosphine is often troublesome. However, in our case, all the target compounds were easily separated from polar triphenylphosphine oxide due to the fact that isocyanides are of relatively low polarity.

To establish the mechanism of the current process we used ³¹P NMR spectroscopy to monitor the progress of the reaction. As shown in Scheme [2], the ³¹P NMR signal of triphenylphosphine appeared at δ = –4.25 in deuterochloroform. When an equimolar amount of iodine was added to the solution, a signal appeared at δ = –16.4, which was due to the ‘spoke’ species A.[13a] When formamide 1b was introduced into the mixture, this signal was slightly shifted to δ = –14.0, and a new minor signal appeared at δ = 43.8. Bricklebank et al. investigated the reaction of tri­phenylphosphine with iodine in detail in deuterochloroform; they revealed that the chemical shift of the ionic structure, [Ph₃PI]⁺, appeared at δ = 44.8 and was mostly not affected by its counterions.[13b] Thus, we speculated that the signal at δ = 43.8 resulted from complex B or from similar structures, in which the key structural feature was a [Ph₃PI]⁺ cation, and the addition of formamide 1 accelerated the ionization of the ‘spoke’ species A to form the ionic complex B.[13b] [c] After triethylamine had been added, the signal at δ = –14.0 shifted to δ = –16.5, and that at δ = 43.8 quickly disappeared. At the same time, a new resonance appeared at δ = 29.8, which was assigned to triphenylphosphine oxide. The addition of triethylamine gradually weakened the intensity of the signal at δ = –16.5 and simultaneously led to an increase in the intensity of the signal at δ = 29.8. After five hours at room temperature, no further perceptible change was observed in the ³¹P NMR spectrum. This observation was consistent with the consumption of formamide 1b along with the formation of isonitrile 2b and triphenylphosphine oxide, which was monitored by TLC. Thus, the formation of isonitrile 2b was presumed to occur via α-elimination of a proton and triphenylphosphine oxide from intermediate phosphonium salt C with the aid of a base, similar to the triphenylphosphine/carbon tetrachloride mediated mechanism proposed by Appel et al.[10c] Bae and co-workers investigated the synthesis of O ⁶-(benzotriazol-1-yl)inosine nucleosides promoted by the reagent combination of triphenylphosphine and iodine. They proved that the signal due to the nucleoside phosphonium salt appeared at δ = 66.2.[13d] However, the ³¹P NMR spectroscopic signal of phosphonium salt intermediate C was not observed in our system, which is most possibly due to its low concentration.

Scheme 2 Postulated pathway for the synthesis of an isonitrile mediated by triphenylphosphine

In conclusion, the dehydration of various N-substituted formamides with the reagent combination of triphenylphosphine and molecular iodine afforded smoothly the corresponding isocyanides in high yields. Electronic effects and steric hindrance resulting from substituents on the aromatic ring did not affect significantly the progress of these reactions. Both acid- and alkali-sensitive substrates produced the expected isonitriles in good yields without the side-chain protecting groups being affected. We believe that this method represents a mild, convenient, efficient and cost-effective route to prepare various isocyanides.

Commercially available reagents were used as received. Formamides 1a, 1b, 1d, 1g and 1h were prepared using the direct formic acid amidation method,[14a] formamides 1c, 1i and 1j were obtained using ZnO-catalyzed formic acid amidation,[14b] formamides 1e, 1f and 1l were synthesized via ethyl formate amidation,[9] and formamide 1k was prepared using the mixed anhydride method.[14c] Formamides 1m and 1n were prepared according to the literature.[14d] All solvents for chromatographic separations were distilled before use. Petroleum ether (PE) refers to the fraction boiling in the 60–90 °C range. Column chromatography was carried out using Haiyang 200–300 mesh silica gel (Qingdao, China). FT-IR spectra (wavelength range = 4000–400 cm^–1) were obtained using a Bruker TENSOR-27 FT-IR Spectrometer (Bruker). Samples were prepared as KBr pellets. ¹H and ¹³C NMR spectra were recorded on Bruker 300 MHz or 600 MHz spectrometers at 293 K. Chemical shifts (δ) were internally referenced to the residual solvent signals (CDCl₃ at 7.26 ppm for ¹H, and at 77.00 ppm for ¹³C) relative to tetramethylsilane. Data are reported as follows: multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad, br s = broad singlet), coupling constant(s) (Hz), integration. The structures of all the known products were confirmed by comparison with the spectroscopic data of authentic samples. The yields in Table [2] and Scheme [1] refer to those of isolated products (average of two runs).

Isocyanides 2; General Procedure

To a stirred solution of formamide 1 (1.0 mmol) and I₂ (381 mg, 1.5 mmol) in CH₂Cl₂ (3 mL) was added Ph₃P (394 mg, 1.5 mmol), followed by the dropwise addition of Et₃N (415 μL, 301 mg, 3 mmol). The mixture was stirred at r.t. until the consumption of the form­amide was complete (TLC monitoring, typically 1 h), and then diluted with CH₂Cl₂ (10 mL) and washed with ice-cold sat. aq Na₂S₂O₃ solution (10 mL). The aq phase was extracted with CH₂Cl₂ (2 × 10 mL). Each portion of the organic phase was sequentially washed with deionized H₂O (10 mL) and brine (10 mL), dried over anhydrous Na₂SO₄, and filtered. The combined organic phase was concentrated under reduced pressure and purified by column chromatography (silica gel, typically PE as the eluent) to give the corresponding isocyanide 2. Any deviations from this procedure are noted in Table [2] and Scheme [1].

4-Methoxyphenyl Isocyanide (2a)[10b]

Yield: 119 mg (90%); brown oil.

IR (KBr): 2125 (s) cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.19 (d, J = 8.7 Hz, 2 H), 6.78 (d, J = 8.9 Hz, 2 H), 3.72 (s, 3 H).

¹³C NMR (75 MHz, CDCl₃): δ = 162.4 (t, J = 5.8 Hz), 159.4, 127.2, 118.8 (t, J = 14.9 Hz), 114.1, 55.1.

4-Bromophenyl Isocyanide (2b)[15a]

Yield: 164 mg (90%); white amorphous solid.

IR (KBr): 2125 (m) cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.53 (d, J = 8.6 Hz, 2 H), 7.25 (d, J = 8.4 Hz, 2 H).

¹³C NMR (75 MHz, CDCl₃): δ = 165.8 (t, J = 6.2 Hz), 132.6, 127.8, 125.4 (t, J = 13.8 Hz), 123.3.

2-Nitrophenyl Isocyanide (2c)[15b]

Yield: 124 mg (84%); yellow amorphous solid.

IR (KBr): 2125 (w) cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 8.11 (dd, J = 1.4 Hz, 8.2 Hz, 1 H), 7.73 (dt, J = 1.3 Hz, 7.7 Hz, 1 H), 7.67–7.57 (m, 2 H).

¹³C NMR (75 MHz, CDCl₃): δ = 173.8 (br), 144.1 (br), 134.2, 130.1, 129.8, 125.5, 120.9 (t, J = 16.9 Hz).

4-Methylphenyl Isocyanide (2d)[15c]

Yield: 105 mg (90%); brown oil.

IR (KBr): 2125 (s) cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.25 (d, J = 8.2 Hz, 2 H), 7.17 (d, J = 8.2 Hz, 2 H), 2.37 (s, 3 H).

¹³C NMR (151 MHz, CDCl₃): δ = 163.5 (t, J = 5.6 Hz), 139.6, 129.9, 126.1, 124.1 (t, J = 13.5 Hz), 21.2.

4-Benzyloxyphenyl Isocyanide (2e)[9]

Yield: 174 mg (83%); pale yellow amorphous solid.

IR (KBr): 2125 (s) cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.45–7.38 (m, 4 H), 7.38–7.33 (m, 1 H), 7.31 (d, J = 8.9 Hz, 2 H), 6.94 (dt, J = 8.9 Hz, 2.6 Hz, 2 H), 5.08 (s, 2 H).

¹³C NMR (150.9 MHz, CDCl₃): δ = 163.0 (br), 159.0, 136.1, 128.7, 128.3, 127.7, 127.4, 119.8 (t, J = 13.4 Hz), 115.5, 70.4.

Ethyl 4-Isocyanobenzoate (2f)[15a]

Yield: 151 mg (86%); pale brown amorphous solid.

IR (KBr): 2128 (s) cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 8.07 (dt, J = 8.7 Hz, 2.0 Hz, 2 H), 7.43 (d, J = 8.6 Hz, 2 H), 4.39 (q, J = 7.1 Hz, 2 H), 1.39 (t, J = 7.1 Hz, 3 H).

¹³C NMR (151 MHz, CDCl₃): δ = 167.2 (br), 164.9, 131.3, 130.8, 129.9 (t, J = 13.1 Hz), 126.4, 61.5, 14.2.

4-Chlorophenyl Isocyanide (2g)[15a]

Yield: 117 mg (85%); white solid.

IR (KBr): 2128 (s) cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 7.41–7.26 (m, 4 H).

¹³C NMR (75 MHz, CDCl₃): δ = 165.4 (br), 135.2, 129.6, 127.5, 124.8 (t, J = 13.3 Hz).

2-Chlorophenyl Isocyanide (2h)[15d]

Yield: 118 mg (86%); white solid.

¹H NMR (300 MHz, CDCl₃): δ = 7.47 (dd, J = 7.9 Hz, 1.3 Hz, 1 H), 7.42 (dd, J = 7.6 Hz, 1.3 Hz, 1 H), 7.39–7.26 (m, 2 H).

¹³C NMR (75 MHz, CDCl₃): δ = 168.9 (br), 130.6, 130.2, 130.0, 127.8, 127.4, 125.3 (t, J = 15.4 Hz).

4-Nitrophenyl Isocyanide (2i)[10b]

Yield: 117 mg (79%); white amorphous solid.

IR (KBr): 2130 (s) cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 8.29 (d, J = 8.9 Hz, 2 H), 7.58 (d, J = 8.8 Hz, 2 H).

¹³C NMR (151 MHz, CDCl₃): δ = 170.0 (br), 147.6, 131.3 (t, J = 12.0 Hz), 127.5, 125.0.

3-Nitrophenyl Isocyanide (2j)[15d]

Yield: 127 mg (86%); white amorphous solid.

IR (KBr): 2142 (m) cm^–1.

¹H NMR (300 MHz, CDCl₃): δ = 8.28 (d, J = 8.1 Hz, 1 H), 8.22 (s, 1 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.66 (t, J = 8.0 Hz, 1 H).

¹³C NMR (75 MHz, CDCl₃): δ = 167.6 (br), 148.2, 132.1, 130.6, 127.1 (t, J = 11.9 Hz), 124.1, 121.5.

2,6-Dimethylphenyl Isocyanide (2k)[14c]

Yield: 108 mg (82%); white amorphous solid.

IR (KBr): 2122 (s) cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.18 (t, J = 7.6 Hz, 1 H), 7.09 (d, J = 7.6 Hz, 2 H), 2.42 (s, 6 H).

¹³C NMR (151 MHz, CDCl₃): δ = 167.8 (br), 134.8, 128.6, 127.7, 126.7 (t, J = 12.9 Hz), 18.8.

2-Methoxy-4-nitrophenyl Isocyanide (2l)[9]

Yield: 146 mg (82%); light yellow amorphous solid.

¹H NMR (300 MHz, CDCl₃): δ = 7.86 (dd, J = 8.9 Hz, 2.1 Hz, 1 H), 7.84 (br s, 1 H), 7.51 (d, J = 8.4 Hz, 1 H), 4.05 (s, 3 H).

¹³C NMR (151 MHz, CDCl₃): δ = 173.0 (br s), 155.5, 148.4, 128.1, 121.1 (t, J = 14.4 Hz), 115.8, 107.1, 56.8.

tert-Butyl (2-Isocyanoethyl)carbamate (2m)[15e]

The product was purified by column chromatography on silica gel [PE→PE–EtOAc, 80:20 (v/v)].

Yield: 151 mg (89%); light yellow oil.

IR (KBr): 2150 (s) cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 5.15 (s, 1 H), 3.49 (br s, 2 H), 3.34 (br s, 2 H), 1.42 (s, 9 H).

¹³C NMR (151 MHz, CDCl₃): δ = 157.4 (br), 155.6, 80.0, 41.9 (t, J = 5.9 Hz), 39.7, 28.2.

(9H-Fluoren-9-yl)methyl (2-Isocyanoethyl)carbamate (2n)[10a]

The product was purified by column chromatography on silica gel (PE→CH₂Cl₂).

Yield: 228 mg (78%); white amorphous solid.

IR (KBr): 2152 (m) cm^–1.

¹H NMR (600 MHz, CDCl₃): δ = 7.78 (d, J = 7.5 Hz, 2 H), 7.59 (d, J = 7.4 Hz, 2 H), 7.41 (t, J = 7.4 Hz, 2 H), 7.33 (t, J = 7.4 Hz, 2 H), 5.42 (s, 1 H), 4.44 (d, J = 6.8 Hz, 2 H), 4.22 (t, J = 6.8 Hz, 1 H), 3.51 (t, J = 4.6 Hz, 2 H), 3.44–3.39 (m, 2 H).

¹³C NMR (151 MHz, CDCl₃): δ = 157.7 (t, J = 11.3 Hz), 156.2, 143.6, 141.2, 127.7, 127.0, 124.9, 119.9, 66.9, 47.1, 41.7 (t, J = 5.3 Hz), 40.1.

Acknowledgment

The authors thank the National Natural Science Foundation of China (No. 20971105) and the Fundamental Research Funds for the Central Universities (XDJK2012B011) for financial support.

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