English

• The privileged structure of amide functionality in organic compounds can be found in natural products, pharmaceuticals, agrochemicals, materials and polymers.^[1] Due to their many applications in academia and industry, secondary and tertiary amides have led to intense efforts to develop new methods for their synthesis.^[2] In contrast, researches on the synthesis of primary amides are relatively inactive due to the limitation of nitrogen sources. Traditionally, the transformation of carboxylic acid derivatives is the most commonly used method for the construction of the primary amide. For instance, nitrile hydrolysis, ^[3] ammonolysis of ester, anhydride or amide, ^[4] acid to carboxamide^[5] and acid chloride to primary amide^[6] (Scheme 1) with ammonia have been extensively studied.

  Scheme 1

  

  Scheme 1.  Some synthetic approaches to primary amides from carboxylic acid derivatives (TCT＝2, 4, 6-trichloro-1, 3, 5-triazine)

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  Among these, the amination of acid chloride is particularly valuable due to its high electrophilicity. In this context, gaseous ammonia and ammonium hydroxide had been used as amino-sources for these reactions. Although gaseous ammonia is among the largest volume and least expensive bulk chemical, reactions performed with gaseous ammonia often require tedious operation. On the other hand, aqueous ammonia is instability and its concentration decreases over time, especially in a warm environment, thus the amination with ammonium hydroxide is also not laboratory-friendly.^[7] Therefore, the identificating an alternative amine source for synthesis of primary amides is highly desirable.

  Ammonium salts, cheap and stable solids, have been utilized as nitrogen sources for the transition-metal catalyzed C—N bond formation and aminocarbonylation reactions.^[8] With these procedures, aryl halides can be converted into corresponding primary amines or amides. Moreover, these methods are also useful to incorporate ¹⁵N-labelled amine-moiety into the desired functional molecules since the ¹⁵N-labelled ammonium salts are cheap and easy to obtain.^[9] However, super stoichiometric amounts of strong base were generally required in all of these reaction systems to releasing NH₃ in situ from the ammonium salts, leading to wasteful by-product generation. Recently, we reported a Pd-catalyzed hydroaminocarbonylation of alkenes to primary amides with NH₄Cl in the absence of base.^[10a] The mechanistic studies disclosed that the solvent NMP (N-methyl pyrrolidone) played a key role for promoting the reaction, which not only served as solvent, but also functioned as base to capture the acid to promote the corresponding amination reaction. Inspired by these results, we envisioned that ammonium salts would be good surrogates of gaseous ammonia or aqueous ammonia for establishing an efficient amination reaction to prepare primary amides in the presence of NMP. Herein, we reported an efficient amidation reaction for the rapid synthesis of primary amides with ammonium salts as amine sources. The reaction was performed in the absence of base with NMP as solvent and acid-binding reagent. Moreover, amine hydrochloride salts could also be used as amine sources for the amidation reaction, affording to construct secondary and tertiary amides.

  1.   Results and discussion

  Initially, 3-phenylpropanoyl chloride (1a) and NH₄Cl (2a) were chosen as model substrates to optimize the reaction condition. As shown in Table 1, 95% isolated yield was obtained when the reaction was performed at 120 ℃ for 12 h with NMP as solvent (Table 1, Entry 1). To our delight, when we shortened the reaction time to 1 h, the same yield of the desired product 3aa was achieved (Table 1, Entry 2). Subsequently, other polar solvents containing amide group, which may also capture the released acid, were tested under the otherwise same reaction conditions. As expected, NMP was found to be the better solvent than N, N-dimethyl-formamide (DMF) and N, N-dimethylacetamide (DMA) (Table 1, Entries 3 and 4). It was interesting to find that the corresponding N, N-dimethyl-3-phenyl-propanamide was formed in more than 20% yield when DMF and DMA was served as solvent. The reason may attributed to that the C—N bond in DMF and DMA were easy to broken under the present reaction conditions. THF could not be utilized as solvent for the present reaction (Table 1, Entry 5), although the catalytic hydroaminocarbonylation reaction of olefins with amine hydrochloride salts developed by Beller and co-workers^[11] could be conducted in THF. Other etheric solvents including dioxane and anisole only obtained trace amounts of the amide product, suggesting that an amide-containing solvent was essential for facilitating the reaction by capturing the released HCl (Table 1, Entries 6 and 7). Moreover, toluene was not a suitable solvent for this reaction. With NMP as solvent, we proceeded to reduce the amounts of NH₄Cl and NMP to maximize the economy of the reaction. Unfortunately, the yields of 3aa decreased to 68%~77% when the loading of NH₄Cl or the volume NMP was decreased (Table 1, Entries 9~13). Finally, the impact of temperature was investigated. The results showed that 120 ℃ was essential for obtaining excellent yield (Table 1, Entries 14~19), although the reaction could be conducted at room temperature.

  Table 1

  

  Table 1.  Optimization of the reaction conditions^a

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  Entry	NH4Cl/equiv.	Solvent	T/℃	t/h	Yield/%
  1	2.0	NMP	120	12	95
  2	2.0	NMP	120	1	95
  3	2.0	DMF	120	1	56
  4	2.0	DMA	120	1	70
  5b	2.0	THF	120	1	Trace
  6b	2.0	1, 4-Dioxane	120	1	Trace
  7b	2.0	Anisole	120	1	Trace
  8b	2.0	Toluene	120	1	0
  9	1.5	NMP	120	1	77
  10	1.2	NMP	120	1	74
  11	1.2	NMP	120	12	77
  12c	2.0	NMP	120	1	68
  13c	2.0	NMP	120	12	74
  14	2.0	NMP	100	1	75
  15	2.0	NMP	100	12	81
  16	2.0	NMP	80	12	80
  17	2.0	NMP	60	12	63
  18	2.0	NMP	40	12	25
  19	2.0	NMP	25	12	23
  a Reaction conditions: 1a (1.0 mmol), solvent (5.0 mL), isolated yield. b The result of reaction was determined by GC-MS and GC analysis. c NMP (3 mL).

  Upon establishing the optimized reaction conditions for the present reaction, we next turned our attention to examining the scope of ammonium salts and alkylamine hydrochloride salts (Table 2). A number of ammonium salts [NH₄F, NH₄Br, NH₄I, (NH₄)₂CO₃, NH₄OAc and NH₄H-CO₃] were screened in place of ammonium chloride. When other ammonium halides used as amino sources, yields of the desired primary amide decreased to 62%~70% (Table 2, Entries 2~4). Other ammonium salts, such as (NH₄)₂-CO₃, NH₄OAc and NH₄HCO₃, could also be utilized as amine source for giving the desired amide 3aa in moderate yields (Table 2, Entries 5~7). Finally, the reaction of the acid chloride with aniline and diethylamine hydrochlorides yielded the corresponding secondary and tertiary amides in excellent isolated yields (Table 2, Entries 8 and 9).

  Table 2

  

  Table 2.  Substrate scope of the ammonium and amine salts^a

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  Entry	"N" source	Yield/%
  1	NH4Cl	95
  2	NH4F	70
  3	NH4Br	64
  4	NH4I	62
  5	(NH4)2CO3	63
  6	NH4OAc	54
  7	NH4HCO3	31
  8	PhNH2·HCl	96
  9	Et2NH·HCl	91
  a Reaction conditions: 1a (1.0 mmol), 2 (2.0 mmol), NMP (5.0 mL), 120 ℃, 1 h, isolated yield.

  After investigating the generality of ammonium and alkylamine hydrochloride salts, a series of acid chlorides were employed in the present amidation reaction with ammonium chloride. As shown in Table 3, the aromatic acid chlorides bearing electron-donating and -withdrawing groups on the phenyl ring gave the corresponding products 3ba~3ga in 53%~85% yields. In general, the substrates with electron-deficient aryl groups showed better reactivity than the corresponding electron-rich aromatic acid chlorides (3ea versus 3ca, 3da). For example, it is necessary to prolong reaction times for 4-methoxybenzoyl chloride to insure higher conversion. In addition, compared with the model substrate 1a, benzoyl chloride and phenylacetyl chloride showed lower conversion and selectivity (3ba, 3ia vs. 3aa). It is noteworthy that the reaction efficiency of 3- or 4-substituted benzamide was better than 2-substituted one (3ea, 3fa versus 3ga), which may be attributed to the steric hindrance effect on the reactivity. Particularly, 2-phenyl- butanoyl chloride reacted well to afford the desired primary amide 3ka in 79% yield. As expected, when the heteroaryl acid chloride, such as 2-thiopheneacetyl chloride, was subjected to this reaction, a good yield (78%) could be obtained. In addition, the reaction allowed for the introduction of typical functional groups. For example, cinnamamide 3ma and the ester-containing 3na could be obtained smoothly. Finally, aliphatic acid chlorides were compatible with this process under the optimized reaction conditions, furnishing the products in good yields (3oa and 3pa).

  Table 3

  

  Table 3.  Substrate scope of the acid chlorides^a

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  a Reaction conditions: 1 (1.0 mmol), 2a (2.0 mmol), NMP (5.0 mL), 120 ℃, 1 h, isolated yield. b 12 h.

  Finally, to demonstrate scalability, the reaction was per- formed on a preparative scale (10 mmol) with 3-phenylpro- panoyl chloride as a substrate. The target reaction proceeded smoothly at 120 ℃, affording the desired primary amide 3aa in 84% yield (Eq. 1).

  (1)

  2.   Conclusions

  In summary, a practical amidation reaction for synthesis of primary amides is presented, in which the simple NH₄Cl was identified as a practical and convenient amine source. The amidation reaction between acid chlorides and NH₄Cl could be performed in the absence of bases with NMP as solvent. The NMP utilized here play a key role for trapping HCl released from NH₄Cl, thereby driving the reaction in the absence of extra bases. Furthermore, the amidation reaction can be extended to other alkylamine hydrochloride salts to synthesize secondary and tertiary amides, thus providing a practical process for synthesis of amides from simple starting materials. Compared to many other approaches to primary amides, the present method avoids tedious operation of ammonia gas or aqueous ammonia, which provides a rapid and practical approach to primary amides.

  3.   Experimental

  3.1   General considerations

  NMR spectra were recorded on a BRUKER Avence Ⅲ 400 MHz spectrometers. Chemical shifts were reported in parts per million down field from TMS with the solvent resonance as the internal standard. High resolution mass spectra (HRMS) were recorded on a Bruker MicroTOF-QII mass (ESI). Melting points were measured using an X-4A melting point detector and uncorrected. GC analysis were performed on Agilent 7890B with Hp-5 column. GS-MS analysis were performed with an Agilent 7890B/5977B GC-MS system. All non-aqueous reactions and manipulations were using standard Schlenk techniques. All solvents before use were dried and degassed by standard methods and stored under nitrogen atmosphere. All reactions were monitored by thin layer chromatography (TLC) with silica gel-coated plates. Acid chlorides and ammonium salts were purchased from Energy Chemical, and were used without further purification unless otherwise stated.

  3.2   General procedure for the amidation of acid chlorides

  In a glove box, a mixture of acid chlorides 1 (1.0 mmol), ammonium salts 2 (2.0 mmol), and NMP (5.0 mL) was added into a 25 mL of flame-dried Young-type tube. After taken out from the glove box, the reaction mixture was stirred at 120 ℃ for an hour. When the reaction was finished, products were measured by GC-MS. Then solvent was removed under reduced pressure and the residue was purified by flash column chromatography on a silica gel column [V(petroleum ether):V(ethyl acetate)＝5:1~2:1] to give the desired product 3.

  3-Phenylpropanamide (3aa): white solid, 142.2 mg, 95% yield. m.p. 100~101 ℃ (lit.^[12a] 99.5~101 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.26~7.31 (m, 2H), 7.19~7.22 (m, 3H), 5.61 (br, 1H), 5.40 (br, 1H), 2.97 (t, J＝8.0 Hz, 2H), 2.53 (t, J＝7.6 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 174.7, 140.8, 128.7, 128.4, 126.4, 37.6, 31.5; HRMS (ESI) calcd for C₉H₁₁NONa [M+Na]⁺ 172.0733, found 172.0729.

  N-Phenyl-3-phenylpropanamide (3ah): white solid, 217.0 mg, 96% yield. m.p. 95~96 ℃ (lit.^[12b] 95~96 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.42~7.49 (m, 3H), 7.18~7.26 (m, 7H), 7.05~7.09 (m, 1H), 3.01 (t, J＝7.6 Hz, 2H), 2.62 (t, J＝7.6 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 170.7, 140.7, 137.8, 129.0, 128.6, 128.4, 126.4, 124.3, 120.1, 39.3, 31.6; HRMS (ESI) calcd for C₁₅H₁₅NONa [M+Na]⁺ 248.1046, found 248.1039.

  N, N-Diethyl-3-phenylpropanamide (3ai): yellow oil, 186.1 mg, 91% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.27~7.30 (m, 2H), 7.18~7.23 (m, 3H), 3.35 (q, J＝6.8 Hz, 2H), 3.19 (q, J＝7.2 Hz, 2H), 2.98 (t, J＝8 Hz, 2H), 2.59 (t, J＝7.6 Hz, 2H), 1.08~1.12 (m, 6H); ¹³C NMR (100 MHz, CDCl₃) δ: 171.4, 141.5, 128.5, 126.1, 41.9, 40.3, 35.1, 31.7, 14.3, 13.1; HRMS (ESI) calcd for C₁₃H₁₉NONa [M+Na]⁺ 228.1359, found 228.1347.

  Benzamide (3ba): white solid, 92.4 mg, 76% yield. m.p. 127~128 ℃ (lit.^[12c] 125~128 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 7.99 (br, 1H), 7.87~7.89 (m, 2H), 7.50~7.51 (m, 1H), 7.43~7.46 (m, 2H), 7.38 (br, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 168.0, 134.3, 131.3, 128.3, 127.5; HRMS (ESI) calcd for C₇H₇NONa [M+Na]⁺ found 144.0422.

  4-Methylbenzamide (3ca): white solid, 91.6 mg, 68% yield. m.p. 159~161 ℃ (lit.^[12c] 160~162 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 7.90 (br, 1H), 7.77 (d, J＝7.2 Hz, 2H), 7.24~7.28 (m, 3H), 2.34 (s, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 167.9, 141.2, 131.6, 128.9, 127.6, 21.1; HRMS (ESI) calcd for C₈H₉NONa [M+Na]⁺ 158.0576, found 158.0580.

  4-Mtehoxybenzamide (3da): white solid, 116.5 mg, 77% yield. m.p. 165~166 ℃ (lit.^[12c] (164~166 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 7.86~7.87 (m, 3H), 7.22 (br, 1H), 6.96 (d, J＝8.0 Hz, 2H), 3.79 (s, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 168.1, 162.1, 129.8, 126.9, 113.8, 55.7; HRMS (ESI) calcd for C₈H₉NO₂Na [M+Na]⁺ 174.0525, found 174.0529.

  4-Chlorobenzamide (3ea): white solid, 131.0 mg, 85% yield. m.p. 176~178 ℃ ((lit.^[12c] 173~176 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 8.06 (br, 1H), 7.88 (d, J＝8.4 Hz, 2H), 7.50 (d, J＝8.4 Hz, 2H), 7.47 (br, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 167.1, 136.3, 133.2, 129.6, 128.5; HRMS (ESI) calcd for C₇H₆ClNONa [M+Na] 178.0030, found 178.0025.

  3-Chlorobenzamide (3fa): white solid, 116.8 mg, 75% yield. m.p. 135~137 ℃ (lit.^[12c] 134~137 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 8.10 (s, 1H), 7.90 (s, 1H), 7.82 (d, J＝7.6 Hz, 1H), 7.47~7.60 (m, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 167.0, 136.7, 133.6, 131.5, 130.7, 127.8, 126.6; HRMS (ESI) calcd for C₇H₆ClNONa [M+Na]⁺ 178.0030, found 178.0038.

  2-Chlorobenzamide (3ga): white solid, 81.9 mg, 53% yield. m.p. 140~141 ℃ (lit.^[12c] 142~143 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.76~7.78 (m, 1H), 7.32~7.43 (m, 3H), 6.42 (br, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 168.5, 133.9, 131.9, 130.9, 130.7, 130.5, 127.3; HRMS (ESI) calcd for C₇H₆ClNONa [M+Na]⁺ 178.0030, found 178.0029.

  2-Naphthamide (3ha): white solid, 112.7 mg, 66% yield. m.p. 193~195 ℃ (lit.^[12c] 192~194 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 8.49 (s, 1H), 8.15 (s, 1H), 7.94~8.01 (m, 4H), 7.48~7.62 (m, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 168.1, 134.3, 132.3, 131.8, 129.0, 128.0, 127.9, 127.7 (2C), 126.8, 124.5; HRMS (ESI) calcd for C₁₁H₉NONa [M+Na]⁺ 194.0576, found 194.0576.

  2-Phenylacetamide (3ia): white solid, 99.9 mg, 74% yield. m.p. 158~159 ℃ (lit.^[12d] 157~158 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.34~7.38 (m, 2H), 7.26~7.31 (m, 3H), 5.92 (br, 1H), 5.45 (br, 1H), 3.58 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.7, 134.9, 129.4, 129.1, 127.4, 43.3; HRMS (ESI) calcd for C₈H₉NONa [M+Na]⁺ 158.0576, found 158.0580.

  2-(4-Fluorophenyl)acetamide (3ja): a white solid, 114.7 mg, 75% yield. m.p. 155~156 ℃ (lit.^[12e] 156~157 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 7.50 (br, 1H), 7.28~7.31 (m, 2H), 7.09~7.14 (m, 2H), 6.93 (br, 1H), 3.38 (s, 2H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 172.4, 162.4, 160.0, 132.8, 132.8, 131.1, 131.0, 115.1, 114.9, 41.4; ¹⁹F NMR (376 MHz, DMSO-d₆) δ: -117.0; HRMS (ESI) calcd for C₈H₈FNONa [M+Na]⁺ 176.0482, found 176.0486.

  2-Phenylbutanamide (3ka): white solid, 128.5 mg, 79% yield. m.p. 83~84 ℃ (lit.^[12f] 83.5~84.6 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 7.44 (br, 1H), 7.26~7.32 (m, 4H), 7.19~7.22 (m, 1H), 6.82 (br, 1H), 3.30 (t, J＝7.2 Hz, 1H), 1.90~1.97 (m, 1H), 1.55~1.62 (m, 1H), 0.81 (t, J＝7.2 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 174.7, 141.2, 128.1, 127.7, 126.5, 53.0, 26.1, 12.3; HRMS (ESI) calcd for C₁₀H₁₃NONa [M+Na]⁺ 186.0889, found 186.0885.

  2-(Thiophen-2-yl)acetamide (3la): yellow solid, 109.8 mg, 78% yield. m.p. 146~148 ℃ (lit.^[12g] 148 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 7.52 (br, 1H), 7.33~7.34 (m, 1H), 6.90~6.97 (m, 3H), 3.59 (s, 2H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 171.3, 137.8, 126.6, 126.1, 124.8, 36.4; HRMS (ESI) calcd for C₆H₇SNONa [M+Na]⁺ 164.0141, found 164.0141.

  (2E)-3-Phenyl-2-propenamide (3ma): white solid, 131.1 mg, 89% yield. m.p. 148~149 ℃ ((lit.^[12h] 147~149 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.63 (d, J＝15.6 Hz, 1H), 7.51~7.53 (m, 2H), 7.37~7.38 (m, 3H), 6.46 (d, J＝15.6 Hz, 1H), 5.88 (br, 1H), 5.72 (br, 1H); ¹³C NMR (100 MHz, CDCl₃) δ: 168.0, 142.7, 134.6, 130.1, 129.0, 128.1, 119.6; HRMS (ESI) calcd for C₉H₉NONa [M+Na]⁺ 170.0576, found 170.0575.

  Ethyl 4-amino-4-oxobutanoate (3na): white solid, 81.3 mg, 56% yield. m.p. 73~74 ℃ (lit.^[12i] 75 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 6.14 (br, 1H), 5.96 (br, 1H), 4.09~4.17 (m, 2H), 2.61~2.66 (m, 2H), 2.49~2.55 (m, 2H), 1.22~1.28 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 174.3, 173.1, 60.7, 30.2, 29.3, 14.1; HRMS (ESI) calcd for C₆H₁₁NO₃Na [M+Na]⁺ 168.0631, found 168.0627.

  Cyclohexanecarboxamide (3oa): white solid, 91.4 mg, 72% yield. m.p. 184~186 ℃ (lit.^[3d] 186~188 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 5.66 (br, 1H), 5.50 (br, 1H), 2.15 (tt, J＝11.6, 3.6 Hz, 1H), 1.89~1.92 (m, 2H), 1.79~1.82 (m, 2H), 1.66~1.70 (m, 1H), 1.38~1.47 (m, 2H), 1.22~1.34 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 178.9, 44.9, 29.8, 25.8, 25.8; HRMS (ESI) calcd for C₇H₁₃NONa [M+Na]⁺ 150.0889, found 150.0898.

  Decanamide (3pa): a white solid, 126.3 mg, 74% yield. m.p. 97~99 ℃(lit.^[12j] 96~98 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 7.23 (br, 1H), 6.68 (br, 1H), 2.01 (t, J＝7.6 Hz, 2H), 1.43~1.49 (m, 2H), 1.23 (m, 12H), 0.85 (t, J＝6.8 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 174.6, 35.3, 31.5, 29.1, 29.0, 28.9, 28.9, 25.3, 22.3, 14.1; HRMS (ESI) calcd for C₁₀H₂₁NONa [M+Na]⁺ 194.1515, found 194.1505.

  Supporting Information  ¹H NMR, ¹³C NMR and ¹⁹F NMR spectra of products. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn.

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  Scheme 1  Some synthetic approaches to primary amides from carboxylic acid derivatives (TCT＝2, 4, 6-trichloro-1, 3, 5-triazine)

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  Table 1.  Optimization of the reaction conditions^a

  Entry	NH4Cl/equiv.	Solvent	T/℃	t/h	Yield/%
  1	2.0	NMP	120	12	95
  2	2.0	NMP	120	1	95
  3	2.0	DMF	120	1	56
  4	2.0	DMA	120	1	70
  5b	2.0	THF	120	1	Trace
  6b	2.0	1, 4-Dioxane	120	1	Trace
  7b	2.0	Anisole	120	1	Trace
  8b	2.0	Toluene	120	1	0
  9	1.5	NMP	120	1	77
  10	1.2	NMP	120	1	74
  11	1.2	NMP	120	12	77
  12c	2.0	NMP	120	1	68
  13c	2.0	NMP	120	12	74
  14	2.0	NMP	100	1	75
  15	2.0	NMP	100	12	81
  16	2.0	NMP	80	12	80
  17	2.0	NMP	60	12	63
  18	2.0	NMP	40	12	25
  19	2.0	NMP	25	12	23
  a Reaction conditions: 1a (1.0 mmol), solvent (5.0 mL), isolated yield. b The result of reaction was determined by GC-MS and GC analysis. c NMP (3 mL).

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  Table 2.  Substrate scope of the ammonium and amine salts^a

  Entry	"N" source	Yield/%
  1	NH4Cl	95
  2	NH4F	70
  3	NH4Br	64
  4	NH4I	62
  5	(NH4)2CO3	63
  6	NH4OAc	54
  7	NH4HCO3	31
  8	PhNH2·HCl	96
  9	Et2NH·HCl	91
  a Reaction conditions: 1a (1.0 mmol), 2 (2.0 mmol), NMP (5.0 mL), 120 ℃, 1 h, isolated yield.

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  Table 3.  Substrate scope of the acid chlorides^a

  a Reaction conditions: 1 (1.0 mmol), 2a (2.0 mmol), NMP (5.0 mL), 120 ℃, 1 h, isolated yield. b 12 h.

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