Access to ( E )- N ′-benzylidene- N -(2-(phenylsulfonyl)ethyl)acetohydrazide via C(sp 2 )−H activation and reduction of ( E )- N ′-benzylideneacetohydrazide with (vinylsulfonyl)benzene

Abstract

A novel route for C(sp³)-N bond formation via C(sp²)−H activation/reduction by metal-free which uses (E)-N′-benzylideneacetohydrazide and (vinylsulfonyl)benzene to synthesize derivatives of (E)-N′-benzylidene-N-(2-(phenylsulfonyl)ethyl)acetohydrazide has been reported. This methodology features good functional group tolerance and convenient operation. In addition, it uses inexpensive and insensitive chemical reagents as raw materials and provides an atom- and efficient method for the preparation of (E)-N′-benzylidene-N-(2-(phenylsulfonyl)ethyl)acetohydrazides.

Keywords

(vinylsulfonyl)benzene carboxylic anhydride C-H activation

A novel route for C(sp³)-N bond formation via C(sp²)−H activation/reduction by metal-free which uses (E)-N′-Benzylideneacetohydrazide and (vinylsulfonyl)benzene to synthesize derivatives of (E)-N′-Benzylidene-N-(2-(phenylsulfonyl)ethyl)acetohydrazide have been reported.

C−N bond formation is significant and plays an important role in synthetic chemistry because amines and their derivatives are privileged structures for alkaloids, pharmaceuticals, and organic materials.^1–3 Many methods to construct C−N bonds have been reported, such as reductive amination, nucleophilic amination, electrophilic amination, hydroamination, and cross-coupling reactions such as Ullmann coupling, Chan−Lam coupling, and Buchwald–Hartwig coupling which catalyzed by transition metal.⁴ More recently, many strategies for C−N bond formation through C–H bond activation have been gradually developed. For example, Kilian Muñiz’s group reported a method for an intermolecular C(sp³)H amidation via palladium-catalyzed.⁵ And Alabugin developed a strategy that builds a C−N bond through C(sp³)−H aminations under metal-free conditions with unprotected anilines.⁶ Also, Wang’s group has summarized several examples to construct C−N bonds by copper-catalyzed C−H functionalization.⁷ Similarly, C−N bonds building between C(sp²)−H and N(sp²)−H bonds also have attracted the attention of synthetic chemists. For example, Cho’s group⁸ has developed an efficient strategy to produce the corresponding nitrogen-containing scaffolds through the tandem reaction of 2-aminoazoles and 2-(2-bromoaryl)indoles promoted by CuI and base under microwave irradiation (Scheme 1a). Next, Wang and co-workers⁹ delivered a method to synthesize isoquinolinones and pyridinones through palladium-catalyzed regioselective C−H functionalization/annulation reaction of amides and allylbenzenes (Scheme 1b). Besides, a strategy for photochemical C−N coupling was reported from 2-([1,1’-biphenyl]-2-yl)-1H-benzo[d]imidazoles¹⁰ (Scheme 1c) or pyrazoles¹¹ (Scheme 1d) with arenes. Notably, an unprecedented approach of C(sp²)−N bond formation through deacetylation/intramolecular aryl migration under metal-free conditions was delivered by Han’s group¹² (Scheme 1e). In comparison with C(sp²)−N bond formation, metal-free C(sp³)−N bond building from C(sp²)−H and N(sp²)−H bonds is more attractive and challenging. Herein, we describe the strategy of C(sp³)−N bond formation via C(sp²)−H activation/reduction from (vinylsulfonyl)benzene with (E)-N′-benzylideneacetohydrazide under metal-free conditions. This methodology features good functional group tolerance and convenient operation (Scheme 1f).

Scheme 1.

Many C–N bond formation between C(sp²) and N(sp²)−H bonds.

First, various solvents were screened, and the best yield of 75% was obtained when using CH₃CN as a solvent (Table 1, entries 1–6). A number of bases, such as Et₃N, DBU, KOH, and C₅H₅N, were also tested, and all of the yields were poor (Table 1, entries 7–10). After this, the screening of different additives such as Et₃N • 3HCl, C₅H₅N • HCl, and C₅H₅N • HF was performed at standard conditions, but the yields of 3a were lower than Et₃N • 3HF (Table 1, entries 11–13). The yield of 3a slightly decreased when the temperature was reduced to 100 °C or increased to 120 °C (Table 1, entries 14 and 15). On the contrary, Et₃N • 3HF was important for this reaction (Table 1, entries 16 and 17). Similarly, when shortening or extending the reaction time, the yield of the product was slightly reduced (Table 1, entry 18). Also, the yield was good when under an O₂ atmosphere but had a lower yield under an N₂ atmosphere (Table 1, entry 19).

Table 1.

Optimization of the conditions for C–N coupling.^a,b

Entry	Solvent	Base	Additive	Temp (°C)	Yield (%)

1	DMF	Cs₂CO₃	Et₃N • 3 HF	110	33
2	CH₃CN	Cs₂CO₃	Et₃N • 3 HF	110	75
3	CH₃OH	Cs₂CO₃	Et₃N • 3 HF	110	48
4	DCE	Cs₂CO₃	Et₃N • 3 HF	110	nr
5	DMSO	Cs₂CO₃	Et₃N • 3 HF	110	70
6	Acetone	Cs₂CO₃	Et₃N • 3 HF	110	30
7	CH₃CN	Et₃N	Et₃N • 3 HF	110	24
8	CH₃CN	DBU	Et₃N • 3 HF	110	50
9	CH₃CN	KOH	Et₃N • 3 HF	110	12
10	CH₃CN	C₅H₅N	Et₃N • 3 HF	110	32
11	CH₃CN	Cs₂CO₃	Et₃N • HCl	110	34
12	CH₃CN	Cs₂CO₃	C₅H₅N • HCl	110	11
13	CH₃CN	Cs₂CO₃	C₅H₅N • HF	110	51
14	CH₃CN	Cs₂CO₃	Et₃N • 3 HF	100	68
15	CH₃CN	Cs₂CO₃	Et₃N • 3 HF	120	70
16	CH₃CN	Cs₂CO₃	–	110	nr
17	CH₃CN	Cs₂CO₃	Et₃N • 3 HF	110	19^c, 71^d
18	CH₃CN	Cs₂CO₃	Et₃N • 3 HF	110	69^e, 74 ^f
19	CH₃CN	Cs₂CO₃	Et₃N • 3 HF	110	69^g, 41^h

Reaction conditions: 1a (0.2 mmol), (vinylsulfonyl)benzene 2 (0.4 mmol), base (2.0 equiv.), additive (3.0 equiv.) and solvent (2.0 mL), air atmosphere, sealed tube, 110 °C for 12 h.

Isolated yields.

Et₃N • 3 HF (2.0 equiv.).

Et₃N • 3 HF (4.0 equiv.).

8 h.

16 h.

O_2.

N_2.

The results of coupling/reduction reactions between various (E)-N′-benzylideneacetohydrazides 1 and (vinylsulfonyl)benzene 2 under the optimized conditions (Table 1, entry 2) are shown in Table 2. Para-substituents with electron-donating groups(3b and c), halogen substituents (3d–f), and withdrawing character (3g) were well tolerated. Furthermore, meta-substituents such as 3-CH₃ (3i), 3-OMe (3j), 3-F (3k), 3-Br (3l), and 3-CN (3m) produced the products in good yields. Ortho-substituents with electron-donating groups (3o–q) provided the (E)-N′-benzylidene-N-(2- (phenylsulfonyl)ethyl)acetohydrazide in good yields. However, ortho-substituents with halogens (3r–t) and electron-withdrawing groups (3u) all did not provide the corresponding target compounds. And, all of the nitro- groups such as 4-NO₂ (3h), 3-NO₂ (3n), and 2-NO₂ (3v) could not afford the corresponding products. Similarly, (E)-N′-(2,4-dimethylbenzylidene)acetohydrazide (3w) also afforded the corresponding product in synthetically useful yield (61%). In addition, 2-furaldehyde (3x) gave a 53% yield, respectively. Fortunately, under standard conditions, when the acetyl group was replaced by benzoyl (3z) had a 64% yield but benzenesulfonyl (3aa) or methyl (3ab), we did not get the expected compound.

Table 2.

Synthesis of (E)-N′-benzylidene-N-(2-(phenylsulfonyl) ethyl)acetohydrazides.^a,b

Reaction conditions: 1 (0.2 mmol), (vinylsulfonyl)benzene 2 (0.4 mmol), Cs₂CO₃ (2.0 equiv.), Et₃N • 3 HF (3.0 equiv.) and MeCN (2.0 mL), air, sealed tube, 110 °C for 12 h.

Isolated yields.

Replaced the MeCN with DMSO.

To show the synthetic utility of this procedure, we next performed a gram-scale reaction with 10 mmol of 1a under standard reaction conditions, which was obtained in 54% yield (Scheme 2).

Scheme 2.

Synthetic applications.

Next, to learn about this reaction mechanism, a series of control experiments were conducted. First, it was known that no target product (4a or 4b) was produced when using allylbenzene (2aa) (Scheme 3a) or styrene (2ab) (Scheme 3b) to replace (vinylsulfonyl)benzene (2). These results indicate that (vinylsulfonyl)benzene is crucial for facilitating this reaction. Furthermore, employing N′-phenylacetohydrazide (1aa) (Scheme 3c) or N-benzylacetamide (1ab) (Scheme 3d) or N-phenylacetamide (1ac) (Scheme 3e) as raw material which replaces (E)-N′-benzylideneacetohydrazide (1a), we have not detected 4c or 4d or 4e. This suggested that the hydrazone group is crucial in this reaction process.

Scheme 3.

Control experiments.

According to the previous related studies^13–17 and the above-mentioned results, a plausible mechanism of C(sp²)-H activation/reduction is depicted in Scheme 4. First, Et₃N • 3 HF reacted with Cs₂CO₃ to produce H₂CO₃ which can release a proton, and then a proton reacted with 1a to yield the intermediate (A). Second, intermediate (A) released a proton under the action of alkali to generate intermediate (B) which reacted with compound 2 to produce intermediate (C). And, intermediate (C) obtained a proton to generate intermediate (D). After this, the desired product 3a was afforded when the intermediate (D) released a proton with the help of alkali.

Scheme 4.

Postulated reaction mechanism.

In conclusion, we have developed a method of C(sp³)-N bond formation by metal-free via C(sp²)−H activation/reduction from (vinylsulfonyl)benzene and (E)-N′-Benzylideneacetohydrazide. This methodology not only provides valuable strategies to syntheses of various (E)-N′-benzylidene-N-(2-(phenylsulfonyl)ethyl)acetohydrazides under mild reaction conditions, but also the materials are commercially available. Notably, the protocol provides progress in metal-free, atom- and step-economical nature which is considered as environmental friendliness and operational simplicity.

Experimental section

General information

All of the chemicals were obtained commercially and did not purify before use. The ¹H NMR and ¹³C NMR spectra were recorded on a Bruker Avance II 400 spectrometer. All products were purified by silica gel column chromatography (200–300 mesh) and using ethyl acetate and petroleum ether (60–90 °C) as solvent.

General procedure to the synthesis of (E)-N′-benzylidene-N-(2-(phenylsulfonyl)ethyl)acetohydrazides

A mixture of the (E)-N′-benzylideneacetohydrazide (1a) (32.4 mg, 0.2 mmol), (vinylsulfonyl)benzene (2) (67.2 mg, 0.4 mmol), Cs₂CO₃ (0.4 mmol), Et₃N ^• 3 HF (0.6 mmol), and MeCN (2.0 mL) in a sealed tube was stirred at 110 °C for 12 h. After the reaction, the mixture was cooled down to room temperature, the solvent was removed in vacuum, and the residue was purified by silica gel column chromatography to obtain the product.

(E)-N′-benzylidene-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3a)

White solid, 49.6 mg, 75% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, DMSO-d₆) δ 8.00–7.92 (m, 2H), 7.84–7.77 (m, 1H), 7.75 (s, 1H), 7.69 (d, J = 6.8 Hz, 1H), 7.69–7.65 (m, 3H), 7.48–7.35 (m, 3H), 4.25 (t, J = 7.1 Hz, 2H), 3.71–3.62 (m, 2H), 2.21 (s, 3H). ¹³C NMR (101 MHz, DMSO-d₆) δ 171.84, 140.24, 139.30, 135.04, 134.54, 130.14, 129.92, 129.18, 128.20, 127.45, 50.63, 40.32, 33.72, 21.82. HRMS (ESI+): Calculated for C₁₇H₁₈N₂O₃S, [M+Na]⁺ 331.1111. Found 331.1119.

(E)-N′-(4-methylbenzylidene)-N-(2-(phenylsulfonyl)ethyl) acetohydrazide (3b)

White solid, 48.3 mg, 70% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, DMSO-d₆) δ 8.00–7.92 (m, 2H), 7.86–7.76 (m, 1H), 7.70 (s, 1H), 7.70–7.64 (m, 2H), 7.60–7.50 (m, 2H), 7.25 (d, J = 8.0 Hz, 2H), 4.30–4.16 (m, 2H), 3.72–3.59 (m, 2H), 2.34 (s, 3H), 2.20 (s, 3H). ¹³C NMR (101 MHz, DMSO-d₆) δ 171.76, 140.26, 139.85, 139.28, 134.54, 132.33, 129.92, 129.77, 128.20, 127.42, 50.68, 33.71, 21.80, 21.48. HRMS (ESI+): Calculated for C₁₈H₂₀N₂O₃S, [M+Na]⁺ 367.1092. Found 367.1096.

(E)-N′-(4-(tert-butyl)benzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3c)

White solid, 51.7 mg, 67% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, DMSO-d₆) δ 7.95 (dd, J = 5.2, 3.3 Hz, 2H), 7.83–7.75 (m, 1H), 7.68 (dd, J = 10.7, 4.9 Hz, 3H), 7.58 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.5 Hz, 2H), 4.29–4.15 (m, 2H), 3.67–3.56 (m, 2H), 2.19 (s, 3H), 1.29 (s, 9H). ¹³C NMR (101 MHz, DMSO-d₆) δ 171.76, 152.94, 140.23, 139.29, 134.55, 132.35, 129.93, 128.20, 127.26, 125.96, 50.60, 35.03, 33.71, 31.45, 21.79. HRMS (ESI+): Calculated for C₂₁H₂₆N₂O₃S, [M+Na]⁺ 409.1562. Found 409.1567.

(E)-N′-(4-fluorobenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3d)

White solid, 43.3 mg, 63% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, chloroform-d) δ 7.98–7.91 (m, 2H), 7.90–7.85 (m, 1H), 7.78 (s, 1H), 7.73–7.67 (m, 2H), 7.62–7.57 (m, 2H), 7.15–7.06 (m, 2H), 4.38–4.28 (m, 2H), 3.41–3.31 (m, 2H), 2.34 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 172.77, 165.07 (d, J = 251.69 Hz), 162.58 (d, J = 251.69 Hz), 138.64, 138.23, 134.60 (d, J = 31.3 Hz), 134.29 (d, J = 31.3 Hz), 130.49 (d, J = 3.03 Hz), 130.46 (d, J = 3.03 Hz), 129.74 (d, J = 16.87 Hz), 129.58 (d, J = 16.87 Hz), 129.05 (d, J = 8.38 Hz), 128.97 (d, J = 8.38 Hz), 128.09 (d, J = 13.03 Hz), 127.96 (d, J = 13.03 Hz), 116.11 (d, J = 22.22 Hz), 115.89 (d, J = 22.22 Hz), 51.15, 49.51, 33.88, 21.52. HRMS (ESI+): Calculated for C₁₇H₁₇FN₂O₃S, [M+Na]⁺ 371.0842. Found 371.0865.

(E)-N′-(4-chlorobenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3e)

White solid, 46.6 mg, 60% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, DMSO-d₆) δ 7.94 (dt, J = 9.8, 4.7 Hz, 2H), 7.78 (dd, J = 5.0, 3.1 Hz, 2H), 7.67 (ddd, J = 7.3, 3.1, 1.7 Hz, 4H), 7.55 – 7.48 (m, 2H), 4.24 (t, J = 7.1 Hz, 2H), 3.64 (dd, J = 21.2, 14.5 Hz, 2H), 2.19 (d, J = 5.9 Hz, 3H).¹³C NMR (101 MHz, DMSO-d₆) δ 171.85, 139.30, 139.15, 134.52, 134.02, 129.91, 129.28, 129.08, 128.13, 50.56, 36.32, 33.18, 21.99. HRMS (ESI+): Calculated C₁₇H₁₇ClN₂O₃S, [M+Na]⁺ 387.0546. Found 387.0552.

(E)-N′-(4-bromobenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3f)

White solid, 47.3 mg, 58% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, DMSO-d₆) δ 7.97–7.91 (m, 2H), 7.80–7.74 (m, 2H), 7.70–7.60 (m, 6H), 4.24 (t, J = 7.1 Hz, 2H), 3.66 (t, J = 7.0 Hz, 2H), 2.19 (s, 3H). ¹³C NMR (101 MHz, DMSO-d₆) δ 171.70, 139.30, 134.69, 134.36, 132.19, 130.00, 129.32, 128.05, 123.28, 50.55, 49.02, 34.07, 21.71. HRMS (ESI+): Calculated for C₁₇H₁₇BrN₂O₃S, [M+Na]⁺ 431.0041. Found 431.0045.

(E)-N′-(4-cyanobenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3g)

White solid, 33.4 mg, 47% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, DMSO-d₆) δ 7.95–7.90 (m, 4H), 7.84 (d, J = 8.5 Hz, 3H), 7.78 (d, J = 7.5 Hz, 1H), 7.68 (t, J = 6.9 Hz, 2H), 4.27 (t, J = 7.0 Hz, 2H), 3.69 (t, J = 7.0 Hz, 2H), 2.22 (s, 3H). ¹³C NMR (101 MHz, Chloroform-d) δ 172.97, 138.44, 136.96, 134.43, 132.24, 129.50, 128.24, 127.54, 118.62, 113.02, 51.23, 34.09, 29.46, 21.47. HRMS (ESI+): Calculated for C₁₈H₁₇N₃O₃S, [M+Na]⁺ 378.0888. Found 378.0882.

(E)-N′-(3-methylbenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3i)

Light yellow solid, 46.9 mg, 68% yield, m.p. 151–153 °C. ¹H NMR (400 MHz, DMSO-d₆) δ 7.98 (d, J = 7.3 Hz, 2H), 7.80 (t, J = 7.4 Hz, 1H), 7.73–7.66 (m, 3H), 7.46 (d, J = 7.3 Hz, 2H), 7.33 (t, J = 7.7 Hz, 1H), 7.22 (d, J = 7.5 Hz, 1H), 4.24 (t, J = 7.2 Hz, 2H), 3.64 (t, J = 7.1 Hz, 2H), 2.35 (s, 3H), 2.22 (s, 3H). ¹³C NMR (101 MHz, DMSO-d₆) δ 171.8, 140.3, 139.3, 138.3, 135.0, 134.5, 130.8, 129.9, 129.1, 128.2, 128.1, 124.6, 50.7, 33.7, 21.8, 21.4. HRMS(ESI+): Calculated for C₁₈H₂₁N₂O₃S, [M+H]⁺ 345.1267. Found 345.1276.

(E)-N′-(3-methoxybenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3j)

White solid, 47.6 mg, 66% yield, m.p. 170–172 °C. ¹H NMR (400 MHz, DMSO-d₆) δ 7.97 (d, J = 7.1 Hz, 2H), 7.80 (t, J = 7.3 Hz, 1H), 7.70 (d, J = 7.8 Hz, 3H), 7.36 (t, J = 7.9 Hz, 1H), 7.25 (d, J = 7.7 Hz, 1H), 7.21 (s, 1H), 6.99 (dd, J = 7.9, 2.5 Hz, 1H), 4.25 (t, J = 6.7 Hz, 2H), 3.80 (s, 3H), 3.65 (t, J = 7.0 Hz, 2H), 2.22 (s, 3H). ¹³C NMR (101 MHz, DMSO-d₆) δ 171.9, 159.9, 140.0, 139.3, 136.5, 134.5, 130.3, 129.9, 128.2, 119.9, 115.9, 112.4, 55.6, 50.7, 33.8, 21.8. HRMS(ESI+): Calculated for C₁₈H₂₁N₂O₄S, [M+H]⁺ 361.1217. Found 361.1221.

(E)-N′-(3-fluorobenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3k)

White solid, 39.7 mg, 57% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, chloroform-d) δ 7.94 (dd, J = 5.2, 3.4 Hz, 2H), 7.76 (s, 1H), 7.71 (dt, J = 2.4, 1.5 Hz, 1H), 7.61 (dd, J = 10.6, 4.8 Hz, 2H), 7.40 (td, J = 6.8, 3.5 Hz, 3H), 7.17 – 6.98 (m, 1H), 4.38 – 4.30 (m, 2H), 3.42 – 3.33 (m, 2H), 2.35 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 172.85, 164.33 (d, J = 246.4 Hz), 161.88 (d, J = 246.4 Hz), 138.62, 138.02 (d, J = 3.0 Hz), 137.99 (d, J = 3.0 Hz), 136.57 (d, J = 7.9 Hz), 136.49 (d, J = 7.9 Hz), 134.31, 130.48 (d, J = 8.3 Hz), 130.40 (d, J = 8.3 Hz), 129.75, 129.59, 128.09, 127.97, 123.65 (d, J = 2.8 Hz), 123.62 (d, J = 2.8 Hz), 117.15 (d, J = 21.7 Hz), 116.93 (d, J = 21.7 Hz), 113.10 (d, J = 22.9 Hz), 112.87 (d, J = 22.9 Hz), 51.11, 33.95, 21.52. HRMS (ESI+): Calculated for C₁₇H₁₇FN₂O₃S, [M+Na]⁺ 371.0842. Found 371.0864.

(E)-N′-(3-bromobenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide(3l)

White solid, 44.8 mg, 55% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, DMSO-d₆) δ 7.98–7.92 (m, 2H), 7.85–7.74 (m, 3H), 7.71–7.65 (m, 3H), 7.60 (ddd, J = 8.0, 2.0, 1.0 Hz, 1H), 7.41 (t, J = 7.9 Hz, 1H), 4.25 (t, J = 7.1 Hz, 2H), 3.77–3.62 (m, 2H), 2.21 (s, 3H). ¹³C NMR (101 MHz, DMSO-d₆) δ 172.00, 139.32, 138.90, 137.56, 134.57, 132.59, 131.37, 130.01, 129.90, 128.19, 126.16, 122.55, 50.25, 33.78, 21.85. HRMS (ESI+): Calculated for C₁₇H₁₇BrN₂O₃S, [M+Na]⁺ 431.0041. Found 431.0043.

(E)-N′-(3-cyanobenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3m)

Colorless transparency liquid, 36.9 mg, 52% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, chloroform-d) δ 8.07–7.90 (m, 3H), 7.88 (d, J = 7.9 Hz, 1H), 7.82 (s, 1H), 7.73 (t, J = 7.5 Hz, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.62 (t, J = 7.7 Hz, 2H), 7.54 (t, J = 7.8 Hz, 1H), 4.65–4.19 (m, 2H), 3.43–3.37 (m, 2H), 2.37 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 172.82, 138.58, 136.84, 135.58, 134.38, 132.94, 131.42, 130.23, 129.73, 129.63, 127.93, 118.34, 113.19, 51.18, 34.04, 21.55. HRMS (ESI+): Calculated for C₁₈H₁₇N₃O₃S, [M+Na]⁺ 378.0888. Found 378.0913.

(E)-N′-(2-methylbenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3o)

White solid, 40.6 mg, 59% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, DMSO-d₆) δ 7.99–7.94 (m, 2H), 7.89 (s, 1H), 7.82–7.75 (m, 1H), 7.74–7.63 (m, 3H), 7.37–7.04 (m, 3H), 4.27 (dd, J = 8.3, 6.1 Hz, 2H), 3.64 (dd, J = 8.2, 6.1 Hz, 2H), 2.41 (s, 3H), 2.20 (s, 3H). ¹³C NMR (101 MHz, DMSO-d₆) δ 171.95, 139.29, 139.17, 137.35, 134.55, 132.88, 131.36, 129.94, 129.82, 128.17, 126.93, 126.54, 50.33, 40.46, 33.65, 21.96, 20.01. HRMS (ESI+): Calculated for C₁₈H₂₀N₂O₃S, [M+Na]⁺ 367.1092. Found 367.1099.

(E)-N′-(2-methoxybenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3p)

White solid, 48.2 mg, 56% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, chloroform-d) δ 8.21 (s, 1H), 7.98–7.92 (m, 2H), 7.75–7.67 (m, 2H), 7.63–7.60 (m, 2H), 7.37 (ddd, J = 8.8, 7.4, 1.7 Hz, 1H), 7.02–6.88 (m, 2H), 4.41–4.22 (m, 2H), 3.92 (s, 3H), 3.43–3.33 (m, 2H), 2.33 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 172.86, 158.18, 138.72, 135.59, 134.60, 134.13, 129.75, 129.47, 128.09, 125.84, 120.82, 111.17, 55.68, 50.99, 49.51, 21.62. HRMS (ESI+): Calculated for C₁₈H₂₀N₂O₄S, [M+Na]⁺ 383.1041. Found 383.1046.

(E)-N′-(2-ethoxybenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3q)

White solid, 40.4 mg, 54% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, DMSO-d₆) δ 8.07 (s, 1H), 7.95 (dt, J = 8.5, 1.7 Hz, 2H), 7.85–7.72 (m, 2H), 7.71–7.65 (m, 2H), 7.43–7.36 (m, 1H), 7.10 (d, J = 7.8 Hz, 1H), 7.00 (t, J = 7.4 Hz, 1H), 4.21 (dd, J = 22.0, 14.4 Hz, 2H), 4.12 (m, 2H), 3.55 (dd, J = 8.1, 6.5 Hz, 2H), 2.21 (s, 3H), 1.38 (t, J = 6.9 Hz, 3H).¹³C NMR (101 MHz, DMSO-d₆) δ 172.01, 157.75, 139.20, 135.71, 134.63, 131.67, 129.99, 128.08, 126.08, 123.17, 121.38, 121.09, 113.40, 64.57, 50.24, 33.79, 15.14. HRMS (ESI+): Calculated for C₁₉H₂₂N₂O₄S, [M+Na]⁺ 397.1198. Found 397.1203.

(E)-N′-(2,4-dimethylbenzylidene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3w)

White solid, 43.6 mg, 61% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, chloroform-d) δ 8.08 (s, 1H), 7.92 (dd, J = 5.2, 3.3 Hz, 2H), 7.72–7.67 (m, 1H), 7.65 (d, J = 7.7 Hz, 1H), 7.62–7.57 (m, 2H), 7.05 (d, J = 8.1 Hz, 2H), 4.39–4.32 (m, 2H), 3.40–3.34 (m, 2H), 2.49 (s, 3H), 2.35 (s, 3H), 2.33 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 172.91, 140.02, 138.84, 138.75, 137.18, 134.23, 131.92, 129.56, 129.46, 127.93, 127.11, 126.88, 51.06, 33.70, 21.72, 21.35, 20.07. HRMS (ESI+): Calculated for C₁₉H₂₂N₂O₃S, [M+Na]⁺ 381.1249. Found 381.1253.

(E)-N′-(furan-2-ylmethylene)-N-(2-(phenylsulfonyl)ethyl)acetohydrazide (3x)

White solid, 33.9 mg, 53% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, DMSO-d₆) δ 8.00–7.92 (m, 2H), 7.83–7.75 (m, 2H), 7.69 (dd, J = 11.3, 4.9 Hz, 3H), 6.88–6.73 (m, 1H), 6.62 (dd, J = 3.4, 1.8 Hz, 1H), 4.30–4.13 (m, 2H), 3.64–3.58 (m, 2H), 2.16 (s, 3H). ¹³C NMR (101 MHz, DMSO-d₆) δ 171.68, 150.20, 145.07, 139.25, 134.55, 130.77, 129.92, 128.19, 113.37, 112.51, 50.62, 33.66, 21.65. HRMS (ESI+): Calculated for C₁₅H₁₆N₂O₄S, [M+Na]⁺ 343.0728. Found 343.0740.

(E)-N′-benzylidene-N-(2-(phenylsulfonyl)ethyl)benzohydrazide (3z)

Colorless transparency liquid, 50.2 mg, 64% yield (eluent: ethyl acetate/petroleum ether = 1:10); ¹H NMR (400 MHz, DMSO-d₆) δ 8.03–7.98 (m, 2H), 7.86 (s, 1H), 7.82–7.77 (m, 1H), 7.69 (dd, J = 10.6, 4.8 Hz, 2H), 7.54–7.51 (m, 2H), 7.51–7.48 (m, 1H), 7.45 (s, 1H), 7.44–7.40 (m, 3H), 7.39–7.33 (m, 3H), 4.45 (t, J = 6.9 Hz, 2H), 3.81 (t, J = 7.0 Hz, 2H). ¹³C NMR (101 MHz, DMSO-d₆) δ 170.29, 139.33, 135.46, 134.99, 134.60, 130.72, 130.12, 129.99, 129.74, 129.16, 128.30, 127.77, 127.46, 50.84. HRMS (ESI+): Calculated for C₂₂H₂₀N₂O₃S, [M+Na]⁺ 415.1092. Found 415.1096.

Supplemental Material

sj-docx-1-chl-10.1177_17475198241275297 – Supplemental material for Access to (E)-N′-benzylidene-N-(2-(phenylsulfonyl)ethyl)acetohydrazide via C(sp2)−H activation and reduction of (E)-N′-benzylideneacetohydrazide with (vinylsulfonyl)benzene

Supplemental material, sj-docx-1-chl-10.1177_17475198241275297 for Access to (E)-N′-benzylidene-N-(2-(phenylsulfonyl)ethyl)acetohydrazide via C(sp2)−H activation and reduction of (E)-N′-benzylideneacetohydrazide with (vinylsulfonyl)benzene by Haiyang Wang and Fusheng Liu in Journal of Chemical Research

Footnotes

Data availability statement

The data underlying this study are available in the published article and its Supporting Information.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: We gratefully thank the Science and Technology Development Plan of Tan’an City (2019GX015) and Academic Promotion Program of Shandong First Medical University (2019LJ003) for financial support.

ORCID iD

Haiyang Wang

Supplemental material

Supplemental material for this article is available online.

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