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Synthesis 2025; 57(01): 84-90
DOI: 10.1055/a-2317-6778
paper
Special Topic Dedicated to Prof. H. Ila

Solid-State Mechanochemical Clemmensen Reduction

Debjyoti Bhattacharjee‡
,
Sayan K. Jana‡
,
Biplab Maji  ∗

The authors thank DST-SERB, GoI (grant no. SCP/2022/000352) for financial support. SKJ thanks PMRF for the fellowship.
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Dedicated to Professor Dr. Hiriyakkanavar Ila on the occasion of her 80th birthday

Abstract

Mechanochemical synthesis has emerged as a sustainable alternative to traditional organic reactions, offering several advantages, including reduced solvent usage, lower reaction time, lower energy consumption, and enhanced reaction efficiency. In this study, the application of mechanochemistry to Clemmensen reduction, a classic method for converting aldehydes and ketones into alkanes, was explored. By employing ball milling as a mechanical activation, the feasibility and efficacy of mechanochemical Clemmensen reduction in various substrates were demonstrated. The results indicate that this approach offers comparable or improved yields and functional group compatibility compared to conventional methods while minimizing environmental impact. The reaction optimization strategies and scope of substrates are discussed, highlighting the potential of mechanochemical synthesis for sustainable organic transformations.


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Key words

mechanochemistry - Clemmensen reduction - green chemistry - alkane synthesis - ball milling

In fine chemical synthesis, the removal of functional groups can be as crucial as their introduction. Specifically, the reductive deoxygenation of carbonyl groups to methylene functionalities allows for the conversion of polyfunctional natural products into useful building blocks or bioactive molecules.[1] This process is especially relevant for transforming Friedel–Crafts acylation products and oxygenated feedstocks derived from petroleum or biomass into less common alkylated derivatives.[2]

The Clemmensen reduction has been a classic method for converting aldehydes and ketones to the corresponding methylene compounds for many years.[3] Though the reaction has been known to the community for over a hundred years, it is not well-valued. The pollution caused by the mercuric compounds used in this process has made it undesirable.[4] Despite several modifications over the period, this reaction still suffers from harsh reaction conditions (high temperature, corrosive concentrated acid) and long reaction time, making them unsuitable for a wide range of functional groups.[5] More recently, transition-metal-catalyzed deoxygenation using molecular H2 was reported.[6] Although H2 is an atom economic reducing agent, using H2 requires high-pressure, specialized equipment, and safety percussion to minimize explosion risk.[7] Recently, electrochemical deoxygenation of carbonyl has drawn significant attention to the organic synthetic community as a sustainable alternative to the previous method (Scheme [1]).

Zoom Image
Scheme 1 Overview of the solution-based and mechanochemical Clemmensen reduction

In this regard, Cheng, Wang, and others made a substantial contribution to this field.[8] However, the requirement of high voltage, long reaction time, and, more importantly, the use of huge amounts of solvent diminishes its practicality in organic synthesis.

Recently, mechanochemistry has re-emerged as a prominent organic synthesis technique that was previously only used in crystal engineering, polymorphism, mineral dressing, paints, ceramics, and material sciences.[9] The primary advantage of mechanochemistry for organic synthesis is that it lowers the reaction time and could make the process solvent-free.[9d] [10] Even IUPAC declared solvent-free reactions among the top 10 world-changing techniques in 2019.[11] Since then, mechanochemistry has attracted huge attention from synthetic organic chemists. Ball milling uncovered novel reactivity and selectivity, engaged poorly soluble substrate in organic synthesis, and facilitated sensitive organometallic reactions on air. In this regard, activating zerovalent metals like Zn, Mg, and Mn drag special attention to the synthetic community.[12] The reactive organometallic species were generated without needing specialized equipment and an inert atmosphere. Recently, we considered applying this technique to the years-old Clemmensen reduction so that we have the advantage of lower reaction time, solvent-free, and better functional group compatibility.

Table 1 Optimization of Reaction Conditionsa

Entry

Zn (equiv.)

PTSA·H2O (equiv.)

Time (min)

Ball

Yield of 1P (%)

 1

 4

 4

 90

10 mm × 2

10

 2

 7

 4

 90

10 mm × 2

11

 3

10

 4

 90

10 mm × 2

29

 4

12

 4

 90

10 mm × 2

27

 5

10

 6

 90

10 mm × 2

33

 6

10

 8

 90

10 mm × 2

67

 7

10

10

 90

10 mm × 2

86

 8

 8

10

 90

10 mm × 2

60

 9

 6

10

 90

10 mm × 2

46

10

10

10

 45

10 mm × 2

76

11

10

10

120

10 mm × 2

87

12

10

10

 90

10 mm × 3

84

13

10

10

 90

 8 mm × 2

25

14

10

10

 90

 5.5 mm × 2

12

15b

10

10

 90

10 mm × 2

<5

a Reaction conditions: The reaction was performed in 0.1 mmol scale in 5 mL ss jar with two 10 mm SS balls on a Retsch MM400 mixer mill for 90 min on 30 Hz frequency. Yields are determined via GC-MS analysis of crude reaction mixture using mesitylene as an internal standard.

b Indium powder or Mn powder instead of Zn was used.

We began our investigation for the mechanochemical Clemmensen reduction using [1,1′-biphenyl]-4-carbaldehyde (1) as a model substrate (Table [1]). We first attempted deoxygenative reduction of aldehyde 1 using Zn and PTSA­·H2O in a 5 mL stainless steel (ss) jar with two 10 mm ss balls. The desired product 1P was obtained in 10% yield as the reaction mixture was subjected to milling on a Retsch MM400 mixer mill for 90 min on 30 Hz frequency (Table [1], entry 1). Then, Zn and PTSA·H2O loadings were systematically varied to improve the reaction yield (entries 2–9). Ten equivalents of both reagents were found to be optimum, and 1P was produced with the highest 86% yield (entry 7). Lowering or increasing the milling time did not affect the outcome of the reaction (entries 10, 11). The yields dropped drastically as the size and number of balls varied (entries 12–14). The reactions with In or Mn powder as reducing agents instead of Zn failed to give the product under these conditions (entry 15).

To examine the functional group compatibility, we performed the robustness screening test, which Glorius introduced (Table [2]).[13] An equimolar amount of several additives was added under the standard reaction conditions (Table [1], entry 7), and the yield of the product and recovery of the additives were monitored by the GC-MS analysis (Conditions A, Table [2]). The method can simultaneously offer a discrete and quick assessment of the stability of these chemical motifs as well as the tolerance of the reaction to the given functionality under our reaction conditions. To compare the efficiency of the ball milling reaction with the state-of-the-art conventional reaction, we have performed the same robustness screening in thermal conditions using Zn (7 equiv.), concentrated HCl (11 equiv.) (Conditions B), as reported in ref.[14]

Overall, the comparative screening shows that the ball milling methodology gave a comparable or slightly higher yield of the reductive deoxygenation product than the thermal reaction employing Zn/HCl. Besides, the solid-sate reaction was found to be better regarding functional group compatibility.

Table 2 Robustness Screening to Elucidate the Functional Group Tolerance of the Mechanochemical Method and its Comparison with the Conventional Methoda

Entry

Additive

Conditions A

Conditions B

Yield of 1P (%)

Additive recovery (%)

Yield of 1P (%)

Additive recovery (%)

 1

none

86

–

84

–

 2

A1

95

89

90

81

 3

A2

61

93

41

37

 4

A3

84

74

50

41

 5

A4

81

99

90

85

 6

A5

92

57

15

8

 7

A6

85

99

54

59

 8

A7

81

36

80

41

 9

A8

56

99

52

95

10

A9

73

27

14

 8

11

A10

83

99

29

27

12

A11

91

 1

45

<1

13

A12

25

95

28

90

14

A13

21

70

40

<1

15

A14

40

 1

41

<1

16

A15

41

25

16

<1

17

A16

29

 1

32

<1

18

A17

10

 2

27

 1

19

A18

31

30

21

11

20

A19

38

41

88

91

a The reactions were performed on a 0.1 mmol scale in the presence of one molar equivalent of the given additive. The yield of 1P and the remaining additives are given after the reaction. Color coding should help the ready assessment of the data: green (above 60%), yellow (30–59%), and red (below 30%). See the Supporting Information for the experimental details.

The reaction in the presence of bromobenzene (A1), iodobenzene (A2), terminal A3 and internal alkynes A4, and terminal A5 and internal alkenes A6 proceeded with an excellent yield under milling conditions, and most importantly, an insignificant additive degradation was observed (Table [2], entries 2–7). However, low yields and significant degradation of A2, A3, A5, and A6 were observed under the heating Conditions B. The reaction with benzonitrile (A7) gave a high yield of the product 1P and low additive recovery in both conditions (entry 8). Moderate 1P yield and high additive recovery were noticed for benzyl cyanide (A8, entry 9). Notably, the solid-state reaction better accommodates the sulfide A9 and disulfide A10 functionalities than the conventional thermal reaction (entries 10, 11).

The yield with benzoic acid additive A11 is higher under Conditions A (Table [2], entry 12). The additive recovery is very poor in both conditions. The reactions with benzoate A12 and ether A13 gave moderate yields of 1P with high additive recovery in both conditions (entries 13, 14). Benzamide (A14), aniline (A15), benzylamine (A16), benzyl alcohol (A17), and benzofuran (A18) additives were found to be poorly tolerable in both the reaction conditions (entries 15–19). The reaction with phenol A19 performed well in thermal conditions (entry 20).

Although these results give an overview of which structural motifs are likely to be tolerated by the reaction conditions, they do not provide definitive information on the success of a particular reaction because specific electronic, steric, and conformational effects cannot be considered. However, the design of synthetic pathways and the evaluation of the reaction’s suitability for a particular substrate can both benefit from this knowledge.

Finally, we briefly explored the feasibility of mechanochemical Clemmensen reduction in various substrates, including both aromatic and aliphatic ketones and aldehydes (Scheme [2]). We first varied several aldehyde substrates bearing diverse electronic functional groups 1–13 on an aryl ring. The deoxygenated products were produced in good to excellent yields. Aldehyde-bearing reducible halide functional groups 6 and 7 are tolerated in the reaction conditions, giving a moderate yield of the desired products. Several heterocycles bearing aldehydes 8–11 have also been found to react smoothly under optimized conditions. Pyridine 8, o-lutidine 9, quinoline 10, and indole 11 were sustained with moderate yields. We have also performed reductive deoxygenation of aliphatic aldehyde 12, which yields the desired product in a moderate 48% yield. Furthermore, we have tried polyaromatic aldehyde with poor solubility in organic solvents. Pyrene 13 containing aldehyde yields the desired reductive product in moderate 43% yield.

Then, we tested several ketones under the mechanochemical Clemmensen reduction conditions. First, several acetophenone derivatives were tested. Acetophenone-bearing electron donating groups like free hydroxyl 14, ether 15, and alkyl 16 groups are well tolerated under the reaction conditions. Halogens, including fluoro 17, chloro 18, iodo 19, and bromo 20 groups, are also sustained in these reaction conditions, furnishing moderate to good yields of the desired deoxygenated products. Ketone-bearing terminal alkyne 21 is also tolerated, giving a 43% yield of the reduced product. A 1-tertralone derivative 22 could also be deoxygenated in a high 75% isolated yield. The reaction of diaryl ketone 23 yields the diarylmethane in a moderate 54% yield. The reaction was also compatible with dialkyl ketone 24, which produced a moderate 53% yield of the desired product.

In summary, we have developed a mechanochemical version of the years-old Clemmensen reduction by taking commercially available Zn dust and a solid acid PTSA·H2O. This developed method is solvent-free and reduces reaction time significantly. We believe our process will inspire the synthetic organic community to use mechanochemical ball milling as a valuable alternative to many organic transformations that need prolonged reaction time, intense heating, and wastage of a considerable amount of solvent.

Zoom Image
Scheme 2 Scope of the reaction. Reagents and conditions: Table [1], entry 7. Isolated yield. 1H NMR yields are given in parentheses. NMR yields are determined using 1,3,5-trimethoxybenzene as an internal standard.


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Mechanochemical Clemmensen Reduction; General Procedure A

The carbonyl substrate (0.1 mmol) was placed in a 5 mL stainless steel (ss, 316 grade) milling jar with two 10 mm ss balls. Then, Zn powder (1 mmol, 65 mg) and PTSA·H2O (1 mmol, 190 mg) were weighed in air and directly added to the jar. The jar was then closed in the open air and placed in the ball mill (Retsch MM 400). After grinding for 90 min at 30 Hz frequency, the jar was opened and neutralized with sat. aq Na2CO3 (5 mL). The organics were extracted with CH2Cl2 (2 × 10 mL), filtered over Celite, dried (Na2SO4), and evaporated in vacuo. Crude yields of the products were determined by 1H NMR analysis or GC-MS analysis using 1,3,5-trimethoxybenzene or mesitylene as the internal standard, respectively. The product was then isolated by flash column chromatography (SiO2, Et2O/hexane 0.1:99.9).


#

Solution-Based Clemmensen Reduction; General Procedure B

The carbonyl substrate (0.1 mmol) was placed in a two-necked round bottom flask equipped with a PTFE-quoted magnetic stir bar and a reflux condenser. Then, Zn powder (0.7 mmol, 46 mg), concd HCl (0.6 mmol, 60 μL), and an equal volume of H2O were added to the jar. The reaction mixture was then refluxed for 8 h, while concd HCl (0.08 mmol, 8 μL) was added at each hour interval. After that, the reaction was neutralized with sat. aq Na2CO3 (5 mL). The organics were extracted with CH2Cl2 (2 × 10 mL), filtered (Celite), dried (Na2SO4), and evaporated in vacuo. Crude yields of the products were determined by GC-MS analysis using mesitylene as the internal standard.

The structures of the products and their numbering are provided in the Supporting Information.


#

4-Methyl-1,1′-biphenyl (1P)[15]

Compound 1P was synthesized following the general procedure A. Flash column chromatography afforded the product as a white solid; yield: 26 mg (78%); mp 39–43 °C.

1H NMR (500 MHz, CDCl3): δ = 7.66–7.56 (m, 2 H), 7.56–7.48 (m, 2 H), 7.43 (q, J = 6.7 Hz, 2 H), 7.37–7.30 (m, 1 H), 7.26 (t, J = 6.4 Hz, 2 H), 2.41 (s, 3 H).

13C NMR (126 MHz, CDCl3): δ = 141.3, 138.5, 137.1, 129.6, 128.8, 127.1, 127.1, 127.1, 21.2.


#

2,4′-Dimethyl-1,1′-biphenyl (2P)[16]

Compound 2P was synthesized following the general procedure A. Flash column chromatography afforded the product as a white solid; yield: 29 mg (81%); mp 40–44 °C.

1H NMR (500 MHz, CDCl3): δ = 7.27–7.23 (m, 8 H), 2.41 (s, 3 H), 2.29 (s, 3 H).

13C NMR (126 MHz, CDCl3): δ = 142.0, 139.2, 136.5, 135.5, 130.4, 130.0, 129.2, 128.9, 127.2, 125.9, 21.3, 20.6.


#

4-Isopropyltoluene (3P)[17]

Compound 3P was synthesized following the general procedure A. Flash column chromatography afforded the product as a colorless liquid; yield: 12 mg (47%).

1H NMR (400 MHz, CDCl3): δ = 7.19–7.13 (m, 4 H), 2.92 (hept, J = 7.0 Hz, 1 H), 2.36 (s, 3 H), 1.28 (d, J = 7.0 Hz, 6 H).

13C NMR (101 MHz, CDCl3): δ = 146.0, 135.3, 129.1, 126.4, 33.8, 24.2, 21.1.


#

4-Methylphenol (4P)[18]

Compound 4P was synthesized following the general procedure A. Flash column chromatography afforded the product as a colorless solid; yield: 15 mg (72%); mp 36–39 °C.

1H NMR (500 MHz, CDCl3): δ = 7.04 (d, J = 7.9 Hz, 2 H), 6.74 (d, J = 8.5 Hz, 2 H), 4.89 (s, 1 H), 2.28 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 153.3, 130.2, 130.0, 115.2, 20.5.


#

1-Methoxy-4-methylbenzene (5P)[19]

Compound 5P was synthesized following the general procedure A. Flash column chromatography afforded the product as a colorless liquid; 14 mg (58%).

1H NMR (400 MHz, CDCl3): δ = 7.10 (dt, J = 8.1, 0.7 Hz, 2 H), 6.84–6.80 (m, 2 H), 3.79 (s, 3 H), 2.30 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 157.5, 130.0, 129.9, 113.8, 55.4, 20.5.


#

1-Bromo-4-methylbenzene (6P)[20]

Compound 6P was synthesized following the general procedure A. Flash column chromatography afforded the product as a yellow solid; yield: 18 mg (52%); mp 36–39 °C.

1H NMR (500 MHz, CDCl3): δ = 7.37 (d, J = 8.4 Hz, 2 H), 7.05 (d, J = 9.3 Hz, 2 H), 2.31 (s, 3 H).

13C NMR (126 MHz, CDCl3): δ = 136.9, 131.4, 130.9, 119.2, 21.0.


#

1-Iodo-4-methylbenzene (7P)[20]

Compound 7P was synthesized following the general procedure A. Flash column chromatography afforded the product as a white solid; yield: 24 mg (56%); mp 35–38 °C.

1H NMR (400 MHz, CDCl3): δ = 7.56 (d, J = 8.3 Hz, 2 H), 6.93 (d, J = 7.8 Hz, 2 H), 2.29 (s, 3 H).

13C NMR (126 MHz, CDCl3): δ = 137.6, 137.3, 131.3, 90.3, 21.1.


#

2-Methylpyridine (8P)[21]

Compound 8P was synthesized following the general procedure A. Flash column chromatography afforded the product as a colorless liquid; yield: 7 mg (39%).

1H NMR (500 MHz, CDCl3): δ = 8.46 (d, J = 4.9 Hz, 1 H), 7.52 (t, J = 7.7 Hz, 1 H), 7.11 (d, J = 7.8 Hz, 1 H), 7.06–7.02 (m, 1 H), 2.52 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 158.4, 149.2, 136.3, 123.3, 120.8, 24.5.


#

2,6-Dimethylpyridine (9P)[21]

Compound 9P was synthesized following the general procedure A. Flash column chromatography afforded the product as a white solid; yield: 8 mg (36%); mp 30–34 °C.

1H NMR (400 MHz, CDCl3): δ = 7.42 (t, J = 7.6 Hz, 1 H), 6.92 (d, J = 7.6 Hz, 2 H), 2.49 (s, 6 H).

13C NMR (126 MHz, CDCl3): δ = 157.6, 136.6, 120.2, 24.4.


#

2-Methylquinoline (10P)[22]

Compound 10P was synthesized following the general procedure A. Flash column chromatography afforded the product as an orange liquid; yield: 14 mg (49%).

1H NMR (500 MHz, CDCl3): δ = 7.94 (d, J = 8.3 Hz, 2 H), 7.69–7.66 (m, 1 H), 7.59 (s, 1 H), 7.38 (s, 1 H), 7.18 (d, J = 8.3 Hz, 1 H), 2.66 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 159.1, 147.9, 136.3, 129.5, 128.7, 127.6, 126.6, 125.8, 122.1, 25.4.


#

3-Methyl-1H-indole (11P)[23]

Compound 11P was synthesized following the general procedure A. Flash column chromatography afforded the product as a white solid; yield: 12 mg (41%); mp 89–93 °C.

1H NMR (400 MHz, CDCl3): δ = 7.87 (s, 1 H), 7.59 (d, J = 8.6 Hz, 1 H), 7.35 (dt, J = 8.1, 1.0 Hz, 1 H), 7.20 (ddd, J = 8.2, 7.0, 1.3 Hz, 1 H), 7.13 (ddd, J = 8.0, 7.0, 1.1 Hz, 1 H), 6.99–6.97 (m, 1 H), 2.35 (d, J = 1.1 Hz, 3 H).

13C NMR (126 MHz, CDCl3): δ = 136.4, 128.4, 122.0, 121.6, 119.2, 118.9, 111.8, 111.0, 9.7.


#

Ethylbenzene (12P)[24]

Compound 12P was synthesized following the general procedure A. Flash column chromatography afforded the product as a colorless liquid; yield: 10 mg (48%).

1H NMR (400 MHz, CDCl3): δ = 7.33–7.29 (m, 2 H), 7.24–7.18 (m, 3 H), 2.68 (q, J = 7.6 Hz, 2 H), 1.27 (t, J = 7.6 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 144.4, 128.4, 128.0, 125.7, 29.0, 15.7.


#

1-Methylpyrene (13P)[25]

Compound 13P was synthesized following the general procedure A. Flash column chromatography afforded the product as a yellow solid; yield: 19 mg (43%); mp 73–77 °C.

1H NMR (400 MHz, CDCl3): δ = 8.24 (d, J = 9.2 Hz, 1 H), 8.19 (dd, J = 7.6, 1.9 Hz, 2 H), 8.12–8.09 (m, 2 H), 8.04–8.00 (m, 3 H), 7.88 (dd, J = 7.7, 0.7 Hz, 1 H), 3.00 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 132.3, 131.5, 131.0, 129.8, 129.2, 127.9, 127.6, 127.2, 126.5, 125.8, 125.0, 124.9, 124.9, 124.8, 124.7, 123.7, 19.8.


#

4-Ethylphenol (14P)[26]

Compound 14P was synthesized following the general procedure A. Flash column chromatography afforded the product as a yellow liquid; yield: 16 mg (68%).

1H NMR (400 MHz, CDCl3): δ = 7.07 (d, J = 9.3 Hz, 2 H), 6.76 (d, J = 8.7 Hz, 2 H), 2.59 (q, J = 7.5 Hz, 2 H), 1.21 (t, J = 7.6 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 153.5, 136.7, 129.0, 115.2, 28.1, 16.0.


#

1-Ethyl-4-methoxybenzene (15P)[26]

Compound 15P was synthesized following the general procedure A. Flash column chromatography afforded the product as a colorless liquid; yield: 15 mg (57%).

1H NMR (400 MHz, CDCl3): δ = 7.12 (d, J = 8.8 Hz, 2 H), 6.84 (d, J = 8.8 Hz, 2 H), 3.80 (d, J = 0.5 Hz, 3 H), 2.60 (q, J = 7.6 Hz, 2 H), 1.22 (t, J = 7.6 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 157.7, 136.5, 128.8, 113.8, 55.4, 28.1, 16.0.


#

1-Ethyl-4-methylbenzene (16P)[24]

Compound 16P was synthesized following the general procedure A. Flash column chromatography afforded the product as a colorless liquid; yield: 12 mg (51%).

1H NMR (400 MHz, CDCl3): δ = 7.13 (s, 4 H), 2.65 (q, J = 7.6 Hz, 2 H), 2.35 (s, 3 H), 1.26 (t, J = 7.6 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 141.4, 135.1, 129.1, 127.9, 28.6, 21.1, 15.9.


#

1-Ethyl-4-fluorobenzene (17P)[27]

Compound 17P was synthesized following the general procedure A. Flash column chromatography afforded the product as a yellow solid; yield: 10 mg (42%); mp 49–53 °C.

1H NMR (400 MHz, CDCl3): δ = 7.17–7.12 (m, 2 H), 6.96 (t, J = 8.8 Hz, 2 H), 2.62 (q, J = 7.6 Hz, 2 H), 1.22 (t, J = 7.6 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 161.2 (d, J = 242.8 Hz), 139.9 (d, J = 3.2 Hz), 129.2 (d, J = 7.7 Hz), 115.1 (d, J = 21.0 Hz), 28.2, 15.9.


#

1-Chloro-4-ethylbenzene (18P)[24]

Compound 18P was synthesized following the general procedure A. Flash column chromatography afforded the product as a colorless liquid; yield: 12 mg (43%).

1H NMR (400 MHz, CDCl3): δ = 7.25 (d, J = 8.5 Hz, 2 H), 7.13 (d, J = 8.8 Hz, 2 H), 2.62 (q, J = 7.6 Hz, 2 H), 1.22 (t, J = 7.6 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 142.7, 131.3, 129.3, 128.5, 28.4, 15.6.


#

1-Ethyl-2-iodobenzene (19P)[28]

Compound 19P was synthesized following the general procedure A. Flash column chromatography afforded the product as a yellow liquid; yield: 28 mg (62%).

1H NMR (400 MHz, CDCl3): δ = 7.82 (dd, J = 7.9, 1.3 Hz, 1 H), 7.29 (td, J = 7.4, 1.3 Hz, 1 H), 7.26–7.22 (m, 1 H), 6.89 (td, J = 7.5, 1.9 Hz, 1 H), 2.75 (q, J = 7.5 Hz, 2 H), 1.22 (t, J = 7.5 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 146.6, 139.4, 128.6, 128.5, 127.6, 100.5, 34.3, 14.7.


#

1-Bromo-4-ethylbenzene (20P)[26]

Compound 20P was synthesized following the general procedure A. Flash column chromatography afforded the product as a colorless liquid; yield: 22 mg (58%).

1H NMR (400 MHz, CDCl3): δ = 7.40 (d, J = 8.4 Hz, 2 H), 7.07 (d, J = 8.0 Hz, 2 H), 2.60 (q, J = 7.6 Hz, 2 H), 1.22 (t, J = 7.6 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 143.3, 131.5, 129.8, 119.4, 28.5, 15.6


#

1-Ethyl-4-ethynylbenzene (21P)[29]

Compound 21P was synthesized following the general procedure A. Flash column chromatography afforded the product as an orange liquid; yield: 11 mg (43%).

1H NMR (500 MHz, CDCl3): δ = 7.42 (d, J = 8.2 Hz, 2 H), 7.15 (d, J = 8.5 Hz, 2 H), 3.03 (s, 1 H), 2.65 (q, J = 7.6 Hz, 2 H), 1.23 (t, J = 7.6 Hz, 3 H).

13C NMR (126 MHz, CDCl3): δ = 145.4, 132.3, 128.0, 119.4, 84.0, 76.5, 29.0, 15.4.


#

6-Methoxy-1,2,3,4-tetrahydronaphthalene (22P)[18]

Compound 22P was synthesized following the general procedure A. Flash column chromatography afforded the product as a colorless liquid, yield: 24 mg (75%).

1H NMR (400 MHz, CDCl3): δ = 6.99–6.96 (m, 1 H), 6.67 (ddt, J = 8.3, 2.7, 0.7 Hz, 1 H), 6.61 (d, J = 2.7 Hz, 1 H), 3.77 (s, 3 H), 2.72 (d, J = 18.8 Hz, 4 H), 1.79–1.76 (m, 4 H).

13C NMR (101 MHz, CDCl3): δ = 157.8, 138.6, 130.4, 129.7, 114.2, 112.2, 55.7, 30.2, 29.0, 23.9, 23.6.


#

Diphenylmethane (23P)[18]

Compound 23P was synthesized following the general procedure A. Flash column chromatography afforded the product as a colorless liquid; yield: 18 mg (54%).

1H NMR (500 MHz, CDCl3): δ = 7.30 (ddd, J = 7.5, 6.5, 1.7 Hz, 4 H), 7.21 (td, J = 6.3, 1.7 Hz, 6 H), 4.00 (s, 2 H).

13C NMR (101 MHz, CDCl3): δ = 141.2, 129.0, 128.6, 126.2, 42.0.


#

Cyclohexylbenzene (24P)[30]

Compound 24P was synthesized following the general procedure A. Flash column chromatography afforded the product as a colorless liquid; yield: 17 mg (53%).

1H NMR (500 MHz, CDCl3): δ = 7.36–7.31 (m, 2 H), 7.27–7.20 (m, 3 H), 2.54 (t, J = 11.6 Hz, 1 H), 1.96–1.86 (m, 4 H), 1.80 (d, J = 12.8 Hz, 1 H), 1.52–1.39 (m, 4 H), 1.31 (t, J = 12.7 Hz, 1 H).

13C NMR (101 MHz, CDCl3): δ = 148.2, 128.4, 127.0, 125.9, 44.7, 34.6, 27.1, 26.3.


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Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

The authors thank IISER K for the infrastructure and instrumental facility.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-2317-6778.
  • Supporting Information

Corresponding Author

Biplab Maji
Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata
Mohanpur 741246
India   

Publication History

Received: 22 March 2024

Accepted after revision: 30 April 2024

Accepted Manuscript online:
30 April 2024

Article published online:
21 May 2024

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Scheme 1 Overview of the solution-based and mechanochemical Clemmensen reduction
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Scheme 2 Scope of the reaction. Reagents and conditions: Table [1], entry 7. Isolated yield. 1H NMR yields are given in parentheses. NMR yields are determined using 1,3,5-trimethoxybenzene as an internal standard.