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Synlett 2023; 34(06): 622-628
DOI: 10.1055/a-1874-2406
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Chemical Synthesis and Catalysis in India

Acridine-Based SNS–Ruthenium Pincer Complex-Catalyzed Borrowing Hydrogen-Mediated C–C Alkylation Reaction: Application to the Guerbet Reaction

Nandita Biswas
,
Rahul Sharma
,
Bitan Sardar
,
Dipankar Srimani∗

This work is financially supported by SERB (CRG/2021/000402).
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Abstract

SNS-based ruthenium pincer catalysts were applied in a Guerbet condensation reaction of primary alcohols to give β-alkylated dimeric alcohols in good yields. The ability of these complexes to convert ethanol into butanol was also investigated. The work was then extended toward the C-alkylation of secondary alcohols with primary alcohols to give α-alkylated ketones. Several control experiments showed the involvement of borrowing hydrogen in the protocol.


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Key words

borrowing hydrogen reaction - ruthenium catalysis - alcohols - Guerbet reaction - ketones - butanol

In 1899, the Guerbet reaction was first reported by Marcel Guerbet.[1] This is a condensation reaction of two alcohols with the release of a water molecule to form a final Guerbet alcohol. Studies on Guerbet alcohols and their applications in many sectors are appealing owing to the significant benefits of these products, particularly in the industrial field.[2] The melting temperature of branched Guerbet alcohols is significantly lower than that of their linear equivalents. Consequently, they are widely used as lubricants[3a] and hydraulic fluids for aircraft,[3b] as well as jet fuels.[3c] Branched alcohols are less viscous than their linear counterparts, which is a desirable feature for surfactants in a variety of detergent compositions.[4] Cosmetic emollients produced from Guerbet alcohols have a high oxygen permeability.[5]

The Guerbet reaction is particularly beneficial for producing liquid transportation fuels from sustainable biomass sources. Such fuels will form important components of future energy supplies.[6] Although the Guerbet reaction has a wide range of scientific applications, it undeniably suffers from a number of side reactions, including the formation of undesirable esters and carboxylic acids and their salts (through Cannizaro- and Tischenko-type reactions),[7] [8] which can sometimes poison the catalyst systems.

For these reasons, the Guerbet reaction is receiving much attention but is proving too difficult to implement. To carry out a complicated Guerbet reaction sustainably, we need a good catalytic system that simultaneously displays acidic, basic, and dehydrogenation–hydrogenation characteristics.[9] To maximize the yield of the desired alcohols, suitable reaction conditions and a well-planned catalytic system are important. Acceptorless dehydrogenation[10] and borrowing hydrogen (BH)[11] strategies have recently received considerable attention, due to their sustainable, efficient, and ecologically friendly nature. As a result, the synthesis of Guerbet alcohols through BH catalysis is extremely efficient.

A different approach has been reported for synthesizing branched alcohols[12] in three steps: (1) hydroformylation of an alkene to form an aldehyde, (2) aldol condensation to furnish an α,β-unsaturated aldehyde, and (3) successive hydrogenation to generate a β-alkyl alcohol. The Guerbet condensation reduces this three-step procedure to a one-step strategy (Figure [1]).[13]

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Figure 1 Approaches for the synthesis of branched-chain alcohols

Guerbet reactions have previously been performed in the presence of alkali-metal alkoxides or hydroxides and catalysts such as Raney Ni at 220 °C.[14] Later, reactions catalyzed by tertiary-phosphine ligand complexes of transition metals (Rh, Ru, Pt, or Ir) that proceeded under moderate reaction conditions were reported.[15] Carlini et al. found that a Guerbet conversion of butan-1-ol into 2-ethylhexan-1-ol proceeded in the presence of homogeneous or heterogeneous Pd-based catalysts at 200 °C.[13c] Ishii and co-workers demonstrated a catalytic conversion of ethanol into butan-1-ol at 120 °C by using a catalytic amount of Ir(COD)(acac) in presence of a sacrificial hydrogen acceptor (octa-1,7-diene) with reasonable selectivity.[16] Wass et al. later reported a 22% yield of butan-1-ol with a higher selectivity (94%) by using ruthenium-based homogeneous catalysts in the Guerbet conversion of ethanol to butan-1-ol.[17] Szymczak and co-workers[18] employed an NNN-ruthenium catalyst to give 31% of butan-1-ol with 82% selectivity in only two hours, and this catalyst was found to be faster than previously reported catalysts. Note that obtaining a high yield with good selectivity for this reaction is challenging. In 2017, Liu and co-workers[19a] reported the first Mn-catalyzed valorization of ethanol to butan-1-ol. They demonstrated that with a very low loading (8 ppm) of a PNP-Mn catalyst, ethanol could be converted into butan-1-ol with 92% selectivity and a high turnover number (TON) of 114120. Later, Jones and co-workers[19b] showed that manganese pincer complexes (RPNP)-MnBr(CO)2 (R = i-Pr, Cy, t-Bu, Ph, adamantyl) are effective catalysts for upgrading ethanol to butan-1-ol with a 34% yield and high selectivity. Thus, the synthesis of Guerbet alcohols with high selectivities and yields under mild reaction conditions is an area of importance. Here, we report a Ru-catalyzed[20] Guerbet condensation reaction through a borrowing hydrogen strategy using various Ru pincer catalysts (Figure [2]).[21]

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Figure 2 Ru-pincer catalysts used in the present work

Table 1 Optimization of the Homocoupling of Hexan-1-ola

Entry

Catalyst (mol%)

Base (mmol)

Yieldb (%)

 1

0.5

t-BuOK (1)

85

 2

0.375

t-BuOK (1)

71

 3

0.125

t-BuOK (1)

67

 4

0.5

KOH (1)

93

 5

0.5

CsOH·H2O

99

 6

0.5

K2CO3

81

 7

0.5

NaOH (1)

–

 8c

0.5

NaOH (1)

92

 9

0.125

NaOH (1)

70

10

0.5

NaOH (0.75)

88

11

–

NaOH (1)

–

12d

0.5

NaOH (1)

50

13e

0.5

NaOH (1)

67

a Reaction conditions: 4a (4 mmol), catalyst 1, base, 135 °C, 15 mL Ace pressure tube, 36 h, neat.

b NMR yield with MeCN as an internal standard.

c 24 h.

d Catalyst 2.

e Catalyst 3.

Initially, we used hexan-1-ol (4a) as a model substrate for optimizing the Guerbet reaction. To identify the optimal conditions, various reaction parameters were screened and the yield was measured by NMR spectroscopy with acetonitrile as an internal standard. When a mixture of hexan-1-ol (4 mmol), t-BuOK (1 mmol), and catalyst 1 (0.5 mol%) was heated at 135 °C in a 15 mL Ace pressure tube, 85% 2-butyloctan-1-ol (5b) was obtained selectively (Table [1], entry 1). On changing the catalyst loading from 0.5 mol% to 0.357 mol%, the desired product was obtained in a 71% yield (entry 2). On further lowering of the catalyst loading, the yield of the desired product was unchanged (Table [1], entry 3). Changing the base from t-BuOK to KOH with 0.5 mol% of catalyst 1 furnished a 93% yield of 5b. On the other hand, NaOH gave an excellent selectivity and a 99% yield (entry 5). When, the reaction was conducted for 24 h, keeping other conditions unaltered, a 92% product yield was obtained (entry 8). Further lowering of the catalyst loading and base concentration diminished the product yield (entries 9 and 10). In absence of a catalyst, no product was formed (entry 11). Catalysts 2 and 3 gave yields of 55 and 67%, respectively (entries 12 and 13).

Next, we investigated the scope and shortcomings of the protocol with various alcohols (Scheme [1]). First, by using our developed protocol, we synthesized the valuable Guerbet product 5a from butan-1-ol in 75% yield. 2-Ethylhexan-1-ol (5a) is a low-volatility solvent that can be used in the production of plasticizers and lubricants or as a cetane-number booster. Hexan-1-ol, octan-1-ol, decan-1-ol, dodecan-1-ol, and hexadecan-1-ol similarly gave excellent yields of the corresponding Guerbet alcohols 5b–f (84–90%). When various primary aliphatic alcohol were allowed to react with methanol, the interesting cross-Guerbet products 5g–i were obtained in moderate to good yields. The decreased yields of the cross products are anticipated for the high dehydrogenation enthalpy of methanol (i.e., approx. 31 kcal mol-1) which provides long chain aliphatic alcohols enough time to homocouple to Guerbet products.

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Scheme 1 Substrate scope for the Guerbet reaction. Reaction conditions: 4 (4 mmol), Catalyst 1 (0.5 mol%), NaOH (25 mol%), 135 °C, 15 mL Ace pressure tube, 36 h, neat. a 4 (2 mmol), MeOH (1 mL),

A time-dependent study of the borrowing hydrogen-mediated formation of Guerbet alcohol 5b was conducted using the homogeneous Ru–SNS catalyst to examine the reaction kinetics. Within a few hours of the start of the reaction, both the rapid consumption of hexan-1-ol and the rapid formation of the Guerbet product were detected. However, after three hours, the rate of the reaction decreased and steady formation of the product was observed (Figure [3]).

Table 2 Conversion of Ethanola

Entry

Catalyst

Butanol total TON

1

1

230

2

2

 75

3

3

110

a Reaction conditions: EtOH (1 mL), catalyst (0.045 mol%), NaOH (4.5 mol%), 140 °C, 15 mL Ace pressure tube, 24 h.

Next, we were interested in investigating the ability of our synthetic protocol to produce butan-1-ol from (bio)ethanol. In the current century, when the price of petroleum-based products is quite high, (bio)ethanol might be a possible alternative. However, the use of (bio)ethanol has some significant drawbacks. It has a lower energy density than gasoline and it absorbs water rapidly, resulting in concerns related to storage tank separation and dilution; moreover, it is incompatible with existing engine technology and infrastructure. Butanol isomers, on the other hand, have fuel properties that are similar to those of gasoline and could potentially alleviate many of the problems associated with ethanol. We therefore performed a Guerbet reaction of ethanol. The high reactivity of our catalytic protocol toward the reaction of long-chain aliphatic alcohol to form β-alkylated products caused us to examine whether the Guerbet reaction of ethanol would give branched-chain or straight-chain alcohol products. The selectivity toward conversion of ethanol into butan-1-ol[22] was quite good (92%), but the conversion was low. Among the three catalysts examined, catalyst 1 (Table [2], entry 1) was superior to catalysts 2 and 3 (entries 2 and 3).

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Scheme 2 Substrate scope for Guerbet reactions. Reaction conditions: 6 (1 mmol), 7 (1 mmol) catalyst 1 (0.5 mol%), NaOH (25 mol% with r.t. both alcohols), 135 °C, 15 mL Ace pressure tube, 36h, neat.
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Figure 3 Reaction profile for the Ru-pincer-catalyzed formation of the Guerbet product 5b

Next, to expand the scope of our developed protocol, we were interested in investigating the reactivity of secondary alcohols with primary aromatic and aliphatic alcohols.[23] When 1-phenylethanol and benzyl alcohol were reacted in the presence of 0.5 mol% of catalyst 1 and NaOH (50 mol%) in neat conditions, the reaction furnished the α-alkylated ketone product 8a in 75% yield (Scheme [2]). Next, we explored the effects of various functionalities in both the alcohols. A benzyl alcohol with an electron-donating substituent (4-OMe) furnished the desired products 8b in 70% yield, whereas halogen-containing benzyl alcohols gave moderate yields of products 8c and 8d, and 4-bromobenzyl alcohol gave 8e in low yield, along with the debrominated product 8a. Sterically demanding 2-methoxybenzyl alcohol also coupled with the secondary alcohol quite efficiently to give product 8f in 65% yield. In addition, piperonyl alcohol reacted well in the present protocol to give product 8g. 1(-4-Methoxyphenyl)ethanol and 1-(4-tolyl)ethanol reacted smoothly with various primary alcohols to afford excellent yields of the desired products 8k–u. However, the bromo derivative delivered a mixture of halogenated products 8v or 8w and the dehalogenated products 8a or 8i. The heteroaromatic alcohol (2-thienyl)methanol also delivered a moderate yield of the desired product 8r. Moreover, various aliphatic alcohols coupled smoothly with 1-phenylethanol derivatives furnishing moderate to good yields of the alkylated products 8i, 8j, 8m, 8o, and 8w. However, cyclohexanol was inactive in the present protocol (8x). Finally, structurally important citronellol was also found to be active and it delivered the alkylated product 8y in a good yield without hydrogenation of the isolated double bond.

To shed light on the mechanism, we conducted some control experiments (Scheme [3]). Coupling of alcohols in the absence of a catalyst results in no product formation (Table [1], entry 11). The formation of acetophenone and an aldehyde during the reaction was confirmed by an NMR analysis of the crude reaction mixture. In addition, the α,β-unsaturated species, 8a′ was formed by the reaction of acetophenone and benzaldehyde in the absence of a catalyst (Scheme [3]). This suggests that only the base plays a role in the condensation step. Moreover, when the α,β-unsaturated species 6a′ was allowed to react with alcohol 7a′, alkylated product, product 8a formed under the standard reaction conditions. However, in the absence of a catalyst, only a trace amount of the product was formed. Furthermore, deuterium-labeling experiments were conducted using the deuterated benzyl alcohol 7a-D and 1-phenylethanol, and deuterium incorporation in the alkylated product took place. The above results clearly suggest the involvement of a borrowing hydrogen approach.

Zoom Image
Scheme 3 Control experiments

In summary, we applied an acridine-based SNS Ru catalyst in a Guerbet-type reaction.[24] The reaction was further extended toward coupling of secondary alcohols and primary alcohols to furnish α-alkylated ketones efficiently.[25] Various control studies were performed that suggested the involvement of a borrowing-hydrogen pathway in the reactions.


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Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

N.B and R.S. would like to thank IITG for their fellowships. B.S. would like to thank CSIR for a fellowship. We are grateful to the Department of Chemistry (COE-FAST:5-5/2014-TS VII and FIST:SR/FST/CS-II/2017/23C) and CIF, IIT Guwahati, for NMR facilities, and to NECBH (IIT Guwahati) BT/COE/34/SP28408/2018 for the NMR facility.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-1874-2406.
  • Supporting Information

Corresponding Author

Dipankar Srimani
Department of Chemistry, Indian Institute of Technology Guwahati
Kamrup, Assam, India Pin-781039
India   

Publication History

Received: 20 April 2022

Accepted after revision: 12 June 2022

Accepted Manuscript online:
12 June 2022

Article published online:
08 July 2022

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   Permissions and Reprints All articles of this category
Zoom Image
Figure 1 Approaches for the synthesis of branched-chain alcohols
Zoom Image
Figure 2 Ru-pincer catalysts used in the present work
Zoom Image
Scheme 1 Substrate scope for the Guerbet reaction. Reaction conditions: 4 (4 mmol), Catalyst 1 (0.5 mol%), NaOH (25 mol%), 135 °C, 15 mL Ace pressure tube, 36 h, neat. a 4 (2 mmol), MeOH (1 mL),
Zoom Image
Scheme 2 Substrate scope for Guerbet reactions. Reaction conditions: 6 (1 mmol), 7 (1 mmol) catalyst 1 (0.5 mol%), NaOH (25 mol% with r.t. both alcohols), 135 °C, 15 mL Ace pressure tube, 36h, neat.
Zoom Image
Figure 3 Reaction profile for the Ru-pincer-catalyzed formation of the Guerbet product 5b
Zoom Image
Scheme 3 Control experiments