Chemistry in Water

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Jul 152016

Chemistry in Water

Isley et al. reported the use of the nonionic amphiphile TPGS-750-M (2 wt %) in water to facilitate nucleophilic aromatic substitution reactions (S_NAr) with oxygen, nitrogen, and sulfur nucleophiles. The team eliminated the use of dipolar aprotic organic solvents traditionally required for S_NAr reactions, such as dimethylformamide (DMF), dimethylacetamide (DMAc), dimethyl sulfoxide (DMSO), and N-methyl-2-pyrrolidone (NMP).

Moderate to high yields at ambient or slightly elevated temperatures (up to 45 °C) were observed, and a diverse substrate scope with respect to thermal stability was established. The team additionally demonstrated the ability to recycle the water/micelle mixture by extracting the product with organic solvent. Recycling of the aqueous media resulted in improving the E-factor and reducing aqueous waste ( Org. Lett. 2015, 17,4734−4737).

, Supporting Info

Nucleophilic Aromatic Substitution Reactions in Water Enabled by Micellar Catalysis

Nicholas A. Isley^†, Roscoe T. H. Linstadt^†, Sean M. Kelly^†, Fabrice Gallou^‡, and Bruce H. Lipshutz^*^†

^† Department of Chemistry & Biochemistry, University of California, Santa Barbara, California 93106, United States

^‡ Chemical & Analytical Development, Novartis Pharma AG, 4056 Basel, Switzerland

Org. Lett., 2015, 17 (19), pp 4734–4737

DOI: 10.1021/acs.orglett.5b02240

*E-mail: lipshutz@chem.ucsb.edu.

Wang et al. described the development of a copper-catalyzed hydroxylation of aryl halides in water. The syntheses of phenols generally require the use of energy intensive and/or harsh reaction conditions which can impact the substrate scope. This methodology utilized a hydroxylated phenanthroline ligand to improve solubility in water. Optimization of this method through screening resulted in the selection of copper(I) oxide (Cu₂O) as the copper source and tetrabutyl-ammonium hydroxide (TBAOH) at 110 °C. The TBAOH was proposed to function as both phase transfer catalyst and nucleophile, resulting in high yields and excellent selectivity toward phenol versus biphenyl ether.

The scope of this method with substituted aryl halides was demonstrated, affording excellent yields and high selectivity for para-substituted electron-rich and electron-deficient aryl bromides, as well as meta-substituted bromo-halides. Functional groups such as carboxyl and hydroxyl groups were also tolerated. The team additionally demonstrated a one-pot synthesis of either alkyl aryl ethers or benzofuran by trapping the in situ generated phenol with an alkyl bromide or through intramolecular cyclization ( Green Chem. 2015, 17, 3910−3915).

Graphical abstract: Copper-catalyzed hydroxylation of aryl halides: efficient synthesis of phenols, alkyl aryl ethers and benzofuran derivatives in neat water

Copper-catalyzed hydroxylation of aryl halides: efficient synthesis of phenols, alkyl aryl ethers and benzofuran derivatives in neat water

Yangxin Wang,^a^b Chunshan Zhou^a and Ruihu Wang*^a

*Corresponding authors

^aState Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, China
E-mail: ruihu@fjirsm.ac.cn

^bUniversity of Chinese Academy of Sciences, Beijing, China

Green Chem., 2015, 17, 3910-3915
DOI: 10.1039/C5GC00871A , supporting info,

An efficient catalytic protocol for hydroxylation of aryl halides in water is proposed to prepare phenols, ethers and benzofuran derivatives.

A thorough study of environmentally friendly hydroxylation of aryl halides is presented. The best protocol consists of hydroxylation of different aryl bromides and electron-deficient aryl chlorides by water solution of tetrabutylammonium hydroxide catalyzed by Cu₂O/4,7-dihydroxy-1,10-phenanthroline. Various phenol derivatives can be obtained in excellent selectivity and great functional group tolerance. This methodology also provides a direct pathway for the formation of alkyl aryl ethers and benzofuran derivatives in a one-pot tandem reaction.

Jung et al. reported the use of a continuous flow reactor to synthesize propargylamines in an atom economic fashion using stoichiometric quantities of reagents, water as solvent, and generating only CO₂ and water as byproducts. The team exploited the use of a pressurized tube reactor to achieve temperatures above the boiling point of water, enabling excellent yields (≥88%) and reasonable residence time (2 h).

This procedure improved the atom economy of previously reported methods for this transformation by eliminating the use of transition metal catalysts and excess of reagents. The substrate scope was demonstrated for multiple alkynyl carboxylic acids and secondary amines ( Tetrahedron. Lett. 2015, 56, 4697−4700).

Tetrahedron Letters

Volume 52, Issue 36, 7 September 2011, Pages 4697–4700

Basic alumina supported tandem synthesis of bridged polycyclic quinolino/isoquinolinooxazocines under microwave irradiation

Department of Chemistry, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata 700 032, India

Wang et al. reported the synthesis of an easily accessible diammonium functionalized Ru-alkylidene complex capable of ring-closing metathesis (RCM) and cross metathesis (CM) reactions in water. The NHBoc penultimate intermediate was isolated as an air-stable, nonhygroscopic Ru-alkylidene complex. Acidic cleavage of the Boc groups with trifluoroacetic acid (TFA) in dichloromethane generated the diammonium catalyst as a green solid after removal of volatiles under reduced pressure. The diammonium catalyst (5 mol %) achieved modest to high conversion to cyclic RCM products in D₂O at ambient to elevated temperatures (up to 80 °C). Lowering the catalyst loading to 0.1 mol % established a turnover number (TON) of >900.

Homocoupling of allyl alcohol and long chain alkenylammonium salts provided the desired diammonium cross products in high yield/conversion. Short chain alkenyl-ammonium salts were poor substrates for the CM reaction.

Catalyst deactivation was attributed to the ammonium:free amine equilibration in water followed by Lewis basic nitrogen coordination to the Ru-center (Green Chem. 2015, 17, 3407−3414).

A simple and practical preparation of an efficient water soluble olefin metathesis catalyst

Zhen J. Wang,^a W. Roy Jackson^a and Andrea J. Robinson*^a

*Corresponding authors

^aSchool of Chemistry, Monash University, Clayton 3800, Australia
E-mail: andrea.robinson@monash.edu

Green Chem., 2015,17, 3407-3414

DOI: 10.1039/C5GC00252D, supp info

The same research group additionally reported the divergent functionalization of L-tyrosine to generate a family of tyrosine-derived Ru-alkylidene RCM catalysts. This common ligand precursor approach was utilized to successfully create not only a hydrophilic/water-soluble PEG Ru-alkylidene, but a hydrophobic alkane Ru-alkylidene for solvent-free catalysis and a solid-phase supported Ru-alkylidene to access a potentially recyclable precatalyst system.

The PEG Ru-alkylidene complex displayed poor solubility in water at 40 °C under ultrasonication, providing the desired model RCM product in only 25% conversion. >95% conversion was achieved by utilizing a 1:1 water–MeOH solvent system at 40 °C with 2.5 mol % catalyst loading. It was rationalized in the Green Chemistry report (vide supra) that functionalization of the benzylidene ligand to increase aqueous solubility may be problematic due to the dissociation of the labile ligand during the catalytic cycle, whereas functionalization of nondissociating NHC ligand could sustain the desired solubility throughout the reaction.

The hydrophobic alkane Ru-alkylidene provided solvent-free RCM and CM products in high conversion. The solid-phase Ru-alkylidene also provided the desired RCM products in high conversion and demonstrated stable performance after multiple catalyst recovery/reuse operations. Sustained leaching of Ru metal into the reaction media was monitored and observed for the recycled solid-phase catalyst method. However, this iterative loss of metal did not negatively impact conversion ( J. Org. Chem. 2015, 80, 7205−7211).

Divergent Approach to a Family of Tyrosine-Derived Ru−Alkylidene Olefin Metathesis Catalysts

divergent

Authors	Ellen C. Gleeson, Zhen J. Wang, W. Roy Jackson, and Andrea J. Robinson
Published	Journal of Organic Chemistry
Graphical abstract
Abstract	A simple and generic approach to access a new family of Ru−alkylidene olefin metathesis catalysts with specialized properties is reported. This strategy utilizes a late stage, utilitarian Hoveyda-type ligand derived from tyrosine, which can be accessed via a multigram-scale synthesis. Further functionalization allows the catalyst properties to be tuned, giving access to modified second-generation Hoveyda−Grubbs-type catalysts. This divergent synthetic approach can be used to access solid-supported catalysts and catalysts that function under solvent-free and aqueous conditions.
Citation	Ellen C. Gleeson, Zhen J. Wang, W. Roy Jackson, and Andrea J. Robinson, J. Org. Chem., 2015, 80(14), 7205–7211
Pdf	Article
Doi	10.1021/acs.joc.5b01091

Bhowmick et al. published a review “Water: the most versatile and nature’s friendly media in asymmetric organocatalyzed direct aldol reactions”. This review addressed the various types of organocatalysts based on (1) l-proline, (2) 4-hydroxy-l-proline, (3) amino acid derivatives, (4) enzymes, and (5) other miscellaneous catalysts applied to the aldol reaction in aqueous media. In general, the intermolecular asymmetric aldol reaction has been shown to perform poorly in pure aqueous media and is typically performed in organic solvents such as DMF, DMSO, etc.

However, structural modifications to l-proline and 4-hydroxy-l-proline have generated catalysts capable of asymmetric aldol reactions in aqueous media.

Examples provided in this review highlight (a) instances of enhanced reactivity using water as a solvent, cosolvent, or additive, (b) formation of enzyme mimics that use hydrophobic forces to reinforce substrate/catalyst binding, (c) the use of aqueous media to interrogate proposed transition state geometries, and (d) the pH dependence of organocatalyzed aldol reactions. Limitations presented in the review include (a) substrate specific catalyst activities, (b) multistep/low-yielding synthesis of the organocatalysts, (c) slow catalysis rate in pure aqueous media, (d) high catalyst loading, and (e) poor to moderate selectivity (Tetrahedron: Asymmetry 2015, 26, 1215−1244).

Tetrahedron: Asymmetry

Volume 26, Issues 21–22, 1 December 2015, Pages 1215–1244

Tetrahedron: Asymmetry Report Number 159

Water: the most versatile and nature’s friendly media in asymmetric organocatalyzed direct aldol reactions

Division of Organic Synthesis, Department of Chemistry, Visva-Bharati (A Central University), Bolpur, West Bengal 731 235, India

Hot water’s ability to promote unexpected reactions without any other reagents or catalysts.

Chinese and Japanese chemists have highlighted hot water’s ability to promote unexpected reactions without any other reagents or catalysts. The work should expand our understanding of how to harness the physicochemical properties of water to potentially replace more complex reagents and catalysts.

Above its critical point at 374°C and 218atm the properties of water change quite dramatically, explains Hiizu Iwamura from Nihon University in Tokyo. But even below that point, as water is heated, hydrogen bonding and hydrophobic interactions are disrupted. ‘This means that organic compounds get more soluble and salts become insoluble in hot pressurised water,’ Iwamura says. Dissociation of water into hydroxide (OH^–) and hydronium (H₃O⁺) ions also increases, he adds, so there are higher concentrations of these ions available to act as catalysts for reactions.

Iwamura was synthesising triaroylbenzene molecules for a previous project on molecular magnets, using base-catalysed Michael addition reactions, when he first became interested in whether the reactions might work in water. He teamed up with a chemical engineer colleague, Toshihiko Hiaki, who is more familiar with working at the required temperatures and pressures. Together, they found that 4-methoxy-3-buten-2-one could be transformed into 1,3,5-triacetylbenzene in pressurised water at 150°C, with no other additives (see reaction scheme).¹

Meanwhile, Jin Qu and her team at Nankai University in Tianjin have been investigating water-promoted reactions at lower temperatures, without the need for pressurised vessels, which Qu says is more accessible for many researchers and makes monitoring reactions easier. ‘In 2008, one of my students found he could hydrolyse epoxides in pure water at 60°C, in 90% yields,’ she explains. ‘At first I thought it was not very interesting, just a hydrogen-bonding effect, but as we found more examples I got more interested.’

More than a thermal effect

When Qu’s team hydrolysed an epoxide made from (-)-α-pinene, they found that at room temperature they got (-)-sobrerol, the product they expected. But at 60°C or higher, the sobrerol began to racemise, giving a mixture of the (+)- and (-)-forms (see reaction scheme). ‘We couldn’t understand why this was happening at first,’ says Qu, but eventually it became clear that the allylic alcohol group in the sobrerol, which is much less reactive than the epoxide in pinene, was also being hydrolysed. The same reactions happen at room temperature if acid is added, Qu says, but don’t happen in propanol or other alcoholic and hydrogen-bonding solvents heated to the same temperatures, so it is not simply a thermal effect.

Qu points out that these observations, along with those of Iwamura’s team, show that molecules that might usually be considered unreactive in water can undergo useful transformations. And these reactions can take place without other reagents or solvents, which would create extra waste streams. Also, owing to the decreased solubility of the organic product molecules when the solutions are cooled back to room temperature, they are often easy to purify as well.

Iwamura suggests that there are many other simple acid- and base-catalysed reactions that might be suitable for reacting in hot water. However, reactions with thermally unstable molecules, or those requiring delicate selectivity, are unlikely to be so effective at higher temperatures, he adds. He also makes a distinction between Qu’s work – in which the water molecules are directly involved in the reaction – and his own group’s, in which the water acts as the reaction medium and provides the catalyst. ‘Our reaction did not take place in water heated at reflux,’ Iwamura adds.

However, Hiaki points out that the potential environmental benefits of reduced waste streams will have little impact on industrial chemistry if the reactions remain confined to batch processes. ‘High temperature and pressure is detrimental for the scale up to commercial chemical plants,’ he says. For that reason, the team is developing a flow microreactor system that should be more industry compatible.REFERENCES, 1 T Iwado et al, J. Org. Chem., 2012, DOI: 10.1021/jo301979p, 2 Z-B Xu and J Qu, Chem. Eur. J., 2012 DOI: 10.1002/chem.201202886

Hydration: A process which adds water.