Water as Solvent for Organic and Material Synthesis - ACS Publications

Chapter 6

Water as Solvent for Organic and Material Synthesis Downloaded by NORTH CAROLINA STATE UNIV on September 20, 2012 | http://pubs.acs.org Publication Date: August 15, 2000 | doi: 10.1021/bk-2000-0767.ch006

Chao-Jun Li Department of Chemistry, Tulane University, New Orleans, LA 70118

Water as a potentially benign solvent for reactions and syntheses is discussed. While most laboratory and industrial organic reactions have been carried out in organic solvents, organic reactions in water have attracted more and more attention within the last decade. This resurgence is partly due to the drive for the development of more environmentally safe reaction processes. The use of water for organic and material syntheses, among many other benefits, reduces the volume of organic solvents used in various processes which will result in pollution-prevention.

Introduction When talking about organic and chemical synthesis in water, probably the first question that many people might ask is "why water?" Perhaps a better question is: "why not water?" This question was asked by Professor Breslow in the early 1980s during his study of Diels-Alder reactions and is an area of considerable research interest in the chemical community today. After all, aqueous chemistry is one of the oldest forces of change in the solar system (7), and water has been the solvent for all the biological transformations in nature. Although it is possible not to use solvents in certain reactions for carrying out syntheses the use of solvents is necessary in most occasions for mixing purposes and to avoid by-product formations. When selecting a solvent, water is a good choice for many reasons (2). The most obvious one is cost. Water is the most abundant solvent on earth; therefore, it is much cheaper to use a water solvent for both chemical synthesis and material synthesis. Second, water is not flammable, toxic, or explosive. Third, it is related to synthetic efficiency: when organic synthesis is carried out in water, it may be possible to avoid having to protect functionalities such as hydroxy groups that would potentially increase the overall efficiency of a synthetic scheme. Also, consider operational convenience: if a large scale synthesis is carried out in water in industry, the organic product (which is often insoluble in water) can, in principle, be simply isolated by phase separation. Finally, using water as a solvent hais the potential to reduce organic emissions to the environment. Despite f

62

© 2000 American Chemical Society In Green Chemical Syntheses and Processes; Anastas, P., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2000.

63 these advantages, the most abundant substance on earth is probably the least explored solvent for organic synthesis.

Downloaded by NORTH CAROLINA STATE UNIV on September 20, 2012 | http://pubs.acs.org Publication Date: August 15, 2000 | doi: 10.1021/bk-2000-0767.ch006

Reactions That Can Be Carried Out in Water Another question people may ask is: what kind of reactions can be carried out in water? To put it simply, we know that most major reaction types that have historically been carried out in anhydrous organic solvent in organic chemistry, have their counterparts in water. Among these reactions types, the more notable ones are pericyclic reactions, organometallic reactions, transition metal catalyzed reactions, and lewis acid catalyzed reactions.

Pericyclic

Reactions

In 1980, Breslow (3) made the dramatic observation that the reaction of cyclopentadiene with butenone in water was more than 700 times faster than the same reaction in isooctane. The reaction rate in methanol is comparable to that in a hydrocarbon solvent. Such an unusual acceleration of the Diels-Alder reaction by water was attributed to the "hydrophobic effect" (4) in which the hydrophobic interactions brought together the two nonpolar groups in the transition state. The use of β-cyclodextrin, which simultaneously forms an inclusion complex with the diene and dienophile, and the use of 4.86 M LiCl aqueous solution as solvent, which salts out nonpolar materials dissolved in water (5), further enhanced the rate of aqueous Diels-Alder reactions. The second-order rate constant of the reaction between hydroxymethylanthoraœneandN-ethylmaleimideinwaterat 45°C was over 200 times larger than in acetonitrile (eq. 1). In addition, Grieco has contributed extensively to the studies of aqueous DielsAlder reaction toward the syntheses of a variety of complex natural products. When the Diels-Alder reaction in Scheme 1 was carried out in water, a higher reaction rate and reversal of the selectivity were observed, compared to the same reaction in a hydrocarbon solvent (6). It should be noted that, for the aqueous reaction, the sodium salt of the diene was used. Water soluble co-solvents caused a rapid reduction in rate. The best result was obtained when the reaction was conducted with a five-fold excess of the sodium salt of diene carboxylate. In addition to the study of Diels-Alder reaction in aqueous media, Grieco and coworkers also studied the hetero Diels-Alder reactions (7) with nitrogen-containing dienophiles and [3,3]-sigmatropic rearrangement extensively. For example, the rearrangement of an allyl vinyl ether in water generates the aldehyde efficiently in water (eq. 2) (8). The corresponding methyl ester underwent the facile rearrangement similarly. A solvent polarity study on the rearrangement rate of the allyl vinyl ether was conducted in solvent systems ranging from pure methanol to water at 60°C. The first order rate constant for the rearrangement of the allyl vinyl ether in water was 18 χ 10"^ s"*, compared to 0.79 χ 10"^ s~* in pure methanol. These pioneer works generated the early academic interest of using water as solvent for synthesis. Theoretical and synthetic studies by many renown researchers have greatly advanced the pericyclic reactions in aqueous media (9).

In Green Chemical Syntheses and Processes; Anastas, P., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2000.


Α

Β

ratio Α/Β = 3 :1 (in water) 1 :0.85 (in benzene)

R= Na R= Et

Scheme 1

1.0.01 M pyridine in H 0 60-C,3.5h ^ 2

Na O C(CH ) ^/ +

2

2

6

2.H

+

^

%

C

H

0

^^(CH ) C0 H 2

6

2


65


Organometallic Reactions Metal-mediated carbon-carbon bond formations, using organometallic reagents such as Grignard reagents, are among the most fundamental and important reactions in organic chemistry (70). Such reactions are notorious for their sensitivity toward moisture. Very often, their generation and subsequent reactions have to be handled in a dry-box of inert environment, with the utmost exclusion of water. Thus, it would seem surprising that people would consider carrying out these reactions in aqueous media at all. Such organometallic-type reactions, if successful, could have profound implications for organic chemistry. Yet in the last decade or so, studies have shown that such reactions are in fact very possible in water. Our work and that of others have shown that various metals including tin (77), zinc (72), indium (13), bismuth (14), manganese (75), and even magnesium (16) can be used for such reactions. The most successful study is on reaction of carbonyl compounds with allyl halides (eq. 3) andpropargyl halides. The most effective metal is indium which was discovered by Li and Chan (72), and further developed by Whitesides (77), Paquette (18), Schmidt (79), and others. Progress, although slow, will be made to extend to alkylation of other than allyl and propargyl halides.

Transition Metal Catalyzed Reactions The use of transition metal catalysts for effecting organic transformations has gained increased role in synthesis due to the fact that these catalyzed reactions are usually more selective, the conditions are milder, and these processes are more atom economical (20). They also generate less waste than the use of stoichiometric amounts of reactants. Traditionally, transition metal catalysis has been carried out in organic solvent. Recent studies have shown that many transition metal catalyzed reactions can be carried out efficiently in water (27). For example, palladium catalyzed carbon-carbon bond formations were shown by several groups, e.g. Sinou (22) Genet (23) Beletskaya (24). Casalnuovo and Calabrese reported that by using the water-soluble palladium(O) catalyst Pd(PPti2(w-C6H4S03M))3 (M= Na+, K+) various aryl bromides and iodides reacted with aryl and vinyl boronic acids, terminal alkynes and dialkyl phosphites to give the cross-coupling products in high yields in water (eq. 4) (25). Research from our own group in this area resulted in a novel functional group reshuffling reaction by using ruthenium catalyst (eq. 5) and and a palladium catalyzed simple/practical bis(aryl)acetylene synthesis with acetylene gas (eq. 6) (26).

Lewis Acid Catalyzed Reactions Lewis acids were generally considered water and moisture sensitive. However, recent studies predominantly by Kobayashi and co-workers have shown that many Lewis acids tolerate the presence of a large amount of water in their reactions. For example, a catalytic amount of lanthanide triflate (a stronger Lewis acid) greatly



66

ΟΗ

Μ Η 0

[Pd]

R-X + R'-Y

(3)

R

2

(4)

R-R'

47-100%

OH XPh'

OH

2-4 mol% RuCI (PPh ) 2

3 3

H 0, air atmosphere 49-75%

XPh'

2

[Pd]/Et N 3

CH CN/H 0, R.T. X' 3

2


(5)

67 improved the rate and the yield of the following Mukaiyama Aldol reaction (eq. 7) (27). Subsequently, various reactions have been found to be catalyzed with watertolerant Lewis acids by several groups (28).

Synthesis in Water


Chemical

Synthesis

The use of water as solvent for chemical synthesis could, in principle, lead to huge environmental and economic benefits if designed properly. The best example in this regard is the Ruhrchemie/Rhône-Poulenc's hydroformylation process (29). The hydroformylation process is one of the most successful applications of aqueous medium catalysis in industrial manufacture. It started in 1982 with a series of patents including the synthesis of aldehydes (29), the recovery of rhodium catalyst (30), and the preparation of water-soluble sulfonated phosphane ligands (31). The Ruhrchemie/Rhône-Poulenc's process went into operation two years later. The present annual production of butyraldehyde alone exceeds a quarter of million tons by this process. The product is separated from the catalyst solution by a simple phase separation, and the catalyst solution is recharged to the reactor for further reaction. During the process, the loss of rhodium catalyst in the organic phase is negligible. The reaction provides predominantly n-butyraldehyde (eq. 8).

Organic

Synthesis

Reactions in water developed by many groups have been elegantly applied in the synthesis of natural products (1). Although it is difficult to include all of the studies within this paper, a particular example is noted here. That is the sialic acid synthesis initially developed by Chan and Li (13), and advanced by Whitesides and co-workers (32). In this example, (+)-3-deoxy-D-^/yc^rc>-D-^aA3Cto-nonulosonic acid (KDN, 1) was synthesized by using indium mediated cross-coupling of a carbohydrate with an allyl bromide derivative followed by ozonolysis (Scheme 2). During this synthesis, no protection is required, the water soluble carbohydrate is used directly without the usual required protection-deprotection process involving carbohydrates. The synthesis was later further improved to two steps by Chan's group (33). Stepwise, these syntheses are equivalent to or better than natural syntheses. Such reactions have been applied to many other syntheses in our group (34) as well as in others.

Material Synthesis in Water New Polymerization Processes Many polymerization processes including radical, cationic, and anionic polymerizations can proceed in water (35). Recent studies have shown transition


68

Ο

OSiMe

OH Ο

Yb(OTf)

3

3


Η^Η

(7)

THF/H 0(2:1) r.t. 3-12h 77-94% 2

CH -CH=CH + CO + H 3

2

R'

; H0

C a t H R h (

Water as Solvent for Organic and Material Synthesis - ACS Publications

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