Uses+for+Glycerol+in+Current+Industry


 * Glycerol as a Solvent in Current Industry**

In the past, glycerol has not been used as a solvent in the chemical industry. Recently, developments have been made to prove how glycerol is not only a good replacement for other solvents but can feasibly be considered a **green solvent**, especially used for organic transformations. Examples of how glycerol is starting to be used in the industry are outlined below: Return to Homepage 18]
 * Organic synthesis
 * Enhancing Reaction Selectivity
 * Solvent for Biocatalysis
 * Catalyst Design and Recycling
 * Solvent for Separation
 * Use in Materials Chemistry

** Organic synthesis **
In the past, organic synthesis reactions such as Heck reactions (a reaction between a saturated halide with an alkene to form a substituted alkene), Suzuki reactions (a reaction where an aryl or vinyl boronic acid reacts with an aryl or vinyl halide using a palladium catalyst) and hydrogenation reactions produced high yields and feasible extraction of products (by liquid–liquid phase extraction with ethers or esters) when glycerol was used, replacing conventional solvents. However, no advantage in terms of catalyst activity or reaction selectivity was found when using glycerol in these cases. In 2008 Gu and Jerome found that glycerol as a solvent could be used in order to avoid the use of a conventional catalyst. They noted that in the case of technical grade glycerol, the presence of residual free fatty acid salts may play the role of a catalyst. They reported the “aza-Michael reaction between p-anisidine and n-butyl acrylate can successfully proceed under catalyst-free conditions using glycerol as a sole solvent.” 9] (Figure 1). Many other solvents were found to be un-effective. Similarly in the “Michael addition of indole (**4**) to nitrostyrene (**5**) glycerol was found to be capable of affording the desired product in 80% yield under catalyst free conditions.” 9] (Figure 2)

**Figure 1.** Aza-Michael reaction of p-anisidine in different solvent.9] **Figure 2**. Michael reaction of indole in different solvent systems.9] ====However some organic synthesis reactions could take place with the use of glycerol as a solvent, but needed a catalyst in order to obtain a high yield. One example is the electrophilic activations of aromatic aldehydes with indoles or 1,3-cyclohexanediones with a Lewis acid catalyst. ====

Overall there are some main advantages and disadvantages of using glycerol as a solvent in the organic synthesis reactions:

**Advantages** **Disadvantages**
 * A reduction in waste due to the use of non-conventional catalysts
 * Use of acid-sensitive substrates and easy separation of the reaction products (products are insoluble in glycerol).
 * The use of organic solvents to extract products that are soluble in glycerol
 * The use of a Lewis acid in order to improve reaction yield for less-reactive substrates.

**Enhancing reaction selectivity **

The selectivity of certain reactions has been improved using glycerol as a solvent, in order to produce higher product yields. <span style="font-family: Arial,Helvetica,sans-serif;">One example of such reactions involves p-anisdine with styrene oxide (called a ring-opening reaction), which can be performed without a catalyst by using glycerol. The same selectivity can be performed using water, however glycerol demonstrates a better regioselectivity.

<span style="font-family: Arial,Helvetica,sans-serif;">Another reaction involving styrene, paraformaldehyde and dimedone (Figure 3) shows an extremely larger yield when using glycerol (at 68%) versus other solvents such as water, toluene, nitromethane. In glycerol, the high product yield was obtained due to a high reaction selectivity. In order to achieve maximum selectivity, the Knoevenagel reaction has to be the rate-determining step while the hetero-Diels Alder reaction has to proceed quickly. In the Knoevenagel reaction, due to various reasons such as the structure of glycerol, the hydrogen bonding of glycerol and the insolubility of the by-product 20 in glycerol, the by-product 20 was piled on top of the paraformaldehyde. This coating of paraformaldehyde by 20 observed in glycerol significantly inhibited its decomposition, thus favoring the formation of intermediate 19. In addition, the rate of the hetero-Diels Alder reaction was increased in glycerol because it is a polar protic solvent. This property allows the solvation of reactant intermediates, where the intermediate energy decreases relative to the starting material, so that the rate is fast. Overall, the structure of glycerol, its polarity (which determines solvent solubility) and the intermolecular forces that arise from its structure can make a reaction more selective. The product yield obtained can therefore depend on the way in which a solvent interacts with the reactants.

**Figure 3.** Three-component reaction involving styrene,paraformaldehyde and dimedone and its reaction pathway [9 ] <span style="font-family: Arial,Helvetica,sans-serif;">Finally glycerol has been used uniquely for the high selectivity of desired products for one-pot two step reactions. By using a single reactor, the yield of the product increases, while separation processes and purification of intermediate compounds are avoided. Examples include a reaction involving arylhydrazines, B-ketone esters, formaldehyde and styrenes (Figure 4) and a reaction involving indoles, arylhydrazine, B-ketone, esters (Figure 5).

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">**Figure 4.** One-pot sequential reaction involving phenylhydrazine, ethyl 4-methoxybenzoylacetate, <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">alpha-methylstyrene and paraformaldehdye in glycerol.<span style="font-family: Arial,Helvetica,sans-serif; font-size: 80%; vertical-align: super;">9]

<span style="font-family: Arial,Helvetica,sans-serif;">

**Figure 5**. One-pot sequential reaction involving phenylhydrazine, ethyl 4-methoxybenzoylacetate, 1-ethyl-2-phenylindole and paraformaldehyde in glycerol. 9]


 * S ** ** ol vent for** **biocatalysis**

<span style="font-family: Arial,Helvetica,sans-serif;">Glycerol can be used as a solvent with the use of natural catalysts due to its low toxicity and high affinity for hydrophilic compounds. Such reactions include a Baker’s yeast catalyzed reduction of ketones using glycerol as a solvent and bioreductions of 2**’**-chloroacetophenone using glycerol as a co-solvent. In both reactions involving bio-catalysis a high yield can be obtained using glycerol as a solvent.

<span style="font-family: Arial,Helvetica,sans-serif;">**<span style="color: #008080; font-family: Arial,Helvetica,sans-serif; font-size: 110%;">Catalyst design and recycling **

<span style="font-family: Arial,Helvetica,sans-serif;">Homogeneous catalyst recovery is a process where solvents are used to immoblize catalysts in order for them to be re-used in a cycle. It is very important in green chemistry as it reduces waste and recycles the catalyst. The solvent must have a better solubility with the homogeneous catalyst then with the extracted organic solvents, so glycerol based on its high solubility with ionic compounds could be used for catalyst recycling. Silveria investigated the catalytic formation of bisindolylmethane in glycerol over CeCl3 Lewis acid and found that “the reaction products can be selectively extracted from the glycerol/CeCl3 mixture by liquid phase extraction with ethyl acetate, thus allowing a convenient recycling of both CeCl3 and glycerol.” 9] <span style="font-family: Arial,Helvetica,sans-serif;">Glycerol can also dissolve organomettalics complexes, thus allowing non-ionic catalysts to be recovered as well. One example is the hydrogenation reaction catalyzed by the [Ru(**p**-cumene)Cl2]2 complex using glycerol. This Ru complex catalyst is not ionized in glycerol, and is recycled after extraction of the reaction products with diethyl ether.

<span style="font-family: Arial,Helvetica,sans-serif;">However one example investigated by Jerome and Gu showed that glycerol was not able to immobilize all catalysts due to the insolubility of strongly hydrophobic substrates in glycerol and the generation of side-products owing to the high reactivity of glycerol towards some electrophiles. During the base-catalyzed ring opening of fatty epoxide with fatty acid in glycerol catalyzed by chitosan (a common basic catalyst), the process only took place at the glycerol interface due to the fact that both hydrophobic reactants were not miscible in glycerol resulting in an extremely slow reaction rate. In addition the ring opening if the fatty epoxide of glycerol was observed to react and form unwanted side products. (Figure 6). In order to avoid this problem the catalyst AP (aminopolysaccharide) was used. Briefly, the amphiphilic properties of AP and the hydrophobic core surrounded by amino atalytic sites (preventing the diffusion of glycerol) allowed this catalyst to be very selective and react at a very high reaction rate. This reaction was found to be able to recycle the AP catalyst 10 times by Gu and Jerome, thus implementing how a catalyst can be efficiently recycled and designed to obtain desired products with a high yield using glycerol as a solvent.


 * Figure 6**. Ring-opening of epoxide with carboxylic acid in glycerol 9]

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 110%;"> <span style="font-family: Arial,Helvetica,sans-serif; font-size: 14px; line-height: 21px;">** Solvent for separation ** <span style="color: #008080; font-family: Arial,Helvetica,sans-serif; font-size: 110%;">

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 9pt;">One important bio-fuel is bioethanol, a green alternative to gasoline. In the past, purification of bioethanol by extractive distillation was achieved using monoethyleneglycol, a compound derived from fossil fuels. Dias and co-workers proposed a better method consisting of the replacement of monoethyleneglycol by glycerol (Figure 7). When glycerol was used, the separation process of ethanol was more effective, where the “ethanol, water and glycerol were all recovered with more than 99% purity." 9]

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">**Figure 7**: Configuration of extractive distillation <span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%;">for the purification of bioethanol with glycerol.<span style="font-family: Arial,Helvetica,sans-serif; font-size: 90%; vertical-align: super;">[ 9 ]

<span style="font-family: Arial,Helvetica,sans-serif;"> <span style="color: #008080; font-family: Arial,Helvetica,sans-serif; font-size: 110%;">**Use in Materials Chemistry**

<span style="font-family: Arial,Helvetica,sans-serif;">Green solvents are commonly used in the preparation of materials. Solvents presently used include super critical CO <span style="font-family: Arial,Helvetica,sans-serif; vertical-align: sub;">2 <span style="font-family: Arial,Helvetica,sans-serif;"> and ionic liquids but glycerol shows promising properties for this application. Its high boiling point and low vapor pressure allow it to be used in reactions at high temperatures. Another benefit is the good solubility of inorganic and organic compounds in glycerol.

<span style="font-family: Arial,Helvetica,sans-serif;">One way to prepare metal particles is by heating a metallic salt and reducing it. Polyols are generally used for this application but because glycerol also has a high boiling point and it can also act as a reducing reagent. A possible problem of using glycerol is the degradation at high temperatures, but it has been shown to be an effective solvent in making metal particles. The first example of this was in 2002 by Sinha and Sharma. They showed that "by heating Cu(OH)2, CuO and Cu(OAc)2 under atmospheric conditions in glycerol at a temperature below 240◦C, they successfully obtained some copper particles" 9] The copper particles also had a purity of greater than 99%.

<span style="font-family: Arial,Helvetica,sans-serif;">Application of a similar process that uses glycerol as a solvent and reducing reagent with silver nitrate, can produce silver particles with a high yield and uniformity. The time period for this process is also much shorter than in other polyols used. The size of the silver particles can be altered by changing the amount of silver nitrate to glycerol and the particles are also coated in a thin organic film, which keeps them from sticking together. Glycerol can also act as the reducing reagent with water as the solvent in the production of manganese dioxide nano particles. 9]

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