Economy, atom

Atan economy, a concept that was introduced by Trust in 1991, measures Ihe efficiency of a reaction by comparing the amount of the taigeted final product to the amount of other products gai-erated [11], This concept presents the need to design reactions where the majaity of the reactants are incoipcxated into the desired product. This approach is preferred over others, such as breaking down a complex reactant to obtain a product, due to the feet that in the latter approach, even when reaction yields are 100%, the rest of the starting material normally is wasted. 

MCRs are clear examples of successfully applied atom economy. In these reactions, different molecules are converted into a complex product in an efficient way. Thus, the development of MCRs also implies the development of atom-economical reactions. 

SCHEME 1.5 Syntheses of a large numher of compounds having the same base structure through Ugi four-component condensations carried out by Armstrong and coworkers [51b]. 

Improved atom efficiency can also be achieved if it was possible to carry out synthesis without the use of protecting groups. The protection-deprotection sequence of functional groups increases the nirmber of steps in the synthesis of target compounds. As such, novel chemistry is needed to overcome this. In elegant work reported by Baran et al. [Nature 446 404 2007], a total syrrthesis of a natural product was achieved without any protecting groups. 

The concept of atom economy was developed by B. M. Trost which deals with chemical reactions that do not waste atoms. Atom economy describes the conversion efficiency of a chemical process in terms of all atoms involved. It is widely used to focus on the need to improve the efficiency of chemical reactions. 

A logical extension of B. M. Trost s concept of atom economy is to calculate the percentage atom economy. This can be done by taking the ratio of the mass of the utilized atoms to the total mass of the atoms of all the reactants and multiplying by 100. 

Mass of atoms in the final product Mass of atoms in reactants 

Sheldon has developed a similar concept called percentage atom utilization. For instance, the percentage atom economy and percentage atom utilization calculation for the oxidation reaction of benzene to maleic anhydride is given below  

Percentage atom utilization = mfW (maleic. nhydriJe + 2 carbon dioxide + 2 w.ter)  

One of the fundamental and most important principles of Green Chemistry is that of atom economy. This essentially is a measure of how many atoms of reaetants end up in the final product and how many end up in byproducts or waste. The percentage atom economy can be calculated as 100 times the relative molecular mass (RJVIM) of all atoms used to make wanted product divided by the RMM of all reactants. Box 1.2. The real benefit of atom economy is that it can be calculated at the reaction planning stage from a balanced reaetion equation. Taking the following theoretical reaction  

Relative molecular mass desired products Relative molecular mass of all reactants 

Today most plants use butane as a feed stock because of the lower raw material price. Whilst, at the design stage, the choice of butene over benzene would appear obvious, the two routes do have differing selectiv-ities, negating some of the atom economy benefits of the butene route. 

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A synthetically powerful method, an approach based on cycloaddition chemistry, allows one to assemble the pyridine ring in one step. Not only is this method efficient, atom economy, but also its convergency allows for the preparation for highly substituted systems in which one can, in principle, control all five positions on the pyridine ring. A versatile example of this methodology is the Boger reaction. It has been applied to the synthesis of a very diverse set of targets. 

Maximize atom economy. Synthetic methods should maximize the incorporation of all materials used in a process into the final product so that waste is minimized. 

From the standpoints of both cost and atom economy, water is the ideal nucleophile for synthesis of enantioenriched C2-symmetric 1,2-diols from meso-epoxides. 

L9.96 Waste reduction is an important goal of the green chemistry movement. In many chemical syntheses in industry, not all the atoms required for the reaction appear in the product. Some end up in by-products and are wasted. Atom economy is the use of as few atoms as possible to reach an end product and is calculated as a percentage, using atom economy = (mass of desired product obtained)/(nrass of all reactants consumed) X 100%. 

Calculate the atom economy for the reaction, assuming 100% yield. 

Atom economy, by incorporating all reagents employed in the final product. This also contributes to reduction and/or ehmination of waste ... 

Scheme 1.1 Atom economy for maleic anhydride production routes...

Using benzene typical selectivities of around 65% are obtained commercially whilst for butene it is approximately 55%. If we multiply the theoretical atom economies by these figures we obtain practical atom economies of 28.7% for the benzene route and 35.6% for butene. This is a useful illustration of how the atom economy concept is a valuable additional tool in measuring overall reaction efficiency, and how good atom economy can compensate for poorer yields or selectivities. 

Rearrangements, especially those only involving heat or a small amount of catalyst to activate the reaction, display total atom economy. A classic example of this is the Claisen rearrangement, which involves the rearrangement of aromatic allyl ethers as shown in Scheme 1.2. Although... 

As the name suggests, these reactions involve addition of a regent to an unsaturated group and as such nominally display 100% atom economy. 

Substitutions are very common synthetic reactions by their very nature they produce at least two products, one of which is commonly not wanted. As a simple example 2-chloro-2-methylpropane can be prepared in high yield by simply mixing 2-methylpropan-2-ol with concentrated hydrochloric acid (Scheme 1.10). Here the hydroxyl group on the alcohol is substituted by a chloride group in a facile SnI reaction. Whilst the byproduct in this particular reaction is only water it does reduce the atom economy to 83%. 

Most substitutions have lower atom economies than this and produce more hazardous and a greater variety of by-products. Hexanol is much less reactive than 2-methylpropan-2-ol in substitution reactions one way of converting this to the chloride involves reaction with thionyl chloride (Scheme 1.11) here the unwanted by-products are HCl and SO2 reducing the overall atom economy to 55%. This readily illustrates how, even in... 

Elimination reactions involve loss of two substituents from adjacent atoms as a result unsaturation is introduced. In many instances additional reagents are required to cause the elimination to occur, reducing the overall atom economy still further. A simple example of this is the E2 elimination of HBr from 2-bromopropane using potassium -butoxide (Scheme 1.12). In this case unwanted potassium bromide and /-butanol are also produced reducing the atom economy to a low 17%. 

It is the formation of this material which makes the reaction have a low atom economy and, owing to the cost of disposal (usually by conversion to calcium phosphate and disposal as hazardous waste), has limited its commercial usefulness to high value products. Several methods have been developed to recycle (Ph)3PO into (Ph)3P but these have proved more complex than might be expected. Typically the oxide is converted to the chloride which is reduced by heating with aluminium. Overall this recovery is expensive and also produces significant amounts of waste. 

There are a number of past and present commercial routes to phenol using benzene as a feed stock. Outline two such processes, writing balanced equations for the reactions involved. Compare the two routes in terms of atom economy. 

Anthraquinone is widely use in the manufacture of a range of dyes. Two possible routes for manufacturing anthraquinone are (1) from the reaction of 1,4-naphthoquinone with butadiene and (2) reaction of benzene with phthalic anhydride. Describe mechanisms for both these reactions and identify likely reaction conditions and any other reagents required. Compare the atom economy of the two routes. Identify three factors for each route that may influence the commercial viability. 

Give an example of an SnI and an 8 2 reaction, explaining the mechanism and calculating the atom economy of the reaction. Suggest alternative synthetic routes to your products that are more atom economic. 

Show how styrene can be prepared using the following reactions somewhere in your synthetic procedure, (a) Hofmann elimination, (b) Grignard reaction, (c) Diels-Alder reaction. Compare the atom economies of each process. Identify any issues raised by using this approach to determine the most efficient synthetic route. 

In Chapter 1 the concept of atom economy was discussed as a design tool. Similarly in Chapter 2 the term E-factor was introduced as a measure of the amount of by-products formed per unit weight of product. Unlike atom economy the E-factor is determined from an actual process or can be extrapolated from laboratory work. As a valuable extension to the E-factor concept Sheldon has proposed an Environmental Quotient which is the product of the E-factor and a by-product unfriendliness ... 

The atom economy for this process is 86.5% (100 X 116/134), which is reasonable. To calculate the E-factor and EMY further information is needed. From published literature (Vogel s Practical Organic Chemistry ), a standard procedure is to mix butanol (37 g) with glacial acetic acid (60 g), and a small amount of sulfuric acid catalyst (ignored in all calculations). Following completion of the reaction the mixture is added to water (250 g). The crude ester is washed further with water (100 g), then saturated sodium bicarbonate solution (25 g) and finally water (25 g). After drying over 5 g of anhydrous sodium sulfate the crude ester is distilled to give product (40 g) in a yield of 69%. 

Review a recent synthetic reaction you have carried out in the laboratory. Write a balanced equation for the reaction(s) and calculate the atom economy. From your experimental results calculate the Yield, E-factor and Effective Mass Yield (ignoring any water used). Identify ways in which this reaction could be made greener. 

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