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2 Efficient Organic Synthesis: What Ultrasound Makes Easier
geration to say that the broad scope of power ultrasonics today—it is used in such
widely varied disciplines as polymer science, food technology, materials science and
the treatment of wastewater—has been significantly boosted by the expertise gained
from the field of sonosynthesis over the more than 90 years of its study (Chen et al.
2011; Gallego-Juárez and Graff 2015; Chatel 2017). The benefits offered lead to (i)
the acceleration of chemical reactions; (ii) the use of less forcing conditions; (iii)
more economical processes via the use of cruder reagents; (iv) reductions in the
number of reaction steps required; (v) the initiation of stubborn reactions; (vi) reductions in induction periods; (vii) enhancements in catalytic activity and/or efficiency;
and (viii) enhancements in radical reactions. Such effects are especially noticeable
in heterogeneous sonochemistry, i.e. reactions on and in the vicinity of solid surfaces where, in addition to the enhanced mass and heat transfer caused by ultrasonic
agitation, species released by cavitation into the bulk liquid will also interact with
adsorbed reagents and the catalytic sites of a solid.
2.2 The Need for Metrics
A comparative analysis of the green chemistry credentials of reactions—the use of
non-toxic reagents and solvents, non-hazardous protocols and operational conditions—shows that many syntheses that claim to be green are actually far from being so.
A series of chemistry metrics that assess yield, selectivity, waste, reaction efficiency
and mass productivity, among others, has been introduced. Moreover, process metrics include a number of other categories, such as reactor design, type of mixing,
throughput, inherent hazards, renewability, recyclability, product quality and cost
(Jiménez-González and Constable 2011). They are all useful in making meaningful
comparisons between methods and process options. It is always helpful to remember
that any given reaction can be activated by different methods, which can produce
similar or completely different results (Bruckmann et al. 2008; Tabasso et al. 2015).
The choice of which method to use depends on operation conditions: controllability,
scalability, ease of cleaning and maintenance as well as energy costs.
What can be misleading is the lack of critical appraisal that occurs when syntheses
are carried out under the so-called green conditions (such as solvent-free reactions
and reactions in water), while the amount of volatile solvents required for product
isolation and purification can be overlooked and the fate of waste ignored (Fegade
and Tremblay 2017; Cintas 2016). The systematic use of metrics is thus mandatory,
although it is rarely employed by sonochemists. Percentages for atom economy
or carbon efficiency (for organic reactions), and mass intensity, an adimensional
parameter which relates the total mass in the reaction vessel to the product mass,
serve as useful indications of efficiency (Constable et al. 2002; Jiménez-González
et al. 2012). Even the use of water, which is usually excluded from mass metrics
as it does not constitute an environmental impact per se, could be a major concern
in the future. In many parts of the world, competition for potable (drinking) water
has become a significant issue, meaning that running reactions in water and the
2 Efficient Organic Synthesis: What Ultrasound Makes Easier
geration to say that the broad scope of power ultrasonics today—it is used in such
widely varied disciplines as polymer science, food technology, materials science and
the treatment of wastewater—has been significantly boosted by the expertise gained
from the field of sonosynthesis over the more than 90 years of its study (Chen et al.
2011; Gallego-Juárez and Graff 2015; Chatel 2017). The benefits offered lead to (i)
the acceleration of chemical reactions; (ii) the use of less forcing conditions; (iii)
more economical processes via the use of cruder reagents; (iv) reductions in the
number of reaction steps required; (v) the initiation of stubborn reactions; (vi) reductions in induction periods; (vii) enhancements in catalytic activity and/or efficiency;
and (viii) enhancements in radical reactions. Such effects are especially noticeable
in heterogeneous sonochemistry, i.e. reactions on and in the vicinity of solid surfaces where, in addition to the enhanced mass and heat transfer caused by ultrasonic
agitation, species released by cavitation into the bulk liquid will also interact with
adsorbed reagents and the catalytic sites of a solid.
2.2 The Need for Metrics
A comparative analysis of the green chemistry credentials of reactions—the use of
non-toxic reagents and solvents, non-hazardous protocols and operational conditions—shows that many syntheses that claim to be green are actually far from being so.
A series of chemistry metrics that assess yield, selectivity, waste, reaction efficiency
and mass productivity, among others, has been introduced. Moreover, process metrics include a number of other categories, such as reactor design, type of mixing,
throughput, inherent hazards, renewability, recyclability, product quality and cost
(Jiménez-González and Constable 2011). They are all useful in making meaningful
comparisons between methods and process options. It is always helpful to remember
that any given reaction can be activated by different methods, which can produce
similar or completely different results (Bruckmann et al. 2008; Tabasso et al. 2015).
The choice of which method to use depends on operation conditions: controllability,
scalability, ease of cleaning and maintenance as well as energy costs.
What can be misleading is the lack of critical appraisal that occurs when syntheses
are carried out under the so-called green conditions (such as solvent-free reactions
and reactions in water), while the amount of volatile solvents required for product
isolation and purification can be overlooked and the fate of waste ignored (Fegade
and Tremblay 2017; Cintas 2016). The systematic use of metrics is thus mandatory,
although it is rarely employed by sonochemists. Percentages for atom economy
or carbon efficiency (for organic reactions), and mass intensity, an adimensional
parameter which relates the total mass in the reaction vessel to the product mass,
serve as useful indications of efficiency (Constable et al. 2002; Jiménez-González
et al. 2012). Even the use of water, which is usually excluded from mass metrics
as it does not constitute an environmental impact per se, could be a major concern
in the future. In many parts of the world, competition for potable (drinking) water
has become a significant issue, meaning that running reactions in water and the