**4. Conclusions**

The C2-halogen played a significant role in determining the ratio of di- to tri-deuterated species. With all analogues except the 2-F, conversions of ≥90% and exclusive formation of the di-deuterated species (**53**) were observed with 5% Pt/Al2O3. However with (*E*)-1-(2-fluorophenyl)-3-(4-methoxyphenyl)prop-2-en-1-one this catalyst afforded a 5:95 ratio of **53**:**54** with 97% conversion. Switching to the less active Pd/BaSO4 catalyst afforded 100% conversion of the 2-F analogue, with a best ratio of 89:11 (**53**:**54**). The presence of the fluorine had a significant

As further catalysts are developed for flow hydrogenation, the specificity and robustness of the chemical transformations achievable increase. Flow hydrogenation does require the use of a rare metal catalyst, which can be both expensive and potentially environmentally unsustainable. This negates the toxicity and disposal problems related to classical reducing agents and suggests that flow hydrogenation approaches may be expensive and not environmentally benign. This has led to the development of alternative hydrogenation catalysts such as carbonsupported iron-phenanthroline complexes, nickel nanoparticles, and FeNi alloys. These new

**Catalyst Starting material Product Conditions References**

Substituted anilines (6 examples)

Substituted anilines

Aldehydes and alcohols

60–110°C, 10–20 bar, 0.5 mL min

24–43 Selectivity 51–100%

Olefin yield not reported; nitro reduction up to 99%

25°C, 5 bar, 2.0 mL min−1, >99%

25°C, 15 bar, 1.5 mL min−1, >99%

30°C, 1 bar, 0.5 mL min−1,

30°C, 1 bar, 0.5 mL min−1, 88%

20°C, 1 bar, 1.5 mL min−1, 94%

60–80°C, 6 bar, 37 kg h−1, >99% [53]

[49]

[50]

[51]

[52]

[54]

−1, 98–100%

Various 60–110°C, 1 bar, 0.5 mL min−1,

86–98%

30°C, 1 bar, 94%

effect on the deuteration of this family of chalcones.

282 New Advances in Hydrogenation Processes - Fundamentals and Applications

catalysts show broad spectrum reductive capabilities (**Table 5**).

nitrobenzenes (6 examples)

Alkyne, aldehyde, and halogenated species

and nitrobenzenes (9 examples)

nitrobenzenes (13 examples)

Michael acceptors (14

examples)

**Table 5.** Use of novel catalysts in flow reduction reactions.

**3.9. New catalysts**

1.9% Au/Al2O3 Substituted

Pd-Maghemite Substituted

Designed porous structure

reactor (DPSR) Al2O3-ZnO


Pd0

ARP-Pt Olefins (24 examples)

Pd/C (3%)

Bimodal and trimodal

The body of evidence continues to grow illustrating that flow methodologies, in particular flow hydrogenation, offer significant advantages over batch technologies in medicinal chemistry. Flow chemistry has been demonstrated to enhance yields, simplify reaction work up, improve safety, and allow in-line analysis. The coupling of modular flow systems has allowed automated and semiautomated high yield, low purification requirement synthesis of active pharmaceutical ingredients over multiple cascading steps.

Flow-based reductions continue to provide greater access to new chemical scaffolds for use in drug design and development as well as to provide efficient methods for the production of current pharmaceuticals.
