Raman monitoring

Microwave-assisted synthesis is attractive to researchers for many reasons, including speed, yields, and the potential for reduced solvent use. Raman monitoring offers a convenient way to elucidate the chemical mechanism while instantly, continuously monitoring reaction kinetics. This enables rapid, data-driven process optimizations without concerns about safely and accurately sampling out of a microwave vessel stopped mid-reaction. Pivonka and Empheld of AstraZeneca Pharmaceuticals describe the continuous acquisition of Raman spectra of an amine or Knoevenagel coupling reaction in a sealed microwave reaction vessel at elevated temperatures and pressures [134]. 

E. Widjaja, Y.Y. Tan and M. Garland, Application of band-target entropy minimization to on-line Raman monitoring of an organic synthesis. An example of new technology for process analytical technology, Org. Process Res. Dev., 11, 98-103 (2007). 

N.E. Leadbeater, R.J. Smith and T.M. Barnard, Using in situ Raman monitoring as a tool for rapid optimisation and scale-up of microwave-promoted organic synthesis Esterification as an example, Org. Biomol. Chem., 5, 822-825 (2007). 

M. Mermoux, B. Marcus, L. Abello, N. Rosman and G. Lucazeau, In situ Raman monitoring of the growth of CVD diamond films, J. Raman Spectrosc., 34, 505-514 (2003). 

O Sullivan discussed the influence of particle size on quantitative Raman monitoring in slurries [40], A system of P-form D-mannitol in toluene in the presence of sucrose was studied. It was found that although keeping the number and size of mannitol crystals constant the measured Raman signal varied with different particle size of the sucrose. These results show that particle size must always be taken into consideration in quantitative measurements and a linear relationship can not be taken for granted. 

Savolainen et al. investigated the role of Raman spectroscopy for monitoring amorphous content and compared the performance with that of NIR spectroscopy [41], Partial least squares (PLS) models in combination with several data pre-processing methods were employed. The prediction error for an independent test set was in the range of 2-3% for both NIR and Raman spectroscopy for amorphous and crystalline a-lactose monohydrate. The authors concluded that both techniques are useful for quantifying amorphous content however, the performance depends on process unit operation. Rantanen et al. performed a similar study of anhydrate/hydrate powder mixtures of nitrofurantoin, theophyllin, caffeine and carbamazepine [42], They found that both NIR and Raman performed well and that multivariate evaluation not always improves the evaluation in the case of Raman data. Santesson et al. demonstrated in situ Raman monitoring of crystallisation in acoustically levitated nanolitre drops [43]. Indomethazine and benzamide were used as model... 

One of the basic unit operations is dry mixing that is used in most manufacturing schemes. In Fig. 10.6, an example of the use of Raman monitoring for blend control is shown. In this case the blending procedure is very fast and the mixture is well blended within the 5 min used. De Beer et al. used an in situ Raman immersion probe setup to study an ibuprofen-xanthan gum... 

Fig. 10.6. Raman monitoring of dry mixing of propranolol and excipients in a Turbula blender...

Fig. 10.9. Raman monitoring of tablet content uniformity during tablet manufacturing...

Spatially resolved Raman spectroscopy has provided insights into the physicochemical processes that determine the distribution of the H2PMoOi iCoOV active phase in alumina pellets (Bergwerff et al., 2005). Molybdenum and cobalt complexes were found to diffuse through the pore structure of the alumina pellets at different rates the transport of cobalt complexes was fast, whereas molybdenum complexes required several hours to reach an equilibrated distribution. Spatially resolved Raman monitoring provides information about how preparation conditions affect the distribution of molybdenum ions (Bergwerff et al., 2005). 

Figure 13.12 Raman monitoring in the external mode region upon metal deposition Ag (a), Mg (b), and In (c). The experimental spectra are shown by open symbols and the fitted spectra by red lines. The Lorentzian functions used for curve...

In Raman monitoring of a slurry, the spectmm will be dominated by bands due to the solid, since the scattering cross section of the solid particles exceeds that of the solvent and solute molecules. This offers the opportunity to monitor solvent-mediated form changes in situ without the need for sampling, isolation and analysis. In situ monitoring has many advantages for this type of study... 

Adapted from Ma X, Yuan W, Belt SEJ, James SL Better understanding of mechanochemical reactions Raman monitoring reveals surprisingly simple pseudo-fluid model for a ball milling reaction. Chem Common... 

Marino I-G, Lottici PP, Bersani D, RascheUa R, Lorenzi A, Montenero A (2005) Micro-Raman monitoring of solvent-free TEOS hydrolysis. 1 Non-Cryst Solids 351 495-498 Her R, The Chemistry of SUica, Wiley, New York, 1979... 

Fig. 17 In-situ Raman monitoring of carbon formation on YSZ-Ni anodes operated carbonaceous fuels at OCP and 715 °C. (a) Carbon formation as a function of time for operation with CH3OH fuel, (b) Carbon formation as a function of time for operation with CH4 fuel, (c) Raman spectra of anode surfaces after 30 minutes of operation on CH3OH (blue) and CH4 (red), (d) G peak intensity for both CH3OH (blue) and CH4 (red) as a function of time. Figure reproduced from reference [162].

V Wagner, D Drews, N Esser, DRT Zahn, J Geurts, W Richter. Raman monitoring of semiconductor growth. J Appl Phys 75 7330-7333, 1994. 

Yck) BK, JtK) SW (2007) In situ Raman monitoring triazole formation from self-assembled monolayers of l,4-dieth5mylbenzene on Ag and Au surfaces via click eryclization. J Colloid Interf Sci 311 491 96... 

V. Calvino CasUda, Elena Perez-Mayoral, Miguel A. Bafiares, E. Lozano Diz, Real-time Raman monitoring of dry media heterogeneous alkylation of imidazole with acidic and basic catalysts, Chem. Eng. J. 161 (2010) 371-376. 

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