On-line monitoring of continuous flow chemical synthesis using a portable, small footprint mass spectrometer

Journal of the American Society for Mass Spectrometry

Volumn 25, Issue 10, 2014, Pages 1794-1802

  Bristow, Tony W T ^a   Ray, Andrew D ^a   O'Kearney Mcmullan, Anne ^a   Lim, Louise ^b   McCullough, Bryan ^c   Zammataro, Alessio ^d  

^a ASTRAZENECA   (United Kingdom)

^b UNIVERSITY OF STRATHCLYDE   (United Kingdom)

^c LGC   (United Kingdom)

^d GMS House   (United Kingdom)

Author keywords

Continuous flow chemistry; On line; Reaction monitoring; Small footprint portable mass spectrometer

Indexed keywords

ATMOSPHERIC IONIZATION; ATMOSPHERIC PRESSURE; ELECTROSPRAY IONIZATION; IMPURITIES; IONIZATION; MASS SPECTROMETERS; MASS SPECTROMETRY; OPTIMIZATION; REACTION INTERMEDIATES; SOCIAL NETWORKING (ONLINE); VOLTAGE MEASUREMENT;

ATMOSPHERIC PRESSURE IONIZATION; CONTINUOUS FLOWS; EXPERIMENTAL PARAMETERS; ON-LINE; ON-LINE CHARACTERIZATION; ONLINE MASS SPECTROMETRY; REACTION MONITORING; SMALL FOOTPRINTS;

SYNTHESIS (CHEMICAL);

ACETONITRILE; FORMIC ACID; ISOCYANATE; REAGENT; WATER; ISOCYANIC ACID DERIVATIVE;

ARTICLE; DILUTION; ELECTROSPRAY; FLOW; HYDROLYSIS; HYPERBARISM; IONIZATION; MASS SPECTROMETER; MASS SPECTROMETRY; ONLINE MONITORING; PORTABLE EQUIPMENT; PUMP; REPRODUCIBILITY; STANDARD; STEADY STATE; SYNTHESIS; TEMPERATURE; CHEMICAL STRUCTURE; CHEMISTRY; DEVICES; DRUG DESIGN; DRUG INDUSTRY; EQUIPMENT DESIGN; PROCEDURES;

DRUG DESIGN; DRUG INDUSTRY; EQUIPMENT DESIGN; ISOCYANATES; MASS SPECTROMETRY; MODELS, MOLECULAR; REPRODUCIBILITY OF RESULTS; TEMPERATURE;

EID: 84919882437     PISSN: 10440305     EISSN: 18791123     Source Type: Journal    
DOI: 10.1007/s13361-014-0957-1     Document Type: Article

References (18)

1. Griffiths-Jones, C.M., Hopkin, M.D., Jönsson, D., Ley, S.V., Tapolczay, D.J., Vickerstaffe, E., Ladlow, M.J.: Fully automated flow-through synthesis of secondary sulfonamides in a binary reactor system. Combinat. Chem. 9, 422-430 (2007)
2. Carter, C.F., Lange, H., Ley, S.V., Baxendale, I.R., Wittkamp, B., Goode, J.G., Gaunt, N.L.: ReactIR flow cell: a new analytical tool for continuous flow chemical processing. Organic Process Res. Dev. 14, 393-404 (2010)
3. Pivonka, D.E., Russell, K., Gero, T.: Tools for combinatorial chemistry: in situ infrared analysis of solid-phase organic reactions. Appl. Spectrosc. 50, 1471-1478 (1996)
4. DeThomas, F.A., Hall, J.W., Monfre, S.L.: Real-time monitoring of polyurethane production using near-infrared spectroscopy. Talanta 41, 425-431 (1994)
5. Clegg, I.M., Pearce, J., Content, S.T.: In situ raman spectroscopy: a process analytical technology tool to monitor a de-protection reaction carried out in aqueous solution. Appl. Spectrosc. 66, 151-156 (2012)
6. Schafer, W.A., Hobbs, S., Rehm, J., Rakestraw, D.A., Orella, C., McLaughlin, M., Ge, Z., Welch, C.J.: Mobile tool for HPLC reaction monitoring. Organic Process Res. Dev. 11, 870-876 (2007)
7. Welch, C.J., Gong, X., Cuff, J., Dolman, S., Nyrop, J., Lin, F., Rogers, H.: Online analysis of flowing streams using microflow HPLC. Organic Process Res. Dev. 13, 1022-1025 (2009)
8. Shey, J.Y., Sun, C.M.: Liquid-phase combinatorial reaction monitoring by conventional 1H NMR spectroscopy. Tetrahedron Lett. 43, 1725-1729 (2002)
9. Fabris, D.: Mass spectrometric approaches for the investigation of dynamic processes in condensed phase. Mass Spectrom. Rev. 24, 30-54 (2005)
10. Dell'Orco, P., Brum, J., Matsuoka, R., Badlani, M., Muske, K.: Monitoring process-scale reactions using API mass spectrometry. Anal. Chem. 71, 5165-5170 (1999)
11. Zhu, L., Gamez, G., Chen, H.W., Huang, H.X., Chingin, K., Zenobi, R.: Real-time, on-line monitoring of organic chemical reactions using extractive electrospray ionization tandem mass spectrometry. Rapid Commun. Mass Spectrom. 22, 2993-2998 (2008)
12. McCullough, B.J., Bristow, T., O'Connor, G., Hopley, C.: On-line reaction monitoring by extractive electrospray ionization. Rapid Commun. Mass Spectrom. 25, 1445-1451 (2011)
13. Harry, E.L., Bristow, A.W.T., Wilson, I.D., Creaser, C.S.: Real-time reaction monitoring using ion mobility-mass spectrometry. Analyst 136, 1728-1732 (2011)
14. Roscioli, K.M., Zhanga, X., Li, S.X., Goetzb, G.H., Chengb, G., Zhangc, Z., Siemsa, W.F., Hill Jr., H.H.: Real time pharmaceutical reaction monitoring by electrospray ion mobility-mass spectrometry. Int. J. Mass Spectrom. 336, 27-36 (2013)
15. Malcolm, A., Wright, S., Syms, R.R.A., Moseley, R.W., O'Prey, Shane., Dash, N., Pegus, A., Crichton, E., Hong, G., Holmes, A.S., Finlay, A., Edwards, P., Hamilton, S.E., Welch, C.J.: A miniature mass spectrometer for liquid chromatography applications. Rapid Commun. Mass Spectrom. 25, 3281-3288 (2011)
16. Browne, D.L., Wright, S., Deadman, B.J., Dunnage, S., Baxendale, I.R., Turner, R.M., Ley, S.V.: Continuous flow reaction monitoring using an on-line miniature mass spectrometer. Rapid Commun. Mass Spectrom. 26, 1999-2010 (2012)
17. Loudon, G.M., Radhakrishna, A.S., Almond, M.R., Blodgett, J.K., Boutin, R.H.: Conversion of aliphatic amides into amines with [IJ Bis(trifluoroacetoxy)iodo]benzene. 1. Scope of the reaction. J. Org. Chem. 49, 4212-4216 (1984)
18. Palmiera, A., Ley, S.V., Hammond, K., Polyzos, A., Baxendale, I.R.: A microfluidic flow chemistry platform for organic synthesis: the Hofmann arrangement. Tetrahedron Lett. 50, 3287-3289 (2009)