Organic Process Research & Development
Article
lots (0.616 mol of acetonitrile for each lot), which were added
to 0.274 mol of 1,3-DMA and 4.933 mol of sulfuric acid that
had been initially placed inside the reactor.
(13) Audiger, L.; Watts, K.; Elmore, S. C.; Robinson, R. I.; Wirth, T.
Ritter Reactions in Flow. ChemSusChem 2012, 5, 257−260.
(14) Roberts, S. W.; Shaw, S. M.; Milne, J. E.; Cohen, D. E.; Tveten,
J. T.; Tomaskevitch, J.; Thiel, O. R. Mechanistic Insights and Safety
Evaluation of the Ritter Reaction Utilizing tert-Butyl Acetate as the
tert-Butyl Cation Source. Org. Process Res. Dev. 2012, 16, 2058−2063.
AUTHOR INFORMATION
(15) Battilocchio, C.; Baxendale, I. R.; Biava, M.; Kitching, M. O.;
Ley, S. V. A Flow-Based Synthesis of 2-Aminoadamantane-2-carboxylic
Acid. Org. Process Res. Dev. 2012, 16, 798−810.
Notes
(
16) Manne, S. r.; Sajja, E.; Ghojala, V. r.; Challa, S. Improved
The authors declare no competing financial interest.
Process for Memantine Hydrochloride. PCT Int. Appl. 2009057140,
009.
17) Wanka, L.; Cabrele, C.; Vanejews, M.; Schreiner, P. R. γ-
2
(
ACKNOWLEDGMENTS
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The authors are thankful to Mr. Vikas Mishra (Head, R&D
EHS), Mr. Sunil Kulkarni (Head, Corporate EHS), Dr. Ramesh
Dandala (Head, API-R&D), Mr. Indu Bhushan (Head, FDF-
R&D), Mr. A. Jyothibasu (Head-PD Lab), and Dr. Hari Babu
Aminoadamantanecarboxylic Acids through Direct C−H Bond
Amidations. Eur. J. Org. Chem. 2007, 1474−1480.
(18) Iwata, Y. Thermal Decomposition Behavior of Di-tert-butyl
Peroxide Measured with Differential Adiabatic Calorimeter. Chem. Eng.
Trans. 2013, 31, 835−840.
(CEO & MD) for their support and encouragement. The
authors are also thankful to Mr. B. Venkataramana, Mr. P.
Narendra, and Mr. Rajagopalan Sarangapani for arranging the
required chemicals and necessary information for experiments.
LIST OF SYMBOLS AND ABBREVIATIONS
ARSST, Advanced Reactive System Screening Tool
RC1e, reaction calorimeter
■
1
,3-DMA, 1,3-dimethyladamantane
psig, pounds per square inch (gauge)
Tinitial, initial temperature (°C)
Tonset, onset exothermic temperature (°C)
Tmax, maximum temperature attained as a result of the
exotherm (°C)
Tr, reaction mass temperature (°C)
ΔT , adiabatic temperature rise (°C)
ad
Q , heat of reaction (kJ)
r
MTSR, maximum temperature of a synthesis reaction (°C)
REFERENCES
■
(
1) Crowl, D. A.; Louvar, J. F. Chemical Process Safety: Fundamentals
with Applications; Prentice Hall: New York, 1990.
2) Center for Chemical Process Safety. Guidelines for Process Safety in
Batch Reaction Systems; Wiley-Interscience: New York, 1999.
3) Etchells, J. C. Why Reactions Run Away. Org. Process Res. Dev.
997, 1, 435−437.
4) Frurip, D. J. Selection of the Proper Calorimetric Test Strategy in
Reactive Chemicals Hazard Evaluation. Org. Process Res. Dev. 2008, 12,
287−1292.
5) Stoessel, F. Thermal Safety of Chemical Processes: Risk Assessment
and Process Design; Wiley-VCH: Weinheim, Germany, 2008.
6) Bretherick’s Handbook of Reactive Chemical Hazards, 6th ed.;
Urben, P., Ed.; Elsevier: Amsterdam, 1999; Vol. 1; p 281.
7) Rowe, S. M. Thermal Stability: A Review of Methods and
Interpretation of Data. Org. Process Res. Dev. 2002, 6, 877−883.
8) Veedhi, S.; Sawant, A. Designing a Safer Process for the Reaction
(
(
1
(
1
(
(
(
(
of TFA with Sodium Borohydride in THF by Calorimetric Technique.
J. Therm. Anal. Calorim. 2013, 111, 1093−1097.
(
9) Snee, T. J.; Barcons, C.; Hernandez, H.; Zaldivar, J. M.
Characterization of an Exothermic Reaction Using Adiabatic and
Isothermal Calorimetry. J. Therm. Anal. 1992, 38, 2729−2747.
(
10) Regenass, W. The Development of Stirred-Tank Heat Flow
Calorimetry as a Tool for Process Optimization and Process Safety.
Chimia 1997, 51, 189−200.
(
11) Ubrich, O.; Srinivasan, B.; Lerena, P.; Bonvin, D.; Stoessel, F.
The Use of Calorimetry for On-Line Optimisation of Isothermal Semi-
Batch Reactors. Chem. Eng. Sci. 2001, 56, 5147−5156.
(
́
12) Andre, R.; Bou-Diab, L.; Lerena, P.; Stoessel, F.; Giordano, M.;
Mathonat, C. A New Reaction Calorimeter for Screening Purposes
during Process Development. Org. Process Res. Dev. 2002, 6, 915−921.
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dx.doi.org/10.1021/op400234w | Org. Process Res. Dev. XXXX, XXX, XXX−XXX