We would like to thank Corning for the gift of the glass flow reactor.

Health Warnings and Specification of Reagents 
Benzophenone Hydrazone: May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated. May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated. May cause skin irritation and eye irritation18.
Activated manganese oxide (MnO2): (Health MSDS rating of 2) Hazardous in ca...

<ol>
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M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microreactor+technology+and+continuous+processes+in+the+fine+chemical+and+pharmaceutical+industry:+Is+the+revolution+underway.">Microreactor technology and continuous processes in the fine chemical and pharmaceutical industry: Is the revolution underway.</a> Org Process Res Dev. 12 (5), 905-910 (2008).</li><li>Degennaro, L., Carlucci, C., De Angelis, S., Luisi, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Flow+Technology+for+Organometallic-Mediated+Synthesis.">Flow Technology for Organometallic-Mediated Synthesis.</a> J Flow Chem. 6 (3), 136-166 (2016).</li><li>Roberts, J. D., Watanabe, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Kinetics+and+Mechanism+of+the+Acid-Catalyzed+Reaction+of+Diphenyldiazomethane+with+Ethyl+Alcohol.">The Kinetics and Mechanism of the Acid-Catalyzed Reaction of Diphenyldiazomethane with Ethyl Alcohol.</a> J Am Chem Soc. 72 (11), 4869-4879 (1950).</li><li>Roberts, J. D., Watanabe, W., Mcmahon, R. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Kinetics+and+Mechanism+of+the+Reaction+of+Diphenyldiazomethane+and+Benzoic+Acid+in+Ethanol.">The Kinetics and Mechanism of the Reaction of Diphenyldiazomethane and Benzoic Acid in Ethanol.</a> J Am Chem Soc. 73 (2), 760-765 (1951).</li><li>Roberts, J. D., Watanabe, W., Mcmahon, R. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Kinetics+and+Mechanism+of+the+Reaction+of+Diphenyldiazomethane+with+2,4-Dinitrophenol+in+Ethanol.">The Kinetics and Mechanism of the Reaction of Diphenyldiazomethane with 2,4-Dinitrophenol in Ethanol.</a> J Am Chem Soc. 73 (6), 2521-2523 (1951).</li><li>Roberts, J. D., Regan, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kinetics+and+Some+Hydrogen+Isotope+Effects+of+the+Reaction+of+Diphenyldiazomethane+with+Acetic+Acid+in+Ethanol.">Kinetics and Some Hydrogen Isotope Effects of the Reaction of Diphenyldiazomethane with Acetic Acid in Ethanol.</a> J Am Chem Soc. 74 (14), 3695-3696 (1952).</li><li>Oferrall, R. A., Kwok, W. K., Miller, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Medium+Effects+Isotope+Rate+Factors+++Mechanism+of+Reaction+of+Diphenyldiazomethane+with+Carboxylic+Acids+in+Solvents+Ethanol+++Toluene.">Medium Effects Isotope Rate Factors + Mechanism of Reaction of Diphenyldiazomethane with Carboxylic Acids in Solvents Ethanol + Toluene.</a> J Am Chem Soc. 86 (24), 5553 (1964).</li><li>Aldrich, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Material Safety Data Sheet: Benzophenone Hydrazone. 4.2, 3-6 (2014).</li><li>Science Lab Chemicals &amp; Laboratory Equipment. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Material Safety Data Sheet: Manganese dioxide MSDS. , (2005).</li><li>Science Lab Chemicals &amp; Laboratory Equipment. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Material Safety Data Sheet: Potassium phosphate dibasic MSDS. , 1-5 (2005).</li><li>Science Lab Chemicals &amp; Laboratory Equipment. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Material Safety Data Sheet: Methylene Chloride MSDS. , 3-5 (2005).</li><li>Smith, L. I., Howard, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diphenyldiazomethane.">Diphenyldiazomethane.</a> Org. Synth. 3 (351), (1955).</li><li>Capot Chemical Co. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Material Safety Data Sheet, diphenyldiazomethane. 2017, (2010).</li><li>Science Lab. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Material Safety Data Sheet: P-nitrobenzoic acid MSDS. , 3-5 (2005).</li><li>Science Lab Chemicals &amp; Laboratory Equipment. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Material Safety Data Sheet Ethyl Alcohol 200 proof MSDS. , (2005).</li><li>Science Lab Chemicals &amp; Laboratory Equipment. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Material Safety Data Sheet Toluene MSDS. , 4-5 (2005).</li><li>Science Lab Chemicals &amp; Laboratory Equipment. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Material Safety Data Sheet o-Xylene MSDS. , 3-5 (2005).</li><li>Zheng, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cross-Coupling+between+Difluorocarbene+and+Carbene-Derived+Intermediates+Generated+from+Diazocompounds+for+the+Synthesis+of+gem-Difluoroolefins.">Cross-Coupling between Difluorocarbene and Carbene-Derived Intermediates Generated from Diazocompounds for the Synthesis of gem-Difluoroolefins.</a> Organic Letters. 17, 6150-6153 (2015).</li><li>Reimlinger, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=1,5-Dipolar+cyclizations,+I.+Definition+and+contributions+to+the+Imidazide/Tetrazole+tautomerism.">1,5-Dipolar cyclizations, I. Definition and contributions to the Imidazide/Tetrazole tautomerism.</a> Chem. Ber. 103, 1900 (1970).</li><li>Baumann, M., Garcia, A. M. R., Baxendale, I. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Flow+synthesis+of+ethyl+isocyanoacetate+enabling+the+telescoped+synthesis+of+1,2,4-triazoles+and+pyrrolo-[1,2-c]+pyrimidines.">Flow synthesis of ethyl isocyanoacetate enabling the telescoped synthesis of 1,2,4-triazoles and pyrrolo-[1,2-c] pyrimidines.</a> Org Biomol Chem. 13 (14), 4231-4239 (2015).</li><li>Baumann, M., Baxendale, I. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+synthesis+of+active+pharmaceutical+ingredients+(APIs)+using+continuous+flow+chemistry.">The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry.</a> Beilstein J Org Chem. 11, 1194-1219 (2015).</li><li>Pastre, J. C., Browne, D. L., Ley, S. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Flow+chemistry+syntheses+of+natural+products.">Flow chemistry syntheses of natural products.</a> Chem Soc Rev. 42 (23), 8849-8869 (2013).</li><li>Pirotte, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous+Flow+Polymer+Synthesis+toward+Reproducible+Large-Scale+Production+for+Efficient+Bulk+Heterojunction+Organic+Solar+Cells.">Continuous Flow Polymer Synthesis toward Reproducible Large-Scale Production for Efficient Bulk Heterojunction Organic Solar Cells.</a> Chemsuschem. 8 (19), 3228-3233 (2015).</li><li>Kumar, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Continuous-Flow+Synthesis+of+Regioregular+Poly(3-Hexylthiophene):+Ultrafast+Polymerization+with+High+Throughput+and+Low+Polydispersity+Index.">Continuous-Flow Synthesis of Regioregular Poly(3-Hexylthiophene): Ultrafast Polymerization with High Throughput and Low Polydispersity Index.</a> J Flow Chem. 4 (4), 206-210 (2014).</li><li>Helgesen, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Making+Ends+Meet:+Flow+Synthesis+as+the+Answer+to+Reproducible+High-Performance+Conjugated+Polymers+on+the+Scale+that+Roll-to-Roll+Processing+Demands.">Making Ends Meet: Flow Synthesis as the Answer to Reproducible High-Performance Conjugated Polymers on the Scale that Roll-to-Roll Processing Demands.</a> Adv Energy Mater. 5 (9), 1401996 (2015).</li><li>Grenier, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electroactive+and+Photoactive+Poly[lsoindigo-alt-EDOT]+Synthesized+Using+Direct+(Hetero)Arylation+Polymerization+in+Batch+and+in+Continuous+Flow.">Electroactive and Photoactive Poly[lsoindigo-alt-EDOT] Synthesized Using Direct (Hetero)Arylation Polymerization in Batch and in Continuous Flow.</a> Chem Mater. 27 (6), 2137-2143 (2015).</li><li>Pollet, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Production+of+(S)-1-Benzyl-3-diazo-2-oxopropylcarbamic+Acid+tert-Butyl+Ester,+a+Diazoketone+Pharmaceutical+Intermediate,+Employing+a+Small+Scale+Continuous+Reactor.">Production of (S)-1-Benzyl-3-diazo-2-oxopropylcarbamic Acid tert-Butyl Ester, a Diazoketone Pharmaceutical Intermediate, Employing a Small Scale Continuous Reactor.</a> Ind Eng Chem Res. 48 (15), 7032-7036 (2009).</li><li>Flack, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Al(OtBu)(3)+as+an+Effective+Catalyst+for+the+Enhancement+of+Meerwein-Ponndorf-Verley+(MPV)+Reductions.">Al(OtBu)(3) as an Effective Catalyst for the Enhancement of Meerwein-Ponndorf-Verley (MPV) Reductions.</a> Org Process Res Dev. 16 (3), 1301-1306 (2012).</li><li>Aponte-Guzman, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Tandem,+Bicatalytic+Continuous+Flow+Cyclopropanation-Homo-Nazarov-Type+Cyclization.">A Tandem, Bicatalytic Continuous Flow Cyclopropanation-Homo-Nazarov-Type Cyclization.</a> Ind Eng Chem Res. 54 (39), 9550-9558 (2015).</li><li>Liotta, C. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthetic+Transformations+Employing+Continuous+Flow.">Synthetic Transformations Employing Continuous Flow.</a> ACS- Fall 2013.Synthetic Transformations Employing Continuous Flow. , (2013).</li></ol>

Flow chemistry has gained much attention recently with an average of about 1,500 publications on the topic annually in research areas of Chemistry (29%) and Engineering (25%). Many successful processes have been conducted in flow. In numerous cases, flow chemistry was demonstrated to exhibit superior performances to batch for many applications such as the preparations of pharmaceutically active ingredients30,31, natural products32, and spe...

Green chemistry and engineering are creating a culture change for the future direction of industry1,2,3,4. Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer, and cost savings through the &#34;scaling out&#34; strategy as opposed to the traditional &#34;scaling up&#34;5,6,7,8,9,10.
Although the industries producing high-value products like the pharmaceutical industry have long favored batch processing, the advantages of flow technology have become attractive due to mounting economic competition and commercial production benefits11. For example, when scaling up batch processes, pilot scale units must be built and operated to ascertain accurate heat and mass transfer mechanisms. This is hardly sustainable and subtracts substantially from the marketable patent life of the product. In contrast, continuous flow processing allows for the advantages of scale out, eliminating the pilot-plant phase and engineering associated with production scale-a significant financial incentive. Beyond the economic impact, continuous technology also enables atomic and energy efficient processes. For instance, enhanced mixing improves mass transfer for biphasic systems, leading to improved yields, catalyst recovery strategies, and subsequent recycling schemes. Additionally, the ability to accurately manage the reaction temperature leads to precise control of reaction kinetics and product distribution12. The enhanced process control, quality of product (product selectivity) and reproducibility are impactful both from environmental and financial standpoints.
Flow reactors are available commercially with a wide variety of sizes and designs. In addition, customization of reactors to meet process needs can easily be achieved. Herein, we report experiments conducted in a glass continuous flow reactor (Figure 1). The assembly of microstructures (161 mm x 131 mm x 8 mm) made of glass is compatible with a wide range of chemicals and solvents and is corrosion-resistant over a wide range of temperatures (-25&#8211;200 &#176;C) and pressures (up to 18 bar). The microstructures and their arrangement were designed for multi-injection, high-performance mixing, flexible residence time, and precise heat transfer. All of the microstructures are equipped with two fluidic layers (-25&#8211;200 &#176;C, up to 3 bar) for heat exchange on either side of the reaction layer. Heat transfer rates are proportional to the heat transfer surface area and inversely proportional to its volume. Thus, these microstructures facilitate an optimum surface-to-volume ratio for improved heat transfer. There are two types of microstructures (i.e. modules): &#34;mixing&#34; modules and &#34;linear&#34; modules (Figure 2). The heart-shaped &#34;mixing&#34; modules are designed to induce turbulence and maximize mixing. In contrast, the linear modules provide additional residence time.
As proof of concept, we selected the well-described reaction of diphenyldiazomethane with carboxylic acids13,14,15,16,17. The reaction scheme is shown in Figure 3. The initial transfer of the proton from the carboxylic acid to the diphenyldiazomethane is slow and is the rate-determining step. The second step is rapid and yields the reaction product and nitrogen. The reaction was initially investigated to compare relative acidity of organic carboxylic acids in organic solvent (aprotic and protic). The reaction is first-order in the diphenyldiazomethane and first-order in carboxylic acids.
Experimentally, the reaction was conducted in presence of large excess of carboxylic acid (10 molar equivalents). As a consequence, the rate was pseudo first order with respect to the diphenyldiazomethane. The second order rate constant can then be obtained by dividing the experimentally obtained pseudo first order rate constant by the initial concentration of the carboxylic acid. Initially, the reaction of diphenyldiazomethane with benzoic acid (pKa = 4.2) was investigated. In batch, the reaction appeared to be relatively slow, reaching about 90% conversion in 96 minutes. As the reaction rate is directly proportional to the acidity of the carboxylic acid, we chose as a reaction partner the more acidic carboxylic acid, p-nitrobenzoic acid (pKa =3.4) to shorten the reaction time. The reaction of p-nitrobenzoic acid with diphenyldiazomethane in anhydrous ethanol was thus investigated in batch and flow (Figure 4). The results are provided in detail in the following section.
When the reaction is carried out in ethanol, three products can be formed: (i) benzhydryl-4-nitrobenzoate, which results from the reaction of p-nitrobenzoic acid with the diphenylmethane diazonium intermediate; (ii) benzhydryl ethyl ether that is obtained from reaction of the solvent, ethanol, with the diphenylmethane diazonium; and (iii) nitrogen. The product distribution was not studied as it is well documented in literature; rather we focused our attention to the technology transfer of the batch reaction to continuous flow13,14,15. Experimentally the disappearance of the diphenyldiazomethane was monitored. The reaction proceeds with a vivid color change, which can be visually observed by UV-Vis spectroscopy. This results from the fact that the diphenyldiazomethane is a strongly purple compound whereas all other products from the reaction are colorless. Therefore, the reaction can be visually monitored on a qualitative basis and quantitatively followed by UV spectroscopy (i.e. disappearance of the diphenyl diazomethane absorption at 525 nm). Herein, we first report the reaction of diphenyldiazomethane and p-nitrobenzoic acid in ethanol in batch as a function of time. Secondly, the reaction was successfully transferred and carried out into the glass flow reactor. The progress of the reaction was ascertained by monitoring the disappearance of diphenyldiazomethane using UV-spectroscopy (in batch and flow modes).

<table style="border-collapse:collapse;width:1075pt" width="1433">
	<colgroup>
		<col style="width:189pt" width="252" />
		<col style="width:188pt" width="251" />
		<col style="width:81pt" width="108" />
		<col style="width:617pt" width="822" />
	</colgroup>
	<tbody>
		<tr height="22" style="height:16.5pt">
			<td class="xl16" height="22" style="width:189pt;height:16.5pt" width="252">Thermometer</td>
			<td class="xl17" style="width:188pt" width="251">HB-USA/ Enviro-safe</td>
			<td class="xl17" style="width:81pt" width="108"></td>
			<td class="xl17" style="width:617pt" width="822">Any other instrument scientific company provider works</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Benzophenone hydrazone</td>
			<td class="xl19" style="width:188pt" width="251">Sigma-Aldrich</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Store at 2-8 &#176;C, 96% purity</td>
		</tr>
		<tr height="26" style="height:19.5pt">
			<td class="xl18" height="26" style="width:189pt;height:19.5pt" width="252">Activated MnO2</td>
			<td class="xl19" style="width:188pt" width="251">Fluka</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">&#8805; 90% purity, harmful if inhaled or swallowed. Refer to MSDS for more safety precautions</td>
		</tr>
		<tr height="26" style="height:19.5pt">
			<td class="xl18" height="26" style="width:189pt;height:19.5pt" width="252">Dibasic KH2PO4</td>
			<td class="xl19" style="width:188pt" width="251">Sigma-Aldrich</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Serious eye damage, respiratory irritant. Refer to MSDS for more safety precautions</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Dichloromethane (DCM)</td>
			<td class="xl19" style="width:188pt" width="251">Alfa Aesar</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">&#8805; 99.7% purity, argon packed</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Rotovap</td>
			<td class="xl19" style="width:188pt" width="251">B&#252;chi</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">accessory parts include Welch self-cleaning dry vacuum model 2027, and Neuberger KNP dry ice trap&#160;</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Bump trap</td>
			<td class="xl19" style="width:188pt" width="251">Chemglass</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Any other instrument scientific company provider works&#160;</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Neutral Silica Gel (50-200 mM)</td>
			<td class="xl19" style="width:188pt" width="251">Acros Organic/ Sorbent Technology</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Respiratory irritant if inhaled, refer to MSDS for more safety precautions</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Inert Argon Gas</td>
			<td class="xl19" style="width:188pt" width="251">Airgas</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Always ensure proper regulator is in place before using</td>
		</tr>
		<tr height="43" style="height:32.25pt">
			<td class="xl18" height="43" style="width:189pt;height:32.25pt" width="252">Medium Porosity Sintered Funnel Glass Filter</td>
			<td class="xl19" style="width:188pt" width="251">Sigma-Aldrich</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Any other instrument scientific company provider works</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Aluminum Foil</td>
			<td class="xl19" style="width:188pt" width="251">Reynolds Wrap</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Any other company works. Used to prevent photolytic damage towards DDM</td>
		</tr>
		<tr height="26" style="height:19.5pt">
			<td class="xl20" height="26" style="width:189pt;height:19.5pt" width="252">Para-NO2 benzoic acid</td>
			<td class="xl19" style="width:188pt" width="251">Sigma-Aldrich</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Skin contact irritant, eye irritant, respiratory irritant. Refer to MSDS for more safety precautions</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Pure ethyl alcohol (200 proof)</td>
			<td class="xl19" style="width:188pt" width="251">Sigma-Aldrich</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">&#8805; 99.5% purity, anhydrous. Highly flammable</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Toluene</td>
			<td class="xl19" style="width:188pt" width="251">Sigma-Aldrich</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">&#8805; 99.8% purity, anhydrous. Skin permeator, flammable</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl20" height="22" style="width:189pt;height:16.5pt" width="252">Ortho-xylene</td>
			<td class="xl19" style="width:188pt" width="251">Sigma-Aldrich</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">99% purity, anhydrous. Toxic to organs and CNS. Adhere to specifications dictated within MSDS</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Diphenyl diazo methane</td>
			<td class="xl19" style="width:188pt" width="251">Produced in-house</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Respiratory irritant, refer to MSDS for more safety precautions</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Corning reactor</td>
			<td class="xl19" style="width:188pt" width="251">Corning Proprietary</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Manufactured in 2009. model number MR 09-083-1A</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Stop watch</td>
			<td class="xl19" style="width:188pt" width="251">Traceable Calibration Control Company</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Any other company that provides monitoring with laboratory grade accredidation works</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Analytical balance</td>
			<td class="xl19" style="width:188pt" width="251">Denver Instruments</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Model M-2201, or any analytical balance that has sub-milligram capabilities</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Dram vials</td>
			<td class="xl19" style="width:188pt" width="251">VWR</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">2 dram, 4 dram, and 6 dram vials&#160;</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Micropipettes</td>
			<td class="xl19" style="width:188pt" width="251">Eppendorf</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">2-20 &#956;L and 100-1000 &#956;L micropipettes work</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Glass pipettes</td>
			<td class="xl19" style="width:188pt" width="251">VWR</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Any other instrument scientific company provider works</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">GC-MS</td>
			<td class="xl19" style="width:188pt" width="251">Shimadzu GC</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Software associated: GC Real Time Analysis</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">GC vials</td>
			<td class="xl19" style="width:188pt" width="251">VWR</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Any other providing company works</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Beakers</td>
			<td class="xl19" style="width:188pt" width="251">Pyrex</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">500 mL beakers&#160;</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Syringe pumps</td>
			<td class="xl19" style="width:188pt" width="251">Sigma Aldrich</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Teledyne Isco Model 500D</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Relief valve</td>
			<td class="xl19" style="width:188pt" width="251">Swagelok</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">Spring loaded relieve valve&#160;</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">One-way valves</td>
			<td class="xl19" style="width:188pt" width="251">Nupro&#160;</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">10 psi grade</td>
		</tr>
		<tr height="22" style="height:16.5pt">
			<td class="xl18" height="22" style="width:189pt;height:16.5pt" width="252">Two-way straight valves</td>
			<td class="xl19" style="width:188pt" width="251">HiP</td>
			<td class="xl19" style="width:81pt" width="108"></td>
			<td class="xl19" style="width:617pt" width="822">15,000 psi grade</td>
		</tr>
	</tbody>
</table>

continuous flow chemistry: reaction of diphenyldiazomethane with p-nitrobenzoic acid

Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer and cost savings through the &#34;scaling out&#34; strategy as opposed to the traditional &#34;scaling up&#34;. Herein, we report the reaction of diphenyldiazomethane with p-nitrobenzoic acid in both batch and flow modes. To effectively transfer the reaction from batch to flow mode, it is essential to first conduct the reaction in batch. As a consequence, the reaction of diphenyldiazomethane was first studied in batch as a function of temperature, reaction time, and concentration to obtain kinetic information and process parameters. The glass flow reactor set-up is described and combines two types of reaction modules with &#34;mixing&#34; and &#34;linear&#34; microstructures. Finally, the reaction of diphenyldiazomethane with p-nitrobenzoic acid was successfully conducted in the flow reactor, with up to 95% conversion of the diphenyldiazomethane in 11 min. This proof of concept reaction aims to provide insight for scientists to consider flow technology&#39;s competitiveness, sustainability, and versatility in their research.

Batch Reaction 
Diphenyldiazomethane was prepared according to literature28,29. The compound was crystallized from petroleum ether:ethyl acetate (100:2) and the purple crystalline solid was analyzed by H1 NMR, melting point, and MS. The analyses were consistent with the structure and reported literature values.
The reaction of diphenyldia...

Watch this Scientific Journal Video about Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid at JoVE.com

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

Flow chemistry carries environmental and economic advantages by leveraging superior mixing, heat transfer and cost benefits. Herein, we provide a blueprint to transfer chemical processes from batch to flow mode. The reaction of diphenyldiazomethane (DDM) with p-nitrobenzoic acid, conducted in batch and flow, was chosen for proof of concept.

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid

Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer and ...

The overall goal of this technique is to transfer chemical processes from batch to flow mode as demonstrated by the reaction of diphenyldiazomethane with para-Nitrobenzoic acid in a continuous flow reactor. This method can help identify how best to approach the technology transfer of chemical transformations from batch to flow processes. The main advantage of this techniques are chemical reactions that require precise temperature control and mixing or highly reactive intermediate or reagents.It is essential to first establish reaction kinetics and operational parameters in batch mode. After reaction optimization, the process can be transferred to flow mode. First, check that each high-pressure 500 milliliter syringe pump is connected to its own pump controller.Empty the solvent collection beakers. Place 400 milliliters of reagent grade ethanol in a clean beaker. Transfer one syringe pump inlet feed tube to the beaker and fully open the corresponding pump inlet valve.Then, on the syringe pump controller, select Constant Flow in the port connecting the controller to the pump transducer. Start filling the syringe pump with ethanol at 70 milliliters per minute. Monitor the flow rate reading and the solvent level in the beaker.Express the air from the pump. Once the syringe pump is full and pumping has stopped, close the inlet valve. Repeat this process to fill the second syringe pump with ethanol.Then, open one pump outlet valve and start flowing ethanol through the continuous flow reactor system. Set the flow rate to 30 milliliters per minute. Check for leaks and blockages and verify that the ethanol is flowing through the entire reactor.Once the pump is empty, close the outlet valve and repeat the process with the other syringe pump. Clean each pump in this way, two to three times. Then, close the valves and empty the solvent waste.To begin the synthesis, place the inlet tube of the syringe pump connected to the second module in 100 milliliters of a 0.01 molar solution of DDM in anhydrous ethanol spiked with toluene. Open the pump inlet valve. Draw up the DDM solution at 70 milliliters per minute.If some solution is left in the flask when the pump stops, transfer the pump outlet tube to the flask of DDM solution and open the outlet valve. Decrease the flow rate to 30 milliliters per minute and run the pump until the solution appears in the outlet tube. Then, stop the pump.After drawing up the DDM solution, purge the syringe pump of air until the solution has been fully loaded into the pump. Then, close the outlet valve. Transfer the solution to a cuvette for UV-VIS spectroscopy.Set the DDM pump flow rate to 1.42 milliliters per minute. Fill the other pump with 250 milliliters of a 0.1 molar solution of para-nitrobenzoic acid in anhydrous ethanol spiked with orthoxylene. Set that pump to 3.58 milliliters per minute.Once both pumps have been filled, and their outlet valves are open, start the pumps. Monitor the flow into modules one and two and the mixing in modules three and four. The solution should be colorless after module four.Collect aliquots at 90-second intervals and monitor the reaction with UV-VIS spectroscopy. Once the reaction is complete, clean the pumps twice each with 400 milliliters of ethanol. Flow through the system at 10 milliliters per minute.Then, fill each pump with air and push the air through the system to finish cleaning. The reaction of at least a 10-fold excess of para-nitrobenzoic acid in DDM in a continuous flow reactor was monitored with UV-VIS spectroscopy. Comparison to a batch reaction performed with a 10 to one molar ratio, indicated the successful transfer of the procedure from batch to flow mode.95%reaction completion was achieved within the 11 minute residence time of the continuous flow reaction. Complete conversion could be achieved by extending the residence time to 33 minutes. While attempting this procedure, remember to use appropriate and calibrated temperature, pressure and flow controls.The reactor and pumps must be carefully cleaned before subsequent use for either the same or a different process. After watching this video, you should have a good understanding of how to perform a continuous flow reaction. Flow technology offers significant advantages over batch processing, including the capability to scale out an existing system to larger scales.The ability to acquire data in tandem with flow processes is a powerful tool that can be expanded to many other fields of research. We hope this technique encourages scientists to adopt flow technology as a tool.

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11.3K visualizações.  Georgia Institute of Technology. The overall goal of this technique is to transfer chemical processes from batch to flow mode as demonstrated by the reaction of diphenyldiazomethane with para-Nitrobenzoic acid in a continuous flow reactor. This method can help identify how best to approach the technology transfer of chemical transformations from batch to flow processes. The main advantage of this techniques are chemical reactions that require precise temperature control and mixing or highly reactive intermediate or reagents....