PMID- 37241953
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20230528
LR  - 20230530
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 28
IP  - 10
DP  - 2023 May 20
TI  - An Automated Continuous Synthesis and Isolation for the Scalable Production of 
      Aryl Sulfonyl Chlorides.
LID - 10.3390/molecules28104213 [doi]
LID - 4213
AB  - In this work, a continuous system to produce multi-hundred-gram quantities of 
      aryl sulfonyl chlorides is described. The scheme employs multiple continuous 
      stirred-tank reactors (CSTRs) and a continuous filtration system and incorporates 
      an automated process control scheme. The experimental process outlined is 
      intended to safely produce the desired sulfonyl chloride at laboratory scale. 
      Suitable reaction conditions were first determined using a batch-chemistry design 
      of experiments (DOE) and several isolation methods. The hazards and 
      incompatibilities of the heated chlorosulfonic acid reaction mixture were 
      addressed by careful equipment selection, process monitoring, and automation. The 
      approximations of the CSTR fill levels and pumping performance were measured by 
      real-time data from gravimetric balances, ultimately leading to the incorporation 
      of feedback controllers. The introduction of process automation demonstrated in 
      this work resulted in significant improvements in process setpoint consistency, 
      reliability, and spacetime yield, as demonstrated in medium- and large-scale 
      continuous manufacturing runs.
FAU - Glace, Matthew
AU  - Glace M
AUID- ORCID: 0000-0002-6342-4850
AD  - Department of Chemical and Life Sciences Engineering, Virginia Commonwealth 
      University, Richmond, VA 23284, USA.
FAU - Armstrong, Cameron
AU  - Armstrong C
AUID- ORCID: 0000-0001-6342-0860
AD  - Department of Chemical and Life Sciences Engineering, Virginia Commonwealth 
      University, Richmond, VA 23284, USA.
FAU - Puryear, Nathan
AU  - Puryear N
AUID- ORCID: 0000-0002-2463-9066
AD  - Department of Electrical and Computer Engineering, Virginia Commonwealth 
      University, Richmond, VA 23284, USA.
FAU - Bailey, Colin
AU  - Bailey C
AUID- ORCID: 0009-0008-9935-9094
AD  - Department of Chemical and Life Sciences Engineering, Virginia Commonwealth 
      University, Richmond, VA 23284, USA.
FAU - Moazeni-Pourasil, Roudabeh Sadat
AU  - Moazeni-Pourasil RS
AD  - Department of Chemical and Life Sciences Engineering, Virginia Commonwealth 
      University, Richmond, VA 23284, USA.
FAU - Scott, Drew
AU  - Scott D
AD  - Department of Chemical and Life Sciences Engineering, Virginia Commonwealth 
      University, Richmond, VA 23284, USA.
FAU - Abdelwahed, Sherif
AU  - Abdelwahed S
AD  - Department of Electrical and Computer Engineering, Virginia Commonwealth 
      University, Richmond, VA 23284, USA.
FAU - Roper, Thomas D
AU  - Roper TD
AUID- ORCID: 0000-0002-8923-5505
AD  - Department of Chemical and Life Sciences Engineering, Virginia Commonwealth 
      University, Richmond, VA 23284, USA.
LA  - eng
GR  - 75A50120D00092/Biomedical Advanced Research and Development Authority/
PT  - Journal Article
DEP - 20230520
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
SB  - IM
PMC - PMC10223716
OTO - NOTNLM
OT  - batch design
OT  - chlorosulfonation
OT  - continuous manufacturing
OT  - flow chemistry
OT  - process automation
OT  - pump control system
COIS- The authors declare no conflict of interest.
EDAT- 2023/05/27 09:42
MHDA- 2023/05/27 09:43
PMCR- 2023/05/20
CRDT- 2023/05/27 01:25
PHST- 2023/04/24 00:00 [received]
PHST- 2023/05/16 00:00 [revised]
PHST- 2023/05/17 00:00 [accepted]
PHST- 2023/05/27 09:43 [medline]
PHST- 2023/05/27 09:42 [pubmed]
PHST- 2023/05/27 01:25 [entrez]
PHST- 2023/05/20 00:00 [pmc-release]
AID - molecules28104213 [pii]
AID - molecules-28-04213 [pii]
AID - 10.3390/molecules28104213 [doi]
PST - epublish
SO  - Molecules. 2023 May 20;28(10):4213. doi: 10.3390/molecules28104213.