Continuous-Flow Processes for the Production of Floxacin Intermediates: Efficient C–C Bond Formation through a Rapid and Strong Activation of Carboxylic Acids

AbstractThe development of highly efficient C–C bond formation methods for the synthesis of ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-(dimethylamino)acrylate 1 in continuous flow processes has been described, which is based on the concept of rapid and efficient activation of carboxylic acid. 2,4-Dichloro-5-fluorobenzoic acid is rapidly converted into highly reactive 2,4-dichloro-5-fluorobenzoyl chloride by treating with inexpensive and less-toxic solid bis(trichloromethyl)carbonate. And then it rapidly reacts with ethyl 3-(dimethylamino)acrylate to afford the desired 1. This process can be performed under mild conditions. Compared with the traditional tank reactor process, less raw material consumption, higher product yield, less reaction time, higher operation safety ensured by more the environmentally friendly procedure, and process continuity are achieved in the continuous-flow system.

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Continuous flow processes for the S-alkynylation of cysteine-containing peptides and thioglycoside under catalyst-free, oxidant-free and mild conditions

Green Chemistry ◽

10.1039/d1gc01937f ◽

2021 ◽

Author(s):

Long-Zhou Qin ◽

Xin Yuan ◽

Jie Liu ◽

Meng-yu Wu ◽

Qi Sun ◽

...

Keyword(s):

Continuous Flow ◽

Mild Conditions ◽

Catalyst Free ◽

Flow Processes ◽

Novel Method

Herein, we develop a novel method for the selective alkynylation of cysteine-containing peptides and 1-thioglycoside residues by the use of continuous flow. This method was characterised by the mild conditions...

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Green Synthesis of Phenytoin Sodium

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.518-523.3917 ◽

2012 ◽

Vol 518-523 ◽

pp. 3917-3920 ◽

Cited By ~ 1

Author(s):

Ting Ting Du ◽

Jing Fen Li ◽

Li Jing Min

Keyword(s):

Nitric Acid ◽

Reaction Time ◽

Condensation Reaction ◽

Synthesis Method ◽

Vitamin B1 ◽

Product Yield ◽

Wave Radiation ◽

Mild Conditions ◽

Benzoin Condensation ◽

Phenytoin Sodium

In this study, benzaldehyde was reacted with benzoin condensation, oxidation and cyclization reaction to product phenytoin sodium under the supersonic wave radiation. In the condensation reaction, non-toxic vitamin B1 was used as a reactor instead of highly toxic cyanide on pH=9 at 70 oC. After that, FeCl3 • 6H2O was used as oxidant instead of concentrated nitric acid under the mild conditions. The results were that the yield of phenytoin sodium was up to 56.8%. There were many advantages in this improved synthesis method such as shorter reaction time, higher product purity, lower environmental pollution and higher product yield.

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C–C Bond formation catalyzed by natural gelatin and collagen proteins

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.9.123 ◽

2013 ◽

Vol 9 ◽

pp. 1111-1118 ◽

Cited By ~ 21

Author(s):

Dennis Kühbeck ◽

Basab Bijayi Dhar ◽

Eva-Maria Schön ◽

Carlos Cativiela ◽

Vicente Gotor-Fernández ◽

...

Keyword(s):

Bond Formation ◽

Scale Up ◽

Product Yield ◽

Order Rate Constant ◽

Physiological Conditions ◽

First Order ◽

Bond Forming ◽

Mild Conditions ◽

Nitroaldol Reaction ◽

First Time

The activity of gelatin and collagen proteins towards C–C bond formation via Henry (nitroaldol) reaction between aldehydes and nitroalkanes is demonstrated for the first time. Among other variables, protein source, physical state and chemical modification influence product yield and kinetics, affording the nitroaldol products in both aqueous and organic media under mild conditions. Significantly, the scale-up of the process between 4-nitrobenzaldehyde and nitromethane is successfully achieved at 1 g scale and in good yield. A comparative kinetic study with other biocatalysts shows an increase of the first-order rate constant in the order chitosan < gelatin < bovine serum albumin (BSA) < collagen. The results of this study indicate that simple edible gelatin can promote C–C bond forming reactions under physiological conditions, which may have important implications from a metabolic perspective.

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Quantification of Antibodies against Factor VIII by an Immunonephelometric Method in a Continuous-Flow System

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456328001700508 ◽

1980 ◽

Vol 17 (5) ◽

pp. 256-261 ◽

Cited By ~ 1

Author(s):

F Malagon ◽

F L Elorza ◽

E Martin ◽

A Jimenez

Keyword(s):

Reaction Time ◽

Factor Viii ◽

Continuous Flow ◽

Flow System ◽

Haemophilia A ◽

Continuous Flow System ◽

Automated Method

A new immunonephelometric method is described for the quantification of antibodies against factor VIII in sera from patients suffering from haemophilia A. We have been able to reduce the reaction time to only 16 minutes, which permits its application to emergency cases. Applying Spearman's test, we have correlated the results obtained by the immunonephelometric and Ruggieri's methods, obtaining r = 0·87, p<0·01 for n = 11. From the reproducibility studies we obtained SD = 1·16 as maximum dispersion value. Because it is a fully automated method in a continuous-flow system, the possible manual errors are reduced to a minimum; 60 determinations can be carried out in 1 hour.

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Immobilization of Arabidopsis thaliana Hydroxynitrile Lyase (AtHNL) on EziG Opal

Catalysts ◽

10.3390/catal10080899 ◽

2020 ◽

Vol 10 (8) ◽

pp. 899

Author(s):

José Coloma ◽

Tim Lugtenburg ◽

Muhammad Afendi ◽

Mattia Lazzarotto ◽

Paula Bracco ◽

...

Keyword(s):

Arabidopsis Thaliana ◽

Reaction Time ◽

Continuous Flow ◽

Flow System ◽

Enzyme Stability ◽

Reaction Medium ◽

Specific Rate ◽

Hydroxynitrile Lyase ◽

Continuous Flow System ◽

Space Time Yield

Arabidopsis thaliana hydroxynitrile lyase (AtHNL) catalyzes the selective synthesis of (R)-cyanohydrins. This enzyme is unstable under acidic conditions, therefore its immobilization is necessary for the synthesis of enantiopure cyanohydrins. EziG Opal is a controlled porosity glass material for the immobilization of His-tagged enzymes. The immobilization of His6-tagged AtHNL on EziG Opal was optimized for higher enzyme stability and tested for the synthesis of (R)-mandelonitrile in batch and continuous flow systems. AtHNL-EziG Opal achieved 95% of conversion after 30 min of reaction time in batch and it was recycled up to eight times with a final conversion of 80% and excellent enantioselectivity. The EziG Opal carrier catalyzed the racemic background reaction; however, the high enantioselectivity observed in the recycling study demonstrated that this was efficiently suppressed by using citrate/phosphate buffer saturated methyl-tert-butylether (MTBE) pH 5 as reaction medium. The continuous flow system achieved 96% of conversion and excellent enantioselectivity at 0.1 mL min−1. Lower conversion and enantioselectivity were observed at higher flow rates. The specific rate of AtHNL-EziG Opal in flow was 0.26 mol h−1 genzyme−1 at 0.1 mL min−1 and 96% of conversion whereas in batch, the immobilized enzyme displayed a specific rate of 0.51 mol h−1 genzyme−1 after 30 min of reaction time at a similar level of conversion. However, in terms of productivity the continuous flow system proved to be almost four times more productive than the batch approach, displaying a space-time-yield (STY) of 690 molproduct h−1 L−1 genzyme−1 compared to 187 molproduct h−1 L−1 genzyme−1 achieved with the batch system.

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Polymer Enhancement of Automated Immunological Nephelometric Analysis, as Illustrated by Determination of Urinary Albumin

Clinical Chemistry ◽

10.1093/clinchem/20.4.415 ◽

1974 ◽

Vol 20 (4) ◽

pp. 415-420 ◽

Cited By ~ 101

Author(s):

Jorge Lizana ◽

Kristoffer Hellsing

Keyword(s):

Polyethylene Glycol ◽

Reaction Time ◽

Comparative Study ◽

Continuous Flow ◽

Flow System ◽

Urinary Albumin ◽

Immunological Reaction ◽

Enhancing Effect ◽

Highly Sensitive

Abstract We have developed a new automated immunonephelometric method for determination of albumin in urine, by exploiting the polymer-enhancing effect on the immunological reaction. The original continuous-flow manifold has been simplified and the reaction time shortened to about 3 min. The antiserum was diluted 100-fold in a solution (100 g/liter) of polyethylene glycol (av mol wt, 6000) and mixed with the prediluted sample in the continuous-flow system. The method is highly sensitive and is unaffected by high blank and (or) high absorbance values of the specimens. Day-to-day variation was 3.8-4.3% (CV). Accuracy, as estimated from recovery experiments, was also good. A comparative study of 176 urines with the single radial immunodiffusion technique showed a correlation coefficient of 0.994. We therefore suggest the new method for routine use for determination of urinary albumin, because it is fast, accurate, precise, and sensitive, and requires only small amounts of antiserum.

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Acyl azide generation and amide bond formation in continuous-flow for the synthesis of peptides

Reaction Chemistry & Engineering ◽

10.1039/d0re00034e ◽

2020 ◽

Vol 5 (4) ◽

pp. 645-650 ◽

Cited By ~ 3

Author(s):

Alejandro Mata ◽

Ulrich Weigl ◽

Oliver Flögel ◽

Pius Baur ◽

Christopher A. Hone ◽

...

Keyword(s):

Continuous Flow ◽

Nitrous Acid ◽

Flow System ◽

Bond Formation ◽

Amide Bond ◽

Peptide Coupling ◽

Amide Bond Formation ◽

Acyl Azides ◽

Acyl Azide

Acyl azides were safely generated by using nitrous acid in water and reacted in situ within a flow system. The acyl azide was efficiently extracted into the organic phase containing an amine nucleophile for a highly enantioselective peptide coupling.

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Visible Light-Mediated Oxidative Debenzylation

10.26434/chemrxiv.13135814 ◽

2020 ◽

Author(s):

Cristian Cavedon ◽

Eric T. Sletten ◽

Amiera Madani ◽

Olaf Niemeyer ◽

Peter H. Seeberger ◽

...

Keyword(s):

Reaction Time ◽

Visible Light ◽

Functional Groups ◽

Continuous Flow ◽

Protecting Groups ◽

Benzyl Ether ◽

Complex Molecules ◽

Protective Groups ◽

Benzyl Ethers ◽

Harsh Conditions

Protecting groups are key in the synthesis of complex molecules such as carbohydrates to distinguish functional groups of similar reactivity. The harsh conditions required to cleave stable benzyl ether protective groups are not compatible with many other protective and functional groups. The mild, visible light-mediated debenzylation disclosed here renders benzyl ethers orthogonal protective groups. Key to success is the use of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as stoichiometric or catalytic photooxidant such that benzyl ethers can be cleaved in the presence of azides, alkenes, and alkynes. The reaction time for this transformation can be reduced from hours to minutes in continuous flow. <br>

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Nitrification and Autotrophic Denitrification in Calcium Alginate Beads

Water Science & Technology ◽

10.2166/wst.1987.0199 ◽

1987 ◽

Vol 19 (1-2) ◽

pp. 175-182 ◽

Cited By ~ 16

Author(s):

Z. Lewandowski ◽

R. Bakke ◽

W. G. Characklis

Keyword(s):

Calcium Carbonate ◽

Calcium Ions ◽

Continuous Flow ◽

Calcium Alginate ◽

Microbial Respiration ◽

Flow System ◽

Alginate Beads ◽

Alginate Gel ◽

Gel Beads ◽

Calcium Alginate Gel

Immobilization of nitrifiers and autotrophic denitrifiers (Thiobacillus denitrificans) within calcium alginate gel was demonstrated. Calcium carbonate reagent was immobilized along with bacteria as the stabilizing agent. Protons released as a result of microbial respiration reacted with calcium carbonate producing calcium ions which internally stabilized the calcium alginate gel. The microbially active gel beads were mechanically stable and active for three months in a continuous flow system without addition of calcium.

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