Development of a Liquid-Phase Process for Recycling Resolving Agents within Diastereomeric Resolutions

Abstract Image

Development of a Liquid-Phase Process for Recycling Resolving Agents within Diastereomeric Resolutions

Frederico Castelo Ferreira et al

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Mail to Frederico C. Ferreira

see article at

Org. Process Res. Dev. 10, 784-793 (2006)

http://pubs.acs.org/doi/abs/10.1021/op0600456?prevSearch=enantiomer%2Brecycling&searchHistoryKey=

This paper describes a liquid-phase process for recycling of resolving agents used in the diastereomeric resolution of chiral bases. The process is applicable to the resolution of any chiral base by an organic acid resolving agent which takes place in a polar solvent. The resolving agent is first of all separated from the diastereomeric complex by addition of aqueous HCl. The initial stage of process development is selection of a water-immiscible extracting organic solvent to recover the resolving agent from the resulting acidic aqueous solution. Either distillation or organic solvent nanofiltration is subsequently used to exchange the resolving agent from the extracting organic solvent back into the polar resolution solvent. This choice between these two technologies for solvent exchange depends on the relative boiling points of the two solvents. The resolution of PPI2, a racemic amine by di-p-toluoyl-l-tartaric acid (DTTA), was selected as an example of a typical resolution used in an organic process. Using the conventional process, this resolution requires 1.75 mol equiv of DTTA for each mole of racemic base fed to resolution, and thus the bulk of the DTTA ends up in the mother liquor. Using the recycling process, DTTA from both mother liquor and crystals was recovered and recycled over seven consecutive resolutions, while the final product enantiomeric excess and resolution yield were maintained at 100% and 40%, respectively. In this way the DTTA requirement was decreased from 1.75 to 0.26 DTTA mol equiv, reducing the amount of fresh resolving agent needed for each resolution by 85%.

Medicine for blood cancer-Imatinib mesylate

Description: Description: Description: 316439_232087880179382_121364007918437_579787_929938601_n.jpg

Medicine for Blood Cancer

‘Imitinef Mercilet’ is a medicine which cures blood cancer.
Its available free of cost at “Adyar Cancer Institute in Chennai”.
Create Awareness. It might help someone.Cancer Institute in Adyar, Chennai

‘Imitinef Mercilet’ is apparently an alternative spelling of the drug Imatinib mesylate which is used in the treatment of some forms of leukemia along with other types of cancer. Imatinib, often referred to a “Gleevec”, has proved to be an effective treatment for some forms of cancers. However, “blood cancer” is a generalized term for cancers that affect the blood, lymphatic system or bone marrow. The three types of blood cancer are listed as leukemia, lymphoma, and multiple myeloma. These three malignancies require quite different kinds of treatments. While drugs (including Imatinib), along with other treatments such as radiation can help to slow or even stop the progress of these cancers, there is currently no single drug treatment that can be said to actually cure all such cancers.

Category: Cancer
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Adyar, Chennai -600020
Landmark: Near Michael School
Phone: 044-24910754 044-24910754 ,
044-24911526 044-24911526 , 044-22350241

Buckminsterfullerene Synthesis

Buckminsterfullerene (or buckyball) is a spherical fullerene molecule with the formula C60. It has a cage-like fused-ring structure (Truncated icosahedron) which resembles asoccer ball, made of twenty hexagons and twelve pentagons, with a carbon atom at each vertex of each polygon and a bond along each polygon edge.

Reference :

Science 2002295, 1500. (10.1126/science.1068427)

http://www.slideshare.net/anthonycrasto64/anthony-crasto-buckyball

SEQUENCE IS AS FOLLOWS

Chemical structure

Mg, MeCHO

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Et2O
97 %
Grignard Reaction

Chemical structure

PBr3

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PhH
86 % bromination

Chemical structure

Ph3P

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Chemical structure + Chemical structure

LiOEt

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EtOH, CH2Cl2
71 % (2 steps)
Wittig Reaction

Chemical structure

I2, Propylene oxide

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Cyclohexane
92 %

Chemical structure

NBS, Bz2O2

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CCl4
Wohl-Ziegler Reaction

Chemical structure

KCN, n-Bu4N+ HSO4

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CH2Cl2, H2O
93 % (2 steps)

Chemical structure

KOH

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Ethylene Glycol

Chemical structure

SOCl2

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Chemical structure

AlCl3

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CH2Cl2
51 % (3 steps)
Friedel-Crafts Acylation

Chemical structure

TiCl4

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o-Dichlorobenzene
85 %Aldol Condensation

Chemical structure

FVP

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1100 °C, 0.1-1.0 %

Chemical structure

view my presentation

http://www.slideshare.net/anthonycrasto64/anthony-crasto-buckyball

 

HYDROXYL GROUP PROTECTION BY PNB

MECHANISM

REACTION

wt/vol

MW

moles

density

equivs.

yield

I

0.091 g

386.71

0.0002

1.0

II

0.059 g

167.12

0.0004

1.5

III

0.064 g

206.33

0.0003

1.3

IV

0.007 g

122.17

0.0001

0.2

V

5.0 mL

VI

0.122 g

535.81

0.0002

(97%)

 

Procedure:  25 mL 1-neck flask, stirbar, septum, N2 inlet

Dissolved 0.059 g II, 0.064 g of DCC and 0.007 g of DMAP in 4.0 mL of dry CH2Cl2.  Stirred at rt.  Added a solution of 0.091 g of alcohol I in 1.0 mL of CH2Cl2.  Stirred for 45 min.  The reaction mixture was then concentrated by rotary evaporation to ~ 0.5 mL.  The product was isolated by flash chromatography on silica gel using 10:90 EtOAc-hexanes as eluant.  The product was a clear, colorless oil.

 

1H NMR (CDCl3, 300 MHz) d 8.29 (d, J = 8.4 Hz, ArH), 8.20 (d, J = 8.4 Hz, ArH), 5.97 (dd, J = 15.8, 5.1 Hz, H3), 5.86 (dt, J = 15.8, 5.5 Hz, H2), 5.58 (dq, J= 15.4, 6.2 Hz, H7), 5.41 (dd, J = 15.4, 7.0 Hz, H6), 4.86 (d, J = 5.5 Hz, H1), 3.95 (dd(apparent t), J = 5.9 Hz, H4), 3.85 (dd(apparent t), J = 6.6 Hz, H5), 1.68 (d, J = 6.2 Hz, H8), 0.87 (s, SiC(CH3)3), 0.85 (s, SiC(CH3)3), 0.02 (s, SiCH3), 0.00 (s, Si(CH )2), -0.01 (s, SiCH3).

ARTEMISININ

ARTEMISININ, PRESENTATION

http://www.slideshare.net/anthonycrasto64/anthony-melvin-crasto-presents-artemisinin-11174931

Artemisinin is a photochemical reaction with singlet oxygen forming a hydroperoxide using teraphenylporphyrin asphotosensitizer followed by an ene reaction. This step is then followed by a thermal Hock rearrangement initiated by trifluoroacetic acid. Another round of oxygen adds another hydroperoxide unit and another rearrangement forms artemisinin itself. This sequence takes place in a continuous flow reactor and in the photochemical step all the tubing is wrapped around the lamp for maximum exposure to light.

artemisinin seeberger

Francois Levesque and Peter Seeberger laid out their plans for scaling up the production of the important anti-malarial drug artemisinin (DOI). Their vision: the industrial production from dihydroartemisinic acid in a single continuous flow reaction

Synthesis of Cyclic Peptides by Amide Bond Rearrangement

thumbnail image: Synthesis of Cyclic Peptides by Amide Bond Rearrangement

Derek Macmillan and colleagues, University College London, UK, report a simple new route to cyclic peptides from unactivated linear precursors. In the presence of a thiol, an N→S acyl shift in linear peptides can give thioesters, key components for native chemical ligation (NCL). These transient C-terminal thioesters can be intercepted by an N-terminal cysteine to form a new amide bond through NCL and result in biologically active cyclic products.

The products are of considerable interest because peptide cyclization is known to increase the therapeutic potential of many peptides by increasing their thermal and proteolytic stability as well as oral bioavailability.

Synthesis of Cyclic Peptides through an Intramolecular Amide Bond Rearrangement
D. Macmillan, M. De Cecco, N. L. Reynolds, L. F. A. Santos, P. E. Barran, J. R. Dorin,
ChemBioChem 2011.
DOI: 10.1002/cbic.201100364

volleyball

DR ANTHONY CRASTO

Stereoselective approaches to amides from chiral alcohols

thumbnail image: New Route to Chiral Amides

A Direct and Stereoretentive Synthesis of Amides from Cyclic Alcohols
D. Mondal, L. Bellucci, S. D. Lepore,
Eur. J. Org. Chem. 2011.
DOI: 10.1002/ejoc.201101165

Salvatore Lepore and colleagues, Florida Atlantic University, USA, report a one-pot amidation reaction for cyclic alcohols that gives complete retention of configuration. They use a chlorosulfite leaving group formed in situ by reaction of the alcohol and thionyl chloride. The leaving group is chelated by a TiIV nitrile complex that is also generated in situ by reaction of TiF4 and alkyl or aryl nitrile.

One-pot, stereoretentive amidation of alcohols

The Ti nitrile complex is thought to chelate the chlorosulfite in the transition state to create a carbocation that is rapidly captured by the nitrile nucleophile through a front-side attack mechanism. This is the first experimental verification of secondary hyperconjomers, a theory of non-planar carbocations developed by Sorensen and Schleyer.

Most stereoselective approaches to amides from chiral alcohols require multistep procedures.

volleyball

DR ANTHONY CRASTO

How Nature Makes Earth Aroma —Unusual biosynthesis of geosmin

How Nature Makes Earth Aroma

Unusual biosynthesis of geosmin, a terpene responsible for the pleasant scent of moist soil, is deciphered

Geosmin, ubiquitous in the environment, is a terpene produced by a number of microorganisms, including soil bacteria and cyanobacteria (blue-green algae). Scientists have known about the compound for more than 100 years, but it wasn’t isolated and structurally characterized until 1965.

Besides giving rise to the scent of soil, geosmin and its metabolites can cause undesirable musty smells or off-flavors in water and food. People detect geosmin “at the extraordinarily low threshold of 10 ppt, but no one knows why this should be so or even why geosmin is produced,”says.chemistry professor David E. Cane,

Cane and coworkers suspected that two or more enzymes catalyzing some unknown combination of steps would be required to convert germacradienol to geosmin. But last year, the researchers were surprised to discover that one enzyme alone catalyzes the conversion of farnesyl diphosphate all the way to geosmin by way of germacradienol (J. Am. Chem. Soc. 2006128, 8128).

EARTHY ODORANT A bifunctional bacterial enzyme converts farnesyl diphosphate (left) into germacradienol (center) and subsequently into geosmin (right), which is the volatile compound responsible for the characteristic smell of freshly turned soil.

 

Catalysts Speed It Up

Catalysts Speed It Up

Lowering Activation EnergyA catalyst is like adding a bit of magic to a reaction. Reactions need a certain amount of energy in order to happen. If they don’t have it, oh well, the reaction probably can’t happen. Acatalyst lowers the amount of energy needed so that a reaction can happen more easily. A catalyst is about energy. It doesn’t have to be another molecule. If you fill a room with hydrogen gas (H2) and oxygen gas (O2), very little will happen. If you light a match in that room (or just produce a spark), most of the hydrogen and oxygen will combine to create water molecules (H2O). It is an explosive reaction.

The energy needed to make a reaction happen is called the activation energy. As everything moves around, energy is needed. The energy that a reaction needs is usually in the form of heat. When a catalyst is added, something special happens. Maybe a molecule shifts its structure. Maybe that catalyst makes two molecules combine and they release a ton of energy. That extra energy might help another reaction to occur in something called a chain reaction. In our earlier example, the spark decreased the required activation energy. You could also think of a catalyst like a bridge in some instances. Instead of letting reactions happen in the same (but faster) way, it can offer a new direction or chemical pathway in order to skip steps that require energy.

Catalysts in actionCatalysts are also used in the human body. They don’t cause explosions, but they can make very difficult reactions happen. They help very large molecules to combine. There is another interesting fact about catalysts. You know that catalysts lower the activation energy required for a reaction to occur. With the activation energy lower, the products can also combine more easily. Therefore, the forward and reverse reactions are both accelerated. It changes both rates and usually changes the equilibrium point.

Inhibitors Slow It Down

Inhibitors in actionThere is also something called an inhibitor that works in exactly the opposite way as catalysts. Inhibitors slow the rate of reaction. Sometimes they even stop the reaction completely. You might be asking, “Why would anyone need those?” You could use an inhibitor to make the reaction slower and more controllable. Without inhibitors, some reactions could keep going and going and going. If they did, all of the molecules would be used up. That would be bad, especially in your body. When you are watching television, you have no reason to keep breaking down sugars at the same rates you would if you were working out.