Stereochemistry of [n,m] Sigmatropic Rearrangements

Stereochemistry of [n,m] Sigmatropic Rearrangements

Basically, [n,m] sigmatropic rearrangements can proceed through a chair or boat  transition state. Only the chair transition state has been observed experimentally though both are suprafacial and are allowed in 4n+2 electron systems.


Chair and boat transition states in [n,m] sigmatropic rearrangements
Fig.1Chair



Fig.2Boat



Examples for sigmatropic rearrangements with a chair transition state

 Fig.3Cope rearrangement

 



Fig.4[3,3] Sigmatropic

               
                        6 Electrons
                   
                        Hückel aromatic
                   
                        Supra-supra


 view animation, 2D Animation of the Cope rearrangement

try copy paste of link below, do not miss out on a beautiful animation


http://www.chemgapedia.de/vsengine/supplement/Vlu/vsc/en/ch/2/vlu/pericyclische_reaktionen/pericyclisch_sigmatrop.vlu/Page/vsc/en/ch/2/oc/reaktionen/formale_systematik/pericyclische_reaktionen/sigmatrop/stereochemie_n_m.vscml/Fragment/0d47d3304bb08cfd9c68c1c3590965d2-19.html


Large substituents similar to their behavior in chair conformations of cyclohexane rings prefer an equatorial configuration in the transition state of [3,3] sigmatropic reactions. Heating S,S-3,4-dimethyl-1,5-hexadiene to approximately 200°C  yields in 90% a product derived from a chair transition state with equatorial methyl groups.  The product arising from a diaxial conformation is formed in only 10% yield. Obviously, the reaction does not proceed through the boat transition state.

Enantiomeric Ibuprofen via Environmentally Benign Selective Crystallization

 Ibuprofen was developed by the Boots Group, a pharmacy chain in the United Kingdom, in the 1950’s-1960s. It was discovered by Stewart Adams (along with John Nicholson, Andrew RM Dunlop, Jeffrey Bruce Wilson & Colin Burrows). The Boots group originally licensed Ibuprofen to two large drug companies. The first was Whitehall Laboratories (who sold the product as Advil) and the second was Upjohn who used Bristol-Meyers to market their product “Nuprin”. Boots held the patent until 1985 along with the rights to market it until 1986. Afterwards new products entered the market creating multiple new “generic” brands.

Selective crystallization of ibuprofen/lysinate from 1 mol of (R,S)-(racemic) ibuprofen and ≤0.5 mol of (S)-lysine in aqueous ethanol affords either (S)-(+)-ibuprofen/(S)-lysinate or (R)-ibuprofen/(S)-lysinate (in preponderance) depending on the crystallization conditions. The previously unreported temperature selective diastereo-recognition (TSD) provides simple and efficient means to prepare either enantiomer of ibuprofen from (R,S)-ibuprofen utilizing the same commercially available inexpensive resolving agent, (S)-lysine. The unwanted enantiomeric ibuprofen could be recovered from the mother liquor and racemized by a simple, relatively waste-free thermal process. This racemization method when utilized in conjunction with the selective crystallization technology provides a simple, efficient, and eco-friendly means to prepare (S)-(+)-ibuprofen lysinate in an overall essentially quantitative yield. This technology also incorporates the fundamental principle of atom economy (via direct production of the preferred pharmaceutical salt of (S)-lysine).  

Temperature Selective Diastereo-Recognition (TSD):  Enantiomeric Ibuprofen via Environmentally Benign Selective Crystallization

 see also
http://onlinelibrary.wiley.com/doi/10.1002/aic.11087/abstract;jsessionid=D60C69E3DB7266BE103A2875A7FEA6C5.d02t03?deniedAccessCustomisedMessage=&userIsAuthenticated=false
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read more at
 http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-66322006000300003
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Citalopram/Escitalopram Oxalate, Isolation & Synthesis of Novel Impurities, Emcure paper

Citalopram

Citalopram  brand names: Celexa, Cipramil) is an antidepressantdrug of the selective serotonin reuptake inhibitor (SSRI) class. It has U.S. Food and Drug Administration (FDA) approval to treat major depression, and is prescribed off-label for a number of anxiety conditions.

Escitalopram (trade names Nexito, Anxiset-E (India), Lexapro,Cipralex, Seroplex, Lexamil, Lexam, Entact, Losita(Bangladesh) Reposil (Chile)), is an antidepressant of theselective serotonin reuptake inhibitor (SSRI) class. It is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults and children over 12 years of age with major depressive disorder and generalized anxiety disorder. Escitalopram is the (S)-stereoisomer (enantiomer) of the earlier Lundbeck drugcitalopram

Citalopram/Escitalopram Oxalate: Isolation & Synthesis of Novel Impurities

READ AT

http://pubs.acs.org/doi/abs/10.1021/op300039c

Emcure Pharmaceuticals Ltd, R & D Centre, Pimpri, Pune -411018, India

During process optimization of Escitalopram oxalate novel impurities, 6 and 7 were observed, which were isolated and characterized, and the proposed structure was confirmed by chemical synthesis. Investigation of the cause of impurities formation improved the yield and purity of the drug product during the bulk API synthesis

SPECTROSCOPIC DATA IS AVAILABLE IN SUPPORTING INFORMATION FILE IN THE PAPER

ARTEMETHER, A FORCE AGAINST MALARIA

Artemether  
is an antimalarial for the treatment of multi-drug resistant strains offalciparum malaria. It is combined with Lumefantrine and sold by Novartis under the brand names Riamet and Co-Artem.


It is a methyl ether derivative of artemisinin, which is a peroxide lactone isolated from theChinese antimalarial plant, Artemisia annua. It is also known as dihydroartemisinin methyl ether, but its correct chemical nomenclature is (+)-(3-alpha,5a-beta,6-beta,8a-beta, 9-alpha,12-beta,12aR)-decahydro-10-methoxy-3,6,9-trimethyl-3,12-epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin.


Artemether is highly effective against the blood schizonts of both malarial parasites P. falciparum and P. vivax. It is applied in combination with lumefantrine in clinical treatments of malaria. 
World Health Organization guidelines for the treatment of uncomplicatedfalciparum malaria recommend the use of this artemisinin-based combination therapy, and approved by Swissmedic in December 2008 and recently approved by the United StatesFood and Drug Administration.



READ AT
http://pubs.acs.org/doi/abs/10.1021/op300037e

A 70% overall yield from the two-step conversion of naturally or synthetically derived artemisinin to pure β-artemether is obtained. This corresponds to a usage factor of 1.35 kg of artemisinin needed to produce 1 kg of β-artemether, compared to the current industry average of 1.59 kg.

Kharasch-Sosnovsky Reaction:

Kharasch-Sosnovsky Reaction:

copper catalysed allylic oxidation using an organic peroxide.

reported by M. S. Kharasch and George Sosnovsky in 1958 ((DOI) DOI).

In the original publication the reactants are cyclohexene

and t-butyl perbenzoate with cuprous bromide and the

reaction product is cyclohex-1-en-3-yl benzoate:

 

Mechanism: (review: DOI). The reaction mechanism devised

by Beckwith et al (DOI) contains the following steps:

 

THANKS AND REGARD'S

DR ANTHONY MELVIN CRASTO Ph.D

amcrasto@gmail.com

MOBILE-+91 9323115463

GLENMARK SCIENTIST , NAVIMUMBAI, INDIA

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[3,3]-sigmatropic rearrangement to transfer an allyl group to the imminium carbon

[3,3]-sigmatropic rearrangement to transfer an allyl group to the imminium carbon
REACTION MECHANISM
Starting point is to react the secondary amine with the aldehyde to form a cyclic imminium structure. Once generated, this is nicely set up to undergo a [3,3]-sigmatropic rearrangement to transfer an allyl group to the imminium carbon. The resulting formaldehyde imminium product is then hydrolyzed in the presence of water to afford the product plus an equivalent of formaldehyde





closer inspection, you can see that there is one less carbon in the product than the starting material. Furthermore, there are no reducing agents present, only acid (and presumably water)
 

ENZYMATIC DIELS ALDER REACTION

In a ground-breaking feat of protein engineering, US researchers have designed a synthetic enzyme that catalyses the Diels-Alder reaction - something that has not been seen in nature. The reaction is key to many organic syntheses and suggests that artificial enzymes could soon become part of the synthetic chemist's toolkit.

The Diels-Alder reaction - diene and dienophile undergo a pericyclic [4 + 2] cycloaddition to form a chiral cyclohexene ring. The image also shows the design target active site, with hydrogen bond acceptor and donor groups activating the diene and dienophile and a complementary binding pocket holding the two substrates in an orientation optimal for catalysis Science 16 July 2010:  Vol. 329 no. 5989 pp. 309-313  DOI: 10.1126/science.1190239 http://www.sciencemag.org/content/329/5989/309.abstract