Evaluation of Pd-catalyzed hydrogenations under flow conditions

Originally posted on SynthFlow:

Just finished reading an excellent example from a group in Japan moving a batch hydrogenation to flow. Dr Sajiki’s group developed and evaluated a number of Pd-catalysts and their effectiveness in an H-Cube (Thales Nano) reactor. This evaluation went into detail on both reaction optimization and chemoselectivities, depending on the catalyst type — while scoping a variety of temp, flow and solvents for each of the reactions — it was truly impressive how much work was performed and the amount of information we obtain for the work done. The work was published in Tetrahedron 2014 and featured and a highlight brief in Synfacts 2014.

From the cartoon below, you can see that the substrate was passed through a series of immobilized Pd catalysts to provide different targets depending on their functionality. A variety of pressures, flow rates, and substrate concentrations were studied as part of the optimization process.

Screen Shot 2014-10-18 at 2.27.51 PM

Rather than…

View original 66 more words

PRISMANE 棱晶烷

Chemical structure of prismane
PRISMANE

650-42-0 cas

Tetracyclo[2.2.0.02,6.03,5]hexane

Prismane is a polycyclic hydrocarbon with the formula C6H6. It is an isomer of benzene, specifically a valence isomer. Prismane is far less stable than benzene. The carbon (and hydrogen) atoms of the prismane molecule are arranged in the shape of a six-atomtriangular prismAlbert Ladenburg proposed this structure for the compound now known as benzene.[1] The compound was not synthesized until 1973.[2]
Prismane
Chemical structure of prismane Chemical structure of prismane
CPK model of prismane
Identifiers
CAS number 650-42-0 
ChemSpider 16736515 Yes
Jmol-3D images Image 1
Properties
Molecular formula C6H6
Molar mass 78.11 g mol−1

History

In the mid 19th century, investigators proposed several possible structures for benzene which were consistent with its empirical formula, C6H6, which had been determined by combustion analysis. The first, which was proposed by Kekulé in 1867, later proved to be closest to the true structure of benzene. This structure inspired several others to propose structures that were consistent with benzene’s empirical formula; for example, Ladenburg proposed prismane, Dewar proposed Dewar benzene, and Koerner and Claus proposedClaus’ benzene. Some of these structures would be synthesized in the following years. Prismane, like the other proposed structures for benzene, is still often cited in the literature, because it is part of the historical struggle toward understanding the mesomeric structures and resonance of benzene. Some computational chemists still research the differences between the possible isomers of C6H6.[3]

Properties

Prismane is a colourless liquid at room temperature. The deviation of the carbon-carbon bond angle from 109° to 60° in a triangle leads to a high ring strain, reminiscent of that of cyclopropane but greater. The compound is explosive, which is unusual for a hydrocarbon. Due to this ring strain, the bonds have a low bond energy and break at a low activation energy, which makes synthesis of the molecule difficult; Woodward and Hoffmann noted that prismane’s thermal rearrangement to benzene is symmetry-forbidden, comparing it to “an angry tiger unable to break out of a paper cage.”[4]

The substituted derivative hexamethylprismane (in which all six hydrogens are substituted by methyl groups) has a higher stability, and was synthesized by rearrangement reactionsin 1966.[5]

Synthesis

Synthesis of Prismane

The synthesis starts from benzvalene (1) and 4-phenyltriazolidone, which is a strong dienophile. The reaction is a stepwise Diels-Alder like reaction, forming a carbocation as intermediate. The adduct (2) is then hydrolyzed under basic conditions and afterwards transformed into a copper(II) chloride derivative with acidic copper(II) chloride. Neutralized with a strong base, the azo compound (3) could be crystallized with 65% yield. The last step is a photolysis of the azo compound. This photolysis leads to a biradical which forms prismane (4) and nitrogen with a yield of less than 10%. The compound was isolated by preparative gas chromatography.

 

SYNTHESIS
Chemical structure
MeLi, CH2Cl2, 
Et2O
-45 °C, 45 %
Chemical structure

+

Chemical structure

Et2O, Dioxane
0 °C to RT, 60 min, 50-60 %

Chemical structure
KOH, 
MeOH, H2O
Reflux, 24 h
Chemical structure
CuCl2, HCl,
H2O
65 % (2 steps)
Chemical structure
hν, 
PhMe
30 °C, 5 h, 8 %
Chemical structure
References

 

 

https://www.beilstein-journals.org/bjoc/single/printArticle.htm?publicId=1860-5397-7-30

 

 

http://chemistry.stackexchange.com/questions/8898/does-benzene-have-isomers-and-resonance-structures

References

  1. Ladenburg A. (1869). “Bemerkungen zur aromatischen Theorie“. Chemische Berichte 2: 140–2. doi:10.1002/cber.18690020171.
  2. Katz T. J., Acton N. (1973). “Synthesis of Prismane”. Journal of the American Chemical Society 95 (8): 2738–2739. doi:10.1021/ja00789a084.
  3.  UD Priyakumar, TC Dinadayalane, GN Sastry (2002). “A computational study of the valence isomers of benzene and their group V hetero analogs”New J. Chem. 26 (3): 347–353.doi:10.1039/b109067d.
  4. R. B. Woodward and R. Hoffmann, Angew. Chem., Int. Ed. Engl.8, 789, (1969)
  5.  Lemal D. M., Lokensgard J. P. (1966). “Hexamethylprismane”. Journal of the American Chemical Society 88 (24): pp 5934–5935. doi:10.1021/ja00976a046.

Microwave Labs: Florida State University – Gregory Dudley

Originally posted on Totally Microwave:

Professor Dudley’s recent work in microwave chemistry has certainly heated up the place. His group is trying to dive into more complex studies surrounding microwave acceleration above the normal predicted amount. I have enjoyed the pursuit of his work over the last couple of years and we should see continued efforts coming out soon. Take a look at some of his recent contributions at Florida State — seems the university has a number of efforts in microwave methodologies to keep track.

Screen Shot 2014-10-17 at 4.43.52 PM

View original

Strategies to Macrocycles: Microwave approach

Originally posted on Totally Microwave:

After coming across the phase separation strategy for preparing medium to large macrocycles with  a 1,3-diyne moiety, I thought about the holes in my background in this area — which is a bit strange considering I started my career at Abbott and with all the Erythromycin or macrolide chemistry performed there in general one would think I would have been up on it…alas, about as much as not finding Clarithromycin internally (not really a parting shot, but if the resident experts miss a billion dollar drug how am I expected to keep up — knowing the stories it is easy to miss). ;)

Usually the intro for this topic starts with clinically relevant and natural macrocyclic antibiotics — lots of them, but there is so much more from branching polycyclic peptides to the antifungal and antiparastics adding to the structural diversity. I certainly remember when the epothilone synthetic strategies came…

View original 444 more words

Photoredox with nickel catalysis

redox
Photoredox with nickel catalysis
Something a little more generally applicable is the combination of photoredox chemistry with nickel catalysis. Focus in this article 1 is the coupling alpha-amino carboxyl sp3 carbons with aryl halides see scheme. Yields are generally excellent with examples of heterocyclic halides and of alpha O and aryl amino acids acting as substrates. With mild conditions this looks a versatile route to benzylic amines.
1. Z. Zuo et al Science 2014, 345, 437, http://www.sciencemag.org/content/345/6195/437.abstract
redox

Over the past 40 years, transition metal catalysis has enabled bond formation between aryl and olefinic (sp2) carbons in a selective and predictable manner with high functional group tolerance. Couplings involving alkyl (sp3) carbons have proven more challenging.

Here, we demonstrate that the synergistic combination of photoredox catalysis and nickel catalysis provides an alternative cross-coupling paradigm, in which simple and readily available organic molecules can be systematically used as coupling partners.

By using this photoredox-metal catalysis approach, we have achieved a direct decarboxylative sp3–sp2 cross-coupling of amino acids, as well as α-O– or phenyl-substituted carboxylic acids, with aryl halides. Moreover, this mode of catalysis can be applied to direct cross-coupling of Formula–H in dimethylaniline with aryl halides via C–H functionalization.

Welcome Scientific update to Pune, India 2-3 and 4-5 Dec 2014 for celebrating Process chemistry

Originally posted on New Drug Approvals:

WEBSITE http://www.scientificupdate.co.uk/

SCIENTIFIC UPDATE HAS A REPUTATION FOR ITS HIGH QUALITY EVENTS, BOTH FOR THE SCIENTIFIC CONTENT AND ALSO FOR THE EFFICIENCY OF ITS ORGANISATION. KEEP YOUR SKILLS UP TO DATE AND INVEST IN YOUR CONTINUING PERSONAL PROFESSIONAL DEVELOPMENT.

http://makeinindia.com/

TRAINING COURSE   2-3 DEC 2014

Process Development for Low Cost Manufacturing

When:02.12.2014 – 03.12.2014

Tutors:

Where: National Chemical Laboratory – Pune, India

Brochure:View Brochure

Register http://scientificupdate.co.uk/training/scheduled-training-courses.html

DESCRIPTION

Chemical process research and development is recognised as a key function during the commercialisation of a new product particularly in the generic and contract manufacturing arms of the chemical, agrochemical and pharmaceutical industries.

The synthesis and individual processes must be economic, safe and must generate product that meets the necessary quality requirements.

This 2-day course presented by highly experienced process chemists will concentrate on the development and optimisation of efficient…

View original 1,207 more words