64,302 research outputs found
Greener synthesis of Tadalafil using dimethylcarbonate and ionic liquids
No full textIntroduction
Tadalafil (commercially named Cialis™), a drug for the treatment of male erectile dysfunction, is commonly prepared from L-tryptophan through four steps in which different solvents and reagents are used. As it often happens in drug preparation the overall mass index of the preparation is quite low, causing a great amount of waste to be produced.
Results
Each step of the published synthesis of Tadalafil was investigated in view of the design of a greener and more afficient process by focussing on solvents and on integrating synthetic steps .
Dimethylcarbonate proved to be a good greener alternative to traditional solvents (i.e. nitromethane or ethanenitrile) for the diastereoselective Pictet-Spengler reaction (i.e. the second step of the synthesis). Both its lower toxicity and the water immiscibility contribute to the greenness of the procedure. In addition the last two steps of the preparation could be carried out stepwise in the same reactor by using [C4dmim][NTf2] (an ionic liquid) as the solvent.
These findings allowed us to propose two alternative processes named A and B. The principal improvements of processes A and B compared to the published synthesis is that they both do without solvents such as CH3CN, toluene, CH2Cl2, DMF and DMSO, and both combine the final two steps of by using an ionic liquid as solvent.
Conclusions
In summary processes A and B are high-yielding methods for the preparation of Tadalafil using only [C4dmim][NTf2] (an ionic liquid) and dimethylcarbonate as reaction media. Both have a better mass index than the published process, particularly if the the ionic liquid is recycled
Carbonate based ionic liquids and beyond
No full textIonic liquids appear almost like a different state of matter. Just like mercury, that I enjoyed playing with as a child after bursting thermometers. A liquid metal, and a liquid salt at room temperature are awe-inspiring, as their physical state is counterintuitive. We struggle to accept that a metal may not be hard, and that a salt may be non-crystalline, let alone liquid.
Thus, for sheer curiosity, we started synthesising ammonium and phosphonium ionic liquids. The first hurdle was to make them efficiently, colourless and pure. And this was achieved by using dimethylcarbonate (non-toxic) instead of alkyl halides as quaternarisation reagent. These syntheses were, efficient (100% atom economic), tuneable, halide-free, and produced only CO2 and methanol as by-products.1
But, ionic liquids are not just pretty. So what can we do with them?
Use them as green solvents? Sometimes yes, but often too costly, and not always an elegant or green application.
Unless we can design multiphase solvent systems with other advantages.2-3
It’s might also interesting to take advantage of the chemical properties of their ions,4 or to use them as catalysts,5-6 including for the upgrade of biogenic chemicals.7
The next question might be on how these materials work, e.g. as catalysts,8 and how can these properties be monitored.9 Or whether they can be used to make new devices, e.g. based on their luminescence.10
And why not try to make old compounds, e.g. choline, by these methods?
We will discuss this “genealogy” of applications and of examples, applied to a family of carbonate based ionic liquids.
1. Fabris, M.; Lucchini, V.; Noè, M.; Perosa, A.; Selva, M., Chem. Eur. J. 2009, 15 (45), 12273-12282.
2. Tundo, P.; Perosa, A., Chem. Soc. Rev. 2007, 36 (3), 532-550.
3. Gottardo`, M.`; Selva`, M.`; Perosa`, A. work in progress
4. Noè, M.; Perosa, A.; Selva, M.; Zambelli, L., Green Chem. 2010, 12 (9), 1654-1660.
5. Fabris, M.; Noe, M.; Perosa, A.; Selva, M.; Ballini, R., J. Org. Chem. 2012, 77 (4), 1805-1811.
6. Selva, M.; Noe, M.; Perosa, A.; Gottardo, M., Org. Biomol. Chem. 2012, 10 (32), 6569-6578.
7. Stanley`, J.`; Caretto`, A.`; Perosa`, A. work in progress
8. Lucchini, V.; Noè, M.; Selva, M.; Fabris, M.; Perosa, A., Chem. Commun. 2012, 48 (42), 5178-5180.
9. Lucchini, V.; Fabris, M.; Noe, M.; Perosa, A.; Selva, M., Int. J. Chem. Kinet. 2011, 43 (3), 154-160.
10. Fiorani`, G.; Selva, M.; Perosa`, A.`; Malba, C.; work in progress
X-ray and molecular dynamics studies of butylammonium butanoate-water binary mixtures
No full textThe nanostructural organisation of mixtures of the ionic liquid (butylammonium butanoate) and water at several mole fractions of water has been investigated using small and wide angle X-ray scattering (S-WAXS) and molecular dynamics (MD) simulations. The presence of a first sharp diffraction peak (FSDP) in the pure ionic liquid has been observed, experimentally and theoretically, suggesting the possibility of segregation of domains of different polarity in the system. With increasing dilution in water, the prepeak is shifted towards smaller Q values, and becomes very weak, while the principal peak moves towards larger Q values. These phenomena suggest the disruption of the hydrogen-bonded network of the ionic liquid, primarily through hydrogen bonding of the anion to water, a conclusion supported by MD simulations
Thermal expansion anomalies of R(Fe, M)(12) (R=Y, Nd; M=Mo and Si)
No full textStructural and thermal-expansion anomaly studies on R(Fe,M)(12) (R=Nd and and Y, M=Mo and Si) compounds were performed by x-ray diffraction. Mo atoms occupy the 8i site. While Si atoms occupy the 8f and 8j sites but not the 8i site. Thermal-expansion anomaly shows only in ab plane in the Mo compounds, while becomes very weak and along with only the c axis in the Si compounds. The anomaly was attributed to the contribution of the interactions of short Fe-Fe distances similar to the previous explanation on other R-Fe intermetallics and that of other strongly positive interactions such as 8j-8j. (c) 2005 American Institute of Physics.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000230168300025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Physics, AppliedSCI(E)EICPCI-S(ISTP)
Letter from Thomas R. Bodine, American Friends Service Committee Seattle office, to Mary M. Kimber, May 25, 1942
No full textLetter from Thomas R. Bodine to Mary M. Kimber, asking Kimber to visit individuals from the Puget Sound area incarcerated at Pinedale Assembly Center: Rev. Daisuke Kitigawa, Waichi Oyanagi, Chisako Higuchi, Mutsuo Hasiguchi and Mrs. Matsuoka, Makato Kobukata, the Hirabayashi family, and Violet Yokoyama. A note in pencil at the top of the page: "Burcham." A response letter from Grace and Calvin Coke to Thomas R. Bodine is found in item: chs_ms840_0306.Personal correspondence, organizational records, government documents, publications, and other papers created or collected by Joseph R. Goodman documenting the forced removal and incarceration of Japanese Americans during World War II, as well as organized resistance to incarceration. Included in the collection are records of the Japanese Young Men's Christian Association and the Japanese American Citizens' League in San Francisco, including papers of the Japanese YMCA's executive secretary Lincoln Kanai; Sakai family papers; Goodman's correspondence to and from Japanese American incarcerees, organizations opposing forced removal and incarceration of Japanese Americans, the War Relocation Authority, and others; publications, photographs, and ephemera from the Topaz Relocation Center, where Goodman taught high school; War Relocation Authority records and publications; and newspaper clippings, pamphlets, and reports about forced removal and incarceration created by various government, religious, and civic organizations, in California and nationwide
The influence of the src-family kinases, Lck and Fyn, on T cell differentiation, survival and activation
No full textThe src-family kinases p56lck (Lck) and p59fyn (Fyn) are expressed in T cells and are among the first signaling molecules to be activated downstream of the T cell receptor (TCR). Evidence is emerging that although closely related, these signaling molecules have discrete functions during development, maintenance and activation of peripheral T cells. For example, during thymopoiesis Lck is uniquely able to provide all the signals required for pre-TCRbeta selection, although Fyn can substitute for a subset of these. Positive selection of CD4 single-positive (SP) cells is also critically dependent on the expression of Lck but not Fyn, while differentiation of CD8 SP cells proceeds relatively efficiently in the absence of Lck. In naïve peripheral T cells either Lck or Fyn can transmit TCR-mediated survival signals, and yet only Lck is able to trigger TCR-mediated expansion signals under conditions of lymphopenia. Stimulation of naïve T cells by antigenic stimuli is also severely compromised in the absence of Lck, but more subtly impaired by the absence of Fyn. We discuss recent experiments addressing how these two src-kinase family members interface with downstream signaling pathways to regulate these diverse aspects of T cell behavior
Collaborative computer-mediated music composition in cyberspace
No full textThis article reports on an exploratory investigation of the relationship between prior experience of formal instrumental music tuition (FIMT) and the process of collaborative computer-based music composition. The study linked a school in the UK with a school in Norway to engage in computer-mediated collaborative composition via e-mail. Participants were grouped into composing pairs (one from each country) balanced for prior musical experience. Results revealed prior experience of FIMT was associated with extended and complex musical dialogues, critical engagement with musical ideas and produced an
‘exploratory’ environment. No prior experience of FIMT was associated with uncritical and descriptive dialogues and a ‘cumulative’ environment. Proposals for future research are discussed
A 2 h periodic variation in the low-mass X-ray binary Ser X-1
No full textSpectroscopy of the low-mass X-ray binary Ser X-1 using the Gran Telescopio Canarias have revealed a ?2 h periodic variability that is present in the three strongest emission lines. We tentatively interpret this variability as due to orbital motion, making it the first indication of the orbital period of Ser X-1. Together with the fact that the emission lines are remarkably narrow, but still resolved, we show that a main-sequence K dwarf together with a canonical 1.4 M? neutron star gives a good description of the system. In this scenario, the most likely place for the emission lines to arise is the accretion disc, instead of a localized region in the binary (such as the irradiated surface or the stream-impact point), and their narrowness is due instead to the low inclination (?10°) of Ser X-1
Modes of communication during jazz improvisation
No full textThis study investigated modes of communication adopted by six student jazz musicians during rehearsal and performance. Six one-hour rehearsal sessions and a performance were observed and videotaped for analysis. Results revealed six modes of communication that formed two main categories, verbal and non-verbal, each containing three distinct modes of communication: instruction, cooperation and collaboration. Non-verbal collaborative
mode displayed empathetic attunement, which is a vehicle for empathetic creativity. Empathetic creativity is a theoretical concept proposed by the author based on the concept of empathetic intelligence (Arnold, 2003, 2004). Practical applications of empathetic creativity are discussed with reference to music education, focusing on evaluation of individual contribution to group creative performances
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
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