- 3-Quinuclidinyl-α-methoxydiphenylacetate: A multi-targeted ligand with antimuscarinic and antinicotinic effects designed for the treatment of anticholinesterase poisoning
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Racemic 3-quinuclidinyl-α-methoxydiphenylacetate (MB266) was synthesised. Its activity at muscarinic acetylcholine receptors (mAChRs), and muscle and neuronal nicotinic acetylcholine receptors (nAChRs), was compared to that of atropine and racemic 3-quinu
- Bird, Mike,Gore, Samuel J.,Green, A. Christopher,Lindsay, Christopher D.,Rice, Helen,Tattersall, John E. H.,Timperley, Christopher M.,Whitmore, Charlotte L.
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- The Reaction between Acyl Halides and Alcohols: Alkyl Halide vs. Ester Formation
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In the reaction between an acyl halide and an alcohol the thermodynamically favoured products are the free carboxylic acid and the alkyl halide.The initial reaction is, generally, the formation of an ester and HHal.When the alcohol is very prone to yield an alkyl cation upon protonation by HHal, formed H2O exhibited a superior reactivity and competed successfully with the alcohol for the acyl halide making, therefore, ester formation practically confined to a triggering role.But, in those cases where the cation is less easily formed, ester formation was favoured and, consequently, became the necessary elementary step towards alkyl halide formation.Tis final product, on the other hand, might be extremely slow to form in an SN2 reaction between the protonated ester function and the halide ion.In these instances, therefore, as well as in the cases when a basic solvent competes for the proton of HHal, the ester is the final product.A notable exception of the situation above outlined, is given by α-hydroxy-α-phenylbenzeneacetic acid (2y), which appears to undergo direct chlorine-hydroxyl interchange through a quaternary intermediate (E), in the end collapsing to α-chloro-α-phenyl-benzeneacetic acid (4y).Different systems were compared using CH2Cl2 as a solvent under strictly similar conditions.Some 28 different substrates were tested for reaction with AcCl (1a), whereas the action of eight acyl halides (a) against (RS)-α-methylbenzenemethanol (2n) and α-phenylbenzenemethanol (2p), as well as the effect of five different solvents on the reaction between two alcohols (2p and 2-methyl-2-propanol, 2c) with 1a, were observed.
- Strazzolini, Paolo,Giumanini, Angelo G.,Verardo, Giancarlo
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p. 217 - 254
(2007/10/02)
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- Nucleophilic substitution in diphenylmethyl derivatives. I. Formolysis of diarylmethyl derivatives: an α-substituent effect
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The reactions of formic acid with and without addition of sodium formate with diphenylmethanol (4) and chlorodiphenylmethane (3) were compared to those with hydroxydiphenylacetic (benzilic) acid (12a) and chlorodiphenylacetic acid (14a).Formic acid did not favour any SN1-type reaction on 4, but a strong catalysis by iodide ion was observed.Sodium formate rapidly performed the substitution of the chlorine in 3.A similar outcome was obtained with chloro acid 14a, but the rationalization of the results is different.Chloro acid 14a and its methyl ester 14b were prompt to react, but the equilibria were shiftet to α-formyloxy products 13 only by the addition of HCOONa.HCOOH was unable to perform any reduction on either 3 or 4 or 12a and 14a, a fact which was taken as evidence for concerted substitution mechanism on ion pairs or betaine 15.Mechanistic implications are drawn.
- Strazzolini, Paolo,Giumanini, Angelo G.,Verardo, Giancarlo
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- Diaryldichlorocarbonyl Ylides Derived from Dichlorocarbene and Aromatic Ketones
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The thermal decomposition of phenyl(bromodichloromethyl)mercury (4) in the presence of benzophenone (2) in dry benzene at 80 degC resulted in α-chlorodiphenylacetyl chloride (6) as the only major initial product together with small amounts of dichlorodiphenylmethane (5) and carbon monoxide.Analogous products were observed from fluorenone (3).Dimethyl acetylenedicarboxylate (15) failed to trap the presumed intermediate dihalocarbonyl ylide from either ketone.Attempts to explain the difference in behavior between dihalocarbonyl ylides derived from benzaldehydes and diaryl ketones suggest that in the latter case a twist in the plane of the ylide caused by endo,endo interactions of a chlorine and an aromatic ring leads to rapid closure to oxirane 11 followed by rearrangement to acid chloride 6.Alternative explanations are also explored.
- Martin, Charles W.,Gill, Harpal S.,Landgrebe, John A.
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p. 1898 - 1901
(2007/10/02)
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