Paolo Strazzolini

Selective nitrolytic deprotection of N-BOC-amines and N-BOC-amino acids derivatives

Abstract The extension of the deprotection procedure using HNO3 in CH2Cl2 to a number of appropriately selected N-BOC-masked amines and derivatives of natural amino acids was investigated. The method was found to work effectively with almost all tested substrates, with the exception of activated aromatic amines and heterocycles which underwent unavoidable faster oxidation. Alanine, phenylalanine, serine and lysine derivatives were efficiently deprotected, as well as dipeptide Ala–Phe, preserving the configuration of the substrates and without affecting copresent Z and ester functions, with a remarkable selectivity towards acid sensitive t-butyl esters. The obtained amino acids esters, isolated and characterized in the form of nitrates salts, proved to be suitable intermediates to be used in peptide synthesis.

The reaction between acyl halides and alcohols: Alkyl halide vs. Ester formation

Abstract In the reaction between an acyl halide and an alcohol the thermodynamically favoured prodtcts are the free carboxylic acid and the alkyl halide. The initial reaction is, generally, the formation of an dster and HHal. Vhen the alcohol is very prone tn yield an alkyl cation upon protonation by HHal, formed H 2 O exhibited a supdrior 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. This final product, on the other hand, might be extremely slow to form in an S N 2 reaction between the protonated ester function and the halide ion. In these hnstances, 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 shtuation above ottlined, 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 CH 2 Cl 2 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 (1) 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.

Nitric acid in dichloromethane solution. Facile preparation from potassium nitrate and sulfuric acid

Pure dry HNO3 can be liberated from KNO3 with 96% H2SO4 directly into CH2Cl2 to yield solutions of variable concentration for use in a number of organic reactions. The present method efficiently replaces the employment of 100% HNO3 in some synthetic applications, avoiding the problems associated in storage and handling the acid.

Deprotection of t-Butyl Esters of Amino Acid Derivatives by Nitric Acid in Dichloromethane

Abstract The extension of the deprotection procedure of t-butylated carboxyl function using HNO3 in CH2Cl2 to a number of appropriately selected N-Z-derivatives of natural amino acid esters was investigated. The method was found to work effectively with alanine, phenylalanine, serine and the dipeptide aspartame, but the reagent brought about a number of unwanted transformations with tyrosine, methionine and tryptophan. Suitable protection of functions present in the latter ones allowed selective ester dealkylation, but tyrosine underwent unavoidable fast preliminary ring nitration.

Ketimines From Ketones and Ammonia

Abstract The direct synthesis of ketimines from ammonia and ketones catalyzed by ammonium chloride is described.

Aromatic tertiary amines and n-butyl nitrite

Abstract The reaction between alkyl nitrites, particularly n-butyl nitrite, and tertiary aromatic amines under a variety of experimental conditions promptly yielded products of N-dealkylation-N-nitrosation, ring nitration, ipso-substitution and, occasionally, combinations of these processes. Aminoethers were detected as final products and intermediates on the way to N-nitrosations. Reaction pathways are suggested for some of the observed behaviours on the basis of experimental evidences whereas other alternatives are discarded.

Nitrolysis of carboxylic t-butyl and 1-adamantyl esters

Abstract A cheap, less problematic, efficient and selective reagent for the removal of the t-butyl and 1-adamantyl protecting groups from carboxylic esters was found to be commercial 100% HNO3 in CH2Cl2. Incidentally, 1,1-dimethylethyl nitrate and tricyclo[3.3.1.13,7]dec-1-yl (1-adamantyl) nitrate are coproducts in a clean reaction. The procedure is in many ways superior to the method employing CF3COOH.

N-Dealkylation-N-nitrosation of tertiary aromatic amines by N-butyl nitrite

Abstract N,N-Dialkyl aromatic amines with a variety of ring substituents are N-dealkylated and N-nitrosated efficiently by n-butyl nitrite/ammonium chloride/water at reflux temperature. Ring nitrosation was never observed, but minor amounts of m- and p-nitro amines and/or nitrosamines were formed in some cases. Ring nitration is rather a reaction of the initial substrate than a process occurring on formed nitrosamines. The leaving propensities of the initial N-substituents to yield nitrosamines were in the order benzyl methyl alkyl.

Theoretical investigations on (CO)n(CO2)m cyclic cooligomers

Abstract Ab initio calculations have been performed on the (CO) n (CO 2 ) m cyclic copolymers, where n , m =1,2 with m ≥ n . The cyclic molecules were studied at the HF/6-311G, HF/6-311+G(df), MP2/6-311+G(df) levels and Gaussian-2 theory with reduced Moller–Plesset order, G2MP2. The structures of the three cyclic oligomers investigated, C 2 O 3 , C 3 O 5 and C 4 O 6 are found to have a minimum and the geometries are planar. The energy releases of the dissociation reactions indicate that these molecules are thermodynamically unstable with respect to the parent monomers CO and CO 2 . In addition, the heats of formation for the cyclic molecules were evaluated at the G2MP2 level using an isodesmic approach and bond separation energies.

Heterocycles from heterocycles. 1,3-Diaryl-4,5-imidazolidinediones from 1,3,5-triarylhexahydro-1,3,5-triazines and oxalyl chloride

1,3-Dialkyl-4,5-imidazolidinediones (5) were prepared by the reaction of oxalyl chloride (3) with the corresponding 1,3,5-trialkyl-hexahydro-1,3,5-triazines (4), followed by addition of ethanol, in good to fair yields and fully characterized by MS, IR,1H and13C NMR.