Alkylation acylation

The Knorr synthesis is not particularly sensitive to the nature of R and ie, they may be alkyl, acyl, aryl, or carbalkoxy without significantly affecting the yield. Similarly, good yields are obtained if R and R are acyl or carbalkoxy, but poor yields are obtained if they are alkyl or aryl. 

The 4-piperazinyl nitrogen in pipemidic acid (69) has been alkylated, acylated and sulfonylated in the search for enhanced antibacterial activity, whilst the 3-pyrrolidinyl position in piromidic acid (68) is hydroxylated metabolically and enzymically to (74) (75MI21503), from which acyloxy derivatives have been prepared. 

From a general point of view, the tautomeric studies can be divided into 12 areas (Figure 20) depending on the migrating entity (proton or other groups, alkyl, acyl, metals. ..), the physical state of the study (solid, solution or gas phase) and the thermodynamic (equilibrium constants) or the kinetic (isomerization rates) approach. 

Alkylation, acylation, etc. at the heteroatom lead to onium salts. In small systems these are difficult to isolate, and very weakly nucleophilic counterions must be used, such as... 

FRIEDEL - CRAFTS Alkylation-Acylation Alkylation or acylation ol aromatic compounds by means of alryl halides, alcohols.alkenes, acyl halides in the presence of Lewis acids... 

Prior to tlie advent of tripbenylpbospbine-stab dized CuH [6a, b, 11], Tsuda and Saegusa described use of Gve mole percent MeCu/DtBAL in THE/HMPA to effect bydtoaluminaiion of conjugated ketones and esters [26], Hie likely aluminium etiolate intermediate could be quendied witli water ot TMSCl, ot alkylated/acylated widi various electrophiles fsudi as Mel, allyl bromide, etc. Sdieme 5.5). Mote... 

Ualike the multiple substitutions that often occur in Friedel-Crafts alkylations, acylations never occur more than once on a ring because the product acyl-benzene is less reactive than the nonacylated starting material. We ll account for this reactivity difference in the next section. 

Kinetic deprotonation of 1-alkenyl sulfoxides produces the corresponding a-lithiosulfmyl carbanions59 which have been deuterated, alkylated, acylated (e.g., equation 19)60 and carboxylated. 

Die aus Alkyl-acyl-aminen durch Nitrosierung leicht zuganglichcn N-Nitroso-N-alkyl-carbonsaure-amide3 lassen sich bei 25° mit Natriumboranat in 1,2-Dimethoxy-athan zu prim. Alkoholen (40-80% d.Th.) redu-zieren4 mit Lithiumalanat werden dagegen die entsprechenden Aldehyde erhalten5. 

Nitroso-alkyl-acyl- 263 Nitroso-dialkyl- 696 Nitroso-dimethyl- 696 Nitroso-diphenyl- 538 Nitroso-methvl-phenyl- 696 Octyl-115 Oxo- 4881 Pentyl-... 

In the first step, a resin-bound secondary amine is acylated with bromoacetic acid, in the presence of N,N-diisopropylcarbodiimide. Acylation of secondary amines is difficult, especially when coupHng an amino acid with a bulky side chain. The sub-monomer method, on the other hand, is facilitated by the use of bromoacetic acid, which is a very reactive acylating agent Activated bromoacetic acid is bis-reactive, in that it acylates by reacting with a nucleophile at the carbonyl carbon, or it can alkylate by reacting with a nucleophile at the neighboring ah-phatic carbon. Because acylation is approximately 1000 times faster than alkylation, acylation is exclusively observed. 

The acyl-enzyme can eliminate the 4-chlorine atom to generate this reactive intermediate that can then react with a nearby nucleophile such as His57 to give an alkylated acyl-enzyme derivative in which the inhibitor moiety is bound to the enzyme by two covalent bonds (Scheme 11.5). Inhibition is irreversible.59 The mechanism has been confirmed by X-ray structural analysis of protease-isocoumarin complexes. There is a cross-link between the inhibitor and the Serl95 and His57 residues of PPE.60 Human leukocyte elastase is also very efficiently inactivated.61... 

The addition of perfluoroalkyl iodides to simple olefins has been quite successful under aqueous conditions to synthesize fluorinated hydrocarbons.119 In addition to carbon-based radicals, other radicals such as sulfur-based radicals, generated from RSH-type precursors (R = alkyl, acyl) with AIBN, also smoothly add to a-allylglycines protected at none, one, or both of the amino acid functions (NH2 and/or CO2H). Optimal results were obtained when both the unsaturated amino... 

A further extension to this concept was (dimethylsilyl)propionic acid linker 75 used for the solid-phase synthesis of aryl-containing organic compounds [86], The linker was cleaved smoothly with TFA and has been used for the synthesis of compounds which involved alkylation, acylation, and Mitsunobu reactions. 

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