Carboxy group activation mechanism

Typical reaction conditions for these reagents are shown below. Propose mechanisms by which these heterocyclic molecules can function to activate carboxy groups under these conditions. 

Trialkyl (triaryl)stannyl methacrylates were copolymerized with ethylene and methyl methacrylate and it was shown that the resulting copolymer offers improved mechanical properties as compared to ethylene, and high fungicidal activity. It was suggested that homopolymers and copolymers of triethylstannyl methacrylate contain a covalent and an ionic bond between the carboxy group and the tin atom 63). 

In the case of 13-LOXs, the active site is again penetrated by the substrate using its methyl end first, whereas with 9-LOXs, the substrate is forced into an inverse orientation, favoring penetration with its carboxy group first. Consequently, a radical rearrangement at either [+2] or [-2], respectively, may be facilitated in both cases by the same mechanism within the active site. 

Like the mixed carbonic anhydride (intermediate A from Problem 7(a)), the intermediate imidazolide (intermediate C) is an activated carboxy group that can react with amines to form amides. The addition-elimination mechanism, illustrated below using arrow pushing, involves addition of an amine followed by elimination of imidazole. 

The intrinsic consequences of such strong activation of the carboxy group toward aminolysis are (1) the increased acidity of the C -proton which favors enolization giving 16 and (2) the facile ring closure of the carboxy-activated amino acid or peptide component to oxazol-5(4//)-ones 17 by base catalysis. Both mechanisms lead to loss of stereochemical integrity, i.e. racemization or epimerization as illustrated in Schemes 6 and (for the correct use of the terms racemization or epimerization see Vol. E 22b, Section 7.4). 

Organotin compounds are also active as catalysts in the polymerizations of A -carboxy anhydrides. " The mechanism of the reaction was postulated by Freireich, Gertner, and Zilkha " to consist of addition of the organotin compound to the anhydride and formation of organotin carbamate. It subsequently decarboxylates and leaves an active -N-Sn- group that adds to another molecule of A -carboxyanhydride. This process is repeated in every step of the propagation " ... 

In all 19 optically active amino acids, one of the substituents on the a-carbon is a potentially acidic hydrogen atom. Removal and subsequent reattachment of this proton represents a potential mechanism for enantiomerization of this chiral centre. Chiral integrity is particularly at risk during coupling as the acidity of this proton is greatly enhanced when the carboxy group is activated. In practice, direct enolization does not appears to be an important mechanism for enantiomerization except for amino acids such as phenylglycine, which offer an additional mode of enol stabilization. 

Chromatographic and enzymic studies of the insoluble residues obtained by hydrolysis of various cereal starches with acid have suggested a new model for the structure of waxy maize amylopectin. A review dealing with the mechanism of action of a-amylases has discussed the compositions of the residual oligosaccharides. The results of a study of the catalytic activity of poly(acrylic acid-styrenesulphonic acid) towards amylose in aqueous solution at low pH indicated that interactions between the carboxy-groups of the copolymer and the hydroxy-groups of the substrate make no contribution to the rate of reaction. ... 

Nishibayashi and Sakata recently described the Ru-catalyzed [3+2] cycloaddition of ethynylcyclopropanes bearing two carboxy groups at the homopropargyUc position with aldehydes and aldimines to afford 2-ethynyltetrahydrofurans and pyrrolidines (Scheme 52) [179]. The proposed mechanism requires the formation of the ruthenium allenylidene species II by isomerization of the initially formed vinylidene I. Nucleophilic attack of species II to the aldehyde or aldimine, which are activated by BF3-OEt2, would afford allenylidene III. Final nucleophilic attack on the Cy by the oxygen or nitrogen followed by tautomerization of the vinylidene... 

When unsubstituted, C-5 reacts with electrophilic reagents. Thus phosphorus pentachloride chlorinates the ring (36, 235). A hydroxy group in the 2-position activates the ring towards this reaction. 4-Methylthiazole does not react with bromine in chloroform (201, 236), whereas under the same conditions the 2-hydroxy analog reacts (55. 237-239. 557). Activation of C-5 works also for sulfonation (201. 236), nitration (201. 236. 237), Friede 1-Crafts reactions (201, 236, 237, 240-242), and acylation (243). However, iodination fails (201. 236). and the Gatterman or Reimer-Tieman reactions yield only small amounts of 4-methyl-5-carboxy-A-4-thiazoline-2-one. Recent kinetic investigations show that 2-thiazolones are nitrated via a free base mechanism. A 2-oxo substituent increases the rate of nitration at the 5-position by a factor of 9 log... 

The same metabolite, 11.123, is produced when a carboxy substituent is present at C(3) (i.e., 11.122, R = COOH) [147][148], The mechanism of this activation reaction is also concerted, but, in this case, more extended, with involvement of the carboxylate group and decarboxylation simultaneous with ring cleavage. In vivo in rats, this reaction was clearly slower than for the unsubstituted analogue, with plasma levels of both the prodrug and the metabolite 11.123 being maintained at comparable levels for 24 h. 

Recently, Sargeson s group has studied the hydration of coordinated carboxy-alkoies as model chemistry for the aconitase reaction (61). A key feature of their nxrdel is the activation of the double bond via carboxylate coordination to the metal and subsequent attack by a coordinated cu-hydroxo group. This was a feature of the "ferrous wheel mechanism as well. The model chemistry suggested that a closer examination of carboxyl labeled substrate and substrate analogues was... 

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