Ozonolysis heterocycles, ozone

There are six possible five-membered monocycles 1-6 containing three oxygen or sulfur atoms in the 1,2,3-positions <1996CHEC-II(4)545>. 1,2,3-Trioxolane 1 is the parent compound of the so-called primary ozonides, the primary reaction products in the reaction of alkenes with ozone. They are extremely unstable and rearrange to the more stable ozonides (1,2,4-trioxolanes). This rearrangement represents a key step in the reaction of ozonolysis. However, the parent compound 1 and a few derivatives have been characterized at low temperatures (see Section 6.05.10.1). 1,2,3-Trithiolanes have been synthesized (Section 6.05.10.3) some of them undergo slow decomposition at room temperature. Derivatives of 1,2,3-dioxathiolane 3 are unknown, and the other heterocycles of the mixed types 4-6 are known only in the oxidized forms, mostly as -oxides and J -dioxides, and also A-imino and A-thiono derivatives <1996CHEC-II(4)545>. The A-oxides and AA -dioxides of... 

The ozonolysis of diarylfuroxans was studied by Kinney and Harwood. In their earlier paper,272 they found that benzoic acid was formed from diphenylfuroxan, and they interpreted this as evidence for the presence of a C=C bond in the heterocyclic ring, as in structure 4. Later, the isolation of isomeric anisylphenylfuroxans by Meisenheimer et al.22 came to their attention, and Kinney269 subjected the two forms to ozonolysis. Both formed a yellow ozone adduct of unknown composition, which with cold dilute sodium hydroxide gave the salt of the acid derived from the 3-substituent, together with a red residue which on further hydrolysis with hot hydroxide formed the acid of the 4-substituent (Eq. 10). This work provided valuable support for Meisenheimer s contention that his compounds were positional isomers, both based on the furoxan ring structure (1). 

Numerous heterocyclic compounds can be oxidized with ozone to deliver derivatives useful in synthesis and the reaction products can be tuned according to the additives and conditions in the reaction medium. When treated with ozone, pyrimidine-2-thiones and 2-thiouracils react to give several p3Timidine derivatives (eq 57). Use of aprotic solvents or ozonolysis without an active nucleophile yields dimerization products, whereas ozonolysis in protic solvents or in the presence of a nucleophile leads to the sulfinic acid derivative that can then be converted to several products depending on workup conditions. The parent pyrimidine can be isolated when acid is introduced into the medium, and with an equal volume of water the pyrimidinone product is isolated. While a protic solvent, EtOH in the medium acts as a nucleophile to deliver the 2-ethoxypyrimidine. 

The pentenamides were then treated with ozone. Changes in solvent and temperature (-78° to room temperature) did not alter significantly the course or yield of this reaction. The ozonolysis of the olefin gave an intermediate aldehyde which could not be isolated but cyclized immediately to the desired hydroxypyrrolidi-none, 2. This general procedure was applicable to a large number of heterocyclic amines (Table II). In all cases, good overall yields were obtained. 

N-acylated esters of (cyclohexa-l,4-dienyl)-L-alanine are ozonized aiming at the synthesis of novel uimatural amino acids. The combined reduction and ozonolysis followed by condensation with a suitable nucleophile results in transformation of the aromatic ring of L-Phe to isooxasolyl, N-phenylpyrazolyl and to bicyclic pyrazolo[l,5-a]pyrimidine groups. The preparation of heterocyclic alanine derivatives is reported [89]. 

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