Ring-opening reactivity

Silverman and coworkers have carried out extensive research on the mechanism of inactivation of MAO by cyclopropylamine analogues. They first reported in the early 1980s that A/-cyclopropyl-A/-arylalkylamines are mechanism-based inactivators of MAO [121,125], The mechanism proposed was enzyme-catalyzed one electron oxidation of A/-cyclopropylamines to give reactive ring-opened products which further react with either flavin and/or a cysteine residue, depending on the structure of the inactivator. According to their reports [120,125, 126], 1-phenylcyclopropylamine (50) attached reversibly to a cysteine residue and irreversibly to the flavin when it activated MAO B, whereas 50 modified only the flavin during inactivation of MAO A. In the case of frans-2-phenylcyclopropy-lamine (8a) and A/-cyclopropyl-a-methylbenzylamine (51), both MAO A and B are inactivated by attachment to a cysteine residue (Fig. 3). 

An interesting example of a 2//-l,3-thiazete in equilibrium with its very reactive ring-opened valence tautomer has been reported (75AG(E)766, 77CB2114). 

In some systems, especially in nitrogen bridgehead systems and azolium salts, nucleophiles open the azole ring oxadiazole systems are the more reactive. Ring opening and Dimroth rearrangements in the azine ring can be observed. 

Witz G, Zhang Z, Goldstein BD. 1996. Reactive ring-opened aldehyde metabolites in benzene toxicity. Environ Health Perspect 104 (Suppl 6) 1195-1199. 

Note Acyl glucuronides can undergo acyl migration reactions that may yield more reactive ring-opened produets (Staehulski et al., 2006) ... 

The recently reported rearrangement (1581) of 2-allylamino-4-carboxamido-5-aminothiazoIes to 4-aminoimidazole-5-carboxamide in presence of sodium bicarbonate probably involves the electrophilic reactivity of C-2, which allows the ring opening. 

The greater reactivity of the 5-position of selenazoles, compared to thiazoles, toward electrophilic substitution has also been demonstrated (19). Substituents in the 2-position possessing a mesomeric donor effect increase the reactivity, but, as Haginiwa (19) observed, also increase the tendancy to ring Opening,... 

The reactivity of epoxides toward nucleophilic ring opening is responsible for one of the biological roles they play Squalene 2 3 epoxide for example is the biological... 

Rea.ctlons, Butyrolactone undergoes the reactions typical of y-lactones. Particularly characteristic are ring openings and reactions in which ring oxygen is replaced by another heteroatom. There is also marked reactivity of the hydrogen atoms alpha to the carbonyl group. 

TFEO is by fai the most reactive epoxide of the series. However, ail the reported perfluoroepoxides undergo similar ring-opening reactions. The most important reactions of these epoxides ate those with the fluoride ion or perfluoroalkoxides. The reaction of PIBO and the fluoride ion is an example (27). It also illustrates the general scheme of oligomerization of perfluoroepoxides (eq 5). 

Primary cycloaUphatic amines react with phosgene to form isocyanates. Reaction of isocyanates with primary and secondary amines forms ureas. Dehydration of ureas or dehydrosulfuri2ation of thioureas results in carhodiimides. The nucleophilicity that deterrnines rapid amine reactivity with acid chlorides and isocyanates also promotes epoxide ring opening to form hydroxyalkyl- and dihydroxyalkylaniines. Michael addition to acrylonitrile yields stable cyanoethylcycloalkylarnines. 

Reaction-Injection Molding and Reactive Casting. Reaction-iajection molding (RIM) (22) and reactive casting (23) have been demonstrated on nylon-6, which is polymerized by catalytic ring opening and linear recondensation of S-caprolactam (qv) (24). 

In this section three main aspects will be considered. Firstly, the basic strengths of the principal heterocyclic systems under review and the effects of structural modification on this parameter will be discussed. For reference some pK values are collected in Table 3. Secondly, the position of protonation in these carbon-protonating systems will be considered. Thirdly, the reactivity aspects of protonation are mentioned. Protonation yields in most cases highly reactive electrophilic species. Under conditions in which both protonated and non-protonated base co-exist, polymerization frequently occurs. Further ipso protonation of substituted derivatives may induce rearrangement, and also the protonated heterocycles are found to be subject to ring-opening attack by nucleophilic reagents. 

Small unsaturated rings are usually very reactive undergoing ring opening in a number of ways, and this characteristic has been utilized in heterocyclic synthesis. In their role as dienophiles or dipolarophiles, the initial cycloaddition is usually followed by a valence tautomerism resulting in a six-membered or larger ring system. Several examples exist, however, where this does not occur, and these are described below. 

The pyrazole molecule resembles both pyridine (the N(2)—C(3) part) and pyrrole (the N(l)—C(5)—C(4) part) and its reactivity reflects also this duality of behaviour. The pyridinic N-2 atom is susceptible to electrophilic attack (Section 4.04.2.1.3) and the pyrrolic N-1 atom is unreactive, but the N-1 proton can be removed by nucleophiles. However, N-2 is less nucleophilic than the pyridine nitrogen atom and N(1)H more acidic than the corresponding pyrrolic NH group. Electrophilic attack on C-4 is generally preferred, contrary to pyrrole which reacts often on C-2 (a attack). When position 3 is unsubstituted, powerful nucleophiles can abstract the proton with a concomitant ring opening of the anion. 

Diene moieties, reactive in [2 + 4] additions, can be formed from benzazetines by ring opening to azaxylylenes (Section 5.09.4.2.3). 3,4-Bis(trifluoromethyl)-l,2-dithietene is in equilibrium with hexafluorobutane-2,3-dithione, which adds alkenes to form 2,3-bis-(trifluoromethyl)-l,4-dithiins (Scheme 17 Section 5.15.2.4.6). Systems with more than two conjugated double bonds can react by [6ir + 2ir] processes, which in azepines can compete with the [47t + 27t] reaction (Scheme 18 Section 5.16.3.8.1). Oxepins prefer to react as 47t components, through their oxanorcaradiene isomer, in which the 47r-system is nearly planar (Section 5.17.2.2.5). Thiepins behave similarly (Section 5.17.2.4.4). Nonaromatic heteronins also react in orbital symmetry-controlled [4 + 2] and [8 + 2] cycloadditions (Scheme 19 Section 5.20.3.2.2). 

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