Cyclization reactions unimolecular reaction

The kinetic data for the reaction of primary alkyl radicals (RCH2 ) with a variety of silanes are numerous and were obtained by applying the free-radical clock methodology. The term free-radical clock or timing device is used to describe a unimolecular radical reaction in a competitive study [2-4]. Three types of unimolecular reactions are used as clocks for the determination of rate constants for this class of reactions. The neophyl radical rearrangement (Reaction 3.1) has been used for the majority of the kinetic data, but the ring expansion rearrangement (Reaction 3.2) and the cyclization of 5-hexenyl radical (Reaction 3.3) have also been employed. 

The competitive kinetics of Scheme 3.1 can also be applied to calibrate the unimolecular radical reactions provided that kn is a known rate constant. In particular the reaction of primary alkyl radicals with (Mc3Si)3SiH has been used to obtain kinetic data for some important unimolecular reactions such as the p-elimination of octanethiyl radical from 12 (Reaction 3.5) [12], the ring expansion of radical 13 (Reaction 3.6) [8] and the S-endo-trig cyclization of radical 14 (Reaction 3.7) [13]. The relative Arrhenius expressions shown below for the... 

In contrast to cyclization and rearrangement as the unimolecular reaction, the EZ isomerization of olefins is difficult due to a drastic and unenviable change in the size and shape of the occupied space by substituents on the double bond during isomerization in the crystalline state. Some (Z,Z)-muconic derivatives provide a geometrical isomer as the photoproduct in a high yield, but not a polymer, under UV irradiation in the crystalline state, as is described in the Introduction (Scheme 1 and Table 1). This isomerization is a crystal-to-crystal reaction with an excellent selectivity, which is completely different from ordinary photoisomerizations. 

At this time, no absolute rate constants have been determined for a reaction of an aminium cation radical. However, for synthetic utility, one needs to consider the relative rate constants for competing reactions. Competition between two unimolecular reactions depends only upon the relative rate constants for the processes. For competition between a unimolecular and a bimolecular reaction whose rate constants are comparable, product distributions can easily be controlled by the concentration of the second species in the ratio of rate laws. The ratio of reaction products from cyclization (unimolecular) versus hydrogen atom trapping before cyclization (bimolecular) can be expressed by the equation %(42 + 65)/%41 = Ar/(A H[Y - H]) (Scheme 20). Competition between two bimolecular reactions is dependent on the relative rate constants for each process and the effective, or mean, concentration of each reagent. The ratio of the products from H-atom transfer trapping of the cyclized radical versus self-trapping by the PTOC precursor can be expressed by the equation %42/%65 = (kH /kT) ([Y - H]/[PTOC]). 

Unimolecular reactions of organic radical cations are fragmentation, rearrangement and cyclization, as illustrated by the following generic examples. The specific details of each of these transformations are included in Section 7.4.6. (Note Ar and R represent aryl and alkyl groups, respectively.)... 

In 1965, the American chemists Robert B. Woodward (1917-1979, 1965 Nobel laureate in Chemistry) and Roald HofEcnann (1937-, 1981 Nobel laureate in Chemistry) (ref. 151), well aware of the stereospecificity of many unimolecular cyclization reactions of open conjugated molecules, e.g. cis-1,3-butadiene, developed a vast application of frontier orbitals to this and similar types of reactions. 

All reported syntheses from acyclic precursors of the 1,2-thiazocine ring system have been effected through unimolecular cyclization reactions. The simplest derivative, (47), was prepared via lactamization of the corresponding acyclic co-amino sulfonyl chloride in refluxing toluene (Equation (14)) <56BRP742227>. 

Unimolecular cyclization reactions and both nucleophilic and photochemical addition of the O—O unit to appropriate precursors constitute the primary routes which have been reported for the synthesis of 1,2-dioxocins from acyclic precursors. Barton-type cyclization of appropriately-substituted organic peroxides affords low (52) (Equation (23)) <83LA6io> to modest (54) (Equation (24)) <83LA624> yields of cyclic products. 

Both unimolecular cyclizations and condensation reactions have been used to effect closure of the 1,4-dioxocin ring. Although these are discussed separately below, the condensation reactions presumably occur in a stepwise manner, and thus formally are perhaps better considered to be cyclization reactions also. Photoinduced remote cyclization of ketoethers (157 R = H, Me) affords the corresponding dioxocanones (151) in 48% (R = H) and 76% (R = Me) yield, apparently via an intermediate i/-atom abstraction via a ten-membered ring-transition state (Scheme 42). Compound (151 R = H) is obtained as a single stereoisomer, presumably with trans phenyl groups, while (151 R = Me) is obtained as a ca. 1 1 mixture of cis and trans isomers <91CC1617>. 

Reported syntheses of the 1,5-thiazocine ring system from acychc precursors invariably employ unimolecular cyclization reactions. Intramolecular A-alkylation affords dibenzothiazocine (94) in ca. 80% yield (Equation (32)) <85BCJ1946>, while lactamization reactions afford phthalimide (91) (31 %) (Equation (33)) <88TL181 > and benzo derivatives (103 X = Br, Ar = 2-pyridyl X = Cl, Ar = 2-CIC6H4, 2-FC6H4 X = NO2, Ar = 2-CIC6H4) (Equation (34)) <83EUP72029>. 

High Dilution Although the preparation of five- and six-mem-bered rings from appropriate acyclic precursors usually proceeds without difficulty, the synthesis of larger rings requires more elaborate techniques since bimolecular condensations tend to become more favorable than simple cyclization. To favor the unimolecular reaction at the expense of the bimolecular condensation, high dilution techniques are used, and the apparatus (Fig. 1-14) used for the Dieckmann cyclization of diethyl tetradecan-1,14-dicarboxylate is excellent for this purpose.f... 

Molecularity vs. Mechanism. Cyclization Reactions and Effective Molarity A useful illustration of the distinctions between mechanism, molecularity, and order arises in the analysis of intramolecular versions of typically intermolecular reactions. Consider a classic Sn2 reaction of an amine and an alkyl iodide. The reaction is second order (first order in both amine and alkyl iodide) and bimolecular (two molecules involved in the transition state that s what the "2" in "Sn2" Stands for). The mechanism involves the backside attack of the nucleophilic amine on the C, displacing the iodide in a single step. Now consider a long chain molecule i that terminates in an amine on one end and an alkyl iodide on the other. Now two types of Sn2 reactions are possible. If two different molecules react, we still have a second order, bimolecular, intermolecular reaction. The product would ultimately be a polymer, ii, and we will investigate this type of system further in Chapter 13. Alternatively, an intramolecular reaction could occur, in which the amine reacts with the iodide on the same molecule producing a cyclic product. Hi. This is still called an S 2 reaction, even though it will be first order and unimolecular. 

Control of the concentration of polymer during the cyclization is also vital in order to yield high purity macrocyclics. More concentrated solutions favor the bimolecular oligomerization reaction while more dilute solutions favor the unimolecular cyclization reaction (Figure 1). As a result, the key cyclization reaction is typically carried out in a vast excess of solvent to discourage intermolecular oligomerization. 

The following compounds have been obtained from thiete 1,1-dioxide Substituted cycloheptatrienes, benzyl o-toluenethiosulfinate, pyrazoles, - naphthothiete 1,1-dioxides, and 3-subst1tuted thietane 1,1-dioxides.It is a dienophile in Diels-Alder reactions and undergoes cycloadditions with enamines, dienamines, and ynamines. Thiete 1,1-dioxide is a source of the novel intermediate, vinylsulfene (CH2=CHCH=SQ2). which undergoes cyclo-additions to strained olefinic double bonds, reacts with phenol to give allyl sulfonate derivatives or cyclizes unimolecularly to give an unsaturated sultene. - Platinum and iron complexes of thiete 1,1-dioxide have been reported. 

The attachment of an electron to an organic acceptor generates an umpolung anion radical that undergoes a variety of rapid unimolecular decompositions such as fragmentation, cyclization, rearrangement, etc., as well as bimolecular reactions with acids, electrophiles, electron acceptors, radicals, etc., as demonstrated by the following examples.135"137... 

Nitrosoimines can undergo thermal reaction, a unimolecular, two-step mechanism has been proposed, as shown in Scheme 3.22 [193]. In this mechanism, a concerted electrocyclization is envisioned to form the strained four-membered ring in 41, followed by a presumably forbidden, but highly exothermic, deazetization to give 41. The electrocyclic ring closure is, at first glance, a 4-electron process, analogous to the cyclization of butadiene [194] or acrolein [194, 195]. This would be expected to involve rotation around the C=N bond coupled with C-O bond formation. 

The Arrhenius expression for the reaction of the o(allyloxy)phenyl radical (9) with (Me3Si)3SiH relative to this unimolecular rearrangement [Eq. (4)] has been measured, v/z., og(kclku) (M) = 2.6 - 1.6/0.36 When the competition study was performed, however, reliable absolute rate constants for the cyclization of radical 9 to radical 10 were not available, although a... 

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