Addition-fragmentation

If both addition and fragmentation arc irreversible the kinetics differ little from conventional chain transfer. In the more general case, the rate constant for chain transfer is defined in terms of the rate constant for addition (Aj,jj) and a partition coefficient which defines how the adduct is partitioned between products and starting materials (eq. 19). 

Methods used for evaluating transfer constants are the same as for conventional chain transfer. 

---

Fig. 19. Generic addition fragmentation CT stmcture and the mechanism of action, where F = functional group.

Benzo[Z)]thiophene reacts with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate in a cyclo-addition-fragmentation reaction to yield (143), whereas benzo[A]furan and N- methylindole yield products (144) arising from ring opening and recyclization (76AP679). 

Shells, clams, wood fragments, and other biological materials can also produce concentration cell corrosion. Additionally, fragments can lodge in heat exchanger inlets, locally increasing turbulence and erosion-corrosion. If deposits are massive, turbulence, air separation, and associated erosion-corrosion can occur downstream (see Case History 11.5). 

An introduction to the principles behind SPI-SALI, this ankle presents a theoretical discussion of why SPI-SALI is much less fragmenting than MPI-SALI. Examples are shown which describe the additional fragmentation induced by the desorption beam—in this case ESD is compared to ion sputtering. The main focus of the article is the advantages of SPI-SALI for surface analysis of bulk organic polymers. 

Scheme 13. Intramolecular radical addition/fragmentation in Boger s synthesis of (+)-CC-1065.

Scheme 17. Danishefsky s radical addition/fragmentation process in a synthesis of (+)-3-demethoxyery-thratidinone [( )-93].

Watanabe et al,25-5 52s applied AMS dimer (116) as a radical trap to examine the reactions of oxygen-centered radicals (e.g. r-butoxy, cumyloxy, benzoyloxy). AMS dimer (116) is an addition fragmentation chain transfer agent (see 6.2.3.4) and reacts as shown in Scheme 3,96. The reaction products are macromonomers and may potentially react further. The reactivity of oxygen centered radicals towards 116 appears to be similar to that of S.2 1 Cumyl radicals are formed as a byproduct of trapping and are said to decay mainly by combination and disproportionation. 

Stansbury and Bailey. A review by Colombam on addition-fragmentation processes is also relevant. Monomers used in ring-opening are typically vinyl (e.g. vinylcyclopropane - Scheme 4.20 Section 4.4.2.1) or methylene substituted cyclic compounds (e.g. ketene acetals - Section 4.4.2.2) where addition to the double bond is followed by p-scission. 

General aspects of chain transfer have been reviewed by Chiefari and Rizzardo,3 Barson, 1 Farina/ Fastmond6 and Palit el al1 The use of chain transfer in producing lelechelic and other functional polymers has been reviewed by Boutevin,8 Heitz/ Comer10 and Starks11 and is discussed in Section 7.5.2. There are two main mechanisms which should be considered in any discussion of chain transfer (a) atom or group transfer by homolytie substitution (Section 6.2.2) and (b) addition-fragmentation (Section 6.2.3). 

Various methods for estimating transfer constants in radical polymerization have been devised. The methods are applicable irrespective of whether the mechanism involves homolytic substitution or addition-fragmentation. 

Some transfer agents react by addition-fragmentation (Section 6.2.3) or abstraction-fragmentation mechanisms. Both of these processes involve the formation of a short-lived intermediate. The reaction scheme for addition-fragmentation can be summarized schematically as follows (Scheme 6.3). 

In some cases the product of chain transfer (P T) is itself a transfer agent and chain transfer is reversible. Examples include alkyl iodides (Scheme 6.4) and certain addition-fragmentation transfer agents (e.g. inacromonomers and thiocarbonylthio compounds) (Scheme 6.5). 

This equation can be solved numerically to give values of Clr and Ctr.404 For reversible addition-fragmentation chain transfer (RAFT) (Scheme 6.5), the rate constant for the reverse reaction is defined as shown in eq. 22 ... 

Compounds with a thiocarbonyl a to the S-S bond such as the dithiuram (e.g. 8f2Al and xanthogen disulfides (e.g. 9)M have transfer constants that are much higher than other disulfides. In part, this may be due to the availability of another mechanism for induced decomposition (Scheme 6.9) involving addition to the C S double bond and subsequent fragmentation. Thiocarbonyl double bonds are very reactive towards addition and an addition-fragmentation mechanism has been demonstrated for related compounds (Section 6.2.3.5). 

Most monosulfides generally have very low transfer constants. Exceptions to this rule are allyl sulfides (Section 6,2.3.2) and thiocarbonylthio compounds such as the trithiocarbonatcs and dithiocstcrs (Section 9.5.3) that react by an addition-fragmentation mechanism. 

In the case of allyl peroxides (12 X= CH2, A=CH2, BO),1 1 1 intramolecular homolytic substitution on the 0-0 bond gives an epoxy end group as shown in Scheme 6.18 (1,3-Sn/ mechanism). The peroxides 52-59 are thermally stable under the conditions used to determine their chain transfer activity (Table 6.10). The transfer constants are more than two orders of magnitude higher than those for dialkyi peroxides such as di-f-butyl peroxide (Q=0.00023-0.0013) or di-isopropyl peroxide (C =0.0003) which are believed to give chain transfer by direct attack on the 0-0 bond.49 This is circumstantial evidence in favor of the addition-fragmentation mechanism. 

Other transfer agents which react with propagating species by an addition-fragmentation mechanism include the thionc derivatives (81-83) and RAFT... 

For allyl acetate a significant deuterium isotope effect supports the hydrogen abstraction mechanism (Scheme 6,31).183 Allyl compounds with weaker CTT-X bonds (113 X=SR, S02R, Bi etc.) may also give chain transfer by an addition-fragmentation mechanism (Section 6.2.3). 

Penultimate unit effects are also important in both substitution40"41 and in addition-fragmentation chain transfer.42"44 Some examples are provided in Sections 6.2, 6.2.2.4, 6.2.3.4 and 9.5. 

Depending on the choice of transfer agent, mono- or di-cnd-functional polymers may be produced. Addition-fragmentation transfer agents such as functional allyl sulfides (Scheme 7.16), benzyl ethers and macromonomers have application in this context (Section 6.2.3).212 216 The synthesis of PEG-block copolymers by making use of PEO functional allyl peroxides (and other transfer agents has been described by Businelli et al. Boutevin et al. have described the telomerization of unsaturated alcohols with mercaptoethanol or dithiols to produce telechelic diols in high yield. 

The bond p- to the double bond of the unsaturated disproportionation product 2 is also weaker than other backbone bonds.10 30,32 31 However, it is now believed that the instability of unsaturated linkages is due to a radical-induced decomposition mechanism (Scheme 8.7).30 This mechanism for initiating degradation is analogous to the addition-fragmentation chain transfer observed in polymerizations carried out in the presence of 2 at lower temperatures (see 6.2.3.4, 7.6.5 and 9.5.2). 

Certain monomers may be able to act as reversible deactivators by a reversible addition-fragmentation mechanism. The monomers are 1,1-disubstituted and generate radicals that are unable or extremely slow to propagate or undergo combination or disproportionation. For these polymerizations the dormant species is a radical and the persistent species is the 1,1 -disubstituted monomer. 

Although the term RAFT (an acronym for Reversible Addition-Fragmentation chain Transfer)38" is sometimes used in a more general sense, it was coined to describe, and is most closely associated with, the reaction when it involves thiocarbonylthio compounds. RAFT polymerization, involving the use of xanthates, is also sometimes called MADIX (Macromolccular Design by Interchange of Xambate) 96 The process has been reviewed by Rizzardo et [Pg.502]

Organic chemists have been aware of reversible addition-fragmentation involving xanthate esters in organic chemistry for some time. It is the basis of the Barton-McCombie process for deoxygenation of alcohols (Scheme 9.37).402 404... 

In 1988 a paper by Zard and coworkers4(, reported that xanlhates were a convenient source of alkyl radicals by reversible addition-fragmentation and used the chemistry for the synthesis of a monoadduct to monomer (a maleimide). Many applications of the chemistry in organic synthesis have now been described in papers and reviews by the Zard group.406 407... 

For addition-fragmentation chain transfer, the rate constants for the forward and reverse reaclions are defined as shown in eqs. 21 and 22 respectively. 

---