Pathways for alkylation

FIGURE 2. Proposed pathway for alkylation of germyllithium reagents with alkyl iodides... 

The oxidation pathways for alkylated heteroaromatics start with the formation of a radical species, via hydrogen atom loss or alkyl group homolytic bond cleavage. We calculated these BDEs for methyl- and ethyl-substituted derivatives of several key heteroaromatics (Tables 1-3). Few of these experimental values exist therefore. 

Figure 3. Major fragmentation pathways for alkyl alkylphosphonic acids in positive and negative ion modes...

The major decomposition pathway for alkyls is elimination (Eq. 3.1), which converts a metal alkyl into a hydridometal alkene complex. We study it in detail in Section 7.4. For the moment we need only note that this very common mechanistic type can occur whenever... 

R ) rearrangements is provided by the fact that alkane and alkene products show that H/D scrambling can occur within one R (but not between R and R"). In the dissociative pathway, for alkyl systems the ratio of alkenes to alkanes in the products show that all j8-hydrogen atoms have an equal tendency to be eliminated. They are, however, activated by phenyl groups. An isopropyl group is isomerized to an n-propyl ligand before decomposition occurs. In the nondissociative pathway, ease of j8-elimination from groups appears to rise PtEt < Pt Pr< Pt Bu. Rate constants for overall process (134) vary by a factor of only 4 for various R. 

Figure 8 11 illustrates the close relationship between the E2 and 8 2 pathways for this case and the results cited m the preceding equation clearly show that E2 is faster than 8 2 when a secondary alkyl halide reacts with a strong base... 

Recall from Section 8 13 that the major pathway for reaction of alkoxide ions with secondary alkyl halides IS E2 not Sn2... 

Mass Spectrometry Aldehydes and ketones typically give a prominent molecular ion peak m their mass spectra Aldehydes also exhibit an M— 1 peak A major fragmentation pathway for both aldehydes and ketones leads to formation of acyl cations (acylium ions) by cleavage of an alkyl group from the carbonyl The most intense peak m the mass spectrum of diethyl ketone for example is m z 57 corresponding to loss of ethyl radi cal from the molecular ion... 

Reactions 33 and 35 constitute the two principal reactions of alkyl hydroperoxides with metal complexes and are the most common pathway for catalysis of LPOs (2). Both manganese and cobalt are especially effective in these reactions. There is extensive evidence that the oxidation of intermediate ketones is enhanced by a manganese catalyst, probably through an enol mechanism (34,96,183—185). 

The choice of a pathway for the synthesis of certain compounds is determined by the presence of functional groups at the alkyl substituent. 

The initial series of major tranquilizers consists of alkylated derivatives of 4-aryl-4-hydroxypiperidines. Construction of this ring system is accomplished by a set of rather unusual reactions. Condensation of methylstyrenes with formaldehyde and ammonium chloride afford the corresponding hexahydro-1,3-oxazines (119). Heating these oxazines in the presence of acid leads to rearrangement with loss of water to the tetrahydropyridines. Scheme 1 shows a possible reaction pathway for these transformations. Addition of hydrogen bromide affords the expected 4-bromo compound (121). This last is easily displaced by water to lead to the desired alcohol (122) The side chain (123) is obtained by Friedel-Crafts acylation of p-fluorobenzene with 4-chloro-butyryl chloride. Alkylation of the appropriate arylpiperidinol with 123 affords the desired butyrophenone derivative. Thus,... 

The E2 reaction (for elimination, bimolecular) occurs when an alkyl halide is treated with a strong base, such as hydroxide ion or alkoxide ion (RO-). It is the most commonly occurring pathway for elimination and can be formulated as shown in Figure 11.17. 

The requirement for reduction prior to DNA alkylation and crosslinking was first demonstrated by Iyer and Szybalski in 1964 [29], and can be induced both by chemical reducing agents such as sodium dithionite and thiols in vitro and by various reductive enzymes such as DT-diaphorase (NAD(P)H-quinone oxidoreduc-tase) in vitro and in vivo [47]. Much work to characterize the mechanism of reductive activation and alkylation has been carried out, principally by the Tomasz and Kohn groups, and Figure 11.1 illustrates a generally accepted pathway for mitomycin C [16, 48-50] based on these experiments, which is very similar to the mechanism originally proposed by Iyer and Szybalski [29]. 

The reaction of tetraalkyldistibines with group 13-trialkyls now offers an alternative synthetic pathway for the synthesis of completely alkyl-substituted heterocycles. The first step of the reaction consists of a formation of a 1 1 or... 

The pathways for the degradation of toluene and xylene under denitrifying and sulfate-reducing conditions have been studied most extensively, and they take place by reactions quite different from those used by aerobic bacteria. As an example, two anaerobes affiliated with known sulfate-reducing bacteria isolated from enrichments with crude oil were able to grow at the expense of a number of alkylated benzenes—strain oXySl with toluene, o-xylene, and o-ethyltoluene and strain mXySl with toluene, m-xylene, and m-ethyltoluene (Harms et al. 1999). 

For alkylated phenols, there are different pathways for degradation depending on whether or not oxidation of the alkyl group precedes oxygenation and fission of the ring ... 

Although hydrolysis of alkyl sulfates by sulfatases is noted in Part 1 of this chapter, ether cleavage has been shown to be the major pathway for the degradation of dodecyltriethoxy sulfate (Hales et al. 1986). 

The pathways for the aerobic biodegradation of alkylated benzenes have been elncidated in extensive investigations and have been discussed in Chapter 8, Part 1, so that only salient featnres are briefly snmmarized here. The genes for the degradation of toluene may be either chromosomal or... 

In the presence of a suitably disposed /i-hydrogen—as in alkyl-substituted thiirane oxides such as 16c—an alternative, more facile pathway for thermal fragmentation is available . In such cases the thiirene oxides are thermally rearranged to the allylic sulfenic acid, 37, similarly to the thermolysis of larger cyclic and acyclic sulfoxides (see equation 9). In sharp contrast to this type of thiirane oxide, mono- and cis-disubstituted ones have no available hydrogen for abstraction and afford on thermolysis only olefins and sulfur monoxide . However, rapid thermolysis of thiirane oxides of type 16c at high temperatures (200-340 °C), rather than at room temperature or lower, afforded mixtures of cis- and trans-olefins with the concomitant extrusion of sulfur monoxide . The rationale proposed for all these observations is that thiirane oxides may thermally... 

SCHEME 2.5 Reaction pathways for 9-methyladenine alkylation by o-QM, investigated by DFT. 

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