Butoxy reactions

The proposed mechanism for producing ethanol [64-17-5] from butane involves -scission of a j -butoxy radical (eq. 38). The j -butoxy radicals are derived from j -butylperoxy radicals (reaction 14 (213)) and/or through some sequence involving reaction 33. If 25% of the carbon forms ethanol, over 50% must pass through the j -butoxy radical. Furthermore, the principal fate of j -butoxy radicals must be the P-scission reaction the ethoxy radical, on the other hand, must be converted to ethanol efficiently. 

Methyl ethyl ketone, a significant coproduct, seems likely to arise in large part from the termination reactions of j -butylperoxy radicals by the Russell mechanism (eq. 15, where R = CH and R = CH2CH2). Since alcohols oxidize rapidly vs paraffins, the j -butyl alcohol produced (eq. 15) is rapidly oxidized to methyl ethyl ketone. Some of the j -butyl alcohol probably arises from hydrogen abstraction by j -butoxy radicals, but the high efficiency to ethanol indicates this is a minor source. 

Propionic acid made in butane LPO probably comes by a minor variation of reaction 38 that produces methyl radicals and propionaldehyde. It is estimated that up to 18% of the j -butoxy radicals may decompose in this manner (213) this may be high since propionic acid is a minor product. 

A/-Trimethoxybora2ines are available from reaction of dichloroboranes and 0-methyl-X,X-his(trimethylsilyl)hydroxylamine (eq. 31). The B-trichloro-bora2iQes undergo substitution reactions at the B atoms to give B-tri(/ f -butoxy)- or B-tri(/ f2 -but5i)-A/-trimethoxybora2iaes (101)... 

Large ring heterocyclic radicals are not particularly well known as a class. Their behavior often resembles that of their alicyclic counterparts, except for transannular reactions, such as the intramolecular cyclization of 1-azacyclononan-l-yl (Scheme 1) (72CJCH67). As is the case with alicyclic ethers, oxepane in the reaction with r-butoxy radical suffers abstraction of a hydrogen atom from the 2-position in the first reaction step (Scheme 2) (76TL439). 

Other methods for the preparation of cyclohexanecarboxaldehyde include the catalytic hydrogenation of 3-cyclohexene-1-carboxaldehyde, available from the Diels-Alder reaction of butadiene and acrolein, the reduction of cyclohexanecarbonyl chloride by lithium tri-tcrt-butoxy-aluminum hydride,the reduction of iV,A -dimethylcyclohexane-carboxamide with lithium diethoxyaluminum hydride, and the oxidation of the methane-sulfonate of cyclohexylmethanol with dimethyl sulfoxide. The hydrolysis, with simultaneous decarboxylation and rearrangement, of glycidic esters derived from cyclohexanone gives cyclohexanecarboxaldehyde. 

An example of this reaction is the reaction of cyclohexene with t-butyl perbenzoate, which is mediated by Cu(I). " The initial step is the reductive cleavage of the perester. The t-butoxy radical then abstracts hydrogen from cyclohexene to give an allylic radical. The radical is oxidized by Cu(II) to the carbocation, which captures benzoate ion. The net effect is an allylic oxidation. 

Indirect deactivation by an alkoxy group is apparent in the sluggish reaction of 4-butoxy-2-chloroquinoline with w-butylamine (EtOH, 5 hr, 180°, but not at 80°). The chloro group in 2-chloro-4-ethoxy-quinoline is more reactive than that in the 4-chloro-2-ethoxy isomer toward alkoxides or amines in spite of the usually more effective para indirect deactivation in the former. For kinetic data on quinolines see Tables X and XI, pp. 336 and 338, respectively. 

Reaction of 7-bromo-2-butoxy-3-phenyl-4//-pyrido[l, 2-u]pyrimidin-4-one (203, R = Bu, Ar = Ph) and (4-ClPh)BH2 in the presence of a 2 M solution of Na2C03 and (Ph3P)4Pd afforded 7-(4-chlorophenyl) derivative... 

Alkyl radicals can be obtained by abstraction of a hydrogen atom from an alkyl group by another radical. This method was utilized for the generation of benzyl radicals from toluene with iert-butoxy radical obtained on heating di- er -butyl peroxide. BenzoyP and carboxymethyP radicals have also been obtained by this method. The reaction gives rise to a complex mixture of products and therefore is of rather limited use. 

The assumed transition state for this reaction is shown in Scheme 5.5. The two bulky t-butoxy groups are expected to locate at the two apical positions. One of the 3,3 -phenyl groups would effectively shield one face of an imine, and consequently, a diene attacks from the opposite side. Judging from this model, similar selectivities were expected in the Mannich-type reactions of imines with silyl eno-lates. Actually, when ligand 10 was used in the reaction of imine la with S-ethyl-thio-l-trimethylsiloxyethene, the corresponding / -amino thioester was obtained in 84% ee (Scheme 5.6). As expected, the sense of the chiral induction in this case was the reverse of that observed when using catalyst 6 [12, 25]. 

The allylic position of olefins is subject to attack by free radicals with the consequent formation of stable allylic free radicals. This fact is utilized in many substitution reactions at the allylic position (cf. Chapter 6, Section III). The procedure given here employs f-butyl perbenzoate, which reacts with cuprous ion to liberate /-butoxy radical, the chain reaction initiator. The outcome of the reaction, which has general applicability, is the introduction of a benzoyloxy group in the allylic position. 

A mixture of 17.6 grams of p-n-butoxyacetophenone, 12.1 grams of piperidine hydrochloride, 4.5 grams paraformaldehyde, 0.25 cc concentrated hydrochloric acid, 52.5 cc nitro-ethane, 7.5 cc of 95% ethanol, and 15 cc of toluene was boiled under reflux for one hour, removing water formed in the reaction by means of a condensate trap. The mixture was then cooled. The crystals which formed were collected by filtration, washed with anhydrous ether and recrystallized from methyl ethyl ketone. The crystals thus obtained, which melted at 174°-175°C, were shown by analysis to be 4-n-butoxy-beta-piperidinopropiophen-one hydrochloride. 

In contrast to 2-cyclopentenone, 4-to7-butoxy-3-cyclopentenone gives mixtures of a-1,2- and y-1,4-adducts at — 70°C. Warmer reaction temperatures (0°C) give mainly the syn-y- 1,4-ad-duct, although in poor yield (43%). Addition of HMPA gives mixtures of a- and y-1,4-adducts plus 1,2-adducts. 2(5//)-Furanone gives mixtures of a- and y-1,4-addition products at — 70 C7. 

Relative rate constants for reaction of methyl, trifluoromethyl, trichloromethyl,13 and t-butoxy radicals22,23 with the fluoro-olcfins arc summarized in Table 1.2. Note the following points ... 

However, consideration of polar factors in the traditional sense does not provide a ready explanation for the regiospecificity shown by the r butoxy radicals (which arc electrophilic, Tabic 1.3) in their reactions with the tluoro-olcfins (Tabic 1.2).22,23 Apparent ambiphilicity has been reported21 for other not very electrophilic radicals in their reactions with olefins and has been attributed to the polarizability of die radical. 

The most direct evidence that stereoelectronic effects are also important in these reactions follows from the specificity observed in hydrogen atom abstraction from conformationally constrained compounds,18 60 C-H bonds adjacent to oxygen113"118 or nitrogen110 and which subtend a small dihedral angle with a lone pair orbital (<30°) are considerably activated in relation to those where the dihedral angle is or approaches 90°. Thus, the equatorial H in 20 is reported to be 12 times more reactive towards /-butoxy radicals than the axial 11 in 21.115... 

A further example of the importance of this type of stereoelectronic effect is seen in the reactions of /-butoxy radicals with spiro[2,n]alkanes (22) where it is found that hydrogens from the position a- to the cyclopropyl ring arc specifically abstracted. This can be attributed to the favorable overlap of the breaking C-H bond with the cyclopropyl cr bonds.120131 No such specificity is seen with bicyclo[n, 1,0]alkanes (23) where geometric constraints prevent overlap. 

These examples clearly show that the initiation pathways depend on the structures of the radical and the monomer. The high degree of specificity shown by a radical e.g. i-butoxy) in its reactions with one monomer (e.g. S) must not be taken as a sign that a similarly high degree of specificity will be shown in reactions with all monomers (e.g. MMA). 

Many radicals undergo fragmentation or rearrangement in competition with reaction with monomer. For example, f-butoxy radicals undergo p-scission to form methyl radicals and acetone (Scheme 3.6). 

The radicals formed by imimolecular rearrangement or fragmentation of the primary radicals arc often termed secondary radicals. Often the absolute rate constants for secondary radical formation are known or can be accurately determined. These reactions may then be used as radical clocks",R2° lo calibrate the absolute rate constants for the bimolecular reactions of the primary radicals (e.g. addition to monomers - see 3.4). However, care must be taken since the rate constants of some clock reactions (e.g. f-butoxy [3-scission21) are medium dependent (see 3.4.2.1.1). 

The reaction medium may also modify the reactivity of the primary, or other radicals without directly reacting with them. For example, when f-butoxy reacts... 

For /-butyl peresters there is also a variation in efficiency in the series where R is primary secondary>tertiary. The efficiency of /-butyl peroxypentanoate in initiating high pressure ethylene polymerization is >90%, that of /-butyl peroxy-2-ethylhexanoate ca 60% and that of/-butyl peroxypivalate ca 40%.196 Inefficiency is due to cage reaction and the main cage process in the case where R is secondary or tertiary is disproportionation with /-butoxy radicals to form /-butanol and an olefin.196... 

The low conversion initiator efficiency of di-r-butyl pcroxyoxalatc (0.93-0.97)1-1 is substantially higher than for other peroxyeslers [/-butyl peroxypivalale, 0.63 /-butyl peroxyacetate, 0.53 (60 °C, isopropylbenzene)195]. The dependence of cage recombination on the nature of the reaction medium has been the subject of a number of studies. 12I,1<>0 20CI The yield of DTBP (the main cage product) depends not only on viscosity but also on the precise nature of the solvent. The effect of solvent is to reduce the yield in the order aliphatic>aromatie>protic. It has been proposed199 that this is a consequence of the solvent dependence of p-scission of the f-butoxy radical which increases in the same series (Section 3.4.2.1.1). 

Alkyl radicals, when considered in relation to heteroatom-centered radicals (e.g. r-butoxy, benzoyloxy), show a high degree of chcmo- and rcgiospecificity in their reactions. A discussion of the factors influencing the rate and rcgiospecificity of addition appears in Section 2.3. Significant amounts of head addition arc observed only when addition to the tail-position is sterically inhibited as it is in a,p-disubstituted monomers. For example, with p-alkylacrylates, cyclohexyl... 

The pathways whereby oxygen-centered radicals interact with monomers show marked dependence on the structure of the radical (Table 3.8). For example, with MMA the proportion of tail addition varies from 66% for f-butoxy to 99% for isopropoxycarbonyloxy radical. The reactions of oxygen-centered radicals are discussed in detail in the following sections. 

The reactions of /-butoxy radicals are amongst the most studied of all radical processes. These radicals are generated by thermal or photochemical decomposition of peroxides or hyponitrites (Scheme 3.75). 

The relative amounts of double bond addition, hydrogen abstraction and 13-scission observed are dependent on the reactivity and concentration of the particular monomer(s) employed and the reaction conditions. Higher reaction temperatures are reported to favor abstraction over addition in the reaction of t-butoxy radicals with AMS413 and cyclopentadiene 417 However, the opposite trend is seen with isobutylene.2 1 24... 

Pioneering work by Wallingj94 established that the specificity shown by t-butoxy radical is solvent dependent. Work21 22396 on the reactions of /-butoxy radicals with a series of a-mcthylvinyl monomers has shown that polar and aromatic solvents favor abstraction over addition, and [3-scission over either addition or abstraction. Recently, Weber and Fischer418 and Tsentalovich at a/.410 reported absolute rate constants for [3-scission of r-butoxy radicals in various solvents. These studies indicate that p-scission is strongly solvent dependent while abstraction is relatively insensitive to solvent. 

Table 3.9. Kinetic Data for Reactions of /-Butoxy Radicals in Various...

Grant et a/.397 examined the reactions of hydroxy radicals with a range of vinyl and a-methylvinyl monomers in organic media. Hydroxy radicals on reaction with AMS give significant yields of products from head addition, abstraction and aromatic substitution (Table 3.8) even though resonance and steric factors combine to favor "normal tail addition. However, it is notable that the extents of abstraction (with AMS and MMA) arc less than obtained with t-butoxy radicals and the amounts of head addition (with MMA and S) are no greater than those seen with benzoyloxy radicals under similar conditions. It is clear that there is no direct correlation between reaclion rale and low specificity. 

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. 

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