Hydroperoxides, alkyl

1 Aliphatic hydroperoxides (4R,5R)-[(Hydroperoxydiphenyl)methyl]-2,2-dimethyl-l,3-dioxolan-4- 1.466 1.431 128.6 67 

3 dione (GAKEIH) 2-Azido-6,6-dimethylbicyclo[3.1.1]heptane-2-hydroperoxide (22) (VIQGOR) 1.459 1.452 103.3 69 

5 Allylic hydroperoxides l-Hydroperoxy-3-isopropyl-2-methylenecyclohex-4-ene-3-carboxyUc 1.460 1.440 73.7 71 

10 hydroperoxide (24) (EEXYOWIO) 5,6,7,8-Tetrahydro-6-hydroxy-8-hydroperoxy-2,2,6,8-tetramethyl-7- 1.472 1.450 134.6 76 

11 methylenechroman-5-one (25) (YAWXOJ) l-Hydroperoxy-8-[iert-butyl(dimethyl)siloxy]bicyclo[4.4.1]undeca-2,5-diene-4,11- 1.453 1.430 a 77 

Tertiary alkylhydroperoxides are used most often as oxidizing agents with alkenes since primary or secondary alkylhydroperoxides are susceptible to rearrangement and decomposition. Alkylhydroperoxides are relatively soluble in organic solvents, are more stable, and are easier to handle than hydrogen peroxide.256 Both TBHP and cumyl hydroperoxide are commercially available and widely used. As with hydrogen peroxide, reaction of alkenes with hydroperoxides usually requires transition metal catalysts in order to form 

In the epoxidation reaction, more highly substituted alkenes react faster than less substituted alkenes.259 Reaction of 160 with TBHP and molybdenum hexacarbonyl selectively gave oxidation of the trisubstituted alkene, leading to 161.260 Electron deficient alkenes are less reactive, as illustrated by the epoxidation of 

Another synthetic example illustrates both the epoxidation capabilities of this reaction as well as the stereochemical influence of neighboring alcohol unit noted above with the transformation 163 164. In a synthesis of (-)-malyngolide by Ogasawara and co-workers, allylic alcohol 176 was treated with VO(acac)2 and t-BuOOH, in the presence of 2,6-lutidine, and a 66% yield of 177 was obtained.266 xhe hydroxyl unit directed the epoxidation to the exo face of the bicyclic system, as shown. Also notice that the more substituted alkene was epoxidized rather than the less substituted one, which is also typical of epoxidation reactions of this type, and will be discussed in more detail below, in connection with peroxyacid reactions. 

In basic media, peroxides are deprotonated and the product is a peroxy anion, which reacts with conjugated carbonyl derivatives at the C-terminus (1,4-addition, conjugate addition). Hydrogen peroxide, for example, reacts with base to give the hydroperoxide anion (HOO ), which adds to a, 3-unsaturated ketones, aldehydes 

The chemistry of alkyl hydroperoxides (40) has been reviewed by Porter,217 Sheldon204 and Hiatt.2lS Alkyl hydroperoxides are high temperature sources of alkoxy and hydroxy radicals.219 They are often encountered as components of redox systems. 

The common initiators of this class are f-alkyl derivatives, for example, t-butyl hydroperoxide (59), Aamyl hydroperoxide (60), cumene hydroperoxide (61), and a range of peroxyketals (62). Hydroperoxides formed by hydrocarbon autoxidation have also been used as initiators of polymerization. 

The ROO-H bond of hydroperoxides is weak compared to most other X-H bonds. Thus, abstraction of the hydroperoxidic hydrogen by radicals is usually an 

Primary and secondary hydroperoxides are also susceptible to induced decomposition through loss of an a-hydrogen. The radical formed is usually not stable and undergoes (3-scission to give a carbonyl compound and hydroxy radical.2 3 It is reported that these hydroperoxides may also undergo non-radical decomposition with evolution of hydrogen.137 

With Ti4 and Fe3+ this latter pathway is thought not to occur. The formation of ROO, observed at high hydroperoxide concentrations, is attributed to the occurrence of induced decomposition.226 

2 yljdiphenylmethanol (QEDTEY) 19-(Hydroperoxymethyl)-4jfl,5-epoxy-2-oxa-5/i,10ct -androstane-3,17- 1.465 1.439 111.8 68 

The combination of [FeL(C104)] [H2L = tetrakis(2,6-dichlorophenyl)-porphine] with m-chloroperbenzoic acid, O3, or C FsIO results in the formation of a ligand oxidized complex, [Fe(II)(L )0] . Reduction of this species by le equivalent leads to the formation of [(L)Fe(II)(0)] which is spectroscopically similar to compound II of Horse radish peroxidase. A high-valent chloro-perbenzoic add to the monofluoroiron(III) porphyrin at -78 This 

A number of studies have been reported in which a metal atom catalyzes the oxidation of alkenes by PhIO or its derivatives. Three studies have employed iron or manganese model systems for cytochrome P-450 in the oxidation of alkenes. [Ru(III) (salen)(X)(Y)] catalyze the oxidation of alkenes by PhIO at room temperature.Similarly, ruthenium(II) complexes of bidentate phosphines may be utilized to promote the epoxidation of alkenes in the presence of iodosylbenzene and in low coordinating media. [Ni(cyclam)] promotes the oxidation of 

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Kharasch called this the peroxide effect and demonstrated that it could occur even if peroxides were not deliberately added to the reaction mixture Unless alkenes are pro tected from atmospheric oxygen they become contaminated with small amounts of alkyl hydroperoxides compounds of the type ROOH These alkyl hydroperoxides act m the same way as deliberately added peroxides promoting addition m the direction opposite to that predicted by Markovmkov s rule... 

PEROXIDES AND PEROXIDE COMPOUNDS - ORGANIC PEROXIDES] (Vol 18) tert-Alkyl hydroperoxides... 

Propylene oxide [75-56-9] is manufactured by either the chlorohydrin process or the peroxidation (coproduct) process. In the chlorohydrin process, chlorine, propylene, and water are combined to make propylene chlorohydrin, which then reacts with inorganic base to yield the oxide. The peroxidation process converts either isobutane or ethylbenzene direcdy to an alkyl hydroperoxide which then reacts with propylene to make propylene oxide, and /-butyl alcohol or methylbenzyl alcohol, respectively. Table 1 Hsts producers of propylene glycols in the United States. 

Usually, organoboranes are sensitive to oxygen. Simple trialkylboranes are spontaneously flammable in contact with air. Nevertheless, under carefully controlled conditions the reaction of organoboranes with oxygen can be used for the preparation of alcohols or alkyl hydroperoxides (228,229). Aldehydes are produced by oxidation of primary alkylboranes with pyridinium chi orochrom ate (188). Chromic acid at pH < 3 transforms secondary alkyl and cycloalkylboranes into ketones pyridinium chi orochrom ate can also be used (230,231). A convenient procedure for the direct conversion of terminal alkenes into carboxyUc acids employs hydroboration with dibromoborane—dimethyl sulfide and oxidation of the intermediate alkyldibromoborane with chromium trioxide in 90% aqueous acetic acid (232,233). 

As the temperature is increased through the NTC zone, the contribution of alkylperoxy radicals falls. Littie alkyl hydroperoxide is made and hydrogen peroxide decomposition makes a greater contribution to radical generation. Eventually the rate goes through a minimum. At this point, reaction 2 is highly displaced to the left and alkyl radicals are the dominant radical species. 

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). 

This is basically the same type of induced decomposition that occurs with other peroxide classes, eg, the dialkyl peioxydicaibonates and diacyl peroxides. Table 8. Commercial rerf-Alkyl Hydroperoxides ... 

The addition of an oxygen atom to an olefin to generate an epoxide is often catalyzed by soluble molybdenum complexes. The use of alkyl hydroperoxides such as tert-huty hydroperoxide leads to the efficient production of propylene oxide (qv) from propylene in the so-called Oxirane (Halcon or ARCO) process (79). 

Organic peroxides can be classified according to peroxide stmcture. There are seven principal classes hydroperoxides dialkyl peroxides a-oxygen substitued alkyl hydroperoxides and dialkyl peroxides primary and secondary ozonides peroxyacids diacyl peroxides (acyl and organosulfonyl peroxides) and alkyl peroxyesters (peroxycarboxylates, peroxysulfonates, and peroxyphosphates). 

There are two main subclasses ofhydroperoxid.es organic (alkyl) hydroperoxides, ie, ROOH, and organomineral hydroperoxides, ie, Q(OOH), where Q is sihcon (43), germanium, tin, or antimony. The alkyl group in ROOH can be primary, secondary, or tertiary. Except for ethylbenzene hydroperoxide, only alkyl hydroperoxides are commercially important. 

Physical Properties. Some physical properties of alkyl hydroperoxides (in order of increasing carbon content) are Hsted in Table 1 (44). Descriptions of hydroperoxides are given in the chemical Hterature (1,4—6,10,28,43,45). 

Alkyl hydroperoxides can be Hquids or soHds. Those having low molecular weight are soluble in water and are explosive in the pure state. As the molecular weight increases, ie, as the active oxygen content is reduced, water solubiUty and the violence of decomposition decrease. Alkyl hydroperoxides are stronger acids than the corresponding alcohols and have acidities similar to those of phenols, Alkyl hydroperoxides can be purified through their alkali metal salts (28). 

Alkyl hydroperoxides form stable alkaU metal salts with caustic however, when equimolar amounts of the hydroperoxide and its sodium salt are present in aqueous solution, rapid decomposition to tert-AcohoX and oxygen occurs (28). 

Acids react with alkyl hydroperoxides in two different ways, depending on the hydroperoxide stmcture and the acid strength (45). 

Therefore, first-order, decomposition rates for alkyl hydroperoxides, ie, from oxygen—oxygen bond homolysis, are vaUd only if induced decomposition reactions... 

Although primary and secondary alkyl hydroperoxides are attacked by free radicals, as in equations 8 and 9, such reactions are not chain scission reactions since the alkylperoxy radicals terminate by disproportionation without forming the new radicals needed to continue the chain (53). Overall decomposition rates are faster than the tme first-order rates if radical-induced decompositions are not suppressed. 

An example of a reaction involving transfer of two electrons from the metal is the reduction of alkyl hydroperoxides with staimous chloride (10) (eq. 13). 

The reactions of alkyl hydroperoxides with ferrous ion (eq. 11) generate alkoxy radicals. These free-radical initiator systems are used industrially for the emulsion polymerization and copolymerization of vinyl monomers, eg, butadiene—styrene. The use of hydroperoxides in the presence of transition-metal ions to synthesize a large variety of products has been reviewed (48,51). 

The ultimate fate of the oxygen-centered radicals generated from alkyl hydroperoxides depends on the decomposition environment. In vinyl monomers, hydroperoxides can be used as efficient sources of free radicals because vinyl monomers generally are efficient radical scavengers which effectively suppress induced decomposition. When induced decomposition occurs, the hydroperoxide is decomposed with no net increase of radicals in the system (see eqs. 8, 9, and 10). Hydroperoxides usually are not effective free-radical initiators since radical-induced decompositions significantly decrease the efficiency of radical generation. Thermal decomposition-rate studies in dilute solutions show that alkyl hydroperoxides have 10-h HLTs of 133—172°C. 

Alkyl hydroperoxides are among the most thermally stable organic peroxides. However, hydroperoxides are sensitive to chain decomposition reactions initiated by radicals and/or transition-metal ions. Such decompositions, if not controlled, can be auto accelerating and sometimes can lead to violent decompositions when neat hydroperoxides or concentrated solutions of hydroperoxides are involved. 

Other compounds, eg, azoalkanes, acetone, etc, that yield alkyl radicals either thermally or by uv irradiation have been used with molecular oxygen to prepare alkyl hydroperoxides (r56). 

Many organic peroxides of metals have been hydrolyzed to alkyl hydroperoxides. The alkylperoxy derivatives of aluminum, antimony, arsenic, boron, cadmium, germanium, lead, magnesium, phosphoms, silicon, tin, and zinc yield alkyl hydroperoxides upon hydrolysis (10,33,60,61). 

Saponification of alkyl peroxyesters yields alkyl hydroperoxides and carboxylic acids or their alkali metal salts. a-Ether-substituted peroxides can be hydrolyzed to the unsubstituted alkyl hydroperoxides, eg, tert-huty hydroperoxide from tert-huty 2-oxacyclohexyl peroxide [28627-46-5] (62) ... 

The susceptibihty of dialkyl peroxides to acids and bases depends on peroxide stmcture and the type and strength of the acid or base. In dilute aqueous sulfuric acid (<50%) di-Z fZ-butyl peroxide is resistant to reaction whereas in concentrated sulfuric acid this peroxide gradually forms polyisobutylene. In 50 wt % methanolic sulfuric acid, Z fZ-butyl methyl ether is produced in high yield (66). In acidic environments, unsymmetrical acychc alkyl aralkyl peroxides undergo carbon—oxygen fission, forming acychc alkyl hydroperoxides and aralkyl carbonium ions. The latter react with nucleophiles,... 

Most organomineral peroxides are hydrolytically unstable and readily hydrol2ye to alkyl hydroperoxides or hydrogen peroxide (33,34,44,60,61) ... 

Consequendy, most organomineral peroxides must be prepared and stored under anhydrous conditions. In addition, anhydrous hydrogen chloride converts alkyl-substituted organomineral peroxides to alkyl hydroperoxides (33). 

Synthesis. Dialkyl peroxides are prepared by the reaction of various substrates with hydrogen peroxide, hydroperoxides, or oxygen (69). They also have been obtained from reactions with other organic peroxides. For example, dialkyl peroxides have been prepared by the reaction of hydrogen peroxide and alkyl hydroperoxides with alMating agents, eg, RX and olefins (33,66,97) (eqs. 24—27). 

Reaction conditions depend on the reactants and usually involve acid or base catalysis. Examples of X include sulfate, acid sulfate, alkane- or arenesulfonate, chloride, bromide, hydroxyl, alkoxide, perchlorate, etc. RX can also be an alkyl orthoformate or alkyl carboxylate. The reaction of cycHc alkylating agents, eg, epoxides and a2iridines, with sodium or potassium salts of alkyl hydroperoxides also promotes formation of dialkyl peroxides (44,66). Olefinic alkylating agents include acycHc and cycHc olefinic hydrocarbons, vinyl and isopropenyl ethers, enamines, A[-vinylamides, vinyl sulfonates, divinyl sulfone, and a, P-unsaturated compounds, eg, methyl acrylate, mesityl oxide, acrylamide, and acrylonitrile (44,66). 

Primary and secondary alkyl haUdes and sulfonates react with potassium superoxide to form dialkyl peroxides (101,102) (eq. 28). Dia2oalkanes, eg, dia2omethane, have been used to alkylate hydroperoxides (66) (eq. 29). 

Unsymmetrical dialkyl peroxides are obtained by the reaction of alkyl hydroperoxides with a substrate, ie, R H, from which a hydrogen can be abstracted readily in the presence of certain cobalt, copper, or manganese salts (eq. 30). However, this process is not efficient since two moles of the hydroperoxide are consumed per mole of dialkyl peroxide produced. In addition, side reactions involving free radicals produce undesired by-products (44,66). 

Syimnetiical dialkyl peroxides have been prepared from alkyl hydroperoxides and lead tetraacetate. If tertiary dihydroperoxides are used, then cychc... 

Organomineral peroxides can be prepared by the reaction of certain organometaUic or organometaHoid compounds, R QX, with hydrogen peroxide or alkyl hydroperoxides ... 

Autoxidation of alkanes generally promotes the formation of alkyl hydroperoxides, but d4-tert-huty peroxide has been obtained in >30% yield by the bromine-catalyzed oxidation of isobutane (66). In the presence of iodine, styrene also has been oxidized to the corresponding peroxide (44). 

In the presence of strong acid catalysts such as sulfuric acid, aUphatic (R CHO) aldehydes react with alkyl hydroperoxides, eg, tert-55ky hydroperoxides, to form hydroxyalkyl alkyl peroxides (1), where X = OH R, = hydrogen, alkyl and = tert — alkyl. 

In the presence of strong acid catalysts many commonly used commercial alkyl hydroperoxides decompose to acetone to some extent. Consequendy, the diperoxyketals derived from other ketones and alkyl hydroperoxides are often contaminated with small amounts of diperoxyketals derived from acetone (1, X = OOR, = methyl, R = R = tert — alkyl). 

Miscellaneous OC-Substituted Peroxides. 3-Aryl-3-(/ i alkylperoxy)-phthaHdes (12) are prepared from the corresponding 3-chlorophthaHdes and alkyl hydroperoxide (156). 2-Methyl-2-(/ f2 -alkylperoxy)-l,3-benzodioxan-4-ones (13) are obtained from 0-acetylsaHcyloyl chloride and alkyl hydroperoxides (157). Trisubstituted 2-(/ f2 -alkylperoxy)-l,3-dioxolan-4-ones (14) are synthesized from stericaHy favored a-acyloxy acid chlorides and alkyl hydroperoxides (158). 

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