Oxiranes basicity

The oxirane ring-opening reaction requires the presence of a basic catalyst. An acidic catalyst also works, but the polymerization of the oxirane limits its usehilness. In the case of 2-mercaptoethanol (eq. 8), the product has been found to be autocatalytic, ie, the product is a catalyst for the reaction. 

Molecular orbital calculations predict that oxirane forms the cyclic conjugate acid (39), which is 30 kJ moF stabler than the open carbocation (40) and must surmount a barrier of 105kJmoF to isomerize to (40) (78MI50500). The proton affinity of oxirane was calculated (78JA1398) to be 807 kJ mol (cf. the experimental values of 773 kJ moF for oxirane and 777-823 kJ moF for dimethyl ether (80MI50503)). The basicity of cyclic ethers is discussed in (B-67MI50504). 

The proton affinities (gas phase) of thiirane and other three-membered heterocycles have been determined azirane (902.5), thiirane (819.2), phosphirane (815.0), oxirane (793.3 kJ moF ) (80JA5151). Increasing s character in the lone electron pairs decreases proton affinities. Data derived from NMR chemical shifts in chloroform indicate the order of decreasing basicity is azirane > oxirane > thiirane (73CR(B)(276)335). The base strengths of four-, five- and six-membered cyclic sulfides are greater than that of thiirane. 

Many functional groups are stable to alkaline hydrogen peroxide. Acetate esters are usually hydrolyzed under the reaction conditions although methods have been developed to prevent hydrolysis.For the preparation of the 4,5-oxiranes of desoxycorticosterone, hydrocortisone, and cortisone, the alkali-sensitive ketol side chains must be protected with a base-resistant group, e.g., the tetrahydropyranyl ether or the ethylene ketal derivative. Sodium carbonate has been used successfully as a base with unprotected ketol side chains, but it should be noted that some ketols are sensitive to sodium carbonate in the absence of hydrogen peroxide. The spiroketal side chain of the sapogenins is stable to the basic reaction conditions. 

Tanaka and Kakiuchi (6) proposed catalyst activation via a hydrogen donor such as an alcohol as a refinement to the mechanism discussed by Fischer (7) for anhydride cured epoxies in the presence of a tertiary amine. The basic catalyst eliminates esterification reactions (8). Shechter and Wynstra ( ) further observed that at reaction conditions BDMA does not produce a homopolymerization of oxiranes. 

Since acidity (Lewis or Brpnsted) impacts adversely on the yield of epoxides, Clerici and Ingallina (204) added basic compounds in low concentrations to TS-1 catalysts during epoxidation of alkenes to inhibit the oxirane ring opening and enhanced the epoxide yields. A comprehensive investigation of the influence of pH on product selectivity in epoxidation of allylalcohol, allylchloride, and styrene catalyzed by various titanosilicates was reported recently by Shetti et al (205). 

Chiral p-hydroxyethylammonium catalysts decompose under strongly basic conditions with the extrusion of a tertiary amine to produce chiral oxiranes, which contaminate the reaction products and lead to spurious conclusions about the enantioselective nature of the reaction (Chapter 12). 

When 1,2-diols are subjected to the same reaction conditions required for the formation of sulphonic esters, oxiranes are produced [27]. Presumably, the mono ester is initially formed and, under the basic conditions, intramolecular elimination occurs to produce the oxirane. Partial hydrolysis and ring-closure of a,p-di(tosyloxy) compounds under basic phase-transfer catalytic conditions provides a convenient route to carbohydrate oxiranes [e.g. 28, 29]. Oxiranes have been produced by an analogous method via carbonate esters from partially protected carbohydrates [30],... 

The oxiranes obtained from the reaction of chloromethylsulphones with aldehydes and ketones can be isolated [26, 27], but tend to be unstable in the basic media. Rearrangement of the toluenesulphonyloxiranes produces the sulphonyl aldehydes (Scheme 6.15) [26]. When chiral chloromethylsulphonamides are used, asymmetric... 

Under basic liquiddiquid two-phase conditions the reaction of aryl aldehydes with benzyldibutyltelluronium bromide produces oxiranes [71] although, in some instances, alkenes are formed. 

In an interesting catalysed conversion of trichloroethene by secondary amines into aminoacetamides, the initial steps are thought to involve the p-elimination of HC1 to produce dichloroethyne (Scheme 9.1), which reacts with the secondary amine under the wet conditions to produce the amide [35] the reaction does not work with N-alkylanilines. Such a mechanism is realistic, as it is well known [36] that trichloroethene is converted into the inflammable and explosive dichloroethyne by bases, and quaternary ammonium salts catalyse the formation of the alkyne when trichloroethene is reacted with oxiranes [37]. Chloroethynes have also been obtained by the catalysed reaction of terminal ethynes with carbon tetrachloride under basic conditions [38]. 

Many examples of the phase-transfer catalysed epoxidation of a,(3-unsaturated carbonyl compounds using sodium hypochlorite have been reported [e.g. 7-10]. The addition of transition metal complexes also aids the reaction [11], but advantages in reaction time or yields are relatively insignificant, whereas the use of hexaethyl-guanidinium chloride, instead of a tetra-alkylammonium salt, enhances the rate of epoxidation while retaining the high yields (>95%) [10]. Intermediate (3-haloalkanols are readily converted into the oxiranes under basic conditions in the presence of benzyltriethylammonium chloride [12]. 

Epoxidation of ot.fl-unsaturated ketones by hydrogen peroxide or /-butyl peroxide is promoted by the addition of tetra-n-butylammonium fluoride [10], whereas the corresponding reaction with 1,4-disubstituted but-2-en-l,4-diones is catalysed by quaternary ammonium iodides [11], Oxiranes are also produced by the catalysed reaction of /-butyl peroxide with a,f)-unsaturated sulphonates under basic conditions [12]. 

Direct phase-transfer catalysed epoxidation of electron-deficient alkenes, such as chalcones, cycloalk-2-enones and benzoquinones with hydrogen peroxide or r-butyl peroxide under basic conditions (Section 10.7) has been extended by the use of quininium and quinidinium catalysts to produce optically active oxiranes [1 — 16] the alkaloid bases are less efficient than their salts as catalysts [e.g. 8]. In addition to N-benzylquininium chloride, the binaphthyl ephedrinium salt (16 in Scheme 12.5) and the bis-cinchonidinium system (Scheme 12.12) have been used [12, 17]. Generally, the more rigid quininium systems are more effective than the ephedrinium salts. 

Basic solid liquid two-phase conditions with f-butyl peroxide and N-benzylquininium chloride convert cyclohex-2-enone preferentially into the 2(S),3(S)-oxirane (20% ee) which, upon purification and treatment with hydrazine, yields (S)-cyclohex-2-enol [7]. This reaction contrasts with the direct reduction of cyclohex-2-enone to the /J-isomer by lithium aluminium hydride in the presence of quinine [20]. 

Asymmetric induction using catalytic amounts of quininium or A-methyl-ephedrinium salts for the Darzen s reaction of aldehydes and ketones with phenacyl halides and chloromethylsulphones produces oxiranes of low optical purity [3, 24, 25]. The chiral catalyst appears to have little more effect than non-chiral catalysts (Section 12.1). Similarly, the catalysed reaction of sodium cyanide with a-bromo-ketones produces epoxynitriles of only low optical purity [3]. The claimed 67% ee for the phenyloxirane derived from the reaction of benzaldehyde with trimethylsul-phonium iodide under basic conditions [26] in the presence of A,A-dimethyle-phedrinium chloride was later retracted [27] the product was contaminated with the 2-methyl-3-phenyloxirane from the degradation of the catalyst. 

B. Oxirane Ring Opening with Low Basicity Organolithinm Reagents. . 1199... 

The -deprotonation reaction was initially considered as the normal mode of oxirane isomerization in basic media with a-deprotonation appearing as an alternative pathway when the principal process was slowed. Recent studies based on kinetic studies, calculations and labeling experiments, along with advances in the determination of the organolithium... 

It appears that oxiranes known to give predominantly a-deprotonation in basic media (cyclopentene, cyclooctene and exo-norbomene oxide) are also the more strained (Table 1 entries 3, 6, 7). On the other hand, oxiranes that give mainly -deprotonation (butene, cyclohexene oxide) have lower strain energies and higher a-anion stabilities (Table 1 ... 

In this particular case, remote control by the heteroatom of the substituent is invoked to explain the regioselectivity of the elimination. Complexation of lithium with both oxygens fixes the basic carbon atom close to the -proton . A similar model is proposed to rationalize the reversal to regiospecific a-deprotonation proximate to the hydroxyl group for oxiranes of type 23, the basic site now being close to the a-proton (Scheme 9) ° . 

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