Epoxide

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A generic epoxide.

An epoxide is a cyclic ether with three ring atoms. These rings approximately define an equilateral triangle, which makes it highly strained. The strained ring makes epoxides more reactive than other ethers. Simple epoxides are named from the parent compound ethylene oxide or oxirane, such as in chloromethyloxirane. As a functional group, epoxides feature the epoxy prefix, such as in the compound 1,2-epoxycycloheptane, which can also be called cycloheptene epoxide, or simply cycloheptene oxide.

The chemical structure of the epoxide glycidol, a common chemical intermediate

A polymer formed by reacting epoxide units is called a polyepoxide or an epoxy. Epoxy resins are used as adhesives and structural materials. Polymerization of an epoxide gives a polyether, for example ethylene oxide polymerizes to give polyethylene glycol, also known as polyethylene oxide.

Synthesis[edit]

The dominant epoxides industrially are ethylene oxide and propylene oxide, which are produced respectively on the scales of approximately 15 and 3 million tonnes.[1] The epoxidation of ethylene involves its catalytic reaction of oxygen according to the following stoichiometry:

7 H2C=CH2 + 6 O2 → 6 C2H4O + 2 CO2 + 2 H2O

The direct reaction of oxygen with alkenes is useful only for this epoxide. Other alkenes fail to react usefully, even propylene.

Olefin peroxidation[edit]

Most epoxides are generated by treating alkenes with peroxide-containing reagents, which donate a single oxygen atom. Typical peroxide reagents include hydrogen peroxide, peroxycarboxylic acids (generated in-situ or preformed), and alkyl hydroperoxides. In specialized applications, other peroxide-containing reagents are employed, such as dimethyldioxirane.

The largest scale application of this approach is the production of propylene oxide from propylene using either t-butyl hydroperoxide or ethylbenzene hydroperoxide.[2] More typically for laboratory operations, the Prilezhaev reaction is employed.[3][4] This approach involves the oxidation of the alkene with a peroxyacid such as m-CPBA. Illustrative is the epoxidation of styrene with perbenzoic acid to styrene oxide:[5]

Prilezhaev Reaction

The reaction proceeds via what is commonly known as the "Butterfly Mechanism."[6] The peroxide is viewed as an electrophile, and the alkene a nucleophile. The reaction is considered to be concerted (the numbers in the mechanism below are for simplification).The butterfly mechanism allows ideal positioning of the O-O sigma star orbital for C-C Pi electrons to attack.[7]

Butterfly Mechanism

Hydroperoxides are also employed in catalytic enantioselective epoxidations, such as the Sharpless epoxidation and the Jacobsen epoxidation. Together with the Shi epoxidation, these reactions are useful for the enantioselective synthesis of chiral epoxides. Oxaziridine reagents may also be used to generate epoxides from alkenes.

Metals can also be used as source of peroxides for epoxidation reactions. This catalytic reaction was first explored by the Frill group in 1965 and involved the activation of tert-butyl hydroperoxide (TBHP) with a metal complex. Association of TBHP with the metal generates the active species, which can then present the familiar peroxide structure.[8] The proposed mechanism for metal catalyzed epoxidations shows coordination of the alkene to an empty coordination site on the metal, which positions the alkene to attack the electrophilic peroxide. [9]

Vanadium Catalytic Pathway.png

Metals shown to effectively catalyze this reaction have high oxidation states and are good Lewis bases. The metals found to be most useful in Frill’s study demonstrated the following order of reactivity Mo>W>Ti, V, with molybdenum being the most reactive, and vanadium complexes being the least. Metal catalyzed epoxidations tend to go at slower rates in polar solvents due to competition for coordination sites between the solvent and TBHP. Like other peroxide epoxidations, these reactions are accelerated by higher substitution levels and electron donating groups.[10]

Early work done by the Henbest group showed that allylic alcohols could be used to give facial selectivity when using m-CPBA as an oxidant. This selectivity was reversed when the allylic alcohol was acetylated. This lead the conclusion that hydrogen bonding played a key role in selectivity and the following model was proposed.[11]

Peracid H bonding model.png

Further studies showed that for cyclic allylic alcohols, greater selectivity was seen when the alcohol was locked in the pseudo equatorial position rather than the pseudo axial position.[12] However, it was found that for metal catalyzed systems such as vanadium, reaction rates were accelerated when the hydroxyl group was in the axial position by a factor of 34. Substrates which were locked in the pseudo equatorial position were shown to undergo oxidation to form the ene-one. In both cases of vanadium catalyzed epoxidations, the epoxidzed product showed excellent selectivity for the syn diastereomer.[13]

Conformationally locked directing groups.png

Consistent with Henbest’s work, it was found that the addition of other protecting groups on to allylic alcohols led to a reversal of selectivity in cyclic systems. In the absence of hydrogen bonding, steric effects direct peroxide addition to the opposite face. However, perfluoric peracids are still able to hydrogen bond with protected alcohols and give normal selectivity with the hydrogen present on the peracid.[14]

Fluro binding model.png

Although the presence of an allylic alcohol does lead to increased stereoselectivity, the rates of these reactions are slower than systems lacking alcohols. However, the reaction rates of substrates with a hydrogen bonding group are still faster than the equivalent protected substrates. This observation is attributed to a balance of two factors. The first is the stabilization of the transition state as a result of the hydrogen bonding. The second is the electron withdrawing nature of the oxygen, which draws electron density away from the alkene, lowering its reactivity.[15]

Kinetics with allylic hetero atoms.png

Acyclic allylic alcohols have been shown to have good selectivity as well. In these systems both A1,2 (steric interactions with vinyl) and A1,3 strain are considered. It has been shown that a dihedral angle of 120 best directs substrates which hydrogen bond with the directing group. This geometry allows for the peroxide to be properly positioned, as well as to allow minimal donation from the C-C pi into the C-O sigma star.[16] This donation would lower the electron density of the alkene, and deactivate the reaction. However,vanadium complexes do not hydrogen bond with their substrates. Instead they coordinate with the alcohol. This means that a dihedral angle of 40 allows for ideal position of the peroxide sigma star orbital.[17]

Roation stuff.png

In systems that hydrogen bond, A1,3 strain plays a larger role because the required geometry forces any allylic substituents to have severe A1,3 interactions, but avoids A1,2. This leads to syn addition of the resulting epoxide. In the vanadium case, the required geometry leads to severe A1,2 interactions, but avoids A1,3, leading to formation of the epoxide anti to the directing group. Vanadium catalyzed epoxidations have been shown to be very sensitive to the steric bulk of the vinyl group.[18][19][20]

Vinyl Bulk.png

Homoallylic alcohols have been shown to good directing groups for epoxidations in both cyclic and acyclic systems for substrates which show hydrogen bonding. However these reactions tend to have lower levels of selectivity.[21][22][23]

Homoallylic peracid.png

While hydrogen bonding substrates give the same type of selectivity in allylic and homoallylic cases, the opposite is true of vanadium complexes.

Homoallylic VO.png

A transition state proposed by Mihelich shows that for these reactions, the driving force for selectivity is minimizing A1,3 strain in a pseudo chair structure.

Homoallylic VO model.png

The proposed transition state shows that the substrate will try to assume a conformation which minimizes the allyic strain. To do this, the least sterially bulky R group will rotate to assume the R4 position.[24]

Although peracids and metal catalyzed expoidations show different selectivity in acyclic systems, they show relatively similar selectivity in cyclic systems For cyclic ring systems that are smaller seven or smaller or 10 or lager, similar patterns of selectivity are observed. However it has been shown that for medium sized rings (eight and nine) peracid oxidizers show reverse selectivity, while vanadium catalyzed reactions continue to show formation of the syn epoxide.[25]

Ring size on selectivity.png

Although it is the least reactive metal catalyst for epoxidations, vanadium is highly selective for alkenes with allylic alcohols. Early work done by Sharpless shows its preference for reacting with alkenes with allylic alcohols over more substituted electron dense alkenes. In this case, Vanadium showed reverse regioselectivity from both m-CPBA and the more reactive molybdenum species. Although vanadium is generally less reactive than other metal complexes, in the presence of allylic alcohols, the rate of the reaction is accelerated beyond that of molybdenum, the most reactive metal for epoxidations.[26]

VO selectivity.png

Intramolecular SN2 substitution[edit]

This method is a variant of the Williamson ether synthesis. In this case, an alkoxide ion displaces a chloride atom within the same molecule. The precursor compounds are called halohydrins. For example, with 2-chloropropanol:[27]

Methyloxirane from 2-chloroproprionic acid.png

Approximately half of the world's supply of propylene oxide arises via this route.[2] An intramolecular epoxide formation reaction is one of the key steps in the Darzens reaction.

In the Johnson–Corey–Chaykovsky reaction epoxides are generated from carbonyl groups and sulfonium ylides. In this reaction, a sulfonium is the leaving group instead of chloride.

Nucleophilic epoxidation[edit]

Electron-deficient olefins, such as enones and acryl derivatives can be epoxidized using nucleophilic oxygen compounds such as peroxides. The reaction is a two-step mechanism. First the oxygen performs a nucleophilic conjugate addition to give a stabilized carbanion. This carbanion then attacks the same oxygen atom, displacing a leaving group from it, to close the epoxide ring.

Asymmetric epoxidation[edit]

The carbon atoms of an epoxide are approximately sp3-hybridized, and thus may be stereogenic positions. Depending on the mechanism of the reaction and the geometry of the alkene starting material, cis and/or trans epoxide diastereomers may be formed. In addition, if there are other stereocenters present in the starting material, they can influence the stereochemistry of the epoxidation relative to them. This diastereoselectivity is a form of "substrate control" of the reaction. Finally, epoxidizing agents that possess stereogenic structures can influence the stereochemistry of the epoxide product (see for example the Sharpless epoxidation, Jacobsen epoxidation, Waits–Scheffer epoxidation, and Juliá–Colonna epoxidation). This enantioselectivity is a form of "reagent control" of the reaction.

Reactions[edit]

Typical epoxide reactions are listed below.

EpoxOpen.png
    • Under acidic conditions, the position the nucleophile attacks is affected both by steric effects (as normally seen for SN2 reactions) and by carbocationic stability (as normally seen for SN1 reactions). Under basic conditions, the nucleophile attacks the least substituted carbon, in accordance with standard SN2 nucleophilic addition reaction process.
De-epoxidation with tungsten hexachloride / n-butyllithium
  • Reaction with the NH group in an amine. This covalent bond formation is utilised in epoxy glue with, e.g., Triethylenetetramine (TETA) as a hardener.

Perepoxides[edit]

Perepoxides are epoxides with an additional oxygen atom attached to the epoxide-oxygen. They are isoelectronic and isostructural with the cyclic sulfoxides derived from episulfides. Perepoxides are proposed intermediates in the photosensitized oxidation of alkenes, as occurs when drying oils (a component of some paints and varnishes) are exposed to air in light. Such intermediates arise from the addition of singlet oxygen to the double bond. Perepoxides rapidly rearrange to allylic hydroperoxides.[3]

See also[edit]

References[edit]

  1. ^ Siegfried Rebsdat, Dieter Mayer "Ethylene Oxide" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2005.doi:10.1002/14356007.a10_117 Article Online Posting Date: March 15, 2001.
  2. ^ a b Dietmar Kahlich, Uwe Wiechern, Jörg Lindner “Propylene Oxide” in Ullmann's Encyclopedia of Industrial Chemistry, 2002 by Wiley-VCH, Weinheim. doi:10.1002/14356007.a22_239Article Online Posting Date: June 15, 2000
  3. ^ a b March, Jerry. 1985. Advanced Organic Chemistry, Reactions, Mechanisms and Structure. 3rd ed. John Wiley & Sons. ISBN 0-471-85472-7.
  4. ^ Nikolaus Prileschajew (1909). "Oxydation ungesättigter Verbindungen mittels organischer Superoxyde". Berichte der deutschen chemischen Gesellschaft 42 (4): 4811–4815. doi:10.1002/cber.190904204100. 
  5. ^ Harold Hibbert and Pauline Burt (1941), Styrene Oxide, Org. Synth. ; Coll. Vol. 1: 494 
  6. ^ Bartlett Rec. Chem. Prog 1950, 11 47.
  7. ^ Edwards, J. O. ‘’In Perodixe Reaction Mechanism’’, ‘’Ed.; Wiley:New York’’, ‘’1962’’, 67-106.
  8. ^ Indictor, N.; Brill, W. F. ‘’J. Org. Chem.’’, ‘’’1965’’’, ‘’30 (6)’’, 2074. (doi: 10.1021/jo01017a520).
  9. ^ Butler, A.; Clague, M. J.; Gretchen, E. ‘’Meister Chem. Rev.’’, ‘’’1994’’’, ‘’94(3)’’, 625-638. (doi: 10.1021/cr00027a004).
  10. ^ Sheldon, R. A. ‘’Journal of Molecular Catalysis’’, ‘’’1980’’’, ‘’1’’, 107-206. (doi: 10.1016/0304-5102(80)85010-3).
  11. ^ Henbest, H. B.; Wilson, R. A. L.; ‘’J. Chem. Soc.’’, ‘’’1957’’’, 1958-1965. (doi: 10.1039/JR9570001958).
  12. ^ Chamberlain, P.; Roberts, M. L.; Whitham, G. H.; ‘’J. Chem. Soc.’’, ‘’’1970’’’, ‘’0’’, 1374-1381. (doi: 10.1039/J29700001374).
  13. ^ Weyerstahl, P.; Marschall-Weyerstahl, H.; Pennninger, J.; Walther, L. ‘’Tetrahedron’’, ‘’’1987’’’, ‘’43’’, 5287-5298. (doi: 10.1016/S0040-4020(01)87705-X).
  14. ^ McKittrick, B. A.; Ganem,B. ‘’Tetrahedron’’, ‘’’1985’’’, ‘’40’’, 4895-4898. (doi:10.1016/S0040-4039(00)94979-7).
  15. ^ Hoveyda, A. H.; Evans, D. A.; Fu, G. C. ‘’Chem. Rev.’’, ‘’’1993’’’, ‘’93’’, 1307-1370. (doi: 10.1021/cr00020a002).
  16. ^ Houk, K. N.; Paddon-Row, M. N.; Rondan, N. G.; Wu, Y. D.; Brown, F. K.; Spellmeyer, D. C.; Metz, J. T.; Li, Y .; Loncharich, R. J. ‘’Science’’, ‘’’1986’’’, ‘’231’’, 1108-1117.
  17. ^ Waldemar, A.; Wirth, T. ‘’Accounts of Chemical Research’’, ‘’’1999’’’, ‘’32.8’’, 703-710.
  18. ^ Mihelich, E. D. ‘’Tetrahderon Lett.’’, ‘’’1979’’’, ‘’20’’, 4729-4732. (doi: 10.1016/S0040-4039(01)86695-8).
  19. ^ Rossiter, B. E.; Verhoeven, T. R.; Sharpless, K. B. ‘’Tetrahedron Lett.’’,‘‘’1979’’’, “20 (49)”, 4733-4736. (doi: 10.1016/S0040-4039(01)86696-X).
  20. ^ Narula, A. S. ‘’Tetrahedron Lett.’’, ‘’’1979’’’, ‘’23 (52)’’, 2279-5582.(doi: 10.1016/S0040-4039(00)85899-2).
  21. ^ Darby, A. C.; Henbest, H. B.; McClenaghan I. ‘’Chem. Ind.’’, ‘’’1962’’’, 462-463.
  22. ^ Cragg, G. M. L.; Meakins, G. D. ‘’J. Chem. Soc.’’, ‘’’1965’’’, 2054-2063. (doi: 10.1039/JR9650002054).
  23. ^ Johnson, M. R.; Kishi, Y. ‘’Tetrahedron Lett.’’, ‘’’1979’’’, 4347-4350.
  24. ^ Mihelich, E. D.; Daniels, K.; Eickhoff, D. J.; ‘’J. Am. Chem. Soc.’’, ‘’’1981’’’, ‘’103 (25)’’, 7690-7692. (doi: 10.1021/ja00415a067).
  25. ^ Itoh, T.; Jitsukawa, K.; Kaneda, K.; Teranishi, S. ‘’J. Am. Chem. Soc.’’, ‘’’1979’’’, ‘’101 (1)’’, 159-169. (doi: 10.1021/ja00495a027).
  26. ^ Sharpless, K. B.; Michaelson, R. C. ‘’J. Am. Chem. Soc.’’, ‘’’1973’’’, ‘’95 (18)’’
  27. ^ Koppenhoefer, B.; Schurig, V. (1993), (R)-Alkyloxiranes of High Enantiomeric Purity from (S)-2-Chloroalkanoic Acids via (S)-2-Chloro-1-Alkanols: (R)-Methyloxirane, Org. Synth. ; Coll. Vol. 8: 434 
  28. ^ K. Barry Sharpless, Martha A. Umbreit, Marjorie T. Nieh, Thomas C. Flood (1972). "Lower valent tungsten halides. New class of reagents for deoxygenation of organic molecules". J. Am. Chem. Soc. 94 (18): 6538–6540. doi:10.1021/ja00773a045.