Inorganic chemistry, anortho ester is afunctional group containing threealkoxy groups attached to one carbon atom, i.e. with the general formulaRC(OR')3. Orthoesters may be considered as products of exhaustivealkylation of unstableorthocarboxylic acids and it is from these that the name 'ortho ester' is derived. An example isethyl orthoacetate,CH3C(OCH2CH3)3, more correctly known as 1,1,1-triethoxyethane.[1] Intotal synthesis, bicyclic OBO ortho esters are used asprotecting groups for carboxylic acids and esters.
Ortho esters are traditionally, but inefficiently[2] prepared through thePinner reaction ofnitriles andalcohols in the presence of one equivalent of hydrogen chloride. The reaction requires anhydrous conditions,[1] and ideally a nonpolar solvent.[3]: 6 It begins with formation ofimido ester hydrochloride:
Upon standing in the presence of excess alcohol, this intermediate converts to the ortho ester:[citation needed]
A major side-reaction converts the alcohol to the corresponding alkyl chloride.[2]
Acid chlorides can also drive the reaction from the corresponding amide, e.g.:[4]: 154
Although a less common method, ortho esters were first produced by reaction of 1,1,1-trichloroalkanes with sodium alkoxide:[1]
Compounds with an adjacent hydrogen atom on R tend to undergo elimination instead.[3]: 12 Traditionalesters can be converted to α,α‑dichloro ethers withphosphorus pentachloride. The resulting halogenated compounds undergo ether synthesis like the trichloroalkanes.[4]: 162
Carboxylic acids naturally form a trithio ortho ester when heated with amercaptan of appropriate stoichiometry.[5] The resulting compound undergoestransesterification to a traditional orthoester in the presence ofzinc chloride.[4]: 156
Transesterification from a cheaper ortho ester is also possible;[4] but performs best with unstabilized (electron-poorer) ortho esters. Stabilized ortho-esters tend to collapse to the corresponding non-ortho ester.[2]: 555–556
Ortho esters are readilyhydrolyzed in mild aqueous acid to formesters:
For example,trimethyl orthoformate CH(OCH3)3 may be hydrolyzed (under acidic conditions) tomethyl formate andmethanol;[6] and may be further hydrolyzed (under alkaline conditions) to salts offormic acid and methanol.[7]
Adamantane-structured orthoesters, formally derived from all-cis-1,3,5-trihydroxycyclohexane, hydrolyze particularly slowly, for which reason they have been used asprotecting groups.[8]
TheJohnson–Claisen rearrangement is the reaction of anallylic alcohol with an ortho ester containing a deprotonatablealpha carbon (e.g.triethyl orthoacetate) to give aγ,δ-unsaturatedester.[9]
In theBodroux–Chichibabin aldehyde synthesis an ortho ester reacts with aGrignard reagent to form analdehyde; this is an example of aformylation reaction.
Examples of orthoesters include the reagentstrimethyl orthoformate andtriethylorthoacetate. Another example is the bicyclic OBO protecting group (4-methyl-2,6,7-trioxa-bicyclo[2.2.2]octan-1-yl) which is formed by the action of(3-methyloxetan-3-yl)methanol [wd] on activated carboxylic acids in the presence ofLewis acids such asBF3. The group is base stable and can be cleaved in two steps under mild conditions. Mildly acidic hydrolysis yields the ester oftris(hydroxymethyl)ethane which is then cleaved using e.g. an aqueous carbonate solution.[10]
The threefold symmetry of thecyclohexanehexol isomerscyllo-inositol (scyllitol) yields the triply-bridged orthoformate estersscyllitol orthoformate with anadamantane-like skeleton, andscyllitol bis-orthoformate with adiamantane-like skeleton.[11]
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