Ortho ester: Difference between revisions
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{{short description|Chemical group with the structure RC(OR')3}} |
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[[File:Orthoesters General Formulae V.1.png|thumb| |
[[File:Orthoesters General Formulae V.1.png|thumb|250px|right|The general formula of orthoesters.]] |
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| ⚫ | In [[organic chemistry]], an '''ortho ester''' is a [[functional group]] containing three [[alkoxy group]]s attached to one carbon atom, i.e. with the general formula RC( |
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| ⚫ | In [[organic chemistry]], an '''ortho ester''' is a [[functional group]] containing three [[alkoxy group]]s attached to one carbon atom, i.e. with the general formula {{chem2|RC(OR')3}}. Orthoesters may be considered as products of exhaustive [[alkylation]] of unstable [[Ortho acid|orthocarboxylic acid]]s and it is from these that the name 'ortho ester' is derived. An example is [[ethyl orthoacetate]], {{chem2|CH3C(OCH2CH3)3}}, more correctly known as 1,1,1-triethoxyethane.<ref name=Patai>{{cite book|title=Carboxylic Acids and Esters|chapter=Ortho Esters|author=E. H. Cordes|editor=Saul Patai|year=1969|doi=10.1002/9780470771099.ch13 |
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== Synthesis == |
== Synthesis == |
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Ortho esters can be prepared by the [[Pinner reaction]], in which [[nitrile]]s react with [[alcohol]]s in the presence of one equivalent of hydrogen chloride. The reaction proceeds by formation of [[Carboximidate |
Ortho esters can be prepared by the [[Pinner reaction]], in which [[nitrile]]s react with [[Alcohol (chemistry)|alcohol]]s in the presence of one equivalent of hydrogen chloride. The reaction proceeds by formation of [[Carboximidate|imido ester hydrochloride]]: |
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:RCN + |
:RCN + {{prime|R}}OH + HCl → [RC(O{{prime|R}})=NH<sub>2</sub>]<sup>+</sup>Cl<sup>−</sup> |
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Upon standing in the presence of excess alcohol, this intermediate converts to the ortho ester: |
Upon standing in the presence of excess alcohol, this intermediate converts to the ortho ester: |
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:[RC( |
:[RC(O{{prime|R}})=NH<sub>2</sub>]<sup>+</sup>Cl<sup>−</sup> + 2{{nbsp}}{{prime|R}}OH → RC(O{{prime|R}})<sub>3</sub> + NH<sub>4</sub>Cl |
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The reaction requires anhydrous conditions,<ref name=Patai/> and ideally a nonpolar solvent.<ref name=Monograph>{{cite book|title=Carboxylic Ortho Acid Derivatives|series=Organic Chemistry|volume=14|first=Robert H.|last=DeWolfe|year=1970|publisher=Academic Press|location=New York, NY|lccn=70-84226}}</ref>{{rp|6}} |
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The reaction requires anhydrous conditions.<ref name=Patai/> |
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Acid chlorides can also drive the reaction from the corresponding amide, e.g.:<ref name=Review>{{cite journal|doi=10.1055/s-1974-23268|title=Synthesis of carboxylic or carbonic ortho esters|first=Robert H.|last=DeWolfe|journal=Synthesis|date=March 1974|issue=3 |pages=153–172 }}</ref>{{rp|154}} |
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:HCONH<sub>2</sub> + BzCl → HC(OBz)NH<sub>2</sub>Cl |
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:HC(OBz)NH<sub>2</sub>Cl + ROH → HC(OR)<sub>3</sub> + NH<sub>4</sub>Cl + BzOH. |
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Although a less common method, ortho esters were first produced by reaction of 1,1,1-trichloroalkanes with sodium alkoxide:<ref name=Patai/> |
Although a less common method, ortho esters were first produced by reaction of 1,1,1-trichloroalkanes with sodium alkoxide:<ref name=Patai/> |
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:RCCl<sub>3</sub> + 3{{nbsp}} |
:RCCl<sub>3</sub> + 3{{nbsp}}NaO{{prime|R}} → RC(O{{prime|R}})<sub>3</sub> + 3{{nbsp}}NaCl |
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Compounds with an adjacent hydrogen atom on R tend to undergo elimination instead.<ref name=Monograph/>{{rp|12}} Traditional [[ester]]s can be converted to α,α{{nbh}}dichloro ethers with [[phosphorus pentachloride]]. The resulting halogenated compounds undergo ether synthesis like the trichloroalkanes.<ref name=Review/>{{rp|162}} |
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Carboxylic acids naturally form a trithio ortho ester when heated with a [[mercaptan]] of appropriate stoichiometry.<ref>{{cite journal|first=J.|last=Houben|journal=Berichte der Deutschen Chemischen Gesellschaft|title=Über die Condensation von Mercaptanen mit Ameisensäure zu Orthotrithio-ameisensäureestern|lang=de|trans-title=On the condensation of mercaptans with formic acid unto formic acid trithio ortho esters|orig-date=2 Oct 1912|pages=2942–2946|volume=45|doi=10.1002/cber.19120450319 |via=the [[Internet Archive]]}}</ref> The resulting compound undergoes [[transesterification]] to a traditional orthoester in the presence of [[zinc chloride]].<ref name=Review/>{{rp|156}} Traditional transesterification from a cheaper ortho ester is also possible.<ref name=Review/> |
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==Reactions== |
==Reactions== |
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=== Hydrolysis === |
=== Hydrolysis === |
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Ortho esters are readily [[hydrolysis|hydrolyzed]] in mild aqueous acid to form [[ester]]s: |
Ortho esters are readily [[hydrolysis|hydrolyzed]] in mild aqueous acid to form [[ester]]s: |
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: RC( |
: RC(O{{prime|R}})<sub>3</sub> + H<sub>2</sub>O → RCO<sub>2</sub>{{prime|R}} + 2 {{prime|R}}OH |
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For example, [[trimethyl orthoformate]] CH(OCH<sub>3</sub>)<sub>3</sub> may be hydrolyzed (under acidic conditions) to [[methyl formate]] and [[methanol]];<ref>{{Clayden|page=345}}</ref> and may be further hydrolyzed (under alkaline conditions) to salts of [[formic acid]] and methanol.<ref>United States Patent Application 20070049501, Saini; Rajesh K.; and Savery; Karen, March 1, 2007</ref> |
For example, [[trimethyl orthoformate]] CH(OCH<sub>3</sub>)<sub>3</sub> may be hydrolyzed (under acidic conditions) to [[methyl formate]] and [[methanol]];<ref>{{Clayden|page=345}}</ref> and may be further hydrolyzed (under alkaline conditions) to salts of [[formic acid]] and methanol.<ref>United States Patent Application 20070049501, Saini; Rajesh K.; and Savery; Karen, March 1, 2007</ref> |
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===Johnson–Claisen rearrangement=== |
===Johnson–Claisen rearrangement=== |
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The [[ |
The [[Claisen rearrangement#Johnson.E2.80.93Claisen rearrangement|Johnson–Claisen rearrangement]] is the reaction of an [[allyl]]ic alcohol with an ortho ester containing a deprotonatable [[alpha carbon]] (e.g. [[triethyl orthoacetate]]) to give a {{no wrap|γ,δ-unsaturated}} [[ester]].<ref>{{cite journal|last1=Johnson|first1=William Summer.|last2=Werthemann|first2=Lucius.|last3=Bartlett|first3=William R.|last4=Brocksom|first4=Timothy J.|last5=Li|first5=Tsung-Tee.|last6=Faulkner|first6=D. John.|last7=Petersen|first7=Michael R.|title=Simple stereoselective version of the Claisen rearrangement leading to trans-trisubstituted olefinic bonds. Synthesis of squalene|journal=Journal of the American Chemical Society|date=February 1970|volume=92|issue=3|pages=741–743|doi=10.1021/ja00706a074}}</ref> |
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:[[Image:Johnson-Claisen Rearrangement Scheme.png|450px|The Johnson–Claisen rearrangement]] |
:[[Image:Johnson-Claisen Rearrangement Scheme.png|450px|The Johnson–Claisen rearrangement]] |
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:[[file:Hygromycin b.svg|thumb|[[Hygromycin B]], an [[antibiotic]], is one of several naturally occurring ortho esters.]] |
:[[file:Hygromycin b.svg|thumb|[[Hygromycin B]], an [[antibiotic]], is one of several naturally occurring ortho esters.]] |
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[[File:Obo-group.png|thumb|right|100px|'''OBO''': 4-methyl-2,6,7-trioxa-bicyclo[2.2.2]octan-1-yl]] |
[[File:Obo-group.png|thumb|right|100px|'''OBO''': 4-methyl-2,6,7-trioxa-bicyclo[2.2.2]octan-1-yl]] |
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[[ |
Examples of orthoesters include the reagents [[trimethyl orthoformate]] and [[triethylorthoacetate]]. Another example is the bicyclic OBO protecting group (4-methyl-2,6,7-tri'''o'''xa-'''b'''icyclo[2.2.2]'''o'''ctan-1-yl) which is formed by the action of (3-methyloxetan-3-yl)methanol on activated carboxylic acids in the presence of Lewis acids. The group is base stable and can be cleaved in two steps under mild conditions, mildly acidic hydrolysis yields the ester of tris(hydroxymethyl)ethane which is then cleaved using e.g. an aqueous carbonate solution.<ref>{{cite book|last1=Kocieński|first1=Philip J.|title=Protecting groups|date=2005|publisher=Thieme|location=Stuttgart|isbn=978-3-13-135603-1|edition=3.}}</ref> |
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The threefold symmetry of the [[cyclohexanehexol]] isomer [[scyllo-inositol|''scyllo''-inositol]] (scyllitol) yields the triply-bridged orthoformate esters [[scyllitol orthoformate]] with an [[adamantane]]-like skeleton, and [[scyllitol bis-orthoformate]] with two fused adamantane-like skeletons. |
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<ref name=leeh1985>Hyo Won Lee and Yoshito Kishi (1985): "Synthesis of mono- and unsymmetrical bis-orthoesters of ''scyllo''-inositol". ''Journal of Organic Chemistry'', volume 50, issue 22, pages 4402–4404 {{doi|10.1021/jo00222a046}}</ref> |
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==See also== |
==See also== |
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Latest revision as of 15:07, 1 October 2024
In organic chemistry, an ortho ester is a functional group containing three alkoxy groups attached to one carbon atom, i.e. with the general formula RC(OR')3. Orthoesters may be considered as products of exhaustive alkylation of unstable orthocarboxylic acids and it is from these that the name 'ortho ester' is derived. An example is ethyl orthoacetate, CH3C(OCH2CH3)3, more correctly known as 1,1,1-triethoxyethane.[1]
Synthesis
[edit]Ortho esters can be prepared by the Pinner reaction, in which nitriles react with alcohols in the presence of one equivalent of hydrogen chloride. The reaction proceeds by formation of imido ester hydrochloride:
- RCN + R′OH + HCl → [RC(OR′)=NH2]+Cl−
Upon standing in the presence of excess alcohol, this intermediate converts to the ortho ester:
- [RC(OR′)=NH2]+Cl− + 2 R′OH → RC(OR′)3 + NH4Cl
The reaction requires anhydrous conditions,[1] and ideally a nonpolar solvent.[2]: 6
Acid chlorides can also drive the reaction from the corresponding amide, e.g.:[3]: 154
- HCONH2 + BzCl → HC(OBz)NH2Cl
- HC(OBz)NH2Cl + ROH → HC(OR)3 + NH4Cl + BzOH.
Although a less common method, ortho esters were first produced by reaction of 1,1,1-trichloroalkanes with sodium alkoxide:[1]
- RCCl3 + 3 NaOR′ → RC(OR′)3 + 3 NaCl
Compounds with an adjacent hydrogen atom on R tend to undergo elimination instead.[2]: 12 Traditional esters can be converted to α,α‑dichloro ethers with phosphorus pentachloride. The resulting halogenated compounds undergo ether synthesis like the trichloroalkanes.[3]: 162
Carboxylic acids naturally form a trithio ortho ester when heated with a mercaptan of appropriate stoichiometry.[4] The resulting compound undergoes transesterification to a traditional orthoester in the presence of zinc chloride.[3]: 156 Traditional transesterification from a cheaper ortho ester is also possible.[3]
Reactions
[edit]Hydrolysis
[edit]Ortho esters are readily hydrolyzed in mild aqueous acid to form esters:
- RC(OR′)3 + H2O → RCO2R′ + 2 R′OH
For example, trimethyl orthoformate CH(OCH3)3 may be hydrolyzed (under acidic conditions) to methyl formate and methanol;[5] and may be further hydrolyzed (under alkaline conditions) to salts of formic acid and methanol.[6]
Johnson–Claisen rearrangement
[edit]The Johnson–Claisen rearrangement is the reaction of an allylic alcohol with an ortho ester containing a deprotonatable alpha carbon (e.g. triethyl orthoacetate) to give a γ,δ-unsaturated ester.[7]
Bodroux–Chichibabin aldehyde synthesis
[edit]In the Bodroux–Chichibabin aldehyde synthesis an ortho ester reacts with a Grignard reagent to form an aldehyde; this is an example of a formylation reaction.
Examples
[edit]
Hygromycin B, an antibiotic, is one of several naturally occurring ortho esters.
Examples of orthoesters include the reagents trimethyl orthoformate and triethylorthoacetate. 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 on activated carboxylic acids in the presence of Lewis acids. The group is base stable and can be cleaved in two steps under mild conditions, mildly acidic hydrolysis yields the ester of tris(hydroxymethyl)ethane which is then cleaved using e.g. an aqueous carbonate solution.[8]
The threefold symmetry of the cyclohexanehexol isomer scyllo-inositol (scyllitol) yields the triply-bridged orthoformate esters scyllitol orthoformate with an adamantane-like skeleton, and scyllitol bis-orthoformate with two fused adamantane-like skeletons. [9]
See also
[edit]- Acetal, C(OR)2R2
- Orthocarbonate, C(OR)4.
References
[edit]- ^ a b c E. H. Cordes (1969). "Ortho Esters". In Saul Patai (ed.). Carboxylic Acids and Esters. PATAI'S Chemistry of Functional Groups. pp. 623–667. doi:10.1002/9780470771099.ch13. ISBN 9780470771099.
- ^ a b DeWolfe, Robert H. (1970). Carboxylic Ortho Acid Derivatives. Organic Chemistry. Vol. 14. New York, NY: Academic Press. LCCN 70-84226.
- ^ a b c d DeWolfe, Robert H. (March 1974). "Synthesis of carboxylic or carbonic ortho esters". Synthesis (3): 153–172. doi:10.1055/s-1974-23268.
- ^ Houben, J. "Über die Condensation von Mercaptanen mit Ameisensäure zu Orthotrithio-ameisensäureestern" [On the condensation of mercaptans with formic acid unto formic acid trithio ortho esters]. Berichte der Deutschen Chemischen Gesellschaft (in German). 45: 2942–2946. doi:10.1002/cber.19120450319 – via the Internet Archive.
- ^ Clayden, Jonathan; Greeves, Nick; Warren, Stuart; Wothers, Peter (2001). Organic Chemistry (1st ed.). Oxford University Press. p. 345. ISBN 978-0-19-850346-0.
- ^ United States Patent Application 20070049501, Saini; Rajesh K.; and Savery; Karen, March 1, 2007
- ^ Johnson, William Summer.; Werthemann, Lucius.; Bartlett, William R.; Brocksom, Timothy J.; Li, Tsung-Tee.; Faulkner, D. John.; Petersen, Michael R. (February 1970). "Simple stereoselective version of the Claisen rearrangement leading to trans-trisubstituted olefinic bonds. Synthesis of squalene". Journal of the American Chemical Society. 92 (3): 741–743. doi:10.1021/ja00706a074.
- ^ Kocieński, Philip J. (2005). Protecting groups (3. ed.). Stuttgart: Thieme. ISBN 978-3-13-135603-1.
- ^ Hyo Won Lee and Yoshito Kishi (1985): "Synthesis of mono- and unsymmetrical bis-orthoesters of scyllo-inositol". Journal of Organic Chemistry, volume 50, issue 22, pages 4402–4404 doi:10.1021/jo00222a046