Dioxolane: Difference between revisions

{{about|1,3-dioxolane|the other dioxolane isomer|1,2-dioxolane}}

|Verifiedfields = changed

|Watchedfields = changed

|verifiedrevid = 444710218

|Reference=<ref>[http://www.sigmaaldrich.com/catalog/ProductDetail.do?N4=184497|SIAL&N5=SEARCH_CONCAT_PNO|BRAND_KEY&F=SPEC 1,3-Dioxolane] at [[Sigma-Aldrich]]</ref>

|Name = Dioxolane

|ImageFileL1 = 1,3-dioxolane-2D-skeletal.png

|ImageFileR1 = 1,3-dioxolane-3D-balls.png

|PIN = 1,3-Dioxolane<ref>{{cite book | title = Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = [[Royal Society of Chemistry|The Royal Society of Chemistry]] | date = 2014 | location = Cambridge | page = 145 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4| chapter = Front Matter }}</ref>

|SystematicName = 1,3-Dioxacyclopentane

|OtherNames = Dioxolane <br /> 5-Crown-2 <br /> Formal glycol<ref>[https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=12586 formal glycol - PubChem Public Chemical Database]</ref>

|Section1 = {{Chembox Identifiers

|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

|ChemSpiderID = 12066

|PubChem = 12586

|ChEBI_Ref = {{ebicite|correct|EBI}}

|ChEBI = 87597

| ChEMBL = 3187281

|EINECS = 211-463-5

|InChI = 1/C3H6O2/c1-2-4-5-3-1/h1-3H2

|InChIKey = SNQXJPARXFUULZ-UHFFFAOYAS

|StdInChI_Ref = {{stdinchicite|correct|chemspider}}

|StdInChI = 1S/C3H6O2/c1-2-4-5-3-1/h1-3H2

|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

|StdInChIKey = SNQXJPARXFUULZ-UHFFFAOYSA-N

|CASNo_Ref = {{cascite|correct|CAS}}

|CASNo = 646-06-0

|UNII_Ref = {{fdacite|correct|FDA}}

|UNII = Y57RBG19JL

| UNNumber = 1166

|SMILES = O1CCOC1

|Section2 = {{Chembox Properties

|Formula = C₃H₆O₂

|MolarMass = 74.08 g/mol

|Density = 1.06 g/cm³

|MeltingPtC = -95

|BoilingPtC = 75}}

|Section7 = {{Chembox Hazards

| GHS_ref=<ref>{{cite web |title=1,3-Dioxolane |url=https://pubchem.ncbi.nlm.nih.gov/compound/12586#section=Safety-and-Hazards |website=pubchem.ncbi.nlm.nih.gov |language=en}}</ref>

| GHSPictograms = {{GHS02}}

| GHSSignalWord = Danger

| HPhrases = {{H-phrases|225}}

| PPhrases = {{P-phrases|210|233|240|241|242|243|280|303+361+353|370+378|403+235|501}}

}}

'''Dioxolane''' is a [[Heterocyclic compound|heterocyclic]] [[acetal]] with the [[chemical formula]] (CH₂)₂O₂CH₂. It is related to [[tetrahydrofuran]] (THF) by replacement of the [[methylene group]] (CH₂) at the 2-position with an oxygen atom. The corresponding saturated 6-membered C₄O₂ rings are called [[dioxane]]s. The [[isomer]]ic 1,2-dioxolane (wherein the two oxygen centers are adjacent) is a [[organic peroxide|peroxide]]. 1,3-dioxolane is used as a [[solvent]] and as a co[[monomer]] in [[polyacetal]]s.

==As a class of compounds==

'''Dioxolanes''' are a group of [[organic compound]]s containing the dioxolane ring. Dioxolanes can be prepared by [[acetalization]] of [[aldehyde]]s and [[ketalization]] of [[ketone]]s with [[ethylene glycol]].<ref>{{OrgSynth

|prep=CV5P0303}}</ref>

[[File:Dioxolane synthesis.png|center|synthesis of dioxolane group]]

(+)-''cis''-Dioxolane is the [[trivial name]] for {{chem name|<small>L</small>-(+)-''cis''-2-methyl-4-trimethylammoniummethyl-1,3-dioxolane iodide}} which is a [[muscarinic acetylcholine receptor]] [[agonist]].

==Protecting groups==

Organic compounds containing [[carbonyl group]]s sometimes need [[protecting group|protection]] so that they do not undergo reactions during transformations of other [[functional group]]s that may be present. A variety of approaches to protection and deprotection of carbonyls<ref name = Greene /> including as dioxolanes<ref name = Greene2>{{cite book|chapter = 1,3-Dioxanes, 1,3-Dioxolanes|first1 = Theodora W.|last1 = Greene|first2 = Peter G. M.|last2 = Wuts|title = Greene's Protective Groups in Organic Synthesis|edition = 3rd|publisher = [[Wiley-Interscience]]|year = 1999|pages = 308–322, 724–727|url = https://www.organic-chemistry.org/protectivegroups/carbonyl/dioxanes-dioxolanes.htm|access-date = June 20, 2017|isbn = 9780471160199|archive-date = December 7, 2016|url-status = live|archive-url = https://web.archive.org/web/20161207144346/http://www.organic-chemistry.org/protectivegroups/carbonyl/dioxanes-dioxolanes.htm}}</ref> are known. For example, consider the compound methyl cyclohexanone-4-carboxylate, where [[lithium aluminium hydride]] reduction will produce 4-hydroxymethylcyclohexanol. The ester functional group can be reduced without affecting the [[ketone]] by protecting the ketone as a [[ketal]]. The ketal is produced by acid catalysed reaction with [[ethylene glycol]], the reduction reaction carried out, and the protecting group removed by hydrolysis to produce 4-hydroxymethylcyclohexanone.

[[File:Acetal-protection-example.png|centre|400px]]

[[Tetrakis(3,5-bis(trifluoromethyl)phenyl)borate|NaBArF₄]] can also be used for deprotection of acetal or ketal-protected carbonyl compounds.<ref name = Greene>{{cite book|chapter = Dimethyl acetals|first1 = Theodora W.|last1 = Greene|first2 = Peter G. M.|last2 = Wuts|title = Greene's Protective Groups in Organic Synthesis|edition = 3rd|publisher = [[Wiley-Interscience]]|year = 1999|pages = 297–304, 724–727|url = https://www.organic-chemistry.org/protectivegroups/carbonyl/dimethylacetals.htm|access-date = June 20, 2017|isbn = 9780471160199|archive-date = December 3, 2016|url-status = live|archive-url = https://web.archive.org/web/20161203200424/http://www.organic-chemistry.org/protectivegroups/carbonyl/dimethylacetals.htm}}</ref><ref name = Greene2 /> For example, deprotection of 2-phenyl-1,3-dioxolane to [[benzaldehyde]] can be achieved in water in five minutes at 30&nbsp;°C.<ref>{{cite journal|title = Deprotection of Acetals and Ketals in a Colloidal Suspension Generated by Sodium Tetrakis(3,5-trifluoromethylphenyl)borate in Water|first1 = Chih-Ching|last1 = Chang|first2 = Bei-Sih|last2 = Liao|first3 = Shiuh-Tzung|last3 = Liu|journal = [[Synlett]]|year = 2007|volume = 2007|issue = 2|pages = 283–287|doi = 10.1055/s-2007-968009}}</ref>

::PhCH(OCH₂)₂ &nbsp; + &nbsp; [[water|H₂O]] &nbsp; <chem>->[\ce{NaBAr4}][\text{30 °C / 5 min}]</chem>&nbsp;PhCHO&nbsp;+&nbsp;[[ethylene glycol|HOCH₂CH₂OH]]

==Natural products==

[[Neosporol]] is a [[natural product]] that includes a 1,3-dioxolane [[moiety (chemistry)|moiety]], and is an isomer of [[sporol]] which has a 1,3-dioxane ring.<ref name = NatProd>{{cite book|chapter-url = https://books.google.com/books?id=OjO78KV6USAC&pg=PA222|chapter = 10. Neosporol, Sporol|pages = 222–224|series = The Total Synthesis of Natural Products|volume = 11|title = Part B: Bicyclic and Tricyclic Sesquiterpenes|editor1-first = Michael C.|editor1-last = Pirrung|editor2-first = Andrew T.|editor2-last = Morehead|editor3-first = Bruce G.|editor3-last = Young|publisher = [[John Wiley & Sons]]|year = 2000|isbn = 9780470129630}}</ref> The [[total synthesis]] of both compounds has been reported, and each includes a step in which a dioxolane system is formed using [[trifluoroperacetic acid]] (TFPAA), prepared by the [[hydrogen peroxide - urea|hydrogen peroxide &ndash; urea]] method.<ref name = UHP>{{cite journal|last1 = Ziegler|first1 = Fredrick E.|last2 = Metcalf|first2 = Chester A.|last3 = Nangia|first3 = Ashwini|last4 = Schulte|first4 = Gayle|title = Structure and total synthesis of sporol and neosporol|journal = [[J. Am. Chem. Soc.]]|year = 1993|volume = 115|issue = 7|pages = 2581–2589|doi = 10.1021/ja00060a006}}</ref><ref name = eEROS2012>{{cite encyclopedia|doi = 10.1002/047084289X.rt254.pub2|encyclopedia = [[Encyclopedia of Reagents for Organic Synthesis|e-EROS Encyclopedia of Reagents for Organic Synthesis]]|title = Trifluoroperacetic Acid|first1 = Kenneth C.|last1 = Caster|first2 = A. Somasekar|last2 = Rao|first3 = H. Rama|last3 = Mohan|first4 = Nicholas A.|last4 = McGrath|first5 = Matthew|last5 = Brichacek|year = 2012|isbn = 978-0471936237}}</ref> This method involves no water, so it gives a completely [[anhydrous]] peracid,<ref>{{cite journal|title = Oxidation Reactions Using Urea–Hydrogen Peroxide; A Safe Alternative to Anhydrous Hydrogen Peroxide|journal = [[Synlett]]|year = 1990|volume = 1990|issue = 9|pages = 533–535|doi = 10.1055/s-1990-21156|first1 = Mark S.|last1 = Cooper|first2 = Harry|last2 = Heaney|author-link2 = Harry Heaney|first3 = Amanda J.|last3 = Newbold|first4 = William R.|last4 = Sanderson}}</ref> necessary in this case as the presence of water would lead to unwanted [[side reaction]]s.<ref name = UHP />

:[[trifluoroacetic anhydride|{{chem|CF|3|COOCOCF|3}}]] &nbsp; + &nbsp; [[hydrogen peroxide - urea|{{chem|H|2|O|2|•CO(NH|2|)|2}}]] &nbsp; → &nbsp; [[trifluoroperacetic acid|{{chem|CF|3|COOOH}}]] &nbsp; + &nbsp; [[trifluoroacetic acid|{{chem|CF|3|COOH}}]] &nbsp; + &nbsp; [[urea|{{chem|CO(NH|2|)|2}}]]

In the case of neosporol, a [[Prilezhaev reaction]]<ref>{{cite book|chapter = Prilezhaev reaction|pages = 274–281|last = Hagen|first = Timothy J.|chapter-url = https://books.google.com/books?id=WZ0DxnPNAdAC&pg=PA274|title = Name Reactions of Functional Group Transformations|editor1-first = Jie Jack|editor1-last = Li|editor2-first = E. J.|editor2-last = Corey|editor2-link = Elias James Corey|publisher = [[John Wiley & Sons]]|year = 2007|isbn = 9780470176504}}</ref> with trifluoroperacetic acid is used to convert a suitable [[allyl alcohol]] precursor to an [[epoxide]], which then undergoes a ring-expansion reaction with a proximate [[carbonyl]] functional group to form the dioxolane ring.<ref name = UHP /><ref name = eEROS2012 />

[[File:Neosporol epoxidation-rearrangement.png|frameless|center|700px]]

A similar approach is used in the total synthesis of sporol, with the dioxolane ring later expanded to a dioxane system.<ref name = NatProd />

{{Muscarinic acetylcholine receptor modulators}}

[[Category:Muscarinic agonists]]

[[Category:Solvents]]

[[Category:Protecting groups]]

[[Category:Formals]]