dioxolane

Dioxolanes are a group of organic compounds containing the dioxolane ring. Dioxolanes can be prepared by acetalization of aldehydes and ketalization of ketones with ethylene glycol.{{OrgSynth

|author=R. A. Daignault, E. L. Eliel

|year=1973

|title=2-Cyclohexyloxyethanol (involves acetalisation of cyclohexanone)

|volume=

|pages=

|collvol=5

|collvolpages=303

|prep=CV5P0303}}

File:Dioxolane synthesis.png

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

Organic compounds containing carbonyl groups sometimes need protection so that they do not undergo reactions during transformations of other functional groups that may be present. A variety of approaches to protection and deprotection of carbonyls including as dioxolanes{{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}} 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

NaBArF₄ can also be used for deprotection of acetal or ketal-protected carbonyl compounds.{{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}} For example, deprotection of 2-phenyl-1,3-dioxolane to benzaldehyde can be achieved in water in five minutes at 30 °C.{{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}}

::PhCH(OCH₂)₂   +   H₂O   ->[\ce{NaBAr4}][\text{30 °C / 5 min}] PhCHO + HOCH₂CH₂OH

Neosporol is a natural product that includes a 1,3-dioxolane moiety, and is an isomer of sporol which has a 1,3-dioxane ring.{{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}} 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 method.{{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}}{{cite encyclopedia|doi = 10.1002/047084289X.rt254.pub2|encyclopedia = 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}} This method involves no water, so it gives a completely anhydrous peracid,{{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}} necessary in this case as the presence of water would lead to unwanted side reactions.

:trifluoroacetic anhydride   +   hydrogen peroxide - urea   →   trifluoroperacetic acid   +   trifluoroacetic acid   +   urea

In the case of neosporol, a Prilezhaev reaction{{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}} 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.

File:Neosporol epoxidation-rearrangement.png

A similar approach is used in the total synthesis of sporol, with the dioxolane ring later expanded to a dioxane system.

• Dioxane

{{reflist}}

• [http://www.epa.gov/oppt/chemrtk/pubs/summaries/dioxlne/c12846.pdf environmental and toxicological data]

{{Muscarinic acetylcholine receptor modulators}}

Category:Muscarinic agonists

Category:Solvents

Category:Protecting groups

Category:Formals