Why not strait to Iodosafrole? Why always Bromo to Finklestein?

The availability of iodine and it's compounds are restricted in many parts of the world  Thus halogens such as bromine or chlorine are used for the carbonium ion rearrangement reaction The mechanisms involved are explained in the attached chapter from an organic chemistry textbook  The end results from the effort applied 

Are there any reasons why the RxN won't run properly with NaOI or KI directly into GAA (or DMSO), and H2SO4?

Yes, the obvious reason of I₂ formation. Add H2SO4 to a Salt solution of Iodide and see if you can prevent the formation of the purple color. If you can't then there is your answer.

One could possibly use H3PO4 then, dissolved and dried in a solvent, and use this acid to free the HI instead?
It is indeed strong enough, and it also does not oxidise the HI to I2 like H2SO4 does, but its main issue is there is in commercial concentrated one 85% only so maybe sodium sulfate to a solution of H3PO4 airtight sealed proper dried could omit the whole bromination step for those who can get iodine easily i would say.

Your DMSO smells?
Pure DMSO shouldnt smell bad at all, just a bit sweet glycol-like .
Dimethylsulfide is contaminating yours, just to notice it could maybe interfere there, i dont know?

Why reinventing the wheel. Bromo-finkel-gas (Nh3,menh2n in ipa) boom... as outlined exatly in other posts. it has worked for me! ONCE. i understand modifications and such but stick to true and tried stuff. i remember a guy here, did a finkelstein in IPA.. i really felt bad for him or for his lack of research..

HI can be problematic. I- is much more easily oxidized than Br-, and a stronger nucleophile besides, allowing it to affect the stability of the ether ring, and it's kind of unstable in the presence of oxygen anyway. The thing is, I've read a whole lot of attempts with HI, and many of them just didn't work very well, and most of the attempts I've seen to use HBr did work pretty well.

http://its.goofyti.me/u/http://parazite.pp.fi/hiveboard/picproxie_docs/000537223-The_Cleavage_of_Ethers.pdf

The rate of the reaction declines with increasing water content of the acid (84,147). Hydrogen bromide reacts more rapidly than hydrogen chloride and less rapidly than hydrogen iodide (84,147). Hydrogen bromide reacts about six times as rapidly as hydrogen chloride (84) while, under these conditions, hydrogen iodide reacts too fast for measurement.

I am getting geared up to try an HBr run.

Thank you for the information. So does anyone have any idea what could have separated out of these HI attempts? After basifying, then separating, then washing with water, my solvent layer contains a dark red oil that can be isolated through vaccuum distillation or rotovapping. It doesn't contain I2 because by the final wash the separation between aqueous and organic is perfect (I2 would wash into water right?)

I need to get set up for TLC on this stuff until I can get NMR.

I'd like to post all my notes and pictures of the glass rig, but I'm a bit nervous about that. I'm using a proxy for everything on this forum but who knows who is lurking here. Would you all agree my nervousness is justified?


-pbinteger.

Iodine Solubility. http://en.wikipedia.org/wiki/Iodine#Solubility
Being a nonpolar molecule, iodine is highly soluble in nonpolar organic solvents, including ethanol (20.5 g/100 ml at 15 °C, 21.43 g/100 ml at 25 °C), diethyl ether (20.6 g/100 ml at 17 °C, 25.20 g/100 ml at 25 °C), chloroform, acetic acid, glycerol, benzene (14.09 g/100 ml at 25 °C), carbon tetrachloride (2.603 g/100 ml at 35 °C), and carbon disulfide (16.47 g/100 ml at 25 °C).[27] Elemental iodine is poorly soluble in water, with one gram dissolving in 3450 ml at 20 °C and 1280 ml at 50 °C. Aqueous and ethanol solutions are brown reflecting the role of these solvents as Lewis bases. Solutions in chloroform, carbon tetrachloride, and carbon disulfide are violet, the color of iodine vapour.

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Hydrobromic acid has a pKa of -9, making it a stronger acid than hydrochloric acid, but not as strong as hydroiodic acid (pKa of  ~ –9 (approximate, in water, see leveling effect), pKa of 2.8 (in acetonitrile).

The larger the value of pKa, the smaller the extent of dissociation. A weak acid has a pKa value in the approximate range -2 to 12 in water. Acids with a pKa value of less than about -2 are said to be strong acids; a strong acid is almost completely dissociated in aqueous solution, to the extent that the concentration of the undissociated acid becomes undetectable. pKa values for strong acids can, however, be estimated by theoretical means or by extrapolating from measurements in non-aqueous solvents in which the dissociation constant is smaller, such as acetonitrile and dimethylsulfoxide. http://en.wikipedia.org/wiki/Acid_dissociation_constant

Leveling effect or solvent leveling refers to the effect of solvent on the properties of acids and bases. The strength of a strong acid is limited ("leveled") by the basicity of the solvent.
Ionization of acids is less in an acidic solvent than in water. For example, hydrogen chloride is a weak acid when dissolved in acetic acid. This is because acetic acid is a much weaker base than water.
http://en.wikipedia.org/wiki/Acid_dissociation_constant#Acidity_in_nonaqueous_solutions

Hydrobromic acid. http://en.wikipedia.org/wiki/Hydrobromic_acid
Hydroiodic acid. http://en.wikipedia.org/wiki/Hydrogen_iodide
Leveling effect. http://en.wikipedia.org/wiki/Leveling_effect
Acid dissociation constant. http://en.wikipedia.org/wiki/Acid_dissociation_constant

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Bromosafrole & Iodosafrole Experiment.

(1a) Add 10mls of 47% w/w Hydrobromic acid in a 50ml flask, and cool to 1-2 oC. Add 1ml of safrole, stopper, and swirl. Do not shake.
(1b) Add 10mls of 47% w/w Hydroiodic acid in a 50ml flask, and cool to 1-2 oC. Add 1ml of safrole, stopper, and swirl. Do not shake.

Keep 1a & 1b at 1-2 oC for 12 hours, swirling every 3 hours.


To LIMIT the Hydrobromic acid and Hydroiodic acid strength (their pKa) we use Glacial Acetic Acid as the solvent. THIS SHOULD BE DONE BY DISSOLVING HBr GAS AND HI GAS IN GAA.

(2a) Add 100mls of Glacial Acetic Acid and 10mls of 47% w/w Hydrobromic acid in a 200ml flask, and cool to 1-2 oC. Add 1ml of safrole, stopper, and swirl. Do not shake.
(2b) Add 100mls of Glacial Acetic Acid and 10mls of 47% w/w Hydroiodic acid in a 200ml flask, and cool to 1-2 oC. Add 1ml of safrole, stopper, and swirl. Do not shake.

Keep 2a & 2b at 1-2 oC for 12 hours, swirling every 3 hours.

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After 12 hours reaction time, work-up flasks 1a-b and 2a-b to extract the Bromosafrole (1a & 2a reaction products) & Iodosafrole (1b & 2b reaction products).

Next post will be to test IF the methylenedioxy ring HAS BEEN CLEAVED??

wait a second...

I kept this reaction REEEALLLLY cold... like -30c. I doubt there was much cleavage with HI at that temperature.  Maybe 1%???

Methylenedioxy ring cleaverage.

Complete Ring cleaverage will result in a Catechol, 1,2-dihydroxybenzene (http://en.wikipedia.org/wiki/Catechol) while partial results in Guaiacol (http://en.wikipedia.org/wiki/Guaiacol).

Both are related to phenol, and therefore share some similar aromatic acid properties.

THE ACIDITY OF PHENOL. http://www.chemguide.co.uk/organicprops/phenol/acidity.html Phenol reacts with sodium hydroxide solution to give a colourless solution containing sodium phenoxide.


Refs on cleaverage.

http://www.erowid.org/archive/rhodium/chemistry/eugenol.mdma.html

http://www.ncbi.nlm.nih.gov/pubmed/8004695

http://onlinelibrary.wiley.com/doi/10.1002/chin.199443063/abstract;jsessionid=F672F81DDBF11F2F46FACD1C37212E7D.d04t01?deniedAccessCustomisedMessage=&userIsAuthenticated=false

The Reaction of Safrole Derivatives with Aluminum Chloride: Improved Procedures for the Preparation of Catechols or their mono-O-Methylated Derivatives and a Mechanistic Interpretation. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532001000300005

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Testing Reagents for Phenols and related compounds.

Basic solutions of catechol react with iron(III) to give the red [Fe(C6H4O2)3]^3-. Ferric chloride gives a green coloration with the aqueous solution, whilst the alkaline solution rapidly changes to a green and finally to a black colour on exposure to the air. http://en.wikipedia.org/wiki/Catechol#With_metal_ions

Tests for Phenols and Nitro Groups. http://www.wellesley.edu/Chemistry/chem211lab/Orgo_Lab_Manual/Appendix/ClassificationTests/phenol_amine_nitro.html

Iron(III) chloride is sometimes known as ferric chloride.

Iron(III) ions form strongly coloured complexes with several organic compounds including phenol. The colour of the complexes vary from compound to compound. The reaction with iron(III) chloride solution can be used as a test for phenol. If you add a crystal of phenol to iron(III) chloride solution, you get an intense violet-purple solution formed.

Note:  The test is often done using "neutral" iron(III) chloride solution. Dilute ammonia solution is added dropwise to iron(III) chloride solution to give a faint precipitate of iron(III) hydroxide. Then that precipitate is removed by adding a small amount of the original iron(III) chloride solution.

http://www.chemguide.co.uk/organicprops/phenol/other.html

Vogel, 5th edition, page 1212 - 1213 for phenol. Enol page 1213 - 1214.


Phenolic compounds with a substituent in the para position may not quantitatively produce color with 4-aminoantipyrine. However, para substituents of phenol such as carboxyl, halogen, hydroxyl, methoxyl, or sulfonic acid groups do produce color with 4-aminoantipyrine. http://www.astm.org/Standards/D1783.htm

www.jbc.org/content/72/2/649.full.pdf
www.jbc.org/content/71/2/445.full.pdf

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In conclusion...

(1) Control: Add 1 drop of safrole to Phenol test reagent. Observe colour and any precipitation.

(2) Flasks of synthesised Bromosafrole & Iodosafrole are diluted with ether and extracted with a dilute sodium hydroxide solution. This will result in a sodium phenoxide with the Catechol, or Guaiacol compounds.

(3) Separate the sodium hydroxide solution layer from the ether/Bromosafrole or Iodosafrole solution and acidify. Solvent extract with fresh (2X) ether, and distill ether off to see what phenol related compounds result.

(4) Test isolated 'phenol related compound' with Phenol test reagent.

but seriously... has anyone here.... other than jon pulled this off and gotten decent yields?

if so, are you willing to share your lab notes?

Also... where is jon -- he hasn't posted anything since September.