Author Topic: Aluminium iodide in ether cleavage  (Read 13046 times)

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Aluminium iodide in ether cleavage
« on: March 31, 2003, 07:33:00 AM »
New reagents 31a,b: aluminium iodide, a highly regioselective ether-cleaving reagent with novel cleavage pattern

MV Bhatt, JR Babu
Tetrahedron Letters 25(32) (1984) 3497-3500

Abstract - AlI3 is an easily accessible and versatile ether-cleaving reagent.

Article - Boron and silicon halides have been widely used for the cleavage of dialkyl and aryl alkyl ethers. 1a,b,2,3,4 Although AlCl3 5 has been employed for the cleavage of certain types of ethers, its usefulness for ether cleavage is rather limited. Brief reports on the ether-cleaving property of AlBr3 and AlI3 have not been followed up to explore the full synthetic potential of these reagents.6,7,8
The Lewis acid strenght of aluminium halides increase in the order 9: AlCl3 < AlBr3 < AlI3. One could expect AlI3 to be a highly reactive reagent.

Inverse reactivity pattern - In CH3CN, AlI3 cleaves aromatic aliphatic ethers much faster than dialkyl ethers. For example, anisole is cleaved in 12 hr at 80°C, whereas cyclohexyl methyl ether requires 52 hr under the same conditions. This is further illustrated in the case of 1-methoxy-2-phenoxy ethane. We find AlI3 alone gives phenol, whereas other reagents give 2-phenoxy ethanol (see Table I). This behaviour of AlI3 is in contrast to the normal reactivity pattern of silicon and boron reagents (Scheme I).

Scheme I

             |                 |
             |                 |
     AlI3 -> |                 | <- BCl3, BBr3,
             |                 |    Cl3SiI, Me3SiI
Table I - Cleavage of PhOCH2CH2OMe with various reagents

|       | SUBSTR:REAGENT |  TEMP (°C)  |          |   PhOH  | PhOCH2CH2OH |SUBSTR |
  AlI3         1:1              4/82      MeCN       75.07        -           -
  BCl3         3:1             15/65      CHCl3      traces      47          25.4
  BCl3         1:1             11/65      CHCl3        33        58.7         -
  BBr3         3:1             22/25      CH2Cl2     traces      44.3        19.04
  Me3SiCl      1:1             12/25      MeCN       traces      55.1        33.5
  SiCl4        1:1             16/25      MeCN/      traces       75           6
  /NaI                                    CH2Cl2

Novel solvent effects - Another noteworthy feature is that the rates of cleavage of certain ethers are reversed in CS2 and in CH3CN. 1,3-benzodioxole (0.5 hr) and o-dimethoxybenzene (0.5 hr) are cleaved faster than anisole (12 hr) in CH3CN whereas the reverse is observed in CS2 (see Table II).
In CS2 and in C6H6 secondary alkyl groups, after they are converted to the corresponding iodides during ether cleavage undergo isomerization to give a mixture of products. This does not take place in CH3CN medium in which even labile ether like allyl phenyl ether gives phenol and allyl iodide. No ring alkylation products could be detected (see Table II, entry 3)

Table II - Cleavage of ethers with AlI3

                    REAGENT                       SYSTEM         REFLUX (HR)

1. anisole             1:1          phenol           A              12             94
                       1:1          phenol           B               1             90.3
                       1:1          phenol           C               1.5           90.4
2. p-dimethoxy-        1:1       4-MeO-phenol        C               3             74.2
   benzene             2:1       hydroquinone        C               4             85
3. allyl phenyl        1:1       o-allylphenol       C               d             26
   ether                         phenol                                             4.5
                       1:1          phenol           A               5             89
4. 1,3-benzo-          1:1         catechol          A               0.5           70.5
   dioxole             2:1         catechol          B               5.5           68.0
                       2:1         catechol          C               7             80
7. o-dimethoxy-        3:1         catechol          C              19             84
   benzene                         guaiacol                                         2
                       2:1         catechol          B               7.5           91
                       1:1         catechol          A               0.75          80
9. tetrahydro-         1:1       4-iodobutanol       A               5             70
   furan                        1,4-diiodobutane                                    5.8

Solvent system: A = CH3CN, B = benzene, C = CS2.
d = 3.5 hours at ca -70°C

Preparation of AlI3 - Dry aluminium foil (250 mg, 9.3 mmol) and iodine (1.9 g, 15 mmol) were refluxed in dry CS2 (10 mL) or dry CH3CN (8 mL) till the iodine colour disappeared (ca 3 hours).

Cleavage of 1,3-benzodioxole in CS2 - To a freshly prepared solution of AlI3 (10 mmol) in CS2, 1,2-benzodioxole (610 mg, 5 mmol) in CS2 (2 mL) was added and refluxed till there was no more starting material (7 hours, TLC). The cooled reaction mixture was decomposed with ice, extracted with ether and washed with thiosulphate solution. The thiosulphate solution was extracted once again with ether and the combined ether extract was dried over anhydrous MgSO4. The solvent was removed and the product was chromatographed (TLC silica gel, 3:1 hexane:EtOAc) to obtain catechol, 440 mg (80%), mp 106°C (Lit 10 mp 104.8-105.8°C).

Cleavage of allyl phenyl ether in CH3CN - To a freshly prepared solution of AlI3 (5 mmol) in CH3CN, allyl phenyl ether (670 mg, 5 mmol) in CH3CN was added and the concentration of the solution was adjusted to ca 1 M with respect to both reagent and reactant. The reaction mixture was refluxed till there was no more starting material (5 hours, TLC), cooled and poured into water. The mixture was extracted with ether and the aqueous extract was washed with 5% NaOH solution. After acidification of the alkaline aqueous solution, it was extracted into ether, dried over anhydrous MgSO4 and the solvent was removed. The crude product after short path distillation yielded phenol; 418 mg (89%).

1a. MV Bhatt, J Organomet Chem 156, 221 (1978)
1b. MV Bhatt e.a., Synthesis 1048 (1982)
2. for a recent review, see "Cleavage of ethers". MV Bhatt e.a., Synthesis 249-282 (1983)
3. ME Jung e.a., JOC 42, 3761 (1977); Synthesis 588 (1978); Tetrahedron Lett 3657 (1978)
4. GA Olah e.a., JOC 44, 1247 (1979); TL Ho e.a., Angew Chem 88, 847 (1976); Angew Chem Int Edn Eng 15, 774 (1976)
5. C Hartmann e.a., Ber 25, 3531 (1892)
6. P Pfiffer e.a., J prakt Chem NF 147, 293 (1937)
7. E Mincione, Ric Sci 39, 424 (1969)
8. S Cabiddu e.a. Ann di Chim 62, 505 (1972)
9. DPN Satchell e.a., Chem Rev 69, 251 (1969); JKM Divitt e.a., Spectrochim Acta 30, 1021 (1974)
10. JJ Lander e.a., JACS 67, 322 (1945)

Acknowledgements - The authors wish to express their appreciation to CSIR for funding this project.


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Eugenol Demethylation & Other Ether Cleavages
« Reply #1 on: July 12, 2004, 11:07:00 AM »
Conception, Characterization and Correlation of New Marine Odorants
Philip Kraft, Walter Eichenberger

European Journal of Organic Chemistry, No. 19, pp. 3735-3743 (2003)


[...] In the next step, the methyl ether protecting groups of 5,6-dimethoxy-1-methylindane (10) had to be cleaved. For this we decided to employ trimethylsilyl iodide (TMSI)7 in acetonitrile.8 The cleavage of 10 with TMSI was conducted at room temp. to afford after the usual workup and purification by silica-gel FC in 93% yield 1-methylindan-5,6-diol (11). This diol 11 had already been reported by Ayer and Singer9 as the unintended product of an attempt to correlate 4-(3,4-dihydroxyphenyl)butan-2-one with zingerone (vanillyl acetone) by demethylation of the latter with TMSI. Yet, the reported yield was only about 30%, and the synthesis is less practical and less generally applicable than our approach. The spectroscopic data of 11 prepared on our route matched with those reported by Ayer and Singer.9

[...] The allyl analogue 27 was synthesized from eugenol by cleavage of the phenolic methyl ether group employing lithium chloride in refluxing DMF according to a method of Piras and co-workers.20 4-Allylpyrocatechol was obtained in 50% yield after 44 h reaction time, usual workup and purification by silica-gel FC.


Demethylation of 5,6-dimethoxy-1-methylindane (10) with TMSI

At room temp. under N2, Me3SiI (TMSI, 27.5 mL, 202 mmol) was added dropwise with stirring in the course of 90 min into a solution of 10 (19.4 g, 101 mmol) in MeCN (150 mL). Stirring was continued at room temp. for 2.5 days, with an additional quantity of Me3SiI (TMSI, 10.0 mL, 73.5 mmol) being added after 48 h. The reaction mixture was poured into water (500 mL), and extracted with Et2O (2 × 200 mL). The combined extracts were washed with 40% aq. NaHSO3 (100 mL), water (100 mL) and brine (50 mL), dried (Na2SO4) and concentrated in a rotary evaporator. Silica-gel FC (pentane/Et2O, 2:1, Rf = 0.28) furnished 1-methylindan-5,6-diol (11, 15.5 g, 93%), the spectroscopic data of which matched with those reported9.

Demethylation of Eugenol to 4-allylpyrocatechol with LiCl/DMF

LiCl (292 g, 6.89 mol) was added to a solution of eugenol (354 mL, 2.30 mmol) in DMF (3.7 L), and the mixture was refluxed for 44 h, with additional portions of LiCl (292 g, 6.89 mol) being added after 4 h, 22 h and 29 h. The reaction mixture was allowed to cool down to room temp., and diluted with toluene (2 L). The formed precipitate was filtered off and washed with toluene, the washings were combined with the organic solution and concentrated in a rotary evaporator. Silica-gel FC (Et2O/pentane, 1:1, Rf = 0.37) provided 4-allylpyrocatechol (173 g, 50%).


Quantitative dealkylation of alkyl ethers via treatment with trimethylsilyl iodide. A new method for ether hydrolysis.
Jung, Michael E.; Lyster, Mark A.

Journal of Organic Chemistry 42, 3761-4 (1977)


PhOMe was kept 21 h at 50° in CDCl3 containing a 0.3-fold molar excess of Me3SiI to give 100% PhOSiMe3 and 100% MeI. The cleavage of 25 other ethers is reported under these conditions. Me3SiI is prepared by refluxing (Me3Si)2O with Al and I. The mechanism of the ether cleavage is discussed.
____ ___ __ _

Synthetic methods and reactions. 62.
Transformations with chlorotrimethylsilane/sodium iodide, a convenient in situ iodotrimethylsilane reagent.

Olah, George A.; Narang, Subhash C.; Gupta, B. G. Balaram; Malhotra, Ripudaman

Journal of Organic Chemistry 44, 1247-51 (1979)


A new, convenient, inexpensive alternative to Me3SiI reagent is explored. A mixture of Me3SiCl-NaI in MeCN is a better reagent than Me3SiI for the cleavage of esters, lactones, carbamates and ethers. Cleavage of esters and lactones (10 examples) occurred somewhat slower with the present system than with Me3SiI. On the other hand, ethers (7 examples) cleaved much more readily with the present system. A feasible mechanism is proposed for this disparity. Carbamates (6 examples) also underwent facile cleavage to give the corresponding amines. The general applicability of the method was shown using various types of substrates. The facile conversion of alcs. to iodides using the present method is also reported. Conversion of alcs. to iodides is much faster with Me3SiCl-NaI than with Me3SiI, and iodides are formed in excellent yield.
____ ___ __ _

Phenolic metabolites of the bird's nest fungus Nidula niveo-tomentosa
William A. Ayer and Peter P. Singer, Phytochemistry 19(12), 2717-2721 (1980)


The metabolites of the bird's nest fungus Nidula niveo-tomentosa have been examined. Niduloic acid (3-hydroxy-5-(p-hydroxyphenol) pentanoic acid) is a new natural product. 4-(p-Hydroxyphenyl)-2-butanone, 4-(p-hydroxyphenyl)-2-butanol, trans-4-p-hydroxyphenylbut-3-en-2-one, 4-(3?,4?-dihydroxyphenyl)-2-butanol, 4-(3?,4?-dihydroxyphenyl)-2-butanone, zingerone 3-(p-hydroxyphenyl)-1,2-propanediol are also metabolites of this fungus. An interesting reductive cyclization of zingerone, effected by iodotrimethylsilane, is reported.
____ ___ __ _

Dealkylation of Activated Alkyl Aryl Ethers Using Lithium Chloride in Dimethylformamide
Angela M. Bernard, M. Rossella Ghiani, Pier Paolo Piras, Antonio Rivoldini

Synthesis 287-289 (1989)


Alkyl aryl ethers having electron-withdrawing substituents in the ortho or para positions are easily cleaved with lithium chloride in dimethylformamide.
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Post 444300 (missing)

(Lego: "Dealkylation with LiCl/DMF", Methods Discourse)