New reagents 31a,b: aluminium iodide, a highly regioselective ether-cleaving reagent with novel cleavage patternMV 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.
6,7,8The 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
| |
Ph-|-O---CH2-CH2---O-|-Me
| |
AlI3 -> | | <- BCl3, BBr3,
| | Cl3SiI, Me3SiI
Table I - Cleavage of PhOCH2CH2OMe with various reagents
+-------+----------------+-------------+----------+-------------------------------+
|REAGENT| MOLE RATIO | TIME (HR)/ | SOLVENT | PRODUCTS ISOLATED YIELD (%) |
| | 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
/NaI
SiCl4 1:1 16/25 MeCN/ traces 75 6
/NaI CH2Cl2
(1:1)
+-------+----------------+-------------+----------+---------+-------------+-------+
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
ENTRY SUBSTRATE SUBSTRATE: PRODUCT SOLVENT TIME OF YIELD(%)
REAGENT SYSTEM REFLUX (HR)
RATIO
----------------------------------------------------------------------------------------
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%).
References
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Acknowledgements - The authors wish to express their appreciation to CSIR for funding this project.