Transesterification with vinyl Acetate
3.3 Molecular iodine catalyzed selective acetylation of alcohols with venyl acetate
3.3.1 Molecular Iodine in Organic Synthesis
In recent years molecular iodine has drawn considerable attention as an inexpensive, non- toxic, non-metallic and readily available catalyst for various organic transformations under mild and convenient conditions in excellent yields and with high selectivity.1-36
Das et al. have reported the Cross-Aldol condensation of aromatic aldehydes with cyclic ketones in the presence of catalytic amount of iodine at room temperature which afforded α,α'-bis(substituted-benzylidene) cycloalkanones in high yields.37
Chu et al. have described a simple and efficient method for the Michael reaction between various mercaptans and α,β-unsaturated Ketones 6 using a catalytic amount of iodine to generate the 1,4-adduct 7 (Scheme 3.8)38.
R R
R R
O
R R
R SR
O
R
+
3
1 2 R4SH
I2 (5 mol%)
neat 1 2 4
3
R1 = R2 = R3 = R4 = alkyl, aryl, H
6 7
Scheme 3.8
Karade et al. have reported the roll of molecular iodine as efficient co-catalyst for the facile oxidation of alcohols with hypervalent(III)iodine.39 Yadav and coworkers have reported that the molecular iodine efficiently catalyzes the allylation of both aromatic and aliphatic aldehydes 8 with allyltrimethylsilane 9 in MeCN at 0 oC to afford the corresponding homoallyl alcohols 10 in high yields in a short reaction time (Scheme 3.9).40
R H
O SiMe3 I2 (Cat.)
R OH Acetonitrile, 0 oC
+
8 9 10
Scheme 3.9
Karimi et al have described the deoxygenation of a variety of alkyl and aryl sulfoxides using
Part I Chapter III
3- mercaptopropionic acid as a reducing agent and a catalytic amount of either I2 (5-10 mol%) in MeCN at ambient temperature.41 Saikia and coworkers have reported the regioselective 1,2-hydroxy and methoxy iodination of alkenes 11 by molecular iodine and aqueous hydrogen peroxide(30%). When acetonitrile is used as the solvent, hydroxyiodoalkane was obtained. On the other hand, when methanol was used as the solvent, methoxyiodoalkane was observed (Scheme 3.10).42
R R
I2/aq.H2O2 MeOH or CH3CN / r.t
R R
OR
I
R1 = R2 = H, alkyl, aryl
1 2 1 2
3
11 (12) R3 = H
(13) R3 = Me
Scheme 3.10
Rungnapha et al. have reported a convenient method for C-glycosidation (alkynylation) with various silylacetylenes 15 to D-glucal 14 by iodine molecule via iodo–oxonium intermediates provided exclusively the α-acetylene glycoside products 16 (Scheme 3.11).43
OAc O OAc
OAc
Me3Si R I2 CH2Cl2
OAc O OAc
OAc R
+
14 15 16
Scheme 3.11
Takasu et al. have reported the synthesis of medium-sized cyclic -haloketones by radical mediated ring-opening reaction of molecular iodine catalyzed (2+2)- cloaddition products.44 Banik et al.a remarkably simple molecular iodine-catalyzed protection method for various carbonyl compdounds as ketals 17 (Scheme 3.12).45
Deka et al. have reported the microwave-assisted selective monotetrahydropyranylation of
Results and discussion Part I Chapter III
R' R''
O
R' R''
O O O
H OH
I2 (5 mol %)
R' = R'' = alkyl, aryl, H 17
Scheme 3.12
symmetrical diols catalyzed by iodine.46 Yadav and coworkers have reported the chemoselective hydrolysis of terminal isopropylidene acetals 18 in acetonitrile using molecular iodine as a mild and efficient catalyst (Scheme 3.13)47
O O
O
O O OMe
O O
O H
O
H O OMe
30 mol% I2/acetonitrile r.t, 2h
18 19
Scheme 3.13
Kaimal and his group have reported that transesterification of alcohols can be performed with esters in the presence of molecular iodine at reflux (Scheme 3.14).48
+ +
Where R = R' = H, alkyl, aryl R'' = R''' = alkyl, aryl R
OH
R' R
O
R'
R'''OH
R'' OR'''
O R''
O I2
Scheme 3.14
3.3.2 Results and discussion:
Molecular iodine is found to catalyze the acetylation of alcohols with vinyl acetate effectively. We argued that if the carbonyl group and double bond of vinyl acetate was activated by iodonium ions and simultaneously reacted with a nucleophile, acetylated products would be obtained in shorter times under this reaction conditions. This proved to be the case when benzyl alcohol and the vinyl acetate were stirred at room temperature with a
Results and discussion Part I Chapter III
catalytic amount of molecular iodine (10 mol%) yields the corresponding acetate in good yield (Scheme 3.15).49
R R'
OH
OAc
R R'
OAc
CH3CHO +
I2 / rt
+ R = R' = alkyl,aryl,H
Scheme 3.15
In order to evaluate the efficiency of iodine, the generality of the reaction studied using various aliphatic, benzylic and allylic alcohols (Table 3.4). Both primary and secondary alcohols can be converted to the corresponding acetates in good yields. Electron donating groups accelerate the reaction of benzylic alcohols. Sterically hindered secondary alcohols (entries 11, 12 & 13) can also be acetylated in good yields. Entries 10 and 13 witness the mildness of this method towards acid sensitive groups. Phenols give only trace amounts of acetylated products and therefore alcohols can be chemo selectively acetylated (entries 14 and 15). Tertiary alcohols were found to react slowly under these reaction conditions. Tertiary butyl alcohol gave only an 18% yield after a prolonged reaction time (24 h) while the tertiary benzylic alcohol (entry 17) remained unreacted. The reaction completed quickly when carried out neat. It also worked well in solvents such as toluene and THF, but takes longer times.
Thus, reaction of menthol completed within 4.5 h with 94% yield when carried out in 4 equivalents of vinyl acetate. On the other hand the same reaction took 13 h to complete when carried out in THF giving 92% yield. Interestingly, no iodo product was observed in the case of olefinic substrates (entries 4 and 9). The advantage of this reaction is that like acetic anhy- dride or acetyl chloride it does not generate any acidic waste, as a result the reaction medium is neutral. The only by-product, acetaldehyde can be removed by evaporation.
Results and discussion Part I Chapter III
Table 3.4: Acetylation of alcohols with vinyl acetate using molecular iodine
OH OAc
MeO
OH
MeO
OAc
O2N
OH
OH
OH
OH
14
OH
O2N
OAc
OAc
OAc OAc
OH OAc
OAc
14
OH
8
OH
8
O O
OH
O O
OAc
1
2 3 4 5 6
8
97
93
4 4.5 96
4 Substrate
Entry Time / h Product Yield(%)
89
93 91
89 4
1.5 6
4.5
98
4
7 4 91
9
7 87
10
aYield refers to isolated yield. The compounds are characterized by 1H NMR,13C and IR spectroscopy and comparison with the literature.
Results and discussion Part I Chatper III
OH
OH
O H
OH
OAc
OAc
O H
OAc
OAc O
O
O H
H H
H H
H
O O
AcO
H H
H H
H
OH O
H
OH
O H
OAc
OH OAc
92
12
16
2
78 93
4.5
Trace 14
5
4
95
3
12 11
13
14
15
17 0
94
Entry Substrate Time(h) Product Yield (%)a
aYield refers to isolated yield. The compounds are characterized by 1H NMR,13C and IR spectroscopy and comparison with the literature.