International Journal of Organic Chemistry, 2011, 1, 233-241
doi:10.4236/ijoc.2011.14034 Published Online December 2011 (http://www.SciRP.org/journal/ijoc)
233
Rate Enhancements in the Acetylation and Benzoylation of
Certain Aromatic Compounds with Vilsmeier-Haack
Reagents Using Acetamide, Benzamide and Oxychlorides
under Non-Conventional Conditions
Marri Venkateswarlu, Kamatala Chinna Rajanna*, Mukka Satish Kumar,
Utkoor Umesh Kumar, Soma Ramgopal, Pondichery Kuppuswamy Saiprakash
Department of C hemi st ry , Osmania University, Hyderabad, India
Received August 8, 2011; revised September 21, 2011; accepted October 3, 2011
Abstract
Acetylation and benzoylation reactions of certain aromatic aldehydes, ketones with Vilsmeier-Haack Re-
agents using Acetamide and Oxychloride (SOCl2 or POCl3) under conventional (thermal) and non conven-
tional [microwave irradiated (MIR), ultrasonic assisted and solvent free mortar pestle (grinding)] conditions.
Reactions afforded good to excellent yields of products with both the VH reagents, reaction times were fairly
less in the case of [amide/POCl3] than those of [amide/SOCl2] reagent. Reactions are dramatically acceler-
ated in under sonicated and microwave irradiations with a trend: MIR (few seconds) >> Sonication (minutes)
> Grinding (min) >> thermal (several hrs).
Keywords: Acetylation, Benzoylation, Vilsmeier-Haack Reagent (VHR), Acetamide, Benzamide,
Micro Wave Irradiation, Grinding, Sonication
1. Introduction
Acetylation (or ethanoylation in IUPAC nomenclature) des-
cribes a reaction that introduces an acetyl functional
group into a chemical compound, while benzoylation
introduces a benzoyl group into an organic compound.
These reactions are included in the category of the most
important transformations in Organic Synthesis [1-3]. A re-
action involving the replacement of the hydrogen atom
of a hydroxyl group with an acetyl group (CH3 CO) yie-
lds a specific ester, the acetate. Acetylation is one of the
principal metabolic pathways of the sulfonamides. It is
also one of the important synthetic bio-transformations
which operate in the metabolism of drugs in which me-
tabolites are produced that are more readily excreted than
the parent drug. However, dogs are exceptional amongst
the domesticated species in that acetylation does not oc-
cur in their tissues. Acetylation of the N-terminal alpha-
amine of proteins is a widespread modification in eukar-
yotes. Forty to fifty percent of yeast proteins and be-
tween 80% to 90% of human proteins are modified in
this manner. The pattern of modification is found to be
the same throughout evolution.
Among the various protecting groups used for the hy-
droxyl group, acetyl is one of the most common groups,
being stable in the acid reaction conditions and also eases
of removal by mild alkaline hydrolysis [1,2]. The most
commonly used reagent combination for this reaction
uses acid anhydride in the presence of acid or base cata-
lysts [3]. Various metal salts [4-16] such as CoCl2, TiCl4-
AgClO4, TaCl5, TaCl5-SiO2, Ce(III) triflate, Sn(IV) por-
phyrine and some metal triflates [17-21] such as Sc
(OTf)3, MeSiOTf, In(OTf)3, Cu(OTf)2 and Bi(OTf)3,
bis(cyclopentadienyl) zirconium dichloride [22], I2 [23],
1,3-dibromo-5,5-dimethylhydentoin or trichloroisocya-
nuric acid [24] have been investigated to meet the de-
mand for more efficient and selective methods.
Benzoylation reaction is generally carried out using
benzoyl chloride with a Lewis acid as the benzoylating
agent. In addition to benzoyl chloride [1-2], a number of
reagents [25-29] such as, benzoic anhydride, benzoy-
ltetrazole, 2-benzoyl-1-methylpyridinium chloride, S-ben-
zoic-O,O-diethylphosphoro-dithoic anhydride, benzoyl
cyanide, can be used for carrying out this reaction. Though
benzoyl chloride may be a health hazard due to its toxic-
ity, nevertheless it is widely used because of its ready

M. VENKATESWARLU ET AL.
234
availability and low cost. The reaction is usually cata-
lyzed by bases like pyridine, triethylamine and sodium
hydroxide [30-31]. Recently Satya Paul et al. [32] de-
veloped a rapid, economic and environmentally friendly
method for benzoylation of -NH2, -OH and -SH groups
using PhCOCl-Py/basic alumina. The developed reagent
system was found to a good alternative to classical
method since the benzoylation underwent expeditiously
with high yields under solvent-free conditions.
Vilsmeier-Haack reagent (VH) is one of the most ef-
ficient synthetic organic reagents for formylation and
acetylation reactions. VH reagents could be prepared fo-
rm equimolar mixture of formamide or N, N’-dialkyl for-
mamides such as N, N’-dimethyl formamide (DMF), N,
N’-diethyl formamide (DEF), along with oxy halides
such as POCl3 and SOCl2 at freezing temperatures. Recent
reports on Vilsmeier-Haack (VH) reactions revealed that
organic compounds in general and hydrocarbons with
excess pi-electrons in particular undergo formylation
very easily on synthetic scale [33-49]. However, these re-
actions are known to afford acetyl derivatives when N,
N’-dialkyl formamides are replaced by acetamide or N,
N’-dialkyl acetamides such as N, N’-dimethyl acetamide
(DMA) and N, N’-diethyl acetamide (DEA) in VH re-
agent. However, not many systematic reports are pub-
lished in this direction. In view of this the author has em-
barked on a systematic synthetic study of certain VH
acetylation and benzoylation reactions using (Acetamide
+ SOCl2)/(Acetamide + POCl3) or (Benzamide + SOCl2)/
(Benzamide + POCl3) as VH regents. A set of organic
compounds such as aldehydes and ketones are used in
these studies, which have been found their importance in
a number of industrially important and biologically im-
portant reactions.
2. Experinental Details
2.1. General Procedure for Preparation of
Vilsmeier-Haack Reagent
The Vilsmeier Haack (VH) adduct is prepared afresh be-
fore use from SOCl2 and acetamide (ACTAM). To a
chilled (at –50˚C) actamide (ACTAM) in dichloro ethane
(DCE) or acetonitrile (ACN), calculated amount of PO-
Cl3 was slowly added drop wise to get VH reagent and
stored under cold conditions. Similar procedure is ado-
pted for the preparation of VH reagent with Benzamide
(BNZAM).
2.2. General Procedure for Vilsmeier-Haack
Synthesis in Reflux Condition
A centimolar (0.01 mol) organic substrate (aromatic al-
dehydes, ketones), about 0.015 moles of VH reagent and
solvent DCE were taken in a cleaned in a Round bottom
flask and refluxed till the reaction is completed. After
completion of the reaction, as confirmed by TLC, the
reaction mixture is treated with 5% sodium thio sulphate
solution, followed by the addition of pet ether. The or-
ganic layer was separated, dried over Na2SO4 and evapo-
rated under vacuum, purified with column chromatogra-
phy using DCE: n-hexane (8:2) as eluent to get pure pro-
duct. This methodology has also been successfully used
for ACN mediated reactions. This methodology has been
successfully is adopted for CAN mediated reactions. The
yields of major products are compiled in Tables 1 to 4.
2.3. General Procedure for Vilsmeier-Haack
Synthesis under Solvent Free Conditions by
Grinding in Mortar with Pestle
A centimolar (0.01mol) organic substrate (aldehydes, ke-
tones or acetophenone), and about 0.015 moles of VH
reagent were taken in a previously cleaned mortar and
grounded till the reaction is completed. After completion
of the reaction, as checked by TLC, the reaction mixture
is treated with 5% sodium thio sulphate solution, fol-
lowed by the addition of pet ether. The organic layer was
separated, dried over Na2SO4 and evaporated under vac-
uum, purified with column chromatography using DCE:
n-hexane (8:2) as eluent to get pure product. The yields
of major products are given in Tables 1 to 4.
2.4. General Procedure for Sonicated
Vilsmeier-Haack Synthesis
A centimolar (0.01mol) organic substrate (aldehydes, ke-
tones or acetophenone), about 0.015 moles of VH re-
agent and solvent DCE were taken in a cleaned in a
Round bottom flask and clamped in a sonicator and pro-
gress of the reaction is monitored by TLC. After comple-
tion of the reaction, as ascertained by TLC, the reaction
mixture is treated with 5% sodium thio sulphate solution,
followed by a the same work-up procedure as mentioned
the above section to get the final product. This method-
ology has also been successfully for ACN mediated reac-
tions. The yields of major products are shown in Tables
1 to 4.
2.5. General Procedure for MW Irradiated
Vilsmeier-Haack Synthesis
Methodology adopted for MW assisted VH synthesis is
almost similar to that used in the above section. A cen-
timolar (0.01 mol) organic substrate (aldehydes, ketones
or acetophenone), about 0.015 moles of VH reagent and

M. VENKATESWARLU ET AL.
235
Table 1. VH acetylation reactions with (Acetamide + SOCl2) and carbonyl compounds.
Thermal (Room temp) Grinding (Solvent free)Sonication Microwave (300 watt)
Entry Substrate
RT (hrs) Yield (%)RT (min)Yield (%)RT (min)Yield (%) RT (sec) Yield (%)
1 Benzaldehyde 13 68 120 70 90 65 200 70
2 Salicyl adehyde 13 70 140 75 90 78 200 75
3 4-OH benzaldehyde 11 80 110 83 90 79 180 80
4 4-OMe benzaldehyde 12 64 110 63 90 67 200 68
5 4-Cl benzaldehyde 11 67 100 63 90 67 200 65
6 4-Br benzaldehyde 12 7 110 69 90 63 200 77
7 4-NO2 benzaldehyde 11 78 110 80 90 78 190 82
8 Cinamaldehyde 13 69 130 70 90 69 200 73
9 Acetophenone 12 76 110 73 90 80 190 77
10 2-OH acetophenone 11 78 110 80 90 76 190 81
11 4-OH acetophenone 11 69 110 74 90 71 200 68
12 4-Me acetophenone 10 64 140 61 90 66 200 65
13 3-OH acetophenone 11 69 110 73 90 71 200 71
14 4-Br acetophenone 13 65 110 69 90 66 200 64
15 4-NO2 acetophenone 12 85 100 80 90 79 180 81
Table 2. VH acetylation reactions with (Acetamide + POCl3) and carbonyl compounds.
Thermal (Room temp) Grinding (Solvent free)Sonication Microwave (300 watt)
Entry Substrate
RT (hrs) Yield (%)RT (min)Yield (%)RT (min)Yield (%) RT (sec) Yield (%)
1 Benzaldehyde 11 69 120 70 90 65 200 70
2 Salicyladehyde 12 70 140 75 90 78 200 75
3 4-OH benzaldehyde 11 83 110 80 90 80 180 79
4 4-OMe benzaldehyde 12 67 110 68 90 67 200 68
5 4-Cl benzaldehyde 11 70 100 69 90 70 200 67
6 4-Br benzaldehyde 12 72 110 66 90 63 200 77
7 4-NO2 benzaldehyde 11 79 110 82 90 78 190 82
8 Cinamaldehyde 13 70 130 71 90 73 200 68
9 Acetophenone 12 77 110 74 90 77 190 80
10 2-OH acetophenone 11 76 110 80 90 69 190 81
11 4-OH acetophenone 11 74 110 75 90 71 200 80
12 4-Me acetophenone 12 66 140 65 90 66 200 69
13 3-OH acetophenone 11 68 110 73 90 77 200 71
14 4-Br acetophenone 13 64 110 69 90 68 200 64
15 4-NO2 acetophenone 12 80 100 84 90 79 180 85

M. VENKATESWARLU ET AL.
236
Table 3. VH benzoylation reactions with (Benzamide + SOCl2) and carbonyl compounds.
Thermal (Room temp) Grinding (Solvent free)Sonication Microwave (300 watt)
Entry Substrate
RT (hrs) Yield (%)RT (min)(Yield) (%)RT (min)Yield (%) RT (sec) Yield (%)
1 Benzaldehyde 12 65 120 67 90 62 200 69
2 Salicyladehyde 12 70 110 75 90 76 200 72
3 4-OH benzaldehyde 11 80 110 81 90 79 190 76
4 4-OMe benzaldehyde 13 67 130 63 90 66 200 68
5 4-Cl benzaldehyde 13 63 130 67 90 65 220 62
6 4-Br benzaldehyde 12 70 130 68 90 63 200 72
7 4-NO2 benzaldehyde 11 81 100 80 90 75 180 82
8 Cinamaldehyde 13 62 110 70 90 67 200 71
9 Acetophenone 12 74 110 76 90 80 190 79
10 2-OH acetophenone 12 80 110 78 90 81 190 76
11 4-OH acetophenone 12 71 110 74 90 69 200 72
12 4-Me acetophenone 11 64 140 61 90 66 200 65
13 3-OH acetophenone 11 69 110 73 90 71 200 68
14 4-Br acetophenone 11 68 110 65 90 63 200 64
15 4-NO2 acetophenone 10 85 100 80 90 79 180 81
Table 4. VH benzoylation reactions with (Benzamide + POCl3) and carbonyl compounds.
Thermal (Room temp) Grinding (Solvent free)Sonication Microwave (300 watt)
Entry Substrate
RT (hrs) Yield (%)RT (min)(Yield) (%)RT (min)Yield (%) RT (sec) Yield (%)
1 Benzaldehyde 11 69 120 70 90 65 200 70
2 Salicyladehyde 12 70 140 75 90 78 200 75
3 4-OH benzaldehyde 11 83 110 80 90 80 180 79
4 4-OMe benzaldehyde 12 67 110 68 90 67 200 68
5 4-Cl benzaldehyde 11 75 100 69 90 76 200 74
6 4-Br benzaldehyde 12 76 110 67 90 65 200 77
7 4-NO2 benzaldehyde 11 79 110 82 90 80 190 82
8 Cinamaldehyde 13 73 130 71 90 73 200 75
9 Acetophenone 12 77 110 79 90 77 190 80
10 2-OH acetophenone 11 76 110 80 90 69 190 81
11 4-OH acetophenone 11 75 110 77 90 73 200 80
12 4-Me acetophenone 12 67 140 65 90 68 200 69
13 3-OH acetophenone 11 70 110 74 90 77 200 73
14 4-Br acetophenone 13 69 110 70 90 68 200 67
15 4-NO2 acetophenone 12 81 100 84 90 79 180 84

M. VENKATESWARLU ET AL.
237
solvent DCE were taken in a cleaned in a Round bottom
flask and clamped in a laboratory MW oven. Progress of
the reaction, under micro wave irradiated conditions, is
followed by TLC. After completion of the reaction, as
ascertained by TLC, the reaction mixture is treated with
5% sodium thio sulphate solution, followed by a the
same work-up procedure as mentioned the above section
to get the final product. This methodology has also been
successfully extended for ACN mediated reactions. The
yields of major products are presented in Tables 1 to 4.
2.6. Product Analysis
TLC pure products were characterized by spectroscopic
methods. The melting points were determined on Mettler
FP 51 (Neo Pharma Instrument Corp.) and are not cor-
rected. We have recorded H NMR spectra on a Jeol FX-
90A instrument in chloroform-d using TMS as internal
standard. The mass spectra were recorded on a VG mi-
cromass 70-70H spectrometer. The IR was recorded on a
Nicolet 740 FT-IR spectrometer. The UV was recorded
on Shimadzu-240 UV-Visible spectrophotometer. Spec-
troscopic data for certain representative isolated products
compiled Tables 5 and 6.
3. Results and Discussion
Aromatic compounds such as Benzaldehyde and Aceto-
phenone derivatives underwent acetylation under Vils-
meier-Haack conditions in fairly good to very good
yields when treated with [Acetamide/SOCl2] and [Ace-
tamide/POCl3] respectively under conventional and non-
conventional conditions. However, to check the generali-
ty of the reaction an array of substituted aromatic alde-
hydes and ketones are used as substrates under present
reaction conditions as shown in Scheme 1 . The yields of
major products are compiled in Tables 1 to 4. The pro-
ducts were characterized by 1H-NMR, Mass spectra with
authentic samples and found to be satisfactory. It is of
interest to note that orthohydroxy acetophenone (OHAP)
underwent cyclization followed by acetylation and af-
forded acetyl chromone as described in earlier workers.
However, Meta (MHAP) and para hydroxy acetopheno-
nes (PHAP) did not undergo cyclization but afforded
acetyl derivatives. The difference in the reactivity of
OHAP from MHAP and PHAP could be attributed to the
fact that the -OH group is away from the carbonyl (main)
functional group which is favorable to form a stable ring
through cyclization.
Data for VH synthesis of acetylation/benzoylation re-
actions are presented in tables 1 to 4 and Figures 1 and 2,
which clearly indicate remarkable rate enhancements and
increase in reaction yields from thermal reactions to mi-
crowave assisted reactions with an increasing trend: MIR
>> Sonication >> Grinding (mortar-pestle) > thermal.
Reactions are too sluggish under times in thermal condi-
tions even at elevated temperatures. The reaction times
are in the range of 10 to 12 hours. However, the reactions
are completed only in 100 - 120 min under solvent free
conditions suggesting that the present method could be
employed for small scale. Progress of the reaction under
solvent free conditions might be due to the heat energy
generated from the mechanical energy when the reac-
tionmixture is grounded in the mortar. The yields are
highly superior over corresponding solution phase reac-
tions. Since the reaction time of solvent free reaction is at
least six times less than corresponding solution phase
reaction and avoids the use of toxic solvents, this meth-
odology could be considered as a green chemistry ori-
ented synthesis of VH reactions. Rate enhancements in
the case of grinding reactions could be probably attrib-
uted to the faster activation of molecules due to the di-
rection friction followed by conversion of mechanical
energy into heat energy. In the case of sonicated reac-
tions reaction times are further reduced to 90 minutes.
The rate accelerations under sonicated could be explain-
ed by the cavitation phenomenon. Activation of mole-
cules is done by the in situ energy released due to the
rupture of cavitation bubbles generated by ultrasonic wa-
ves. It is also of interest to note that the reactions times
are reduced from several minutes to only few seconds
under microwave irradiation (MIR). The extremely faster
reaction rates in MIR system could be due to the bulk
activation of molecules rather than random activation.
X
R
II
Y
O
VHR = (i) Acetam ide / SOCl2 or POC l3
(ii) Benzamide / SO Cl2 or POCl3
X
Y
(i) Thermal(Stirring at room temp)
(ii) Grinding(Solvent free)
(iii) Sonication
(iv) Micro wave irradiation(300 watts)
Where R = CH3 when VHR = (Acetamide + SOCl2) or (Acetamide + POCl3); R = C6H5 when VHR = (Benzamide + SOCl2) or (Benzamide + POCl3); Y= CHO,
COCH3; X = electron donating or electron withdrawing groups.
Scheme 1. Acetylation and benzoylation of benzaldehydes and acetophenones unde r Vilsmeier Haack conditions.

M. VENKATESWARLU ET AL.
238
Table 5. Spectroscopic data for VH acety l ation of ar omatic c arbony l compounds.
Spectroscopic data
Entry Substrate Product
m/z 1H NMR
1 Benzaldehyde 3-Acetyl Benzaldehyde 148 δ 2.65 (s 3H, CH3); δ 7.66 (m 1H, Ar); δ 8.2 (d 2H, Ar)
δ 8.5 (s 1H, Ar); δ 9.9 (s 1H, Ar-CHO)
2 Salicyladehyde 3-Acetyl Salicyladehyde 164 δ 2.65 (s 3H, CH3);δ 7.2 (m 1H, Ar);δ 7.6 (d 1H, Ar)
δ 7.9 (d 1H, Ar);δ 10.3 (s 1H, Ar-CHO);δ 11.05 (s 1H, Ar-OH)
3 4-OH benzaldehyde 3-Acetyl 4-OH benzaldehyde 164 δ 2.65 (s 3H, CH3); δ 7.1 (d 1H, Ar); δ 7.95 (d 1H, Ar)
δ 8.3 (s 1H, Ar); δ 9.5 (s 1H, Ar-CHO); δ 10.5 (s 1H, Ar-OH)
4 4-OMe benzaldehyde 3-Acetyl 4-OMe benzaldehyde 178 δ 2.65 (s 3H, CH3); δ 3.93 (s 3H, Ar-OCH3); δ 7.15 (d 1H, Ar)
δ 8.0 (d 1H, Ar); δ 8.4 (s 1H, Ar); δ 10.05 (s 1H, Ar-CHO)
5 4-Cl benzaldehyde 3-Acetyl 4-Cl benzaldehyde 182 δ 2.65 (s 3H, CH3); δ 7.65 (d 1H, Ar); δ 8.05 (d 1H, Ar)
δ 8.4 (s 1H, Ar); δ 9.95 (s 1H, Ar-CHO)
6 4-Br benzaldehyde 3-Acetyl 4-Br benzaldehyde 226 δ 2.63 (s 3H, CH3); δ 7.78 (d 1H, Ar); δ 7.95(d 1H, Ar)
δ 8.5 (s 1H, Ar); δ 10.0 (s 1H, Ar-CHO)
7 4-NO2 benzaldehyde 3-Acetyl 4-NO2 benzaldehyde 193 δ 2.66 (s 3H, CH3); δ 8.35 (d 1H, Ar); δ 8.55 (d 1H, Ar)
δ 8.75 (s 1H, Ar); δ 9.95 (s 1H, Ar-CHO)
8 Cinnamaldehyde 3-Acetyl Cinnamaldehyde 174
δ 2.65 (s 3H, CH3); δ 6.75 (d 1H, =CH); δ 7.0 (m 1H, Ar)
δ 7.53 (d 1H, Ar); δ 7.68 (s 1H, Ar-CH=); δ 7.85 (d 1H, Ar)
δ 8.05 (s 1H, Ar); δ 9.9 (s 1H, Ar-CHO)
9 Acetophenone 3-Acetyl Acetophenone 162 δ 2.8 (s 6H, CH3); δ 6.7 (m 1H, Ar); δ 8.2 (d 2H, Ar)
δ 8.6 (s 1H, Ar)
10 2- OH acetophenone 3-Acetyl Chromone 187 δ 2.6 (s 3H, CH3); δ 6.65 (d 2H, Ar); δ 7.4 (m 2H, Ar)
δ 8.2 (s 1H, Ar)
11 4-OH acetophenone 3-Acetyl 4-OH acetophenone 178 δ 2.8 (s 6H, CH3); δ 7.0 (d 1H, Ar); δ 8.0 (d 1H, Ar)
δ 8.6 (d 1H, Ar) ;δ 11.4 (d 1H, Ar-OH)
12 4-Me acetophenone 3-Acetyl 4-Me acetophenone 176 δ 2.8 (s 6H, CH3); δ 5.3 (s 3H, Ar-CH3 ); δ 7.05 (d 1H, Ar)
δ 7.53 (d 1H, Ar); δ 7.75 (s 1H, Ar)
13 3-OH acetophenone 3-Acetyl 3-OH acetophenone 178 δ 2.8 (s 3H, CH3); δ 7.45 (s 1H, Ar); δ 7.6 - 7.8 (m 5H, Ar)
δ 7.95 (s 2H, Ar); δ 10.05 (s 1H, Ar)
14 4-Br acetophenone 3-Acetyl 4-Br acetophenone 240 δ 2.8 (s 6H, CH3); δ 7.4 (d 1H, Ar); δ 8.05 (d 1H, Ar)
δ 8.7 (d 1H, Ar)
15 4-NO2 acetophenone 3-Acetyl 4-NO2 acetophenone 207 δ 2.8 (s 6H, CH3); δ 7.5 (d 1H, Ar); δ 8.1 (d 1H, Ar)
δ 8.8 (d 1H, Ar)
Figure 1. VH acetylation of be nzaldehy de under thermal and
non-conventional conditions.
Figure 2. VH benzoylation of 4-OHAP under thermal and
non-conventional conditions.

239 M. VENKATESWARLU ET AL.
Table 6. Spectroscopic data for VH benzoylation of aromatic carbonyl compounds.
Spectral data
Entry Substrate Product m/z 1H NMR
1 Benzaldehyde 3-Benzoyl Benzaldehyde 210 δ 7.35 (m 4H, Ar); δ 7.65 (d 2H, Ar); δ 8.0 (d 2H, Ar)
δ 8.37 (s 1H, Ar); δ 10.05 (s 1H, Ar-CHO)
2 Salicyladehyde 3-Benzoyl Salicyladehyde 258 δ 7.35-7.92 (m 8H, Ar); δ 10.1 (s 1H CHO); δ 10.7 (s 1H, Ar-OH )
3 4-OH benzaldehyde 3-Benzoyl 4-OH benzaldehyde 258 δ 7.3 (m 4H, Ar); δ 7.6 (d 1H, Ar ); δ 8.0 (d 2H, Ar )
δ 8.3 (s 1H, Ar ); δ 9.95 (s 1H, Ar-CHO ); δ 10.95 (s 2H, Ar-OH )
4 4-OMe benzaldehyde 3-Benzoyl 4-OMe benzaldehyde240
δ 3.7 (s 3H, OCH3); δ 7.4 (m 4H, , Ar); δ 7.75 (d 1H, Ar)
δ 7.9 (d 2H, Ar); δ 7.75 (d 1H, Ar); δ 7.9 (d 2H, Ar)
δ 8.2 (d 1H, Ar); δ 10.05 (s 1H, Ar-CHO)
5 4-Cl benzaldehyde 3-Benzoyl 4-Cl benzaldehyde 244 δ 7.4 (m 4H, Ar); δ 7.7 (d 1H, Ar); δ 8.3 (d 2H, Ar)
δ 8.45 (s 1H, Ar); δ 10.0 (s 1H, Ar-CHO)
6 4-Br benzaldehyde 3-Benzoyl 4-Br benzaldehyde 288 δ 7.4 (m 4H, Ar ); δ 7.7 (d 1H, Ar); δ 8.0 (d 2H, Ar)
δ 8.2 (d 1H, Ar); δ 9.8 (s 1H, Ar-CHO)
7 4-NO2 benzaldehyde 3-Benzoyl 4-NO2 benzaldehyde 255 δ 7.35 (m, 4H Ar); δ 7.65 (d ,1H, Ar ); δ 8.05 (d, 2H, Ar)
δ 8.35 (s 1H, Ar); δ 9.95 (s 1H, Ar-CHO)
8 Cinnamaldehyde 3-Benzoyl Cinnamaldehyde 235 δ 6.75 (d ,1H, =CH ); δ 7.4 (m, 1H, Ar); δ 7.45 (d 1H, Ar)
δ 7.5-7.8 (m 7H, Ar); δ 8.05 (d 1H, =CH ); δ 9.9 (s 1H, Ar)
9 Acetophenone 3-Benzoyl Acetophenone 224 δ 2.8 (s 3H, CH3); δ 7.8 (m 5H, Ar); δ 7.6 (m 1H, Ar)
δ 7.95 (d 2H, Ar); δ 8.45 (s 1H, Ar)
10 2-OH acetophenone 3-Benzoyl Chromone 250 δ 6.34 (s 1H, Ar); δ 7.4 (m 6H, Ar); δ 7.65 (d 2H, Ar)
δ 7. 9 (d 1H, Ar)
11 4-OH acetophenone 3-Benzoyl 4-OH acetophenone 240 δ 2.9 (s 3H, CH3); δ 7.3 (m 3H, Ar); δ 7.6 (d 2H, Ar)
δ 8.45 (m 2H, Ar); δ 8.8 (s 1H, Ar);δ 10.9 (s 1H, Ar-OH)
12 4-Me acetophenone 3-Benzoyl 4-Me acetophenone 238 δ 2.45 (s 3H, CH3); δ 2.85 (s 3H, CH3-C=O); δ 7.5 (m 3H, Ar)
δ 7.7 (d 2H, Ar); δ 8.5 (m 2H, Ar); δ 8.9 (s 1H, Ar)
13 3-OH acetophenone 3-Benzoyl 3-OH acetophenone 240 δ 2.8 (s 3H, CH3); δ 7.45 (s 1H, Ar); δ 7.6 - 7.8 (m 5H, Ar)
δ 7.95 (s 2H, Ar); δ 10.05 (s 1H, Ar)
14 4-Br acetophenone 3-Benzoyl 4-Br acetophenone 302 δ 2.65 (s 3H, CH3); δ 7.4 (m 3H, Ar); δ 7.7 (d 2H, Ar)
δ 8.5 (m 2H, Ar); δ 8.7 (s 1H, Ar)
15 4-NO2 acetophenone 3-Benzoyl -NO2 acetophenone 269 δ 2.9 (s 3H, CH3); δ 7.3 (m 3H, Ar); δ 7.6 (d 2H, Ar)
δ 8.45 (m 2H, Ar); δ 8.8 (s 1H, Ar)
4. Conclusions
In conclusion Vilsmeier-Haack Reagents [Acetamide and
Oxychloride (SOCl2 or POCl3)] with aromatic aldehydes,
ketones afforded acetyl derivatives under conventional
(thermal) and non conventional [microwave irradiated
(MIR), ultrasonic assisted and solvent free mortar pestle
(grinding)] conditions with a trend: MIR (few seconds)
>> Sonication (minutes) > Grinding (min) >> thermal
(several hrs). Even though both the VH reagents afforded
good to excellent yields of products reaction times were
fairly less in the case of [Acetamide/POCl3] than those of
[Acetamide/SOCl2] reagent.
5. Acknowledgements
The authors thank CSIR, New Delhi for financial support
in the form of Emeritus Scientist grant awarded to Prof.
P. K. Saiprakash.
6. References
[1] T. W. Greene and P. G. M Wuts, “Protection Groups in
Organic Synthesis,” 3rd Edition, John Wiley, New York,
1999.
[2] G. Sartori, R. Ballini, F. Bigi, G. Bosica, R. Maggi and P.
Righi, “Protection (and Deprotection) of Functional Groups
in Organic Synthesis by Heterogeneous Catalysis,” Che-
mical Reviews, Vol. 104, No. 1, 2004, pp. 199-250.
[3] A. L. Pearson and W. J. Roush, “Handbook of Reagents
for Organic Synthesis; Activating Agents and Protecting
Groups,” John Wiley, Chichester, 1999.
[4] D. Harton, “Organic Synthesis Collective,” Wiley, New
York, 1991.

M. VENKATESWARLU ET AL.
240
[5] R. L. Zhdarov and S. M. Zherodarova, “Chemical Meth-
ods of Oligonucleotide Synthesis,” Synthesis, Vol. 1975,
No. 4, 1975, pp. 222-245. doi:10.1055/s-1975-23714
[6] G. Hoefle and W. Steglich, “N,N-Dimethyl-4-pyridi-
namine, a Very Effective Acylation Catalyst,” Angewandte
Chemie International Edition in English, Vol. 8, No. 12,
1969, p. 981. doi:10.1002/anie.196909811
[7] G. Hoefle, W. Steglich and H. Vorbrueggen, “4-Dialkyl-
aminopyridines as Highly Active Acylation Catalysts.
New Synthetic Method (25),” Angewandte Chemie Inter-
national Edition in English, Vol. 17, No. 8, 1978, pp.
569-583.
[8] E. F. V. Scriven, “4-Dialkylaminopyridines: Super Acy-
lation and Alkylation Catalysts,” Chemical Society Re-
views, Vol. 12, No. 2, 1983, pp. 129-161.
doi:10.1039/cs9831200129
[9] T. Sano, K. Ohaschi and T. Oreyama, “Remarkably Fast
Acylation of Alcohols with Benzoyl Chloride Promoted
by TMEDA,” Synthesis, Vol. 7, 1999, pp. 1141-1144.
[10] E. Vedejs, N. S. Bennett, L. M. L. Conn, S. T. Diver, M.
Gingras, S. Lin, P. A. Oliver and A. L. Peterson, “Tribu-
tylphosphine-Catalyzed Acylations of Alcohols: Scope
and Related Reactions,” Journal of Organic Chemistry,
Vol. 58, No. 25, 1993, pp. 7286-7288.
[11] E. Vedejs and S. T. Diver, “Tributylphosphine: A Re-
markable Acylation Catalyst,” Journal of the American
Chemical Society, Vol. 115, No. 8, 1993, pp. 3358-3359.
doi:10.1021/ja00061a056
[12] E. Vedejs, O. Daugulis and S. T. Diver, “Enantioselective
Acylations Catalyzed by Chiral Phosphines,” Journal of
Organic Chemistry, Vol. 61, No. 2, 1996, pp. 430-431.
doi:10.1021/jo951661v
[13] A. C. Cope and E. C. Herrich, “Organic Synthesis Col-
lective,” Wiley, New York, 1963.
[14] S. Chandrasekhar, T. R. Chander and M.Takhi, “Acyla-
tion of Alcohols with Acetic Anhydride Catalyzed by
TaCl5: Some Implications in Kinetic Resolution,” Tetra-
hedron Letters, Vol. 39, No. 20, 1998, pp. 3263-3266.
doi:10.1016/S0040-4039(98)00465-1
[15] R. Dalpozzo, A. De Nino, L. Maiuolo, P. A. Procopio, M.
Nardi, G. Bartoli and R. Romeo, “Highly Efficient and
Versatile Acetylation of Alcohols Catalyzed by Ce-
rium(III) Triflate,” Tetrahedron Letters, Vol. 44, No. 30,
2003, pp. 5621-5624.
doi:10.1016/S0040-4039(03)01358-3
[16] M. Moghadam, S. Tangestaninejad, V. Mirkhani, I. M.
Baltrork and R. Shabani, “Rapid and Efficient Acetyla-
tion of Alcohols and Phenols with Acetic Anhydride Cata-
lyzed by Electron-Deficient Tin(IV) Porphyrin,” Journal of
Moecular Catalysis A: Chemical, Vol. 219, No. 1, 2004,
pp. 73-78. doi:10.1016/j.molcata.2004.05.004
[17] K. Ishihara, M. Kubota, H. Kurihara and H. Yamamoto,
“Scandium Trifluoromethanesulfonate as an Extremely
Active Lewis Acid Catalyst in Acylation of Alcohols
with Acid Anhydrides and Mixed Anhydrides,” Journal
of Organic Chemistry, Vol. 61, No. 14, 1996, pp. 4560-
4567. doi:10.1021/jo952237x
[18] P. A. Procopiou, S. P. D. Baugh, S. S. Flack and G. G. A.
Inglis, “An Extremely Powerful Acylation Reaction of
Alcohols with Acid Anhydrides Catalyzed by Trimethyl-
silyl Trifluoromethanesulfonate,” Journal of Organic Ch-
emistry, Vol. 63, No. 7, Vol. 63, 1998, pp. 2342-2347.
doi:10.1021/jo980011z
[19] K. K. Chauhan, C. G. Frost, I. Love and D. Waite, “In-
dium Triflate, an Efficient Catalyst for Acylation Reac-
tions,” Synlett, Vol. 11, 1999, pp. 1743-1744.
doi:10.1055/s-1999-2941
[20] D. Chandra, P. Saravanan, R. K. Singh and V. K. Singh,
“Lewis Acid Catalyzed Acylation Reactions: Scope and
Limitations,” Tetrahedron, Vol. 58, No. 7, 2002, pp. 1369-
1374. doi:10.1016/S0040-4020(01)01229-7
[21] A. Orita, G. Tañáis and A. Kakuda, “Highly Efficient and
Versatile Acylation of Alcohols with Bi(OTf)3 as Cata-
lyst,” Angewandte Chemie International Edition, Vol. 39,
No. 16, 2000, pp. 2877-2879.
doi:10.1002/1521-3773(20000818)39:16<2877::AID-AN
IE2877>3.0.CO;2-V
[22] M. L. Kantam, K. Aziz and P. R. Likhar, “Bis(Cyclo-
pentadienyl) Zirconium Dichloride Catalyzed Acetylation
of Phenols, Alcohols and Amines,” Catalysis Communi-
cations, Vol. 7, No. 7, 2006, pp. 484-487.
doi:10.1016/j.catcom.2005.10.001
[23] J. W. J. Bosco, A. Agrahari and A. K. Saikia, “Molecular
Iodine Catalyzed Selective Acetylation of Alcohols with
Vinyl Acetate,” Tetrahedron Letters, Vol. 47, No. 24,
2006, pp. 4065-4068.
[24] M. A. Zolfigol, A. Khazaei, A. G. Choghamarani, A.
Rostami and M. Hajjami, “Acylation of Alcohols Cata-
lyzed by Using 1,3-Dibromo-5,5-dimethylhydentoin or
Trichloroisocyanuric Acid,” Catalysis Communications,
Vol. 7, No. 6, 2006, pp. 399-402.
doi:10.1016/j.catcom.2005.12.004
[25] H. T. Clarke and E. Rahrs, “Organic Syntheses. Collec-
tive Volumes,” Coll, Vol. 1, 1941, p. 91.
[26] J. Stawinski, T. Hozumi and S. A. Narang, “Ben-
zoyltetrazole: A Mild Benzoylating Reagent for Nucleo-
sides,” Journal of the Chemical Society, Chemical Com-
munications, Vol. 3, 1976, pp. 243-244.
doi:10.1039/c39760000243
[27] M. Yamada, Y. Watabe, T. Sakakibara and R. Sudoh,
“Preparation of a Water-Soluble Acylating Agent: Ben-
zoylation of Acids, Amines, and Phenols with 2-Benzoy-
lthio-1-methylpyridinium Chloride in Aqueous Phase,”
Journal of the Chemical Society, Chemical Communica-
tions, Vol. 4, 1979, pp. 179-180.
doi:10.1039/c39790000179
[28] F. A. Carey and K.O. Hodgson, “Efficient Syntheses of
Methyl 2-O-Benzoyl- 4, 6- O-benzylidene-α-D-glucopyra-
no-side and Methyl 2-O-Benzoyl-4,6-O-benzylidene-α-D-
ribo-hexopyranosid-3-ulose,” Carbohydrate Research, Vol.
12, No. 3, 1970, pp. 463-465.
doi:10.1016/S0008-6215(00)80628-X
[29] T. W. Greene, “Protective Groups in Organic Synthesis,”
Wiley, New York, 1981.

M. VENKATESWARLU ET AL.
241
[30] C. B. Reese, “Protective Groups in Organic Chemistry,”
Plenum, London, 1973.
[31] S. Paul, P. Nanda and R. Gupta, “PhCOCl-Py/Basic Alu-
mina as a Versatile Reagent for Benzoylation in Sol-
vent-Free Conditions,” Molecules, Vol. 8, 2003, pp. 374-
380. doi:10.3390/80400374
[32] G. A. Olah, St. J. Kuhn, “Friedls Craft’s and Related
Reactions,” John Wiley and Sons, New York, 1964.
[33] H. Ulrich, “The Chemistry of Imidoyl Halides,” Plenum
Press, New York, 1968.
[34] R. Bonnet, “The Chemistry of the Carbon Nitrogen Dou-
ble Bond,” John Wiley Sons, New York, 1970.
doi:10.1002/9780470771204.ch13
[35] E. Compaigne and W. L. Archer, “Organic Synthesis,”
John Wiley and Sons, New York, 1953.
[36] G. F. Smith, “Indoles. Part I. The Formylation of Indole
and Some Reactions of 3-Formylindole,” Journal of the
Chemical Society, Vol. 1, 1954, pp. 3842-3846.
doi:10.1039/jr9540003842
[37] R. N. Silverstein, C. Ryskiewez, C. Willert and R. C.
Kocher, “Improved Synthesis of 2-Pyrrolealdehyde and
of N-Methyl-2-Pyrrolealdehyde. Further Studies of Pyr-
role Alcohols,” Journal of Organic. Chemistry, Vol. 20,
No. 5, 1955, pp. 668-672. doi:10.1021/jo01123a019
[38] A. Lorenz and R. Winzinger, “Über die Vinylenho-
mologen der Triphenylmethanfarbstoffe II,” Helvetica
Chimica Acta, Vol. 28, No. 1, 1945, pp. 600-612.
doi:10.1002/hlca.660280183
[39] H. H. Boshard and H. Zollinger, “Die Synthese von Al-
dehyden und Ketonen mit Amidchloriden und Vils-
meier-Reagenzien,” Helvetica Chimica Acta, Vol. 42, No.
5, 1959, pp. 1659-1671.
[40] S. Alumi, P. Linda, G. Marino, S. Santine and G. Salvelli,
“The Mechanism of the Vilsmeier-Haack Reaction. Part
II. A Kinetic Study of the Formylation of Thiophen De-
rivatives with Dimethylformamide and Phosphorus Oxy-
chloride or Carbonyl Chloride in 1,2-Dichloroethane,”
Journal of the Chemical Society, Perkin Transactions,
Vol. 2, No. 14, 1972, pp. 2070-2073.
[41] P. Linda, A. Lucccarelli, G. Marino and G. Savelli, “The
Mechanism of the Vilsmeier-Haack Reaction. Part III.
Structural and Solvent Effects,” Journal of the Chemical
Society, Perkin Transactions, Vol. 2, No. 13, 1974, pp.
1610-1612.
[42] Z. Arnold and A. Holy, “Collection Czech,” Chemical
Communications, Vol. 27, 1962, pp. 2886-2895.
[43] T. D. Smith, “The Reaction of NN-Dimethylformamide
with Phosphorus Trichloride,” Journal of the Chemical
Society A: Inorganic, Physical, Theoretical, 1966, pp.
841-842.
[44] G. J. Martin, S. Poignant, M. L. Filleux and M. T. Que-
meneeuer, “Recherches sur la Reaction de Vilsmeier-
Haack etude du Mecanisme de Formation du Complexe
par des Mesures Cinetiques en Resonance Magnetique
Nucleaire,” Tetrahedron Letters, Vol. 11, No. 58, 1970,
pp. 5061-5064.
[45] G. J. Martin and S. Poignant, “Nuclear Magnetic Reso-
nance Investigations of Carbonium Ion Intermediates.
Part I. Kinetics and Mechanism of Formation of the Vils-
meier-Haack Reagent,” Journal of the Chemical Society,
Perkin Transactions, Vol. 2, 1972, pp. 1964-1966.
doi:10.1016/S0040-4039(00)96986-7
[46] K. C. Rajanna, F. Soloman, M. M. Ali and P. K. Saip-
rakash, “Vilsmeier-Haack Formylation of Coumarin De-
rivatives. A Solvent Dependent Kinetic Study,” Interna-
tional Journal of Chemical Kinetics, Vol. 28, No. 12,
1996, pp. 865-875.
doi:10.1002/(SICI)1097-4601(1996)28:12<865::AID-KI
N1>3.0.CO;2-L
[47] J. G. Dingwall, D. H. Reid and K. Wade, “Studies of
Heterocyclic Compounds. Part VI. NN-Dimethylth- io-
form-Amide: A New Reagent in the Vilsmeier Reaction,”
Journal of the Chemical Society C: Organic, Vol. 6, 1969,
pp. 913-915.
[48] T. L. Davis and W. E. Yelland, “Addition of Butylamine
to Butyl Isocyanide,” Journal of the American Chemical
Society, Vol. 59, No. 10, 1937, pp. 1998-1999.
doi:10.1021/ja01289a059
[49] A. Cipiciani, S. Clementi, P. Linda, G. Marino and G.
Savelli, “Kinetics and Mechanism of N-Substitution of
Indoles and Carbazoles in Vilsmeier-Haack Acetylation,”
Journal of the Chemical Society, Perkin Transactions,
Vol. 2, 1977, pp. 1284-1287.