Fe(HSO4)3 : An efficient, heterogeneous and reusable catalyst for C-alkylation of β-dicarbonyl compounds

Article abstract of DOI:10.1007/s12039-014-0630-z

Fe(HSO₄)₃(FHS) was used as an efficient catalyst for the heterogeneous addition of a series of benzylic and allylic alcohols to various β-dicarbonyl compounds, which afforded moderate to excellent yields of C-alkylated products in 1,2-dichloroethane. In comparison with the previous methods, the present research surprisingly exhibited higher reaction yields without formation of any by-products which could be formed by self-condensation of alcohols. Moreover, the catalyst can be readily recovered and reused up to five times with almost maintained reactivity and yields.

Full text of DOI:10.1007/s12039-014-0630-z

c
J. Chem. Sci. Vol. 126, No. 6, November 2014, pp. 1903–1912. ꢀ Indian Academy of Sciences.
Fe(HSO4)3: An efficient, heterogeneous and reusable catalyst
for C-alkylation of β-dicarbonyl compounds
SAMANEH KHAFAJEH, BATOOL AKHLAGHINIA∗, SOODABEH REZAZADEH and
HOSSEIN ESHGHI
Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran
e-mail: akhlaghinia@um.ac.ir
MS received 1 December 2013; revised 4 February 2014; accepted 9 February 2014
Abstract. Fe(HSO4)3(FHS) was used as an efficient catalyst for the heterogeneous addition of a series of
benzylic and allylic alcohols to various β-dicarbonyl compounds, which afforded moderate to excellent yields
of C-alkylated products in 1,2-dichloroethane. In comparison with the previous methods, the present research
surprisingly exhibited higher reaction yields without formation of any by-products which could be formed by
self-condensation of alcohols. Moreover, the catalyst can be readily recovered and reused up to five times with
almost maintained reactivity and yields.
Keywords. β-Dicarbonyl compounds; ferric hydrogen sulphate Fe(HSO4)3; C-alkylation; heterogeneous
catalyst.
ruthenium complex,19 as well as montmorillonite,20
p-toluenesulphonic acid21 have been demonstrated to
facilitate dehydrative substitution of allylic and ben-
zylic alcohols with β-dicarbonyl compounds. In com-
parison to the traditional synthetic procedures, appli-
cation of Lewis and BrÖnsted acids which has been
successful in the alkylation of 1,3-dicarbonyl com-
pounds using alcohols as electrophiles directly,1–5,22
offers several potential advantages, such as wide availa-
bility of starting materials and generation of H2O as
the only side product. Despite this, many of these
methods have major or minor disadvantages such as
low yield of products, side product formation and
tedious work-up procedures. In this study, ferric hydro-
gen sulphate Fe(HSO4)3, was used as an efficient
catalyst for alkylation of a wide variety of β-dicarbonyl
compounds.
1. Introduction
Alkylation of β-dicarbonyl compounds is one of the
most common methodologies for C–C bond construc-
tion as a fundamental task in generating a wide range
of valuable synthetic intermediates that are utilized
in the synthesis of functional materials, natural prod-
ucts, and pharmaceuticals in organic synthesis. In recent
years, among a variety of approaches for the alky-
lation of β-dicarbonyl compounds, direct addition of
β-dicarbonyl compounds to alcohols (affording alky-
lated β-dicarbonyl compounds) has attracted much
interest because only H2O is generated as the side
product.1–7 In traditional protocols, hydroxy groups
usually require pre-activation through transformation
into good leaving groups such as halides, carboxy-
lates, carbonates, and phosphonates before treating with
β-dicarbonyl compounds.8 Salt wastes which were pro-
duced inevitably in such processes would set lim-
its for the industrial application and for the scope 2. Experimental
of substrates. In the last few years, chemists have
2.1 General
focused on some acid-catalysed intermolecular addi-
tions of β-dicarbonyl compounds to alcohols, consid-
ering them to be the most promising approaches in
this field. Various Lewis acids such as InCl3,1,9 InBr3,10
FeCl3,11–15 Fe(ClO4)3,16 M(OTf)3,17,18 Lewis acidic
The products were purified by column chromatogra-
phy. Purity determinations of the products were accom-
plished by TLC on silica gel polygram STL G/UV
254 plates. Melting points of products were determined
with an Electrothermal Type 9100 melting point appa-
ratus. The FT-IR spectra were recorded on an Avatar
370 FT-IR Therma Nicolet spectrometer. The NMR
spectra were provided on Brucker Avance 400 MHz
∗For correspondence
1903

1904
Samaneh Khafajeh et al.
instruments in CDCl3. Mass spectra were recorded with (COO), 136.7 (C), 128.7 (CH), 127.6CH), 126.4 (CH),
a CH7A Varianmat Bremem instruments at 70 eV; in 63.5(CH), 61.4 (CH), 32.1(CH3), 30.1(CH2), 14.0
m/z (rel %). Elemental analyses were performed using (CH3) ppm; MS (EI) m/z (%) 296 [M+, 3%], 253
a Thermofinnigan Flash EA 1112 Series instrument. [M+– CH3C=O], 223 [M+- CH3CH2OC=O], 181
1
The known products were characterized by IR and H [M+-(CH3C=O, CH3CH2OC=O)], 167 [M+− 129,
NMR spectra and comparison of their melting points 100%], 105 [M+ -(CH3C=O, CH3CH2OC=O, Ph),
(or those of the derivatives) with authentic samples. 95%], 77 [M+− 219, 72%], 43 [M+− 253, 60%];
Catalysts were prepared and purified by the method Elemental analysis data for C19H20O3: C, 77.00; H,
described in literature.23
6.80; Found: C, 76.95; H, 6.77.
2.2c Diethyl 2-benzhydrylmalonate (table 2, entry 3):
Solid, yield 87%, mp 50–51.5◦C (Lit. 53◦C);25 FT-IR
(KBr) νmax 3080, 3062, 3028, 2925, 2859, 1736 (C=O),
1714(C=O), 1660, 1493, 1453, 1265, 1059, 744 cm−1;
1H NMR (400 MHz, CDCl3, 25◦C) δ 7.84–7.49 (m,
10H, Ph); 4.82 (d, J = 12.4 Hz,1H, (Ph)2CH), 4.76
(d, J = 12.4 Hz, 1H, CHC=O), 3.97 (q, J = 6.8 Hz,
4H, 2 × OCH2CH3), 0.99 (t, J = 6.8 Hz, 6H, 2 ×
OCH2CH3) ppm; 13C NMR (100 MHz, CDCl3, 25◦C)
δ 167.2(COO), 136.7(C), 128.5(CH), 127.6(CH), 126.4
(CH), 63.5 (CH2), 61.4(CH), 30.1(CH), 14.0(CH3)
ppm; MS (EI) m/z (%) 326 [M+,10%], 325 [M+-
H], 324 [M+-2H], 249 [M+-Ph, 72%], 181 [M+-
2(CH3CH2O C=O), 75%], 167 [M+-(CH3CH2 OC=
O)2 CH, 75%], 166 [M+-((CH3CH2OC=O)2 CH,
H),100%], 104 [M+-222].
2.2 General procedure for benzylation
of acetylacetone catalysed by ferric hydrogen sulphate
Ferric hydrogen sulphate (0.06 g) was added to a
solution of acetylacetone (1 mmol, 0.1 g) in 1,2-
dichloroethane (2 mL) at 86◦C. Benzhydrol (2 mmol,
0.368 g) was dissolved in 1,2-dichloroethane (2 mL)
and added to the reaction mixture dropwise during 1 h.
Progress of the reaction was monitored by TLC. After
completion of the reaction, the catalyst was removed by
filtration. The filtrate was washed with distilled water
(3 × 4) and dried over Na2SO4. The concentrated
residue was passed through a short silica gel column
chromatography using EtOAc/hexane (1:10) as an elu-
ent. After removing the solvent under reduced pressure,
3-benzhydryl pentane-2,4-dione was obtained in 80%
yield.
2.2d Diethyl 2-benzhydryl-2-ethylmalonate (table 2,
entry 4): Solid, yield 85%, mp 66.5–68◦C( Lit. 67–
69◦C);26 FT-IR (KBr) νmax 3064, 2974, 2941, 2876,
1756 (C=O), 1732 (C=O), 1658, 1450, 1277, 1232,
1153, 1037, 702 cm−1;1H NMR (400 MHz, CDCl3,
25◦C) δ 7.39–7.25 (m, 10H, Ph), 5.83 (s, 1H, CHPh),
4.30 (q, J = 7.2 Hz, 4H, 2 × OCH2 CH3), 1.94
(q, J = 7.2 Hz, 2H, CH2CH3), 1.27 (t, J = 7.2
Hz, 6H, 2 × OCH2CH3), 0.90 (t, J = 7.2 Hz,
3H, CH2CH3) ppm;13C NMR (100 MHz, CDCl3,
25◦C) δ169.5(COO), 145.9 (C), 128.4(CH), 127.4(CH),
125.4(CH), 70.3(C), 61.3(CH2), 39.5(CH), 25.2(CH2),
14.1(CH3), 11.8 (CH3) ppm; MS (EI) m/z (%) 354
[M+, 3%], 309 [M+- CH3CH2O, 65%], 281 [M+- CH3
CH2OC=O, 60%], 187 [M+- (Ph)2CH, 85%], 104 [M+-
250, 100%], 77 [M+-277,62%], 45 [M+-309, 65%];
Elemental analysis data for C22H26O4: C,74.55; H, 7.39;
Found: C, 74.35; H, 7.30.
2.2a 3-Benzhydryl-pentane-2,4-dione (table2,entry1):
Solid, yield 80%, mp 93.5–95◦C (Lit. 93–95◦C);1 FT-IR
(KBr) νmax 3060, 3027, 2958, 2923, 2850, 1729(C=O),
1698, 1462, 1265, 744 cm−1;1H NMR (400 MHz,
CDCl3, 25◦C) δ 7.39–7.31 (m, 8H, aryl H), 7.21–7.18
(m, 2H, aryl H), 4.81 (d, J = 12.4 Hz, 1H, CHPh),
4.74 (d, J = 12.4 Hz,1H, CHC=OCH3), 2.02(s, 6H,
2 × C=OCH3) ppm; 13C NMR (100 MHz, CDCl3,
25◦C) δ 201.9 (COO), 145.0 (C), 129.5(CH), 128.5
(CH), 127.9 (CH), 51.6 (CH), 30.6(CH3), 26.7(CH)
ppm; MS (EI) m/z (%) 266 [M+, 3%], 181 [M+-
2 (CH3C=O)], 167 [M+-((CH3C=O)2CH, H), 100%],
104 [M+-(2 (CH3C=O), Ph), 50%].
2.2b Ethyl 2-benzhydryl-3-oxobutanoate (table 2,
entry 2): Solid, yield 75%, mp 84–85.5◦C (Lit. 88–
90◦C);24 FT-IR (KBr) νmax 3084, 3060, 3031, 2990,
2953, 1736 (C=O), 1703(C=O), 1662, 1494, 1361,
1
1145, 752, 701 cm−1; H NMR (400 MHz, CDCl3,
25◦C) δ 7.39–7.25 (m, 10H, Ph), 4.86 (d, J = 6.4 Hz, 2.2e Dimethyl2-benzhydryl-2-chloromalonate (table 2,
1H, CHCO), 4.23 (q, J = 7.2 Hz, 2H,OCH2CH3) 3.38 entry 5): Solid, yield 90%, mp 87–89.5◦C; FT-IR
(d, J = 6.4 Hz 1H, CHPh), 2.40 (s, 3H, CH3CO), 1.27 (KBr) νmax 3080, 3056, 3023, 2924, 2852, 1772 (C=O),
1
(t, J = 7.2 Hz, 3H, OCH2 CH3) ppm; 13C NMR 1751 (C=O), 1437, 1309, 1197, 1167, 702 cm−1; H
(100 MHz, CDCl3, 25◦C) δ 200.8 (C=O), 167.2 NMR (400 MHz, CDCl3, 25◦C) δ 7.84–7.49 (m, 10H,

C-alkylation of β-dicarbonyl compounds
1905
aryl H), 5.58 (s, 1H, CH Ph), 3.63 (s, 6H, 2 × COCH3) (C), 128.5 (CH),127.4(CH), 125.4 (CH), 70.3(CH),
ppm; 13C NMR (100 MHz, CDCl3, 25◦C) δ 169.8 32.5 (CH3), 28.3(CH), 25.1 (CH3) ppm; MS (EI) m/z
(C=O), 147.6(C), 132.4(CH), 130.1 (CH), 128.3(CH), (%)204 [M+,8%], 189 [M+-CH3, 90%], 105 [M+-
84.1(C), 54.6(CH3), 44.6(CH) ppm; MS (EI) m/z (CH3C=O)2CH, 95%], 99 [M+-105, 60%]; Elemental
(%) 334 [M++2,4%], 332 [M+, 12.5%], 297 [M+- analysis data for C13H16O2: C, 76.44; H, 7.90; Found:
Cl], 179 [M+-(Cl, 2(CH3OC=O)), 95%], 167 [M+- C, 76.35; H, 7.34.
(CH3OC=O)2 CCl, 77%], 105 [M+-(2 (CH3OC=O),
Ph, Cl), 85%]; Elemental analysis data for C18H17ClO4:
C, 64.97; H, 5.15; Found: C, 64.65; H, 5.48.
2.2i Ethyl 2-acetyl-3-phenylbutanoate (table 2,
entry 9): Oil,28 yield 70%; FT-IR (neat) νmax 3056,
3029, 2974, 2934, 2876, 1748 (C=O), 1715 (C=O),
1
2.2f 5-benzhydryl-2,2-dimethyl-1,3-dioxane-4,6-dione 1453, 1358, 1205, 1177, 1022, 701 cm−1; H NMR
(table 2, entry 6): Solid, yield 95%, mp 133– (400 MHz, CDCl3, 25◦C) δ 7.23–7.05 (m, 5H, Ph),
134◦C(Lit. 134–135◦C);27 FT-IR (KBr) νmax 3084, 3.88 (q,J = 7.2 Hz, 2H, OCH2CH3), 3.64 (d, J = 10.8
3060, 3030,2949, 1752(C=O), 1727(C=O), 1495, Hz,1H, CHCO), 3.59–3.52 (m, 1H, CHCH3), 1.85 (s,
1
1301, 1220, 1160, 756 cm−1; H NMR (400 MHz, 3H, CH3CO), 1.23 (d, J = 6.8 Hz,3H, CH3CH),0.93 (t,
CDCl3, 25◦C) δ 7.46–7.23 (m, 10H, aryl H), 5.60 (d, J = 7.2 Hz, 3H, OCH2CH3) ppm; 13C NMR (100 MHz,
J = 6.4Hz, 1H, CHCO), 3.97 (d, J = 6.4 Hz, 1H, CH CDCl3, 25◦C) δ 200.2 (C=O), 165.5 (COO), 147.9 (C),
Ph), 1.27 (s, 6H,2 × CH3), ppm;13C NMR (100 MHz, 128.9 (CH), 128.0(CH), 127.8 (CH), 67.3(CH), 65.4
CDCl3, 25◦C) δ 171.0 (C=O), 146.0(C), 129.2(CH), (CH2), 28.1(CH3), 27.2 (CH), 16.5(CH3), 14.9 (CH3)
128.6 (CH), 127.7(CH), 101.7(C), 58.1(CH), 30.8(CH), ppm; MS (EI) m/z (%) 234 [M+, 12%], 219 [M+-CH3,
26.0(CH3) ppm; MS (EI) m/z (%) 310 [M+], 270 [M+- 72%], 157 [M+-Ph, 82%], 105 [M+-129, 85%], 77
C=C=C, 40%], 269 [M+- (C=C=C,H), 43%], 267 [M+-157, 95%].
[M+ - OC=O,85%], 181 [M+ -(130H), 90%], 167 [M+
- 143, 85%]; Elemental analysis data for C19H18O4: C,
2.2j Diethyl 2-(1-phenylethyl)malonate (table 2, entry
73.53; H, 5.85; Found: C,73.35; H, 5.80.
10): Oil29 yield 70%; FT-IR (neat) νmax 3060, 2984,
2941, 2908, 2872, 1752 (C=O), 1735 (C=O), 1370,
1
2.2g 2-benzhydryl-3-hydroxy-5,5-dimethylcyclohex- 1331, 1269, 1190, 1150, 1035, 698 cm−1; H NMR
2-enone (table 2, entry 7): Solid, yield 75%, mp (400 MHz, CDCl3, 25◦C) δ 7.39–7.26 (m, 5H, Ph),
120–122◦C; FT-IR (KBr) νmax 3456, 3060, 3031, 2962, 4.68–4.62 (m, 1H, CH Ph), 4.28(q, J = 7.2 Hz,4H,
2925, 2872, 1737 (C=O), 1714 (C=O), 1061, 1493, 2 × OCH2CH3), 3.65 (d,J = 7.6 Hz, 1H, CHCOO),
1
1266, 740 cm−1; H NMR (400 MHz, CDCl3, 25◦C) 1.51 (d, J = 7.6 Hz, 3H, CH3CH), 1.20 (t, J = 7.2
δ 15.36 (s,1H, OH-C=C), 7.45–7.22 (m, 10H, aryl Hz,6H, 2 × OCH2CH3) ppm;13C NMR (100 MHz,
H), 4.68 (s, 1H, CH Ph), 2.98 (d,J = 6.8 Hz, 2H, CDCl3, 25◦C) δ 170.0 (COO), 148. 1(C), 132.4
CH2C=O) 1.84 (d, J = 6.8 Hz, 2H, CH2COH) 1.28 (CH), 130.1(CH), 128.3 (CH), 64.9 (CH2), 61.1 (CH),
(s, 6H, 2 × CH3) ppm; 13C NMR (100 MHz, CDCl3, 27.5(CH), 20.1(CH3), 14.8 (CH3) ppm; MS (EI) m/z
25◦C) δ 196.8 (C=O), 186.5 (C), 141.1 (C), 129.3 (%) 264 [M+,5%], 249 [M+-CH3, 80%], 159 [M+-
(CH), 128.7 (CH), 126.9(CH), 110.7(C), 57.8(CH2), (PhCHCH3), 98%], 105 [M+-159, 85%], 77 [M+-187,
60.0 (CH2), 36.7(CH), 34.1(C), 29.7 (CH3) ppm; MS 90%].
(EI) m/z (%) 306 [M+, 10%], 305 [M+-H], 229 [M+-
Ph, 65%], 167 [M+-139, 85%], 139 [M+-(Ph)2CH, 60
2.2k Diethyl 2-ethyl-2-(1-phenylethyl) malonate
%], 77 [M+-229, 80%]; Elemental analysis data for
(table 2, entry 11): Oil,30 yield 75%; FT-IR (neat)
C21H22O2: C, 82.32; H, 7.24; Found: C, 82.50; H, 7.30
νmax 3056, 2963, 2925, 2878, 2851, 1756 (C=O),
1732 (C=O), 1466, 1267, 1207, 745 cm−1;1H NMR
2.2h 3-(1-Phenylethyl)pentane-2,4-dione (table 2, (400 MHz, CDCl3, 25◦C) δ 7.38–7.24 (m, 5H, Ph),
entry 8): Solid, yield 70%, mp 43–45◦C(Lit.46– 4.87 (q, J = 6.4 Hz, 4H, 2 × OCH2CH3), 4.19 (q,
47◦C);24 FT-IR (KBr) νmax 3088, 3060, 3027, 2965, J = 6.4 Hz,1H, CHPh), 1.92 (q, J = 6.4 Hz,2H,
2929, 2872, 1728 (C=O), 1698, 1600, 1493, 1356, CH2CH3), 1.48 (d, J = 6.4 Hz, 3H, CH3CHPh), 1.27
1
700 cm−1; H NMR (400 MHz, CDCl3, 25◦C) δ 7.31– (t, J = 6.4 Hz, 6H, 2 × OCH2 CH3), 0.60 (t, J =
7.26 (m, 5H, Ph), 3.89 (d,J = 7.2 Hz, 1H,CHCO), 6.4 Hz, 3H, CH2CH3) ppm;13C NMR (100 MHz,
3.21–3.16 (m, 1H, CHCH3), 2.64 (s, 6H, 2 × CH3CO), CDCl3, 25◦C) δ 169.5(COO), 139.9 (C), 128.4(CH),
1.50 (d, J = 6.4 Hz,3H, CH3CH) ppm; 13C NMR 127.4(CH), 125.4(CH), 70.3(C), 61.3(CH2), 33.5(CH),
(100 MHz, CDCl3, 25◦C) δ 204.0 (C = O), 145.8 25.2(CH2), 22.2(CH3), 14.1(CH3), 11.8 (CH3) ppm;

1906
Samaneh Khafajeh et al.
MS (EI) m/z (%) 292 [M+,10%], 277 [M+-CH3, 75%], 18.1 (CH3) ppm; MS (EI) m/z (%) 244 [M+, 5%], 229
219 [M+-(COOCH2CH3), 95%], 77 [M+-215, 90%],43 [M+-CH3, 66%], 167 [M+-Ph, 57%], 105 [M+-139,
[M+-249, 98%].
85%], 77 [M+-167, 78%]; Elemental analysis data
for C16H20O2 : C, 78.65;H, 8.25; Found: C,78.49; H,
8.59.
2.2l Dimethyl 2-chloro-2-(1-phenylethyl) malonate
(table 2, entry 12): Solid, yield 80%, mp 38–39.5◦C;
FT-IR (KBr) νmax 3056, 3029, 2974, 2934, 2876, 1772
(C=O), 1751(C=O), 1495, 1437, 1309, 1259, 1197,
2.2o Ethyl 2-acetyl-3-phenylpent-4-enoate (table 2,
entry 15): Oil,32 yield 85%; FT-IR (neat) νmax 3081,
3059, 3025, 2923, 2854, 1740(C=O), 1711(C=O),
1157, 1022, 736, 701 cm−1; H NMR (400 MHz,
1
1
1600, 1493, 1452, 1029, 746, 696 cm−1; H NMR
CDCl3, 25◦C) δ 7.37–7.25 (m, 5H, Ph), 4.62 (q, J =
7.2 Hz,1H, CHCH3), 3.81 (s, 6H, 2 × OCH3), 1.36
(d,J = 7.2 Hz, 3H,CHCH3) ppm; 13C NMR (100 MHz,
CDCl3, 25◦C) δ 169.8 (COO), 147.6(C), 132.4 (CH),
130.1(CH), 128. 3(CH), 84.1(C), 51.6(CH3), 32.4(CH),
10.1 (CH3) ppm; MS (EI) m/z (%) 272 [M++2, 4%],
(400 MHz, CDCl3, 25◦C) δ 7.41–7.18 (m, 5H,
Ph), 6.29–6.19 (m, 1H, CHCH=CH2), 4.86 (d, J =
7.6 Hz,2H, CH=CH2), 4.59 (t, J = 7.6 Hz,1H,
CHCH=CH2), 4.35 (q,J = 7.2 Hz, 2H, OCH2CH3),
3.17 (d, J = 7.6 Hz, 1H, CHC=O), 2.10 (s, 3H,
CH3CO); 2.19 (t, J = 7.2 Hz,3H,OCH2CH3) ppm;
13C NMR (100 MHz, CDCl3, 25◦C) δ 196.82 (C=O),
170.0(COO), 140.1 (C), 137.6(CH), 132.4(CH),
130.1(CH), 128.3 (CH), 115.1(CH2), 64.9(CH),
61.1(CH2), 30.1(CH), 27.5(CH3), 14.8(CH3) ppm; MS
(EI) m/z (%) 246 [M+,12%], 201 [M+- CH3CH2O,
98%], 169 [M+- Ph,82%], 129 [M+-117, 80%], 77
[M+-169, 82%].
270 [M+, 10%], 239 [M+-CH3O, 92%], 235 [M+
-
Cl, 80%], 193 [M+ - ph, 70%], 179 [M+-( Ph, CH3),
80%], 164 [M+-(CH3CHPh, H), 85%], 105 [M+ -165,
85%], 77 [M+ -193, 60%]; Elemental analysis data for
C13H15ClO4: C, 57.68; H, 5.59; Found: C, 58.07; H,
5.62.
2.2m 2,2-Dimethyl-5-(1-phenylethyl)-1,3-dioxane-4,
6-dione (table 2, entry 13): Solid, yield 80%, mp
99.5–101.5◦C (Lit.101◦C);31 FT-IR (KBr) νmax 3064,
3031, 2959, 2930, 2872, 1727 (C=O), 1454, 1276,
2.2p Ethyl 2-(3-methoxybenzyl)-3-oxobutanoate (table
2, entry 16): Solid, yield 65%, mp 64–65.5◦C (Lit.65–
67◦C);33 FT-IR (KBr) νmax 3056, 3029, 2974, 2954,
2876, 1744 (C=O), 1718 (C=O), 1604, 1585, 1490,
1465, 1316, 1267, 736 cm−1; MS (EI) m/z (%) 250
[M+, 8%], 220 [M+- CH3O,95%], 206 [M+- CH3 CH
2O], 177 [M+- CH3CH2O C=O], 175 [M+-(CH3O,
CH3CH2O), 90%], 121 [M+- 129, 85%], 107[M+-
143, 80%]; Elemental analysis data for C14H18O4: C,
67.18;H, 7.25; Found: C, 67.15;H, 7.30.
1207, 1071, 702 cm−1; H NMR (400 MHz, CDCl3,
1
25◦C) δ 7.41–7.27 (m, 5H, Ph), 4.95–4.89 (m, 1H,
CHCH3), 3.55 (d, J = 7.2 Hz,1H, CHCO), 1.88(s,
6H, 2 × CH3), 1.52(d, J = 6.8 Hz,3H, CHCH3)
ppm; 13C NMR (100 MHz, CDCl3, 25◦C) δ 166.7
(C=O), 145.9(C), 128.4(CH), 127.4(CH), 125.4(CH),
104.3(C), 61.5(CH), 29.7(CH), 25.1(CH3), 14.0(CH3)
ppm; MS (EI) m/z (%) 248 [M+, 4%], 233 [M+-
CH3], 208 [M+- C=C=C], 105 [M+-143, 100%],
77 [M+-171, 57%], 28 [M+-220, 66%]; Elemental
analysis data for C14H16O4: C, 67.73; H, 6.50; Found:
C, 67.35; H, 6.30
2.2q Ethyl 2-benzyl-3-oxobutanoate (table 2, entry
17): Oil,34 yield 85%; FT-IR (neat) νmax 3031, 2977,
2929, 1740 (C=O), 1716 (C=O), 1650, 1450, 1367,
1317, 1245, 1152, 1040, 898, 755 cm−1; MS (EI) m/z
(%) 220 [M+, 5%], 205 [M+- CH3, 75%], 175 [M+-
CH3CH2O, 92%], 129 [M+-PhCH2, 75%], 77 [M+-143,
75%], 45 [M+- 175, 88%] .
2.2n 3-hydroxy-5,5-dimethyl-2-(1-phenylethyl)
cyclohex-2-enone (table 2, entry 14): Solid, yield
85%, mp 109.5–110.5◦C; FT-IR (KBr) νmax 3476, 3060,
3030, 2957, 2924, 2853, 1717 (C=O), 1620, 1496,
1453, 1265, 1115, 743, 699 cm−1; 1H NMR (400 MHz,
CDCl3, 25◦C) δ 15.00(s, 1H, OH-C=C), 7.41–7.27 2.2r Ethyl 2-(4-chlorobenzyl)-3-oxobutanoate (table
(m, 5H, Ph), 3.56 (q, J = 7.2 Hz, 1H, CHCH3), 2.49 2, entry 18): Oil,35 yield 90%; FT-IR (neat) νmax 3080,
(d, J = 7.2 Hz, 2H, CH2C=O), 1.99 (d, J = 7.2 Hz, 3056, 3023, 2924, 2852, 1743 (C=O), 1716 (C=O),
2H, CH2COH), 1.41 (d, J = 7.2 Hz, 3H, CHCH3), 1648, 1410, 1367, 1318, 1252, 1041, 1014, 800 cm−1;
1.05 (s, 6H, 2 × CH3) ppm;13C NMR (100 MHz, MS (EI) m/z (%) 256 [M++2, 4%], 254 [M+, 10%],
CDCl3, 25◦C) δ 196.8 (C=O), 180.0 (COH), 137.6(C), 219 [M+- Cl, 80%], 209 [M+- CH3CH2O, 75%], 143
132.4(CH), 130.1(CH), 128.3(CH), 110.1 (C), 52.3 [M+-ClPh, 75%], 77 [M+-177, 82%], 43 [M+-211,
(CH2), 46.6 (CH2), 43.7(CH), 30.0(C), 28.9 (CH3), 80%].

C-alkylation of β-dicarbonyl compounds
1907
3. Results and Discussion
of acetylacetone with benzhydrol in the presence
of 20 mol% of Fe(HSO4)3. The catalytic effect of
[Fe(HSO4)3 was efficiently decreased in toluene,
CHCl3, CH2Cl2, 1,4-dioxane and CH3NO2 (table 1,
entries 8–12). No product was obtained when the reac-
tion was performed in refluxing H2O, CH3CN, THF
and acetone (table 1, entries 13–16). As shown in
table 1, when the reaction was performed in the pres-
ence of Fe(HSO4)3/silica, 3-benzhydryl pentane-2,4-
dione was obtained in longer reaction time (table 1,
entry 17).
Optimization of reaction conditions was carried out
for the reaction of acetylacetone and benzhydrol in
the presence of Fe(HSO4)3 under various reaction
parameters in order to achieve maximum chemical
yield at the lowest reaction time and lowest reac-
tion temperature. The general reaction is outlined
in scheme 1 and the representative results are shown in
table 1.
In the absence of any catalyst and solvent, there
was no conversion to 3-benzhydryl pentane-2,4-dione
(table 1, entries1-2). At room temperature, in the pres-
ence of 20 mol% of Fe(HSO4)3, there is no tendency
between acetylacetone and benzhydrol to produce the
desired product (table 1, entry 3). In refluxing 1,2-
dichloroethane, Fe(HSO4)3 was identified as a cata-
lyst for 3-benzhydryl pentane-2,4-dione formation in
high yield but in prolonged reaction time (table 1,
entry 4). During optimization reactions of acetylacetone
with benzhydrol, we notice that the rate of addition of
benzhydrol plays an important role in the yield of alky-
lated product. Quick addition of benzhydrol leads to the
formation of excess amount of symmetric ether which
was obtained from self-condensation of benzhydrol.
To prevent self-condensation of benzhydrol in all of
the following reactions, addition of benzhydrol should
be performed dropwise, which consumes more time.
In this manner, alkylated product was obtained as the
chief product. In an effort to develop better reaction
conditions, using 1/2 molar ratio of acetylacetone/
benzhydrol in refluxing 1,2-dichloroethane produces
corresponding alkylated product in short reaction time
(10 min), as addition of benzhydrol should be carried
out more slowly, the time of reaction was prolonged
up to 2 h (table 1, entry 5). The best amount of cat-
alyst in the formation of 3-benzhydryl pentane-2,4-
dione from the reaction of acetylacetone with benzhy-
drol is 20 mol%. Increasing the amount of catalyst up
to 30 mol% does not have any influence on the reac-
tion rate but applying 10 mol% of Fe(HSO4)3 yields
the product in longer reaction time (table 1, entries 6
and 7).
Under these optimized conditions, addition of diffe-
rent alcohols to diverse β-dicarbonyl compounds was
investigated in the presence of Fe(HSO4). The results
are summarized in table 2. To prevent side product
formation, addition of alcohols to the reaction mixture
should be performed drop by drop and preparation
of alkylated products should be prolonged. Accor-
ding to the results obtained from table 2, in the pres-
ence of Fe(HSO4)3, alkylation reactions of different β-
dicarbonyl compounds by benzhydrol, 1-phenylethanol
and cinnamyl alcohol were completed faster than alky-
lation with benzyl alcohol and substituted benzyl alco-
hols, due to higher stability of the carbocation interme-
diate. Reaction of acyclic and cyclic β-dicarbonyl com-
pounds with benzhydrol was carried out in the presence
of Fe(HSO4)3 and the corresponding products were
produced in good to excellent yields (table 2, entries
1–7). Reaction of β-dicarbonyl compounds with 1-
phenyl ethanol, cinnamyl alcohol, benzyl alcohol and
substituted benzyl alcohols are also effective and yields
of desired products are comparable to those of the reac-
tion with benzhydrol (table 2, entries 8–18). Surpri-
singly, this method gave good yields with primary ben-
zylic alcohols. Reaction of ethyl acetoacetate with ben-
zyl alcohol and substituted benzyl alcohol affords mo-
derate yield and much longer reaction time is needed.
In comparison, presence of the electron-donating subs-
tituent in benzene ring can increase reactivity of ben-
zylic alcohol, while the electron-withdrawing subs-
tituent in benzene ring seems to have a negative effect
on benzylation reaction (table 2, entries 16–18). The
catalyst is inapplicable for conversion of isopropyl alco-
hol (aliphatic secondary alcohol) to its corresponding
product. On the basis of the proposed mechanism
in scheme 2 and the experimental results obtained
from table 2, alcohols with more stable carbocations
are applicable for C-alkylation of β-dicarbonyl com-
pounds. Also, it is seen from table 2 that more acidic
β-dicarbonyl compounds were alkylated faster than
the others. Lower acidic diethyl malonate and diethyl
ethyl malonate react with benzhydrol in longer reac-
tion time than dimethyl chloro malonate (e.g., compare
Different solvents were screened for the preparation
of 3-benzhydryl pentane-2,4-dione from the reaction
Scheme 1. C-alkylation of β -dicarbonyl compounds.

1908
Samaneh Khafajeh et al.
Table 1. Synthesis of 3-benzhydryl pentane-2,4-dione in the presence of Fe(HSO4)3 in various solvents, different molar
ratios of reactants at different temperatures.
Molar ratio of
Acetylacetone/
benzhydrol
Entry
Catalyst (mol%)
Solvent
Temperature (◦C)
Time (h)
Conversion (%)
1
2
3
4
5
6
7
8
1/1
1/1
1/1
1/1
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
1/2
none
none
20
20
20
30
10
20
20
20
20
20
20
20
20
20
20
None
Room temperature
Room temperature
Room temperature
Reflux
24
24
24
24
2
2
3
0
0
0
1,2-Dichloroethane
1,2-Dichloroethane
1,2-Dichloroethane
1,2-Dichloroethane
1,2-Dichloroethane
1,2-Dichloroethane
Toluene
CHCl3
CH2Cl2
1,4-Dioxane
CH3NO2
100
100
100
100
100
100
100
100
100
0
0
0
0
100
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
3
7
9
10
11
12
13
14
15
16
17
12
24
8
24
24
24
24
4
H2O
CH3CN
THF
Acetone
1,2-Dichloroethane
Reflux
∗Reaction was performed in the presence of Fe(HSO4)3/Silica
entries 3, 4 with 5). In general, the reaction proceeded of β-dicarbonyl compound in the presence of catalyst.
smoothly for all cases and C-alkylated products were In our experiments, completion of the reaction was
obtained without formation of any side products (sym- confirmed by disappearance of the β-dicarbonyl com-
metric ethers), in very good to excellent yields. As alco- pounds or alcohols on TLC followed by disappearance
hols sensitive to acid- catalyzed dehydration also toler- of OH stretching frequency of enol or alcohol at 3400–
1
ated this method, alkylation reaction by using 1-phenyl 3200 cm−1 in FTIR spectra. In HNMR spectrum, CH
ethanol does not suffer from formation of styrene which proton of C-alkylated product showed (4.74–3.64 ppm)
can be obtained by dehydration of alcohol in acidic a downfield shift as compared to the CH protons of β-
media (table 2, entries 8–14).
dicarbonyl compound. Also, in 13C NMR, a signal at
As shown in table 2, 5,5-dimethylcyclohexane-1,3- 110–61 ppm is assigned to the alkylated carbon which
dione which is in equilibrium with its enol form 3- was shifted to downfield. The structure of all products
hydroxy-5,5-dimethylcyclohex-2-enone, was alkylated was further confirmed by mass spectrometry and CHN
by benzhydrol and 1-phenyl ethanol to 2-benzhydryl-3- analysis.
hydroxy-5,5-dimethylcyclohex-2-enone and 3-hydroxy
On the basis of these observations, we are prompted
-5,5-dimethyl-2-(1-phenylethyl)cyclohex-2-enone, res- to propose the following mechanism (scheme 2) for
pectively in the presence of Fe(HSO4)3. The FT-IR alkylation of β-dicarbonyl compound with alcohols.
spectra of the corresponding products show absorption
It is seen that the addition reaction is in fact a
bands around 3600–3200 and 1737–1714 cm−1 due to BrØnsted acid catalysed reaction. The catalytic process
hydroxyl and carbonyl groups of the more stable enol begins with concomitant conversion of β-dicarbonyl
1
form of the alkylated product. Also, in H NMR spec- compound to enolic form I and protonation of alcohol,
trum, a signal at 15 ppm is assigned to the OH proton by hydrogen sulphate which subsequently affords sta-
of the more stable enol form of the C-alkylated product ble carbocation III from protonated form II by dehydra-
(table 2, entry 7, 14).
tion process. Nucleophilic attack of I to carbocation III
Order of addition of the reactants (β-dicarbonyl com- gives the C-alkylated product and releases the proton
pound and alcohol) is a very important factor in alky- for the next catalytic cycle. Symmetric ether IV as by-
lation reactions in the presence of Fe(HSO4)3. To mini- product was produced by the reaction of carbocation III
mize formation of side products (symmetric ethers), with alcohol. Also, the nucleophilic attack of alcohol
alcohol should be added drop by drop to the solution to I leads to V which by losing alkoxy group produces

C-alkylation of β-dicarbonyl compounds
1909
Table 2. Alkylation of structurally different β-dicarbonyl compounds in the presence of Fe(HSO4)3.
Molar ratio
of dione/
alcohol
Isolated
Time (h) Yield (%)
Entry
1
β-dicarbonyl compound
Alcohol
Product
O
O
Acetylacetone
Benzhydrol
1/2
2
2
80
75
87
85
O
O
O
2
3
4
Ethyl acetoacetate
Diethyl malonate
Benzhydrol
Benzhydrol
Benzhydrol
1/1
2/1
2/1
O
O
O
O
O
O
O
2.5
3
O
O
O
O
Diethyl ethyl malonate
O
Cl
5
6
Dimethyl chloro malonate
Benzhydrol
Benzhydrol
2/1
2/1
1.5
90
95
O
O
O
O
2,2-Dimethyl-1,3-dioxane-4,6-dione
1
O
OH
7∗
5,5-Dimethylcyclohexane-1,3-dione
Acetylacetone
Benzhydrol
1/2
1/2
1
3
75
70
O
O
8
1-Phenylethanol
O
O
O
O
9
Ethyl acetoacetate
1-Phenylethanol
1-Phenylethanol
1/1
2/1
3.5
3.5
70
70
O
O
O
10
Diethyl malonate

1910
Samaneh Khafajeh et al.
Table 2. (contd.)
Molar ratio
of dione/
alcohol
Time Isolated
(h) Yield (%)
Entry
11
β-dicarbonyl compound
Alcohol
Product
O
O
O
O
Diethyl ethyl malonate
1-Phenylethanol
2/1
2/1
4
75
80
O
O
O
O
Cl
12
13
Dimethyl chloromalonate
1-Phenylethanol
1-Phenylethanol
1-Phenylethanol
2.5
O
O
O
O
2,2-Dimethyl-1,3-dioxane-4,6-dione
2/1
1/2
1.5
1.5
80
85
O
OH
14∗ 5,5-Dimethylcyclohexane-1,3-dione
O
O
O
15
16
17
Ethyl acetoacetate
Ethyl acetoacetate
Ethyl acetoacetate
Cinnamyl alcohol
3-Methoxy benzyl alcohol
Benzyl alcohol
1/1
1/1
1/1
3
5
6
85
65
85
O
O
O
O
O
O
O
O
O
O
18
Ethyl acetoacetate
4-Chlorobenzyl alcohol
1/1
7.5
90
Cl
∗Substrate is in equilibrium with its enol form (3-hydroxy-5,5-dimethylcyclohex-2-enone).
All products were identified by comparing their spectral data with those of the authentic samples
O-alkylated product VII. No symmetric ether and O-
Fe(HSO4)3 acts as a recyclable catalyst for alky-
alkylated product have been formed during alkylation lation of β-dicarbonyl compounds in refluxing 1,2-
reaction in the presence of Fe(HSO4)3. Further investi- dichloroethane. The catalyst can be easily recovered
gation on the elucidation of the mechanism and scope of from the reaction mixture by filtration. Solid residue
this reaction are currently underway in our laboratory.
was washed thoroughly with 1,2-dichloroethane and

C-alkylation of β-dicarbonyl compounds
1911
R2
O
R2
R1
R1
IV
OH
R2
R1
OH
R2
OH2
R2
Fe(HSO4)3
Fe(HSO4)3
-H2O
R1
R1
R2
III
R1
OH
O
II
R3
R4
O
O
OH
I
O
R1
R2
R3
R4
R3
R4
-H+
OH
R1
If R3
R2
O
O
or
R =
OR
R3
R4
4
R1
R2
OH
OH
O
O
O
O
R4
R3
R3
OR
R3
OR
OR
-R4
VII
VI
V
Scheme 2. Proposed mechanism for catalytic addition of β-dicarbonyl compound to alcohol.
acetone to remove all organic compounds and then 4. Conclusion
dried at 120◦C. Using this treatment, recyclabilty of the
In this study, we not only investigate another catalytic
activity of Fe(HSO4)3 in organic synthesis but also
develop a method for a general and highly efficient
Fe(HSO4)3-catalysed C-alkylation of a variety of β-
dicarbonyl compounds (acyclic and cyclic β-diketones,
β-keto esters and β-diester) using benzylic and allylic
alcohols as electrophiles. It is remarkable that this
methodology is attractive in comparison to the con-
ventional methods because this method offers several
advantages: (i) The catalyst is stable and reusable and
offers easy handling. Moreover, isolation of the product
by simple filtration of the solid acid is much easier; (ii)
This method gives satisfactory yields of the C-alkylated
products without formation of any side product.
catalyst was evaluated for the reaction of acetylacetone
with benzhydrol (table 3). The recovered catalyst was
reused at least five times without any decrease in the
yield of 3-benzhydryl pentane-2,4-dione. The 6th run
gave 85% conversion after 2 h, but complete conversion
and similar yield were obtained after 3 h.
Table 3. Reaction of acetylacetone with benzhydrol in the
presence of reused Fe(HSO4)3.
Isolated
Yield (%)
Run
Time (h)
Conversion (%)
1
2
2
2
100
100
80
80
3
4
2
2
100
100
80
80
5
2
2/3
100
85/100
80
70/80
Supplementary Information
6a
aSecond number in third column corresponds to conversion
after 3 h
The electronic supporting information can be seen at
www.ias.ac.in/chemsci.

1912
Samaneh Khafajeh et al.
15. Salehi P, Iranpoo N and Behbahani F K 1998
Acknowledgements
Tetrahedron 54 943
The authors thank the Ferdowsi University of Mashhad
Research Council (Grant no. p/3/24394) for partial
financial support.
16. Thirupathi P and Kim S S 2010 Tetrahedron 66 2995
17. Noji M, Konno Y and Ishii K 2007 J. Org. Chem. 72
5161
18. Huang W, Wangn J, Shen Q and Zhou X 2007 Tetrahe-
dron Lett. 48 3969
19. Liu P N, Zho Z Y and Lau C P 2007 Chem. Eur. J. 13
8610
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