American Journal of Analytical Chemistry, 2010, 1, 1-13
doi:10.4236/ajac.2010.11001 Published Online May 2010 (http://www. SciRP.org/journal/ajac)
Enantioresolution of a Series of Chiral Benzyl Alcohols by
HPLC on a Dinitrobenzoylphenylglycine Stationary Phase
after Achiral Pre-Column Derivatization*
Svilen P. Simeonov, Anton P. Simeonov, Aleksandar R. Todorov, Vanya B. Kurteva
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria
Received March 24, 2010; revised April 21, 2010; accepted April 23, 2010
Abstract
High performance liquid chromatography method for the separation of a series of chiral benzyl alcohols on
N-(3,5-dinitrobenzoyl)-D-phenylglycine stationary phase (Macherey Nagel, Chiral-2) after pre-column achiral
derivatization was developed. Cheap and easy available aromatic acid chlorides were used as derivatization
agents. Good to excellent separations of the enantiomers were achieved in all cases in relatively short ana-
lytical runs. It was shown that the enantiorecognition depends on the substituents both in the starting alcohol
and in the acid chloride. The method presents an efficient alternative to the direct analyses on polysaccharide
and cyclodextrine-derived stationary phases.
Keywords: HPLC, DNBPG, Enantioseparation, Benzyl Alcohols, Achiral Pre-Column Derivatization,
Benzoates, Chlorobenzoates, Naphthoates
1. Introduction
Chiral benzyl alcohols are an important class of organic
compounds, which exist as structural subunits in many
natural and biologically active compounds. They are also
widespread products from variety of test transformations
used for determination of asymmetric induction caused
by different asymmetric catalysts [1-7]. Therefore; the
determination of the enantiomeric purity of the products
is a crucial step in the preparation of single-enantiomer
drugs and chiral catalysts and the development of new
and more versatile methods continues to attract attention.
High performance liquid chromatography (HPLC) on
chiral stationary phases (CSPs) is among the most gen-
eral and powerful techniques for separation of optical
isomers [8-13]. The efficiency of the separation is
strongly dependant on the structure of the stationary
phase (SP) used. Of the numerous CSPs available on the
market, Brush- type or Pirkle-type columns, containing a
low-molecular-weight chiral molecule (chiral selector)
covalently bound to the silica gel surface, are the most
widely investigated [14-16]. Among them, the phases
based on derivatives of α-amino acids, inexpensive and
readily available enantiomerically pure materials, are the
most broadly exploited. “Pirkle I-phases” based on dini-
trobenzoylphenylglycine (DNBPG) selector, covalently
bonded to aminopropyl silica via a spacer, are one of the
first and intensively used. The main advantages of these
phases are the relatively low cost of the columns and
their availability in both enantiomeric forms, which is of
great importance for trace analysis where the small peak
should be eluted first. However, their application is lim-
ited in respect to analyte character. DNBPG has two am-
ide groups, which can undergo dipole-dipole interactions
and/or hydrogen bonding with suitable molecules. As
these interactions are responsible for the separation, the
phases are generally inefficient for direct analysis of
some important classes of compounds, such as amines,
amino acids, alcohols, amino alcohols, etc.
The enantiomeric distributions of chiral benzyl alco-
hols were usually analyzed by direct HPLC on polysac-
charide [17-25] or cyclodextrine-derived [26-30] station-
ary phases, while the records on the application of
Brush-type CSPs are quite limited. Enantiomers of ary-
lalkylcarbinols have been resolved upon a CSP com-
prised of DNBPG ionically bonded directly to γ-amino-
propyl silica [31-33]. Sterically congested diarylcarbi-
nols have been resolved by using Pirkle DNBPG ionic or
covalent columns and has suggested that the efficient
enantiorecognition was achieved due to steric hindrance
*Dedicated to the 75th anniversary of Prof. Maria Lyapova

S. P. SIMEONOV ET AL. 2
and hydrogen bonding [34]. Phenyl and anthranyl alka-
nols have been efficiently resolved on SPs with chiral
quinidine-carbamate selectors [35-37]. Phases, obtained
via immobilization of (R,R)-3,5-dinitrobenzoyl-1,2-di-
phenylethane-1,2-diamine with anchoring groups of var-
ied length and structural type, have been efficiently ap-
plied in the enantiorecognition of a series of arylalkylcar-
binols [38-42]. Such a CSP, (S,S)-Whelk-O 1, has been
used both for the direct resolution of diarylmethanols and
for their indirect analyzes as acetates and pivalates, the
latter being more efficient [43]. Esters, carbonates and
carbamates are among the most popular derivatives for
indirect resolution of carbinols [44-50]. The diastereoi-
somers obtained after chiral derivatizations have been
analyzed on a variety of phases [51-59], while achirally
derivatized carbinols have resolved mainly on polysac-
charide-derived CSPs [60-63] and only few articles re-
ported on the application of Pirkle-type phases for the
separation of ethers [64], esters [43,65], carbamates [66-
68]. To the best of our knowledge, the enantiorecognition
of 3,5-dinitro benzoates [65] is the only record in the lit-
erature on the resolution of chiral benzyl alcohols as es-
ters of aromatic acids on DNBPG.
In this paper, we present an effective liquid chromatog-
raphy method for enantioseparation of benzyl alcohols on
one of the cheapest dinitrobenzoylphenylglycine chiral
stationary phase (Macherey Nagel, Chiral-2) after achiral
pre-column derivatizations as benzoates, chlorobenzoates
and naphthoates. The protocol, we believe, is of practical
significance as an alternative to the highly efficient direct
enantiorecognitions on polysaccharide and cyclodextrine-
derived phases.
2. Results and Discussion
A series of known racemic chiral benzyl alcohols 1-5
was obtained by reduction of the parent ketones with
NaBH4 according to a standard procedure. The alcohols
were easily converted into the ester derivatives 7-11 by
refluxing with an acid chloride in pyridine, as shown on
Scheme 1.
These derivatization agents were chosen in an attempt
to increase the interactions between the analyte and the
π-acceptor DNBPG stationary phase. Two alternative
work-up protocols were applied for the isolation of the
Scheme 1. Preparation of benzyl alcohols 1-5 and deriva-
tives 7-12.
products. When ethyl acetate was used for extraction, the
esters 7-11 were isolated in high to excellent yields
(80-95%) after purification by HPFC on silica gel. In the
second scheme, hexane was used instead of ethyl acetate
and the target derivatives were isolated in lower yields
(50-65%) due to their limited solubility in hexane, but
pure enough to be analyzed without chromatography
purification, which shortened significantly the general
analyzing process. Despite reducing the yield of the es-
ters, the results are explicit as indicated by the same
chromatograms obtained after both purification ways.
The latter shows that the hexane extraction is the prefer-
able work-up, except for alcohols available in a highly
limited scale.
The ester derivatives 7-11 were analyzed by HPLC on
Chiral-2 MN column, consisting DNBPG chiral selector,
at 25℃ with mobile phases composed of hexane, i-pro-
panol, and trifluoroacetic acid (TFA) in varied propor-
tions. Excellent to very good separations were achieved
in all cases (Table 1). The retention factors k1 and k2
were recalculated towards To, which was determined by
using benzene as a standard. All resolution parameters
were calculated by the software, adjacent to the appara-
tus, ChemStation for LC 3D Rev. B.01.01.
As a first series, the esters with phenyl alcohols 1-3,
derivatives possessing substituents only at the acid com-
ponent, were analyzed. The derivatives 7-9 were eluted
with hexane/iPr-OH/TFA 100:0.03:0.05 and effective
separations were achieved in fast analytical runs, reten-
tion times of 5-16 min.
Our expectations were to observe better separation
when increasing the π-character of the molecule; naph-
thoates vs benzoates, chlorobenzoates vs benzoates, di-
chlorobenzoates vs monochlorobenzoates. However, ben-
zoates and naphthoates showed commensurable effi-
ciency (Table 1), while a chlorine substituent led to bet-
ter separation only when ortho-positioned (7b-9b), con-
trary to 3-chloro and 4-chlorobenzoates (7c-9c and
7d-9d), which were the less effective derivatives. More-
over, the insertion of a second chlorine substituent led to
lower resolution, 7e-9e vs 7b-9b. The best resolution
factors within this series were obtained for 2-chloro-
benzoates, 2.86, 2.07 and 1.85 for 7b, 8b and 9b, fol-
lowed by 2,4-dichlorobenzoates, 2.52, 1.82 and 1.48 for
7e, 8e and 9e, respectively. The most effective enantio-
separations are illustrated on Figure 1.
As a second series, the esters of alcohols containing
nitro-substituent at the aromatic ring, 4 and 5, were ob-
tained and analyzed. To achieve effective combination
separation/retention time, more polar mobile phase was
used, hexane/iPr-OH/TFA 100:0.1:0.05. As seen on Ta-
ble 1, the two groups of derivatives, 10a-10f and 11a-11f,
follow different separation patterns. Commensurable
resolution factors were obtained for the esters with
2-nitrophenyl alcohol 10a-10f. The retention times of 25-

S. P. SIMEONOV ET AL. 3
Table 1. Resolution of the enantiomers of the benzyl alcohol derivatives 7-12.
Alcohols Derivatives Resolution of the enantiomersa
Compd R1 R
2 Compd Ar k1 k 2 α R S
7a Ph 2.87 3.30 1.11 2.41
7b 2-ClPh 4.05 4.69 1.13 2.86
7c 3-ClPh 1.79 2.07 1.11 1.88
7d 4-ClPh 1.90 2.20 1.11 1.83
7e 2,4-Cl2Ph 1.78 2.10 1.11 2.52
1 H Et
7f 2-naphtyl 3.82 4.39 1.12 2.48
8a Ph 3.33 3.67 1.08 1.65
8b 2-ClPh 4.68 5.21 1.09 2.07
8c 3-ClPh 1.22 1.38 1.07 1.12
8d 4-ClPh 0.83 0.91 1.05 1.01
8e 2,4-Cl2Ph 2.14 2.41 1.08 1.82
2 H Me
8f 2-naphtyl 4.42 4.87 1.08 1.68
9a Ph 3.55 3.83 1.07 1.42
9b 2-ClPh 4.78 5.26 1.08 1.85
9c 3-ClPh 1.55 1.67 1.05 1.08
9d 4-ClPh 2.31 2.50 1.06 1.19
9e 2,4-Cl2Ph 2.19 2.40 1.07 1.48
3 H Bn
9f 2-naphtyl 4.79 5.18 1.07 1.21
10a Ph 12.67 13.73 1.08 1.73
10b 2-ClPh 8.49 9.24 1.08 1.79
10c 3-ClPh 8.07 8.68 1.07 1.60
10d 4-ClPh 8.63 9.28 1.07 1.75
10e 2,4-Cl2Ph 8.35 8.90 1.06 1.34
4 2-NO2 Me
10f 2-naphtyl 18.70 20.29 1.08 1.79
11a Ph 15.33 16.26 1.06 1.34
11b 2-ClPh 8.31 8.68 1.04 0.78
11c 3-ClPh 7.10 7.43 1.04 0.97
11d 4-ClPh 7.13 7.49 1.04 0.97
11e 2,4-Cl2Ph 7.93 8.25 1.04 0.78
5 4-NO2 Me
11f 2-naphtyl 14.34 15.25 1.06 1.32
12a Ph 1.08 1.33 1.17 1.23
12b 2-ClPh 1.70 1.97 1.13 2.11
12c 3-ClPh 0.76 0.93 1.15 1.65
12d 4-ClPh 0.76 0.96 1.17 1.85
12e 2,4-Cl2Ph 0.79 0.96 1.14 1.47
6 2-MeO Et
12f 2-naphtyl 1.98 2.39 1.18 3.22
aFlow rate: 1 mL/min; Detection: 280 nm UV; Column temperature: 25℃; Eluent: hexane/iPr-OH/TFA 100:0.03:0.05 for 7-9; hexane/iPr-OH/
TFA 100:0.1:0.05 for 10 and 11; hexane/iPr-OH/TFA 100:0.5:0.05 for 12; k1: retention factor of the first eluted enantiomer; k2: retention factor
of the second eluted enantiomer; α: separation factor; RS: resolution factor.
27 min were observed for 10b-10e, while slower elution
was detected for 10a and 10f, 36-40 and 53-57 min, re-
spectively. These results show that the monochloroben-
zoates 10b-10d are the derivatives of choice within this
series, 10b being the preferable example. In the case of
the esters with 4-nitrophenyl alcohol 5, the simple ben-
zoate 11a and naphthoate 11f showed the best resolution
factors, 1.34 and 1.32, respectively (Table 1), while 2-
chlorobenzoate 11b and 2,4-dichlorobenzoate 11e were
the less effective derivatives, 0.78. Thus, 11a and 11f are
the preferred derivatives of 5 despite the slower elution
process in respect to 11b-11e, 40-46 vs 21-26 min. The
separations of the enantiomers of 10b and 11a are illus-
trated on Figure 2.
The method was further extended towards the non-
racemic 1-(2-methoxyphenyl)propanol 6, obtained by
addition of diethylzink to the corresponding aldehyde in
the presence of а chiral catalyst by our colleagues [69],
who supplied us with a sample. The unknown ester de-
rivatives 12a-12f were obtained and purified via the
same protocols (Scheme 1) and were afterward analyzed.
Relatively polar mobile phase was used, hexane/iPr-
OH/TFA 100:0.5:0.05, and efficient separations were
achieved in very fast elution, 4-8 min. As seen on Table
1, benzoate 12a was the less effective, 1.23, while the
best separation was achieved for naphthoate 12f, RS 3.22,
which is consistent with the initial expectations. Inside
chlorinated derivatives, 2-chlorobenzoate 12b showed
the best resolution factor, while dichlorosubstituted
compound 12e was the less efficient. The chroma-
tograms of the frontier examples 12a and 12f are given
on Figure 3.
As seen, the separation is good enough even in the case
of 12a to be used for an explicit determination of the en-
antiomeric excess. The latter is confirmed by the fact that
the obtained ee values of the derivatives 12a-12f are in full
congruence with the enantiomeric excess of the starting
alcohol 6, determined by chiral GC analysis [69]. The

S. P. SIMEONOV ET AL. 4
Figure 1. Chromatographic resolution of 1-phenyl-1-alkanol derivatives 7b, 8b and 9b.
Figure 2. Chromatographic resolution of 1-(nitrophenyl)propanol derivatives 10b and 11a

S. P. SIMEONOV ET AL. 5
Figure 3. Chromatographic resolution of 1-(2-methoxyphenyl)propanol derivatives 12a and 12f.
ppearance of the minor (R)-isomer as a first signal pre-
series of chiral racemic benzyl alcohols and a non-
4. Experimental
ts were purchased from Aldrich,
erck and Fluka and were used without any further pu-
tions were performed on an Agilent 1100
Sy
a
sents an additional advantage of the particular analysis
protocol especially when high degree of enantioselectivity
is achieved. The same pattern is valid for the non-racemic
derivatives 7, where the minor (R)-enantiomer elutes
first.
General: All reagen
M
rification. Fluka silica gel/TLC-cards 60778 with fluo-
rescent indicator 254 nm were used for TLC chromatog-
raphy and Rf-values determination. The high perform-
ance flash chromatography (HPFC) purifications were
carried out on a Biotage HorizonTM system (Charlottes-
ville, Virginia, USA) on silica gel. The melting points
were determined in capillary tubes on SRS MPA100
OptiMelt (Sunnyvale, CA, USA) automated melting
point system. The NMR spectra were recorded on a
Bruker Avance DRX 250 and Bruker Avance II+ 600
(where indicated) spectrometers (Rheinstetten, Germany)
in deuterochloroform; the chemical shifts were quoted in
ppm in δ-values against tetramethylsilane (TMS) as an
internal standard and the coupling constants were calcu-
lated in Hz.
The high performance liquid chromatography (HPLC)
enantiosepara
3. Conclusions
A
racemic example were analyzed by liquid chromatography
on DNBPG stationary phases after achiral pre-column
derivatization. Bulk chemistry acid chlorides were used
as derivatization agents and the corresponding esters
were obtained in high yields after fast and simple syn-
thetic protocol. Good to excellent separations of the en-
antiomers were achieved in all cases in relatively short
analytical runs. The presented method gives possibility
to determine the enantiomeric purity or enantioselectivity
in the preparation of benzyl alcohols on one of the
cheapest and widely exploited stationary phases in a fast,
simple, and explicit procedure. Despite being slower than
the direct enantiorecognition, we believe, the protocol
should be useful to the synthetic community as an alter-
native way, especially when other chiral columns are not
available in the laboratory. Additionally, the obtained
broad library of chiral benzyl alcohol esters offers possi-
bility to select a convenient derivative according to the
available reagents.
stem fitted with diode array detector and manual in-
jector with a 20 µL injection loop. A stainless-steel Nu-
cleosil Chiral-2 column (Macherey-Nagel GmbH &Co.
KG, Düren, Germany) was used; 250 × 4 mm, particle
size 5 μm, pore size 100 Å, chiral selector
N-(3,5-dinitrobenzoyl)-D-phenylglycine. The analyses
were performed at 25 ℃with a flow rate of 1.0 mL/min.
The HPLC grade solvents were purchased from

S. P. SIMEONOV ET AL. 6
) in MeOH (20 mL) NaBH
(3
NMR 0.88 (t, 3H, J 7.4, CH), 1.75
(m
6.5, CH), 2.12
(b
:20); H NMR 2.02 (bs, 1H, OH), 2.98 (m, 2H,
C
H NMR 1.52 (d, 3H, J 6.4, CH), 2.99 (s, 1H,
O
H NMR 1.52 (d, 3H, J 6.5, CH), 2.26 (bd,
1H
cohol 1-6 (1 mmol) in pyridine (2 mL) an acid
ch
Ac. The organic layer was dried over NaSO ,
ev
d hexane. The organic layer was dried over NaSO
an
, J 7.4, CH), 1.99 (m, 2H,
C
94 (t, 3H, J 7.4, CH3), 2.00 (m,
2H
0); m. p. 63-64℃; 1H NMR
0.
ne:EtOAc 90:10); H NMR 0.95 (t, 3H, J 7.4,
CH
); H NMR 0.94 (t, 3H, J 7.4, CH), 2.00
(m
0.97 (t, 3H J 7.4, CH), 2.04
(m
NMR 1.66 (d, 3H, J 6.6,
Sigma-Aldrich and Labscan.
Synthesis of chiral racemic benzyl alcohols 1-5: To a
solution of a ketone (20 mmol4
0 mmol) was added portionwise and the mixture was
stirred at room temperature for 0.5-1 h. The solvent was
removed in vacuo and the products were partitioned be-
tween water and CH2Cl2. The organic layer was dried
over Na2SO4, evaporated to dryness, and purified by
HPFC on silica gel.
1-Phen yl-1-prop anol 1 [70]: 92% yield; Rf 0.48 (hex-
ane:EtOAc 80:20); 1H 3
, 2H, CH2), 2.24 (bd, 1H, J 1.7, OH), 4.53 (td, 1H, J
1.7, 7.3, CH), 7.32 (m, 5H, CH-Ph).
1-Phenylethanol 2 [71]: 93% yield; Rf 0.38 (hexane:
EtOAc 80:20); 1H NMR 1.47 (d, 3H, J 3
s, 1H, OH), 4.85 (q, 1H, J 6.5, 12.9, CH), 7.33 (m, 5H,
CH-Ph).
1,2-Diphenylethanol 3 [72]: 59% yield; Rf 0.48 (hexane:
EtOAc 801
H2), 4.86 (dd, 1H, J 5.5, 7.8, CH), 7.24 (m, 10H,
CH-Ph).
1-(2-Nitrophenyl)ethanol 4 [73]: 88% yield; Rf 0.35
(CH2Cl2); 13
H), 5.37 (q, 1H, J 6.2, 12.5, CH), 7.39 (ddd, 1H, J 1.5,
7.4, 8.1, CH-Ar), 7.62 (ddd, 1H, J 1.3, 7.4, 7.9, CH-Ar),
7.80 (dd, 1H, J 1.5, 7.9, CH-Ar), 7.85 (dd, 1H, J 1.3, 8.1,
CH-Ar).
1-(4-Nitrophenyl)ethanol 5 [74]: 97% yield; Rf 0.40
(CH2Cl2); 13
, J 3.4, OH), 5.02 (qd, 1H, J 3.4, 6.5, 13.0, CH), 7.54
(dt, 2H, J 2.4, 8.8, CH-Ar), 8.18 (dt, 2H, J 2.4, 8.8,
CH-Ar).
Synthesis of the derivatives 7-12: To a solution of a
benzyl al
loride (1.1 mmol) was added and the mixture was re-
fluxed for 30 min. Sat. aq. K2CO3 was added and the
mixture was stirred for 15 min at room temperature.
Work-up:
Method 1: The products were partitioned between wa-
ter and EtO2 4
aporated to dryness, and purified by HPFC on silica
gel.
Method 2: The products were partitioned between wa-
ter an2 4
d evaporated to dryness.
1-Phenylpropyl benzoate 7a [75]: 91% yield; Rf 0.56
(CH2Cl2); 1H NMR 0.94 (t, 3H3
H2), 5.94 (t, 1H, J 6.8, CH-O), 7.35 (m, 8H, CH-Ar),
8.08 (m, 2H, CH-Ar); 13C NMR 9.8 (CH3), 29.4 (CH2),
77.7 (CH-O), 126.3 (2 CH-Ar), 127.7 (CH-Ar), 128.2 (2
CH-Ar), 128.3 (2 CH-Ar), 129.4 (2 CH-Ar), 130.4 (Cquat),
132.7 (CH-Ar), 140.5 (Cquat), 165.6 (C=O); HPLC: eluent
hexane/iPr-OH/TFA 100:0.03:0.05, retention times tR-1
10.33 and tR-2 11.47 min.
1-Phenylpropyl 2-chlorobenzoate 7b: 82% yield; Rf
0.72 (CH2Cl2); 1H NMR 0.
, CH2), 5.94 (t, 1H, J 6.8, CH-O), 7.26 (m, 8H,
CH-Ar), 7.80 (dd, 1H, J 1.9, 7.6, CH-Ar); 13C NMR 9.8
(CH3), 29.2 (CH2), 78.6 (CH-O), 126.3 (CH-Ar), 126.5
(2 CH-Ar), 127.7 (CH-Ar), 128.2 (2 CH-Ar), 130.2
(Cquat), 130.8 (CH-Ar), 131.2 (CH-Ar), 132.2 (CH-Ar),
133.4 (Cquat), 139.9 (Cquat), 164.7 (C=O); HPLC: eluent
hexane/iPr-OH/TFA 100:0.03:0.05, retention times tR-1
13.48 and tR-2 15.18 min.
1-Phenylpropyl 3-chlorobenzoate 7c: 81% yield; Rf
0.65 (hexane:CH2Cl2 60:4
96 (t, 3H J 7.4, CH3), 2.02 (2H, m, CH2), 5.91 (t, 1H, J
6.8, CH-O), 7.35 (m, 6H, CH-Ar), 7.52 (ddd, 1H, J 1.2,
2.0, 8.0, CH-Ar), 7.96 (dt, 1H, J 1.3, 7.7, CH-Ar), 8.04 (t,
1H, J 1.8, CH-Ar); 13C NMR 9.9 (CH3), 29.4 (CH2), 78.5
(CH-O), 126.5 (2 CH-Ar), 127.8 (CH-Ar), 128.0
(CH-Ar), 128.5 (2 CH-Ar), 129.6 (CH-Ar), 129.7
(CH-Ar), 132.3 (Cquat), 132.9 (CH-Ar), 134.5 (Cquat),
140.2 (Cquat), 164.7 (C=O); HPLC: eluent hexane/iPr-OH/
TFA 100:0.03:0.05, retention times tR-1 7.45 and tR-2
8.20 min.
1-Phenylpropyl 4-chlorobenzoate 7d: 60% yield; Rf
0.53 (hexa1
3), 2.01 (m, 2H, CH2), 5.91 (t, 1H, J 6.8, CH-O), 7.31
(m, 7H, CH-Ar), 8.01 (dt, 2H, J 2.3, 9.0, CH-Ar); 13C
NMR 9.9 (CH3), 29.4 (CH2), 78.2 (CH-O), 126.4 (2
CH-Ar), 127.9 (CH-Ar), 128.4 (2 CH-Ar), 128.6 (2
CH-Ar), 129.0 (Cquat), 131.0 (2 CH-Ar), 139.3 (Cquat),
140.3 (Cquat), 165.0 (C=O); HPLC: eluent hexane/
iPr-OH/TFA 100:0.03:0.05, retention times tR-1 7.73 and
tR-2 8.54 min.
1-Phenylpropyl 2,4-dichlorobenzoate 7e: 96% yield;
Rf 0.72 (CH2Cl 1
2 3
, 2H, CH2), 5.92 (t, 1H, J 6.8, CH-O), 7.23 (dd, 1H, J
2.0, 8.4, CH-Ar), 7.33 (m, 5H, CH-Ar), 7.41 (d, 1H, J
2.0, CH-Ar), 7.79 (d, 1H, J 8.4, CH-Ar); 13C NMR 9.8
(CH3), 29.2 (CH2), 79.0 (CH-O), 126.5 (2 CH-Ar),
126.8 (CH-Ar), 127.9 (CH-Ar), 128.3 (2 CH-Ar), 128.5
(Cquat), 130.8 (CH-Ar), 132.4 (CH-Ar), 134.7 (Cquat),
138.0 (Cquat), 139.8 (Cquat), 163.9 (C=O); HPLC: eluent
hexane/iPr-OH/TFA 100:0.03:0.05, retention times tR-1
7.43 and tR-2 8.27 min.
1-Phenylpropyl 2-naphthoate 7f [76]: 79% yield; Rf
0.80 (CH2Cl2); 1H NMR3
, 2H, CH2), 6.01 (t, 1H, J 6.8, CH-O), 7.30 (m, 3H,
CH-Ar), 7.44 (m, 4H, CH-Ar), 7.77 (dd, 2H, J 7.0, 8.6,
CH-Ar), 7.87 (dd, 1H, J 2.2, 6.9, CH-Ar), 8.10 (dd, 1H,
J 1.7, 8.6, CH-Ar), 8.63 (s, 1H, CH-Ar); 13C NMR 9.8
(CH3), 29.4 (CH2), 77.8 (CH-O), 125.1 (CH-Ar), 126.3
(2 CH-Ar), 126.4 (CH-Ar), 127.5 (CH-Ar), 127.6 (Cquat),
127.7 (CH-Ar), 127.9 (CH-Ar),128.0 (CH-Ar), 128.3 (2
CH-Ar), 129.1 (CH-Ar), 130.8 (CH-Ar), 132.3 (Cquat),
135.3 (Cquat), 140.5 (Cquat), 165.8 (C=O); HPLC: eluent
hexane/iPr-OH/TFA 100:0.03:0.05, retention times tR-1
12.87 and tR-2 14.39 min.
1-Phenylethyl benzoate 8a [77]: 51% yield; Rf 0.40
(hexan e:CH 2Cl2 60:40); 1H

S. P. SIMEONOV ET AL.7
C
f
(d, 3H, J 6.6,
C
60:40); m. p. 134-136℃; H NMR
1.
R 1.69 (d, 3H, J
6.
hexane:CH Cl 60:40); H NMR 1.67 (d, 3H, J
6.
ne:CH2Cl2 40:60); H NMR 1.71 (d, 3H, J 6.6,
C
Ac 90:10); m. p. 67-68℃ (lit. [80] 70℃); H
N
.19 (A part of
A
(hexane:EtOAc 90:10); m. p. 73-74℃; H NMR
3.
-101℃; H NMR
3.
H3), 6.14 (q, 1H, J 6.6, 13.2, CH-O), 7.38 (m, 8H,
CH-Ar), 8.08 (m, 2H, CH-Ar); 13C NMR 22.3 (CH3),
72.8 (CH-O), 126.0 (2 CH-Ar), 127.8 (CH-Ar), 128.3 (2
CH-Ar), 128.5 (2 CH-Ar), 129.6 (2 CH-Ar), 130.5
(Cquat), 132.8 (CH-Ar), 141.7 (Cquat), 165.7 (C=O);
HPLC: eluent hexane/iPr-OH/TFA 100:0.03:0.05, reten-
tion times tR-1 11.56 and tR-2 12.47 min.
1-Phenylethyl 2-chlorobenzoate 8b: 45% yield; R
0.59 (hexane:CH2Cl2 60:40); 1H NMR 1.68
H3), 6.14 (q, 1H, J 6.6, 13.2, CH-O), 7.35 (m, 8H,
CH-Ar), 7.82 (ddd, 1H, J 0.5, 1.7, 7.7, CH-Ar); 13C
NMR 22.2 (CH3), 73.8 (CH-O), 126.2 (2 CH-Ar), 126.5
(CH-Ar), 128.0 (CH-Ar), 128.5 (2 CH-Ar), 130.4 (Cquat),
131.0 (CH-Ar), 131.3 (CH-Ar), 132.4 (CH-Ar), 133.6
(Cquat), 141.2 (Cquat), 164.9 (C=O); HPLC: eluent hexane/
iPr-OH/TFA 100:0.03:0.05, retention times tR-1 15.16
and tR-2 16.58 min.
1-Phenylethyl 3-chlorobenzoate 8c [78]: 48% yield; Rf
0.64 (hexane:CH2Cl21
69 (d, 3H, J 6.6, CH3), 6.14 (dd, 1H, J 6.6, 13.2, CH-O),
7.41 (m, 6H, CH-Ar), 7.53 (ddd, 1H, J 1.2, 2.1, 8.0,
CH-Ar), 7.96 (dt, 1H, J 1.4, 7.8, CH-Ar), 8.05 (t, 1H, J
2.0, CH-Ar); 13C NMR 22.2 (CH3), 73.5 (CH-O), 126.1
(2 CH-Ar), 127.8 (CH-Ar) 128.0 (CH-Ar) 128.6 (2
CH-Ar), 129.6 (CH-Ar), 132.3 (CH-Ar), 132.9 (CH-Ar),
133.7 (Cquat), 134.5 (Cquat), 141.4 (Cquat), 164.6 (C=O);
HPLC: eluent hexane/iPr-OH/TFA 100:0.03:0.05, reten-
tion times tR-1 5.94 and tR-2 6.35 min.
1-Phenylethyl 4-chlorobenzoate 8d: 99% yield; Rf
0.72 (hexane:CH2Cl2 40:60); 1H NM
6, CH3), 6.14 (dd, 1H, J 6.6, 13.2, CH-O) 7.37 (m, 7H,
CH-Ar), 8.02 (ddd, 2H, J 2.0, 2.3, 8.4, CH-Ar); 13C
NMR 22.3 (CH3), 73.2 (CH-O), 126.0 (2 CH-Ar), 128.0
(CH-Ar), 128.5 (2 CH-Ar), 128.6 (2 CH-Ar), 129.0
(Cquat), 131.0 (2 CH-Ar), 139.3 (Cquat), 141.5 (Cquat),
164.9 (C=O); HPLC: eluent hexane/iPr-OH/TFA
100:0.03:0.05, retention times tR-1 4.88 and tR-2 5.10
min.
1-Phenylethyl 2,4-dichlorobenzoate 8e: 86% yield; Rf
0.70 (1
2 2
6, CH3), 6.12 (q, 1H, J 6.6, 13.2, CH-O), 7.34 (m, 7H,
CH-Ar), 7.79 (d, 1H, J 8.4, CH-Ar); 13C NMR 22.2
(CH3), 74.1 (CH-O), 126.2 (2 CH-Ar), 126.9 (CH-Ar),
128.1 (CH-Ar), 128.5 (2 CH-Ar), 128.6 (Cquat), 130.9
(CH-Ar), 132.5 (CH-Ar), 134.9 (Cquat), 138.2 (Cquat),
141.0 (Cquat), 164.0 (C=O); HPLC: eluent hexane/iPr-OH/
TFA 100:0.03:0.05, retention times tR-1 8.39 and tR-2
9.10 min.
1-Phenylethyl 2-naphthoate 8f [79]: 50% yield; Rf
0.63 (hexa1
H3), 6.20 (q, 1H, J 6.6, 13.2, CH-O), 7.32 (m, 3H,
CH-Ar), 7.50 (m, 4H, CH-Ar), 7.82 (m, 2H, CH-Ar),
7.91 (dd, 1H, J 1.7, 7.3, CH-Ar), 8.09 (dd, 1H, J 1.7, 8.6,
CH-Ar), 8.63 (s, 1H, CH-Ar); 13C NMR 22.3 (CH3), 73.0
(CH-O), 125.2 (CH-Ar), 126.0 (2 CH-Ar), 126.5
(CH-Ar), 127.6 (CH-Ar), 127.7 (Cquat), 127.8 (CH-Ar),
128.0 (CH-Ar), 128.1 (CH-Ar), 128.5 (2 CH-Ar) 129.3
(CH-Ar), 131.0 (CH-Ar), 132.4 (Cquat), 135.4 (Cquat),
141.8 (Cquat), 165.9 (C=O); HPLC: eluent hexane/iPr-OH/
TFA 100:0.03:0.05, retention times tR-1 14.48 and tR-2
15.68 min.
1,2-Diphenylethyl benzoate 9a [80]: 73% yield; Rf 0.43
(hexane:EtO 1
MR 3.19 (A part of ABX, 1H, JAX 6.0, JAB 13.8, ½
CH2), 3.35 (B part of ABX, 1H, JBX 7.8, JAB 13.8, ½
CH2), 6.18 (dd, 1H, J 6.0, 7.6, CH-O), 7.18 (m, 5H,
CH-Ar), 7.30 (m, 5H, CH-Ar), 7.41 (m, 2H, CH-Ar),
7.53 (m, 1H, CH-Ar), 8.04 (m, 2H, CH-Ar); 13C NMR
43.2 (CH2), 77.2 (CH-O), 126.5 (2 CH-Ar), 126.6
(CH-Ar), 127.9 (CH-Ar), 128.2 (2 CH-Ar), 128.3 (2
CH-Ar), 128.4 (2 CH-Ar), 129.6 (4 CH-Ar), 130.4 (Cquat),
132.9 (CH-Ar), 136.9 (Cquat), 140.1 (Cquat), 165.6 (C=O);
HPLC: eluent hexane/iPr-OH/TFA 100:0.03:0.05, reten-
tion times tR-1 12.14 and tR-2 12.97 min.
1,2-Diphenylethyl 2-chlorobenzoate 9b: 65% yield; Rf
0.63 (hexane:EtOAc 90:10); 1H NMR 3
BX, 1H, JAX 6.4, JAB 13.7, ½ CH2), 3.36 (B part of
ABX, 1H, JBX 7.6, JAB 13.7, ½ CH2), 6.20 (dd, 1H, J 6.4,
7.6, CH-O), 7.28 (m, 13H, CH-Ar), 7.73 (ddd, 1H, J 0.6,
1.5, 8.0, CH-Ar); 13C NMR 43.0 (CH2), 78.1 (CH-O),
126.5 (CH-Ar), 126.6 (CH-Ar), 126.7 (2 CH-Ar), 128.1
(CH-Ar), 128.3 (2 CH-Ar), 128.4 (2 CH-Ar), 129.6 (2
CH-Ar), 130.2 (Cquat), 131.0 (CH-Ar), 131.4 (CH-Ar),
132.4 (CH-Ar), 133.8 (Cquat), 136.7 (Cquat), 139.6 (Cquat),
164.7 (C=O); HPLC: eluent hexane/iPr-OH/TFA
100:0.03:0.05, retention times tR-1 15.43 and tR-2 16.72
min.
1,2-Diphenylethyl 3-chlorobenzoate 9c: 56% yield; Rf
0.40 1
19 (A part of ABX, 1H, JAX 6.1, JAB 13.8, ½ CH2), 3.35
(B part of ABX, 1H, JBX 7.7, JAB 13.8, ½ CH2), 6.17 (dd,
1H, J 6.1, 7.7, CH-O), 7.17 (m, 5H, CH-Ar), 7.33 (m, 6H,
CH-Ar), 7.51 (dd, 1H, J 1.2, 2.1, CH-Ar), 7.90 (dt, 1H, J
1.4, 7.8, CH-Ar), 7.99 (td, 1H, J 1.6, 2.1, CH-Ar); 13C
NMR 43.1 (CH2), 77.8 (CH-O), 126.5 (2 CH-Ar), 126.7
(CH-Ar), 127.7 (CH-Ar), 128.1 (CH-Ar), 128.3 (2
CH-Ar), 128.4 (2 CH-Ar), 129.5 (2 CH-Ar),129.6
(CH-Ar), 129.7 (CH-Ar), 132.1 (Cquat), 132.9 (CH-Ar),
134.5 (Cquat), 136.7 (Cquat), 139.7 (Cquat), 164.4 (C=O);
HPLC: eluent hexane/iPr-OH/TFA 100:0.03:0.05, reten-
tion times tR-1 6.80 and tR-2 7.12 min.
1,2-Diphenylethyl 4-chlorobenzoate 9d: 80% yield; Rf
0.49 (hexane:EtOAc 90:10); m. p. 1001
18 (A part of ABX, 1H, JAX 6.0, JAB 13.8, ½ CH2), 3.34
(B part of ABX, 1H, JBX 7.6, JAB 13.8, ½ CH2), 6.16 (dd,
1H, J 6.0, 7.6, CH-O), 7.17 (m, 5H, CH-Ar), 7.32 (m, 5H,
CH-Ar), 7.39 (dd, 2H, J 0.6, 8.4, CH-Ar), 7.96 (dd, 2H, J
0.6, 8.4, CH-Ar); 13C NMR 43.1 (CH2), 77.5 (CH-O),
126.5 (2 CH-Ar), 126.6 (CH-Ar), 128.91 (CH-Ar), 128.3
(2 CH-Ar), 128.4 (2 CH-Ar), 128.7 (2 CH-Ar), 128.8

S. P. SIMEONOV ET AL. 8
90:10); H NMR 3.18 (A part of
A
; H NMR 3.24
(A
2 (hexane:CHCl 50:50); H NMR (600 MHz)
1.
R 0.30 (hexane:CHCl 50:50); m. p. 64-65℃; H
N
:50); H NMR 1.79 (d, 3H, J
6.
H NMR (600
M
p: 69-71℃; H
N
(hexane:CHCl 50:50); m. p. 80-82℃; H NMR
1.
165.6 (C=O); HPLC: eluent hexane/iPr-OH/TFA
(Cquat), 129.5 (2 CH-Ar), 133.0 (2 CH-Ar), 136.8 (Cquat),
139.4 (Cquat), 139.8 (Cquat), 164.8 (C=O); HPLC: eluent
hexane/iPr-OH/TFA 100:0.03:0.05, retention times tR-1
8.85 and tR-2 9.34 min.
1,2-Diphenylethyl 2,4-dichlorobenzoate 9e: 75 % yield;
Rf 0.42 (hexane:EtOAc 1
BX, 1H, JAX 6.3, JAB 13.8, ½ CH2), 3.34 (B part of
ABX, 1H, JBX 7.7, JAB 13.8, ½ CH2), 6.19 (dd, 1H, J 6.3,
7.7, CH-O), 7.13 (m, 2H, CH-Ar), 7.24 (m, 5H, CH-Ar),
7.33 (m, 4H, CH-Ar), 7.44 (d, 1H, J 2.0, CH-Ar), 7.69 (d,
1H, J 8.4, CH-Ar); 13C NMR 43.0 (CH2), 78.4 (CH-O),
126.6 (CH-Ar), 126.7 (2 CH-Ar), 126.9 (CH-Ar), 128.2
(CH-Ar), 128.3 (2 CH-Ar), 128.4 (2 CH-Ar), 129.5 (2
CH-Ar), 131.0 (CH-Ar), 132.5 (CH-Ar), 134.9 (Cquat),
136.6 (Cquat), 138.2 (Cquat), 139.4 (Cquat), 163.8 (C=O);
HPLC: eluent hexane/iPr-OH/TFA 100:0.03:0.05, reten-
tion times tR-1 8.51 and tR-2 9.09 min.
1,2-Diphenylethyl 2-naphthoate 9f: 70% yield; Rf 0.67
(hexane:EtOAc 85:15); m. p. 99-100℃1
part of ABX, 1H, JAX 6.1, JAB 13.8, ½ CH2), 3.41 (B
part of ABX, 1H, JBX 7.5, JAB 13.8, ½ CH2), 6.25 (dd, 1H,
J 6.1, 7.5, CH-O), 7.18 (m, 5H, CH-Ar), 7.34 (m, 5H,
CH-Ar), 7.41 (m, 2H, CH-Ar), 7.54 (tdd, 2H, J 1.6, 6.9,
12.3, CH-Ar), 7.85 (d, 2H, J 8.6, CH-Ar), 7.94 (dd, 1H, J
1.8, 7.7, CH-Ar), 8.05 (dd, 1H, J 1.6, 8.6, CH-Ar), 8.59
(s, 1H, CH-Ar); 13C NMR 43.2 (CH2), 77.4 (CH-O),
125.2 (CH-Ar), 126.5 (2 CH-Ar), 126.6 (2 CH-Ar),
127.6 (Cquat), 127.7 (CH-Ar), 128.0 (CH-Ar), 128.1
(CH-Ar), 128.2 (CH-Ar), 128.3 (2 CH-Ar), 128.4 (2
CH-Ar), 129.4 (CH-Ar), 129.6 (2 CH-Ar), 131.1
(CH-Ar), 132.5 (Cquat), 135.5 (Cquat), 136.9 (Cquat), 140.1
(Cquat), 165.8 (C=O); HPLC: eluent hexane/iPr-OH/TFA
100:0.03:0.05, retention times tR-1 15.45 and tR-2 16.49
min.
1-(2-Nitrophenyl)ethyl benzoate 10a [81]: 80% yield;
Rf 0.31
2 2
79 (d, 3H, J 6.5, CH3), 6.57 (q, 1H, J 6.5, 12.9, CH-O),
7.43 (t, 1H, J 7.3, CH-Ar), 7.45 (t, 2H, J 7.8, CH-Ar),
7.58 (t, 1H, J 7.4, CH-Ar), 7.62 (t, 1H, J 7.4, CH-Ar),
7.74 (d, 1H, J 7.9, CH-Ar), 7.97 (d, 1H, J 8.2, CH-Ar),
8.07 (d, 2H, J 7.3, CH-Ar); 13C NMR 22.1 (CH3), 68.7
(CH-O), 124.4 (CH-Ar), 127.1 (CH-Ar), 128.3 (CH-Ar),
128.4 (2 CH-Ar), 129.6 (2 CH-Ar), 129.8 (Cquat), 133.2
(CH-Ar), 133.6 (CH-Ar), 138.1 (Cquat), 147.6 (Cquat),
165.4 (C=O); HPLC: eluent hexane/iPr-OH/TFA
100:0.1:0.05, retention times tR-1 36.51 and tR-2 39.34
min.
1-(2-Nitrophenyl)ethyl 2-chlorobenzoate 10b: 82%
yield; 1
f2 2
MR 1.79 (d, 3H, J 6.5, CH3), 6.62 (q, 1H, J 6.5, 12.9,
CH-O), 7.433 (m, 1H, CH-Ar), 7.44 (m, 3H, CH-Ar),
7.64 (tdd, 1H, J 0.4, 1.3, 7.8, CH-Ar), 7.79 (dd, 1H, J 1.5,
7.9, CH-Ar), 7.84 (ddd, 1H, J 0.6, 1.7, 7.6, CH-Ar), 7.98
(dd, 1H, J 1.3, 8.2, CH-Ar); 13C NMR 22.1 (CH3), 69.6
(CH-O), 124.5 (CH-Ar), 126.6 (CH-Ar), 127.5 (CH-Ar),
128.5 (CH-Ar), 129.8 (Cquat), 131.1 (CH-Ar), 131.5
(CH-Ar), 131.6 (Cquat), 132.7 (CH-Ar), 133.7 (CH-Ar),
137.6 (Cquat), 147.6 (Cquat), 164.6 (C=O); HPLC: eluent
hexane/iPr-OH/TFA 100:0.1:0.05, retention times tR-1
25.35 and tR-2 27.34 min.
1-(2-Nitrophenyl)ethyl 3-chlorobenzoate 10c: 86% yield;
Rf 0.48 (hexane:CH2Cl2 501
5, CH3), 6.57 (q, 1H, J 6.5, 12.9, CH-O), 7.39 (t, 1H, J
7.7, CH-Ar), 7.44 (ddd, 1H, J 1.6, 7.2, 8.2, CH-Ar), 7.54
(ddd, 1H, J 1.2, 2.2, 8.0, CH-Ar), 7.63 (td, 1H, J 1.3, 7.9,
CH-Ar), 7.70 (td, 1H, J 1.7, 7.9, CH-Ar), 7.95 (m, 2H,
CH-Ar), 8.02 (td, 1H, J 1.7, 2.0, CH-Ar); 13C NMR 22.0
(CH3), 69.2 (CH-O), 124.5 (CH-Ar), 127.0 (CH-Ar),
127.7 (CH-Ar), 128.5 (CH-Ar), 129.6 (2 CH-Ar), 129.8
(CH-Ar), 131.6 (Cquat), 133.2 (CH-Ar), 133.7 (CH-Ar),
134.6 (Cquat), 137.6 (Cquat), 147.7 (Cquat), 164.2 (C=O);
HPLC: eluent hexane/iPr-OH/TFA 100:0.1:0.05, reten-
tion times tR-1 24.22 and tR-2 25.84 min.
1-(2-Nitrophenyl)ethyl 4-chlorobenzoate 10d: 79%
yield; Rf 0.31 (hexane:CH2Cl2 50:50); 1
Hz) 1.79 (d, 3H, J 6.5, CH3), 6.56 (q, 1H, J 6.5, 13.0,
CH-O), 7.42 (d, 2H, J 8.5, CH-Ar), 7.45 (td, 1H, J 0.8,
8.2, CH-Ar), 7.63 (t, 1H, J 7.6, CH-Ar), 7.70 (d, 1H, J
7.6, CH-Ar), 7.97 (d, 1H, J 8.4, CH-Ar), 7.99 (d, 2H, J
8.5, CH-Ar); 13C NMR 22.1 (CH3), 69.1 (CH-O), 124.6
(CH-Ar), 127.1 (CH-Ar), 128.3 (Cquat), 128.5 (CH-Ar),
128.8 (2 CH-Ar), 131.2 (2 CH-Ar), 133.7 (CH-Ar),
137.8 (Cquat), 139.7 (Cquat), 147.7 (Cquat), 164.6 (C=O);
HPLC: eluent hexane/iPr-OH/TFA 100:0.1:0.05, reten-
tion times tR-1 25.70 and tR-2 27.46 min.
1-(2-Nitrophenyl)ethyl 2,4-dichlorobenzoate 10e: 76%
yield; Rf 0.32 (hexane:CH2Cl2 50:50); m1
MR 1.79 (d, 3H, J 6.5, CH3), 6.60 (q, 1H, J 6.5, 12.9,
CH-O), 7.31 (dd, 1H, J 2.0, 8.4, CH-Ar), 7.45 (ddd, 1H, J
1.5, 7.3. 8.2, CH-Ar), 7.48 (d, 1H, J 2.1, CH-Ar), 7.64
(ddd, 1H, J 1.2, 7.6, 8.0, CH-Ar), 7.75 (dd, 1H, J 1.5, 7.9,
CH-Ar), 7.82 (d, 1H, J 8.4, CH-Ar), 7.98 (dd, 1H, J 1.2,
8.2, CH-Ar); 13C NMR 22.1 (CH3), 69.9 (CH-O), 124.6
(CH-Ar), 127.1 (CH-Ar), 127.4 (CH-Ar), 128.0 (Cquat),
128.6 (CH-Ar), 131.1 (CH-Ar), 132.6 (CH-Ar), 133.7
(CH-Ar), 134.9 (Cquat), 137.4 (Cquat), 138.6 (Cquat), 147.7
(Cquat), 163.7 (C=O); HPLC: eluent hexane/iPr-OH/TFA
100:0.1:0.05, retention times tR-1 24.97 and tR-2 26.44
min.
1-(2-Nitrophenyl)ethyl 2-naphthoate 10f: 70% yield;
Rf 0.341
2 2
84 (d, 3H, J 6.5, CH3), 6.64 (q, 1H, J 6.5, 12.9, CH-O),
7.42 (ddd, 1H, J 1.5, 7.4, 8.2, CH-Ar), 7.58 (m, 3H,
CH-Ar), 7.78 (dd, 1H, J 1.5, 7.9, CH-Ar), 7.88 (m, 2H,
CH-Ar), 7.96 (m, 1H, CH-Ar), 7.97 (dd, 1H, J 1.4, 8.2,
CH-Ar), 8.06 (dd, 12H, J 1.7, 8.6, CH-Ar), 8.62 (s, 1H,
CH-Ar); 13C NMR 22.1 (CH3), 68.9 (CH-O), 124.5
(CH-Ar), 125.1 (CH-Ar), 126.7 (CH-Ar), 127.1 (CH-Ar),
127.8 (CH-Ar), 128.2 (CH-Ar), 128.4 (2 CH-Ar), 129.3
(CH-Ar), 129.9 (Cquat), 131.2 (CH-Ar), 132.4 (Cquat),
133.6 (CH-Ar), 135.6 (Cquat), 138.1 (Cquat), 147.8 (Cquat),

S. P. SIMEONOV ET AL.9
1
1H
19 (q, 1H, J 6.6, 13.3, CH-O),
7.
-O),
7.
13.3,
C
, J 6.6, CH), 6.17 (q, 1H, J 6.6, 13.2,
C
J 6.6, CH), 6.23 (q, 1H, J 6.6, 13.3, CH-O),
7.
J 7.4, CH3), 1.97 (m, 2H, CH2), 3.85 (s, 3H,
O
), 1.98 (m, 2H, CH), 3.86 (s,
3H
3H
100:0.1:0.05, retention times tR-1 52.59 and tR-2 56.85
min.
1-(4-Nitrophenyl)ethyl benzoate 11a [82]: 82% yield;
Rf 0.40 (hexane:CH2Cl2 40:60); m. p. 94-95℃ (lit. [82]
94.8-95.5℃); H NMR 1.70 (d, 3H, J 6.7, CH3), 6.18 (q,
, J 6.6, 13.2, CH-O), 7.46 (m, 2H, CH-Ar), 7.59 (m,
3H, CH-Ar), 8.09 (dt, 2H, J 1.4, 7.0, CH-Ar), 8.23 (dt,
2H, J 1.9, 8.8, CH-Ar); 13C NMR 22.4 (CH3), 71.8
(CH-O), 124.0 (2 CH-Ar), 126.7 (2 CH-Ar), 128.5 (2
CH-Ar), 129.7 (2 CH-Ar), 129.9 (Cquat), 133.3 (CH-Ar),
147.5 (Cquat), 149.1 (Cquat), 165.6 (C=O); HPLC: eluent
hexane/iPr-OH/TFA 100:0.1:0.05, retention times tR-1
43.59 and tR-2 46.09 min.
1-(4-Nitrophenyl)ethyl 2-chlorobenzoate 11b: 66% yield;
Rf 0.60 (hexane:CH2Cl2 40:60); m. p. 52-53℃; 1H NMR
1.71 (d, 3H, J 6.6, CH3), 6.
33 (m, 1H, CH-Ar), 7.45 (m, 2H, CH-Ar), 7.62 (dt, 2H,
J 1.7, 8.6, CH-Ar), 7.85 (ddd, 1H, J 0.5, 1.6, 8.6, CH-Ar),
8.23 (dt, 2H, J 2.0, 8.8, CH-Ar); 13C NMR 22.3 (CH3),
72.7 (CH-O), 123.9 (2 CH-Ar), 126.7 (CH-Ar), 126.9 (2
CH-Ar), 129.7 (Cquat), 131.2 (CH-Ar), 131.4 (CH-Ar),
132.8 (CH-Ar), 133.8 (Cquat), 147.6 (Cquat), 148.5 (Cquat),
164.7 (C=O); HPLC: eluent hexane/iPr-OH/TFA 100:0.1:
0.05, retention times tR-1 24.86 and tR-2 25.85 min.
1-(4-Nitrophenyl)ethyl 3-chlorobenzoate 11c: 88% yield;
Rf 0.53 (hexane:CH2Cl2 40:60); m. p. 54-55℃; 1H NMR
1.71 (d, 3H, J 6.6, CH3), 6.17 (q, 1H, J 6.6, 13.3, CH
40 (t, 1H, J 7.9, CH-Ar), 7.55 (ddd, 1H, J 1.2, 2.2, 8.1,
CH-Ar), 7.59 (dt, 2H, J 2.2, 8.8, CH-Ar), 7.96 (dt, 1H, J
1.4, 7.7, CH-Ar), 8.04 (dd, 1H, J 1.7, 2.0, CH-Ar), 8.23
(dt, 2H, J 2.2, 8.8, CH-Ar); 13C NMR 22.2 (CH3), 72.3
(CH-O), 123.9 (2 CH-Ar), 126.7 (2 CH-Ar), 127.8
(CH-Ar), 129.6 (CH-Ar), 129.8 (CH-Ar), 131.6 (Cquat),
133.3 (CH-Ar), 134.6 (Cquat), 147.6 (Cquat), 148.6 (Cquat),
164.3 (C=O); HPLC: eluent hexane/iPr-OH/TFA 100:0.1:
0.05, retention times tR-1 21.62and tR-2 22.50 min.
1-(4-Nitrophenyl)ethyl 4-chlorobenzoate 11d: 64%
yield, Rf 0.50 (hexane:CH2Cl2 40:60); m. p. 61-63℃; 1H
NMR 1.70 (d, 3H, J 6.6, CH), 6.16 (q, 1H, J 6.6,
3
H-O), 7.43 (dt, 2H, J 2.2, 8.7, CH-Ar), 7.59 (dt, 2H, J
2.2, 8.7, CH-Ar), 8.01 (dt, 2H, J 2.2, 8.7, CH-Ar), 8.23
(dt, 2H, J 2.2, 8.7, CH-Ar); 13C NMR 22.3 (CH3), 72.2
(CH-O), 124.0 (2 CH-Ar), 126.8 (2 CH-Ar), 128.3 (Cquat),
128.9 (2 CH-Ar), 131.0 (2 CH-Ar), 139.9 (Cquat), 147.6
(Cquat), 148.8 (Cquat), 164.8 (C=O); HPLC: eluent hex-
ane/iPr-OH/TFA 100:0.1:0.05, retention times tR-1 21.71
and tR-2 22.66 min.
1-(4-Nitrophenyl)ethyl 2,4-dichlorobenzoate 11e: 22%
yield; Rf 0.63 (hexane:CH2Cl2 60:40); m. p. 111-113℃;
1H NMR 1.71 (d, 3H3
H-O), 7.32 (dd, 1H, J 2.0, 8.4, CH-Ar), 7.49 (d, 1H, J
2.0, CH-Ar), 7.61 (dt, 2H, J 2.2, 8.7, CH-Ar), 7.83 (d, 1H,
J 8.4, CH-Ar), 8.23 (dt, 2H, J 2.2, 8.7, CH-Ar); 13C NMR
22.2 (CH3), 73.0 (CH-O), 123.9 (2 CH-Ar), 126.9 (2
CH-Ar), 127.1 (CH-Ar), 127.9 (Cquat), 131.1 (CH-Ar),
132.6 (CH-Ar), 135.0 (Cquat), 138.7 (Cquat), 147.6 (Cquat),
148.2 (Cquat), 163.8 (C=O); HPLC: eluent hexane/iPr-OH/
TFA 100:0.1:0.05, retention times tR-1 23.85 and tR-2
24.70 min.
1-(4-Nitrophenyl)ethyl 2-naphthoate 11f: 17% yield; Rf
0.54 (hexane:CH2Cl2 40:60); m. p. 65-66℃; 1H NMR
1.74 (d, 3H, 3
57 (m, 2H, CH-Ar), 7.62 (dt, 2H, J 2.2, 8.9, CH-Ar),
7.88 (m, 2H, CH-Ar), 7.96 (ddd, 1H, J 0.6, 1.6, 7.6,
CH-Ar), 8.08 (dd, 1H, J 1.7, 8.6, CH-Ar), 8.22 (dt, 2H, J
2.1, 8.9, CH-Ar), 8.64 (s, 1H, CH-Ar); 13C NMR 22.3
(CH3), 71.9 (CH-O), 123.9 (2 CH-Ar), 125.0 (CH-Ar),
126.7 (2 CH-Ar), 126.8 (CH-Ar), 127.0 (Cquat), 127.8
(CH-Ar), 128.3 (CH-Ar), 128.4 (CH-Ar), 129.3 (CH-Ar),
131.2 (CH-Ar), 132.4 (Cquat), 135.6 (Cquat), 147.5 (Cquat),
149.1 (Cquat), 165.7 (C=O); HPLC: eluent hexane/iPr-OH/
TFA 100:0.1:0.05, retention times tR-1 40.97 and tR-2
43.40 min.
1-(2-Methoxyphenyl)propyl benzoate 12a: 66% yield;
Rf 0.46 (hexane:CH2Cl2 60:40); 1H NMR (600 MHz)
0.98 (t, 3H,
CH3), 6.37 (t, 1H, J 6.4, CH-O), 6.88 (d, 1H, J 8.2,
CH-Ar), 6.93 (t, 1H, J 7.4, CH-Ar), 7.23 (ddd, 1H, J 1.5,
7.8, 8.3, CH-Ar), 7.39 (dd, 1H, J 1.4, 7.6, CH-Ar), 7.44 (t,
2H, J 7.6, CH-Ar), 7.54 (tt, 1H, J 1.4, 7.4, CH-Ar), 8.11
(dd, 2H, J 1.2, 8.4, CH-Ar); 13C NMR 9.9 (CH3), 28.6
(CH2), 55.5 (OCH3), 72.3 (CH-O), 110.5 (CH-Ar), 120.5
(CH-Ar), 126.1 (CH-Ar), 128.3 (2 CH-Ar), 128.5
(CH-Ar), 129.4 (Cquat), 129.6 (2 CH-Ar), 130.7 (Cquat),
132.8 (CH-Ar), 156.2 (Cquat), 165.8 (C=O); HPLC: elu-
ent hexane/iPr-OH/TFA 100:0.5:0.05, retention times
tR-1 5.55 and tR-2 6.21 min.
1-(2-Methoxyphenyl)propyl 2-chlorobenzoate 12b: 99
% yield; Rf 0.20 (hexane:CH2Cl2 70:30); 1H NMR (600
MHz) 0.99 (t, 3H, J 7.4, CH3 2
, OCH3), 6.40 (t, 1H, J 6.4, CH-O), 6.88 (d, 1H, J 8.2,
CH-Ar), 6.94 (t, 1H, J 7.4, CH-Ar), 7.25 (ddd, 1H, J 1.4,
7.2, 8.7, CH-Ar), 7.30 (dd, 1H, J 1.1, 7.4, CH-Ar), 7.41
(m, 3H, CH-Ar), 7.864 (dd, 1H, J 1.5, 7.7, CH-Ar); 13C
NMR 9.9 (CH3), 28.4 (CH2), 55.5 (OCH3), 73.2 (CH-O),
110.5 (CH-Ar), 120.5 (CH-Ar), 126.5 (2 CH-Ar), 128.6
(CH-Ar), 128.9 (Cquat), 130.6 (Cquat), 131.0 (CH-Ar),
131.4 (CH-Ar), 132.3 (CH-Ar), 133.6 (Cquat), 156.3
(Cquat), 165.0 (C=O); HPLC: eluent hexane/iPr-OH/TFA
100:0.5:0.05, retention times tR-1 7.20 and tR-2 7.92 min.
1-(2-Methoxyphenyl)propyl 3-chlorobenzoate 12c: 95
% yield; Rf 0.11 (hexane:CH2Cl2 70:630); 1H NMR (600
MHz) 0.98 (t, 3H, J 7.4, CH3), 1.98 (m, 2H, CH2), 3.86 (s,
, OCH3), 6.36 (t, 1H, J 6.4, CH-O), 6.88 (d, 1H, J 8.3,
CH-Ar), 6.94 (t, 1H, J 7.5, CH-Ar), 7.25 (ddd, 1H, J 1.0,
7.3, 8.2, CH-Ar), 7.37 (m, 2H, CH-Ar), 7.51 (dt, 1H, J
0.8, 8.0, CH-Ar), 7.98 (d, 1H, J 7.7, CH-Ar), 8.07 (s, 1H,
CH-Ar); 13C NMR 9.9 (CH3), 28.5 (CH2), 55.5 (OCH3),
72.9 (CH-O), 110.6 (CH-Ar), 120.6 (CH-Ar), 126.2
(CH-Ar), 127.8 (CH-Ar), 128.7 (CH-Ar), 129.0 (Cquat),
129.6 (CH-Ar), 129.7 (CH-Ar), 132.5 (Cquat), 132.8

S. P. SIMEONOV ET AL. 10
4, CH (m,
2H
Hz) 0.98 (t, 3H, J 7.4, CH), 1.97 (m, 2H, C
3.
, J 7.4, CH), 2.02 (m, 2H, C
3.
and Dr. Kalina Kostova for
of 1-(2-methoxyphenyl)pro-
anol. The financial support by the National Researc
] R. Noyori and M. Kitamura, “Enantioselective Addition
allic Reagents to Carbonyl Compounds:
er, Multiplication, and Amplification,”
pp. 833-856.
etric Organozinc
Asymmetric Catalysis,” Accounts
s of n-Sulfonylated β-Amino Alcohols with
ew York, 2003.
004.
(CH-Ar), 134.4 (Cquat), 156.2 (Cquat), 165.6 (C=O);
HPLC: eluent hexane/iPr-OH/TFA 100:0.5:0.05, reten-
tion times tR-1 4.69 and tR-2 5.15 min.
1-(2-Methoxyphenyl)propyl 4-chlorobenzoate 12d: 99%
yield; Rf 0.19 (hexane:CH2Cl2 70:30); m. p. 169- 170℃;
1H NMR (600 MHz) 0.97 (t, 3H, J 7.3), 1.98
, CH2), 3.86 (s, 3H, OCH3), 6.35 (t, 1H, J 6.4, CH-O),
6.88 (d, 1H, J 8.2, CH-Ar), 6.94 (t, 1H, J 7.5, CH-Ar),
7.24 (ddd, 1H, J 1.5, 7.6, 8.3, CH-Ar), 7.36 (dd, 1H, J 1.2,
7.5, CH-Ar), 7.41 (d, 2H, J 8.5, CH-Ar), 8.041 (d, 2H, J
8.5, CH-Ar); 13C NMR 9.9 (CH3), 28.5 (CH2), 55.5
(OCH3), 72.6 (CH-O), 126.2 (CH-Ar), 128.6 (CH-Ar),
128.7 (2 CH-Ar), 129.1 (Cquat), 129.2 (Cquat), 129.4
(CH-Ar), 131.0 (2 CH-Ar), 131.9 (CH-Ar), 139.2 (Cquat),
156.2 (Cquat), 164.9 (C=O); HPLC: eluent hexane/iPr-OH/
TFA 100:0.5:0.05, retention times tR-1 4.71 and tR-2 5.22
min.
1-(2-Methoxyphenyl)propyl 2,4-dichlorobenzoate 12e:
99% yield; Rf 0.27 (hexane:CH2Cl2 70:30); 1H NMR
(600 M3 2
86 (s, 3H, OCH3), 6.38 (t, 1H, J 6.4, CH-O), 6.89 (d,
1H, J 8.2, CH-Ar), 6.95 (t, 1H, J 7.5, CH-Ar), 7.26 (ddd,
1H, J 1.57, 7.6, 8.1, CH-Ar), 7.29 (dd, 1H, J 2.0, 8.4,
CH-Ar), 7.38 (dd, 1H, J 1.6, 7.6, CH-Ar), 7.47 (d, 1H, J
2.0, CH-Ar), 7.84(d, 1H, J 8.4, CH-Ar); 13C NMR 9.9
(CH3), 28.4 (CH2), 55.5 (OCH3), 72.5 (CH-O), 110.5
(CH-Ar), 120.5 (CH-Ar), 126.5 (CH-Ar), 127.0 (CH-Ar),
128.6 (Cquat), 128.7 (CH-Ar), 128.9 (Cquat), 131.0
(CH-Ar), 132.6 (CH-Ar), 134.8 (Cquat), 138.1 (Cquat),
156.3 (Cquat), 164.1 (C=O); HPLC: eluent hex-
ane/iPr-OH/TFA 100:0.5:0.05, retention times tR-1 4.79
and tR-2 5.23 min.
1-(2-Methoxyphenyl)propyl 2-naphthoate 12f: 94% yield;
Rf 0.22 (hexane:CH2Cl2 70:30); m. p. 73-75℃; 1H NMR
(600 MHz) 1.02 (t, 3H
H), [5] L. Pu, “Asymmetric Alkynylzinc Additions to Aldehydes
and Ketones,” Tetrahedron, Vol. 59, No. 50, December
2003, pp. 9873-9886.
Fou
3 2
85 (s, 3H, OCH3), 6.44 (t, 1H, J 6.4, CH-O), 6.87 (d,
1H, J 8.3, CH-Ar), 6.94 (t, 1H, J 7.5, CH-Ar), 7.24 (ddd,
1H, J 1.6, 7.8, 8.8, CH-Ar), 7.46 (dd, 1H, J 1.6, 7.6,
CH-Ar), 7.51 (td, 1H, J 1.6, 8.2, CH-Ar), 7.55 (td, 1H, J
1.1, 8.1, CH-Ar), 7.86 (t, 2H, J 9.0, CH-Ar), 7.95 (d, 1H,
J 8.1, CH-Ar), 8.13 (dd, 1H, J 1.6, 8.6, CH-Ar), 8.67 (s,
1H, CH-Ar); 13C NMR 10.0 (CH3), 28.6 (CH2), 55.5
(OCH3), 72.4 (CH-O), 110.5 (CH-Ar), 120.5 (CH-Ar),
125.3 (CH-Ar), 126.2 (CH-Ar), 126.6 (CH-Ar), 127.7
(CH-Ar), 128.0 (Cquat), 128.1 (CH-Ar), 128.2 (CH-Ar),
128.5 (CH-Ar), 129.3 (CH-Ar), 129.4 (Cquat), 131.0
(CH-Ar), 132.5 (Cquat), 135.5 (Cquat), 156.2 (Cquat), 165.9
(C=O); HPLC: eluent hexane/iPr-OH/TFA 100:0.5:0.05,
retention times tR-1 7.95 and tR-2 9.06 min.
5. Acknowledgements
H), [9] G. Gübitz and M. G. Schmid, “Chiral Separations: Meth-
ods and Protocols,” Methods in Molecular Biology, Vol.
243, Humana Press, Totowa, 2
We thank Irena Zagranyarska
supplying us with a sample
ph
Fund of Bulgaria for the purchase of Bruker Avance II+
600 NMR spectrometer, Project UNA-17/2005, is also
gratefully acknowledged.
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