MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2005; 43: 869–872
Spectral Assignments and Reference Data
Complete assignments of 1H and 13C NMR
data for ten phenylpiperazine derivatives
the structure of these active metabolites, it was supposed that the
hydroxyl group on the phenyl or naphthyl ring was essential to the
activity of Naftopidil’s metabolites. According to metabolic rule of
Naftopidil, three active metabolites had been used as leading com-
pounds to design and synthesize new derivatives. Ten new resulting
derivatives had been obtained, among which many showed potent
antihypertension activity in the artery-expanding experiment. In
this paper, we report the complete 1H and 13C NMR assignment for
those phenylpiperazine derivatives (1–10). To our knowledge, it is
the first time unambiguous 1H and 13C NMR assignments for those
compounds are given, by the aid of 2D NMR techniques.
Zhihui Xiao,1∗ Mu Yuan,2 Si Zhang,1 Jun Wu,1 Shuhua Qi1
and Qingxin Li1
1
Guangdong Key Laboratory of Marine Materia Medica, South China
Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou
510301, China
2
The Key Laboratory of Chemistry for Natural Products of Guizhou
Province and Chinese Academy of Sciences, Guiyang 550002, China
RESULTS AND DISCUSSION
Received 21 March 2005; revised 1 June 2005; accepted 9 June 2005
Syntheses
The intermediate chemicals were purified before they were used
in the next steps. The general procedure for the preparation
of target compounds 6 is shown in Scheme 1. Starting ˇˇ0-
dichlorodiethylamine hydrochloride 1 was electrophilic substituted
by appropriate substitutedanilinesto affordthe desiredphenylpiper-
azine hydrochloride 2. 4 was obtained by reaction of epichlorohydrin
with 3 in alkali water. 4 and 5 were refluxed in anhydrous ethanol
to obtain target compounds. A similar method was designed for the
synthesis of all the target compounds 6.3–5 Compounds 2 were pre-
pared and separated according to the method described elsewhere.6
Preparation of 4 was performed according to the general procedure
described elsewhere.7
Ten phenylpiperazine derivatives were designed and
synthesized. The first complete assignments of 1H and
13C NMR chemical shifts for these phenylpiperazine
derivatives were achieved by means of 1D and 2D NMR
techniques, including 1H–1H COSY, HSQC and HMBC
spectra. Copyright 2005 John Wiley & Sons, Ltd.
KEYWORDS: NMR; 1H NMR; 13C NMR; 2D NMR;
phenylpiperazine derivatives; complete NMR assignments
1H NMR, 13CNMR spectral assignments
INTRODUCTION
The structures of compounds 1–10 are presented in Scheme 2.
The complete assignments of 1H and 13C NMR chemical shifts
of the compounds are listed in Table 1 and Table 2, respec-
tively.
Naftopidil, ((R, S)-1-(2-methoxyphenyl)-1-piperazinyl-3- (1-naph-
thyl-oxy-2-propanol)),
a
phenylpiperazine derivative provided
novel ˛1-
by Boehringer Mannheim (FRG) Company, was
a
adrenoceptor antagonist and a new antihypertensive drug.1 The
metabolism of Naftopidil and the pharmacodynamic action of its
metabolites had been previously investigated. Three major metabo-
lites including O-demethyl-Naftopidil, (phenyl) hydroxyl-Naftopidil
and (naphthyl) hydroxyl-Naftopidil were found to have similar
affinities to the ˛1-adrenoceptor as their parent compound.2 From
The obvious signal assignments were made from 1H, 13C NMR
and DEPT spectra according to the chemical shifts and multiplicities.
Other remaining 1H and 13C NMR signals were assigned with the
aid of 2D NMR spectra including 1H–1H COSY, HSQC and HMBC
spectra.
The 1H and 13C NMR data (Table 1 and 2) combined with DEPT,
1H–1H COSY, and HSQC experiments suggested the presence of
two fragments –CH2 –CH (OH)–CH2 –, –N (CH2 –CH2)2 –N– and
an Aryl ring. For example, In the HMBC spectrum (Fig. 1) of 1, long-
range correlations were observed from the protons at υ 4.23 and 4.16
(H2-11) of the fragment –11CH2 –12CH(OH) –13CH2 – to the C-1 (υ
154.34), C-12 (υ 65.67) and C-13 (υ 60.87). And the methylene proton
(H2-13) at υ 2.75 of the fragment –11CH2 –12CH(OH)–13CH2 – was
ŁCorrespondence to: Zhihui Xiao, Guangdong Key Laboratory of Marine
Materia Medica, South China Sea Institute of Oceanology, Chinese Academy
of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
E-mail: xzh 77@yahoo.com.cn
Contract/grant sponsor: National Natural Science Foundation of China;
Contract/grant number: 30060087.
Scheme 1. Synthesis of compounds 1–10.
Copyright 2005 John Wiley & Sons, Ltd.