Solventless lactam synthesis by intramolecular cyclizations of α-iminoester derivatives under microwave irradiation

Article abstract of DOI:10.3390/12030439

We have previously reported a new synthesis of amides from esters and amines under microwave irradiation, offering much higher yields than those achieved with conventional heating [1]. We have now extended these studies to the ring closure of neat iminoes

Full text of DOI:10.3390/12030439

Molecules 2007, 12, 439-454
molecules
ISSN 1420-3049
http://www.mdpi.org
Full Paper
Solventless Lactam Synthesis by Intramolecular Cyclizations of
α-Iminoester Derivatives under Microwave Irradiation
Fatima-Zohra Zradni 1,*, Jack Hamelin 2 and Aicha Derdour 1,†
1
Faculté des Sciences, Département de Chimie, Université d’Es-sénia, Oran, B.P 1524, Algeria;
†E-Mail: derdouraicha@yahoo.fr
2
Groupe d'Ingénierie Chimique et Molécules pour le Vivant 3(ICMV3)-UMR 6226, Université de
Rennes 1, Campus de Beaulieu, 35042 Rennes, France; E-mail: jack.hamelin@orange.fr
* Author to whom correspondence should be addressed; E-mail: fzradnidz@yahoo.fr; Tel/Fax: (+213)
41 58 70 57
Received: 27 January 2007; in revised form: 17 February 2007 / Accepted: 7 March 2007 /
Published: 12 March 2007
Abstract: We have previously reported a new synthesis of amides from esters and
amines under microwave irradiation, offering much higher yields than those achieved
with conventional heating [1]. We have now extended these studies to the ring closure of
neat iminoesters I2, I3 and I4-I6 to give five- and six-membered ring lactams L5, L6 and
larger lactams L7-L9 (where I means imine and L means lactam), respectively, under
both classical heating conditions and microwave irradiation.
Keywords: Medium-sized ring lactams; imine alkylation; Schiff bases; microwave
irradiation.
Introduction
Lactams are of considerable interest in a number of areas, ranging from drug discovery to the
polymer industry, and consequently their synthesis has been, and still is, a topic of significant interest
for organic chemists. Among the numerous methods developed radical strategies [2], especially
intramolecular cyclizations of unsaturated α-carbamoyl radicals [3,4] or in our case imines, have been

Molecules 2007, 12
440
shown to be some of the best tools for the construction of a variety of lactam skeletons ranging from β-
lactams to medium- or larger sized ones. Encouraged by our recent results on the synthesis of amides
under microwave irradiation [1], and by other publications in which this original synthetic method was
used, we now report that neat imines can be utilised for lactam synthesis by simple cyclization either
under classical heating conditions or under microwave irradiation (Scheme 1).
Scheme 1
R
R
R
(ii)
(i)
PhCHO
CO2Me
CO2Me
N
CO2Me
CO2Me Ph
H N
Cl
N
Ph
3
1a-c
n
a: R= Me
b: R= Ph
c: R= iPr
n= 2-5,7
O
NH
n-1
R
∆
CO2CH3
or M.W
Reagents:(i) Et3N/MgSO4; (ii) Alkylating agent
Medium-sized (5 to 10-membered) ring lactams find widespread use in organic chemistry as key
intermediates in the synthesis of more complex structures, or as core structures in natural products or
pharmaceutically important compounds. Until now, the generation of such rings has been a challenge.
During the past decade increasing interest has focused on the generation of cyclic and hairpin peptides
and medium-sized rings were thought to represent suitable fragments. Furthermore, a range of
complex natural products characterized by possessing such lactam structures and their total synthesis is
a broad field for organic chemists to test new strategies and to develop new methods.
Microwave-assisted heating under controlled conditions has been shown to be an invaluable
technology for medicinal chemistry and drug discovery applications, since it often dramatically reduces
reaction times, typically from days or hours to minutes or even seconds. Compound libraries can then
be rapidly synthesized using this new, enabling technology [5-9]. In our work we have used a
monomode Synthewave® 402 type of microwave oven, with a maximum working volume under the
microwave field of 40 mL and a maximum power of 300W. The samples are placed in a cylindrical
quartz reactor (three available diameters: Ø = 1.8, 3 and 4 cm). This oven, formerly marketed by the
Prolabo company, is controlled by means of the SYNSOFT® software package.
The aim of the present paper is to present and discuss a simple and new strategy for the formation
of C-C bonds through a direct alkylation of α-iminoesters under solvent free conditions, using
potassium tert-butoxide as base, and then, the cyclisation of the products under microwave irradiation
to synthesize five- to ten-membered ring lactams. In particular, we present the results of our study on
the intramolecular cyclization reactions of α-iminoesters derived from the aldimine 1. Our results show
that these cyclization reactions are highly effective and give access to useful heterocyclic ring systems.

Molecules 2007, 12
441
Results and Discussion
The Michael reactions of imines have been used in numerous synthetic applications by our team
[10] and by others and the method has facilitated the preparation of numerous compounds endowed
with biological properties such as terpenes, steroids, and alkaloids. For our part, we have used the
intramolecular cyclization of these imines for the formation of lactams with five to ten bonds.
Deprotonation of aldimine I1 under solid-liquid PTC conditions using K2CO3 as a base [11] gives a
highly active carbanion, whose reaction with methyl acrylate gives the alkylated product I2 in good
yield (70 to 85%) (Scheme 2). The reaction is carried out by simply stirring solid K2CO3, an aldimine
I1a-c, methyl acrylate and N-benzylcinchonidinium bromide (N-BCB) as catalyst [11] in acetonitrile
at room temperature for 4 to 5 hours. The results are summarized in Table 1. These Michael adducts
then cyclize to provide five membered ring lactams L5 (Scheme 2), either under classical heating or
under microwave activation.
Scheme 2
O
O
R
R
O
MeO
Ph
MeO
Ph
NH
OMe
R
CO2CH3
N
N
K2CO3 , N-BCB
or M.W
O
CH CN,
RT
CO2CH3
3
I2a-c
I1a-c
L5a-c
Table 1
Time
Yield
(%)
70
I2
R
(h)
5
a
b
c
Me
iPr
5
81
Phenyl
4
85
The α-alkylation of N-benzylidene imines I1a-c with longer chains is easily performed by the
solventless treatment with bromoester derivatives catalysed by potassium tert-butoxide (t-BuOK) to
give compounds I3-I6, which underwent cyclization to give six, seven-to ten-membered ring lactams
L6-L9 , in excellent yields under microwave irradiation (Schemes 3-4)
Scheme 3
O
Br
O
R
n
R
Cl, H3N
R
Ph
MeO
Ph
CO2CH3
Ph
CHO
CO2H
N
OMe
n
MgSO4
Et3N
t-BuOK
N
r.t, 2-4
h
CO2CH3
I1a-c
I3 : n= 3
I4 : n= 4
I5 : n= 5
I6 : n= 7
I1a : R= Me
I1b : R= Ph
I1c : R= iPr

Molecules 2007, 12
442
However, whereas the compounds L6 are stable and isolable, the seven, eight and ten membered
lactams L7-L9 are somewhat unstable and readily open up to give the corresponding amino acids A7,
A8 and A9 (Scheme 5).
Scheme 4
O
O
H
N
R
R
O
R
O
MeO
Ph
MeO
Ph
Br-(CH2)3-CO2CH3
t-BuOK
N
N
OMe
CO2Me
or M.W
I3a-c
L6a-c
I1a-c
Scheme 5
O
O
R
R
OH
R
H
O
N
MeO
H2N
CO2Me
O
CO2Me
OMe
n
N
or M.W
I4a-c : n= 4
I5a-c : n= 5
I6a-c : n= 7
n'
n'
L7a-c : n'= 1
L8a-c : n'= 2
L9a-c : n'= 4
A7a-c : n'= 1
A8a-c : n'= 2
A9a-c : n'= 4
Previous work has shown that the alkylation of asymmetric imines can be effected under liquid–
liquid [12], solid–liquid [13] and micellar phase-transfer conditions [14] and that homogeneous
reaction conditions involving phosphazene bases [15] are also similarly effective. However, after a
number of attempts to alkylate α-iminoesters using numerous and various conditions described in the
literature [16-19], the results were rather poor. After several such attempts, we finally found a very
simple and suitable way to alkylate imines in excellent yields under mild conditions with various
bromoalkylesters E (where E represents esters) (Table 2). Medium-sized macrocyclic lactams of 8, 9
and 10 members have been traditionally harder to form than their smaller and larger-sized counterparts
[20]. In fact and for our case, the five and six membered ring lactams are easily obtained, contrary to
higher members cycles which open up to give the corresponding amino acids in the mass spectrometer.
Alkylation and intramolecular cyclization reactions of α-iminoester derivatives
The α-iminoesters of type 1 were readily prepared by the condensation of the corresponding amino
acids with benzaldehyde by standard procedures. N-Benzylcinchonidinium bromide (N-BCB) [11]
catalysed the alkylation of compound I1 with methyl acrylate, giving α-amino esters I2 with 70–85%
yield (Table 1). These reactions were carried out under solid–liquid phase transfer conditions using
solid potassium carbonate as the base. To prepare imines I3 to I6, the aldimines I1 were alkylated with
bromoalkyl ester derivatives under solvent free conditions using potassium tert-butoxide (t-BuOK) as
base (Table 2).

Molecules 2007, 12
443
Table 2
Products Time (h)
Starting materials
Yield (%)
I1a
I1a
I1a
I1a
I1b
I1b
I1b
I1b
I1c
I1c
I1c
I1c
Br-(CH2)3-CO2Me (E3)
Br-(CH2)4-CO2Me (E4)
Br-(CH2)5-CO2Me (E5)
Br-(CH2)7-CO2Me (E6)
Br-(CH2)3-CO2Me (E3)
Br-(CH2)4-CO2Me (E4)
Br-(CH2)5-CO2Me (E5)
Br-(CH2)7-CO2Me (E6)
Br-(CH2)3-CO2Me (E3)
Br-(CH2)4-CO2Me (E4)
Br-(CH2)5-CO2Me (E5)
Br-(CH2)7-CO2Me (E6)
I3a
I4a
I5a
I6a
I3b
I4b
I5b
I6b
I3c
I4c
I5c
I6c
2
3
91
98
97
97
85
98
97
96
89
87
86
83
4
4
2
3
4
5
2.5
3
4
6
The resulting imines I2-I6 were cyclized under either classical heating conditions or microwave
irradiation to give the five to ten-membered ring lactams L5-L9 (Tables 3-5) in good yields after
washing with diethyl ether. Best yields were achieved with the latter technique. The isolated lactams
were fully characterized by 1H- and 13C-NMR spectra and mass spectrometry.
Table 3: Intramolecular cyclization of imines 1 with R = Me
T°C Time
Yield
(%)
T°C
Time
(min)
Yield
(%)
Substrate
Product
a
(days)
M.W
Me
H3CO2C
H
N
CO2CH3
O
140
150
2
79
78
120
130
25
20
85
81
CO2CH3
N
Ph
CO2CH3
H3CO2C
Me
H
N
O
CO2CH3
3.5
N
Ph
CO2CH3
H
Me
H3CO2C
N
O
150
160
170
4
5.5
5
65
55
40
135
135
135
30
30
30
85
85
83
CO2CH3
N
Ph
CO2CH3
H
H3CO2C
Me
N
CO2CH3
O
N
Ph
H
Me
H3CO2C
CO2CH3
N
O
CO2CH3
N
4
Ph
a) Oil bath temperature previously set before the experiment.

Molecules 2007, 12
444
Table 4: Intramolecular cyclization of imines 1 with R = Ph
T°C Time Yield T°C Time Yield
Substrate
Product
a
(days) (%) M.W (min) (%)
Ph
H3CO2C
H
N
O
CO2CH3
140
2
80
100
15
86
CO2CH3
N
Ph
Ph
H3CO2C
Ph
CO2CH3
Ph
H
N
O
CO2CH3
145
145
3
69
62
115
115
20
30
88
79
N
Ph
CO2CH3
Ph
H
Ph
N
H3CO2C
O
3.5
CO2CH3
N
Ph
CO2CH3
Ph
H
N
MeO2C
Ph
150
160
3.5
4
56
48
120
120
30
30
78
79
CO2CH3
O
N
Ph
Ph
H
CO2CH3
Ph
H3CO2C
N
O
CO2CH3
N
4
Ph
a) Oil bath temperature previously set before the experiment.
Table 5: Intramolecular cyclization of imines 1 with R = i-Pr
T°C Time Yield T°C Time Yield
Substrate
Product
a
(days) (%) M.W (min) (%)
iPr
H3CO2C
H
N
CO2CH3
iPr
O
140
140
2
3
79
70
100
110
20
25
85
82
CO2CH3
CO2CH3
N
Ph
H3CO2C
iPr
CO2CH3
iPr
H
N
O
N
Ph
CO2CH3
iPr
H
iPr
H3CO2C
N
O
145
3.5
55
110
30
80
CO2CH3
N
Ph

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445
Table 5. Cont
CO2CH3
H3CO2C
Ph
iPr
CO2CH3
iPr
HN
150
3.5
4.5
53
120
120
30
30
78
76
O
N
CO2CH3
iPr
H3CO2C
H
N
iPr
O
155
46.7
CO2CH3
N
4
Ph
a) Oil bath temperature previously set before the experiment.
A high temperature (up to 135°C) was required for efficient cyclization of imines to give the five
to ten-membered lactams. The cyclization was achieved either under classical heating or microwave
irradiation, with the latter being a much more efficient procedure (Figure 1). No products could be
isolated by classical heating with the same temperature conditions used under microwaves, but we did
obtain them with lower yields after extended periods (2-5 days) at high temperatures.
Figure 1
Yield ver sus t ime f or six member ed lact am at
135°C
100
80
60
40
20
0
1
6
11
16
21
26
Time ( min)
Classical Heating
M icrowave irradiation
Based on our results, we suggest the following mechanistic scenario for the intramolecular
cyclization reactions of these iminoesters (Scheme 6).
Scheme 6
R
R
Ph
R
MeO
N
Ph
N
CO2CH3
HN
CO2CH3
moisture
CO2CH3
n
µ.ω
n
n
O
O
O
+
MeOH
+
Ph CHO
OCH3

Molecules 2007, 12
446
Conclusions
In summary, it is clear that intramolecular cyclization reaction of α-iminoesters under microwave
irradiation is an efficient class of reaction. The cyclizations of α-iminoester derivatives of the type 1,
provide an easy access to a variety of lactam systems with different ring sizes in good yields.
Experimental
General
NMR spectra were measured on a Bruker AVANCE 300 spectrometer operating at 300 (1H) and
75 (13C) MHz, respectively, using CDCl3 as solvent and TMS as internal standard and mass spectra
Varian MAT 311 instrument. The masses recorded for the seven-, eight- and ten- membered ring
lactams correspond to the peaks resulting from their hydrolysis followed by decarboxylation in the
mass spectrometer. The alkylating agents methyl 4-bromobutyrate (E3) and methyl 5-bromovalerate
(E4) were commercial products (from Acros), while methyl 6-bromohexanoate (E5) and methyl 8-
bromooctanoate (E6) were obtained by esterification of their corresponding acid chlorides.
General procedure for the synthesis of α-iminoesters.
The α-iminoesters were prepared according to the procedure reported by Longmire et al. [21].
Triethylamine (l eq) and anhydrous magnesium sulphate (light excess) were added at 0°C to a stirred
suspension of the appropriate amino acid methyl ester hydrochloride (alanine, phenylalanine or valine,
1 eq), in dry dichloromethane (10 mL) and the mixture was stirred for l h before the addition of the
benzaldehyde (l eq). The reaction mixture was stirred overnight at room temperature after which it was
filtered and the solvent removed in vacuo. The residue was taken up in diethyl ether (10 mL) and
washed with brine (3×5 mL). The combined organic phases were then dried over MgSO4 and
evaporated to dryness to afford the desired products.
Representative procedure for the catalytic phase-transfer alkylation of I1.
To a mixture of aldimine I1 (10 mmol) and catalyst (N-BCB, 1mmol) in acetonitrile (10 mL) solid
potassium carbonate (2 mmol) and methyl acrylate (10 mmol) were added. The reaction mixture was
stirred vigorously at room temperature (r.t) for 5 hours. Then, the mixture was filtered, washed with
water and acetonitrile. The filtrate was concentrated under reduced pressure and the residue was taken
up in ether. The ether solution was washed with saturated sodium chloride and dried over MgSO4.
After ether evaporation, the alkylated product 2 was obtained. The details of I2a-c have been given in
Table 1.

Molecules 2007, 12
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General procedure for alkylation of α-iminoesters I1.
In a two-neck flask, provided with a refluxing condenser and equipped with a magnetic stirring
bar was added an equimolar mixture of aldimine 1 and the alkylation agent (E3-E6). After 15 min of
stirring, a slight excess (1.2 eq) of potassium tert-butoxide (t-BuOK) was added. The mixture was
stirred for 2-6 h at room temperature (r.t), the product was then extracted with methylene chloride
(CH2Cl2). The solvent was removed under reduced pressure and the alkylated imines were distilled on
a Büchi apparatus. The details of the alkylated imines have been given in Table 2.
General Procedure for the preparation of lactams: Method A (MWI).
The typical procedure for the different size lactams synthesis is as follows: benzylidene imines I2-I6
(1eq, 10-2 mol) are placed in the Ø: 2.5 cm reactor of a Synthewave ®402) focused microwave oven
and irradiated for the specified temperature and time (see Tables 3-5). Upon completion of the
reaction, the mixture was extracted with CH2Cl2 and washed with ether. After evaporation of the
solvent, the resulting product was analyzed by 1H-NMR, 13C-NMR and mass spectra.
Method B (Conventional heating)
Reactions were performed under the same conditions using a previously heated oil bath, set at a
temperature slightly higher (about 20°C) than the temperature measured in the microwave oven. As
this study was done only for the comparison purposes and to see the influence of reaction times on the
yields, the products were only analysed by 1H-NMR.
Methyl 2-(benzylideneamino)propanoate (I1a): C11H13NO2; Yield: 91%; Colorless oil, bp: 85°C/
1
6.3x10-2Torr (lit [23] mp 105-107 °C/2 Torr); H-NMR δ: 1.52-1.54 (d, 3H, J= 3 Hz, CH3), 3.74 (s,
3H, MeCO), 4.12-4.19 (q, 1H, J= 6.81 Hz, CH), 7.38-7.43 (m, 5H, Ph), 8.31 (s, 1H, CH=); 13C-NMR
δ: 19.45 (CH3), 52.42 (OCH3), 67.98 (CH), 128.35 (ArCH), 128.51 (ArCH), 131.13 (ArCH), 135.69
(ArC), 163.04 (HC=N), 176.99 (C=O); MS m/z: found [M-.CH3]+ 176.07115, requires 176.0711.
Dimethyl 2-(benzylideneamino)-2-methylpentanedioate (I2a) [23]: C15H19NO4: Yield: 70%; yellow oil,
bp: 90°C/6.3x10-2Torr; 1H-NMR δ: 1.50 (s, 3H, CH3), 2.12-2.16 (t, 2H, J=7.75 Hz, CH2), 2.43-2.54 (t,
2H, J= 8.21 Hz, CH2), 3.62 (s, 3H, MeCO), 3.71 (s, 3H, MeCO), 7.27-7.41 (m, 5H, Ph), 8.26 (s, 1H,
CH=); 13C NMR δ: 25.88 (CH3), 30.46 (CH2), 32.67 (CH2), 51.60 (OCH3), 53.09 (OCH3), 62.83 (CH),
127 (ArCH), 128.59 (ArCH), 128.85 (ArCH), 135.69 (ArC), 163.23 (HC=N), 174.92 (C=O), 178.17
(C=O); MS m/z: Found [M-.CH3]+ 262.1099, requires 262.1079; Found [M-.OCH3]+ 246.1153,
requires 246.1130.
Dimethyl 2-(benzylideneamino)-2-methylhexanedioate (I3a): C16H21NO4; Yield: 91%; yellow oil, bp:
1
90°C/6.3x10-2Torr; H-NMR δ: 1.60 (s, 3H, CH3), 1.75-1.82 (qt, 2H, J= 7.8 Hz, CH2), 1.98-2.06 (t,
2H, J=9 Hz, CH2), 2.24-2.30 (t, 2H, J=8.2 Hz, CH2), 3.61 (s, 3H, MeCO), 3.70 (s, 3H, MeCO), 7.15-
7.81 (m, 5H, Ph), 8.33 (s, 1H, CH=); 13C-NMR δ: 19.88 (CH2), 24.76 (CH3), 33.46 (CH2), 35.67

Molecules 2007, 12
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(CH2), 52.43 (OCH3), 54.70 (OCH3), 61.41 (CH), 126.68 (ArCH), 128.14 (ArCH), 130.85 (ArCH),
136.69 (ArC), 160.23 (HC=N), 174.42 (C=O), 176.27 (C=O); MS m/z: Found [M-.CO2CH3]+
232.3061, requires 232.3070.
Dimethyl 2-(benzylideneamino)-2-methylheptanedioate (I4a): C17H23NO4; Yield: 98%; yellow oil, bp:
1
85°C/8x10-2Torr; H-NMR δ: 1.52 (s, 3H, CH3), 1.37-1.77 (m, 4H, 2CH2), 1.91-2.01 (t, 2H, J=6 Hz,
CH2), 2.32-2.40 (t, 2H, J=12 Hz, CH2), 3.68 (s, 3H, MeCO), 3.78 (s, 3H, MeCO), 7.33-7.82 (m, 5H,
Ph), 8.28 (s, 1H, CH=); 13C-NMR δ: 23.10 (CH2), 23.82 (CH2), 25.22 (CH3), 33.90 (CH2), 39.74
(CH2), 51.47 (OCH3), 52.15 (OCH3), 68.42 (CH),127.83 (ArCH), 128.79 (ArCH), 130.87 (ArCH),
136.36 (ArC), 159.26 (HC=N), 174.05 (C=O), 174.68 (C=O); MS m/z: Found [M-.OCH3]+ 274.1443,
requires 274.1452; Found [M-.CO2CH3]+ 246.1494, requires 246.1493.
Dimethyl 2-(benzylideneamino)-2-methyloctanedioate (I5a): C18H25NO4; Yield: 97.3%; yellow oil, bp:
85°C/8x10-2Torr; 1H-NMR δ: 1.33-1.39 (qt, 2H, J= 6 Hz, CH2), 1.50 (s, 3H, CH3), 1.61-1.69 (qt, 2H,
J=5.46 Hz, CH2), 1.90-1.98 (qt, 2H, J=5.2 Hz, CH2), 2.29-2.34 (t, 2H, J=8 Hz, CH2), 3.66 (s, 3H,
13
MeCO), 3.75 (s, 3H, MeCO), 7.35-7.80 (m, 5H, Ph), 8.26 (s, 1H, CH=); C-NMR δ: 23.11 (CH2),
23.88 (CH2), 24.78 (CH2), 29.42 (CH3), 34.00 (CH2), 39.94 (CH2), 51.48 (OCH3), 52.14 (OCH3),
68.51 (CH), 128.28 (ArCH), 128.56 (ArCH), 130.85 (ArCH), 136.06 (ArC), 159.18 (HC=N), 174.21
(C=O), 175.22 (C=O); MS m/z: Found [M-.CO2CH3]+ 260.1650, requires 260.1646.
Dimethyl 2-(benzylideneamino)-2-methyldecanedioate (I6a): C20H29NO4; Yield: 96.7%; yellow oil, bp:
1
80°C/9x10-2Torr; H-NMR δ: 1.22-1.46 (m, 6H, 3CH2), 1.52 (s, 3H, CH3), 1.60-1.73 (t, 2H, J=7.04
Hz, CH2), 1.86-2.19 (m, 4H, 2CH2), 2.29-2.33 (t, 2H, J=7.59 Hz, CH2), 3.69 (s, 3H, MeCO), 3.78 (s,
13
3H, MeCO), 7.32-7.80 (m, 5H, Ph), 8.28 (s, 1H, CH=); C-NMR δ: 22.78 (CH2), 23.18 (CH2), 23.31
(CH2), 24.45 (CH2), 28.57 (CH2), 29.42 (CH3), 34.01 (CH2), 40.24 (CH2), 51.38 (OCH3), 51.80
(OCH3), 63.50 (CH), 128.27 (ArCH), 128.54 (ArCH), 131.06 (ArCH), 137.06 (ArC), 162.26 (HC=N),
174.12 (C=O), 176.21 (C=O); MS m/z: Found [M-.CO2CH3]+ 288.1963, requires 288.1980.
Methyl (benzylideneamino)(phenyl)acetate (I1b): C16H15NO2; Yield:78%; pale yellow solid, mp:
63°C, (from EtOH); 1H-NMR δ: 3.77 (s, 3H, MeCO), 5.23 (s, 1H, CH), 7.28-7.87 (m, 10H, 2Ph), 8.37
(s, 1H, CH=); 13C-NMR δ: 52.52 (OCH3), 69.78 (CH), 127.84 (ArCH), 128.12 (ArCH), 128.40
(ArCH), 128.68 (ArCH), 128.72 (ArCH), 131.28 (ArCH), 135.68 (ArC), 138.11 (ArC), 163.81
(HC=N); 171.58 (C=O); MS m/z: Found [M-.CO2CH3]+ 194.0969, requires 194.0980.
Dimethyl 2-(benzylideneamino)-2-phenylpentanedioate (I2b): C20H21NO4; Yield: 85%; yellow oil, bp:
1
85°C/8x10-2Torr; H-NMR δ: 2.32-2.44 (t, 2H, J=6.5 Hz, CH2), 2.48-2.64 (t, 2H, J=7 Hz, CH2), 3.63
13
(s, 3H, MeCO), 3.79 (s, 3H, MeCO), 7.24-7.74 (m, 10H, 2Ph), 8.39 (s, 1H, CH=); C-NMR δ: 30.12
(CH2), 31.05 (CH2), 50.42 (OCH3), 52.52 (OCH3), 70.18 (CH), 126.74 (ArCH), 127.12 (ArCH),
128.39 (ArCH), 128.78 (ArCH), 129.52 (ArCH), 131.33 (ArCH), 135.58 (ArC), 137.21 (ArC), 163.78
(HC=N), 173.78 (C=O), 174.65 (C=O); MS m/z: Found M+. 339.1470, requires 339.1502.

Molecules 2007, 12
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Dimethyl 2-(benzylideneamino)-2-phenylhexanedioate (I3b): C21H23NO4; Yield: 85.6%; yellow oil,
1
bp: 92°C/10-2Torr; H NMR δ: 1.52-1.80 (qt, 2H, J=5.16 Hz, CH2), 2.28-2.32 (t, 2H, J=6 Hz, CH2),
2.38-2.46 (t, 2H, J=6.7 Hz, CH2), 3.63 (s, 3H, MeCO), 3.77 (s, 3H, MeCO), 7.33-7.89 (m, 10H, 2Ph),
8.22 (s, 1H, CH=); 13C-NMR δ: 19.28 (CH2), 27.05 (CH2), 29.25 (CH2), 51.32 (OCH3), 52.29 (OCH3),
69.28 (CH), 127.14 (ArCH), 127.21 (ArCH), 128.30 (ArCH), 128.88 (ArCH), 129 (ArCH), 131.13
(ArCH), 136.08 (ArC), 137.11 (ArC), 161.78 (HC=N), 174.58 (C=O), 175.15 (C=O); MS m/z: Found
[M-.CO2CH3]+ 294.1494, requires 294.1489.
Dimethyl 2-(benzylideneamino)-2-phenylheptanedioate (I4b): C22H25NO4; Yield: 98%; yellow oil, bp:
90°C/10-1Torr; 1H-NMR δ: 1.24-1.46 (m, 4H, 2CH2), 1.56-1.64 (t, 2H, J=9 Hz, CH2), 2.23-2.26 (t, 2H,
J=4.23 Hz, CH2), 3.60 (s, 3H, MeCO), 3.73 (s, 3H, MeCO), 7.27-7.81 (m, 10H, 2Ph), 8.17 (s, 1H,
CH=); 13C-NMR δ: 23.43 (CH2), 25.26 (CH2), 33.88 (CH2), 40.29 (CH2), 51.40 (OCH3), 52.35
(OCH3), 74.89 (CH), 126.84 (ArCH), 127.40 (ArCH), 128.39 (ArCH), 128.49 (ArCH), 128.60
(ArCH), 131.11 (ArCH), 136.37 (ArC), 141.92 (ArC), 161.16 (HC=N), 173.76 (C=O), 176.15 (C=O);
MS m/z: Found [M-.CO2CH3]+ 308.1650, requires 308.1657.
Dimethyl 2-(benzylideneamino)-2-phenyloctanedioate (I5b): C23H27NO4; Yield: 97.11%; yellow oil,
1
bp: 90°C/2x10-1Torr; H-NMR δ: 1.27-1.62 (m, 6H, 3CH2), 1.79-1.83 (t, 2H, J=7.5 Hz, CH2), 2.18-
2.26 (t, 2H, J=4.4 Hz, CH2), 3.63 (s, 3H, MeCO), 3.72 (s, 3H, MeCO), 7.33-7.89 (m, 10H, 2Ph), 8.28
13
(s, 1H, CH=); C-NMR δ: 23.46 (CH2), 24.70 (CH2), 29.43 (CH2), 33.98 (CH2), 40.49 (CH2), 51.42
(OCH3), 52.32 (OCH3), 74.97 (CH), 126.85 (ArCH), 127.35 (ArCH), 128.36 (ArCH), 128.48 (ArCH),
128.60 (ArCH), 131.07 (ArCH), 139.27 (ArC), 141.81 (ArC), 161.06 (HC=N), 174.56 (C=O), 175.75
(C=O); MS m/z: Found [M-.CO2CH3]+ 322.1807, requires 322.1805.
Dimethyl 2-(benzylideneamino)-2-phenyldecanedioate (I6b): C25H31NO4; Yield: 96.5%; yellow oil,
1
bp: 95°C/2x10-1Torr; H-NMR δ: 1.28-1.47 (t, 3H, J=13 Hz, CH2), 1.58-1.80 (m, 4H, 2CH2), 1.83-
1.85 (t, 2H, J=11.5 Hz, CH2), 2.22-2.35 (m, 4H, 2CH2), 2.58-2.80 (t, 2H, J=11 Hz, CH2), 3.62 (s, 3H,
13
MeCO), 3.70 (s, 3H, MeCO), 7.14-7.87 (m, 10H, 2Ph), 8.21 (s, 1H, CH=); C-NMR δ: 19.86 (CH2),
23.70 (CH2), 25.43 (CH2), 29.03 (CH2), 30.19 (CH2), 34.05 (CH2), 40.58 (CH2), 51.32 (OCH3), 52.12
(OCH3), 73.67 (CH), 126.89 (ArCH), 128.34 (ArCH), 128.48 (ArCH), 128.59 (ArCH), 129.50
(ArCH), 130.06 (ArCH), 138.37 (ArC), 142.71 (ArC), 161.26 (HC=N), 173.46 (C=O), 174.75 (C=O);
MS m/z: Found [M-.CO2CH3]+ 350.2120, requires 350.2117.
Methyl 2-(benzylideneamino)-3-methylbutanoate (I1c): C13H17NO2; Yield: 94.5%; yellow oil, bp:
85°C/2x10-2Torr; 1H-NMR: δ: 0.99-0.94 (dd, 6H, J= 6.88 Hz, 2CH3), 2.37-2.43 (m, 1H, J= 6 Hz, CH),
3.67-3.71 (d, 1H, J= 12 Hz, CH), 3.75 (s, 3H, MeCO), 7.39-7.84 (m, 5H, Ph), 8.26 (s, 1H, CH=); 13C-
NMR δ: 18.66 (CH3), 19.51 (CH3), 31.73 (CH), 51.93 (OCH3), 80.39 (CH), 128.32 (ArCH), 128.51
(ArCH), 131.07 (ArCH), 135.69 (ArC), 163.33 (HC=N), 172.44 (C=O); MS m/z: Found [M-
.CO2CH3]+ 160.2434, requires 160.2441.
Dimethyl 2-(benzylideneamino)-2-isopropylpentanedioate (I2c): C17H23NO4; Yield: 81.2%; yellow oil,
1
bp: 90°C/10-2Torr; HNMR δ: 0.95-1.01 (dd, 6H, J= 9 Hz, 2CH3), 1.13-1.18 (t, 2H, J= 3 Hz, CH2),

Molecules 2007, 12
450
2.34-2.43 (m, 1H, J= 9 Hz, CH), 2.70-2.96 (t, 2H, J= 9 Hz, CH2), 3.78 (s, 3H, MeCO), 3.82 (s, 3H,
MeCO), 7.44-7.80 (m, 5H, Ph), 8.28 (s, 1H, CH=); 13C-NMR δ: 19.80 (CH3), 20.17 (CH3), 29.85
(CH2), 30.25 (CH), 31.13 (CH2), 50.91 (OCH3), 52.06 (OCH3), 68.20 (C), 128.59-136.8 (Ar), 162.23
(HC=N), 174.64 (C=O), 175.33 (C=O); MS m/z: Found [M-.CO2CH3]+ 246.1619, requires 246.1627.
Dimethyl 2-(benzylideneamino)-2-isopropylhexanedioate (I3c): C18H25NO4 ; Yield: 89%; yellow oil,
1
bp: 90°C/2x10-1Torr; H-NMR δ: 0.93-1.05 (dd, 6H, J= 9 Hz, 2CH3), 2.04-2.21 (qt, 2H, J= 2.3 Hz,
CH2), 2.37-2.44 (t, 2H, J= 10.7 Hz, CH2), 2.51-2.57 (m, 1H, J= 12 Hz, CH), 3.37-3.43 (t, 2H, J= 3 Hz,
CH2), 3.69 (s, 3H, MeCO), 3.75 (s, 3H, MeCO), 7.34-7.82 (m, 5H, Ph), 8.25 (s, 1H, CH=); 13C-NMR
δ: 20.15 (CH3), 20.57 (CH3), 21.11 (CH2), 29.95 (CH2), 30.23 (CH), 31.03 (CH2), 51.82 (OCH3),
52.03 (OCH3), 62.42 (C), 128.79-136.77 (Ar), 163.03 (HC=N), 175.34 (C=O), 175.69 (C=O); MS m/z:
Found [M-.CO2CH3]+ 260.1778, requires 260.1784.
Dimethyl 2-(benzylideneamino)-2-isopropylheptanedioate (I4c): C19H27NO4; Yield: 86.7%; yellow oil,
bp: 96°C/ 6.3.10-4Torr; 1H-NMR δ: 0.93-1.05 (dd, 6H, J= 9 Hz, 2CH3),1.60-2.00 (m, 4H, J= 6.72 Hz,
2CH2), 2.22-2.43 (qt, 1H, J= 4.57 Hz, CH), 2.44-2.47 (t, 1H, J= 3 Hz, CH2), 3.40-3.45 (t, 2H, J= 4.05
13
Hz, CH2), 3.70 (s, 3H, MeCO), 3.77 (s, 3H, MeCO), 7.44-7.90 (m, 5H, Ph), 8.37 (s, 1H, CH=); C-
NMR δ: 19.76 (CH3), 19.98 (CH3), 20.15 (CH2), 20.66 (CH2), 30.17 (CH), 31.28 (CH2), 32.07 (CH2),
52.32 (OCH3), 52.63 (OCH3), 71.60 (C), 128.80-136.57 (Ar), 162.33 (HC=N), 173.84 (C=O), 174.29
(C=O); MS m/z: Found [M-.OCH3]+ 302.1932, requires 302.1940.
Dimethyl 2-(benzylideneamino)-2-isopropyloctanedioate (I5c): C20H29NO4\Yield: 86%; yellow oil, bp:
1
106°C/6x0-4Torr; H-NMR δ: 0.95-1.01 (dd, 6H, J= 9 Hz, 2CH3),1.45-1.87 (m, 6H, J= 9.87 Hz,
3CH2), 1.90-2.04 (qt, 1H, J= 4.57 Hz, CH), 2.33-2.40 (t, 1H, J= 10.6 Hz, CH2), 3.39-3.47 (t, 2H, J=
4.71 Hz, CH2), 3.70 (s, 3H, MeCO), 3.78 (s, 3H, MeCO), 7.32-7.91 (m, 5H, Ph), 8.29 (s, 1H, CH=);
13C-NMR δ: 18.96 (CH3), 19.07 (CH3), 19.73 (CH2), 19.98 (CH2), 20.05 (CH2), 31.07 (CH), 31.76
(CH2), 32.01 (CH2), 51.62 (OCH3), 52.23 (OCH3), 78.90 (C), 128.70-136.82 (Ar), 156.53 (HC=N),
175.18 (C=O), 176.08 (C=O); MS m/z: Found [M-.CO2CH3]+ 288.2089, requires 288.2097.
Dimethyl 2-(benzylideneamino)-2-isopropyldecanedioate (I6c): C22H33NO4; Yield: 83.4%; yellow oil,
bp: 110°C/10-3Torr; 1H-NMR δ: 0.93-1.00 (dd, 6H, J= 4.57 Hz, 2CH3),1.61-1.94 (m, 11H, CH, 5CH2),
2.33-2.40 (t, 1H, J= 10.44 Hz, CH2), 3.39-3.45 (t, 2H, J= 8.37 Hz, CH2), 3.69 (s, 3H, MeCO), 3.76 (s,
13
3H, MeCO), 7.37-7.82 (m, 5H, Ph), 8.26 (s, 1H, CH=); C-NMR δ: 18.63 (CH3), 19.48 (CH3), 21.11
(CH2), 23.40 (CH2), 28.08 (CH2), 31.59 (CH), 31.71 (CH2), 31.95 (CH2), 51.49 (CH2), 51.91 (CH2),
62.11 (OCH3), 64.25 (OCH3), 80.37 (C), 128.54-135.68 (Ar), 163.28 (HC=N), 172.41 (C=O), 173.52
(C=O); MS m/z: Found [M-.CO2CH3]+ 316.2406, requires 316.2410.
Methyl 2-methyl-5-oxopyrrolidine-2-carboxylate (L5a): C7H11NO3; Yield: 85%, viscous and brown
1
aspect; H-NMR δ: 1.47 (s, 3H, CH3), 1.92-2.02 (t, 2H, J= 8.32 Hz, CH2), 2.32-2.48 (t, 2H, J= 5.87
13
Hz, CH2), 3.70 (s, 3H, MeCO), 6.10 (large s, 1H, NH); C-NMR δ: 25.88 (CH3), 30.46 (CH2), 32.67
(CH2), 53.09 (CH3CO), 62.83 (C), 174.91 (C=O), 178.17 (C=O); MS m/z: Found [M-.CO2CH3]+
98.0608, requires 98.0605.

Molecules 2007, 12
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Methyl 2-methyl-6-oxopiperidine-2-carboxylate (L6a): C8H13NO3; Yield: 81%, brown pasty solid; 1H-
NMR δ: 1.41 (s, 3H, CH3), 1.58-1.70 (qt, 2H, J= 7.56 Hz, CH2), 2.22-2.40 (t, 2H, J= 11.63 Hz, CH2),
3.40-3.53 (t, 2H, J= 10.43 (CH2), 3.75 (s, 3H, MeCO), 6.59 (large s, 1H, NH); 13C-NMR δ: 20.55
(CH3), 22.39 (CH2), 30.60 (CH2), 32.04 (CH2), 51.12 (CH3CO), 59.71 (C), 172.00 (C=O), 174.35
(C=O); MS m/z: Found [M-.CO2CH3]+ 112.07624, requires 112.0769.
Methyl 2-methyl-7-oxoazepane-2-carboxylate (L7a): C9H15NO3; Yield: 85%, brown paste; 1H-NMR δ:
1.01-1.74 (m, 4H, 2CH2),1.46 (s, 3H, CH3), 2.35-2.42 (t, 2H, J= 9 Hz, CH2), 3.15-3.36 (t, 2H, J= 10.03
Hz, (CH2), 3.71 (s, 3H, MeCO), 5.93 (large s, 1H, NH); 13C-NMR : δ: 23.10 (CH2), 23.74 (CH2), 23.81
(CH3), 29.69 (CH2), 33.89 (CH2), 52.12 (CH3CO), 68.41 (C), 174.03 (C=O), 174.66 (C=O); MS m/z:
Found [M-.OCH3]+ 172.1047, requires 172.1052.
1
Methyl 2-methyl-8-oxoazocane-2-carboxylate (L8a): C10H17NO3; Yield: 85%, brown paste; H-NMR
δ: 1.20-1.74 (m, 6H, 3CH2),1.53 (s, 3H, CH3), 2.27-2.35 (t, 2H, J= 10.13 Hz, CH2), 3.23-3.41 (t, 2H,
J= 5.21 Hz, (CH2), 3.69 (s, 3H, MeCO), 5.84 (large s, 1H, NH); 13C-NMR δ: 23.15 (CH2), 23.74
(CH2), 23.81 (CH3), 29.69 (CH2), 33.89 (CH2), 52.12 (CH3CO), 68.41 (C), 174.03 (C=O), 174.66
(C=O); MS m/z: Found [M-.CO2H]+ 172.1320, requires 172.1337.
Methyl 2-methyl-10-oxoazecane-2-carboxylate (L9a): C12H21NO3; Yield: 83%, brown paste; 1H-NMR
δ: 1.03-1.29 (m, 10H, 5CH2),1.49 (s, 3H, CH3), 1.58-1.72 (t, 2H, J= 12.5 Hz, CH2), 2.26-2.36 (t, 2H,
J= 11 Hz, (CH2), 3.66 (s, 3H, MeCO), 5.56 (large s, 1H, NH); 13C-NMR δ: 18.85 (CH2), 19.25 (CH2),
20.35 (CH2), 24.25 (CH2), 25.37 (CH2), 29.69 (CH3), 34.57 (CH2), 35.79 (CH2), 51.46 (CH3CO),
66.31 (C), 175.00 (C=O), 175.75 (C=O); MS m/z: Found [M-.CO2H]+ 200.1642, requires 200.16505.
1
Methyl 5-oxo-2-phenylpyrrolidine-2-carboxylate (L5b): C12H13NO3 : Yield: 86%, brown dough, H
NMR (300 MHz, CDCl3): δ: 2.60-2.66 (t, 2H, J= 3.95 Hz, CH2),3.01-3.08 (t, 2H, J= 9 Hz, CH2), 3.79
13
(s, 3H, MeCO), 5.78 (large s, 1H, NH), 7.35-7.79 (m, 5H, Ph), C NMR (75 MHz, CDCl3): δ: 20.24
(CH2), 21.87 (CH2), 30.36 (CH3CO), 66.51 (C), 126.74 (ArCH), 127.12 (ArCH), 128.39 (ArCH),
128.78 (ArCH), 129.52 (ArCH), 131.33 (ArCH), 135.58 (ArC), 137.21 (ArC), 176.70 (C=O), 176.88
(C=O); m/z: Found [M-.CO2Me]+ 160.0758, requires 160.07624.
1
Methyl 6-oxo-2-phenylpiperidine-2-carboxylate (L6b): C13H15NO3; Yield: 88%, brown paste; H-
NMR δ: 1.55-1.68 (qt, 2H, J= 6 Hz, CH2), 2.25-2.31 (t, 2H, J= 5 Hz, CH2), 2.40-2.49 (t, 2H, J= 4.35
Hz, CH2), 3.80 (s, 3H, MeCO), 6.52 (large s, 1H, NH), 7.33-7.90 (m, 5H, Ph); 13C-NMR δ: 17.28
(CH2), 30.88 (CH2), 33.04 (CH2), 53.13 (CH3CO), 65.61 (C), 125.05 (ArCH), 128.30 (ArCH), 129.00
(ArCH), 140.71 (ArC), 171.80 (C=O), 171.99 (C=O); MS m/z: Found [M+.] 233.1061, requires
233.10519.
1
Methyl 7-oxo-2-phenylazepane-2-carboxylate (L7b): C14H17NO3; Yield: 79%, brown paste; H-NMR
δ: 1.37-1.59 (qt, 2H, J= 6 Hz, CH2), 1.63-1.76 (qt, 2H, J= 3.5 Hz, CH2), 2.23-2.41 (t, 2H, J= 11 Hz,
CH2), 3.41-3.47 (t, 2H, J= 9 Hz, CH2), 3.70 (s, 3H, MeCO), 6.02 (large s, 1H, NH), 7.32-7.83 (m, 5H,
Ph); 13C-NMR δ: 22.94 (CH2), 24.82 (CH2), 36.14 (CH2), 37.64 (CH2), 52.81 (CH3CO), 65.19 (C),

Molecules 2007, 12
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125.01-127.92 (ArH), 141.75 (ArC), 174.85 (C=O), 176.02 (C=O); MS m/z: Found [M-.COOH]+
220.1331, requires 220.13375.
1
Methyl 8-oxo-2-phenylazocane-2-carboxylate (L8b): C15H19NO3; Yield: 78%, brown paste; H-NMR
δ: 1.10-1.84 (m, 6H, 3CH2), 2.21-2.41 (t, 2H, J= 12 Hz, CH2), 2.98-3.05 (t, 2H, J= 9 Hz, CH2), 3.73 (s,
13
3H, MeCO), 6.32 (large s, 1H, NH), 7.33-7.86 (m, 5H, Ph); C-NMR δ: 21.74 (CH2), 22.22 (CH2),
23.14 (CH2), 36.36 (CH2), 36.93 (CH2), 52.86 (CH3CO), 65.36 (C), 125.01-127.92 (ArH), 141.31
(ArC), 175.81 (C=O), 176.83 (C=O); MS m/z: Found [M-.COOH]+ 234.1488, requires 234.1494.
Methyl 10-oxo-2-phenylazecane-2-carboxylate (L9b): C17H23NO3; Yield: 79%, brown paste; 1H-NMR
δ: 0.92-1.36 (m, 10H, 5CH2), 1.47-1.76 (t, 2H, J= 9.31 Hz, CH2), 2.21-2.37 (t, 2H, J= 10.63 Hz, CH2),
13
3.71 (s, 3H, MeCO), 6.36 (large s, 1H, NH), 7.34-8.06 (m, 5H, Ph), C-NMR δ: 18.84 (CH2), 19.04
(CH2), 20.43 (CH2), 22.42 (CH2), 30.61 (CH2), 36.73 (CH2), 37.43 (CH2), 52.81 (CH3CO), 65.52 (C),
125.11-128.35 (ArH), 141.00 (ArC), 176.37 (C=O), 176.76 (C=O); MS m/z: Found [M-.COOH]+
262.1789, requires 262.1807.
1
Methyl 2-isopropyl-5-oxopyrrolidine-2-carboxylate (L5c): C9H15NO3; Yield: 85%, brown paste; H-
NMR δ: 1.01-1.06 (dd, 6H, J= 9 Hz, 2CH3), 1.08-1.30 (m, 1H, J= 6 Hz, CH), 2.93-3.00 (t, 2H, J= 9
13
Hz, CH2), 3.58-3.65 (t, 2H, J= 9 Hz, CH2), 3.77 (s, 3H, MeCO), 6.09 (large s, 1H, NH); C-NMR δ:
18.56 (CH3), 19.15 (CH3), 28.25 (CH), 30.13 (CH2), 30.3 (CH2), 53.03 (OCH3), 69.77 (C), 172.92
(C=O), 174.51 (C=O); MS m/z: Found [M-.CO2CH3]+ 126.1030, requires 126.1052.
1
Methyl 2-isopropyl-6-oxopiperidine-2-carboxylate (L6c): C10H17NO3; Yield: 82%, brown paste; H-
NMR δ: 1.04-1.29 (dd, 6H, J= 9 Hz, 2CH3), 1.82-1.95 (qt, 2H, J= 6.5 Hz, CH2), 2.03-2.09 (m, 1H, J=
6 Hz, CH), 2.18-2.24 (t, 2H, J= 9 Hz, CH2), 2.36-2.42 (t, 2H, J= 9 Hz, CH2), 3.71 (s, 3H, MeCO), 6.31
(large s, 1H, NH); 13C-NMR δ: 18.60 (CH3), 19.16 (CH3), 20.13 (CH2), 29.65 (CH), 31.14 (CH2),
34.13 (CH2), 53.28 (OCH3), 65.43 (C), 172.55 (C=O), 173.58 (C=O); MS m/z: Found [M]+ 199.1196,
requires 199.1208.
1
Methyl 2-isopropyl-7-oxoazepane-2-carboxylate (L7c): C11H19NO3; Yield: 80%, brown paste; H-
NMR δ: 1.04-1.27 (dd, 6H, J= 9 Hz, 2CH3), 1.32-1.45 (m, 4H, 2CH2), 1.66-1.84 (t, 2H, J= 6 Hz, CH2),
2.06-2.17 (m, 1H, J= 6 Hz, CH), 2.35-2.45 (t, 2H, J= 9 Hz, CH2), 3.70 (s, 3H, MeCO), 6.90 (large s,
1H, NH); 13C-NMR δ: 20.12 (CH3), 19.86 (CH3), 21.24 (CH2), 23.23 (CH2), 25.92 (CH2), 29.46 (CH),
34.67 (CH2), 52.68 (OCH3), 69.52 (C), 175.18 (C=O), 175.41 (C=O); MS m/z: Found [M-COOH]+
186.1356, requires 186.1365.
Methyl 2-isopropyl-8-oxoazocane-2-carboxylate (L8c): C12H21NO3; Yield: 78%, black paste; 1H-NMR
δ: 0.80-1.01 (m, 6H, 3CH2), 1.05-1.27 (dd, 6H, J= 9 Hz, 2CH3), 1.89-1.95 (t, 2H, J= 6 Hz, CH2), 2.01-
2.07 (m, 1H, J= 6 Hz, CH), 2.38-2.44 (t, 2H, J= 9 Hz, CH2), 3.69 (s, 3H, MeCO), 7.13 (large s, 1H,
NH), 13C-NMR δ: 19.43 (CH2), 21.43 (CH2), 21.89 (CH2), 24.32 (CH3), 25.46 (CH3), 28.20 (CH2),
31.27 (CH), 33.65 (CH2), 52.78 (OCH3), 68.72 (C), 174.98 (C=O), 176.38 (C=O); MS m/z: Found [M-
COOH]+ 200.1513, requires 200.1521.

Molecules 2007, 12
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1
Methyl 2-isopropyl-10-oxoazecane-2-carboxylate (L9c): C14H25NO3; Yield: 76%, black paste; H-
NMR δ: 0.86-1.02 (dd, 6H, J= 6 Hz, 2CH3), 1.17-1.44 (m, 10H, 5CH2), 1.65-1.96 (m, 1H, J= 6 Hz,
CH), 2.21-2.34 (t, 2H, J= 9 Hz, CH2), 3.40-3.56 (t, 2H, J= 10.5 Hz, CH2), 3.70 (s, 3H, MeCO), 6.28
(large s, 1H, NH); 13C-NMR δ: 19.13 (CH3), 19.45 (CH3), 21.79 (CH2), 20.13 (CH2), 25.24 (CH2),
26.05 (CH), 28.15 (CH2), 30.63 (CH2). 35.12 (CH2), 35.67 (CH2), 52.98 (OCH3), 68.83 (C), 173.65
(C=O), 176.68 (C=O); MS m/z: Found [M-COOH]+ 228.18151, requires 228.1834.
Acknowledgments
The authors thank the Ministry of Higher Study and Research of Algeria for financial support.
References and Notes
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