N-Methoxy-N-methyl-3-bromopropionamide: A new three carbon homologating agent for the synthesis of unsymmetrical 1,4-diketones

Article abstract of DOI:10.1016/S0040-4020(01)00571-3

A synthetic route based on a three carbon homologation of an α-aminonitrile was developed for the synthesis of unsymmetrical 1,4-diketones. The key steps were the alkylation of various aryl and heteroaryl α-aminonitriles with N-methoxy-N-methyl-3-bromopropionamide followed by the addition of a Grignard reagent to the alkylated product and then subsequent hydrolysis.

Full text of DOI:10.1016/S0040-4020(01)00571-3

TETRAHEDRON
Pergamon
Tetrahedron 57 82001) 6065±6069
N-Methoxy-N-methyl-3-bromopropionamide: a new three carbon
homologating agent for the synthesis
of unsymmetrical 1,4-diketones
V. Selvamurugan and I. S. Aidhenp
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India
This work is dedicated to Professor M. S. Wadia
Received 12 February 2001; revised 1 May 2001; accepted 24 May 2001
AbstractÐA synthetic route based on a three carbon homologation of an a-aminonitrile was developed for the synthesis of unsymmetrical
1,4-diketones. The key steps were the alkylation of various aryl and heteroaryl a-aminonitriles with N-methoxy-N-methyl-3-bromo-
propionamide followed by the addition of a Grignard reagent to the alkylated product and then subsequent hydrolysis. q 2001 Elsevier
Science Ltd. All rights reserved.
1. Introduction
3-bromopropionic acid would be the simplest equivalent
possible. For acyl anion, we were attracted by the less
frequently used a-aminonitriles 113 due to the simplicity
and convenience involved in their preparation on a multi-
gram scale. It also prevented the use of obnoxious smelling
propane and ethane dithiols in large quantities for the more
commonly used alkyl and aryl dithianes14 as acyl anion
equivalents.
1,4-Diketones are useful intermediates for the preparation of
®ve membered carbocyclic and heterocyclic compounds.1
The most versatile process to 1,4-diketones in the literature
involves conjugate acylation2 of the enones, for which
various acyl anions have been developed.3 Another attrac-
tive route to 1,4-diketones involves acylation of homo-
enolates4 with acid halides. Symmetrical 1,4-diketones can
be prepared by homocoupling of carbonylmethyl radicals,5
metal enolates6 and a-halocarbonyls.7 In contrast coupling
of carbonylmethyl anions and cations for unsymmetrical
1,4-diketones has remained a challenge until recently.8 In
another approach, Echavarren9 made an elegant use of the
stannane, 8E)-1,2-bis 8tri-n-butylstannyl)ethene, as ethane
1,2-dianion equivalent, for the synthesis of unsymmetrical
1,4-diketones by reaction with acid chlorides under palla-
dium catalysed conditions. Similarly, acetylene dimag-
nesium bromide or dilithium acetylide have been used10 as
ethane 1,2-dianions during preparation of alkynediols,
which subsequently served as a potential precursor for facile
palladium catalysed isomerisation to 1,4-diketones.11
2. Results and discussion
Scheme 1 summarizes our initial results. Amide 3a was
obtained in good yield 878%) by the reaction of the carb-
anion from the aminonitrile 1a 8R1ˆPh) and 215 in DMFat
room temperature. Although a weak cyano stretching
frequency at 2258 cm21was observed in the IR spectrum
of 3a, a ®rm evidence for the presence of cyano function-
ality in 3a came from a peak at 116.6 ppm in its 13C NMR
spectrum. Since it is an established fact that no overaddition
of the organometallic reagent 8RLi or RMgX) occurs to
Weinreb amides, in a model reaction 3a was treated with
3 equiv. of butylmagnesium bromide in THFat 2788C and
no reaction occurred at this temperature. However, a clean
In this paper, we outline an alternative approach to unsym-
metrical 1,4-diketones using the disconnection shown in
Fig. 1. It was clear and obvious that the success of the
proposed route would exclusively rely on the availability
of a stable synthetic equivalent for the three carbon synthon
Y. It appeared that the corresponding Weinreb amide12 of
1
reaction ensued at 08C in 1 h as indicated by TLC. The H
NMR spectrum of the isolated product on work up was
clearly indicative of a clean reaction at the amide carbonyl
Keywords: 1,4-diketone; Weinreb amide; homologating agent; Grignard
reagent; a-aminonitrile.
Corresponding author. Fax: 191-44-2350509;
p
Figure 1.
e-mail: isingh@pallava.iitm.ernet.in
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020801)00571-3

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V. Selvamurugan, I. S. Aidhen / Tetrahedron 57 (2001) 6065±6069
Scheme 1. Reagents: 8i) NaH, DMF, rt, 6 h; 8ii) R2MgBr, THF, 08C, 1 h; 8iii) CuSO4, aq. MeOH, re¯ux, 3 h.
by the absence of singlets at d 3.49 8±OCH3) and 3.07
8N±CH3). Direct hydrolysis of the product 4a by the use
of CuSO4´5H2O in aqueous methanol at re¯ux conditions,16
®nally afforded the unsymmetrical 1,4-diketone 5a, in an
isolated yield of 76% after puri®cation.
reaction, when substrate 2 was ®rst reacted with 3 equiv.
of butylmagnesium bromide in THFat 0 8C, it afforded in
good yields, N-methyl heptanamide as the sole product.
Substrate 2 probably underwent a facile E2 elimination
forming in situ N-methoxy-N-methyl acrylamide, which
underwent Michael reaction followed by deformylation18
or vice versa with the additional 2 equiv. of butylmag-
nesium bromide affording the heptanamide after aqueous
work up.
Various other aryl and heteroaryl aminonitriles 81b±f) were
prepared according to Dyke's procedure17 and conveniently
alkylated with 2 affording 3b±f in good yields 8Table 1).
Compounds 3b±f were puri®ed by chromatography over
silica gel and thoroughly dried before their reaction with
various alkyl and aryl Grignard reagents. In all cases
clean reaction occurred in 1±1.5 h at 08C affording the inter-
mediates 4b±i. These intermediates 4b±i were then directly
hydrolysed to furnish the corresponding unsymmetrical
1,4-diketones 5a±i in good isolated yields 8Table 2). The
sequence, ®rst the reaction of acyl anion with 2 followed by
the reaction with Grignard reagent is crucial and vital for the
success of the route as reversal in the order of the reactions
fails to afford the desired products. In an independent
3. Conclusion
To conclude, a strategy based on a new disconnection, and
making use of 2 as a new valuable three carbon homolo-
gating agent has been realized. Although a convenient use of
a-aminonitriles as acyl anion equivalents have been made
here, the ready availability of more commonly used
dithianes as acyl anion equivalents makes the approach
even more versatile and ¯exible.
Table 1. Alkylation of a-aminonitriles 1a±f with 2
4. Experimental
4.1. General
Entry
a-Aminonitrile
R1
Product
Yield 8%)a
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
C6H5
3a
3b
3c
3d
3e
3f
78
75
71
3-ClC6H4
4-CH3C6H4
4-CH3OC6H4
2-Furyl
All the solvents and reagents were distilled before use. Dry
solvents were prepared as per standard procedures. Reac-
tions requiring inert atmosphere were carried out under dry
nitrogen atmosphere. Melting points were determined in
capillary using a Toshniwal melting point apparatus and
are uncorrected. NMR spectra were recorded on Bruker
8300 MHz 1H, 75 MHz 13C) or Jeol 8400 MHz 1H,
100 MHz 13C) NMR spectrometers using TMS as an
internal standard. IR spectra were recorded on Shimadzu
IR 470 instrument. Elemental analyses were performed on
a Heraeus CHN analyzer. The TLC for monitoring the
course of the reaction were performed on the silica gel
8Merck, TLC grade) coated on a glass plate 87£2.5 cm)
followed by staining in iodine vapours. For column
chromatography, silica gel 8100±200 mesh) was used,
unless otherwise indicated.
75
72b
70b
2-Thienyl
a
Isolated yield.
1 h at 08C, then 5 h at rt.
b
Table 2. Various unsymmetrical 1,4-diketones 5a±i were prepared
Product
R1
R2
Yield 8%)a
5a
5b
5c
5d
5e
5f
5g
5h
5i
C6H5
C6H5
C4H9
76
72
69
70
79
75
73
72
68
1-Naphthyl
8CH3)2CH
4-CH3C6H4
C4H9
4-CH3OC6H4
1-Naphthyl
C4H9
3-ClC6H4
3-ClC6H4
3-ClC6H4
4-CH3C6H4
4-CH3OC6H4
2-Furyl
4.2. Preparation of starting materials
2-Thienyl
C6H5
a
Isolated yield based on 3.
a-Aminonitriles 1a±f were prepared according to the

V. Selvamurugan, I. S. Aidhen / Tetrahedron 57 (2001) 6065±6069
6067
general procedure described in the literature.17 N-Methoxy-
N-methyl-3-bromopropionamide 2 was prepared according
to the procedure described in the literature.15 All Grignard
reagents were prepared according to the classical procedure.
173.2 ppm; Anal. calcd for C18H25N3O3: C, 65.23; H,
7.60; N, 12.68. Found: C, 65.18; H, 7.48; N, 12.55.
4.3.4. 4-Cyano-4-,4-methoxyphenyl)-4-morpholino-N-
methoxy-N-methylbutyramide ,3d). Yield 75%; colour-
less syrup; Rfˆ0.30 8hexane/EtOAc, 8:2); IR 8CHCl3): n
2891, 2255, 1689, 1444, 1378 cm21 1H NMR 8CDCl3,
;
4.3. General procedure for the alkylation of a-amino-
nitriles ,1a±f) with 2
300 MHz): dH 1.98 8t, 2H, ±CCH2CH2±, Jˆ6.5 Hz),
2.25±2.48 8m, 6H, ±CH2CH2CO±, ±N8CH2)2±), 3.10 8s,
3H, ±NCH3), 3.58 8s, 3H, ±OCH3), 3.70 8s, 3H, Ar±
OCH3), 3.75 8m, 4H, ±O8CH2)2), 7.55±7.61 8m, 4H, Ar±
H) ppm; 13C NMR 8CDCl3, 75 MHz): dC 26.1 8t), 31.2 8t),
32.2 8q), 49.4 8t), 59.7 8q), 65.8 8t), 66.4 8q), 68.9 8s), 116.8
8s), 118.9 8d), 125.5 8d), 129.5 8s), 159.9 8s), 172.5 98s) ppm;
Anal. calcd for C18H25N3O4: C, 62.23; H, 7.25; N, 12.10.
Found: C, 62.19; H, 7.18; N, 12.35.
Sodium hydride 80.36 g, 15 mmol, 60% suspension in
paraf®n oil) was washed with dry hexane and suspended
in dry DMF810 mL) under a nitrogen atmosphere. A solu-
tion of an a-aminonitrile 810 mmol) in dry DMF810 mL)
was added at room temperature 808C in case of 3e and 3f).
The resulting red coloured suspension was stirred for 0.5 h
and N-methoxy-N-methyl-3-bromopropionamide 2 82 g,
10 mmol) in dry DMF810 mL) was added. After stirring
for 6 h, the excess of NaH was destroyed with saturated
NH4Cl solution. The organic portion was extracted with
EtOAc 83£50 mL). The combined organic extracts were
washed with brine, dried over Na2SO4 and concentrated
under reduced pressure. The residue was column chromato-
graphed on neutral alumina with hexane/EtoAc 89:1) as an
eluent to afford 3a±f.
4.3.5. 4-Cyano-4-,2-furyl)-4-morpholino-N-methoxy-N-
methylbutyramide ,3e). Yield 72%; colourless syrup;
Rfˆ0.32 8hexane/EtOAc, 8:2); IR 8CHCl3): n 2864, 2240,
1
1680, 1462, 1388 cm21; H NMR 8CDCl3, 300 MHz): dH
2.11 8t, 2H, ±CCH2CH2±, Jˆ6.5 Hz), 2.49±2.67 8m, 6H, ±
CH2CH2CO±, ±N8CH2)2±), 3.11 8s, 3H, ±NCH3), 3.56 8s,
3H, ±OCH3), 3.65 8m, 4H, ±O8CH2)2), 6.32 8d, 1H, Ar±H,
Jˆ3.6 Hz), 6.50 8m, 1H, Ar±H) 7.40 8d, 1H, Ar±H, Jˆ
1.8 Hz) ppm; 13C NMR 8CDCl3, 75 MHz): dC 27.2 8t),
30.7 8t), 32.6 8q), 48.5 8t), 61.1 8q), 65.0 8t), 66.6 8s),
110.3 8s), 111.0 8d), 116.1 8d), 143.5 8d), 148.1 8s), 173.0
8s) ppm; Anal. calcd for C15H21N3O4: C, 58.62; H, 6.89; N,
13.67. Found: C, 58.89; H, 6.78; N, 13.75.
4.3.1. 4-Cyano-4-morpholino-4-phenyl-N-methoxy-N-
methylbutyramide ,3a). Yield 78%; colourless solid; mp
42±448C; Rfˆ0.35 8hexane/EtOAc, 8:2); IR 8CHCl3): n
1
2976, 2258, 1683, 1436, 1376 cm21; H NMR 8CDCl3,
300 MHz): dH 1.95 8t, 2H, ±CCH2CH2±, Jˆ6.3 Hz),
2.21±2.42 8m, 6H, ±CH2CH2CO±, ±N8CH2)2±), 3.07 8s,
3H, ±NCH3), 3.49 8s, 3H, ±OCH3), 3.70 8m, 4H,
±O8CH2)2), 7.35±7.43 8m, 3H, Ar±H), 7.55±7.57 8m, 2H,
Ar±H) ppm; 13C NMR 8CDCl3, 75 MHz): dC 26.9 8t), 30.9
8t), 33.4 8q), 48.2 8t), 60.7, 8q), 66.4, 8t), 69.9, 8s), 116.6, 8s),
126.4 8d) 128.1 8d), 128.5 8d), 136.5 8s), 172.0 8s) ppm;
Anal. calcd for C17H23N3O3: C, 64.33; H, 7.30; N, 13.24.
Found: C, 64.28; H, 7.42; N, 13.35.
4.3.6. 4-Cyano-4-morpholino-4-,2-thienyl)-N-methoxy-
N-methylbutyramide ,3f). Yield 70%; colourless syrup;
Rfˆ0.29 8hexane/EtOAc, 8:2); IR 8CHCl3): n 2872, 2245,
1689, 1472, 1389 cm21;1H NMR 8CDCl3, 300 MHz): dH
1.99 8t, 2H, ±CCH2CH2±, Jˆ6.5 Hz), 2.38±2.52 8m, 6H,
±CH2CH2CO±, ±N8CH2)2±), 3.07 8s, 3H, ±NCH3), 3.61
8s, 3H, ±OCH3), 3.68 8m, 4H, ±O8CH2)2), 7.11 8d, 1H,
Ar±H, Jˆ3.8 Hz), 7.15 8m, 1H, Ar±H), 7.30 8d, 1H, Ar±
H, Jˆ4.1 Hz) ppm; 13C NMR 8CDCl3, 75 MHz): dC 26.1 8t),
31.7 8t), 32.8 8q), 49.1 8t), 61.5 8q), 65.6 8t), 66.8 8s), 116.27
8s), 123.1 8d), 124.4 8d), 126.8 8d), 138.0 8s), 173.1 8s) ppm;
Anal. calcd for C15H21N3O3S: C, 55.71; H, 6.54; N, 12.99.
Found: C, 55.86; H, 6.58; N, 12.81.
4.3.2. 4-,3-Chlorophenyl)-4-cyano-4-morpholino-N-meth-
oxy-N-methylbutyramide ,3b). Yield 75%; colourless
solid; mp 45±488C; Rfˆ0.48 8hexane/EtOAc, 8:2); IR
1
8CHCl3): n 2986, 2255, 1688, 1436, 1375 cm21; H NMR
8CDCl3, 300 MHz): dH 1.85 8t, 2H, ±CCH2CH2±, Jˆ
6.5 Hz), 2.25±2.51 8m, 6H, ±CH2CH2CO±, ±N8CH2)2±),
3.10 8s, 3H, ±NCH3), 3.58 8s, 3H, ±OCH3), 3.70 8m, 4H,
±O8CH2)2), 7.55±7.61 8m, 4H, Ar±H) ppm; 13C NMR
8CDCl3, 75 MHz): dC 25.7 8t), 31.8 8t), 33.5 8q), 49.5 8t),
61.1 8q), 66.8 8t), 69.9 8s), 117.6 8s), 125.1 8d), 126.7 8d),
128.1 8d), 129.5 8d), 134.9 8s), 136.4 8s), 171.4 8s) ppm;
Anal. calcd for C17H22ClN3O3: C, 58.03; H, 6.30; N,
11.94. Found: C, 57.98; H, 6.38; N, 12.05.
4.4. General procedure for the addition of Grignard
reagents to 3a±f
To a solution of 3 82.5 mmol) in THF820 mL), the appro-
priate Grignard reagent 87.5 mmol) was added under a nitro-
gen atmosphere at 08C. The mixture was stirred for a 1.5 h
period. The hydrolysis was achieved by the cautious addition
of saturated NH4Cl solution. After returning to room tempera-
ture, the two phases were separated and the aqueous phase
was extracted with EtOAc 83£20 mL). The organic phases
were combined, washed with brine and dried over Na2SO4.
Removal of the solvent under reduced pressure gave the
crude product 4a±i, which was directly hydrolysed without
further puri®cation following a literature procedure.16
4.3.3. 4-Cyano-4-,4-methylphenyl)-4-morpholino-N-meth-
oxy-N-methylbutyramide ,3c). Yield 71%; colourless
solid; mp 35±388C; Rfˆ0.38 8hexane/EtOAc, 8:2); IR
1
8CHCl3): n 2955, 2254, 1683, 1435, 1375 cm21; H NMR
8CDCl3, 300 MHz): dH 1.85 8t, 2H, ±CCH2CH2±, Jˆ
6.3 Hz), 2.21 8s, 3H, Ar±CH3), 2.28±2.50 8m, 6H,
±CH2CH2CO±, ±N8CH2)2±), 3.10 8s, 3H, ±NCH3), 3.61
8s, 3H, ±OCH3), 3.70 8m, 4H, ±O8CH2)2), 7.33±7.41 8m,
4H, Ar±H) ppm; 13C NMR 8CDCl3, 75 MHz): dC 21.3 8q),
26.1 8t), 32.3 8t), 33.6 8q), 49.8 8t), 62.5 8q), 65.7 8t), 66.8 8s),
116.6 8s), 126.5 8d), 128.4 8d), 129.2 8s), 137.8 8s),
4.5. General procedure for the hydrolysis of 4a±i
To the crude product obtained from the above reaction, a

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V. Selvamurugan, I. S. Aidhen / Tetrahedron 57 (2001) 6065±6069
solution of CuSO4´5H2O 80.6 g, 2.5 mmol) and 3:1 aqueous
CH3OH 815 mL) was added and heated at re¯ux. After
stirring for 3 h, the reaction mixture was cooled to room
temperature and the organic portion was extracted with
EtOAc 83£20 mL). The combined organic extracts were
dried over Na2SO4 and concentrated under reduced pressure
to give the crude product which on puri®cation by column
chromatography 810% EtOAc in hexane) afforded the pure
1,4-diketones 5a±i.
8s), 198.7 8s) ppm; Anal. calcd for C18H18O3: C, 76.57; H,
6.43. Found: C, 76.49; H, 6.52.
4.5.5. 1-,2-Furyl)-1,4-octanedione ,5h). Yield 72%;
colourless solid; mp 45±488C; Rfˆ0.29 8hexane/EtOAc,
9:1); IR 8CHCl3): n 2960, 1718, 1683, 1571, 1468,
1
1254 cm21; H NMR 8CDCl3, 300 MHz): dH 0.84 8t, 3H,
CH3CH2±, Jˆ7.2 Hz) 1.25 8m, 2H, CH3CH2CH2±) 1.50 8m,
2H, ±CH2CH2CH2±) 2.43 8t, 2H, CH2CH2CO±, Jˆ
7.2 Hz)), 2.77 8t, 2H, ±COCH2CH2±, Jˆ6.3 Hz), 3.06 8t,
2H, ±CH2CH2CO±, Jˆ6.3 Hz), 6.47 8dd, 1H, Ar±H, Jˆ
3.0, 1.4 Hz), 7.14 8d, 1H, Ar±H, Jˆ3.0 Hz), 7.52 8d, 1H,
Ar±H, Jˆ1.4 Hz) ppm; 13C NMR 8CDCl3, 75 MHz): dC
13.7 8q), 22.1 8t), 22.5 8t), 29.2 8t), 35.6 8t), 42.4 8t), 116.5
8d), 116.9 8d), 146.2 8d), 152.3 8s), 187.7 8s), 209.3 8s) ppm;
Anal. calcd for C12H16O3: C, 69.21; H, 7.74. Found: C,
69.11; H, 7.84.
1,4-diketones 5a,9 5b,4b 5g,4b and 5i11f are known com-
pounds and their physical and spectroscopic data 8IR, H
1
NMR) agreed with the reported values. Other products
were characterized as follows.
4.5.1. 1-,3-Chlorophenyl)-5-methylhexane-1, 4-dione
,5c). Yield 69%; colourless syrup; Rfˆ0.41 8hexane/
EtOAc, 9:1); IR 8CHCl3): n 2976, 1715, 1689, 1459,
1420, 1340 cm21;1H NMR 8CDCl3, 300 MHz): dH 1.14 8d,
6H, ±CH8CH3)2, Jˆ7.4 Hz), 2.69 8m, 1H, ±CH8CH3)2),
2.89 8t, 2H, ±CH2CH2±, Jˆ6.4 Hz), 3.20 8t, 2H, ±
CH2CH2±, Jˆ6.4 Hz), 7.34±7.51 8m, 2H, Ar±H), 7.84±
7.92 8m, 2H, Ar±H) ppm; 13C NMR 8CDCl3, 75 MHz): dC
18.2 8q), 32.3 8d), 33.8 8t), 40.8 8t), 126.0 8d), 128.1 8d),
129.7 8d), 132.7 8d), 134.8 8s), 138.2 8s), 197.4 8s), 212.9
8s) ppm; Anal. calcd for C13H15ClO2: C, 65.41; H, 6.33.
Found: C, 65.50; H, 6.38.
4.5.6. Addition of butylmagnesium bromide to 2. To a
solution of 2 82.5 mmol) in THF815 mL), butylmagnesium
bromide 87.5 mmol) was added under a nitrogen atmosphere
at 08C. The mixture was stirred for a 1.5 h period. The
hydrolysis was achieved by the cautious addition of satu-
rated NH4Cl solution. After returning to room temperature,
the two phases were separated and the aqueous phase was
extracted with EtOAc 83£15 mL). The organic phases were
combined, washed with brine and dried over Na2SO4.
Removal of the solvent under reduced pressure gave the
crude product which on puri®cation by column chroma-
tography 820% EtOAc in hexane) afforded N-methyl-
heptanamide as a colourless syrup.
4.5.2. 1-,3-Chlorophenyl)-4-,4-methylphenyl)-1,4-buta-
nedione ,5d). Yield 70%; colourless solid; mp 108±
1108C; Rfˆ0.32 8hexane/EtOAc, 9:1); IR 8CHCl3): n
1
2912, 1689, 1606, 1504, 1414, 1337, 1315 cm21; H NMR
Yield 0.25 g, 871%); Rfˆ0.35 8hexane/EtOAc, 7:3); IR
8CDCl3, 300 MHz): dH 2.39 8s, 3H, Ar±CH3), 3.39 8m, 4H,
±CH2CH2±), 7.23±7.53 8m, 4H, Ar±H), 7.89±7.98 8m, 4H,
Ar±H) ppm; 13C NMR 8CDCl3, 75 MHz): dC 21.6 8q), 32.4
8t), 32.6 8t), 126.1 8d), 128.18d), 128.2 8d), 129.2 8d), 129.8
8d), 132.9 8d), 134.1 8s), 134.9 8s), 138.7 8s), 143.9 8s), 197.5
8s), 197.9 8s) ppm; Anal. calcd for C17H15ClO2: C, 71.20; H,
5.27. Found: C, 70.99; H, 5.19.
1
8CHCl3): n 2955, 1660, 1342, 1177, 1121 cm21; H NMR
8CDCl3, 400 MHz): dH 0.80 8t, 3H, CH3CH2±, Jˆ7.3 Hz),
1.20 8m, 6H, CH38CH2)3CH2CH2CO±), 1.55 8m, 2H,
±CH2CH2CH2CO±) 2.15 8t, 2H, ±CH2CH2CO± Jˆ
7.3 Hz) 2.75 8d, 3H, ±NHCH3, Jˆ5 Hz), 6.40 8br s,
±NHCH3) ppm; 13C NMR 8CDCl3, 75 MHz): dC 13.8 8q),
22.3 8t), 25.6 8t), 26.0 8t), 28.8 8t), 31.4 8t), 36.4 8q), 174.2
8s) ppm; Anal. calcd for C8H17NO: C, 67.09; H, 11.96; N,
9.78. Found: C, 67.18; H, 11.88; N, 9.77.
4.5.3. 1-,3-Chlorophenyl)-1,4-octanedione ,5e). Yield
79%; colourless solid; mp 38±408C; Rfˆ0.35 8hexane/
EtOAc, 9:1); IR 8CHCl3): n 2960, 1718, 1686, 1459,
1
1414, 1344 cm21; H NMR 8CDCl3, 300 MHz): dH 0.82
Acknowledgements
8t, 3H, CH3CH2±, Jˆ7.3 Hz) 1.25 8m, 2H, CH3CH2CH2±)
1.50 8m, 2H, ±CH2CH2CH2±) 2.42 8t, 2H, CH2CH2CO±,
Jˆ7.3 Hz)), 2.76 8t, 2H, ±COCH2CH2±, Jˆ6.3 Hz), 3.13
8t, 2H, ±CH2CH2CO±, Jˆ6.3 Hz), 7.27±7.40 8m, 2H,
Ar±H), 7.73±7.83 8m, 2H, Ar±H) ppm; 13C NMR 8CDCl3,
75 MHz): dC 13.6 8q), 22.1 8t), 25.7 8t), 32.2 8t), 35.8 8t),
42.3 8t), 125.9 8d), 127.9 8d), 129.9 8d) 132.7 8d), 134.6 8s),
138.0 8s), 197.1 8s), 209.1 8s) ppm; Anal. calcd for
C14H17ClO2: C, 66.53; H, 6.78. Found: C, 66.71; H, 6.91.
We are grateful to DST, New Delhi for ®nancial support
8project no. SP/S1/G-06/2000) for this research and RSIC
8IIT), Chennai for the spectral data. One of us 8V. S.) thanks
IIT, Chennai for the fellowship and Dr Jaimala Singh,
CLRI, Chennai for constant support.
References
4.5.4.
1-,4-Methoxyphenyl)-4-,4-methylphenyl)-1,4-
butanedione ,5f). Yield 75%; colourless syrup; Rfˆ0.42
1424, 1345 cm21; H NMR 8CDCl3, 300 MHz): dH 2.28
8s, 3H, Ar±CH3), 3.42 8s, 4H, ±CH2CH2±), 3.83 8s, 3H,
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129.8 8d), 130.2 8s), 134.16 8s), 138.3 8s), 158.8 8s), 197.6
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