Reaction of methyl diazoacetate with aldehydes, amines, thiols, alcohols and acids over transition metal-exchanged clays

Article abstract of DOI:10.1039/a905028k

Metal-exchanged clays (M = Rh and Cu) catalyze effectively the reaction of methyl diazoacetate with various aldehydes, affording the corresponding β-keto esters in high yields. They have also been effective in the decomposition of methyl diazoacetate to form metallocarbenes which, in turn, successfully insert into X-H (X = N, O, S, CO₂) bonds of a variety of amines, aldehydes, thiols and acids, thereby producing the corresponding esters. The Royal Society of Chemistry 1999.

Full text of DOI:10.1039/a905028k

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Reaction of methyl diazoacetate with aldehydes, amines, thiols,
alcohols and acids over transition metal-exchanged clays
Prodeep Phukan, Jakkam Madan Mohan and Arumugam Sudalai*
Process Development Division, National Chemical Laboratory, Pune 411 008, India.
E-mail: sudalai@dalton.ncl.res.in
Received (in Cambridge, UK) 23rd June 1993, Accepted 23rd September 1999
Metal-exchanged clays (M = Rh and Cu) catalyze effectively the reaction of methyl diazoacetate with various
aldehydes, affording the corresponding β-keto esters in high yields. They have also been effective in the
decomposition of methyl diazoacetate to form metallocarbenes which, in turn, successfully insert into X–H (X = N,
O, S, CO2) bonds of a variety of amines, aldehydes, thiols and acids, thereby producing the corresponding esters.
Table 1 The reaction of benzaldehyde with methyl diazoacetate over
various clay catalystsa
In recent years, use of aluminosilicates, particularly clays, has
gained importance for catalysis of various useful organic trans-
formations. These clays are predominantly composed of
hydrous phyllosilicates, referred to as clay minerals.1 They often
exhibit high surface acidity and this property has been har-
nessed to realize useful organic transformations. Many clay
mineral crystals carry an excess negative electric charge owing
to internal substitution by lower-valent cations and thereby
increase internal reactivity in chemical combination and ion
exchange. The cation-exchanged clays are found to catalyze
various organic transformations and many reports are found in
the recent literature.
Carbene-insertion reactions are of current interest as these
methods allow us an easy process of C–C and C–X (X = N, O,
S) bond formation. Insertion of carbenes into aliphatic C–H
and polar X–H bonds have been used increasingly for the syn-
thesis of carbo- and heterocycles.2 From this point of view, β-
keto esters serve as potential synthetic intermediates. Due to the
presence of both electrophilic and nucleophilic sites, β-keto
esters make their place unique in organic synthesis.3 We report
herein the insertion of the carbene generated from methyl
diazoacetate to X–H bonds (X = C, N, S, O) of various com-
pounds such as aldehydes, amines, thiols, acids and alcohols
catalyzed by metal-exchanged clays.
Entry
Catalyst
t/h
Yieldb
1
2
3
4
5
6
7
8
No catalyst
Mont K10
15
15
5
5
12
2
0
0
CuII-Mont K10
RhIII-Mont K10
MnIII-Mont K10
Rh-SiO2
80
78
20
55
52
0
Rh-Al2O3
Rh/C
5
15
a Reaction conditions: benzaldehyde (5 mmol), methyl diazoacetate (5.5
mmol), catalyst (10 wt%), benzene (10 mL), 80 ЊC. b Isolated yield after
chromatographic purification.
esters on a large scale by this method. Synthesis of β-keto esters
by reaction of acetyl chloride with ethyl hydrogen malonate is
also reported.7 Balaji et al.8 recently reported a synthetic
method to obtain β-keto esters from aldehydes using H-β-
zeolite as a catalyst. Aromatic aldehydes were observed to be
less reactive than aliphatic ones, while alkyl and aryl ketones
were totally unreactive. We have systematically studied the
reaction between aldehydes and methyl diazoacetate over
various transition metal exchanged clays as catalysts to afford
β-keto esters (Scheme 1).
Results and discussion
a. Synthesis of ꢀ-keto esters
Synthetic routes to β-keto esters essentially involve acylation of
acetate anions, carboxylic acid derivatives and malonate anions
mostly with acyl halides.3 However, these methods need low
temperatures and use of strong bases such as lithium amides.
The direct condensation of methyl diazoacetate with aldehydes
has the potential to generate a practical methodology for the
synthesis of β-keto esters; nevertheless, studies on such a reac-
tion have been limited.
The earliest example concerns BF3ؒdiethyl ether-catalyzed
transformation of sugar aldehydes to the corresponding β-keto
esters, albeit in rather low yields.4 Holmquist and Roskamp5
have investigated the SnCl2-catalyzed reaction of aldehydes
with ethyl diazoacetate to develop a method for β-keto esters.
However, this method was suitable only for aliphatic aldehydes;
aromatic aldehydes led to poor yields of the corresponding
β-keto esters. Dhavale et al.6 reported activated alumina-
promoted reaction of aldehydes with ethyl diazoacetate leading
to β-keto esters. The requirement of activated alumina in large
quantities constitutes a limitation in the preparation of β-keto
Scheme 1
Initially, a systematic study was undertaken with various
metal-exchanged clay catalysts and it was found that both CuII
and RhIII Mont K10 clays showed excellent activity for the con-
densation of methyl diazoacetate with benzaldehyde (Table 1).
The reaction failed in the case of Mont K10 clay alone as well
as with Rh/C as catalyst. We have further subjected various
aldehydes for reaction with methyl diazoacetate under the influ-
ence of the best catalyst CuII-Mont K10 clay (Table 2). Both
aromatic and aliphatic aldehydes underwent condensation to
yield the β-keto esters in good yields. An interesting feature
from the β-keto ester products from aromatic aldehydes is that
the products comprised both keto and enol components, as
1
indicated by the splitting of a H NMR signal at around δ 4.
J. Chem. Soc., Perkin Trans. 1, 1999, 3685–3689
This journal is © The Royal Society of Chemistry 1999
3685

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Table 2 Synthesis of β-keto esters using Cu-Mont K10 as catalysta
Entry
Substrate
Product
t/h
Yield (%)b
1
2
3
4
5
6
Benzaldehyde
Methyl 3-oxo-3-phenylpropionate
5
5
5
2
2
3
80
69
72
70
90
62
4-Methoxybenzaldehyde
3,4-Dimethoxybenzaldehyde
4-Chlorobenzaldehyde
Decanal
Methyl 3-(4-methoxyphenyl)-3-oxopropionate
Methyl 3-(3,4-dimethoxyphenyl)-3-oxopropionate
Methyl 3-(4-chlorophenyl)-3-oxopropionate
Methyl 3-oxododecanoate
Isobutyraldehyde
Methyl 4-methyl-3-oxopentanoate
a Reaction conditions: aldehyde (5 mmol), methyl diazoacetate (5.5 mmol), Cu-Clay (10 wt%), benzene (10 mL), 80 ЊC. b Isolated yield after
chromatographic purification.
Table 3 Cu-Mont K10-catalyzed insertion of methyl diazoacetate into
products, comprising 47% of the N-alkylated product A and
20% of the imine B. The yield of the imine increases with
increasing chain length of the alkyl substituent on the nitrogen
atom. For example, use of N-butylaniline resulted in 34% of
the imine as a side-product. The formation of the imines could
be rationalized as arising from elimination of the n-alkyl side-
chain leading to a doubly conjugated system.
an NH bonda
c. Synthesis of ꢁ-thiol, ꢁ-acetoxy and ꢁ-oxa esters
Aryl or alkyl thioesters are important compounds for the syn-
thesis of biologically active compounds such as ∆α,β-buteno-
lides,12 α-methylene lactones and cyclic ketones via alkylative
elimination.12 Further, polyunsaturated compounds having
β-oxa, γ-oxa, β-thia and γ-thia substituents have been found to
possess antimalarial and neutrophil-stimulatory activity.13
Reaction of thiols and alcohols with diazoacetate has already
been studied by using copper compounds such as cupric [cop-
Yieldb (%)
Entry
R
RЈ
t/h
A
B
1
2
3
4
5
6
7
Ph
H
H
H
H
Me
Et
n-Bu
3
3
3
4
3
3
3
82
50
93
82
61
47
68
2-Methylphenyl
1-Naphthyl
Cyclohexyl
Ph
Ph
Ph
per()] chloride,14 rhodium compounds such as RhCl3ؒ3H2O,
13–20
RhCl(PPh3)3,15 Rh2(OAc)4
and ruthenium complexes.21 It
20
has recently been reported that Cu(acac)2 catalyzes insertion
reactions of diazoketones with various acids.22 We report here
the study of Cu- and Rh-exchanged montmorillonite clay
as heterogeneous catalysts to achieve insertion reactions of
carbenes into X–H (X = S, O, CO2) bonds (Scheme 2).
a Reaction conditions: substrate (5 mmol), methyl diazoacetate (7
mmol), Cu-Clay (10 wt%), benzene (10 mL), 80 ЊC, 3 h. b Isolated yield
after chromatographic purification.
Another significant feature of the work is the enhancement in
the rate of the reaction observed for Cu-Mont K10 as catalyst,
as compared with the earlier work where longer reaction times
are generally required for the reaction to achieve good yields.8
The catalyst, recovered by filtration, was successfully reused
in the case of benzaldehyde without affecting the reactivity of
the process. In order to check for leaching of ruthenium
from the catalyst the filtrate was analyzed for metal content by
atomic absorption spectroscopy and no metal leaching was
observed.
Scheme 2
Table 4 shows the results of reaction of various thiols, acids
and alcohols with methyl diazoacetate in the presence of Cu-
and Rh-clay as catalysts. It can be seen from Table 4 that
thiols and acids react at a faster rate than dialcohols. While Cu-
clay catalyzes efficiently the insertion of methyl diazoacetate
into thiols and acids at 25 ЊC, insertion into OH of alcohols
with Cu-clay as catalyst did not proceed at all at 25 ЊC. How-
ever, Rh-clay has been found to be a good catalyst for O–H
insertions of alcohols at 60 ЊC.
The catalytic pathway for these insertion reactions with
methyl diazoacetate can be explained by initial formation of
metal-carbenoid species. The carbene first coordinated to the
heteroatom to produce an intermediate ylide, which further
rearranged to give the inserted product.
b. Synthesis of ꢁ-amino esters
With the advent of rhodium() acetate as a superior catalyst,
intramolecular metal carbenoid insertions into unactivated C–
H bonds have emerged as an effective strategy for C–C bond
formation. On the other hand, the study of metal-carbenoid
insertions into X–H (X = heteroatom) bonds has been rela-
tively limited; nonetheless, such reactions have led to methods
for pharmaceutically important compounds. The Rh-catalyzed
carbene-insertion reaction is used as a powerful methodology
for the synthesis of various antibiotics such as aza-β-lactams,9
Thienamycin,10 1-oxacephem,11 etc. Thus there is great impor-
tance in the development of a new methodology for NH-
insertion reactions. We found that Cu-clay is an excellent
heterogeneous catalyst for this transformation (Table 3).
Both aromatic and aliphatic amines underwent the insertion
reaction, affording good yields of the product. The reaction of
secondary amines has an interesting feature. The reaction of N-
methylaniline under the conditions described above furnished
N–H-inserted product in 61% yield. However, reaction of N-
ethylaniline with methyl diazoacetate furnished a mixture of
Conclusions
Metal-exchanged clays efficiently catalyze the insertion reaction
of methyl diazoacetate into the X–H bond of amines, thiols,
acids and alcohols. Reactivity of insertion into N–H of amines,
S–H of thiols, and O–H of acids is much higher than that of
O–H insertion of alcohols. A Cu-Clay catalyst can efficiently
promote the insertion reaction in the case of thiols and acids
but is not effective for O–H insertion. On the other hand,
3686
J. Chem. Soc., Perkin Trans. 1, 1999, 3685–3689

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Table 4 Reaction of methyl diazoacetate with acids, thiols and alcohols in the presence of M-exchanged clay catalysts
Entry
Substrate
Solvent
Catalyst
Temp. (T/ЊC)
t/h
Yield (%)a
1
2
3
4
5
6
7
8
9
Thiophenol
Thiophenol
Butanethiol
Ethyl 2-mercaptoacetate
Crotonic acid
Cinnamic acid
2-Phenylbutyric acid
Ethanol
Ethanol
Ethanol
Benzene
Cu-Clay
Cu-Clay
Cu-Clay
Cu-Clay
Cu-Clay
Cu-Clay
Cu-Clay
Cu-Clay
Cu-Clay
Rh-Clay
Rh-Clay
Rh-Clay
80
25
25
25
25
25
25
25
80
60
60
60
5
8
10
8
5
5
84
82
73
75
95
96
91
NR
18
63
62
67
Dichloromethane
Dichloromethane
Dichloromethane
Dichloromethane
Dichloromethane
Dichloromethane
Dichloromethane
Benzene
5
12
12
12
12
12
10
11
12
Butan-1-ol
Benzyl alcohol
a Isolated yield after chromatographic purification. NR = not recorded.
Table 5 Metal content and surface areas of various clays
Entry Catalyst
Surface area/m2 gϪ1 Metal content (wt%)
Rh-Clay is found to be effective for O–H insertion at 60 ЊC in
the presence of excess of alcohol without any solvent.
Experimental
1
2
3
CuII-Mont K10
238.9
RhIII-Mont K10 238.0
MnIII-Mont K10 255.0
0.39
0.39
0.45
All solvents are distilled before use. ‘Petroleum ether’ refers to
the fraction with boiling range 60–80 ЊC. Compounds are puri-
fied by flash chromatography over silica gel. IR spectra were
recorded on a Perkin-Elmer 137 E spectrometer. H and 13C
1
cm Ϫ1) 3300, 1730, 1695, 1590, 1450; H NMR (200 MHz;
CDCl3) δ 3.8 (s, 3H), 3.95 (s, 3H), 4.0 and 4.05 (2s, 2H), 6.90–7.3
(m, 4H); 13C NMR (50 MHz; CDCl3) δ 191.87, 167.65, 163.90,
132.11, 130.98, 130.55, 114.24, 113.79, 61.13, 55.48, 52.17.
Methyl 3-(3,4-dimethoxyphenyl)-3-oxopropionate. IR (CH-
1
NMR spectra were recorded on a Bruker 200 MHz instrument
using TMS as an internal standard. Mass spectra (MS) were
recorded on an automated Finnigan MAT 1020C mass spec-
trometer using an ionization energy of 70 eV. Microanalyses
were done on a Carlo EA1108 elemental analyzer.
Cl3; cmϪ1) 3320, 1730, 1695, 1600, 1510, 1260; H NMR (200
1
MHz; CDCl3) δ 3.75 (s, 3H), 3.85 (s, 3H), 3.90 and 3.95 (2s, 2H),
6.70–6.90 (m, 3H); 13C NMR (50 MHz; CDCl3) δ 191.63,
167.67, 153.87, 149.21, 129.29, 126.74, 123.53, 110.49, 61.43,
56.18, 55.98, 52.20.
Preparation of metal-exchanged clays
The metal-exchanged clays were prepared by stirring clay with
dilute solutions of CuCl2, RhCl3 and Mn(NO3)2, respectively.
For example, a mixture containing CuCl2 (0.3 g) and mont-
morillonite clay (25 g) in distilled water (600 mL) was stirred
vigorously at room temperature for 24 h. It was centrifuged and
the clay was washed repeatedly with distilled water until the
discarded filtrate was free from ClϪ ions. Finally, the clay was
dried at 110 ЊC for 12 h. The metal content of the clays was
determined by an electron-disperse X-ray microscope (EDX)
connected to a JEOL, scanning electron microscope. Sur-
face area was determined by the Brunaver–Emmette–Teller
(BET) method. The X-ray diffraction (XRD) and FT IR
spectra of these samples show that they are crystalline; how-
ever, no significant differences were observed between their
structures.
Methyl 3-(4-chlorophenyl)-3-oxopropionate. IR (CHCl3;
1
cmϪ1) 1740, 1710, 1590, 810; H NMR (200 MHz; CDCl3)
δ 3.90 (s, 3H), 3.80, 4.10 and 5.80 (3s, 2H), 6.80 (d, J 8.2 Hz,
2H), 7.20 (d, J 8.2 Hz, 2H).
Methyl 3-oxododecanoate. IR (CHCl3; cmϪ1) 1725, 1695,
1450; 1H NMR (200 MHz; CDCl3) δ 0.85–1.00 (m, 10H), 1.10–
1.30 (m, 9H), 3.50 (s, 2H), 3.70 (s, 3H).
Methyl 4-methyl-3-oxopentanoate. IR (CHCl3; cmϪ1) 1735,
1
1700, 1470; H NMR (200 MHz; CDCl3) δ 0.95 (d, J 7.7 Hz,
6H), 2.0 (m, 1H), 3.70 (s, 2H) 3.90 (s, 3H).
Reaction of methyl diazoacetate with amines
General procedure. A solution of aniline in dry benzene was
treated with 1.2 molar equivalents of methyl diazoacetate, and
the catalyst Cu-clay (10% by weight of the substrate) was intro-
duced. The mixture was refluxed and the progress of the reac-
tion was monitored by TLC. When the starting material almost
disappeared (3–4 h), the reaction mixture was cooled to room
temperature and the catalyst was filtered off. Evaporation of
the solvent and passage of the residue through a column of
SiO2 yielded the product in a pure form. Yields of products are
given in Table 3.
The metal content and the surface area of the clays are given
in Table 5.
Reaction of methyl diazoacetate with aldehydes
General procedure. Into a solution of the aldehyde in dry
benzene were introduced 1.1 equivalents of methyl diazoacetate
and Cu-clay catalyst (10% w/w). The mixture was refluxed until
the disappearance of the aldehyde as monitored by TLC and
until the cessation of nitrogen evolution (3–4 h). When the reac-
tion mixture had cooled to room temperature the catalyst was
filtered off, and washed twice with benzene. The combined ben-
zene extract was distilled and the residue was passed through a
column of silica gel eluting with 2% ethyl acetate in petroleum
ether. The yields of the products are given in Table 2.
Methyl N-phenylglycinate. IR (neat; cmϪ1) 3350, 1710,
1
1600, 1500, 1420, 1200, 1000, 750, 680, 500; H NMR (200
MHz; CDCl3) δ 3.80 (s, 3H), 3.95 (s, 2H), 4.25 (br s, 1H), 6.60
(d, J 8.3 Hz, 2H), 6.80 (t, J 8.3 Hz, 1H), 7.20 (t, J 7.3 Hz, 2H);
MS (m/z, % rel. intensity) 165 (Mϩ, 20), 106 (100), 93 (10), 77
(30), 65 (10), 59 (10), 51 (20).
Methyl N-(2-methylphenyl)glycinate. Bp 152 ЊC/15 mmHg
(bath temp.); IR (neat; cmϪ1) 3050, 2900, 1740, 1600, 1500,
1430, 1200; 1H NMR (200 MHz; CDCl3) δ 2.25 (s, 3H), 3.85 (s,
3H), 4.0 (s, 2H), 4.20 (br s, 1H), 6.55 (d, J 7.2 Hz, 1H), 6.75 (t,
J 8.1 Hz, 1H), 7.15 (t, J 8.1 Hz, 2H); MS (m/z, % rel. intensity)
Methyl 3-oxo-3-phenylpropionate. IR (CHCl3; cmϪ1) 1720,
1
1690, 1445; H NMR (200 MHz; CDCl3) δ 3.80 (s, 3H), 3.90,
4.00 and 5.90 (3, 2H), 7.30–7.50 (m, 5H); 13C NMR (50 MHz;
CDCl3) δ 192.25, 168.01, 133.90, 133.30, 129.00, 125.70, 86.90
(enolic), 61.01, 52.14.
Methyl 3-(4-methoxyphenyl)-3-oxopropionate. IR (CHCl3,
J. Chem. Soc., Perkin Trans. 1, 1999, 3685–3689
3687

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179 (Mϩ, 20), 120 (100), 106 (40), 91 (35), 86 (20), 84 (30), 77
(20), 65 (20), 59 (35), 51 (15) (Found: C, 67.24; H, 7.28; N, 7.76.
Calc. for C10H13NO2: C, 67.02; H, 7.31; N, 7.82%).
3H), 3.8 (q, J 7.0 Hz, 2H) (Found: C, 43.41; H, 6.22; S, 16.58.
Calc. for C7H12O4S: C, 43.74; H, 6.29; S, 16.67%).
Methyl 3-oxohex-4-enoate. IR (CHCl3; cmϪ1) 2990, 1710,
1440, 1270, 1140; 1H NMR (200 MHz; CDCl3) δ 2.13 (d, J 0.4
Hz, 3H) 3.8 (s, 3H), 4.75 (s, 2H), 5.95 (d, J 14.6 Hz, 1H), 7.1 (m,
1H) (Found: C, 53.19; H, 6.43. Calc. for C7H10O4: C, 53.16; H,
6.37%).
Methyl N-(1-naphthyl)glycinate. Mp 72–74 ЊC; IR (neat;
1
cmϪ1) 3100, 2920, 1720, 1240; H NMR (200 MHz; CDCl3)
δ 3.80 (s, 3H), 4.0 (s, 2H), 6.40 (br s, 1H), 7.23 (br s, 3H), 7.45
(m, 2H), 7.80 (m, 2H) (Found: C, 72.49; H, 6.06; N, 6.56. Calc.
for C13H13NO2: C, 72.54; H, 6.09; N, 6.51%).
Methyl N-hexylglycinate. Bp 75 ЊC/15 mmHg (bath temp.);
Methyl 3-oxo-5-phenylpent-4-enoate. IR (CHCl3; cm Ϫ1) 2990,
1700, 1610, 1420, 1295, 1150; 1H NMR (200 MHz; CDCl3) δ 3.8
(s, 3H), 4.8 (s, 2H), 6.55 (d, J 16.2 Hz, 1H), 7.40 (m, 3H), 7.55
(m, 2H), 7.8 (d, J 16.2 Hz, 1H); MS (m/z, % rel. intensity) 220
(Mϩ, 2), 189 (3), 131 (5), 113 (100), 91 (82), 77 (13). (Found: C,
65.25; H, 5.46. Calc. for C12H12O4: C, 65.45; H, 5.49%).
1
IR (neat; cmϪ1) 3000, 2850, 1730, 1440; H NMR (200 MHz;
CDCl3) δ 0.90–1.35 (m, 5H), 1.50–1.80 (m, 6H), 2.40 (m, 1H),
3.40 (s, 2H), 3.65 (s, 3H); MS (m/z, % rel. intensity) 171 (Mϩ,
10), 128 (70), 112 (100), 83 (15), 68 (65), 56 (75).
Methyl N-methyl-N-phenylglycinate. Bp 152 ЊC/7 mmHg
1
(bath temp.); IR (neat; cmϪ1) 1720, 1590, 1250; H NMR (200
MHz; CDCl3) 3.0 (s, 3H), 3.65 (s, 3H), 4.0 (s, 2H), 6.6 (m, 3H),
6.9 (m, 2H); MS (m/z, % rel. intensity) 179 (M ϩ, 30), 128 (40),
120 (100), 106 (40), 91 (20), 77 (40), 64 (10) (Found: C, 66.99; H,
7.40; N, 7.79. Calc. for C10H13NO2: C, 67.02; H, 7.31; N, 7.82%).
Methyl N-ethyl-N-phenylglycinate. IR (CHCl3; cmϪ1) 1710,
Methyl 3-oxo-4-phenylhexanoate. IR (neat; cmϪ1) 2920, 1730,
1480, 1370, 1140; H NMR (200 MHz; CDCl3) δ 0.95 (t, J 7.3
1
Hz, 3H), 1.85 (m, 1H), 2.2 (m, 1H), 3.6 (t, J 7.3 Hz, 1H), 3.7 (s,
3H), 4.6 (d, J 15.8 Hz, 2H), 7.3 (m, 5H); 13C NMR (75 MHz;
CDCl3) δ 11.62, 26.42, 51.62, 52.70, 60.39, 126.94, 127.73,
128.20, 138.24, 167.74, 172.96; MS (m/z, % rel. intensity) 236
(Mϩ, 6), 205 (2), 146 (29), 119 (56), 104 (5), 91 (100), 85 (6),
77 (9), 65 (5), 57 (16) (Found: C, 66.13; H, 6.79. Calc. for
C13H16O4: C, 66.08; H, 6.82%).
1
1600, 1250; H NMR (200 MHz; CDCl3) δ 1.20 (t, J 8.0 Hz,
3H), 3.37 (q, J 4.1 Hz, 2H), 3.60 (s, 3H), 4.00 (s, 2H), 6.52 (m,
3H), 7.0 (m, 2H); MS (m/z, % rel. intensity) 193 (Mϩ, 25), 178
(5), 163 (10), 134 (100), 120 (5), 105 (30), 91 (5), 77 (10) (Found:
C, 67.47; H, 7.80; N, 7.29. Calc. for C11H15NO2: C, 68.37; H,
7.82; N, 7.25%).
Methyl ethoxyacetate. IR (neat; cmϪ1) 2980, 1720, 1220,
Methyl (phenylimino)acetate. IR (CHCl3; cmϪ1) 2875, 1615,
1
1
1140, 1030; H NMR (200 MHz; CDCl3) δ 1.05 (t, J 5.4 Hz,
1560, 1480, 1210; H NMR (200 MHz; CDCl3) δ 3.85 (s, 3H),
3H), 3.8 (s, 3H), 4.05 (q, J 5.4 Hz, 2H), 4.65 (s, 2H).
6.7 (m, 3H), 7.1 (m, 2H), 8.15 (s, 1H).
Methyl N-butyl-N-phenylglycinate. Bp 176 ЊC/3 mmHg (bath
temp.); IR (neat; cmϪ1) 1710, 1600; 1H NMR (200 MHz;
CDCl3) δ 1.00 (t, J 7.4 Hz, 3H), 1.40 (q, J 4.1 Hz, 2H), 1.65 (m,
2H), 3.40 (t, J 6.0 Hz, 2H), 3.60 (s, 3H), 3.85 (s), 3.90 (s) and
4.20 (s) (together 2H), 6.70 (t, J 7.1 Hz, 3H), 7.25 (t, J 8.1 Hz,
2H); MS (m/z, % rel. intensity) 221 (Mϩ, 50), 193 (10), 178 (50),
163 (18), 162 (100), 150 (20), 134 (10), 120 (90), 106 (45), 91
(10), 77 (15) (Found: C, 70.46; H, 8.60; N, 6.40. Calc. for
C13H19NO2: C, 70.56; H, 8.65; N, 6.33%).
Methyl butoxyacetate. IR (neat; cmϪ1) 2980, 1720, 1395,
1240, 1130, 1005; H NMR (200 MHz; CDCl3) δ 0.9 (t, J 5.4
Hz, 3H), 1.45 (m, 2H), 1.6 (m, 2H), 3.85 (s, 3H), 4.0 (t, J 6 Hz,
2H), 4.65 (s, 2H).
1
Methyl benzyloxyacetate. IR (neat; cmϪ1) 3000, 1720, 1595,
1
1240, 1110, 1040, 980; H NMR (200 MHz; CDCl3) δ 3.8 (s,
3H) 4.65 (s, 4H), 7.35 (m, 5H).
General procedure for reaction of methyl diazoacetate with
thiols, acids and alcohols
Acknowledgements
P. P. thanks CSIR (New Delhi) for a research fellowship.
J. M. M. is thankful to the Director, NCL, for permission to
carry out work at NCL.
To a mixture of thiophenol (0.5 g, 4.5 mmol) and 25 mg (5 wt%)
of Cu-Clay in 5 mL of dichloromethane was added dropwise
methyl diazoacetate (0.86 g, 6.8 mmol) at room temperature
and the mixture was stirred until the reaction was complete
(TLC). The catalyst was filtered off and the dichloromethane
was evaporated. The crude product was chromatographed
with ‘petroleum ether’ as eluent to give 0.7 g of methyl 2-
(phenylthio)acetate as colorless oil. In the case of alcohols,
methyl diazoacetate (0.86 g, 6.8 mmol) and 25 mg of Cu-clay
were heated at 60 ЊC. The reaction mixture was filtered, excess
alcohol removed and the crude product was chromatographed
with ‘petroleum ether’ as eluent. Yields of products are given in
Table 4.
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1
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