One-pot route to new α,α-difluoroamides and α-ketoamides

Article abstract of DOI:10.1021/jo034487g

New α,α-difluoroamides (4a-d, 6a-d) and α-ketoamides (5a-d, 7a-d) result from one-pot reactions of α-ketoacids, RCOCO₂H (R = C₆H₅, CH₃, CH₃CH₂, thienyl) (1a-d) with bis(2-methoxyethyl)aminosulfur trifluoride [(CH₃-OCH₂CH₂)₂NSF₃] (2) (Deoxofluor) or diethylaminosulfur trifluoride [(CH₃CH₂)₂NSF₃)] (3) (DAST). Product yields depend on reaction times and the ratio of reagents used. Longer reaction times (～36 h) with a 1:2 ratio of α-ketoacids and 2 or 3 gave major yields of the α,α-difluoroamides, and shorter reaction times (～1 h) produced α,α-ketoamides as the major products. Reactants in a 1:1 ratio resulted in α-ketoamides only.

Full text of DOI:10.1021/jo034487g

utilized.16 N-Terminally blocked aminoaldehydes with an
isonitrile and a carboxylic acid give amino-R-acyloxy
carboxamides, which can be deprotected to form, e.g.,
peptidyl R-ketoamides.17 The syntheses of R,R-difluoro-
amides have not been reported via a direct fluorination
route but rather by utilizing, e.g., R,R-difluoro-â-keto-
esters with amines.18
On e-P ot Rou te to New r,r-Diflu or oa m id es
a n d r-Ketoa m id es
Rajendra P. Singh and J ean’ne M. Shreeve*
Department of Chemistry, University of Idaho,
Moscow, Idaho 83844-2343
We now report that R-ketoamides as well as R,R-
difluoroamides are readily obtained in one-pot reactions
of R-ketoacids with the nucleophilic fluorinating reagents,
Deoxofluor and DAST. While earlier we demonstrated the
direct fluorination of cyclic amides,3 neither reagent could
be reacted successfully with acyclic R-ketoamides. In an
effort to synthesize R-ketoacid fluorides and R,R-difluo-
roacid fluorides by using Deoxofluor and DAST as
fluoride ion sources, we found that, in contrast with the
reactions of these reagents with monocarboxylic acids,
R-ketoacids did not yield isolable acid fluorides but rather
R,R-difluoroamides. We have demonstrated the applica-
tion of Deoxofluor and DAST with R-ketoacids to generate
R,R-difluoroamides or R-ketoamides as the major product
as a function of reaction time and reaction stoichiometry
used.
jshreeve@uidaho.edu
Received April 16, 2003
Abstr a ct: New R,R-difluoroamides (4a -d , 6a -d ) and R-ke-
toamides (5a -d , 7a -d ) result from one-pot reactions of
R-ketoacids, RCOCO2H (R ) C6H5, CH3, CH3CH2, thienyl)
(1a-d) with bis(2-methoxyethyl)aminosulfur trifluoride [(CH3-
OCH2CH2)2NSF3] (2) (Deoxofluor) or diethylaminosulfur
trifluoride [(CH3CH2)2NSF3)] (3) (DAST). Product yields
depend on reaction times and the ratio of reagents used.
Longer reaction times (∼36 h) with a 1:2 ratio of R-ketoacids
and 2 or 3 gave major yields of the R,R-difluoroamides, and
shorter reaction times (∼l h) produced R-ketoamides as the
major products. Reactants in a 1:1 ratio resulted in R-ke-
toamides only.
Initially, benzoylformic acid (1a ) was reacted with
Deoxofluor (2) in 1:2 molar ratio at room temperature in
dichloromethane. After 1 h, the reaction was quenched
with aqueous sodium bicarbonate solution. The dichlo-
romethane layer was analyzed by GCMS, which showed
the complete conversion of benzoylformic acid into the
corresponding mixture of R,R-difluoroamide (4a ) and
R-ketoamide (5a ) in a ratio of 14:86. When the reaction
was carried out using DAST (3) under similar conditions,
the R,R-difluoroamide (6a ) and the R-ketoamide (7a ) were
obtained in a ratio of 25:75. Interestingly, prolonging the
reaction time increases the yield of the R,R-difluoroamide.
For example, when 1a was reacted either with 2 or 3
under similar conditions for 36 h, the yields of the R,R-
difluoroamides, 4a and 6a , were increased to ∼90%. It
has also been found that the reaction of 1a either with 2
or 3 in a 1:1 ratio in methylene chloride for 1 h or even
after 36 h gave the respective R-ketoamide 5a or 7a in
>92% yields (Table 1). Under these conditions, only very
small amounts of the R,R-difluoroamide were obtained.
Reaction of pyruvic acid (1b) with 2 or 3 (1:2 ratio) also
produced a mixture of R,R-difluoroamides (4b or 6b) and
R-ketoamides (5b or 7b), and their yields were variable
with time. Compounds 1c and 1d were similarly con-
verted into the corresponding R,R-difluoroamides (4c, 4d ,
6c, 6d ) and R-ketoamides (5c, 5d , 7c, 7d ) by reacting
either with 2 or 3 (Scheme 1, Table 1).
Direct fluorination of cyclic amides with Deoxofluor
[bis(2-methoxyethyl)aminosulfur trifluoride]1 or DAST
[diethylaminosulfur trifluoride]2 occurs in good yields.
However, regardless of the conditions employed, a similar
methodology was not successful with acyclic R-keto-
amides. These two reagents are also utilized frequently
to generate acid fluorides from simple aliphatic or
aromatic acids.3-5 R-Ketoamides and R,R-difluoroamides
are important constituents of many biologically signifi-
cant materials.6-8 Syntheses of R-ketoamides are often
accomplished in a multistep process involving the dicar-
bonylation of aryl, heteroaryl, and vinyl halides in the
presence of carbon monoxide and a catalytic amount of
palladium compound and a secondary amine,9-15 or the
ruthenium-catalyzed oxidation of alkynylamines can be
(1) Singh, R. P.; Majumder, U.; Shreeve, J . M. J . Org. Chem. 2001,
66, 6263-6267.
(2) Middleton, W. J .; Bingham, E. M. J . Org. Chem. 1980, 45, 2883-
2887.
(3) Singh, R. P.; Shreeve, J . M. Synthesis 2002, 2561-2579 and
references therein.
(4) Hudlicky´, M. Org. React. 1988, 35, 513-637.
(5) Lal, G. S.; Pez, G. P.; Pesaresi, R. J .; Prozonic, F. M.; Cheng, H.
J . Org. Chem. 1999, 64, 7048-7054.
(6) Lyons, W. E.; Dteiner, J . P.; Snyder, S. H.; Dawson, T. M. J .
Neurosci. 1995, 15, 2985-2988.
(7) Dubowchik, G. M.; Vrudhula, V. M.; Dasgupta, B.; Ditta, J .;
Chen, T.; Sheriff, S.; Sipman, K., Witmaer, M.; Tredup, J .; Vyas, G.
M.; Verdoon, T. A.; Bollini, S.; Vinitsky, A. Org. Lett. 2001, 3, 3987-
3990.
(8) Hamilton, G. S.; Steiner, J . P. J . Med. Chem. 1998, 41, 5119s
5123. Gold, B. G. Mol. Neurobiol. 1997, 73, 285-289.
(9) Uosumi, Y. J P 2003002869, J anuary 8, 2003; Chem. Abstr. 2003,
138, 73088.
All the compounds are found to be stable in air and
water. Since R,R-difluoroamides are less polar than
R-ketoamides, these two products were easily separated
(10) Ozawa, F.; Soyama, H.; Yanahihara, H.; Aoyama, I.;.Takino,
H.; Izawa, K.; Yamamoto, T.; Yamamoto, A. J . Am. Chem. Soc. 1985,
107, 3235-3245.
(14) Ozawa, F.; Soyama, H.; Yamamoto, T.; Yamamoto, A. Tetra-
hedron Lett. 1982, 23, 3383-3386.
(15) Kobayashi, T.; Tanaka, M. J . Organomet. Chem. 1982, 233,
C64-C66.
(11) Kobayashi, T.; Tanaka, M. J . Organomet. Chem. 1982, 233,
C64-C66.
(16) Muller, P.; Godoy, G. Tetrahedron Lett. 1982, 23, 3661-3664.
(17) Semple, J . E.; Levy, Odile, E. WO 2000035868, J une 22, 2000;
Chem. Abstr. 2000, 133, 59100.
(18) Watanabe, S.; Fujita, T.; Sakamoto, M.; Takeda, H.; Kitazume,
T.; Yamazaki, T. J . Fluorine Chem. 1997, 82, 1-7.
(12) Mutin, R.; Lucas, C.; Thivolle-Cast, J .; Dufaud, V.; Dany, F.;
Basset, J . M. J . Chem. Soc., Chem. Commun. 1998, 896-897.
(13) Sakamoto, M.; Shimizu, I.; Yamamoto, A. Chem. Lett. 1995,
1101.
10.1021/jo034487g CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/27/2003
J . Org. Chem. 2003, 68, 6063-6065
6063

TABLE 1. Rea ction of Deoxoflu or (2) a n d DAST (3) w ith
SCHEME 2
r-Ketoa cid a
volatile product via 19F NMR spectral analysis. No
evidence is found for the intermediate formation of the
possible acid fluoride (RCOCOF) intermediate from the
R-ketoacid on the basis of 19F NMR studies during the
course of the reaction. The intermediacy of A and B has
also been supported by 19F NMR spectra. Since reactions
of monocarboxylic acids do not yield amides with 2 or 3,
we are convinced that in the case of R-ketoacids, the
R-carbonyl in A and the CF2 group in B cause the
adjacent carbonyl to be very electron deficient and subject
to facile attack by the NR′2 group to give the amides as
the final products.
In summary, the present report describes a straight-
forward one-pot synthetic route to R,R-difluoroamides and
R-ketoamides in good yields. Depending on the product
required, it is possible to synthesize either amide in good
yield by terminating the reaction after different time
intervals or by utilizing suitable stoichiometric ratios.
a
All reactions were carried out at 25 °C with 5 mmol of R-keto
acid and 10 mmol of Deoxofluor or DAST in 15 mL of methylene
chloride. Relative % yield was determined by GC. c Reaction was
b
carried out with a 1:1 molar ratio of 1a and 2.
SCHEME 1
Exp er im en ta l Section
Caution: Deoxofluor and DAST react rapidly and exothermi-
cally with water, liberating HF. Reactions with these compounds
should be carried out at <80 °C.
In a typical experiment, R-ketoacid (1a ) (5 mmol) was dis-
solved in dichloromethane (15 mL), and Deoxofluor (2) or DAST
(3) (10 mmol) in dichloromethane was added dropwise at room
temperature. The reaction mixture was stirred at 25 °C for 36
h, and then the reaction was quenched by the slow addition of
aqueous NaHCO3 solution until effervescence was complete. The
dichloromethane layer was separated, dried over anhydrous
MgSO4, and filtered. Removal of solvent gave a mixture of 4a /
5a (90:10 based on GC) or 6a /7a (92:8 based on GC). Products
were separated by silica gel chromatography using an ethyl
acetate and hexane mixture (2:1).
by silica gel chromatography using ethyl acetate and
hexane mixtures (2:1). The new compounds were char-
acterized by IR, NMR (1H, 19F, 13C), and MS spectral and
elemental analyses. Known compounds were character-
ized by comparing their spectroscopic data with that
reported in the literature.
Amide formation was not observed when benzoic acid
or monoaliphatic acids were reacted with 2 and 3.1-3 This
suggests that the R-keto group in the substrate plays a
major role. A possible reaction mechanism is proposed
in Scheme 2. It is known that acids react similarly to
alcohols with Deoxofluor or DAST. The first step is the
formation of intermediate A with the loss of HF. Since
R-keto esters such as A react selectively with Deoxofluor
or DAST only at the R-carbonyl group, we believe the
fluorination proceeds in the presence of an additional
equivalent of 2 or 3 to give intermediate B. The inter-
mediates A and B are hydrolytically unstable, and, on
hydrolysis, amides are formed as the final products with
the release of SOF2 (Scheme 2) that was identified as a
Com p ou n d 4a : isolated yield ) 84%; viscous liquid; IR (Nujol
mull) 2928, 1668, 1448, 1365, 1257, 1114, 1082, 1019, 1082, 1019,
974, 920, 800, 775, 736, 700, 646 cm-1 19F NMR (CDCl3) δ
;
-94.44 (s, 2F); 1H NMR (CDCl3) δ 3.19 (s, 3H), 3.24 (s, 3H), 3.31
(t, 2H, J ) 5.5 Hz), 3.43 (t, 2H, J ) 5.5 Hz), 3.51 (t, 2H, J ) 5.2
Hz), 3.63 (t, 2H, J ) 5.2 Hz), 7.30-7.55 (m, 5H); 13C NMR
(CDCl3) δ 48.89, 49.21 (t, J ) 3.6 Hz), 59.6, 59.7, 70.80, 72.86,
116.4 (t, J C-F ) 248.7 Hz), 126.1 (t, J ) 5.6 Hz), 129.5, 131.68
(t, J ) 1.6 Hz), 134.5 (t, J ) 24.8 Hz), 164.5 (t, J ) 29.7 Hz); MS
(EI) m/z (species, rel int) 286 (M+ - H, 1), 2 72 (M+ - CH3, 1),
255 [M+ - (OCH3 + H), 24), 210 (M+ - C6H5, 42), 127 (C6H5-
CF2+, 100), 77 (C6H5+, 23), 59 (CH3OCH2CH2+, 33). Anal. Calcd
for C14H19F2NO3: C, 58.53; H, 6.67. Found: C, 58.00; H, 6.53.
Com p ou n d 4b: viscous liquid; IR (Nujol mull) 2930, 1664,
1455, 1388, 1255, 1177, 1117, 1019, 927, 758 cm-1 19F NMR
;
(CDCl3) δ -92.66 (q, 2F, J ) 20 Hz); 1H NMR (CDCl3) δ 1.77 (t,
3H, J ) 20 Hz), 3.27 (s, 3H), 3.28 (s, 3H), 3.48 (overlapped t,
4H, J ) 5.5 Hz), 3.59 (t, 2H, J ) 5.5 Hz), 3.72 (t, 2H, J ) 5.2
Hz); 13C NMR (CDCl3) δ 32.1 (t, J ) 25.5 Hz), 47.9, 48.1, 58.9,
70.1, 72.1, 119.4 (t, J C-F ) 250.2 Hz), 163.8 (t, J ) 30.5 Hz);
MS (EI) m/z (species, rel int) 225 (M+ , 1), 210 (M+ - CH3, 1),
193 [M+ - (OCH3 + H), 22), 180 (M+ - CH2OCH3, 77), 150
6064 J . Org. Chem., Vol. 68, No. 15, 2003

[M+ - (CH2OCH3 + 2CH3), 69], 65 (CH3CF2+, 37), 58, (CH3OCH2-
CH+, 100). Anal. Calcd for C9H17F2NO3: C, 47.99; H, 7.61.
Found: C, 48.12; H, 7.56.
2H, J ) 5.4 Hz), 7.28 (dd, 1H, J ) 5.0, Hz, 2.0 Hz), 7.98 (d, 1H,
J ) 5 Hz), 8. 56 (d, 1H, J ) 5.0 Hz); MS (EI) m/z (species, rel
+
int) 271 (M+, 12), 160 (M+ - C4H3SCO, 41), 111 (C4H3SCO
,
Com p ou n d 4c: viscous liquid; IR (Nujol mull) 2892, 1665,
100), 83 (C4H3S+, 6), 59 (CH3OCH2CH2+, 42). Anal. Calcd for
1452, 1363, 1273, 1182, 1116, 1012, 974, 756 cm-1
;
19F NMR
C
12H17NO4S: C, 53.12; H, 6.32. Found: C, 53.22 H, 6.24.
1
(CDCl3) δ -93.50 (t, 2F, J ) 18.5 Hz); H NMR (CDCl3) δ 0.97
(t, 3H, J ) 7.5 Hz), 2.11 (tq, 2H, J ) 18.5 Hz, J ) 7.5 Hz), 3.25
(s, 3H), 3.26 (s, 3H), 3.47 (overlapped triplet, 4H), 3.57 (t, 2H,
J ) 5.5 Hz), 3.69 (t, 2H, J ) 5.5 Hz); 13C NMR (CDCl3) δ 6.2,
28.6 (t, J ) 24.5 Hz), 48.3, 48.5, 59.2, 70.5, 72.5, 120.2 (t,
J C-F ) 254.0 Hz), 164.2; MS (EI) m/z (species, rel int) 239 (M+,
Com p ou n d 6a : isolated yield ) 85% (36 h reaction time);
viscous liquid; IR (Nujol mull) 2929, 1662, 14451, 1365, 1115,
1081, 1084, 1020, 971, 920, 801, 775, 736, 645 cm-1 19F NMR
;
(CDCl3) δ -95.23 (s, 2F); 1H NMR (CDCl3) δ 0.95 (t, 3H, J ) 7.0
Hz), 1.09 (t, 3H, J ) 7.0 Hz), 3.16 (q, 3H, J ) 7.0), 3.49 (q, 2H.
J ) 7.0 Hz), 7.30-7.50. (m, 5H); 13C NMR (CDCl3) δ 13.0, 14.6,
42.2, 42.8 (t, J ) 4 Hz), 116.3 (t, J C-F ) 248.6 Hz), 126.0 (t, J )
5.6 Hz), 129.5, 131.5 (t, J ) 1.8 Hz), 134.6 (t, J ) 24.8 hz), 163.6
(t, J ) 29.7 Hz); MS (EI) m/z (species, rel int) 227 (M+, 1), 2 12
(M+ - CH3, 1), 198 [M+ - CH2CH3, 1), 127 (PhCF2+, 37), 100
[CON(CH2CH3)2+, 100], 72 [N(CH2CH3)2+, 59]. Anal. Calcd for
1), 224 (M+ - CH3, 1), 207 [M+ - (OCH3 + H), 14), 194 (M+
-
CH2OCH3, 33), 164 [M+ - (CH2OCH3 + 2CH3), 100], 79 (CH3-
CF2+, 37), 59 (CH3OCH2CH2+, 58), 58 (CH3OCH2CH+, 46). Anal.
Calcd for C10H19F2NO3: C, 50.20; H, 8.00. Found: C, 50.26;
H, 7.92.
Com p ou n d 4d : viscous liquid; IR (Nujol mull) 2930, 1662,
C
12H15F2NO: C, 63.42; H, 6.65. Found: C, 64.00; H, 6.53.
1441, 1372, 1261, 1110, 1080, 1015, 972, 918, 801, cm-1 19F
;
Com p ou n d 6b: IR (Nujol mull) 2935, 1660, 1462, 1380, 1245,
NMR (CDCl3) δ -94.05 (s, 2F); 1H NMR (CDCl3) δ 3.18 (s, 3H),
3.26 (s, 3H), 3.28 (t, 2H, J ) 5.5 Hz), 3.45 (t, 2H, J ) 5.5 Hz),
3.50 (t, 2H, J ) 5.2 Hz), 3.65 (t, 2H, J ) 5.2 Hz), 7.28 (dd, 1H,
J ) 5.02, Hz, 2.0 Hz), 7.94 (d, 1H, J ) 5 Hz), 8.52 (d, 1H, J )
5.0 Hz); 13C NMR (CDCl3) δ 48.7, 49.1, 59.9, 59.2, 70.5, 72.5,
116.5 (t, J C-F ) 248.5 Hz), 127.1, 128.8, 131.0 (t, J ) 28.5 Hz),
1170, 1035, 930, 752, 642 cm-1 19F NMR (CDCl3) δ -92.93 (q,
;
2F, J ) 20 Hz); 1H NMR (CDCl3) δ 0.94 (t, 3H, J ) 7.0 Hz), 1.08
(t, 3H, J ) 7.0 Hz), 1.75 (t, 3H, J ) 20 Hz), 3.15 (q, 2H, J ) 7.0),
3.49 (q, 2H. J ) 7.0 Hz); MS (EI) m/z (species, rel int) 165 (M+,
52), 150 (M+ - CH3, 32), 100 (M+ - CONEt2, 91), 72 (NEt2
,
+
100), 65 (CH3CF2, 51). Anal. Calcd for C7H13F2NO: C, 50.90; H,
7.93. Found: C, 50.83; H, 7.85.
164.4 (t, J ) 29.5 Hz); MS (EI) m/z (species, rel int) 293 (M+
,
-
1), 278 (M+ - CH3, 1), 261 [M+ - (OCH3 + H), 7], 216 [M+
Com p ou n d 6c: viscous liquid; IR (Nujol mull) 2890, 1670,
(2OCH3 + H), 12], 160 (C4H2SCF2+, 29), 133 (C4H3SCF2+, 100),
59 (CH3OCH2CH2+, 20), 58 (CH3OCH2CH+, 7). Anal. Calcd for
C12H17F2NO3S: C, 49.14; H, 5.84. Found: C, 49.14; H, 5.80.
Com p ou n d 5a . Yield from a run where 1a and 3 were used
in a 1:1 ratio and the reaction was stopped after 1 h: 87%;
viscous liquid; IR (Nujol mull) 2962, 1678, 1639, 1446, 1446,
1455, 1363, 1275, 1179, 1112, 1015, 978, 745 cm-1
;
19F NMR
1
(CDCl3) δ -93.25 (t, 2F, J ) 18.6 Hz); H NMR (CDCl3) δ 0.96
(t, 3H, J ) 7.0 Hz), 0.97 (t, 3H, J ) 7.5 Hz), 1.08 (t, 3H, J ) 7.0
Hz), 2.11 (tq, 2H, J ) 18.5 Hz, J ) 7.5 Hz), 3.15 (q, 2H, J )
7.0), 3.50 (q, 2H, J ) 7.0 Hz); MS (EI) m/z (species, rel int) 179
(M+, 28), 164 (M+ - CH3, 15), 100 (M+ - CONEt2, 91), 79 (CH3-
CH2CF2+, 20), 72 (NEt2+, 72). Anal. Calcd for C8H15F2NO: C,
53.60; H, 8.44. Found: C, 53.42; H, 8.46.
1
1366, 1260, 1179, 1114, 1015, 969, 865, 798, 772, 687 cm-1; H
NMR (CDCl3) δ 3.07 (s, 3H), 3.34 (s, 3H), 3.38 (t, 2H, J ) 5.6
Hz), 3.48 (t, 2H, J ) 5.6 Hz), 3.60 (t, 2H, J ) 5.2 Hz), 3.72 (t,
2H, J ) 5.4 Hz), 7.20-7.90 (m, 5H); 13C NMR (CDCl3) δ 45.7,
48.7, 59.0, 59.3, 70.9, 71, 129.0, 130.3, 134.6, 168.1, 191; MS (EI)
m/z (species, rel int) 265 (M+, 48), 160 (M+ - C6H5CO, 97), 105
(C6H5CO+, 100), 77 (C6H5+, 60), 59 (CH3OCH2CH2+, 68). Anal.
Calcd for C14H19NO4: C, 63.38; H, 7.22. Found: C, 63.67; H,
6.97.
Com p ou n d 6d : viscous liquid; IR (Nujol mull) 2935, 1666,
1455, 1361, 1112, 1087, 1022, 972, 918, 800, 771, 732 cm-1
;
19F
1
NMR (CDCl3) δ -95.82 (s, 2F); H NMR (CDCl3) δ 0.95 (t, 3H,
J ) 7.0 Hz), 1.08 (t, 3H, J ) 7.0 Hz), 3.16 (q, 3H, J ) 7.0), 3.47
(q, 2H. J ) 7.0 Hz), 7.27 (dd, 1H, J ) 5.0, Hz, 2.1 Hz), 7.97 (d,
1H, J ) 5 Hz), 8.58 (d, 1H, J ) 5.0 Hz); MS (EI) m/z (species,
rel int) 233 (M+, 2), 133 (C4H3SCF2+, 31), 100 [CON(CH2CH3)2
,
+
Com p ou n d 5b: viscous liquid; IR (Nujol mull) 2960, 1665,
100], 72 [N(CH2CH3)2+, 73]. Anal. Calcd for C10H13F2NOS: C,
51.49; H, 5.62. Found: C, 51.55; H, 5.60.
1448, 1370, 1255, 1170, 1123, 1021, 928, 762 cm-1 1H NMR
;
(CDCl3) δ 1.78 (s, 3H), 3.22 (s, 3H), 3.26(s, 3H), 3.42 (overlapped
t, 4H, J ) 5.5 Hz), 3.60 (t, 2H, J ) 5.5 Hz), 3.71 (t, 2H, J ) 5.2
Hz); MS (EI) m/z (species, rel int) 203 (M+ , 19), 160 (M+ - CH3-
CO, 100), 133 [N(CH2CH2OCH3)2)]+, 4), 59 (CH3OCH2CH2+, 78).
Anal. Calcd for C9H17NO4S: C, 53.19; H, 8.43. Found: C, 53.02;
H, 8.30.
Com p ou n d 5c: viscous liquid; IR (Nujol mull) 2935, 1639,
1449, 1363, 1207, 1195, 1119, 1047, 972, 808; 1H NMR (CDCl3)
δ 1.00 (t, 3H, J ) 7.2 Hz), 2.70 (q, 2H, J ) 7.2 Hz), 3.19 (s, 3H),
3.24 (s, 3H), 3.33 (t, 2H, J ) 5.2 Hz), 3.47 (overlapped triplet,
4H), 3.53 (t, 2H, J ) 5.5 Hz); 13C NMR (CDCl3) 6.8, 32.9, 45.7,
48.3, 58.7, 58.9, 70.1, 70.7, 168.2, 201.6; MS (EI) m/z (species,
rel int) 217 (M+ , 7), 160 (M+ - CH3CH2CO, 100), 59 (CH3OCH2-
CH2+, 91), 57 (CH3CH2CO+, 46). Anal. Calcd for C10H19NO4: C,
55.28; H, 8.81. Found: C, 55.30; H, 8.76.
Com p ou n d 7a . Isolated yield when the reaction was stopped
after 1 h using 1a and 3 in a 1:2 ratio: 74%. This product was
characterized by comparison with the spectroscopic data re-
ported.10
Com p ou n d 7d : viscous liquid; IR (Nujol mull) 2938, 1671,
1458, 1358, 1108, 1076, 1012, 968, 913, 812, 771 cm-1; 1H NMR
(CDCl3) δ 0.95 (t, 3H, J ) 7.0 Hz), 1.08 (t, 3H, J ) 7.0 Hz), 3.16
(q, 3H, J ) 7.0), 3.47 (q, 2H. J ) 7.0 Hz), 7.30 (dd, 1H, J ) 5.0,
Hz, 2.0 Hz), 7.96 (d, 1H, J ) 5 Hz), 8.55 (d, 1H, J ) 5.0 Hz); MS
(EI) m/z (species, rel int) 211 (M+, 3), 111 (C4H3SCO+, 37), 100
[CON(CH2CH3)2+, 83], 72 [N(CH2CH3)2+, 100]. Anal. Calcd for
C
10H13NO2S: C, 56.85; H, 5.62. Found: C, 56.76; H, 5.58.
Ack n ow led gm en t. We are grateful to Drs. G. Knerr
and A. Blumenfeld for measuring MS and NMR spectra,
respectively.
Com p ou n d 5d : low-melting solid; IR (Nujol mull) 2965, 1672,
1642, 1438, 1362, 1271, 1180, 1115, 1012, 958, 864, 791 cm-1
;
1H NMR (CDCl3) δ 3.07 (s, 3H), 3.34 (s, 3H), 3.38 (t, 2H, J ) 5.6
Hz), 3.48 (t, 2H, J ) 5.6 Hz), 3.60 (t, 2H, J ) 5.2 Hz), 3.72 (t,
J O034487G
J . Org. Chem, Vol. 68, No. 15, 2003 6065