Nitroketene acetal chemistry. 3. Facile synthesis of nitroacetic acid triarylmethyl ortho esters from 1,1-Di(methylsulfanyl)-2-nitroethylene

Article abstract of DOI:10.1021/jo050308e

The reaction of 1,-di(methylsulfanyl)-2-nitroethylene, benzyl alcohols, and sodium hydride furnishes crystalline triarylmethyl ortho esters of nitroacetic acid.

Full text of DOI:10.1021/jo050308e

SCHEME 1a
Nitroketene Acetal Chemistry. 3. Facile
Synthesis of Nitroacetic Acid
Triarylmethyl Ortho Esters from
1,1-Di(methylsulfanyl)-2-nitroethylene
H. Surya Prakash Rao* and S. Sivakumar
Department of Chemistry, Pondicherry University,
Pondicherry 605 014, India
a Reagents and conditions: (i) NaH, dry THF, rt, 6-12 h; (ii)
CH3COOH.
hspr@yahoo.com
Received February 18, 2005
sweetener, polymer, and liquid crystal chemistry and as
vehicles for drug delivery.5 Furthermore, the nitro group
in 3 could serve as a precursor for the nitrile oxide,
enroute to 1,3-dipolar cycloaddition reactions.6
Previously Beuvich and co-workers reported the syn-
thesis of several phenolic ortho esters of nitroacetic acid
by the reaction of 1,1-dichloro-2-nitroethylene and phe-
nols in the presence of sodium methoxide in methanol.7
Similarly, Francotte and co-workers reported the syn-
thesis of the trimethyl ortho ester of nitroacetic acid,
1,1,1-trimethoxy-2-nitroethane from 1,1-dichloro-2-nitro-
ethylene or 1,1,2-trichloro-2-nitroethylene.8 They have
also reported a facile acid-catalyzed synthesis of 3-(ni-
tromethyl)-2,4,10-trioxatricyclo[3.3.1.13,7]decane from 1,1,1-
trimethoxy-2-nitroethane. Essentially following the pro-
tocol developed by pioneering studies of ortho ester
synthesis by Corey and Raju,9 recently Fenk6 developed
a four-step route to 4-methyl-1-(nitromethyl)-2,6,7-
trioxabicyclo[2.2.2]octane, a nitroacetic acid ortho ester
useful in the synthesis of 4,5-dihydroisoxazole deriva-
tives. Thus, there is a continuing interest in the develop-
ment of new synthetic routes for the stable nitroacetic
acid ortho esters. We now report a facile synthesis of
hitherto unknown arylmethyl ortho esters of nitroacetic
acid 3 starting from 1,1-di(methylsulfanyl)-2-nitroethyl-
ene 1 and the arylmethyl alcohols 2 as depicted in
Scheme 1.
The reaction of 1,1-di(methylsulfanyl)-2-nitroethylene,
benzyl alcohols, and sodium hydride furnishes crystalline
triarylmethyl ortho esters of nitroacetic acid.
The nitroketene dithioacetals of the type 1 are well-
known as two-carbon synthons and for their push-pull
electronic nature.1 The Michael acceptor characteristics
of the nitroethylene portion of 1 and the possibility of
substitution of the two methylsulfanyl groups with
nucleophiles have been well exploited for the synthesis
of a variety of heterocycles.2 Furthermore, the 1,1-di-
(methylsulfanyl)ethylene moiety in 1 is a latent carbox-
ylic acid and the nitro group is a latent amino group.
Thus, the nitroketene dithioacetal 1 can be viewed as
glycine equivalent. In continuation of our interest in
exploiting multifunctional systems of the type 1 for the
synthesis of molecules of diverse structures,3 we reasoned
that sequential attack of oxygen nucleophiles on C-1 of
1,1-di(methylsulfanyl)-2-nitroethylene 1 followed by elimi-
nation of the methylsulfanyl groups could lead to ortho
esters of nitroacetic acid 3.
There are several grounds to develop convenient
synthesis of ortho esters. The ortho esters are well-known
to serve as convenient protecting groups for carboxylic
acids since they are stable under basic conditions and
are readily hydrolyzed under mild acidic conditions.4 Not
surprisingly, ortho esters found widespread use in syn-
thetic, biological, and commercial applications. Specifi-
cally, the ortho esters of nitroacetic acid 3 have been
shown to be useful in the fields of adhesive, artificial
Reaction of 1,1-di(methylsulfanyl)-2-nitroethylene 1
with 3 equiv of sodium phenylmethanoate in benzyl
alcohol at room temperature for 12 h provided crystalline
tribenzyl ortho ester 3a in 30% yield after due workup
and purification. The yield increased to 95% when the
reaction of 1 was conducted in dry THF using sodium
(5) (a) Casida, J. E. Arch. Insect Biochem. 1993, 22, 13-23. (b)
Goodman, M.; Oh, Y. S. U.S. Patent 529,827, 1994; Chem. Abstr. 121:
1017045. (c) Tokuyama Soda Co. Ltd. Japan JP 58,213,781, 1983;
Chem. Abstr. 100:197826. (d) Pasche, R.; Zaschke, H.; Hauser, A.;
Demus, D. Liq. Cryst. 1989, 6, 397-407. (e) Corey, E. J.; Shimoji, K.
J. Am. Chem. Soc. 1983, 105, 1662-1664. (f) Corey, E. J.; De, B. J.
Am. Chem. Soc. 1984, 106, 2735-2736. (g) Corey, E. J.; Desai, M. C.;
Engler, T. A. J. Am. Chem. Soc. 1985, 107, 4339-4341. (h) Ishizone,
T.; Tominaga, T.; Kitamura, K.; Hirao, A.; Nakahama, S. Macromol-
ecules 1995, 28, 4829-4836. (i) Sintzet, M. B.; Heller, J.; Ng, S. V.;
Taylor, M. S.; Tabatabay, G.; Gurny, R. Biomaterials 1998, 19, 791-
800.
(1) Metzner, P.; Thullier, A. Sulfur Reagents in Organic Synthesis;
Academic Press: New York, 1994.
(2) (a) Kolb, M. Synthesis 1990, 171-190. (b) Tominaga, Y.; Mat-
suda, Y. J. Heterocycl. Chem. 1985, 22, 937-949.
(3) (a) Rao, H. S. P.; Sakthikumar, L.; Shreedevi. S. Sulfur Lett.
2002, 207-218. (b) Rao, H. S. P.; Sakthikumar, L.; Vanitha, S.; Kumar,
S. S. Tetrahedron Lett. 2003, 44, 4701-4704.
(6) Fenk, C. J. Tetrahedron Lett. 1999, 40, 7955-7959.
(7) Beuvich, V. A.; Nakova, N. Zh.; Perekalin, V. V. J. Org. Chem.
USSR 1979, 1315-1318; Zh. Org. Khim. 1979, 15, 1473.
(8) Francotte, E.; Verbruggen, R.; Viehe, H. G.; Van Meerssche, M.;
Germain, G., Doelercq, J. P. Bull. Soc. Chim. Belg. 1976, 87, 693-
707.
(4) For reviews on the synthesis, reactivity and uses of ortho esters,
see: (a) Pindur, U.; Mu¨ller, J.; Flo. C.; Witzel, H. Chem. Soc. Rev. 1987,
16, 75-87. (b) Pavlova, L. A.; Davidovich, Yu. A.; Rogozhin, S. V. Russ.
Chem. Rev. 1986, 55, 1026-1041. (c) De Wolfe, R. H. Synthesis 1974,
153-172.
(9) Corey, E. J.; Raju, N. Tetrahedron Lett. 1983, 24, 5571-5574.
10.1021/jo050308e CCC: $30.25 © 2005 American Chemical Society
Published on Web 04/15/2005
4524
J. Org. Chem. 2005, 70, 4524-4527

TABLE 1. Conversion of Nitroketene Dithoacetal 1 to the Corresponding Ortho Esters 3a-i
entry
benzyl alcohols 2
ortho esters 3
yield of 3, %
yield of 4, %
1
2
3
4
5
6
7
8
9
C6H5CH2OH, 2a
(C6H5CH2O)3CCH2NO2, 3a
95
80
90
87
90
85
77
80
90
2-ClC6H4CH2OH, 2b
(2-ClC6H4CH2O)3CCH2NO2, 3b
(4-ClC6H4CH2O)3CCH2NO2, 3c
(4-CH3C6H4CH2O)3CCH2NO2, 3d
(4-CH3OC6H4CH2O)3CCH2NO2, 3e
{(3,4,5-(CH3O)3C6H2CH2O}3CCH2NO2, 3f
(1-C10H7CH2O)3CCH2NO2, 3g
(2-C4H3CH2O2)3CCH2NO2, 3h
(2-C4H3SCH2O)3CCH2NO2, 3i
15
4-ClC6H4CH2OH, 2c
4-CH3C6H4CH2OH, 2d
4-CH3OC6H4CH2OH, 2e
3,4,5-(CH3O)3C6H2CH2OH, 2f
1-Naphthylmethanol, 2g
2-Furylmethanol, 2h
12
20
18
2-Thienylmethanol, 2i
SCHEME 2
hydride as base. The nitroketene dithioacetal 1 required
for the present work was prepared from carbon disulfide,
nitromethane, and dimethyl sulfate according to a new
and improved procedure (see Experimental Section). The
structure of 3a was confirmed on the basis of spectro-
scopic (IR, 1H NMR, 13C NMR, DEPT, MS) and analytical
data. The tribenzyl ortho ester 3a displayed character-
istic bands at 1551 and 1383 cm-1 for the nitro group.
1
The H NMR spectrum of 3a displayed two singlets at
4.78 (6H) and 4.85 (2H) ppm for benzylic and nitro-
methylenes, respectively. As anticipated, the proton-
decoupled 13C NMR spectrum of 3a displayed six signals,
two of which were in the aliphatic region.
at -20 °C.6 On the other hand, the benzyl ortho esters 3
are crystalline solids and are stable at room temperature,
which makes them amenable to study their physico-
chemical properties and for use in further transforma-
tions.
Beuvich and co-workers reported the formation of
corresponding O,O-acetal 7 instead of the ortho ester 8
on the reaction of 2,2-dichloronitroethylene 5 with 2-chlo-
rophenol 6, possibly due to steric hindrance to attack by
the third 2-chlorophenolate anion (Scheme 2).7 Interest-
ingly, however, as revealed in Table 1 (entry 2), the
reaction of 1 with 2-chlorobenzyl alcohol 2b furnished
corresponding ortho ester 3b in good yield. Thus, present
work shows that the nitroketene-O,O-acetals are prone
to being transformed to more stable ortho esters in the
presence of alkoxide anions provided there is no steric
resistance to the attack of the third alkoxide anion.
To test the generality of the conversion, the nitroketene
dithioacetal 1 was subjected to reaction with a variety
of benzyl alcohols and sodium hydride in dry THF.
Corresponding benzylic ortho esters 3b-i were obtained
in good yield (Table 1). The ortho esters 3b-i exhibited
analytical and spectral data similar to those of the parent
molecule 3a. In some cases the reactions furnished
known trithio ortho ester 410 in minor quantities (Table
1). It is possible that in some cases where the arylmetha-
noate anion is sluggish to attack 1 in Michael fashion,
as in the cases of 2b and 2f-h, the newly released
methylsulfanyl anion competes to furnish 4 in minor
amounts.
Further confirmation of the structure of ortho esters
3 came from the analysis of single-crystal X-ray data for
nitroacetic acid trifurylmethyl ortho ester 3h.11 The X-ray
crystal structure shows that, in its solid state, the
molecule 3h stabilizes in a conformation where intramo-
lecular CH-O-type hydrogen bonding interaction be-
tween the methylene hydrogen and ether oxygen (259.2
pm) and intermolecular hydrogen bonding interaction
between furan hydrogen with the oxygen of the nitro
group (258.4 pm) dominate.
The small chain alkyl ortho esters of nitroacetic acid
are generally liquids at room temperature and are not
very stable. For example, 4-methyl-1-(nitromethyl)-2,6,7-
trioxabicyclo[2.2.2]octane was reported to be stable only
Hydrolysis of ortho esters is one of the well-studied
reactions in organic chemistry.12 We reasoned that
because of the presence of the electron-withdrawing nitro
group the nitroacetic acid ortho esters 3 are expected to
be more stable in acidic conditions compared to corre-
sponding nonactivated ortho esters. In fact, the triben-
zylic ortho ester 3a was stable up to pH 3 for over 3 days
and decomposed at pH 2.8 in 30 min, whereas some
nonactivated ortho esters were known to hydrolyze at pH
4.75 within a few minutes.13 Based on this result, we
anticipate that the nitroacetic acid ortho esters of type 3
could be used as pro-drugs for anticancerous molecules
having a benzyl alcohol moiety, because under hypoxic
conditions prevalent in cancerous tissues there is a
possibility of reduction of a nitro group to an amino group
and on reduction the drug gets released as a result of
hydrolysis.
(10) Coustard, J.-M. Tetrahedron 1995, 51, 10929-10940.
(11) X-ray Data for 3h. X-ray data were collected at 293 K on a
CCD diffractometer with graphite monochromated Mo KR (radiation
(λ ) 0.7107 Å). Structure was solved by direct methods (SIR 92).
Refinement was done by full-matrix least-squares procedure on F2
using SHELXL-97. The non-hydrogen atoms were refined anisotropi-
cally whereas hydrogen atoms were refined isotropically. C17H17NO8,
MW ) 363.32, colorless crystal, triclinic, space group P-1. Cell
parameters: a ) 9.169 (3) Å, (R ) 92.443 (5) Å, b ) 9.702 (3) Å, (â )
93.616 (5) Å, c ) 10.523 (4) Å, (γ ) 112.089 (5) Å; V ) 863.4 (5) Å3;
Z ) 2, Dc ) 1.397 mg m-3, F (000) ) 380, (µ ) 0.113 mm-1. Total
number of I.s. parameters ) 235, R1 ) 0.0495 for 1815 Fo > 2σ(Fo)
and 0.0524 for all 4278 data. wR2 ) 0.2124, GOF ) 1.001, restrained
GOF ) 1.0, for all data (CCDC 250775).
(12) (a) DeWolfe, R. H. Carboxylic Ortho Derivatives; Academic
Press: New York, 1970. (b) Fife, T. H. Acc. Chem. Rev. 1972, 5, 264-
272. (c) Cordes, E. H.; Bull, H. G. Chem. Rev. 1974, 581-603. (d)
Chiang, Y.; Kresge, A. J.; Lahti, M. O.; Weeks, D. P. J. Am. Chem.
Soc. 1983, 105, 6852-6855. (e) McClelland, R. A.; Moreau, C. Can. J.
Chem. 1985, 3, 2673-2678. (f) Deslongchamps, P.; Dory, Y. L.; Li, S.
Tetrahedron 2000, 56, 3533-3537.
(13) Giner, J.-L.; Xiaoyong. Li; Joseph, J. M. J. Org. Chem. 2003,
68, 10079-10086.
J. Org. Chem, Vol. 70, No. 11, 2005 4525

hexanes-EtOAc); IR (KBr), 3065, 2987, 2929, 1554, 1222, 1098,
755 cm-1; 1H NMR (300 MHz, CDCl3) 7.27 (dd, 3H, J ) 7.2, 6.6
Hz), 7.31-7.38 (m, 3H) 7.20-7.28 (m, 6H), 4.97 (s, 2H), 4.93 (s,
6H) ppm; 13C NMR (CDCl3, 75 MHz),) 134.29, 132.67, 129.23,
129.01(2C), 126.97, 111.71, 75.88, 62.94 ppm. Anal. Calcd for
C23H20NO5Cl3: C, 55.61; H, 4.06; N, 2.82. Found: C, 55.62; H,
4.19; N, 2.74.
In conclusion, in this study we have shown that the
crystalline tribenzylic nitroacetic acid ortho esters 3 could
be prepared conveniently from the readily available
nitroketene dithioacetal 1.
Experimental Section
1-Chloro-4-(1,1-di[(4-chlorobenzyl)oxy]-2-nitroethoxy-
methyl)benzene (3c). Following the general procedure de-
scribed above the reaction of nitroketene dithioacetal 1 (400 mg,
2.42 mmol), 4-chlorobenzyl alcohol (1.04 g, 7.2 mmol), and
sodium hydride (0.25 g, 7.2 mmol) furnished 1.08 g of 1-chloro-
4-(1,1-di[(4-chlorobenzyl)oxy]-2-nitroethoxymethyl)benzene 3c in
90% yield as colorless crystals after column purification: mp
78-80 °C; Rf 0.73 (80:20 hexanes-EtOAc); IR (KBr), 3097, 2977,
Preparation of 1,1-Di(methylsulfanyl)-2-nitroethylene
(1). To a stirred mixture of nitro methane (10 mL, 1.84 mmol)
and carbon disulfide (11.13 mL, 1.84 mmol) in dry methanol (10
mL) under a blanket of dry N2 at 0 °C was slowly added a
solution of potassium hydroxide (23 g, 4.14 mol) in methanol
(20 mL) by using a pressure equalizer funnel, and the mixture
was vigorously stirred at 0 °C for 3 h. The reddish salt formed
in the reaction was filtered and washed with dry methanol (15
mL) followed by dry diethyl ether (15 mL) to furnish 17.6 g of
dipotassium 2-nitro-1,1-ethylenedithiolate (45%) as a dry reddish
powder. The salt was used for the next step immediately.
To the stirred suspension of the salt (17.6 g, 82.6 mmol) in
dry hexanes (50 mL) and dry toluene (5 mL) was added dropwise
freshly distilled dimethyl sulfate (10.4 g, 82.6 mmol) in 10 mL
of dry toluene through a pressure equalizer funnel at 0 °C during
30 min, and the reaction mixture was vigorously stirred for 2 h
at the same temperature to furnish 1,1-di(methylsulfanyl)-2-
nitroethylene 1. The crude product was filtered and recrystal-
lized (ethanol) to get the light yellow crystals (11.58 g, 85%, mp
127 °C, lit.14 127 °C). Analytical and spectral data matched well
with the authentic commercially available sample.
1
2840, 1590, 1315, 1088, 760 cm-1; H NMR (300 MHz, CDCl3)
7.31 (br d, 3H, J ) 8.4 Hz), 7.22 (br d, 3H J ) 8.1 Hz), 4.84 (s,
2H), 4.71 (s, 6H) ppm; 13C NMR (75 MHz, CDCl3) 134.90, 133.90,
128.9, 128.7, 111.39, 76.05, 65.00 ppm. Anal. Calcd for C23H20
-
NO5Cl3: C, 55.76; H, 4.07; N, 2.82. Found: C, 56.22; H, 4.21; N,
3.45.
1-(1,1-Di[(4-methylbenzyl)oxy]-2-nitroethoxymethyl)-4-
methylbenzene (3d). Following the general procedure de-
scribed above, reaction of nitroketene dithioacetal 1 (400 mg,
2.42 mmol), 4-methylbenzyl alcohol (886 mg, 7.2 mmol), and
sodium hydride (0.25 g, 7.2 mmol) furnished 915 mg of 1-(1,1-
di[(4-methylbenzyl)oxy]-2-nitroethoxymethyl)-4-methylben-
zene 3d in 87% yield after column purification as colorless
crystals: mp 88 °C; Rf 0.68 (80:20 hexanes-EtOAc); IR (KBr),
3008, 2957, 2920, 1551, 1315, 1088, 808 cm-1 1H NMR (300
;
General Procedure for Preparation of Nitroacetic Acid
Ortho Esters. To a stirred and cleaned suspension of NaH (60%
suspension in oil; 0.25 gm, 7.2 mmol) in dry THF (5 mL) at 0 °C
was added a solution of benzyl alcohols (7.2 mmol) in dry THF
(4 mL), and the mixture was vigorously stirred at 0 °C for 30
min. Then a solution of 1,1-di(methylsulfanyl)-2-nitroethylene
(400 mg, 2.42 mmol) in dry THF (10 mL) was added dropwise
during 30 min. The reaction mixture was then allowed to stir
at 0 °C for 90 min to 3 h. After completion of the reaction (TLC),
the mixture was carefully acidified with acetic acid up to pH
6.5 followed by dilution with dichloromethane (40 mL). The
organic solution was washed with water (3 × 25 mL) and brine
(2 × 10 mL) and dried over anhydrous Na2SO4. Evaporation of
the solvent under reduced pressure resulted in crude ortho esters
as solids. In cases where further purification was required to
separate ortho esters and thio ortho ester 4, the crude product
were subjected to column chromatography on SiO2 using in-
creasing amounts of ethyl acetate in hexanes as eluent. Evapo-
ration of the pooled fractions having the required ortho ester
resulted in a crystalline product. Analytical samples were
obtained by crystallization from DCM/hexanes. Interestingly, all
of the orothesters in their pure form exhibited yet to be identified
characteristic smells.
1-[1,1-Di(benzyloxy)-2-nitroethoxy]methylbenzene (3a).
Following the general procedure described above, reaction of
nitroketene dithioacetal 1 (400 mg, 2.42 mmol), benzyl alcohol
(786 mg, 7.2 mmol), and sodium hydride (0.25 g, 7.2 mmol)
furnished 900 mg of 1-[1,1-di(benzyloxy)-2-nitroethoxy]methyl-
benzene 3a in 95% yield as colorless crystals: mp 45 °C; Rf 0.68
(80:20 hexanes-EtOAc); IR (KBr), 3035, 2895, 1551, 1237, 1005,
745 cm-1; 1H NMR (300 MHz, CDCl3) 7.30 (m, 5H), 4.85 (s, 2H),
4.78 (s, 6H) ppm; 13C NMR (CDCl3, 136.63, 128.47, 127.92,
127.65, 111.36, 75.76, 65.59 ppm. Anal. Calcd for C23H23NO5:
C, 70.21; H, 5.89; N, 3.56. Found: C, 70.39; H, 5.87; N, 3.63.
1-Chloro-2-(1,1-di[(2-chlorobenzyl)oxy]-2-nitroethoxy-
methyl)benzene (3b). Following the general procedure de-
scribed above the reaction of nitroketene dithioacetal 1 (400 mg,
2.42 mmol), 2-chlorobenzyl alcohol (1.04 g, 7.2 mmol), and
sodium hydride (0.25 g, 7.2 mmol) furnished 959 mg of 1-chloro-
2-(1,1-di[(2-chlorobenzyl)oxy]-2-nitroethoxymethyl)benzene 3b in
80% yield as colorless crystals: mp 61-63 °C; Rf 0.68 (80:20
MHz, CDCl3) 7.23 (d, 6H, J ) 8.1 Hz), 7.15 (d, 3H, J ) 9.0 Hz),
4.83 (s, 2H), 4.73 (s, 6H); 2.34 (s, 9H) ppm; 13C NMR (75 MHz,
CDCl3) 137.70, 133.71, 129.17, 127.86, 111.29, 76.20, 65.51, 21.17
ppm. Anal. Calcd for C26H29NO5: C, 71.70; H, 6.71; N, 3.21.
Found: C, 71.02; H, 6.59; N, 3.24.
1-(1,1-Di[(4-methoxybenzyl)oxy]-2-nitroethoxymethyl)-
4-methoxybenzene (3e). Following the general procedure
described above reaction of nitroketene dithioacetal 1 (400 mg,
2.42 mmol), 4-methoxybenzyl alcohol (1.01 g, 7.2 mmol), and
sodium hydride (0.25 g, 7.2 mmol) furnished 1.08 g of 1-(1,1-di-
[(4-methoxybenzyl)oxy]-2-nitroethoxymethyl)-4-methoxyben-
zene 3e in 90% yield as colorless crystals after column purifi-
cation: mp 44-46 °C; Rf 0.46 (80:20 hexanes-EtOAc); IR (KBr)
3124, 2998, 2959, 1555, 1249, 1046, 822 cm-1 1H NMR (300
;
MHz, CDCl3) 7.27 (d, 6H, J ) 8.7 Hz), 6.87 (d, 6H, J ) 8.1 Hz)
4.81(s, 2H), 4.69 (s, 6H), 3.80 (s, 9H) ppm; 13C NMR (75 MHz,
CDCl3) 159.36, 129.40, 128.78, 113.84, 76.12, 65.29, 55.25 ppm.
Anal. Calcd for C26H29NO8: C, 64.58; H, 6.04; N, 2.89. Found:
C, 64.14; H 5.89; N, 2.80.
1,2,3-Trimethoxy-5-(2-nitro-1,1-di[(3,4,5-trimethoxyben-
zyl)oxy]ethoxymethyl)benzene (3f). Following the general
procedure described above reaction of nitroketene dithioacetal
1 (400 mg, 2.42 mmol), 3,4,5-methoxybenzyl alcohol (1.439 g,
7.2 mmol), and sodium hydride (0.25 g, 7.2 mmol) furnished
1.367 g of 1,2,3-trimethoxy-5-(2-nitro-1,1-di[(3,4,5-trimethoxy-
benzyl)oxy]ethoxymethyl)benzene 3f in 85% yield as colorless
crystal after column purification: mp 103-105 °C; Rf 0.42 (50:
50 hexanes-EtOAc); IR (KBr) 2999, 2968, 2942, 2836, 1595,
1
1550, 1329, 1235, 1096 cm-1; H NMR (300 MHz, CDCl3) 6.56
(s, 6H), 4.88 (s, 2H), 4.74 (s, 6H), 3.83 (s, 27H) ppm; 13C NMR
(75 MHz, CDCl3) 153.69, 138.03, 132.62, 111.80, 105.00, 76.59,
66.19, 61.19, 56.45 ppm. Anal. Calcd for C32H41NO14: C, 57.91;
H, 6.23; N, 2.11. Found: C, 57.78; H, 6.02; N, 1.81.
5-[1,1-Di(1-naphthylmethoxy)-2-nitroethoxy]methyl-1,4-
dihydronaphthalene (3g). Following the general procedure
described above the reaction of nitroketene dithioacetal 1 (400
mg, 2.42 mmol), 1-naphthylmethanol (1.119 g, 7.2 mmol), and
sodium hydride (0.25 g, 7.2 mmol) furnished 1.011 g of 5-[1,1-
di(1-naphthylmethoxy)-2-nitroethoxy]methyl-1,4-dihydronaph-
thalene 3g in 77% yield after column purification as colorless
crystals: mp 127-130 °C; Rf 0.45 (70:30 hexanes-EtOAc); IR
(KBr) 3045, 2903, 1553, 1230, 1080, 777 cm-1 1H NMR (300
;
(14) (a) Gompper, R.; Schaefer, H. Chem. Ber. 1967, 100, 591-604.
(b) Jensen, K. A.; Buchardt, O.; Lohse, C. Acta Chem. Scand. 1967,
21, 2797-2806.
MHz, CDCl3) 8.00 (d, 3H, J ) 9.0 Hz), 7.8-7.9 (m, 6H), 7.3-7.5
(m, 12H), 5.23 (s, 6H), 4.98 (s, 2H) ppm; 13C NMR (75 MHz,
4526 J. Org. Chem., Vol. 70, No. 11, 2005

CDCl3) 133.63, 132.38, 131.51, 128.86, 128.55, 126.37 (2C),
125.87, 125.25, 123.78, 112.13, 76.58, 64.27 ppm. Anal. Calcd
for C35H29NO5: C, 77.33; H, 5.38; N, 2.58. Found: C, 77.36; H,
5.19; N, 3.56.
718 cm-1; 1H NMR (300 MHz, CDCl3) 7.30 (dd, 3H, J ) 5.1, 5.1
Hz), 7.03 (br d, 3H, J ) 3.9 Hz), 6.97 (br d, 3H, J ) 4.8 Hz),
4.94 (s, 6H), 4.77 (s, 2H); 13C NMR (75 MHz, CDCl3) 138.82,
127.12, 126.76, 126.37, 111.20, 76.47, 60.68 ppm. Anal. Calcd
for C17H17NO5S3: C, 49.62; H, 4.16; N, 3.46; S, 23.38. Found:
C, 49.45; H, 4.09; N, 3.86; S, 23.63.
1,1,1-Tri(methylsulfanyl)-2-nitroethane (4). Rf 0.75 (80:
20, hexanes-EtOAc); IR (Neat) 2988, 2919, 1554, 1370, 960, 652
cm-1; 1H NMR (300 MHz, CDCl3) 4.72 (s, 2H), 2.29 (s, 9H) ppm;
13C NMR (75 MHz, CDCl3) 96.18, 80.55, 13.43 ppm.
2-[1,1-Di(2-furylmethoxy)-2-nitroethoxy]methylfuran
(3h). Following the general procedure described above the
reaction of nitroketene dithioacetal 1 (400 mg, 2.42 mmol), furan-
2-yl-methanol (713 mg, 7.2 mmol), and sodium hydride (0.25 g,
7.2 mmol) furnished 604 mg of 2-[1,1-di(2-furylmethoxy)-2-
nitroethoxy]methylfuran 3h in 80% yield after column purifica-
tion as colorless crystals: mp 83-85 °C; Rf 0.56 (70:30 hexanes-
EtOAc); IR (KBr) 3148, 2962, 2982, 1552, 1383, 1062, 749 cm-1
;
Acknowledgment. H.S.P.R. thanks UGC, CSIR,
UGC-SAP and DST-FIST for financial support. We
thank Prof. A. Srikrishna, IISc, Bangalore, for generous
help in recording spectra and helpful discussions. We
thank Prof. T. N. Guru Row, IISc, Bangalore, for X-ray
diffraction data.
1H NMR (300 MHz, CDCl3) 7.42 (dd, 3H, J ) 1.2 Hz), 6.38 (dd,
3H, J ) 3.3 Hz), 6.35 (br d, 3H, J ) 3.0 Hz), 4.76 (s, 2H), 4.74
(s, 6H); 13C NMR (75 MHz, CDCl3) 150.00, 143.11, 111.10,
110.48, 110.13, 75.88, 57.79 ppm. Anal. Calcd for C17H17NO8:
C, 56.20; H, 4.72; N, 3.86. Found: C, 56.51; H, 4.59; N, 4.23.
2-[2-Nitro-1,1-di(2-thienylmethoxy)ethoxy]methylthio-
phene (3i). Following the general procedure described above
the reaction of nitroketene dithioacetal 1 (400 mg, 2.42 mmol),
thiophen-2-yl-methanol (828 mg, 7.2 mmol), and sodium hydride
(0.25 g, 7.2 mmol) furnished 895 mg of 2-[2-nitro-1,1-di(2-
thienylmethoxy)ethoxy]methylthiophene 3i in 90% yield after
column purification as colorless crystals: mp 76 °C; Rf 0.68 (80:
20, hexanes-EtOAc); IR (KBr) 3102, 2934, 2880, 1556, 1068,
Supporting Information Available: 1H and 13C NMR
spectral data for compounds 3a-i and 4 and crystal structure
of 3h in CIF format. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO050308E
J. Org. Chem, Vol. 70, No. 11, 2005 4527