A facile and efficient method for synthesis of the aryloxyimidoyl azides

Article abstract of DOI:10.3184/030823400103165653

A facile and efficient synthesis is introduced for the new aryloxyimidoyl azides in a quantitative yield.

Full text of DOI:10.3184/030823400103165653

44 J. CHEM. RESEARCH (S), 2000
J. Chem. Research (S),
2000, 44–45
SHORT PAPER
A facile and efficient method for synthesis of the
aryloxyimidoyl azides†
Abdoul Hossein Dabbagh*, and Ali Reza Modarresi-Alam
College of Chemistry, Isfahan University of Technology, Isfahan, 84156, Iran
A facile and efficient synthesis is introduced for the new aryloxyimidoyl azides in a quantitative yield.
Organoazides are one of the most important synthetic inter-
mediates for the preparation of nitrogen-containing organic
compounds. The azido functionality not only reacts with
nucleophiles and electrophiles but also serves as a nitrene pre-
cursor on thermolysis or photolysis.1–6 In recent years imidoyl
Scheme 1
azides have been also used as a convenient reagent to generate
the nitrenes.7–12 Some nitrenes have been seldom used due to
One interesting aspect of method B is the synthesis of 3i
handling difficulties and the danger of explosion of their azide
precursors, as well as their low selectivity.1–6,10 Imidoyl azides
show none of the above major difficulties.7–12
(entry 9). This azide was not produced in method A.
Furthermore, addition of THF to the reaction mixture to
increase the solubility of the azide (some of the azide pro-
duced was co-precipitated with Et3N.HX salt) prevented azide
formation (reaction was not completed even after two days).
Method B was also examined with other electrophiles such as
PhSO2Cl, Br-CN (entries 2,3,10). A quantitative yield of the
azides was achieved. For cases where azide is not soluble in
ethyl acetate (e.g. entry 9) or where it is contaminated with
Et3N.HX salt, two work up procedures were developed to
eliminate these problems (see experimental section).
The question raised why the reaction is complete in ethyl
acetate but not with THF and other solvents. This could be
attributed to the equilibrium between azide and 1- or 2-substi-
tuted tetrazole, Scheme 2. In ethyl acetate the equilibrium
favors the azide. Further investigations of the tetrazole-azide
equilibrium are now underway.
In principle, azido/tetrazole equilibrium depends on three
important factors; substituent, solvent and temperature. The
electron-withdrawing groups, when the temperature increases
and the solvent polarity decreases, favor formation of the
azide isomer.14–16
In summary, we have described a facile and convenient syn-
thesis method for a series of new aryloxyimidoyl azides in
ethyl acetate. This method does not require purification or
separation, most importantly by column chromatography and
produces azides in quantitative yields.
In connection with the synthetic value of the imidoyl
azides7–12, we have developed a new synthetic method for ary-
loxyimidoyl azides. A facile and efficient synthesis method is
presented a quantitative yield (near 100% within the experi-
mental error) for these compounds. The imidoyl azides are
generally prepared by reaction of tetrazoles with electron-
withdrawing electrophiles (such as, TsCl, Br-CN, MsCl, etc)
in anhydrous peroxide-free THF and one equivalent of tri-
ethylamine under inert atmosphere (nitrogen or argon). The
reaction mixture must be passed through column chromatog-
raphy, because the reaction is not completive and quantitative
(method A).7–13 In attempts to improve the yield and eliminate
the difficulties associated with this method, the following
improvements were achieved; (a) No need for over purifica-
tion of solvents. (b) No need for separation or purification of
azides by column chromatography or other methods; and (c)
Quantitative yields of azides.
It was found that the reaction was completed quantitatively
in ethyl acetate, at ambient temperature with 1.3 equiv. of
Et3N, the minimum amount required (method B). After filtrat-
ing the reaction mixture, 1 equiv. of Et3N.HX salt was pro-
duced (that is %100 yield). Evaporation of the filtrated
solution under vacuum at ambient temperature (evaporating
along with heating can decompose small amounts of azides)
gave pure azides in quantitative yield. The results are shown in
Table 1 and Scheme 1.
Table 1 Preparation of aryloxyimidoyl azides
Entry
Azide
Ar
Y
X
%Yield
mp (dec.)°C
Method A
Method B
1
2
3a
3b
3c
3d
3e
3f
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
C6H5
2,6-(CH3)2C6H5
4-CH3OC6H4
4-ClC6H4
4-O2NC6H4
2,6-(CH3O)2C6H4
2,6-(CH3O)2C6H4
4-CH3C6H4SO2
C6H5SO2
Cl
Cl
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
76
–
100a
100a
100a
100a
100a
100a
100a
100a
100a
100a
92
97
59
96
94
77
98
117
120
96
3
CN
–
4
4-CH3C6H4SO2
4-CH3C6H4SO2
4-CH3C6H4SO2
4-CH3C6H4SO2
4-CH3C6H4SO2
4-CH3C6H4SO2
C6H5SO2
76
87
78
81
53
0
5
6
7
3g
3h
3i
8
9
10
3j
–
a The yields are quantitative (within the experimental error of 2–3%).
* To receive any correspondence.
† This is a Short Paper, there is therefore no corresponding material in
J Chem. Research (M).

J. CHEM. RESEARCH (S), 2000 45
2150(s), 2120(s), 1660–1440(s), 1330(vs), 1290(s), 1195(s), 1150(s),
1090(s), 815(m), 770(s), 735(s), 690(s), 660(m) cm–1.
N/-(4-methylbenzenesulfonyl) (4-methoxyphenoxy) imidoyl azide
(3f); mp = 77°C (dec.), 1H NMR (90MHz, CD3CN); δ (ppm) 2.42 (s,
3H), 3.80 (s, 3H), 6.85(d, J = 10.5Hz, 2H), 7.05 (d, J = 10.5Hz, 2H),
7.3 (d, J = 7.8Hz, 2H), 7.8 (d, J = 7.8Hz, 2H). IR (KBr); 3060(w),
2950(w), 2900(w), 2850(w), 2170(m), 2150(m), 2120(m),
1440–1660(s), 1330(s), 1300(s), 1250(s), 1200(s), 1150(s), 1090(s),
830(m), 810(m), 730(m) cm–1.
Scheme 2
N/-(4-methylbenzenesulfonyl) (4-chlorophenoxy) imidoyl azide
(3g); mp = 98°C (dec.), 1H NMR (90MHz, CD3CN); δ (ppm) 2.42 (s,
3H), 7.15 (d, J = 9Hz, 2H), 7.25 (d, J = 7.8Hz, 2H), 7.37(d, J = 9Hz,
2H), 7.75 (d, J = 7.8, 2H). IR (KBr); 3100(w), 3050(w), 2900(w),
2850(w), 2170(m), 2125(m), 1659–1480(s), 1330(s), 1300(s),
1205(m), 1150(s), 1080(s), 830(m), 810(m), 690(m) cm–1; Anal.
Calcd for C14H11ClN4O3S; C, 47.93; H, 3.1; N, 15.97; Found: C,
46.60; H, 3.1; N, 16.10.
Experimental
General.- 1H-NMR spectra were recorded at Varian EM 390
(90MHz). The IR spectra were obtained on a Shimadzu Zu-435.
Melting points were taken by the GallenKamp melting point appara-
tus and are uncorrected. The elemental analysis was performed by
Research Institute of Petroleum Industries (RIPI) and Tarbiat
Modarres University Research Center. All starting materials and sol-
vents were purified with the proper purification techniques before
use.17 All reactions were followed with TLC. Tetrazoles were pre-
pared according to literature.8-13,18
N/-(4-methylbenzenesulfonyl) (4-nitrophenoxy) imidoyl azide
1
(3h); mp = 117°C (dec.), H NMR (90MHz, CD3CN); δ (ppm) 2.42
(s, 3H), 7.3 (d, J = 7.8Hz, 2H), 7.4 (d, J = 9Hz, 2H), 7.75 (d, J =
7.8Hz, 2H), 8.3 (d, J = 9Hz, 2H). IR (KBr); 3100(w), 3060(w),
3000(w), 2800(w), 2750(w), 2180(m), 2120(m), 1620–1480(s),
1330–1280(s), 1220(s), 1160(s), 1080(m), 850(m), 810(m), 690(m)
cm–1.
General procedure: Method A – To a solution of tetrazole 1
(10mmol) in 30 ml of peroxide-free anhydrous THF was added 2
(10mmol) in 10 ml THF, with cooling in an ice-salt bath under nitro-
gen (or argon). Triethylamine (10mmol) in 10 ml THF was added
over a period of 30 min. The mixture was stirred and allowed to come
to room temperature, over several h. Filtration, washing with THF,
evaporation of the THF solutions, and chromatography on silica gel,
gives azides. All azides recrystalize in chloroform (or
dichloromethane) and petroleum ether (40–60 °C).
Method B – To a stirred solution of tetrazole 1 (10mmol) and 2 (10
mmol) in 20ml ethyl acetate, in a 50 ml flask equipped with a stop-
per, triethylamine (13mmol) was added drop wise over 5 min at room
temprature. The mixture was stirred over 2–5h. Reaction progress
was monitored by TLC. Filtrate was washed with ethyl acetate.
Evaporation of the ethyl acetate solution (under vacuum and at room
temperature), gave pure azides in a quantitative yield.
In cases where azide is not soluble in ethyl acetate (e.g. entry 9) or
it is contaminated with small amounts of Et3N.HX salt, two work up
procedures were developed to eliminate these problems: (a) the pre-
cipitate (after filtration), was washed several times with THF.
Evaporation of THF produced azide; (b) After evaporating ethyl
acetate (without filtration) the residue was washed with water and
dried under vacuum to give azide.
N/-(4-methylbenzenesulfonyl) (2,6-dimethoxyphenoxy) imidoyl
1
azide (3i); mp = 120°C (dec.), H NMR (90MHz, CDCl3); δ (ppm)
2.42 (s, 3H), 3.80 (s,6H), 6.62 (d, J = 9Hz, 2H), 7.2 (t and d, 3H), 7.9
(d, J = 9Hz, 2H). IR (KBr); 3010(w), 2972(w), 2940(w), 2840(w),
2180(s), 2140(s), 1610–1590(vs), 1580–1560(vs), 1480(s), 1440(w),
1320(s), 1310(s), 1280(s), 1260(s), 1200(w), 1180(w), 1150(s),
1110(s), 1080(s), 997(m), 890(w), 810(w), 760(m), 720(m), 697(w),
670(w), 600(w) cm–1; Anal. Calcd for C16H16N4O5S; C, 51.05; H,
4.29; N, 14.89; Found: C, 50.07; H, 4.40; N, 15.02.
N/-(benzenesulfonyl) (2,6-dimethoxyphenoxy) imidoyl azide (3j);
mp = 96°C (dec.), 1H NMR (90MHz, CDCl3); δ (ppm) 3.80 (s, 6H),
6.60 (d, J = 9Hz, 2H), 7.2 (t, J = 9Hz, 1H), 7.6 (m, 3H), 8.0 (dd, J =
7.5, J = 3Hz, 2H). IR (KBr); 3050(vw), 3000(w), 2940(w), 2840(w),
2180(s), 2140(s), 1630–1590(vs), 1580–1550(vs), 1494(m), 1480(s),
1445(m), 1340–1300(vs), 1290–1280(s), 1260(vs), 1200(m),
1160(vs), 1110 (vs), 1085(s), 1022(w), 1000(w), 880(w),
780–760(m), 730(m), 685(m), 620–600(m), 580–560(m) cm–1.
Received 27 July 1999; accepted 14 October 1999
Paper 9/06124J
N/-(4-methylbenzenesulfonyl) (4-methylphenoxy) imidoyl azide
(3a); mp = 92°C (dec.), 1H NMR (90MHz, CD3CN); δ (ppm) 2.36 (s,
3H), 2.42 (s, 3H), 6.94 (d, J = 9Hz, 2H), 7.15 (d, J = 9Hz, 2H), 7.25
(d, J = 7.8Hz, 2H), 7.72 (d, J = 7.8, 2H). IR (KBr); 3050(w), 3020(w),
2900(w), 2850(w), 2175(s), 2130(s), 1540–1630(vs), 1500(s),
1330(s), 1290(s), 1150(s),1090(s), 815(s), 670(m) cm–1 ; Anal. Calcd
for C15H14N4O3S; C, 54.53; H, 4.27; N, 16.96; Found: C, 53.10; H,
4.2; N, 16.6.
References
1 W. Lwowski (Ed.), Nitrenes, Willey, New York, 1970.
2 F. V. Scriven (Ed.), Azides and Nitrenes, Academic, New York,
1984.
3 W. Lwowski, In Reactive Intermediates, M. R. Jones, R. A. Moss
(Ed.), Willey, New York, vol.3, p.305, 1985; vol.2, p.315, 1981;
vol.1, p.197, 1978.
N/-(benzenesulfonyl) (4-methylphenoxy) imidoyl azide (3b); mp =
1
97 °C (dec.), HNMR (90MHz, CDCl3); δ (ppm) 2.33 (s, 3H), 6.94
4 S. Patai (Ed.), The Chemistry of the Azido Group, Willey, New
York, 1971.
(d, J = 9Hz, 2H), 7.15 (d, J = 9Hz, 2H), 7.6 (m, 3H), 8.1 (dd, J = 6Hz,
J
3Hz, 2H). IR (KBr); 3080(w), 3020(w), 2910(w), 2170(s),
5 E. F. V. Sciven, K. Turnbull, Chem.Rev.,1988, 88, 297.
6 S. G. Alvarez, M. T. Alvarez, Synthesis, 1997, 413.
7 H. A. Dabbagh, S. Ghaelee, J. Org. Chem., 1996, 61, 3439.
8 H. A. Dabbagh, W. Lwowski, J. Org. Chem., 1989, 54, 3952.
9 A. Subbaraj, O. Subbarao, W. Lwowski, J. Org. Chem., 1989, 54,
3945.
10 O. Subba Rao, W. Lwowski, Tetrahedron Lett., 1980, 21, 727.
11 O. Subba Rao, W. Lwowski, J. Heterocycl. Chem., 1980, 17, 187.
12 J. S. McConaghy, W. Lwowski, J. Am. Chem. Soc., 1967, 89, 4450.
13 H. A. Dabbagh, S. Ghaelee, unpublished results.
14 (a) E. Cubero, M. Orozco, F. J. Luque, J. Org. Chem., 1998, 63,
2354. (b) E. Cubero, M. Orozco, F. J. Luque, J. Am. Chem. Soc.
1998, 120, 4723, and references therein.
15 J.-P. Hanun, R. Faure, J.-P. Glay, J. Elguero, J. Heterocycl.
Chem., 1996, 33, 747.
16 A. Y. Denisov, V. P. Krivopalor, V. I. Mamatyuk, V. P. Mamaev,
Magn. Reson. Chem., 1988, 26, 42.
17 (a) M. Casey, J. Leonard, B. lygo, G. Procter, Advanced Practical
Organic Chmistry, Chapman & Hall, Int. NewYork, 1990. (b) W.
L. F. Armarego, D. D. Perrin, Purification of Laboratory
Chemicals, Butterworth-Heinmam, Oxford, 1996.
18 D. Martin, A. Weise, Chem. Ber. 1966, 99, 317.
2130(s), 1605(vs), 1595–1540(vs), 1500(s), 1440(m), 1330(vs),
1300–1280(vs), 1240(w), 1200(s), 1180–1140(vs), 1080(s), 1020(w),
1000–980(m), 880(m), 820(s), 760(w), 740–730(m), 690(m),
610(m), 570(m) cm–1.
N/-(Cyano) (4-methylphenoxy) imidoyl azide (3c); mp = 59°C (dec.),
1H NMR (90MHz, CDCl3); δ (ppm) 2.4 (s, 3H), 7.05 (d, J = 9Hz, 2H),
7.25 (d, J = 9Hz, 2H). IR (KBr); 3010(w), 2950(w), 2900(w), 2190(s),
2160(s), 1640–1600(s), 1600–1580(s), 1560(m), 1500(m),
136–1320(m), 1250(m), 1240–1200(s), 1100(m), 840–800(m) cm–1.
N/-(4-methylbenzenesulfonyl) (phenoxy) imidoyl azide (3d); mp =
96°C (dec.), 1H NMR (90MHz, CD3CN); δ (ppm) 2.42 (s, 3H),
7.1–7.4 (m, 7H), 7.77 (d, J = 7.8, 2H). IR (KBr); 3050(w), 3000(w),
2850(w), 2175(m), 2125(m), 1610(s), 1575(s), 1490(m), 1335(s),
1280(m), 1210(m), 1150(s), 1050(m), 880(m), 770(m), 690(m),
680(m) cm–1; Anal. Calcd for C14H12N4O3S; C, 53.15; H, 3.82; N,
17.71; Found: C, 51.50; H, 3.80; N, 17.10.
N/-(4-methylbenzenesulfonyl) (2,6-methylphenoxy) imidoyl azide
(3e); mp = 94°C (dec.), 1H NMR (90MHz, CD3CN); δ (ppm) 2.08 (s,
6H), 2.42 (s, 3H), 7.09 (s, 3H), 7.3 (d, J = 7.8Hz, 2H), 7.85 (d, J = 7.8,
2H). IR (KBr); 3050(w), 3000(w), 2910(w), 2850(w), 2200(s),