A. A. Fesenko, A. D. Shutalev / Tetrahedron Letters 55 (2014) 1416–1420
1419
boat-like conformations with extraordinarily long C2–NH bonds
(1.480–1.490 Å). The remarkable regioselectivity of the reaction
proceeding exclusively via the N(3)H deprotonated forms of 4a, b
can be explained by the higher acidity of the N(3)H group com-
pared with that of the N(1)H group (0.54–2.32 kcal/mol). The cal-
culations also showed that pyrrolones 7a, b are much more
stable (13.56–14.72 kcal/mol) than the corresponding dihydro-
diazepinones 4a, b.
With 4a as a typical representative, we found that 2,3-dihydro-
1H-1,3-diazepin-2-ones can be converted into 1-carbamoyl-
1H-pyrroles under acidic conditions. However, this reaction pro-
ceeded much more slowly than the transformation of diazepines
3a–c into pyrroles 5a–c.5e Reflux of 4a in 95% EtOH in the presence
of TsOH (0.23 equiv) for three hours afforded a mixture of 5a and
4a in a ratio of 85:15 (Scheme 6). When the amount of TsOH was
increased to 1.01 equivalents, the reaction progressed to give 5a
in 98% yield.11
We assume that this rearrangement started from the addition of
water or EtOH to the C(6)@C(7) double bond and further proceeded
by the scheme analogous to that suggested previously.5e
In summary, a new and convenient approach to functionalized
2,3-dihydro-1H-1,3-diazepin-2-ones based on the thermal
elimination of MeOH from 4-methoxy-2,3,4,5-tetrahydro-1H-1,
3-diazepin-2-ones has been developed. We found that the
prepared 2,3-dihydro-1H-1,3-diazepin-2-ones can be converted
into 1-carbamoyl-1H-pyrroles under acidic conditions. Upon heat-
ing with or without bases, dihydrodiazepinones underwent an
unprecedented rearrangement into 3-(aminomethylene)-2,3-dihy-
dro-1H-pyrrol-2-ones. A plausible mechanism for the rearrange-
ment based on quantum chemical calculations involves initial NH
deprotonation followed by a concerted ring-contraction process.
3-(Aminomethylene)-2,3-dihydro-1H-pyrrol-2-ones were also ob-
tained from the precursors of 2,3-dihydro-1H-1,3-diazepin-2-ones
as a result of cascade reactions.
6. Synthesis of 4a: A solution of compound 3a (0.709 g, 2.17 mmol) in DMSO
(4 mL) was heated under stirring in an oil bath at 133–136 °C (temperature of
the bath) for 30 min. The resulting solution was cooled and ice-cold H2O
(16 mL) was added. The obtained solid was triturated with cooling until a
suspension formed, which was filtered, washed with ice-cold H2O, petroleum
ether, and dried to give 0.624 g of a crude material, which was purified by
column chromatography on silica gel 60 (12.6 g) eluting with CHCl3/petroleum
ether (from 1:3 to 1:1) to give 4a (0.467 g, 73%) as a bright yellow solid. Mp
174.5–175.5 °C (MeCN). IR (Nujol) m
, cmÀ1: 3251 (s), 3141 (m), 3114 (m) (NH),
3068 (w), 3041 (w), 3030 (w), 3021 (w) (C(sp2)H), 1701 (s) (C@O), 1647 (s), 1613
(s) (C@C), 1579 (m), 1493 (m) (CCarom), 748 (s), 692 (s) (CHarom); 1H NMR
3
4
(300.13 MHz, DMSO-d6)
d 8.20 (1H, ddd, JN(1)H,7-H = 5.7, JN(1)H,N(3)H = 2.2,
4
4JN(1)H,6-H = 1.3 Hz, N(1)H), 8.15 (1H, d, JN(3)H,N(1)H = 2.2 Hz, N(3)H), 7.24–7.41
3
(7H, m, ArH), 7.09–7.18 (3H, m, ArH), 5.86 (1H, dd, J7-H,6-H = 8.2,
3J7-H,N(1)H = 5.7 Hz, 7-H), 5.16 (1H, dd, J6-H,7-H = 8.2, J6-H,N(1)H = 1.3 Hz, 6-H);
13C NMR (75.48 MHz, DMSO-d6) d 164.5 (C-2), 143.7 (C-4), 137.9 (C), 136.5 (C),
129.3 (C-7), 128.97 (2CH), 128.95 (2CH), 128.6 (CH), 127.8 (2CH), 126.7 (2CH),
125.4 (CH), 114.6 (C-6), 112.7 (C-5). Anal. Calcd for C17H14N2OS: C, 69.36; H,
4.79; N, 9.52. Found: C, 69.03; H, 4.87; N, 9.79.
3
4
Synthesis of 4b: Compound 4b (0.297 g, 54%; light yellow solid) was obtained
from 3b (0.612 g, 1.97 mmol) in DMSO (5 mL) (132–134 °C, 30 min) after
column chromatography on silica gel 60, eluting with CHCl3/acetone (from 1:0
to 25:1), as described for 4a. Mp 195.5 °C (dec., MeCN). IR (Nujol) m
, cmÀ1: 3318
(s), 3249 (m), 3185 (m), 3148 (m) (NH), 3063 (w) (C(sp2)H), 1707 (s) (C@O),
1662 (m), 1625 (s) (C@C), 1496 (w) (CCarom), 1285 (s), 1149 (s) (SO2), 808 (m)
(CHarom); 1H NMR (300.13 MHz, DMSO-d6) d 8.19–8.24 (2H, m, N(1)H and
3
N
(3)H), 7.66–7.72 (2H, m, ArH), 7.39–7.45 (2H, m, ArH), 5.73 (1H, dd, J7-H,6-
H = 8.7, 3J7-H,N(1)H = 5.5 Hz, 7-H), 5.43 (1H, ddq, 3J6-H,7-H = 8.7, 4J6-H,N(1)H = 1.2, 5J6-
H,CH3 = 0.9 Hz, 6-H), 2.39 (3H, s, CH3 in Ts), 2.13 (3H, d, 5JCH3,6-H = 0.9 Hz, 4-CH3);
13C NMR (75.48 MHz, DMSO-d6) d 161.4 (C-2), 147.0 (C-4), 143.6 (C), 139.4 (C),
129.9 (2CH), 127.1 (C-7), 126.3 (2CH), 120.9 (C-5), 107.6 (C-6), 21.0 (CH3 in Ts),
20.2 (4-CH3). Anal. Calcd for C13H14N2O3S: C, 56.10; H, 5.07; N, 10.07. Found: C,
56.12; H, 5.18; N, 10.16.
Acknowledgements
This research was supported by the Russian Foundation for
Basic Research (No. 12-03-31853) and the Presidential Grant for
Young Scientists (No. MK-2956.2013.3).
Synthesis of 4c: Compound 4c (0.314 g, 53%; light yellow solid) was obtained
from 3c (0.653 g, 1.75 mmol) in DMSO (3.5 mL) (133–135 °C, 30 min) after
column chromatography on silica gel 60, eluting with CHCl3/acetone (from 1:0
to 100:1), as described for 4a. Mp 188.5–189 °C (dec., MeCN). IR (Nujol) m,
cmÀ1: 3335 (s), 3269 (s), 3166 (m) (NH), 3081 (w), 3065 (w), 3015 (w) (C(sp2)H),
1709 (s) (C@O), 1658 (s), 1618 (s) (C@C), 1595 (m), 1486 (w) (CCarom), 1311 (s),
1154 (s) (SO2), 812 (s) (CHarom in Ts), 704 (s) (CHarom in Ph); 1H NMR
Supplementary data
3
4
(300.13 MHz, DMSO-d6)
d 8.33 (1H, ddd, JN(1)H,7-H = 5.6, JN(1)H,N(3)H = 2.1,
4
Supplementary data (IR, 1H and 13C NMR spectra of 4a–c, 7a, b
and computational data) associated with this article can be found,
01.037. These data include MOL files and InChiKeys of the most
important compounds described in this article.
4JN(1)H,6-H = 1.2 Hz, N(1)H), 8.22 (1H, d, JN(3)H,N(1)H = 2.1 Hz, N(3)H), 7.27–7.43
(7H, m, ArH), 7.10–7.15 (2H, m, ArH), 5.86 (1H, dd, J7-H,6-H = 8.5,
3
3J7-H,N(1)H = 5.6 Hz, 7-H), 5.55 (1H, dd, J6-H,7-H = 8.5, J6-H,N(1)H = 1.2 Hz, 6-H),
2.36 (3H, s, CH3); 13C NMR (75.48 MHz, DMSO-d6) d 161.5 (C-2), 147.8 (C-4),
143.3 (C), 139.0 (C), 135.6 (C), 129.4 (2CH), 129.11 (2CH), 129.08 (C-7), 129.0
(CH), 127.5 (2CH), 126.6 (2CH), 123.1 (C-5), 108.1 (C-6), 21.0 (CH3). Anal. Calcd
for C18H16N2O3S: C, 63.51; H, 4.74; N, 8.23. Found: C, 63.34; H, 4.86; N, 8.25.
7. Synthesis of 7a. Method A: A solution of 4a (0.065 g, 0.22 mmol) in py (2 mL)
was refluxed for 7 h under stirring and then the solvent was removed under
3
4
References and notes
vacuum. The residue was cooled and triturated with H2O (1 mL) until
a
suspension formed. The precipitate was filtered, washed with cold dilute HCl,
ice-cold H2O, petroleum ether, and dried to give 7a (0.061 g, 95%; light orange
solid) as a mixture of (E)- and (Z)-isomers (93:7).
Method B: Compound 7a (0.421 g, 77%; light orange solid) as a single (E)-isomer
was obtained from 3a (0.609 g, 1.86 mmol) in py (9.6 mL) (reflux, 7 h) after
column chromatography on silica gel 60, eluting with CHCl3/MeOH (from 1:0
to 200:1), as described in Method A.
Method C: Compound 7a (0.170 g, 37%; light orange solid) as a mixture of
(E)- and (Z)-isomers (96:4) was obtained from 11 (0.617 g, 1.58 mmol) and
DBU (0.060 g, 0.39 mmol) in py (10 mL) (reflux, 6 h) after column
chromatography on silica gel 60, eluting with CHCl3, as described in Method
A. Mp 214.5–215 °C (dec., petroleum ether–EtOAc, 1:1). IR (Nujol) m :
, cmÀ1
3419 (m), 3303 (m), 3222 (m), 3132 (br m) (NH), 3079 (w), 3069 (w), 3063 (w),
3046 (w) (CHarom), 1669 (s) (C@O, C@C), 1628 (m) (NH2), 1581 (w) (CCarom),
1556 (s) (amide-II), 1489 (w) (CCarom), 770 (s), 729 (s), 691 (s) (CHarom); 1H
NMR of the major isomer (300.13 MHz, DMSO-d6) d 10.59 (1H, br s, N(1)H), 8.36
(1H, br dd, 3JNH(A),CH = 15.1, 2JNH(A),NH(B) = 4.7 Hz, NH(A) in NH2), 7.90 (1H, br dd,
2
3JNH(B),CH = 7.6, JNH(B),NH(A) = 4.7 Hz, NH(B) in NH2), 7.64–7.70 (2H, m, ArH),
3
3
7.22–7.40 (5H, m, ArH), 7.13 (1H, dd, JCH,NH(A) = 15.1, JCH,NH(B) = 7.6 Hz, CH@),