Synthesis of 1,3,4-oxadiazinium bromides from 1,1-dimethylhydrazine derivatives and 1,3-dibromopropyne

Article abstract of DOI:10.1007/s11176-005-0246-6

2-Aryl(heteryl, dimethylamino)-6-bromomethylidene-4,4-dimethyl-5H-1,3,4- oxadiazinium bromides were prepared in good yields by the reactions of 1-aroyl(heteroyl)-2,2-dimethylhydrazines and 1,1,4,4-tetramethylsemicarbazide with 1,3-dibromopropyne in MeOH o

Full text of DOI:10.1007/s11176-005-0246-6

Russian Journal of General Chemistry, Vol. 75, No. 3, 2005, pp. 437 439. Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 3, 2005,
pp. 473 475.
Original Russian Text Copyright
2005 by Nakhmanovich, Elokhina, Larina, Abramova, Lopyrev.
Synthesis of 1,3,4-Oxadiazinium Bromides
from 1,1-Dimethylhydrazine Derivatives
and 1,3-Dibromopropyne
A. S. Nakhmanovich, V. N. Elokhina, L. I. Larina, E. V. Abramova, and V. A. Lopyrev
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, Irkutsk, Russia
Received October 13, 2003
Abstract 2-Aryl(heteryl, dimethylamino)-6-bromomethylidene-4,4-dimethyl-5H-1,3,4-oxadiazinium bro-
mides were prepared in good yields by the reactions of 1-aroyl(heteroyl)-2,2-dimethylhydrazines and
1,1,4,4-tetramethylsemicarbazide with 1,3-dibromopropyne in MeOH or MeCN at 20 50 C.
Among diverse transformations of 1,1-dimethylhy-
drazine and its derivatives, their quaternization with
haloalkynes has been studied relatively poorly. The
reactions of 1,1-dimethylhydrazine with propargyl
bromide [1] and propargyl chloride [2] yield 1,1-di-
methyl-1-(propyn-2-yl)hydrazinium bromide and chlo-
ride, respectively. Aroylethynyl bromides react with
1,1-dimethylhydrazine in MeCN at 20 C to give 1-(1-
bromo-2-aroylvinyl)-1,1-dimethylhydrazinium bro-
mides [3]. The reactions of 1,1-dimethylhydrazines
with propargyl bromide and 1,3-dibromopropyne in
MeCN and benzene at 20 C gave in 30 72% yields
the corresponding 1,1-dimethyl-1-(prop-2-ynyl)- and
1,1-dimethyl-1-(3-bromoprop-2-ynyl)hydrazinium
bromides [4].
We found that the reactions of 1-benzoyl-, 1-(4-
bromobenzoyl)-, 1-(2-chlorobenzoyl)-, 1-(4-toluyl)-,
1-(2-thenoyl), and 1-(2-furoyl)-2,2-dimethylhydrazines
Ia If and of 1,1,4,4-tetramethylsemicarbazide Ig with
1,3-dibromopropyne yield 2-aryl(heteryl, dimethyl-
amino)-6-bromomethylidene-4,4-dimethyl-5H-1,3,4-
oxadiazinium bromides IVa IVg. In the first step, hy-
drazines Ia If are alkylated with 1,3-dibromopropyne
at the tertiary nitrogen atom to give 1-aroyl(heteroyl)-
2-(3-bromoprop-2-ynyl)-2,2-dimethylhydrazinium
bromides.
O
O
+
BrC C CH2Br
Me2N NH C R
Me2N NH C R
Br
Br
H2C C CBr
Ia Ig
IIa IIg
R
+
+ N
Me2N
C
Me2N NH=C R
O Br
:OH
H2C C CBr
H2C
CHBr
IVa IVg
IIIa IIIg
R = Ph (a), 4-BrC6H4 (b), 2-ClC6H4 (c), 4-MeC6H4 (d), 2-thienyl (e), 2-furyl (f), Me2N (g).
Although formation of isomeric products, 1-aroyl-
(heteroyl)-2-(3-bromoprop-1-ynyl)-2,2-dimethylhydra-
zinium bromides, could also be expected, our previous
studies [4] of the reactions of 1,1-dimethylhydrazones
with 1,3-dibromopropyne and propargyl bromide
showed that the tertiary nitrogen atom is alkylated
exclusively with the CH2Br fragment. The amide
imide tautomerism of bromides IIa IIf in MeOH or
1070-3632/05/7503-0437 2005 Pleiades Publishing, Inc.

438
NAKHMANOVICH et al.
MeCN solutions results in formation of intermediates
IIIa IIIf, which undergo intramolecular cyclization to
give 1,3,4-oxadiazinium bromides IVa IVf. The struc-
ture of the compounds was proved by elemental anal-
2-(4-Bromophenyl)-6-bromomethylidene-4,4-di-
methyl-5H-1,3,4-oxadiazinium bromide IVb and
1-(4-bromobenzoyl)-2-(3-bromoprop-2-ynyl)-2,2-di-
methylhydrazinium bromide IIb. A solution of 1.78 g
of 1,3-dibromopropyne in 10 ml of MeCN was added
with stirring to a solution of 2.37 g of 1-(4-bromoben-
zoyl)-2,2-dimethylhydrazine Ib in 40 ml of MeCN.
The mixture was stirred for 20 h at 20 C and then
cooled to 0 C. The precipitate was filtered off, washed
on the filtrate with cold MeCN, and vacuum-dried.
Yield of IVb 1.2 g (28%), colorless crystals, mp 154
1
ysis and by H, 13C, and 15N NMR and IR spectros-
copy. The suggested mechanism is confirmed by iso-
lation of 1-(4-bromobenzoyl)-2-(3-bromoprop-2-ynyl)-
2,2-dimethylhydrazinium bromide IIb along with
1,3,4-oxadiazinium bromide IVb in the reaction of
1-(4-bromobenzoyl)-2,2-dimethylhydrazine Ib with
1,3-dibromopropyne.
1
155 C (from acetone). IR spectrum, , cm : 2920
1,1,4,4-Tetramethylsemicarbazide Ig reacts with
1,3-dibromopropyne similarly to give 2-dimethylami-
no-6-bromomethylidene-4,4-dimethyl-5H-1,3,4-oxa-
diazinium bromide IVg in a good yield (76%). The
starting 1,1,4,4-tetramethylsemicarbazide Ig was pre-
pared by the reaction of N,N-dimethylcarbamoyl
chloride with 1,1-dimethylhydrazine in benzene in the
presence of triethylamine at 20 C in 65% yield by the
procedure described in [5].
(CH2), 1625 (C=N), 1580 (C=C), 720 (CBr). 1H
NMR spectrum, , ppm: 3.56 s (6H, Me), 5.02 s (2H,
CH2), 6.84 s (1H, =CHBr), 7.68 7.86 m (4H, C6H4).
13C NMR spectrum, C, ppm: 56.3 (Me), 57.8 (CH2),
95.7 (=CHBr), 126.7 132.7 (C6H4), 139.7 (C=CHBr),
157.4 (C=N). 15N NMR spectrum (reference MeNO2),
N, ppm: 117.6 (N=C), 289.0 (N+Me2). Found, %:
C 32.23; H 2.84; Br 54.61; N 6.49. C12H13Br3N2O.
Calculated, %: C 32.69; H 2.97; Br 54.36; N 6.35.
EXPERIMENTAL
The filtrate after the separation of IVb was concen-
trated, cold diethyl ether was added with vigorous
stirring, and the mixture was cooled to 0 C to precipi-
tate IIb. Yield of IIb 1.37 g (32%), pink crystals, mp
The IR spectra were taken on a Specord IR-75
spectrophotometer (KBr pellets). The H, 13C, and
15N NMR spectra were recorded at 20 C on a Bruker-
400 spectrometer (400.13, 100.62, and 40.54 MHz,
respectively) in DMSO-d6. The internal references
were HMDS and MeNO2.
1
1
156 157 C. IR spectrum, , cm : 3420 (NH), 2930
(CH2), 2240 (C C), 1640 (C=O), 680 (CBr). 1H NMR
spectrum, , ppm: 3.53 s (6H, Me), 4.91 s (2H, CH2),
7.68 7.88 m (4H, C6H4), 10.68 s (1H, NH). Found,
%: C 32.49; H 3.22; Br 53.65; N 6.56. C12H13Br3N2O.
Calculated, %: C 32.69; H 2.97; Br 54.36; N 6.35.
1-Aroyl(heteroyl)-2,2-dimethylhydrazines Ia If
were prepared as described in [6] from 1,1-dimethyl-
hydrazine and benzoyl, 4-bromobenzoyl, 4-chloroben-
zoyl, 4-toluyl, 2-thenoyl, and 2-furoyl chlorides in
benzene at 20 C.
2-(2-Chlorophenyl-5-bromomethylidene-4,4-di-
methyl-5H-1,3,4-oxadiazinium bromide IVc was
prepared similarly to IVa from a mixture of 4.0 g of
1-(2-chlorobenzoyl)-2,2-dimethylhydrazine Ic and
3.96 g of 1,3-dibromopropyne in MeCN. Yield
3.26 g (41%), colorless crystals, mp 170 172 C (from
2-Phenyl-6-bromomethylidene-4,4-dimethyl-5H-
1,3,4-oxadiazinium bromide IVa. A solution of
1.8 g of 1,3-dibromopropyne in 20 ml of absolute
MeOH was slowly added with stirring to a solution
of 1.5 g of 1-benzoyl-2,2-dimethylhydrazine Ia in
30 ml of absolute MeOH. The mixture was heated to
50 C, stirred at this temperature for 5 h, and cooled
to 0 C. The precipitate was filtered off, washed on the
filter with cold ether, and dried in a vacuum. Yield of
1,3,4-oxadiazinium bromide IVa 3.0 g (91%); color-
less crystalline substance, mp 148 149 C. IR spec-
1
MeCN). IR spectrum, , cm : 2925 (CH2), 1630
1
(C=N), 1590 (C=C), 740 (CCl). H NMR spectrum,
, ppm: 3.55 d (6H, Me), 5.08 d (2H, CH2), 6.85 s
(1H, =CHBr), 6.85 7.67 m (4H, C6H4). 13C NMR
spectrum, C, ppm: 55.4 (Me), 57.2 (CH2), 95.6
(=CHBr), 126.6 134.0 (C6H4), 139.2 (C=CHBr),
157.8 (C=N). Found, %: C 36.27; H 3.88; Br 40.44;
Cl 9.32; N 7.08. C12H13Br2ClN2O. Calculated, %: C
36.26; H 3.55; Br 40.20; Cl 9.07; N 7.05.
1
trum, , cm : 2950 (CH2), 1610 (C=N), 1570 (C=C),
690 (CBr). H NMR spectrum, , ppm: 3.53 d (6H,
1
2-(4-Toluyl)-6-bromomethylidene-4,4-dimethyl-
5H-1,3,4-oxadiazinium bromide IVd was prepared
similarly to IVa from a mixture of 1.0 g of 1-(4-tolyl)-
2,2-dimethylhydrazine Id and 1.1 g of 1,3-dibromo-
propyne (reaction time 7 h). Yield 1.5 g (71%), color-
less crystals, mp 144 145 C (from MeCN). IR spec-
Me), 4.91 s (2H, CH2), 6.80 s (1H, =CHBr), 7.61
7.98 m (5H, Ph). 13C NMR spectrum, C, ppm: 55.7
(Me), 57.3 (CH2), 94.8 (C=CHBr), 124.5 133.7 (Ph),
139.1 (CHBr), 157.2 (C=N). Found, %: C 39.64; H
3.85; Br 44.45; N 7.91. C12H14Br2N2O. Calculated,
%: C 39.78; H 3.87; Br 44.20; N 7.93.
1
trum, , cm : 2921 (CH2), 1614 (C=N), 1568 (C=C),
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005

SYNTHESIS OF 1,3,4-OXADIAZINIUM BROMIDES
439
1
683 (CBr). H NMR spectrum, , ppm: 3.15 s (3H,
148.93 (C5), 150.61 (C=N). Found, %: C 34.37; H
3.33; Br 45.65; N 8.02. C10H12Br2N2O2. Calculated,
%: C 34.09; H 3.41; Br 45.45; N 7.95.
C6H4Me), 3.50 s (6H, NMe2), 4.88 d (2H, CH2, J
6.0 Hz), 6.78 s (1H, =CHBr), 7.43 7.87 m (4H,
C6H4). 13C NMR spectrum, C, ppm: 21.3 (C6H4CH3),
55.9 (NMe), 57.5 (CH2), 94.9 (=CHBr), 124.0 129.7
(C6H4), 144.6 (C=CHBr), 157.4 (C=N). Found, %:
C 41.40; H 4.48; Br 42.82; N 7.20. C12H16Br2N2O.
Calculated, %: C 41.49; H 4.25; Br 42.55; N 7.45.
2-Dimethylamino-6-bromomethylidene-4,4-di-
methyl-5H-1,3,4-oxadiazinium bromide IVg was
prepared similarly to IVa from 1.0 g of 1,1,4,4-tetra-
methylsemicarbazide Ig and 1.51 g of 1,3-dibromo-
propyne in MeCN at 80 C. Yield 2.0 g (76%), mp
1
2-(2-Thienyl)-6-bromomethylidene-4,4-dimethyl-
5H-1,3,4-oxadiazinium bromide IVe was prepared
similarly to IVa from 1.7 g of 1-(2-thenoyl)-2,2-di-
methylhydrazine Ie and 3.58 g of 1,3-dibromoprop-
yne. Yield 3.59 g (68%), colorless crystals, mp 136
138 C. IR spectrum, , cm : 2950 (CH2), 1600
(C=N), 1565 (C=C), 730 (CBr), 690 (CS). H NMR
180 182 C. IR spectrum, , cm : 1590 (C=C), 1445
1
(C=N), 1280 (CN), 1070 (COC), 545 (CBr). H NMR
spectrum (DMSO-d6), , ppm: 6.54 s (1H, =CH), 4.61
s (2H, CH2), 3.32 s (6H, N+Me2), 2.92 s (6H, NMe2).
13C NMR spectrum (DMSO-d6), C, ppm: 153.61
(C=N), 140.05 (CH2C=), 91.88 (CHBr), 57.99 (CH2),
56.74 (N+Me2), 36.18 (NMe2). 15N NMR spectrum
1
1
spectrum (DMSO-d6), , ppm: 3.50 s (6H, 2CH3),
4.89 s (2H, CH2), 6.78 s (1H, =CHBr), 7.32 d.d (1H,
(DMSO-d6),
, ppm: 319.2 (NMe2), 296.2
N
(N+Me2), 171.1 (C=N). Found, %: C 28.95; H 4.42;
Br 48.48; N 12.56. C8H15Br2N3O. Calculated, %: C
29.18; H 4.56; Br 48.63; N 12.77.
3
3
3
H3, J 5.0, J 3.4 Hz), 7.88 d (1H, H4, J 3.4 Hz),
8.09 d (1H, H2, 3J 5.0 Hz). 13C NMR spectrum
(DMSO-d6), C, ppm: 56.0 (CH3), 57.9 (CH2), 95.05
(=CHBr), 128.66 (C2), 128.80 (C5), 133.32 (C3),
135.04 (C4), 139.26 (C=CHBr), 154.56 (C=N).
Found, %: C 32.35; H 3.15; Br 43.65; N 7.82; S 8.73.
C10H12Br2N2OS. Calculated, %: C 32.61; H 3.26;
Br 43.48; N 7.61; S 8.70.
REFERENCES
1. Smith, R.F. and Coffman, K.I., Synth. Commun., 1982,
vol. 12, no. 10, p. 801.
2. Konig, K.H. and Zeeh, B., Chem. Ber., 1970, vol. 103,
2-(2-Furyl)-6-bromomethylidene-4,4-dimethyl-
5H-1,3,4-oxadiazinium bromide IVf was prepared
similarly to IVa from 1.54 g of 1-(2-furoyl)-2,2-di-
methylhydrazine If and 3.58 g of 1,3-dibromopropyne.
Yield 4.45 g (87%), colorless crystals, mp 141 142 C.
no. 7, p. 2052.
3. Elokhina, V.N., Nakhmanovich, A.S., Larina, L.I.,
Shishkin, O.V., Baumer, V.N., and Lopyrev, V.A., Izv.
Ross. Akad. Nauk, Ser. Khim., 1999, no. 8, p. 1536.
1
4. Elokhina, V.N., Nakhmanovich, A.S., Karnaukho-
va, R.V., Larina, L.I., and Lopyrev, V.A., Zh. Org.
Khim., 2000, vol. 36, no. 4, p. 502.
IR spectrum, , cm : 2920 (CH2), 1610 (C=N), 1560
1
(C=C), 710 (CBr). H NMR spectrum (DMSO-d6), ,
ppm: 3.44 s (6H, 2CH3), 4.84 s (2H, CH2), 6.77 s
3
3
(1H, CH), 6.84 d.d (1H, H4, J 3.7, J 1.8 Hz), 7.41
5. Smith, R.F., Blondell, R.D., Abgott, R.A., Lipko-
witz, K.B., Richmond, J.A., and Fountain, K.A., J. Org.
Chem., 1974, vol. 39, no. 14, p. 2036.
d.d (1H, H3, J 3.7, J 0.7 Hz), 8.14 d.d (1H, H5, J
3
4
3
1.8, J 0.7 Hz). 13C NMR spectrum (DMSO-d6),
,
4
C
ppm: 56.09 (CH3), 58.08 (CH2), 95.12 (CH), 113.13
(C3), 118.84 (C4), 139.00 (C2), 140.53 (C=CHBr),
6. Hinman, R.L., J. Am. Chem. Soc., 1956, vol. 78, no. 8,
p. 1645.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005