Reactions of 1,3-dibromopropyne with 1-aroyl-2,2-dimethylhydrazines as a new method for the synthesis of substituted 1,3,4-oxadiazinium bromides

Article abstract of DOI:10.1023/A:1015028806581

Reactions of 1-aroyl-2,2-dimethylhydrazines with 1,3-dibromopropyne in MeOH or MeCN at 20-50 °C yield 2-aryl-6-bromomethylidene-4,4-dimethyl-5H-1,3,4-oxadiazinium bromides.

Full text of DOI:10.1023/A:1015028806581

Russian Chemical Bulletin, International Edition, Vol. 50, No. 12, pp. 2475—2476, December, 2001
2475
Reactions of 1,3-dibromopropyne with 1-aroyl-2,2-dimethylhydrazines
as a new method for the synthesis of substituted
1,3,4-oxadiazinium bromides
R. V. Karnaukhova, T. V. Nizovtseva, A. S. Nakhmanovich,« A. I. Albanov, and T. N. Komarova
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences,
1 ul. Favorskogo, 664033 Irkutsk, Russian Federation.
Fax: +7 (395 2) 51 1432. E-mail: k301@irioch.irk.ru
Reactions of 1-aroyl-2,2-dimethylhydrazines with 1,3-dibromopropyne in MeOH or
MeCN at 20—50 °C yield 2-aryl-6-bromomethylidene-4,4-dimethyl-5H-1,3,4-oxadiazinium
bromides.
Key words: 1-aroyl-2,2-dimethylhydrazines, 1,3-dibromopropyne, substituted 1,3,4-oxa-
diazinium bromides, amide-imide tautomerism, alkylation.
Scheme 1
Among a variety of transformations of 1,1-dimethyl-
hydrazine and its derivatives, their quaternization with
alkynyl halides is studied insufficiently to date.
Br
O
The known reactions of 1,1-dimethylhydrazine with
propargyl bromide1 and propargyl chloride2 yield 1,1-di-
methyl-1-(prop-2-ynyl)hydrazinium bromide and chlo-
ride, respectively. Aroylethynyl bromides react with
1,1-dimethylhydrazine to give 1-(2-aroyl-1-bromovinyl)-
1,1-dimethylhydrazinium bromides.3 The reactions
of 1,1-dimethylhydrazones with propargyl bromide
and 1,3-dibromopropyne afford 1,1-dimethyl-1-(prop-
2-ynyl)hydrazonium and 1-(3-bromoprop-2-ynyl)-
1,1-dimethylhydrazonium bromides, respectively, in
30—72% yield.4
O
Me2N NH C
1a—d
Me2N NH C
H2C CBr
R
BrC
C CH2Br
R
C
3a—d
R
Me2N N C
R
N
C
C
:OH Br
Me2N
H2C
O Br
CHBr
H2C
C
CBr
2a—d
4a—d
Results and Discussion
R = Ph (a), 4-BrC6H4 (b), 2-ClC6H4 (c), 4-MeC6H4 (d)
We found that the reactions of 1-benzoyl-, 1-(4-bro-
mobenzoyl)-, and 1-(2-chlorobenzoyl)-2,2-dimethyl-
hydrazines and 2,2-dimethyl-1-(4-toluyl)hydrazine
(1a—d) with 1,3-dibromopropyne give 2-aryl-6-bromo-
methylidene-4,4-dimethyl-5H-1,3,4-oxadiazinium bro-
mides 2a—d. Initially, 1-aroyl-2,2-dimethylhydrazines
1a—d are alkylated with 1,3-dibromopropyne at the
tertiary N atom to form 1-aroyl-2-(3-bromoprop-2-ynyl)-
2,2-dimethylhydrazinium bromides (3a—d) (Scheme 1).
The formation of isomeric compounds, namely,
1-aroyl-2-(3-bromoprop-1-ynyl)-2,2-dimethylhydrazi-
nium bromides, could be expected. However, when
studying the reactions of 1,1-dimethylhydrazones with
1,3-dibromopropyne and propargyl bromide,4 we have
demonstrated that the tertiary N atom is alkylated ex-
clusively with the CH2Br fragment.
the latter were proved by elemental analysis and IR and
1H, 13C, and 15N NMR data.
In the reaction of 1-(4-bromobenzoyl)-2,2-dimethyl-
hydrazine (1b) with 1,3-dibromopropyne, we isolated
not only 1,3,4-oxadiazinium bromide 2b, but also
1-(4-bromobenzoyl)-2-(3-bromoprop-2-ynyl)-2,2-di-
methylhydrazinium bromide (3b), which confirms the
suggested reaction mechanism (see Scheme 1).
Hence, we proposed a new method for the synthesis
of 2-aryl-6-bromomethylidene-4,4-dimethyl-5H-1,3,4-
oxadiazinium bromides by the reactions of 1-aroyl-2,2-
dimethylhydrazine with 1,3-dibromopropyne.
Experimental
As a result of amide-imide tautomerism,5,6 bromides
3a—d in MeOH or MeCN pass into intermediates 4a—d,
which undergo intramolecular cyclization to give
1,3,4-oxadiazinium bromides 2a—d. The structures of
IR spectra were recorded on a Specord IR-75 instrument
1
(KBr pellets). H, 13C, and 15N NMR spectra were recorded
on a Bruker DPX-400 spectrometer (400.13, 100.62, and
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2363—2364, December, 2001.
1066-5285/01/5012-2475 $25.00 © 2001 Plenum Publishing Corporation

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Russ.Chem.Bull., Int.Ed., Vol. 50, No. 12, December, 2001
Karnaukhova et al.
40.54 MHz, respectively) in DMSO-d6 at 20 °C with HMDS
as the internal standard.
3.56 (s, 6 H, Me); 5.02 (s, 2 H, CH2); 6.84 (s, 1 H, =CHBr);
7.68—7.86 (m, 4 H, C6H4). 13C NMR, δ: 56.3 (Me); 57.8
(CH2); 95.7 (=CHBr); 126.7—132.7 (C6H4); 139.7 (C=CHBr);
157.4 (C=N). 15N NMR (relative to MeNO2 as the standard),
δ: –117.6 (N=C); –289.0 (N+Me2).
1-Benzoyl-2,2-dimethylhydrazine (1a) was synthesized as
described earlier5 from 1,1-dimethylhydrazine (3 g, 0.05 mol)
and benzoyl chloride (7.03 g, 0.05 mol) in benzene at 20 °C.
The yield of compound 1a was 1.7 g (21%), white crystals,
m.p. 106—107 °C (from CCl4). Found (%): C, 65.63; H, 7.31;
N, 16.95. C9H12N2O. Calculated (%): C, 65.83; H, 7.37;
N, 17.06. IR, ν/cm–1: 3190 (NH); 1640 (C=O).
1-(4-Bromobenzoyl)-2,2-dimethylhydrazine (1b) was ob-
tained from 4-bromobenzoyl chloride (4.4 g, 0.02 mol) and
1,1-dimethylhydrazine (2.4 g, 0.04 mol) in THF at 40 °C. The
yield of compound 1b was 3.7 g (77%), white crystals, m.p.
148—150 °C (from MeCN). Found (%): C, 44.12; H, 4.82;
Br, 32.74; N, 11.23. C9H11BrN2O. Calculated (%): C, 44.47;
H, 4.56; Br, 32.87; N, 11.52. IR, ν/cm–1: 3200 (NH);
1640 (C=O).
1-(2-Chlorobenzoyl)-2,2-dimethylhydrazine (1c) was syn-
thesized from 1,1-dimethylhydrazine (7.2 g, 0.12 mol) and
2-chlorobenzoyl chloride (10.5 g, 0.06 mol) in THF at 40 °C.
The yield of compound 1c was 6.9 g (58%), white crystals,
m.p. 150—152 °C (from CCl4). Found (%): C, 54.30; H, 6.01;
Cl, 18.20; N, 14.52. C9H11ClN2O. Calculated (%): C, 54.42;
H, 5.58; Cl, 17.85; N, 14.10. IR, ν/cm–1: 3180 (NH);
1640 (C=O).
2,2-Dimethyl-1-(4-toluyl)hydrazine (1d) was obtained from
4-toluyl chloride (5.0 g, 32 mmol) and 1,1-dimethylhydrazine
(3.9 g, 65 mmol) in THF at 40 °C. The yield of compound 1d
was 3.5 g (61%), white crystals, m.p. 103—105 °C (from
MeCN). Found (%): C, 67.32; H, 8.25; N, 15.98. C10H14N2O.
Calculated (%): C, 67.41; H, 7.86; N, 15.73. IR, ν/cm–1: 3222
(NH); 1646 (C=O).
The filtrate was concentrated, cold diethyl ether was added
with vigorous stirring, and the mixture was cooled to 0 °C. The
precipitate that formed was filtered off, washed with cold
ether, and dried in vacuo. The yield of compound 3b was
1.37 g (32%), pink crystals, m.p. 156—157 °C. Found (%):
C, 32.49; H, 3.22; Br, 53.95; N, 6.56. C12H13Br3N2O. Calcu-
–1
lated (%): C, 32.69; H, 2.97; Br, 54.36; N, 6.35. IR, ν/cm
:
3420 (NH); 2930 (CH2); 2240 (C≡C); 1640 (C=O); 680
(C—Br). 1H NMR, δ: 3.53 (s, 6 H, Me); 4.91 (s, 2 H, CH2);
7.68—7.88 (m, 4 H, C6H4); 10.68 (s, 1 H, NH).
6-Bromomethylidene-2-(2-chlorophenyl)-4,4-dimethyl-5H-
1,3,4-oxadiazinium bromide (2c) was obtained as described for
compound 2b from 1-(2-chlorobenzoyl)-2,2-dimethylhydrazine
(1c) (4.0 g, 0.02 mol) and 1,3-dibromopropyne (3.96 g,
0.02 mol) in MeCN. The yield of compound 2c was 3.26 g
(41%), white crystals, m.p. 170—172 °C (from MeCN).
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. IR, ν/cm–1: 2925 (CH2); 1630 (C=N); 1590
(C=C); 740 (C−Cl). 1H NMR, δ: 3.55 (d, 6 H, Me); 5.08 (d,
2 H, CH2); 6.85 (s, 1 H, =CHBr); 6.85—7.67 (m, 4 H, C6H4).
13C NMR, δ: 55.4 (Me); 57.2 (CH2); 95.6 (=CHBr);
126.6—134.0 (C6H4); 139.2 (C=CHBr); 157.8 (C=N).
6-Bromomethylidene-4,4-dimethyl-2-(4-tolyl)-5H-1,3,4-
oxadiazinium bromide (2d) was obtained analogously from
2,2-dimethyl-1-(4-toluyl)hydrazine (1d) (1.0 g, 56 mmol) and
1,3-dibromopropyne (1.1 g, 56 mmol) over 7 h. The yield of
compound 2d was 1.5 g (71%), white crystals, m.p. 144—145 °C
(from MeCN). Found (%): C, 41.40; H, 4.48; Br, 42.82;
N, 7.20. C13H16Br2N2O. Calculated (%): C, 41.49; H, 4.25;
Br, 42.55; N, 7.45. IR, ν/cm–1: 2921 (CH2); 1614 (C=N);
1568 (C=C); 683 (C—Br). 1H NMR, δ: 3.15 (s, 3 H,
C6H4—Me); 3.50 (s, 6 H, NMe2); 4.88 (d, 2 H, CH2,
J = 6.0 Hz); 6.78 (s, 1 H, =CHBr); 7.43—7.87 (m, 4 H,
C6H4). 13C NMR, δ: 21.3 (C6H4—CH3); 55.9 (N—Me); 57.5
(CH2); 94.9 (=CHBr); 124.0—129.7 (C6H4); 144.6 (C=CHBr);
157.4 (C=N).
6-Bromomethylidene-4,4-dimethyl-2-phenyl-5H-1,3,4-
oxadiazinium bromide (2a). A solution of 1,3-dibromopropyne
(1.8 g, 9 mmol) in 20 mL of anhydrous MeOH was slowly
added with stirring to a solution of 1-benzoyl-2,2-dimethylhy-
drazine (1a) (1.5 g, 9 mmol) in 30 mL of anhydrous MeOH.
The reaction mixture was heated to 50 °C, stirred at this
temperature for 5 h, and then cooled to 0 °C. The precipitate
that formed was filtered off, washed with cold ether, and dried
in vacuo. The yield of 1,3,4-oxadiazinium bromide 2a was
3.0 g (91%), white crystals, m.p. 148—149 °C. Found (%):
C, 39.64; H, 3.85; Br, 44.45; N, 7.91. C12H14Br2N2O. Calcu-
–1
lated (%): C, 39.78; H, 3.87; Br, 44.20; N, 7.93. IR, ν/cm
:
References
2950 (CH2); 1610 (C=N); 1570 (C=C); 690 (C—Br). 1H NMR,
δ: 3.53 (d, 6 H, Me); 4.91 (s, 2 H, CH2); 6.80 (s, 1 H,
=CHBr); 7.61—7.98 (m, 5 H, Ph). 13C NMR, δ: 55.7 (Me);
57.3 (CH2); 94.8 (C=CHBr); 124.5—133.7 (Ph); 139.1 (CHBr);
157.2 (C=N).
1. R. F. Smith and K. I. Coffman, Synth. Commun.,
1982, 12, 801.
2. K. H. Konig and B. Zeeh, Chem. Ber., 1970, 103, 2052.
3. V. N. Elokhina, A. S. Nakhmanovich, L. I. Larina, O. V.
Shishkin, V. N. Baumer, and V. A. Lopyrev, Izv. Akad.
Nauk, Ser. Khim., 1999, 1536 [Russ. Chem. Bull., 1999, 48,
1516 (Engl. Transl.)].
4. V. N. Elokhina, A. S. Nakhmanovich, R. V. Karnaukhova,
L. I. Larina, and V. A. Lopyrev, Zh. Org. Khim., 2000, 36,
502 [Russ. J. Org. Chem., 2000, 36 (Engl. Transl.)].
5. N. Campbell and A. C. Smith, J. Org. Chem., 1961, 26, 1191.
6. T. I. Temnikova, Kurs teoreticheskikh osnov organicheskoi
khimii [Theoretical Foundations of Organic Chemistry],
Khimiya, Leningrad, 1968, 622 pp. (in Russian).
6-Bromomethylidene-2-(4-bromophenyl)-4,4-dimethyl-5H-
1,3,4-oxadiazinium bromide (2b) and 1-(4-bromobenzoyl)-2-
(3-bromoprop-2-ynyl)-2,2-dimethylhydrazinium bromide (3b).
A solution of 1,3-dibromopropyne (1.78 g, 9 mmol) in
10 mL of MeCN was added with stirring to a solution of
1-(4-bromobenzoyl)-2,2-dimethylhydrazine (1b) (2.37 g,
9 mmol) in 40 mL of MeCN. The reaction mixture was stirred
at 20 °C for 20 h and then cooled to 0 °C. The precipitate that
formed was filtered off, washed with cold MeCN, and dried in
vacuo. The yield of compound 2b was 1.2 g (28%), white
crystals, m.p. 154—155 °C (from acetone). 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. IR, ν/cm–1: 2920
Received June 4, 2001;
in revised form August 29, 2001
1
(CH2); 1625 (C=N); 1580 (C=C); 720 (C—Br). H NMR, δ: