Haloheterocyclization of 2-allyl(propargyl)oxyquinoline-3-carbaldehydes

Article abstract of DOI:10.1007/s10593-007-0159-x

The reaction of 2-allyl(propargyl)oxyquinoline-3-carbaldehydes with halogens gives 1-bromomethyl(bromomethylidene)-4-formyl-1,2-dihydrooxazolo[3,2- a]quinolinium halides.

Full text of DOI:10.1007/s10593-007-0159-x

Chemistry of Heterocyclic Compounds, Vol. 43, No. 8, 2007
HALOHETEROCYCLIZATION
OF 2-ALLYL(PROPARGYL)OXY-
QUINOLINE-3-CARBALDEHYDES
M. Yu. Onysko and V. G. Lendel
The reaction of 2-allyl(propargyl)oxyquinoline-3-carbaldehydes with halogens gives 1-bromo-
methyl(bromomethylidene)-4-formyl-1,2-dihydrooxazolo[3,2-a]quinolinium halides.
Keywords: 2-allyloxy-3-formylquinoline, 3-formyl-2-propargylquinoline, haloheterocyclization.
There are literature reports of the haloheterocyclization reactions of unsaturated quinoline ethers and
thioethers [1] to give heterocyclic systems with oxa(thia)zolinium rings. In continuation of these studies we have
selected the 2-allyl(propargyl)oxyquinoline-3-carbaldehydes 3, 4 as model compounds for this haloheterocyclization.
These substrates were prepared by conversion of 2-chloro-3-formylquinolines 1 to the corresponding quinolones 2 by
treatment with hydrochloric acid and subsequent alkylation using allyl(propargyl) bromides.
O
O
O
H O, HCl
2
R
N
Cl
R
N
OH
R
N
O
2
a,b
H
1
a,b
CH =CHCH Br
2
2
HC
KOH
CCH Br
2
KOH
O
O
5
4
3
6
7
1
2
O
O
R
N
R
N
8
4
a,b
X2
3
a,b
X2
O
O
O
–
–
n+1
X
2n+1
X 2
+
N
+
N
R
R
O
X
X
7, 8a,b
5
, 6a,b
1
–8 a R = H, b R = Me; 5, 7 Х = Br, n = 0; 6, 8 X = I , n = 1
_
_________________________________________________________________________________________
Uzhgorod National University, Uzhgorod 88000, Ukraine; e-mail: muonysko@list.ru, e-mail:
depchem@univ.uzhgorod.ua. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1204-1207,
August, 2007. Original article submitted March 30, 2006.
1
020
0009-3122/07/4308-1020©2007 Springer Science+Business Media, Inc.

Bromine and iodine were selected as electrophilic agents for the haloheterocyclization. The reactions of
the allyl ethers 3 were carried out in acetic acid or methylene chloride with a twofold excess of the halogen. The
resulting 3-halomethyl-2,3-dihydrooxazolo[3,2-a]quinolinium halides 5, 6 were treated with acetone to give the
monobromide 5 and the triiodide 6. Similar halogenation of the propargyl ethers 4 and work up of the
precipitates obtained with acetone gave compounds 7 and 8.
1
The H NMR spectra of compounds 5 and 6 showed proton signals for the OCH and CH Br groups as
2
2
1
doublets at 5.2-5.4 and 4.1-4.3 ppm in good agreement with literature data [2]. The H NMR spectra of
compounds 7 and 8 showed doublet signals at 7.05-7.13 corresponding to the =CHX protons and multiplet
signals for the OCH protons at 5.36-5.60 ppm. This spectroscopic data agreed with that in the literature [3] and
2
pointed to the formation of tricyclic condensed systems with an exocyclic double bond.
It was interesting to note that the haloheterocyclization of the propargyl ethers 4 did not proceed
1
stereospecifically but gave a mixture of the geometric isomers 7 and 8. According to H NMR data the isomer
ratio was 7:1. It is likely that the E-somer is principally formed, governed by a haloheterocyclization mechanism
via a stage of electrophilic trans addition of halogen to the multiple carbon-carbon bond and subsequent
cyclization at the nucleophilic center. The principal formation of the E-isomer is also explained by its high
1
thermodynamic stability as shown by quantum-chemical calculations. The H NMR spectrum also confirms the
major formation of the E-isomer since the signal for the proton cis to the heteroatom resonates at lower field than
that in the trans position, in agreement with literature data [4-6].
EXPERIMENTAL
1
H NMR spectra were recorded on a Varian VXR-300 (300 MHz) instrument using a mixture of
DMSO-d and CCl as solvent and TMS as internal standard.
6
4
2
-Chloro-3-formylquinoline (1a) and 2-Chloro-3-formyl-7-methylquinoline (1b) were sinthesized as
reported in [7], 3-Formylquinol-2-one (2a) and 3-Formyl-7-methylquinol-2-one (2b) as in [8].
Preparation of Ethers 3, 4 (General Method). A mixture of the quinolone 2a,b (1 mmol), NaOH
(
1.2 mmol) in water (3 ml), and 2-propanol (30 ml) was refluxed for 1 h. The solution obtained was treated with
the alkyl bromide (1.5 mmol) (80% solution of propargyl bromide in toluene) and refluxed for 2 h. The
precipitate was filtered off and recrystallized from ethanol or DMF.
1
2
-Allyloxy-3-formylquinoline (3a). Yield 42%; mp 110-113ºC (ethanol). H NMR spectrum, δ, ppm
(
J, Hz): 4.9 (2H, d, J = 2, OCH ); 5.1 (2H, dd, J = 15, J = 9, =CH ); 5.9 (1H, m, =CH); 7.3 (1H, t, J = 7, H-6);
2
2
7
.46 (1H, d, J = 7, H-5); 7.68 (1H, t, J = 8, H-7); 7.9 (1H, d, J = 8, H-8); 8.5 (1H, s, H-4); 10.3 (1H, s, CHO).
Found, %: N 6.43. C H NO . Calculated, %: N 6.57.
1
3
11
2
1
2
-Allyloxy-3-formyl-7-methylquinoline (3b). Yield 33%; mp 121-123ºC (ethanol). H NMR spectrum,
δ, ppm (J, Hz): 2.65 (3H, d, CH ); 4.7 (2H, d, J = 2, OCH ); 5.0 (2H, dd, J = 15, J = 8, =CH ); 6.01 (1H, m,
3
2
2
=
CH); 7.55 (1H, d, J = 8, H-6); 7.8 (1H, d, J = 8, H-5); 8.05 (1H, s, H-8); 8.85 (1H, s, H-4); 10.3 (1H, s, CHO).
Found, %: N 6.09. C H NO . Calculated, %: N 6.17.
1
4
13
2
1
3
-Formyl-2-propargyloxyquinoline (4a). Yield 58%; mp 193-195ºC (DMF). NMR spectrum, δ, ppm
(
J, Hz): 3.0 (1H, s, ≡CH); 5.1 (2H, s, CH ); 7.35 (1H, t, J = 7, H-6); 7.6 (1H, d, J = 7, H-5); 7.75 (1H, t, J = 8,
2
H-7); 7.9 (1H, d, J = 8, H-8); 8.4 (1H, s, H-4); 10.25 (1H, s, CHO). Found, %: N 6.55. C H NO . Calculated,
1
3
11
2
%
: N 6.64.
-Formyl-7-methyl-2-propargyloxyquinoline (4b). Yield 57%; mp 215-217ºC (ethanol). H NMR
spectrum, δ, ppm (J, Hz): 2.65 (3H, s, CH ); 2.9 (1H, s, ≡CH); 5.0 (2H, s, CH ); 7.45 (1H, d, J = 8, H-6); 7.65
1
3
3
2
(
1H, d, J = 8, H-5); 8.05 (1H, s, H-8); 8.45 (1H, s, H-4); 10.20 (1H, s, CHO). Found, %: N 6.19. C H NO .
1
4
11
2
Calculated, %: N 6.22.
1
021

Preparation of Bromides 5, 7 (General Method). A solution of bromine (2 mmol) in methylene
chloride (5 ml) was added with constant stirring to a solution of the allyl ether 3 or propargyl ether 4 (1 mmol) in
methylene chloride (10 ml) and DMF (1 ml). After 2 h the precipitate was filtered off, treated with acetone, and
again filtered.
1
-Bromomethyl-4-formyl-1,2-dihydro[1,3]oxazolo[3,2-a]quinolinium Bromide (5a). Yield 70%; mp
1
2
20-222ºC . H NMR spectrum, δ, ppm (J, Hz): 4.1 (2H, d, J = 7, CH Br); 5.3 (2H, d, J = 8, OCH ); 6.1 (1H, m,
2
2
CH); 7.45 (1H, t, J = 7, H-7); 7.55 (1H, d, J = 7, H-6); 7.75 (1H, t, J = 8, H-8); 8.05 (1H, d, J = 8, H-9); 8.7 (1H,
s, H-5); 10.45 (1H, s, CHO). Found, %: N 3.69. C H Br NO . Calculated, %: N 3.75.
1
3
11
2
2
1
-Bromomethyl-4-formyl-8-methyl-1,2-dihydro[1,3]oxazolo[3,2-a]quinolinium Bromide (5b). Yield
1
6
5%; mp 228-230ºC. H NMR spectrum, δ, ppm (J, Hz): 2.80 (3H, s, CH ); 4.2 (2H, d, J = 6, CH Br); 5.35 (2H,
3
2
d, J = 8, OCH ); 6.0 (1H, m, CH); 7.5 (1H, d, J = 7, H-7); 7.75 (1H, d, J = 7, H-6); 8.15 (1H, s, H-9); 8.65 (1H,
2
s, H-5); 10.35 (1H, s, CHO). Found, %: N 3.55. C H Br NO . Calculated, %: N 3.62.
1
4
13
2
2
1
-Bromomethylidene-4-formyl-1,2-dihydro[1,3]oxazolo[3,2-a]quinolinium Bromide (7a). Yield
1
5
9%; mp 137-138ºC. H NMR spectrum, δ, ppm (J, Hz): 5.35 (2H, m, OCH ); 7.05 (1H, 2s, =CHBr); 7.40 (1H,
2
t, J = 7, H-7); 7.50 (1H, d, J = 7, H-6); 7.75 (1H, t, J = 8, H-8); 8.05 (1H, d, J = 8, H-9); 8.55 (1H, s, H-5); 10.35
(
1H, s, CHO). Found, %: N 3.69. C H Br NO . Calculated, %: N 3.77.
1
3
9
2
2
1
-Bromomethylidene-4-formyl-8-methyl-1,2-dihydro[1,3]oxazolo[3,2-a]quinolinium Bromide (7b).
1
Yield 55%; mp 141-143ºC. H NMR spectrum, δ, ppm (J, Hz): 2.75 (3H, s, CH ); 5.40 (2H, m, OCH ); 7.08
3
2
(
1H, 2s, =CHBr); 7.45 (1H, d, J = 8, H-7); 7.65 (1H, d, J = 8, H-6); 8.15 (1H, s, H-9); 8.5 (1H, s, H-5); 10.45
(
1H, s, CHO). Found, %: N 3.60. C H Br NO . Calculated, %: N 3.64.
1
4
11
2
2
Preparation of Iodides 6, 8 (General Method). A solution of iodine (2 mmol) in acetic acid (20 ml)
was added with constant stirring to a solution of the allyl ether 3 or propargyl ether 4 (1 mmol) in acetic acid (10
ml). After 2-3 h the precipitate was filtered off, treated with acetone, and again filtered.
4
-Formyl-1-iodomethyl-1,2-dihydro[1,3]oxazolo[3,2-a]quinolinium Triiodide (6a). Yield 52%; mp
1
1
72-174ºC. H NMR spectrum, δ, ppm (J, Hz): 4.35 (2H, d, J = 8, CH I); 5.45 (2H, d, J = 6, OCH ); 6.1 (1H, m,
2
2
CH); 7.45 (1H, t, J = 7, H-7); 7.65 (1H, d, J = 7, H-6); 7.75 (1H, t, J = 8, H-8); 7.95 (1H, d, J = 8, H-9); 8.7 (1H,
s, H-5); 10.5 (1H, s, CHO). Found, %: N 1.88. C H I NO . Calculated, %: N 1.94.
1
3
11 4
2
4
-Formyl-1-iodomethyl-8-methyl-1,2-dihydro[1,3]oxazolo[3,2-a]quinolinium Triiodide (6b). Yield
4
5
5%; mp 178-180ºC.
1
-Bromomethylidene-4-formyl-1,2-dihydro[1,3]oxazolo[3,2-a]quinolinium Triiodide (8a). Yield
9%; mp 137-138ºC.
1
-Bromomethylidene-4-formyl-8-methyl-1,2-dihydro[1,3]oxazolo[3,2-a]quinolinium Triiodide (8b).
1
Yield 57%; mp 225-227ºC. H NMR spectrum, δ, ppm (J, Hz): 2.73 (3H, s, CH ); 5.60 (2H, m, OCH ); 7.13 (1H,
3
2
2
s, =CHI); 7.25 (1H, d, J = 8, H-7); 7.45 (1H, d, J = 8, H-6); 8 15 (1H, s, H-9); 8.55 (1H, s, H-5); 10.24 (1H, s,
CHO). Found, %: N 2.00. C H I NO . Calculated, %: N 1.91.
1
4
11 4
2
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