Synthesis of pseudobaptigenin analogs

Article abstract of DOI:10.1023/A:1025470418642

Homologs of the natural isoflavonoid pseudobaptigenin containing benzodioxane and benzodioxepane fragments were synthesized. Methanesulfonyl, carbamoyl, aminomethyl, and coumarin-containing isoflavone derivatives were prepared.

Full text of DOI:10.1023/A:1025470418642

Chemistry of Natural Compounds, Vol. 39, No. 3, 2003
SYNTHESIS OF PSEUDOBAPTIGENIN ANALOGS
S. P. Bondarenko, M. S. Frasinyuk, and V. P. Khilya
UDC 547.814.5
Homologs of the natural isoflavonoid pseudobaptigenin containing benzodioxane and benzodioxepane
fragmentswere synthesized. Methanesulfonyl, carbamoyl, aminomethyl, andcoumarin-containingisoflavone
derivatives were prepared.
Key words: isoflavonoids, alkylation, acylation, aminomethylation, 4-chloromethylcoumarins, urethanes.
We carried out alkylation, acylation, and aminomethylation of isoflavones 1a-j in order to modify pseudobaptigenin
1 [1, 2].
O
O
HO
O
O
1
We used substituted 4-chloromethylcoumarins, derivatives of which exhibited antifungal properties, as the alkylating
reagents [3]. The starting 4-chloromethylcoumarins were prepared by reaction of 4-chloroacetoacetic ester with substituted
phenols in the presence of conc. H SO (Pechmann reaction).
2
4
New isoflavones 2a-e, which contain chromone and coumarin fragments, were synthesized by alkylation in a
DMF—acetone mixture in the presence of potash.
One of the methods for modifying the synthesized isoflavones 1a-j was Mannich aminomethylation. The Mannich
basespreparedfrom theisoflavonesarecentral-nervous-system andrespiratory-pathwayregulators. Theyexhibitanticonvulsive,
antiallergic, and analgesic activities [4, 5]. Mannich bases based on the natural flavolignan silybin possess hepatoprotective
and hypocholesteric activities [6]. Therefore, it seemed interesting to synthesize analogs that contain benzodioxane and
benzodioxepane fragments.
The desired Mannich bases3a-f, 4a-e, and5aandb were prepared according tothe literature [7] using various aminals.
We found that reaction of equivalent amounts of aminal and isoflavone in boiling dioxane leads to aminomethylation
of the chromone ring at the 8-position. It should be noted that isoflavones containing an ester in the second position are easily
aminomethylated whereas aminolysis by the amine does not occur. This feature can be used for further modification of the
isoflavones and to open a promising route to the preparation of aminomethyl derivatives with labile substituents.
Derivatives of sulfonic acids exhibit a wide spectrum of biological activity, for example, sulfamide preparations are
used as chemotherapeutic antibacterial agents. Therefore, it was interesting to synthesize analogous modified isoflavones 6a-c.
Derivatives of sulfonic acids of isoflavones were prepared from the corresponding 7-hydroxyisoflavones 1e, f, and i by reaction
with methtanesulfonyl chloride in pyridine.
It was interesting toprepare urethanes during the studyofthe reactivityof phenolic hydroxyls ofisoflavones. However,
we did not find conditions for the reaction of 7-hydroxyisoflavones with isocyanates, which may be due to the insignificant
reactivity of the hydroxyl and the reversibility of the reaction. We achieved the goal by reacting N,N-disubstituted carbamoyl
chlorides. As it turned out, their reaction with 7-hydroxyisoflavones proceeds readily in pyridine at room temperature to
form 7a-l.
Taras Shevchenko Kiev University, the Ukraine, 252033, Kiev, ul. Vladimirskaya, 64, fax (380) 442 351 273, e-mail:
mfras@i.kiev.ua. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 206-210, May-June, 2003. Original article
submitted June 16, 2003.
0009-3130/03/3903-0265$25.00 ©2003 Plenum Publishing Corporation
265

R
8
R
5
R
7
R
R
9
X
R
R
4
6
N
N
O
R
3
O
O
HO
R
2
O
O
HO
2
O
O
O
R
2
O
O
O
O
O
R
1
R
1
O
O
R
1
3a- f
4a - e
2a - e
O
HO
R
2
N
O
O
R
1
O
O
HO
R
2
(CH )n
2
O
O
O
1a - j
R
1
R
10
5a, b
N
O
O
S O
O
R
9
O
R
2
O
O
O
R
2
O
O
R
1
R
1
(CH )n
O
(CH )n
O
2
2
O
6a - c
7a - l
1a f 6a b 7a b e f i j
1g j 6c 7c d g h k l
, , , , , : n = 3
- , , , , , , , , : n =2; - ,
,
1a 2a c 3a d f 4a c e 5a
, , , , , , , , , : R1 = H;
1b d g h 2d 3b c e 4b d 5b 7a c g h i k
, , , , , , , , , , , : R1 = Et;
-
,
,
,
,
1e f i j 2b e, 6a c 7b d f j l
, , , , - , - , , : R1 = Pr;
,
,
2a,b
2c
2d,e
: R3 = R4 = R6 = H, R5 = OMe;
: R3 = R5 = Me, R4 = R6 = H; : R3 = R5 = H, R4 = R6 = Me;
3a
4a
c
3d,e 3f
- : R7 = Me, R8 = R9 = H;
: R7 = R9 = H, R8 = Me; : R7 = R8 = H, R9 = Me;
4e
4b
: X = bond; : X = NMe;
4c,d
: X = NCH2CH2OH; : X = CH2CH2;
7a - d
: R9 = R10 = Me,
7e-h
7i-l
: R9R10 = CH2CH2OCH2CH2;
: R9 = R10 = Ph,
1a,b,e,g,i, 2a e 3a,b,d,f 4a,c,e 5a 6a,c 7e,g i
l
- ,
,
,
,
,
,
- : R2 = Me;
1d, 3c,e 4b d 5b
, , : R2 = CO2Et
1c,f,h,j 6b,7a d f h
, , : R2 = Me;
,
-
,
EXPERIMENTAL
The course of reactions and purity of compounds were monitored by TLC on Sorbfil UV-254 (Russia) and Merk
(Germany) plates. The eluent was a CHCl :CH OH (95:5) mixture. PMR spectra (δ, ppm, J/Hz) were measured on VXR-300
3
3
and Mercury 400 instruments (Varian, 300 and 400 MHz, respectively) in DMSO-d and CDCl relative to TMS (internal
6
3
standard). Elemental analyses of all compounds agreed with those calculated.
1a j
Starting isoflavones - were prepared as before [1, 2].
General Method for Preparing 7-Coumarylmethoxyisoflavonoes 2a-e.
A hot solution of the appropriate
7-hydroxychromone (10 mmol) in absolute acetone (15 mL) and DMF (15 mL) was treated with freshly calcined K CO
2
3
(2.1 g, 15 mmol), stirred and heated to 60°C, treated with the appropriate 4-chloromethylcoumarin (12 mmol), left for 20 h
(completion of the reaction determined by TLC), and poured into acidic ice water (100 mL). The resulting precipitate was
filtered off and crystallized from propan-2-ol.
266

4-[3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-4-oxo-4H-chromen-7-yloxymethyl]-5,7-dimethylchromen-2-one (2a),
3
3
4
mp 285-286°C. PMR spectrum: 4.28 [4H, m, O(CH ) O], 6.91 (1H, d, H-5′, J = 8.4), 7.07 (1H, dd, H-6′, J = 8.4, J = 2.4),
2 2
4
4
3
4
3
7.15 (d, H-2′, J = 2.4), 7.39 (1H, d, H-8, J = 2.0), 7.29 (1H, dd, H-6, J = 8.4, J = 2.0), 8.10 (1H, d, H-5, J = 8.4), 8.44 (1H,
s, H-2), coumarin protons: 2.37, 2.72 (3H, 3H, 2s, CH -5 and CH -7), 5.69 (2H, s, CH O-4), 6.58 (1H, s, H-3), 7.08 (1H, br.s,
3
3
2
H-8), 7.15 (1H, br.s, H-6).
4-([3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-4-oxo-6-propyl-4H-chromen-7-yl]oxymethyl)-5,7-dimethyl-2H-chromen-
3
3
3
2-one (2b), mp 226-227°C. PMR spectrum: 0.94 (3H, t, J = 7.6), 1.65 (2H, m, J = 7.6), 2.7 (2H, q, J = 7.6) 6-CH CH CH ,
3
2
2
3
3
4
4
4.27 [4H, m, O(CH ) O], 6.91 (1H, d, H-5′, J = 8.4), 7.06 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.14 (d, H-2′, J = 2.4), 7.34 (1H,
2 2
s, H-8), 7.92 (1H, s, H-5), 8.44 (1H, s, H-2); coumarin protons: 2.38, 2.74 (3H, 3H, 2s, CH -5 and CH -7), 5.72 (2H, s,
3
3
CH O-4), 6.52 (1H, s, H-3), 7.08 (1H, br.s, H-8), 7.15 (1H, br.s, H-6).
2
4-[3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-4-oxo-4H-chromen-7-yloxymethyl]-6,8-dimethylchromen-2-one (2c),
3
3
4
mp 294-295°C. PMR spectrum: 4.28 [4H, m, O(CH ) O], 6.91 (1H, d, H-5′, J = 8.4), 7.07 (1H, dd, H-6′, J = 8.4, J = 2.4),
2 2
4
4
3
4
3
7.15 (d, H-2′, J = 2.4), 7.53 (1H, d, H-8, J = 2.0), 7.32 (1H, dd, H-6, J = 8.4, J = 2.4), 8.08 (1H, d, H-5, J = 8.4), 8.46 (1H,
s, H-2); coumarin protons: 2.36, 2.38 (3H, 3H, 2s, CH -6 and CH -8), 5.53 (2H, s, CH O-4), 6.63 (1H, s, H-3), 7.37 (1H, br.s,
3
3
2
H-5), 7.58 (1H, br.s, H-7).
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-6-ethyl-7-(7-methoxy-2-oxo-2H-chromen-4-ylmethoxy)-chromen-4-one (2d),
3
3
mp 241-242°C. PMR spectrum: 1.24 (3H, t, J = 7.8), 2.77 (2H, q, J = 7.8), 6-CH CH ; 4.27 [4H, m, O(CH ) O], 6.91 (1H,
3
2
2 2
3
3
4
4
d, H-5′, J = 8.4), 7.02 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.15 (d, H-2′, J = 2.4), 7.54 (1H, s, H-8), 7.91 (1H, s, H-5), 8.45 (1H,
3
4
s, H-2); coumarin protons: 3.89 (3H, s, 7-MeO), 5.53 (2H, s, CH O-4), 6.43 (1H, s, H-3), 7.02 (1H, dd, H-6, J = 8.8, J = 2.4),
2
4
3
7.06 (1H, d, H-8, J = 2.4), 7.88 (1H, d, H-5, J = 8.8).
3-(2,3-Dihydrobenzo[1,4]diioxan-6-yl)-7-(7-methoxy-2-oxo-2H-chromen-4-ylmethoxy)-6-propylchromen-4-one
3
3
3
(2e), mp 233-234°C. PMR spectrum: 0.94 (3H, t, J = 7.6), 1.63 (2H, m, J = 7.6), 2.72 (2H, q, J = 7.6) 6-CH CH CH ; 4.27
3
2
2
3
3
4
4
[4H, m, O(CH ) O], 6.89 (1H, d, H-5′, J = 8.4), 7.06 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.14 (d, H-2′, J = 2.4), 7.52 (1H, s,
2 2
H-8), 7.87 (1H, s, H-5), 8.43 (1H, s, H-2); coumarin protons: 3.87 (3H, s, 7-MeO), 5.49 (2H, s, CH O-4), 6.39 (1H, s, H-3), 7.01
2
3
4
4
3
(1H, dd, H-6, J = 8.8, J = 2.4), 7.04 (1H, d, H-8, J = 2.4), 7.85 (1H, d, H-5, J = 8.8).
General Method for Preparing 8-Dialkylaminomethylisoflavones 3a-f, 4a-e, and 5a and b. A boiling solution of
the appropriate isoflavone (10 mmol) in absolute dioxane (20 mL) was treated with aminal (15 mmol), boiled for 3-4 h
(completion of the reaction determined by TLC), cooled. The dioxane, released amine, and unreacted aminal were evaporated
in vacuum. The solid was recrystallized from propan-2-ol.
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-7-hydroxy-8-(2-methylpiperidin-1-ylmethyl)-chromen-4-one (3a), mp179-
2
180°C. PMR spectrum: 1.21, 1.12-3.26 (3H, d, 9H, m, piperidine protons), 3.88, 4.27 (2H, 2d, J = 15.3, CH -8), 4.28 [4H,
2
3
3
4
4
m, 0(CH ) O], 6.91 (1H, d, H-5′, J = 8.4), 7.03 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.09 (d, H-2′, J = 2.4), 6.84 (1H, d,
2 2
3
3
J = 9.0, H-6), 8.09 (1H, d, J = 9.0, H-5), 7.85 (1H, s, H-2).
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-6-ethyl-7-hydroxy-8-(2-methylpiperidin-1-ylmethyl)-chromen-4-one (3b),
3
3
mp 143-144°C. PMR spectrum: 1.26 (3H, t, J = 7.8), 2.69 (2H, q, J = 7.8) 6-CH CH ; 1.20, 1.12-3.26 (3H, m, 9H, m,
3
2
3
piperidine protons), 3.75-4.50 (2H, m, CH -8), 4.28 [4H, m, O(CH ) 0], 6.91 (1H, d, H-5′, J = 8.4), 7.03 (1H, dd, H-6′,
J = 8.4, J = 2.4), 7.09 (d, H-2′, J = 2.4), 7.96 (1H, d, J = 9.0, H-5), 7.84 (1H, s, H-2).
2
2 2
3
4
4
3
Ethyl 3-(2,3-dihydrobenzo[1,4]dioxan-6-yl)-6-ethyl-7-hydroxy-8-(2-methylpiperidin-1-ylmethyl)-4-oxo-4H-
3
3
chromen-2-carboxylate (3c), mp 155-156°C. PMR spectrum: 1.06 (3H, t, J = 7.8), 2.69 (2H, q, J = 7.8) 6-CH CH ; 1.25
3
2
3
3
(3H, t, J = 8.0), 4.17 (2H, q, J = 8.0) 2-CH CH OOC; 1.19, 1.33-3.19 (3H, m, 9H, m, piperidine protons), 3.80-4.53 (2H, m,
CH -8), 4.27 [4H, m, O(CH ) O], 6.88 (1H, d, H-5′, J = 8.4), 6.74 (1H, dd, H-6′, J = 8.4, J = 2.4), 6.83 (d, H-2′, J = 2.4),
3
2
3
3
4
4
2
2 2
3
7.88 (1H, d, J = 9.0, H-5).
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-7-hydroxy-8-(3-methylpiperidin-1-ylmethyl)-chromen-4-one (3d), mp183-
184°C. PMR spectrum: 0.92, 0.76-3.13 (3H, d, 9H, m, piperidine protons), 3.98 (2H, s, CH -8), 4.28 [4H, m, O(CH ) O], 6.91
2
2 2
3
3
4
4
3
(1H, d, H-5′, J = 8.4), 7.03 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.09 (d, H-2′, J = 2.4), 6.86 (1H, d, J = 9.0, H-6), 8.12 (1H, d,
3
J = 9.0, H-5), 7.85 (1H, s, H-2).
Ethyl 3-(2,3-dihydrobenzo[1,4]dioxan-6-yl)-6-ethyl-7-hydroxy-8-(3-methylpiperidin-1-ylmethyl)-4-oxo-4H-
3
3
chromen-2-carboxylate (3e), mp 204-205°C. PMR spectrum: 1.07 (3H, t, J = 7.8), 2.70 (2H, q, J = 7.8) 6-CH CH ; 1.26
3
2
3
3
(3H, t, J = 8.0), 4.17 (2H, q, J = 8.0) 2-CH CH OOC; 0.92, 0.88-3.19 (3H, m, 9H, m, piperidine protons), 4.04 (2H, s, CH -8),
3
2
2
267

3
3
4
4
4.28 [4H, m, O(CH ) O], 6.89 (1H, d, H-5′, J = 8.4), 6.75 (1H, dd, H-6′, J = 8.4, J = 2.4), 6.83 (d, H-2′, J = 2.4), 7.91 (1H,
d, J = 9.0, H-5).
2 2
3
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-7-hydroxy-8-(4-methylpiperidin-1-ylmethyl)-chromen-4-one (3f), mp190-
191°C. PMR spectrum: 0.97, 1.21-3.16 (3H, d, 9H, m, piperidine protons), 3.99 (2H, s, CH -8), 4.27 [4H, m, O(CH ) O], 6.91
2
2 2
3
3
4
4
3
(1H, d, H-5′, J = 8.4), 7.02 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.09 (d, H-2′, J = 2.4), 6.86 (1H, d, J = 9.0, H-6), 8.10 (1H, d,
3
J = 9.0, H-5), 7.85 (1H, s, H-2).
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-7-hydroxy-8-pyrrolidin-1-ylmethylchromen-4-one (4a), mp 206-207°C.
PMR spectrum: 1.82-2.00, 2.65-2.85 (4H, 4H, 2m, pyrrolidine protons), 4.15 (2H, s, CH -8), 4.27 [4H, m, O(CH ) O], 6.86
2
2 2
3
3
4
4
3
(1H, d, H-5′, J = 8.4), 7.03 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.09 (d, H-2′, J = 2.4), 6.87 (1H, d, J = 9.0, H-6), 8.11 (1H, d,
3
J = 9.0, H-5), 7.86 (1H, s, H-2).
Ethyl 3-(2,3-dihydrobenzo[1,4]dioxan-6-yl)-6-ethyl-7-hydroxy-8-(4-methylpiperazin-1-ylmethyl)-4-oxo-4H-
3
3
chromen-2-carboxylate (4b), mp 200-201°C. PMR spectrum: 1.08 (3H, t, J = 7.8), 2.70 (2H, q, J = 7.8) 6-CH CH ; 1.25
3
2
3
3
(3H, t, J = 8.0), 4.18 (2H, q, J = 8.0) 2-CH CH OOC; 2.00-3.17 (8H, m, piperazine protons), 2.34 (3H, s, NCH ), 4.07 (2H,
s, CH -8), 4.27 [4H, m, O(CH ) O], 6.88 (1H, d, H-5′, J = 8.4), 6.73 (1H, dd, H-6′, J = 8.4, J = 2.4), 6.82 (d, H-2′, J = 2.4),
3
2
3
3
3
4
4
2
2 2
3
7.91 (1H, d, J = 9.0, H-5).
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-7-hydroxy-8-[4-(2-hydroxyethyl)-piperazin-1-ylmethyl]-chromen-4-one
(4c), mp 174-175°C. PMR: 2.20-3.20 (8H, m, piperazine protons), 2.60, 3.64 (4H, m, NCH CH O), 4.04 (2H, s, CH -8), 4.28
2
2
2
3
3
4
4
[4H, m, O(CH ) O], 6.90 (1H, d, H-5′, J = 8.4), 7.02 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.09 (d, H-2′, J = 2.4), 6.88 (1H, d,
2 2
3
3
J = 9.0, H-6), 8.12 (1H, d, J = 9.0, H-5), 7.87 (1H, s, H-2).
Ethyl3-(2,3-dihydrobenzo[1,4]dioxan-6-yl)-6-ethyl-7-hydroxy-8-[4-(2-hydroxyethyl)-piperazin-1-ylmethyl]-4-oxo-
3
3
4H-chromen-2-carboxylate (4d), mp 210-211°C. PMR spectrum: 1.08 (3H, t, J = 7.8), 2.69 (2H, q, J = 7.8) 6-CH CH ;
3
2
3
3
1.25 (3H, t, J = 8.0), 4.18 (2H, q, J = 8.0) 2-CH CH OOC; 2.20-3.20 (8H, m, piperazine protons), 2.61, 3.64 (4H, m,
NCH CH O), 4.08 (2H, s, CH -8), 4.27 [4H, m, O(CH ) O], 6.89 (1H, d, H-5′, J = 8.4), 6.74 (1H, dd, H-6′, J = 8.4, J = 2.4),
3
2
3
3
4
2
2
2
2 2
4
3
6.82 (d, H-2′, J = 2.4), 7.96 (1H, d, J = 9.0, H-5).
8-Azepan-1-ylmethyl-3-(2,3-dihydrobenzo[1,4]dioxan-6-yl)-7-hydroxychromen-4-one (4e), mp196-197°C. PMR
spectrum: 1.57-1.90, 2.69-2.94 (8H, 4H, 2m, azepan protons), 4.10 (2H, s, CH -8), 4.28 [4H, m, O(CH ) O], 6.91 (1H, d, H-5′,
2
2 2
3
3
4
4
3
3
J = 8.4), 7.03 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.09 (d, H-2′, J = 2.4), 6.87 (1H, d, J = 9.0, H-6), 8.12 (1H, d, J = 9.0, H-5),
7.85 (1H, s, H-2).
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-7-hydroxy-8-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-ylmethyl)-chromen-
4-one (5a), mp 200-201°C. PMR spectrum: 0.84-3.33 (18H, m, base protons), 3.98, 4.26 (2H, 2d, J = 11.4, CH -8), 4.27 [4H,
m, O(CH ) O], 6.91 (1H, d, H-5′, J = 8.4), 7.03 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.09 (d, H-2′, J = 2.4), 8.12 (1H, d,
2
2
3
3
4
4
2 2
3
J = 9.0, H-5), 7.85 (1H, s, H-2).
Ethyl 3-(2,3-dihydrobenzo[1,4]dioxan-6-yl)-6-ethyl-7-hydroxy-4-oxo-8-(1,3,3-trimethyl-6-azabicyclo[3.2.1]oct-6-
3
3
ylmethyl)-4H-chromen-2-carboxylate (5b), mp 158-159 C. PMR spectrum: 1.07 (3H, t, J = 7.8), 2.71 (2H, q, J = 7.8)
3
3
6-CH CH ; 1.25 (3H, t, J = 8.0), 4.17 (2H, q, J = 8.0) 2-CH CH OOC; 0.91-3.36 (18H, m, base protons), 4.00, 4.30 (2H, 2d,
3
2
3
2
2
3
3
4
J = 14.0, CH -8), 4.27 [4H, m, O(CH ) O], 6.88 (1H, d, H-5′, J = 8.4), 6.74 (1H, dd, H-6′, J = 8.4, J = 2.4), 6.82 (d, H-2′,
2
2 2
4
3
J = 2.4), 7.91 (1H, d, J = 9.0, H-5).
General Method for Synthesizing 6a-c and 7a-l. A solution of the appropriate 7-hydroxyisoflavone (10 mmol) in
the minimal amount of absolute pyridine was treated with the acid chloride (12 mmol). The reaction mixture was held for
1 d at room temperature and then poured into icewater. The resulting precipitate was filtered off and crystallized from alcohol
(6a-c) or propan-2-ol (7a-c).
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-4-oxo-6-propyl-4H-chromen-7-yl methanesulfonate (6a), mp 148-149°C
3
3
3
(ethanol). PMR spectrum: 0.93 (3H, t, J = 7.6), 1.63 (2H, m, J = 7.6), 2.75 (2H, q, J = 7.6) 6-CH CH CH ; 3.63 (3H, s,
3
4
2
2
3
3
7-CH SO O), 4.27 [4H, m, O(CH ) O], 6.92 (1H, d, H-5′, J = 8.4), 7.06 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.13 (d, H-2′,
J = 2.4), 7.75 (1H, s, H-8), 8.07 (1H, s, H-6), 8.52 (1H, s, H-2).
3
2
2 2
4
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-2-methyl-4-oxo-6-propyl-4H-chromen-7-ylmethanesulfonate (6b), mp 123-
3
3
3
124°C. PMR spectrum: 0.92 (3H, t, J = 7.6), 1.62 (2H, m, J = 7.6), 2.74 (2H, q, J = 7.6) 6-CH CH CH ; 2.29 (3H, s, 2-CH ),
3
2
2
3
3
3
4
3.62 (3H, s, 7-CH SO O), 4.28 [4H, m, O(CH ) O], 6.91 (1H, d, H-5′, J = 8.4), 6.72 (1H, dd, H-6′, J = 8.4, J = 2.4), 6.78
(d, H-2′, J = 2.4), 7.72 (1H, s, H-8), 7.97 (1H, s, H-6).
3
2
2 2
4
268

3-(3,4-Dihydro-2H-benzo[b][1,4]dioxepan-7-yl)-4-oxo-6-propyl-4H-chromen-7-yl methanesulfonate (6c), mp112-
3
3
3
113°C. PMR spectrum: 0.93 (3H, t, J = 7.6), 1.63 (2H, m, J = 7.6), 2.76 (2H, q, J = 7.6) 6-CH CH CH ; 3.63 (3H, s,
3
3
2
2
4
3
7-CH SO O), 4.16 (4H, m), 2.13 (2H, m) O(CH ) O; 7.02 (1H, d, H-5′, J = 8.4), 7.18 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.24
(d, H-2′, J = 2.4), 7.76 (1H, s, H-8), 8.04 (1H, s, H-6), 8.55 (1H, s, H-2).
3
2
4
2 3
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-6-ethyl-2-methyl-4-oxo-4H-chromen-7-yl dimethylcarbamate (7a), mp218-
3
3
219°C. PMR spectrum: 1.17 (3H, t, J = 7.8), 2.632 (2H, q, J = 7.8) 6-CH CH ; 2.27 (3H, s, 2-CH ), 2.96, 3.11 [6H, 2s,
3
2
3
3
3
4
7-(CH ) NCOO], 4.28 [4H, m, O(CH ) O], 6.90 (1H, d, H-5′, J = 8.4), 6.72 (1H, dd, H-6′, J = 8.4, J = 2.4), 6.78 (d, H-2′,
3 2
2 2
4
J = 2.4), 7.43 (1H, s, H-8), 7.90 (1H, s, H-6).
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-2-methyl-4-oxo-6-propyl-4H-chromen-7-yl dimethylcarbamate (7b),
3
3
3
mp 214-215°C. PMR spectrum: 0.89 (3H, t, J = 7.6), 1.57 (2H, m, J = 7.6), 2.60 (2H, q, J = 7.6) 6-CH CH CH ; 2.27 (3H,
3
2
2
3
s, 2-CH ), 2.96, 3.10 [6H, 2s, 7-(CH ) NCOO], 4.27 [4H, m, O(CH ) O], 6.90 (1H, d, H-5′, J = 8.4), 6.72 (1H, dd, H-6′,
J = 8.4, J = 2.4), 6.78 (d, H-2′, J = 2.4), 7.44 (1H, s, H-8), 7.88 (1H, s, H-6).
3
3 2
2 2
3
4
4
3-(3,4-Dihydro-2H-benzo[b][1,4]dioxepan-7-yl)-6-ethyl-2-methyl-4-oxo-4H-chromen-7-yl dimethylcarbamate (7c),
3
3
3
mp 161-162°C. PMR spectrum: 0.93 (3H, t, J = 7.6), 1.63 (2H, m, J = 7.6), 2.76 (2H, q, J = 7.6) 6-CH CH CH ; 2.27 (3H,
3
2
2
3
s, 2-CH ), 2.95, 3.10 [6H, 2s, 7-(CH ) NCOO], 4.18 (4H, m), 2.12 (2H, m) O(CH ) O; 7.01 (1H, d, H-5′, J = 8.4), 6.85 (1H,
dd, H-6′, J = 8.4, J = 2.4), 6.89 (d, H-2′, J = 2.4), 7.44 (1H, s, H-8), 7.90 (1H, s, H-6).
3
3 2
2 3
3
4
4
3-(3,4-Dihydro-2H-benzo[b][1,4]dioxepan-7-yl)-2-methyl-4-oxo-6-propyl-4H-chromen-7-yl dimethylcarbamate
3
3
(7d), mp 152-153°C. PMR spectrum: 1.17 (3H, t, J = 7.8), 2.63 (2H, q, J = 7.8) 6-CH CH ; 2.27 (3H, s, 2-CH ), 2.95, 3.10
3
3
2
3
3
[6H, 2s, 7-(CH ) NCOO], 4.18 (4H, m), 2.12 (2H, m) O(CH ) O; 7.01 (1H, d, H-5′, J = 8.4), 6.85 (1H, dd, H-6′, J = 8.4,
J = 2.4), 6.89 (d, H-2′, J = 2.4), 7.44 (1H, s, H-8), 7.90 (1H, s, H-6).
3 2
2 3
4
4
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-4-oxo-6-propyl-4H-chromen-7-yl diphenylcarbamate (7e), mp 95-96°C.
3
3
3
PMR spectrum: 0.78 (3H, t, J = 7.6), 1.32 (2H, m, J = 7.6), 2.49 (2H, q, J = 7.6) 6-CH CH CH ; 4.26 [4H, m, O(CH ) O],
3
2
2
2 2
3
3
4
4
6.91 (1H, d, H-5′, J = 8.4), 7.05 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.13 (d, H-2′, J = 2.4), 7.28-7.60 (10H, m, Ph NCOO-7),
2
7.72 (1H, s, H-8), 7.95 (1H, s, H-6), 8.46 (1H, s, H-2).
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-2-methyl-4-oxo-6-propyl-4H-chromen-7-yl diphenylcarbamate (7f),
3
3
3
mp 176-177°C. PMR spectrum: 0.78 (3H, t, J = 7.6), 1.32 (2H, m, J = 7.6), 2.48 (2H, q, J = 7.6) 6-CH CH CH ; 2.27 (3H,
3
2
2
3
3
4
4
s, 2-CH ), 4.27 [4H, m, O(CH ) O], 6.89 (1H, d, H-5′, J = 8.4), 6.72 (1H, dd, H-6′, J = 8.4, J = 2.4), 6.78 (d, H-2′, J = 2.4),
3
2 2
7.32-7.53 (10H, m, Ph NCOO-7), 7.69 (1H, s, H-8), 7.85 (1H, s, H-6).
2
3-(3,4-Dihydro-2H-benzo[b][1,4]dioxepan-7-yl)-6-ethyl-4-oxo-4H-chromen-7-yl diphenylcarbamate (7g), mp 93-
3
3
94°C. PMR spectrum: 0.99 (3H, t, J = 7.8), 2.56 (2H, q, J = 7.8) 6-CH CH ; 4.16 (4H, m), 2.12 (2H, m) O(CH ) O; 7.01 (1H,
3
4
2
2 3
3
3
4
d, H-5′, J = 8.4), 7.17 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.24 (d, H-2′, J = 2.4), 7.28-7.60 (10H, m, Ph NCOO-7), 7.74 (1H,
2
s, H-8), 7.98 (1H, s, H-6), 8.51 (1H, s, H-2).
3-(3,4-Dihydro-2H-benzo[b][1,4]dioxepan-7-yl)-6-ethyl-2-methyl-4-oxo-4H-chromen-7-yl diphenylcarbamate(7h),
3
3
mp 140-141°C. PMR spectrum: 0.99, J/Hz (3H, t, J = 7.8), 2.55 (2H, q, J = 7.8) 6-CH CH ; 2.28 (3H, s, 2-CH ), 4.17
3
2
3
3
3
4
4
(4H, m), 2.12 (2H, m) O(CH ) O; 7.00 (1H, d, H-5′, J = 8.4), 6.85 (1H, dd, H-6′, J = 8.4, J = 2.4), 6.89 (d, H-2′, J = 2.4),
2 3
7.32-7.52 (10H, m, Ph NCOO-7), 7.69 (1H, s, H-8), 7.87 (1H, s, H-6).
2
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-6-ethyl-4-oxo-4H-chromen-7-yl morpholine-4-carboxylate (7i), mp 216-
3
3
217°C. PMR spectrum: 1.19 (3H, t, J = 7.8), 2.65 (2H, q, J = 7.8) 6-CH CH ; 3.40-3.55, 3.55-3.80 [8H, m, N(CH CH ) O],
3
3
2
2
2 2
3
4
4
4.27 [4H, m, O(CH ) O], 6.91 (1H, d, H-5′, J = 8.4), 7.05 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.13 (d, H-2′, J = 2.4), 7.54 (1H,
2 2
s, H-8), 8.01 (1H, s, H-6), 8.47 (1H, s, H-2).
3-(2,3-Dihydrobenzo[1,4]dioxan-6-yl)-4-oxo-6-propyl-4H-chromen-7-yl morpholine-4-carboxylate (7j), mp194-
3
3
3
195°C. PMR spectrum: 0.91 (3H, t, J = 7.6), 1.57 (2H, m, J = 7.6), 2.61 (2H, q, J = 7.6) 6-CH CH CH ; 3.42-3.50, 3.61-3.72
3
2
3
2
3
4
[8H, m, N(CH CH )O], 4.27 [4H, m, O(CH ) O], 6.91 (1H, d, H-5′, J = 8.4), 7.05 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.13 (d,
H-2′, J = 2.4), 7.54 (1H, s, H-8), 7.99 (1H, s, H-6), 8.46 (1H, s, H-2).
2
2
2 2
4
3-(3,4-Dihydro-2H-benzo[b][1,4]dioxepan-7-yl)-6-ethyl-4-oxo-4H-chromen-7-yl morpholine-4-carboxylate (7k),
3
3
mp 162-163°C. PMR spectrum: 1.19 (3H, t, J = 7.8), 2.66 (2H, q, J = 7.8) 6-CH CH ; 3.42-3.50, 3.62-3.72 [8H, m,
3
2
3
3
4
N(CH CH )O], 4.16 (4H, m), 2.13 (2H, m) O(CH ) O; 7.02 (1H, d, H-5′, J = 8.4), 7.18 (1H, dd, H-6′, J = 8.4, J = 2.4), 7.25
(d, H-2′, J = 2.4), 7.55 (1H, s, H-8), 8.01 (1H, s, H-6), 8.50 (1H, s, H-2).
2
2
2 3
4
269

3-(3,4-Dihydro-2H-benzo[b][1,4]dioxepan-7-yl)-4-oxo-6-propyl-4H-chromen-7-yl morpholine-4-carboxylate (7l),
3
3
3
mp 187-188°C. PMR spectrum: 0.91 (3H, t, J = 7.6), 1.57 (2H, m, J = 7.6), 2.62 (2H, m, J = 7.6) 6-CH CH CH ; 3.42-3.52,
3
2
2
3
3.58-3.75 [8H, m, N(CH CH )O], 4.16 (4H, m), 2.13 (2H, m) O(CH ) O; 7.02 (1H, d, H-5′, J = 8.4), 7.18 (1H, dd, H-6′,
J = 8.4, J = 2.4), 7.24 (d, H-2′, J = 2.4), 7.56 (1H, s, H-8), 7.99 (1H, s, H-6), 8.49 (1H, s, H-2).
2
2
4
2 3
3
4
REFERENCES
1.
2.
3.
4.
5.
6.
7.
A. Aitmambetov, L. G. Grishko, and V. P. Khilya, Khim. Prir. Soedin., 808 (1993).
A. Aitmambetov, L. G. Grishko, and V. P. Khilya, Khim. Prir. Soedin., 814 (1993).
R. Singh, R. P. Singh, and O. P. Malik, Indian J. Chem., Sect. B, 28, 996 (1989).
P. Da Re and L. Verlicchi, Ann. Chim. (Rome), 50, No. 10, 1273 (1960).
P. Da Re, I. Setnikar, and L. Verlicchi, J. Org. Chem., 25, No. 7, 1097 (1960).
A. Bonati, E. Bombardelli, and B. Gabetta, Brit. 1,383,053, 5 Feb 1975; Chem. Abstr., 83, 43342u (1975).
M. S. Frasinyuk, A. V. Turov, and V. P. Khilya, Khim. Geterotsikl. Soedin., 1072 (1998).
270