SU1578126A1 - Method of obtaining substituted 3-iodine-7-dialkyl-aminocoumarines - Google Patents

Abstract

The invention relates to substituted coumarins, in particular compounds of the general f-ly, where R 1 = CH 3, CL, morpholino group

R 3-H and R 2 - C 2H 5 or (R 2 + R 3) - (CH 2) 3 -, which can be used in the manufacture of laser dyes and optical brighteners. The goal is to increase the yield and expand the range of target products. The synthesis of the latter is carried out by iodination of the compound of the total f-ly @, where R 1, R 2 and R 3 have the indicated values, using iodine in the presence of a catalyst — pyridine at their molar ratio of 1: (4-6): 5 in dioxane or tetrahydrofuran at a temperature of mainly 20-40 ° C. Under these conditions, it is possible to expand the range of target substances and increase their yield by 10–13% (to 98.4%). 1 hp f-ly, 3 tab.

Description

This invention relates to an improved process for producing substituted 7-dialkylaminocoumarins, namely 3-iodo-7-dialkylaminocoumarins, which can be used in the manufacture of laser dyes and optical brighteners.

The purpose of the invention is to increase the yield and expansion of the range of target products due to the interaction of the corresponding 7-aminocoumarin with iodine in the medium of diokean or tetrahydrofuran in the presence of pyridine as a catalyst with an appropriate molar ratio of reagents and catalyst.

The method is illustrated by the following example.

Example 1. 3-Iodine-4-methyl 7-diethyl amino acid and N,

To a solution of 1 g (4.33 mmol) of 4-methyl-7-diethylaminocoumarin in 50 ml of dioxane, a solution of 5.5 g (2G, 65 mmol) of iodine in 20 mp of dioxane and 4 ml of pyridine is added with stirring. at 20 ° C. The reaction mass is treated with a saturated solution of sodium thiosulfate, extract

are benzene. The organic layer is evaporated, the residue is recrystallized from hexane-acetone. Yield 1.52 g (98.3%). 5

PRI mme r 2. 3-Iodine-4-chloro-7-diethylaminocoumarin.

To a solution of 0.5 g (2 mmol) of 4-chloro-7-diethylaminboumarin in 30 ml of dioxane, with stirring, is pouredJQ

a solution of 3.0 g (12 mmol) of iodine in 30 ml of dioxane and 2 ml of pyridine. The mixture is stirred at 25 ° C. for 5 hours. The reaction mixture is worked up in the same manner as in Example 1. The yield is 0.68 g (90.7%). 15

PRI me R 3. Z-Iod-4-morpholino-7-diethylaminocoumarin,

To a solution of 0.5 g (1.66 mmol) of 4-morpholino-7-diethylaminocoumarin in 30 ml of dioxane with stirring20

1.7 g (7.6 mmol) iodine solution and 2 ml of pyridine are poured. The mixture is stirred at 20 ° C for 6 hours. The reaction mixture is worked up as in Example 1. The yield is 0.6 g (84.5%). 25

EXAMPLE 4 2,3,6,7-Tetrahydro-9-methyl-10-iodo-1H, 5H-quinolizino-9.9a, 1-gh 3 coumarin.

To a solution of 0.25 g (1 mmol) of coumarin-102 in 30 ml of THF, a solution of 1 g (4 mmol) of iodine in 20 ml of THF and 1 ml of pyridine is poured. Stirred for 5 h at, the reaction mass is treated as described in example 1. Yield 0.32 g (85.3%). 35

EXAMPLE 5: 2,3,6,7-Tetrahydro-9-chloro-10-iodine, 1H, 5H-HINOLIZINO-C9, .9a, 1-gh 3 coumarin.

A solution of 1.6 g (6 mmol) iodine in 20 ml of dioxane and 2 ml of pyridine is poured into a ravator of 0.28 g (1 mmol) of the starting coumarin in 50 ml of dioxane 40. Stirred for 6 h at 20 C. The reaction mass is treated as in the example. Yield 0.35 g45

(87.6%).

The physico-chemical characteristics of 3-iodinemarines are presented in table 1.

The dependence of the yield of the target JQ products and conversion on the reaction conditions is presented in Tables 2 and 3 for the example of obtaining 3-iodo-4-methyl-7-diethylaminocoumarin.

Thus, from Table 2, 3 it is possible that the use of pyridine in an amount of less than 5: 1 leads to a decrease in conversion and an increase in the duration of the process, an increase in

the amount of pyridine does not increase the efficiency of the process.

The use of 4-6-fold molar amount of iodine in relation to the initial coumarin is optimal, since the use of a smaller amount of iodine significantly reduces conversion and increases the reaction time, and the use of large excess iodine leads to a decrease in the yield of the target product due to the occurrence of side reactions of polyiodication and oxidation. To achieve this goal, the use of aprotic low-polar oxygen-containing solvents, dioxane and tetrahydrofuran (THF), in which the initial coumarins dissolve well and iodine is satisfactory, is also optimal. In other solvents, the reaction is slower or is associated with the formation of by-products .

Lowering the temperature below 20 ° € slightly reduces the yield of the target product, and increasing it to 40 ° C will also lower the yield of the target product.

This method allows to increase the yield of target products by 10-13% and expand their range (all the compounds obtained, except for 3-iodo-7-methyl-7-diethylaminocoumarin; are new).

i

Formula iz gain

1. A process for the preparation of okoumarins substituted with 3-iodo-7-dialkyls of general formula I

ft

R3YYV3

 RaN VV Out

where R is methyl, chlorine atom, QQ group

with RJ, hydrogen and ethyl, or E together form a group (SND), by reacting the corresponding 7-aminocoumarin with iodine in the medium of an organic solvent in the presence of a catalyst, it is characterized by the fact that, in order to increase the yield and expand the range target products as

1I3-4

1700

“,

4, i 3.9

C "H" 110.1

 ci 130

 Et

 n

1715

41.3 3.5 3.7С, 4Н „НО, С1141.2 3.4 3.8

1A5

1700

, 7.7 4.9 6.5CpH HjO, 47.9 5.0 6.5

132

1690

50.4 4.2 3.7

214

1690

44.9 3.3 3.5 C, su tt, 2 3.3 3.3

Spreadsheets

The dependence of the yields of the target product on the reaction conditions

Dioxane

and

10 10 10

PMR spectrum к, k.d.

& ptd, T

1 4,4 4,0

2 3,4 3,8

, 9 5.0 6.5

7.45 (Ш, ц, 9П, Н-5), 6,6598.3

(1H, DD, 9Ga, 2.5 Ta, H-6)

6.50 (W, d, 2.5 ha, H-8),

3.38 (4H, k, 7.0 Gp (CH),

{2.40 (3H, d, CH,), 1.18

(6H, t, 7.0 MS) (CI),

7.60 (1H, d, 9 Ha, H-5), 6.60 90.7

(1H, dd, 9 Ha, 2.5 Hz, B-6),

6.57 (1H, d, 2.5 t.N-8).

3.43 (4H.it, 7 Hz, (CH,),),

1.22 (6H, t, 7 Ha, XCH / J

7.56 (1H, d, 9 Ha, H-5), 84.5

6.55 (IH, yes, 9 Hz, 2.5 Gp, H-6), 6.46 (W, d, 2.5 Hz, H-8), 3.93 f4H, r, 5 Hz, ( CHj 3.52 (4H, t, 5 Hz, (CH,), 1, 3.40 (4H, x, 7 HZ, (CHJ-), 1.20 (N.N.G. 7 Hz, (CH, ),)

4.4 3.8

3.3 3.6

7.53 (1H, C, HS), 3.74 (4H, q, 5 GN, (CHt) t), 3.37 (2H.T, 5 nt.CHj, 3.27 (2H.T, 5 HZ, CH,), 2.26 (4H, m, (CHt),)

7.24 (IH, s, H-5) 3.28 (4H.K, 5 GI, (fH,) t), 2.86 (2H.T, 5 rn.CHj, 2.7T (2H.T, 5 Hz, SI, 1.97 (4H, m, (CHt),)

85.3

a 2

24 20 6

20 53 90

96.8 97.7 97.8

15781268

Continued table. 2

Table3

The dependence of the yields of the target product on the reaction conditions

Claims (6)

Claim 1. The method of obtaining substituted 3-iodine-7-dialkylaminocoumarins of General formula I K 'where R ^ is methyl, a chlorine atom, the group _/ at Ry is hydrogen and R is ethyl, or B. ₄ and R 4 together form a group (CHj) ^, by reacting the corresponding 7-aminocoumarin with iodine in an organic solvent in the presence of a catalyst , distinguish -. The reason is that, with a chain for increasing the yield and expanding the assortment of target products, a compound of the general formula of value is used as the corresponding 7-aminocoumarin, dioxane or tetrahydrofuran as an organic solvent, and pyridine as a catalyst, and the process is carried out at a paint ratio of the compound of formula II, iodine and catalyst equal to 1: (4-6): 5, respectively. 2. The method according to p. |, Distinguishing between s and u with the fact that the process is carried out at 20-40 C. Table I 4.4 4.0 47.1 3.9 With "And" I ° "1 47.1 Me Et 113-4 H 90.7 ci 130 Et Η 1715 41.3 3,5 3,7 With „“ „IN, QI 41.2 3.4 3.8 145 1700 47.7 4.9 ^6.5 g> ^{I and <0 "1} 47.9 5,0 8.5 (1H, d, 9 Hz, H-5), (IH, yes, 9 Hz, 2.5 Hz, H-6), 6.46 (1H, d, 1 _____... 7.56 6.55 h-ό), v, n, d, 3.93 (4N, t, 5 Hz, 3.52 (4H, t, 5 Hz, 3.40 (4H, q, 7 Hz, 1.20 (6N-G, 7 Hz, 84.5 R, - Me, • (sir, 132 1690 50,4 4.2 3,7 C „H ,, ΕΟ, Ι .50.7 4.4 3.8 H, = Cl, B _t + R, • (CH,), 214 1690 44.9 3.3 3,5 46.2 3.3 3.8 >> m, 2.5 Hz. H-8), (cn) /, (CH,), 1,. (sn ‘)), (CH J J. 3.74 d) j CH,), 85.3 Table a 2 the dependence of the yields of the target product from the reaction conditions The molar ratio of iodine to coumarin Solvent The molar ratio of pyridine and coumarin Temperature ° C - Reaction time, h Conversion% Exit,% 1 2 3 4 5 6 7 1 Dee Ocean 10 20 24 20 96.8 2 _and _- 10 20 20 53 97.7 4 - 10 20 6 90 97.8 Ί Continuation of the table. 2 --- * —------------ I --'--- 1 2 3 4 ί 6 7 6 10 20 3 100 98.5 8 - 10 20 2,5 100 92.4 YU 10 20 1,5 100 73.3 6 - N— 10 fifteen 3 92 97.5 6 -eleven- 10 40 3 100 97.0 6 - eleven- 10 60 3 100 81.2 6 - eleven- 10 80 3 100 36.5 6 - eleven - 10 100 3 100 4.0 6 THF 10 0 3 40 98.0 6 - eleven- 10 10 3 78 98.3 b Dioxane 0 20 3 12 97.5 1 20 3 28 98.2 6 Dioxane 20 20 3 100 97.7 Table 3 The dependence of the yields of the target product on the reaction conditions Solvent The molar ratio of iodine to coumarin Temperature ~ reaction, С The molar ratio of pyridine and coumarin Reaction time h Conversion% Exit,% Dioxane 5: 1 20 0 3 12 97 - and - 5: 1 20 eleven 3 28 98 - eleven - 5: 1 20 3: 1 4 60 96 - and - 5: 1 20 5: 1 4 100 97 - eleven - 5: 1 20 7: 1 4 100 96 . ! T__ 5: 1. 20 10: 1 3 100 97 - N— 5: 1 20- 20: 1 3 100 97 CH ^ Cl, 5: 1 20 5: 1 4 70 90 EtOAC 5: 1 20 5: 1 4 60 83 C. ₆ H ₄ 5: 1 20 5: 1 4 55 87 MESP 5: 1 20 5: 1 4 92 75 DMF 5: 1 20 5: 1 4 95 68 DMSO 5: 1 20 5: 1 4 100 56 Compiled by I. Dyachenko Editor T. Lazorenko Tehred L. Serdyukova Corrector N. Revskaya Order 1883 Circulation 324 Subscription ChIIIPI of the State Committee for Inventions and Discoveries under the USSR SCST 113035, Moscow, Zh-35, Raushskaya nab., D. 4/5 Production and Publishing House Patent, Uzhhorod, st. Gagarina, 10