CS267399B1 - 2-arylimino-3-triphenylphosphonium indolates and method of their preparation - Google Patents

Abstract

The present invention relates to novel 2-arylimino-3-triphenylphosphonium of the indoles of formula I. Compounds of formula (I) are attributed to N- -aryl-N - (2-benzyltriphenylphosphonium) thiourea of formula II are caused by tosyl chloride and substances selected from the group consisting of alkali hydroxides and alcoholates in lower alcohols in a temperature range of 0 to 100 ° C. New bad The compounds are useful in the production of biologically effective indole alkaloid analogues.

Description

GONDA JOZEF RNDr. CSc., KRISTIAN PAVOL prof. DrSc., KOŠICE

2-Arylimino-3-triphenylphosphonium indolates and process for their preparation (57) The solution relates to novel 2-arylimino-3-triphenylphosphonium indolates of formula I. The compounds of formula I are prepared by reacting N-aryl-N '- (2 -benzyltriphenylphosphonium) thioureas of formula II are treated with tosyl chloride and substances selected from the group consisting of alkali hydroxides and alcoholates in a lower alcohol environment in the temperature range from 0 to 100 ° C. The novel compounds are useful in the production of biologically active analogs of indole alkaloids.

CH ₂ -P (C ₆ H _{s) 3} Br <

NH-CS-NH

CS 267 399 Bl

The invention relates to 2-arylimino-3-triphenylphosphonium indolates of the formula I.

wherein R denotes H, 2-CH 2, 4-CH 2, 4-04.0, 3-Cl and a process for their preparation.

Heterocyclic phosphorus ylides are important intermediates in the synthesis of biologically active substances [J. J. Pappas, E. Gantzer: Heterocycl. Chem. 6, 265 (1969)].

A study of the literature has shown that 2-arylamino-3-triphenylphosphonium indolates are new compounds not yet described in the literature.

The process for the preparation of 2-arylimino-3-triphenylphosphonium indolates according to the invention consists in applying to the bromides of N-aryl-N- (2-benzyltriphenylphosphonium) thioureas of the general formula II

CH ₂ -P (C ₆ H ₅ ) ₃ Br ⁽ )

NH-CS-NH

> R where R denotes H, 2-CH 2, 4-CH 2, 4-CH, 0.3-Cl, is treated with tosyl chloride in the presence of substances selected from the group consisting of alkali hydroxides or alcoholates in a lower alcohol environment in the temperature range 0-100 ° C.

The 2-arylimino-3-triphenylphosphonium indolates of the present invention are a novel and reactive type of heterocyclic ylide capable of reacting with carbonyl compounds into the Wittig reaction to form 2-arylimino-3-alkylidene indoles which are useful for the synthesis of biologically active analogs of indole alkaloids.

The following examples illustrate but do not limit the invention:

Example 1

To a suspension of 5.83 g of N-phenyl-N- (2-benzyltriphenylphosphonium) thiourea bromide in 50 ml of methanol was added 0.66 g of sodium methanolate. The reaction mixture was stirred for 5 min. cooled to 10 ° C and over a further 5 min. 2.1 g of tosyl chloride are added portionwise. 1.3 g of sodium methanolate are then added to the reaction mixture. The solution was stirred at 45-50 ° C until the dark red color of the transient ylide formed turned yellow. The reaction mixture was filtered hot and allowed to stand overnight. The precipitated 2-phenylimino-3-triphenylphosphonium indolate is crystallized from chloroform-hexane; (physical chemical properties are given in Table 1).

Example 2

To a suspension of 5.97 g of N- (4-tolyl) -N- (2-benzyltriphenylphosphonium) thiourea in 100 ml of ethanol cooled to 5 ° C was added 0.4 g of sodium hydroxide in 20 ml of ethanol with stirring. After 10 min. 2 g of solid tosyl chloride are added and the mixture is stirred for a further 10 minutes. Finally, 0.9 g of sodium hydroxide in 30 ml of ethanol is added to the reaction mixture and heated to 60-65 ° C. After 30 min. insoluble salts are filtered off and the reaction mixture is allowed to stand overnight. The precipitated residue is crystallized from chloroform-hexane or ethanol.

The obtained 2-arylimino-3-triphenylphosphonium indolates are lived crystalline substances (physical-chemical properties are given in Table 1).

The structure of the compounds was proved by IR, 1 H NMR and ¹³ C NMR spectra and mass spectra (Tables 2 and 3).

Spectral measurements

IR spectra were measured on a Specord IR 75 spectrophotometer (Carl Zeiss Jena). 1 H NMR spectra were measured on a Tesla BS 567 100 MHz spectrometer and ¹³ C NMR (25.04 MHz) on a Tesla BS 567 spectrometer. Mass spectra were read on an MS 902S spectrometer (AEI 'Manchester) at 70 eV.

Table 1

Physico-chemical properties of 2-arylimino-3-triphenylphosphonium indolates of formula III

Product of formula III R ' Formula (mol. hni.) Yield (m.p., ° C) (NH) Calculated / found %C % H % N IIIa ^(! ” C „H„ N, P 67 3198 82.03 5.38 5.97 CH, (468.5) " 118-121 82.00 5.33 5.91 iflb c „h ₂₇ n ₂ p 43 3206 82.13 5.64 5.80 2-CH ₃ C ₀ H ₄ (482.6) 76-78 82.19 5.72 5.75 lile c „h„ n ₂ p 71 3200 82.13 5.64 5.80 4-CH, CTI, (48¾ ² 163-166 82.03 5.67 5.75 llkl ^ C „H„ N, OP 76 3180 79.49 5.46 5.62 4-CH.OC II (498.6) 141-143 79.53 5.39 5.60 lile CJL.CIN ,! ’ 52 3203 76.41 4.81 5.57 3-ClC ₆ H ₄ 'fedi.o) ² 164-166 < ^{! 1} ) 76.41 4.81 5.57

I i

CS 267 399 Bl ^{3 4}

I ”Mass spectrum, ni / z (rel. Int.,%): 483 (M +, 16). 368 (53), 262 (95), 222 (98), 183 (100), 151 (41), 131 (40) .104 (86). .

^b M.p. for the methanol addition compound. the free base is unstable.

¹ Mass spectrum, ni / z (rel. Int.,%); 499 (M ⁺ , 23), 384 (63), 262 (90), 238 (75), 222 (95), 199 (100), 107 (61).

Table 2

Ή NMR spectrum; 2-arylimino-3-triphenylphosphonium indolates of formula III

4 Product H-7 (d) H-6 (dd) H-5 (dd) H-4 (d) P (C _r H ₅ RH Other protons purple 6.90 6.73 6.63 6.25 7.05-7.90 5.05 s (NH) II Ib 7.00 6.81 6.63 6.25 7.35-7.80 5.43 s (NH) 2.18 s (CH) lile b b b 6.30 7.51-7.88 3.79 s (NH) 3.38 s (CH) líkl 6.98 6.75 6.58 6.23 7.43-7.88 4.91 s (NH) 3.72 s (CH)

^b 6.33-7.03 m (H-7, H-6, H-5 overlap with Η-Ar (4-tolyl).

Table 3 "C NMR spectra of 2-arylimino-3-triphenylphosphonium indolates of formula III

C-atom _Xj (C, P), Hz purple IIIc Illd 1 ' 123.1 124.1 123.1 (x = l) (90.1) (88.3) (90.1) 2 ’ 133.2 134.2 133.5 (x = 2) (9.4) (11.3) (11.3) 3 ' 129.7 129.7 129.5 (x = 3) (11.3) (11.1) (11.3) 4 ' 133.1 133.6 133.3 (x = 4) (2.8) (2.1) (-) 2 157.8 159.3 158.6 (x = 2) (14.9) (14.7) (14.1) 3 55.5 55.3 54.4 (x — 1) (120) (120) (120.2) 9 133.8 133.1 133.4 (x = 2) (14.1) (14.1) (15) 8 147.9 149.5 148.4 (x = 3) (18.3) (19.6) (20.1) 7 114.8 115.5 114.7 6 115.4 116.6 1.15.2 5 116.8 117.9 116.9 4 117.5 118.7 117.6 CH, - 20.6 - CH, -N - - - 10 ‘ 142.5 140.1 135.9 11 115.8 116.6 135.9 12 127.6 129.1 113.5 13 118.2 128.6 152.3 14 - - -

Γ, 2 ', 3', 4 '- positions of benzene rings in P (C ₆ H ₅ ) _r

CS 267 399 Bl

Claims (1)

SUBJECT 1. 2-Arylimino-3-triphenylphosphonium indolates of formula I II). H 2 ^{P (C} 6 ^{H 5} 13 ' ^{) (I)} wherein R is H, 2-CH ₃ , 4-CH ₃ , 4-CH ₃ O, 3-Cl 2. Process for the preparation of 2-arylimino-3-triphenylphosphonium of indolates according to item 1 of formula I, characterized in that the bromides of N-aryl-N '- (2-INVENT-benzyltriphenylphosphonium) thioureas of the general formula II (·),) CH ₂ -PIC ₆ H ₅ ) ₃ Br''txlL ( HJ ^^ ^{X is} NH-CS-NH wherein R represents H, _{2-CH3, 4-CH3,} 4-CH, O, C1-3 subjected to the forces tosyl chloride in the presence of heated ingredients from the group comprising hydroxides and alcoholates of alkali in an lower alcohol in the temperature range 0-100 ° C Severography, n. P., MOST