CS267399B1 - 2-arylimino-3-triphenylphosphonium indolalates and a method for their preparation - Google Patents

Abstract

The solution concerns new 2-arylimino-3-triphenylphosphonium indolates of the formula I. The compounds of the formula I are prepared by treating N- -aryl-N'-(2-benzyltriphenylphosphonium) thiourea bromides of the formula II with tosyl chloride and substances selected from the group including alkali hydroxides and alcoholates in an environment of lower alcohols in the temperature range of 0 to 100 °C. The new compounds are useful in the production of biologically active analogs of indole alkaloids.

Description

GONDA JOSEF RNDr. CSc., KRISTIAN PAVOL prof. Eng. DrSc., KOŠICE

2-Arylimino-3-triphenylphosphonium indolates and methods of their preparation (57) The solution concerns new 2-arylimino-3-triphenylphosphonium indolates of formula I. Compounds of formula I are prepared by treating N-aryl-N'-(2-benzyltriphenylphosphonium)thiourea bromides of formula II with tosyl chloride and substances selected from the group including alkaline hydroxides and alcoholates in the environment of lower alcohols in the temperature range of 0 to 100 °C. The new compounds are useful in the production of biologically active analogues 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 general formula I

where R denotes H, 2-CH2, 4-CH3, 4-O4,0, 3-Cl and methods for their preparation.

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

A study of the literature showed that 2-arylinino-3-triphenylphosphonium indolates are new compounds not yet described in the literature.

The essence of the method for preparing 2-arylimino-3-triphenylphosphonium indolates according to the invention consists in reacting N-aryl-N'-(2-benzyltriphenylphosphonium) thiourea bromides of the general formula II

CH ₂ -P(C ₆ H ₅ ) ₃ Br ⁽ )

NH-CS-NH

>R where R denotes H, 2-CH2, 4-CH2, 4-CH20, 3-Cl, reacts with tosyl chloride in the presence of substances selected from the group consisting of alkali hydroxides or alcoholates in the environment of lower alcohols in the temperature range of 0-100 °C.

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

The subject of the invention is illustrated but not limited by the following examples:

Example 1

0.66 g of sodium methanolate was added to a suspension of 5.83 g of N-phenyl-N'-(2-benzyltriphenylphosphonium)thiourea bromide in 50 ml of methanol. The reaction mixture after 5 min. cools down to 10 °C and within another 5 min. 2.1 g of tosyl chloride is added in portions. 1.3 g of sodium methanolate is then added to the reaction mixture. The solution is stirred at 45-50°C until the dark red color of the transient ylide formed changes to yellow. The reaction mixture is filtered while hot and allowed to stand overnight. The precipitated 2-phenylimino-3-triphenylphosphonium indolate is crystallized from a chloroform-hexane mixture; (physico-chemical properties are listed 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, 0.4 g of sodium hydroxide in 20 ml of ethanol is added with stirring. After 10 min. 2 g of solid tosyl chloride are added and stirred for another 10 min. 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 a chloroform-hexane mixture, or ethanol.

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

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

Spectral measurements

IR spectra were measured on a Specord IR 75 spectrophotometer (Carl Zeiss Jena). Ή NMR spectra taken on a 100 MHz Tesla BS 567 spectrometer and ^.3 C NMR (25.04 MHz) on a Tesla BS 567 spectrometer. Mass spectra taken on an MS 902S spectrometer (AEI 'Manchester) at 70 eV.

Table 1

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

Product of formula III R’ Formula (mol. hr.) Yield (mp,°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 - CH3C0H4} (482.6) 76-78 82.19 5.72 5.75 lily 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 lily 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, n/z (rel. int., %): 483 (M+, 16). 368 (53), 262 (95), 222 (98), 183 (100), 151 (41),131 (40).104 (86). .

^b T.p. of the addition compound with methanol. free base is unstable.

¹ Mass spectrum, n/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 general formula III

4 Product H-7 (d) H-6(dd) H-5 (dd) H-4(d) P(C _ø H ₅ RH Other protons lilac 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) lily b b b 6.30 7.51-7.88 3.79 s(NH) 3.38 s(CH) likl 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 general formula III

C-atom _Xj (C,P),Hz lilac IIIc Illd 1’ 123.1 124.1 123.1 (x=1) (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