The preparation of N -acylbenzotriazoles from aldehydes

N -Acyl- ( 3a–g ) and N -alkyl-benzotriazoles ( 10a–c ) were prepared from the corresponding aldehydes or alkanes, respectively, using a slight excess of N -chlorobenzotriazole in the presence of AIBN (2,2’-azobisisobutyronitrile) as an initiator.


Introduction
N-Acylbenzotriazoles are versatile N-and C-acylating agents [1][2][3] for the preparation of primary, secondary and tertiary amides 2 including formamides 4 and oxamides, 5 cinnamoyl hydrazides, 6 enaminones 3 and for the conversion of ketone enolates into β-diketones. 7iterature syntheses of N-acylbenzotriazoles (i) react acid chlorides with 1-(trimethylsilyl)benzotriazole, 8 the sodium salt of benzotriazole, 9 or benzotriazole 10,11 ; (ii) react carboxylic acids with 1-(methanesulfonyl)benzotriazole; 6 or (iii) employ palladium catalyzed carbonylation of diaryliodonium salts in the presence of benzotriazole. 12n cases where the aldehyde is more readily available than the corresponding carboxylic acid, it is convenient to carry out the conversion of aldehyde RCHO into an acylating agent RCOX.Indeed, a number of methods are available for the direct conversion of aldehydes to the corresponding acid halides: (i) by the treatment of aromatic aldehydes with SO 2 Cl 2 in the presence of a phosphonium catalyst; 13 (ii) use of N-chlorosuccinimide; 14,15 (iii) carbon tetrahalides at high temperatures; 16 (iv) vapor phase photochemical halogenation; 17 and (v) iodobenzene dichloride. 18-Chlorobenzotriazole has been widely used as (i) a mild oxidant 19,20 for the preparation of aldehydes, ketones, 21 azo-compounds, 21 sulphoxides, 20 sulfonimidoyl chlorides, 22 nitrile oxides; 23 (ii) a chlorinating agent 24,25 and (iii) for addition reactions to olefins [26][27][28] and isonitriles. 29Rees and Storr showed that the reactions of N-chlorobenzotriazole as an oxidant are radical in nature. 26e now show that N-chlorobenzotriazole (2) conveniently converts aldehydes 1a-g into the corresponding N-acylbenzotriazoles 3a-g (Scheme 1).Alcohols 8a and 8h are also converted into acylbenzotriazoles (Scheme 4), while substituted toluenes give the corresponding Nalkylbenzotriazoles 10a-c.All these reactions take place in the presence of AIBN 15 as a radical initiator.

Results and Discussion
Preparation of N-acylbenzotriazoles 3a-g.Refluxing aldehydes 1a-g with Nchlorobenzotriazole (2) in benzene for 0.5-4h in the presence of catalytic AIBN led to the Nacylbenzotriazole; yields in 53-83 % except for the furyl derivative 3g.(Scheme 1) This resembles the known reaction of aldehydes with N-bromosuccinimide to give the corresponding acid bromides using catalytic amount of AIBN as a radical initiator. 15Results are shown in Table 1.Known products were identified by m.p. and direct comparison of the NMR spectra.Compound 3e is novel and its structure is supported by elemental analysis and its spectra.Treatment of 4-methoxynaphthaldehyde (4) using our standard conditions formed a mixture of two compounds, however using 2 equivalents of N-chlorobenzotriazole gave 1H-1,2,3benzotriazol-1-yl-(3-chloro-4-methoxy-1-naphthyl)methanone (5).(Scheme 2) Boehlow et al. showed that ring halogenation takes place on the reaction of 4-methoxybenzaldehyde with Nbromosuccinimide. 32Compound 5 was identified from its elemental analysis and spectral examination.4-(Dimethylamino)-2-nitrobenzaldehyde (6), on treatment with 2 equiv of Nchlorobenzotriazole gave three ring halogenation products 7a-c (Scheme 3), which were separated by column chromatography.The structures of 7a-c were assigned on the basis of 1 H and 13 C NMR data and elemental analyses.

Scheme 3
The oxidation of alcohols into the corresponding aldehydes by N-chlorobenzotriazole has been reported previously. 19We now show that two equivalents of N-chlorobenzotriazole converted alcohols 8a,h as expected into the corresponding N-acylbenzotriazoles 3a,h (Scheme 4), which were purified by recrystallization.Known 3a was identical with the authentic sample, novel 3h was identified by elemental analysis and 1 H and 13 C NMR spectra.

Scheme 5
Compounds 10a and 10b had singlets at δ 5.84 and 5.82 identical with spectra previously published. 34Novel compound 10c was identified by elemental analysis and by its 1 H and 13 C NMR spectra.

Experimental Section
General Procedures.Melting points were determined on a hot-stage apparatus and are uncorrected.NMR spectra were recorded in CDCl 3 with TMS as the internal standard for 1 H (300 MHz) or a solvent as the internal standard for 13 C (75 MHz).Micro elemental analyses were performed on a Carlo Erba EA-1108 elemental analyzer.Materials.1-Chlorobenzotriazole (2) was synthesized according to the previously published procedure 47 as white crystals mp 103-105 o C (103-105 o C 47 ).4-(Dimethylamino)-2nitrobenzaoldehyde (6) was synthesized according to the published procedure by Baumann et al. 48and was confirmed by the NMR data and CHN analysis.

General procedure for the synthesis of N-acylbenzotriazole from the corresponding aldehydes (3a-g)
The mixture of corresponding aldehyde (11 mmol), N-chlorobenzotriazole (2.70 g, 17.6 mmol) and AIBN (0.1 g, 0.6 mmol) in benzene (80 mL) were refluxed for the specified time (Scheme 1).To the cooled reaction mixture ethyl acetate was added, and the organic layer was washed with saturated aqueous Na 2 CO 3 , brine, and dried over MgSO 4 .The solvent was evaporated to give the crude product, which was purified by recrystallisation from the appropriate solvent to afford the pure compound.

General procedure for the synthesis of N-acylbenzotriazole (3a, 3h) from the corresponding alcohols
The mixture of alcohol (8 mmol) and N-chlorobenzotriazole (1.78 g, 11.6 mmol) in benzene (100 mL) were refluxed for 2 h, then AIBN (0.1 g, 0.6 mmol) and the next portion of Nchlorobenzotriazole (1.70 g, 11.1 mmol) were added.The solution was kept at 80 o C for the specified time (Scheme 1), then stirred at room temperature overnight.To the reaction mixture, ethyl acetate was added and the organic layer was washed with saturated aqueous Na 2 CO 3 , brine and dried over anhyd.MgSO 4 .The solvent was evaporated to give the crude product, which was purified by recrystallisation from the appropriate solvent to afford the pure compound.1H-1,2,3-Benzotriazol-1-yl (phenyl)methanone (3a).White needles from 2-propanol (60 %), mp 112−113 °C (112−113 °C30 ).The spectrum is identical with that for compound 3a prepared from benzaldehyde above.

General procedure for the synthesis of N-alkyl-and N-aryl-benzotriazoles (10a-c)
The a mixture of N-chlorobenzotriazole (2.30 g, 15.0 mmol) and AIBN (0.1 g, 0.6 mmol) in excess of corresponding toluene as a reagent as well as solvent (126.8 mmol) were heated at 105-110 o C for the specified time (Scheme 3).To the cooled reaction mixture, ethyl acetate was added, and the organic layer was washed with saturated aqueous Na 2 CO 3 , brine and dried over anhyd.MgSO 4 .The solvent was evaporated under reduced pressure to give the crude product, which was purified by recrystallization from the appropriate solvent to give the pure compound.