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Synthesis and Some Reactions of Naphthoylacetanilides M. I. Ali, M. M. S. El-Morsy, N. M. Hassan, and M. Sharaf Department of Chemistry, Faculty of Science, University of Cairo, A . R . Egypt

Z. Naturforsch. 33 b, 425-428 (1978); received December 12, 1977

Naphthoylacetanilides The structure of some naphthoylacetanilides (1) obtained from a new route of synthesis

is elucidated via inspection of I R , N M R , and mass spectral data. Napthoylacetanilides condensed with one or two moles of aromatic aldehyde to give 2-(naphthoyl )-cinnamanili-des (2) or 3-aryl-2,2'-dinaphthoyl-glutaric acid dianilides (3). Compound 2b added phenylmercaptan to give 3-phenyl 3-phenylthio-2-naphthoyl-propananilide (4). Reduction of 2b gave 2-benzyl 2-(2-naphthoyl)acetanilide (5). 1 is coupled with aryldiazonium salt to give 2-oxo naphthoylacetanilides-2-arylhydrazones (6). The mechanism of the reactions is discussed.

Examination of the literature revealed that naph-thoylacetanilides have not been investigated in any way. Thus we set out to study the reactions of this class of compounds and to compare them with those of benzoylacetanilides. This work describes the preparation of naphthoylacetanilides (1) and investigates some of the reactions of these anilides. Weizmann [1] in 1906 first prepared ethyl 2-naph-thoylacetate by acting on ethyl sodioacetoacetate with naphthoyl chloride. Naphthoylacetanilides were prepared by the following general procedure. Naphthoic acid was converted, by action of thionyl chloride into naphthoyl chloride, and this was then allowed to react with equimolecular of aceto-acetanilides dissolved in 20% sodium hydroxide solution at 2 °C. The product obtained was then digested with ammonia and ammonium chloride mixture to give naphthoylacetanilides (1).

l a : l b : l c : I d : l e : I f :

l h :

RCOCH 2 CONHAr 1 Ar = C 6 H 5 ; Ar = CeHiCl-p; Ar = C 6 H 5 ; Ar = C 6 H 4 CH 3 -p ;

R = 1-naphthyl, R = 1-naphthyl, R = 2-naphthyl, R = 2-naphthyl,

Ar = C 6 H 4 OCH 3 -p ; R = 2-naphthyl, Ar = CßHiBr-p; R = 2-naphthyl, Ar = CeHLjCl-p; R = 2-naphthyl, Ar = C 6 H 4 N 0 2 - m ; R = 2-naphthyl.

Naphthoylacetanilides are soluble in alcoholic sodium hydroxide. Solution, their alcoholic solution give deep violet colour with ferric chloride. The IR spectrum (KBr) of l a shows peaks at 3270 (NH); 1720 ( C = 0 ) and 1650 cm-i (CONH). The NMR spectrum (CDC13 - f TMS) of Id shows peaks at 9.24 ppm (s, NH), 7.30 ppm (m, aromatic protons), 4.24 ppm (s, CH2) and 2.32 ppm (s, CH3).

Requests for reprints should be sent to Dr. M. M. S. El-Morsy, Department of Chemistry, Faculty of Science, University of Cairo, Giza, A. R . Egypt.

The mass spectrum of 2-naphthoylacetanilide ( l c ) at 70 eV exhibited the expected peaks at 155, 134, 127, 93. The rearrangement ion at m/e 93 (base peak) is common to acetanilides [2] and a recent paper suggestes that this ion probably has the aniline structure [3]. The ions at m/e 170.0 and 119 are the product of y-hydrogen transfer from the amide nitrogen to the naphthoyl moiety. The structure of ions at m/e 170 and 119 are represented 2-acetylnaphthalene enol ion and the molecular ion pheny lisocy anate.

c=o*

m/e 127 (62V.)

NH2

m / e 155 (60V.)

Q ^ C 0 C H 2 C 0 N H - Q

m/e 289 (33V.)

f OH

m / e 170 (25V.)

Naphthoylacetanilides condense with equimolecular amounts of aromatic aldehydes to 2-arylmethylene derivatives; 2-(naphthoyl)cinnamanilides (2).

m/e 93 (100V.)

N-C=0

m/e 119(20%)

0 0 R - L C—NHAr

I CHA/'

0 I

R-C-CHCONHAr j Ar'-CH

I R—C—CHCONHAr

I 0

2 3 2 a : Ar = C 6 H 5 ;

R = 1-naphthyl, 2 b : Ar = C 6 H 5 ;

R = 2-naphthyl, 2 c : AT = C 6 H 5 ;

R = 2-naphthyl, 2 d : Ar = C 6 H 4 OCH 3 -p ; Ar ' = C 6 H 4 NMe 2 -p ;

R = 2-naphthyl,

A t ' = C 6 H 5 ;

Ar ' = C 6 H 5 ;

A t ' = CeHjOCHa-p;

426 M. I. Ali et al. • Synthesis and Some Reactions of Naphthoylacetanilides 426

However, when two moles of naphthoylacetanili-des react with one mole of aromatic aldehyde under the same condition, the bis-compound, 3-aryl-2,2'-dinaphthoyl glutaric acid dianilides (3) were obtained.

3 a : Ar = C 6 H 5 ; Ar' = C 6 H 5 ; R = 1-naphthyl,

3b : Ar = C 6 H 5 ; Ar' = C 6 H 5 ; R = 2-naphthyl,

3c: Ar = C6H5; Ar' '= C6H4OCH3-p; R = 2-naphthyl.

The NMR spectrum (acetone-d6 + TMS) of 2d shows peaks at 9.24 (s, NH), 7.30 (m, aromatic protons); 6.1 (s, CH), 4.28 (s, OCH3) and at 3.75 (d, (CH3)2N). The I R spectrum (KBr) of 2 a shows C = 0 absorption at 1660 cm - 1 , i.e., it is shifted to a lower frequency in comparison with naphthoyl-acetanilides. This can be attributed to conjugation of the CO group with C = C in 2. The IR spectrum (KBr) of 3 shows CO absorption at about 1720 cm - 1

almost with no shift from that of 1. The formation of the bis-compound 3 probably proceeds by the addition of naphthoylacetanilides to the aryl-methylene derivatives (2) first formed. This has been shown by the reaction of naphthoylacet-anilide ( la) with its benzylidene derivative (2a) in presence of piperidine to give (3 a). Here the behav-iour of naphthoylacetanilides towards aromatic aldehyde is in line with the reaction of acetoacet-anilides [4-6] and benzoylacetanilides with aromatic aldehydes. Compound 2 b adds phenylmercaptan to give 3-phenyl-3-phenylthio-2-naphthoyl propan-anilide (4).

RCOCHCONHC6H5 R-COCHCONHC6H5 I I

C6H5-S-CH-C6H5 CH2—CÖHÖ R = 2-naphthyl 2-naphthyl 4 5

When 4 was heated above its melting point, the 2-benzylidene derivative (2b) was obtained [7]. The ease of removal of the addend indicates that the product is the result of simple addition. The IR spectrum (KBr) of 4 reveals CO absorption at Ca 1720 cm - 1 similar to that of naphthoylacetanilide i.e., the C = C double bond in 2 has become saturat-ed. 2-Benzyl-2-naphthoylacetanilide (5) was ob-tained by the reduction of 2 b with zinc dust and acetic acid or by the action of benzyl chloride on l c in presence of sodium ethoxide. Its NMR spectrum shows peaks at 3.47 (d, CH); 4.90 (t, CH2) and 7.80 (m, aromatic). Naphthoylacetanilides couple with

aryldiazonium salts in sodium acetate buffered solution, in presence of sodium hydroxide or pyridine to give 2 oxo naphthoylacetanilide-2-aryl-hydrazones (6).

RCOCCONHAr

N - N H A r ' 6

The NMR spectrum (CCI4 + TMS) of 6 a shows peaks at 9.75 ppm (s, NH); 7.25 ppm (m, aromatic protons) and 3.63 ppm (s, N H ) .

6 a : AT = C6H5; Ar' = CeH5; R = 1-naphthyl,

6b : Ar = C6H4Cl-p; Ar' = C6H4OCH3 -p R = 1-naphthyl,

6 c : AT = C6H5; Ar' = C6H5; R = 2-naphthyl,

6d : AT = CrHÖ; Ar' = C6H4OCH3 -p R = 2-naphthyl,

6e : Ar = C6H4CH3 -p; Ar' = C6H4C1-P; R = 2-naphthyl,

6 f : Ar = C6H4CH3 -p; Ai-' = C 6 H 4 N0 2 -m ; R = 2-naphthyl,

6 g : Ar = Cel^CHg-p; Ar' = C 6 H 4 N0 2 -o ; R = 2-naphthyl,

6 h : Ar = C6H4OCH3 -p; ; Ar' = C6H4Cl-p; R = 2-naphthvl,

6 i : Ar = CelUBr-p; Ar' = C6H5; R = 2-naphthyl,

6 j : Ar = CeHtCl-p; Ar' = CeH^CH^p; 6 j : R = 2-naphthyl,

6 k : Ar = C 6 H 4 N0 2 -m ; Ar' — CeHiBr-p; R = 2-naphthyl,

61: Ar = C 6 H 5 ; Ar' = C6H4Br-p; R = 2-naphthyl.

The hydrazone structure of 6 which conforms with that of the coupling products of diazonium salts with aliphatic components [8, 9] is supported by I R spectra. The IR spectrum (KBr) of 6 a shows a C = 0 absorption at 1660 cm-1 when this is compared with the C = 0 absorption of naphthoylacetanilide ( v c o = 1720 cm - 1) , it appears to have undergone a shift to lower frequency. This can be attributed to its conjugation with C = N and hydrogen bonding [10, 11]. Phenylhydrazone and phenylazo com-pounds have different UV spectra. Azo compounds show a strong band at 270-280 nm, phenylhydra-zones give a weak band (or no band) in this region, but they give a strong absorption band higher than 320 nm [11, 12].

Experimental Melting points are uncorrected. I R spectra were recorded (KBr) on a Carl Zeiss

Infrared spectrophotometer Model " V R 10". The NMR spectra were taken on a Varian EM-390 NMR spectrometer.

M. I. Ali et al. • Synthesis and Some Reactions of Naphthoylacetanilides 427

Naphthoylacetanilides (1) 0.1 mole acetoacetanilide was dissolved in 60 ml

of 20% aqueous sodium hydroxide solution, mixture was cooled to 2 °C and stirred, 0.1 mole of pure naphthoyl chloride was added dropwise from a dropping funnel, if liquid or 0.1 g increments if solid, while the temperature kept below 5 °C. After all the acid chloride was added the mixture was stirred for 1 h at 5 °C, and for an additional 30 min at room temperature. The mixture was diluted with 15 ml of 25% aqueous ammonia solution containing 5.4 g (0.1 mole) of ammonium chloride and stirred for 5 min. The resulting mixture was heated for 40-50 °C. The solid obtained was filtered and crystallised from alcohol. Table I lists the melting points, percent yield and elemental analysis of each anilides.

2- (Naphthoyl)-cinnamanilides (2) 0.01 mole 1, an equimolecular amount of the

appropriate aldehyde and two drops of piperidine were refluxed, in 20 ml ethanol for 2 h and left overnight. 2 is washed with dilute ethanol and crystallised from acetic acid (see Table II).

3-Aryl-2,2'-dinaphthoyl-glutaric acid dianilide (3) 0.01 mole 1, 0.005 mole of the appropriate alde-

hyde and two drops of piperidine were refluxed in 20 ml ethanol for 1 h, cooled and the formed precipitate washed with dilute ethanol and crystal-lised from acetic acid (see Table III).

Addition of naphthoylacetanilides to 2- (naphthoyl)-cinnamanilides

0.005 mole 2, an equimolecular amount of 1 and two drops of piperidine were refluxed in 15 ml ethanol for 1 h and left overnight. 3 was washed with dilute ethanol and crystallised from acetic acid.

3-Phenyl-3-phenylthio-2-naphthoyl-propananilide (4) 1 g 2b, 0.5 g phenylmercaptan and one drop

piperidine were heated on a water bath for 1 h. 4 was washed with petroleum ether (65-80), and crystallised from alcohol, m.p. 175 °C; yield 71%. C 3 2 H 2 5 N O 2 S

Calcd C 78.82 H 5.16 S 6.57, Found C 78.6 H 5.0 S 6.7.

Table I. Naphthoylacetanilides (1).

Analysis Compound m.p . Yield Formula Carbon Hydrogen Halogen Nitrogen

[°C] [ % ] Calcd Found Calcd Found Calcd Found Calcd Found

l a 155 68 C 1 9 H 1 5 N O 2 78.87 l b 118 71 C 1 9 H 1 4 C I N O 2 70.48 l c 144 73 C 1 9 H 1 5 N O 2 78.87 I d 146 75 C20H17NO2 79.18 l e 154 62 C20H17NO3 75.22 I f 155 79 Ci 9 H 1 4 BrN0 2 61.97 l g 148 71 CI9H1 4C1N02 70.48 l h 138 76 CI 9 H 1 4 N 2 0 4 68.26

78.76 5.23 5.18 - - 4.84 4.93 71.0 4.36 4.40 10.95 10.90 4.33 4.21

5.23 - - 4.84 4.76 79.10 5.65 5.50 - - 4.62 4.81

5.37 - - 4.39 4.50 3.83 21.70 22.00 3.80 4.36 10.95 4.33 4.5

68.4 4.22 4.12 - - 8.38

Table II . C-(Naphthoyl)-cinnamanilides (2).

Analysis Compound m.p . Yield Formula Carbon Hydrogen Nitrogen

[°C] [ % ] Calcd Found Calcd Found Calcd Found

2 a 209 2b 199 2c 204 2d 220

89 C26H19NO2 81 C26H19NO2 8 2 C 2 7 H 2 1 N O 3

86 C29H26N203

82.73 82.48 5.07 82.73 5.07 79.59 80.00 5.20 77.31 77.50 5.82

5.20 3.71 3.80 3.71 3.80

4.90 3.44 3.60 5.60 6.22

Table III . 3-Aryl-2,2'-dinaphthoyl-glutaric acid dianilides (3).

Analysis Compound m.p. Yield Formula Carbon Hydrogen Nitrogen

[°C] [%] Calcd Found Calcd Found Calcd Found

3 a 223 82 C45H34N204 81.06 80.88 5.14 5.02 4.20 3b 193 85 C45H34N204 81.06 5.14 4.20 4.10 3c 215 76 C 4 6 H 3 6 N 2 0 5 79.29 79.40 5.21 5.08 4.02 3.90

428 M. I. Ali et al. • Synthesis and Some Reactions of Naphthoylacetanilides 428

Action of heat on 3-phenyl-3-phenylthio-2- naphthoylpropananilide

0.5 g was heated in an oil bath at 180 °C for sometimes and cooled. The product was washed with petroleum ether (60-80), and crystallised from acetic acid, m. p. 199 °C (not depressed on admixture with 2 b).

2-Benzyl-2-naphthoylacetanilide (5) a) 1 g 2 b and 0.5 g zinc dust were refluxed for

5 min in acetic acid. 5 was obtained on dilution with water, and crystallised from ethanol, m.p. 162 °C, yield 75%. C26H21NO2

Found C 82.3 H 5.2 N 3.8, Calcd C 82.29 H 5.58 N 3.7.

b) 0.005 mole naphthoylacetanilide, dissolved in 15 ml absolute ethanol containing 0.1 g sodium metal and 0.005 mole of benzyl chloride were refluxed for 1 h. 5 was obtained on dilution with water and crystallised from ethanol.

2-Oxo - naphthoylacetanilide - 2-arylhydrazones (6)

3 g naphthoylacetanilide were dissolved in 40 ml ethanol (containing 1 g sodium acetate), in pyridine, or in aqueous sodium hydroxide, cooled in an ice bath and treated with an equimolecular amount of the diazotised aromatic amines, and left for 2 h. The product was collected and crystallised from acetic acid (see Table IV).

Table IV . 2-Oxo-naphthoylacetanilide-2-arylhydrazone (6).

Analysis Compound m.p . Yield Formula Carbon Hydrogen Halogen Nitrogen

[°C] [ % ] Calcd Found Calcd Found Calcd Found Calcd Found

6 a 143 85 C25H19N3O2 76.32 76.10 4.87 4.68 - - 10.68 10.50 6 b 187 69 C26H20CIN3O3 - - 7.74 7.8 6 c 161 79 C25H19N3O2 - - - - - - 10.68 10.55 6d 178 74 C26H21N3O3 73.74 74.1 5.0 4.88 - - 9.92 10.1 6e 181 75 C26H2oC1N302 - - - - 9.51 9.39 6f 220 83 C26H20N4O4 69.02 69.3 4.46 4.7 - - 12.38 12.7 6g 209 72 C26H20N4O4 69.02 68.90 4.46 4.5 - - - -6h 237 77 C26H20CIN3O3 68.20 67.90 4.40 4.50 7.74 7.9 9.18 9.5 6i 162 84 C25Hi8BrN302 63.57 - 3.84 - 16.92 16.80 8.9 8.7 6 j 187 67 CMHjoCINAJ 70.66 70.5 4.56 4.4 8.02 8.4 6k 211 86 C25Hi7BrN404 58.04 57.9 3.31 3.19 15.95 15.6 61 178 80 C 2 5Hi 8BrN 302 63.57 63.3 3.84 3.7 - - 8.9 9.0

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