Bull. SOC. Chim. Belg. vol.88/n0 5/1979

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS XXIX*

THIATION OF ETHYL 2-ACYLAMINOBENZOATES

K. Clausen and S . - 0 . Lawesson

Department of Organic Chemistry, Chemical Institute, University of Aarhus, DK-8000 Aarhus C, Denmark

Received 11/05/1979 - Accepted 21/05/1979

ABSTRACT

By heating ethyl 2-acylarninobenzoates, 2, with the dimer of p-methoxy- phenylthionophosphine sulfide, 1, at 80°C a mixture of ethyl 2-thioacylamino- benzoates, 3, 2-substituted 3,1-benzothiazin-k-ones, 4, and 2-substituted 3,1-benzoth~azine-4-thiones, 2, is obtained. By raising the reaction tempe- rature to 140°C 2 is obtained as the only product. In all reactions between - 2 and 1 three phosphorus-containing compounds, 6-8, are isolated. 2-Sub- stituted 3,l-benzoxazin-4-ones, 2 , when reacted with 1 give mixtures of 5 and 2 due to a rearrangement reaction. Carbon-13 NMR data are tabulated for the carbonyl-, thiocarbonyl- and iminocarbons.

INTRODUCTION

It has been found that the dimer of p-methoxyphenylthionophosphine sul-

fide, 1, is a most effective thiation agent for ketones,l carboxamide~,~-~ S-substituted thioesters,7 lactones,1° lactams," and imides."

1 - As improved methods for the preparation of 3,1-benzothiazine-h-thiones, 2, are of potential intere~t,~'-'~ we have investigated the reaction of 2-acyl-

aminobenzoates, 2, with l, and our results are reported in this paper.

RESULTS AND DISCUSSION

Ethyl 2-acylaminobenzoates, 2, react with 1 in anhydrous benzene at 80°C giving a mixture of ethyl 2-thioacylaminobenzoates, 2, 2-substituted 3,l- benzothiazin-4-ones, 4, and 2-substituted 3,1-benzothiazine-4-thiones, 2 (Scheme 1 and Table 1 ) . However, at elevated temperature (140°C) in anhydrous

xylene the reaction gives 3 as the sole product (Table 1). I t is suggested

that the imidothiol form of 2, first formed, undergoes a ring-closure reac- tion, giving 5, which is subsequently transformed by into 5. This mechanism is in accordance with the one proposed by Kurzerle and Jepson et al." and

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accounts f o r all the products isolated. Walter and Bode" on the other hand

suggest that both the amide- and esterfunctions are thiated before a ring- closure occurs.

SCHEME 1

1

0

C-OEt

-C-R I1 S

9

0

C-OEt

N=C-SH

I R 1- EtoH

4 2 -

a: R = H d: R = E - P r b: R = Me e: I? = w - B u c: R = Et f: R = P h

TABLE 1

Experimental data for the reactions of ethyl 2-acylaminobenzoates, 2 , with 1

Yield of ( % ) React . React, temp. (T) time (h) 2 - 4 2

Coiripouiid

2a

2b

2c

2d 2e

2f

- - - - - -

2a

2b

2c

2d 2e

2f

- - - - - -

80

80

80

80

80

80

140 140 140 140 140 140

1

5 5 5 72 1 0

2; 2 1.

22

2: 2:

2q

98 - 62 8 16

47 7 45 44 8 32 2 - 96

67 30

-

-

From the reaction mixtures of ethyl 2-acylaminobenzoates, 2, and 1 we were also able to isolate the following phosphorus-containing products 6 , 2 , and g, of which 6 has been described earlier.2

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s s II II

R-P-S-P-R I I SEt OEt

(€2 = a - 0 - C H , )

The structural elucidation of 2 and 8 is based on IH NMR, 13C NMR, 3 1 P NMR,

mass spectrometry and elemental analyses. The 'H NMR spectrum of 2 contains one singlet (3H) at 3.9 ppm (-0-CH,), one double quartet (4H) at 3.0 ppm (G.'*-~ 14.5 Hz, in agreement with 1iteraturele) (-S-CH,-) and one triplet

(6H) at 1.3 ppm (-CH,). In the 1 3 C NMR spectrum there is one methylene sig-

nal at 28.3 ppm in accordance with literature data for -S-CH2-.Zo In the 3 1 P NMR spectrum there is one singlet at 77.3 ppm also in accordance with lite- rature data.21 The mass spectrum of 2 shows a mass peak m/e 292, The struc- ture of 2 has also been confirmed by an independent synthesis; by reaction of 1 with sodium ethanethiolate and subsequent ethylation using bromoethane (Experimental). The ' H NMR spectrum of contains two singlets at 3.82 and

3.76 ppm ( - 0 - C H , ) due to the existence o f two diastereomeric R,S-pairs, two

quartets at 4.4 ppm (-0-CH,-) and 3.1 ppm (-S-CH,-) and two triplets at 1.48 and 1.36 ppm (-CH,). In the 13C NMR spectrum there are two methylene signals at 62.6 ppm (-0-CH,-) and 27.7 ppm (-S-CH*-), re~pectively.~~ In the 3 1 P NMR spectrum there are two doublets at 81.9 and 69.7 ppm, respectively (Jp-p

19.8 Hz, in agreement with P-S-P coupling constants'@). The mass spectrum of

- 8 shows a mass peak m/e 478. As to the formation o f 2 and 8 it is known that dimers of thionophosphine sulfides react with alcohol to give either 0-alkyl

hydrogen phosphonothiolothionates or dialkyl phosphonothiolothionate~,~~9,~

and it is believed that the formation of 2 and 8 is ascribable to reaction between 1 and ethanol, formed at the ring-closure reaction of 2.

2-Substituted 3,1-benzothiazin-4-ones, i, and 2-substituted 3,l-benzo- thiazine-4-thiones, 2. are also obtained by the reaction of 2-substituted 3,1-benzoxazin-4-ones, 2 , with 1. In accordance with the results obtained earlier when reacting 1 with lactones and isocoumarine~'~ we propose that the reaction proceeds through an intermediate, lo, which rearranges to give 4, which in turn is transformed to 2 by 1 (Scheme 2).

SCHEME 2

b: R = Me f: R = Ph

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As a conclusion, the reaction between 1 and 2 at 80°C gives 2 as the main product in good yields. At 14O"C, 5 is the only product.

EXPERIMENTAL

'H NMR spectra were recorded at 60 MHz on a Varian A-60 spectrometer. 1 3 C NMR spectra and 3 1 P NMR spectra were recorded at 2 0 MHz and 32 MHz, re- spectively, on a Varian CFT-PO spectrometer. TMS was used as internal stan- ard and chemical shifts are expressed in 6-values. 3 ' P chemical shifts are related to 85% H,PO,. The new sign convention is applied (positive values at low field to H , P O , ) . CDCI, was used as solvent. I R spectra were recorded on a Beckman IR-18 spectrometer. Mass spectra were recorded on a Micromass 7070 Mass spectrometer operating at 70 eV using direct inlet. Elementary analyses were carried o u t by Novo Microanalytic Laboratory, Novo Industry A/S, Novo All&, DK-2880 Bagsvard, supervised by n r . R . E. Amsler. Silica gel 60 (Merck) was used for chromatography. M.p.'s and b.p.'s are uncorrected.

Compound 1 was prepared as described earlier.' Ethyl 2-acylaminobenzoates, 2, were prepared from ethyl 2-aminobenzoate

and the appropriate acylating agent.I2 Yields and m.p.'s/b.p.'s are listed in Table 2 together with 1 3 C NMR data and elemental analyses.

TABLE 2

Experimental data for ethyl 2-acylaminobenzoates, 2a-f

0

L O E t

NH-C-R a' II

I I M.P. ( " C ) / 6 ( C = O ) 6(C=O) Analyses ( % ) B.P. ('C/mmHg) amide ester Found Calc. Compound ($1

- 2a 61 592 ' 159.2 167.5 - 2b 52 6424 167.4 167.9

C 6 5 . 2 2 65.14

168'o 2:;; 6.33 0 21.68 21.69 6*83 I - 2c 94 49 172.4

c 66.37 66.36 n 7.31 7.28

- 2d 87 172/12 175.3 167.7 N 5.92 5.95 0 20.70 20.40

- 2e 63 42 C 67.41 67.45 H 7.65 7.68

167'9 N 5.62 5.62 177.1 0 19.22 19.25

- 2f 92 10124 165.0 168.1

General procedure for the reaction of ethyl 2-acylaminobenzoates, 2, with 1. 0.01 mole of ethyl 2-acylaminobenzoate, 2 , and 0.01 mole o f 1 in an- hydrous benzene (80°C) o r anhydrous xylene (140°C)-were refluxed until no more ethyl 2-acylaminobenzoate could be detected (TLC). After evaporation of the solvent, the residue was placed on a silica gel column and the products e- luted with ether/light petroleum (10/90). Yields are listed in Table l. M.p.'s/ b.p.'s of the products are listed in Tables 3-5 together with 1 3 C NMR data and elemental analyses.

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TABLE 3

M.p.'s/b.p.'s, 13C NMR data and elemental analyses for ethyl 2-thioacylaminobenzoates, g,_f

0

C-OEt a'' NH-C-R

II S 9

M.P. ( " C ) / 6 (c=s) fJ (c=0) Analyses (%) B . p . (OC/mmHg) Found Calc.

Compound

C 57.20 112 187.3 166.6 z:::

s 15.60 C 59.26 H 5.81

72 199.4 167.3 N 6.36 0 14.30 S 14.46

165/0.2

39

206.1 167.9

c 60.55 H 6.42 N 5.82 0 13.75 S 13.55 c 62.38 H 6.79

211 .o 168.0 N 5.46 o 12.50 S 12.71

7lZ5 197.2 167.6

57.40 5.30 6.69 15.32 59.17 5.87 6.27 14.33 14.36 60.73 6.37 5.90 13.48 13.51 62.12 6.82 5.57 12.73 12.76 63.36 7.22 5.28 12.08

* n23 1.5865 D

2-Methyl-3,1-benzoxazin-4-one, s, was prepared according t o the pro- cedure given by Errede.2B Yield 85%, m . ~ . 81°C (lit. 81-2°C). I3C NMR: 6(C=N) 159.1, 6(C=O) 159.9.

cedure given by Zentmyer and Wagner.%'Yield : 839, m.p. 123°C (lit. 122.C). 13C NMR: 6(C=N) 156.6, 6(C=O) 168.9.

2-Phenyl-3,1-benzoxazin-4-one, was prepared according to the pro-

Reaction o f 2-methyl-3,1-benzoxazin-4-one, s, with 1. 0.01 mole of L and 0.01 mole of in anhydrous benzene were refluxed for three hours . Af- ter cooling the reaction mixture was separated by column chromatography, giving 4 (26% yield) and 3 (33% yield). The same reaction was run in an- hydrous xylene at 140°C for 1/4 h giving 5 (9% yield) and > (56% yield). as the above-mentioned. At 80°C for 24 h the reaction gave 1% of and 1% of 2. At 140°C for 2 h the reaction gave 48% of 2 and 48% of 2.

Reaction o f 2-phenyl-3,1-benzoxazin-4-one, z, with 1. Same procedure

2-Phenyl-3,1-benzothiazin-4-one, 4f,12 m.p. 116°C (lit. 116°C). Diethyl F-methoxyphenylphosphonotrithioate, 2 . Light yellow oil, nZ3

1.6338. 'H NMR (CDC1,): 6 1.3(6H,t), 3.0(4H,dq,Jp-~ 14.5 Hz), 3.9(3H,s)s) 6.9-7.1(2H,m), 7.8-8.2(2H,m). 13C NMR (CDC1,): b 28.3 (-S-CH,-). 3 1 P NMR (CDC1,): b 77.3. MS: m/e 292(M+,33%), 264(50%), 232(80$), 231(85%), 203(70%),

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TABLE 4

M.p.'s, I3C NMR data and elemental analyses f o r 3,1-benzothiazine-4-ones, k - 2

~~

Compound M . p . ( O C ) 6 (C=N) 6 ( C = O ) Analyses ($) Found Calc.

not isolated

9Z1' 162.7 183.8

* C 62.81 H 4.74 N 7 .23 S 16.67

168 .0 183 .9

c 64.15

- 4d 37 173.5 184 .0 N 6.87 0 8 .18 s 15.64 C 65.79 13 5.97

- 4e** 54 174 .8 184 .7 N 6 .45 0 7.53 S 14.73

H 5 .47

62 .80 4.74 7 .32

16 .76 64.36

5.40 6.82 7.79

15 .62 65.72

5 .98 6 .39 7 .30

14 .62

- 4f*** 1 1 6 l 2 161 .6 183 .7

* ng3 1.6290. **k was isolated in 3% yield, when the reaction was stopped after 1 2 h.

**'obtained from 9f and 1.

TABLE 5

M.p.fs, I 3 C NMR data and elemental analyses for 3,1-benzothiazine-4-thiones,&-~

II S 1

Compound M. p. ("C) M. p. ("c) (lit. ) ' 6 (C=N) 6(c=s)

113 1 1 4 154 .5 208.3 2 5b 97 99 164.1 211 .1

64 63 169.2 2 1 1 . 1 22

z! 2.2

z

-

91 91 173 .5 211.5

79 80 175.7 2 1 1 . 1

126 128 162.7 210 .3

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199(75%), 140(60%), 108(100%). Analyses: (Found: C 45.61, H 5.90, P 10.58. C,,H,,OPS, requires: C 45.18, H 5.86, P 10.59%).

mole o f 1, 0.02 mole o f ethanethiol and 0.02 mole of sodium in 10 ml ethanol were stirred for 1 h at room temperature. Then 0.02 mole of bromoethane was added and the mixture stirred for 12 h. The reaction mixture was separated by column chromatography, giving 2 in 42% yield.

(Et,O), m.p. 109-112’C. lH NMR (CDC1,): 6 1.36(3H,t), 1.48 3H t , 3.1(2H.q), 3.76(3H, (CDCl3)\’2’62.6 [-O-CH,-), 27.7 (-S-CH,-). 3 1 P NMR (CDC1,): 6 81.9 (d, Jp-p 19.8 Hz , 69.2 (d, Jp-p 19.8 Hz). MS: m/e 478 (M+,lO%), 417(60%), 231(95%), 215(9O% , 187(lOO%). Analyses: (Found: C 45.49, H 5.25, P 12.87. CI,H,,O,P,S, requires: C 45.17, H 5.05, P 12.94%).

Preparation of 2 f r o m 1, sodium ethanethiolate and bromoethane. 0.01

0-Ethyl-S-ethyl di(p-methoxyphenyl)thiophosphonate, 8. White powder

3.82 3H,s), 4.4(2H.q), 6.5-6.8(4H,rn), 7.4-7.8T4H:mI. 13C NMR

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