Bull. SOC. Chim. Belg. vo1.87/n07/1978

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS XXVI."

SYNTHESIS AND 13C NMR SPECTRA OF N,N-DIALKYL THIOAMIDES

H.FRITZ,* P.HUG,' s. -O.LAWESSON,~ ** E.LOGEMANN,~ B.S.PEDERSEN,~ H.SAUTER,' S.SCHEIBYEb and T.WIMCLER'

'Ciba-Geigy AG, CH-4002 Base1 Switzerland

bDepartment of Organic Chemistry, University of Aarhus, DK-8000 Aarhus C Denmark

"University of Freiburg im Breisgau Germany

Received 25/5/ 78 - Accepted 7/6 4 8

ABSTRACT - By a new thiation reagent,', 4 1' the dimer of p-methoxyphenylthiono- phosphine sulfide, 2 , a series of thioamides have been prepared in almostquan- titative yields from the corresponding amides. Carbon-13 NMR spectra of tertia- r y thioamides of formic, acetic, trifluoroacetic, propionic and butyric acids have been completely assigned with the aid of extensive double resonance and shift reagent experiments and the data obtained have been compared with those of the analogous amides.' Aleo a linear relation between the "C chemicalshifts of >C=S of the thioamides and >C=O of the corresponding amides has been found by a least square linear regression analysis: 6(C=S) = 1.60- 6(C=O) - 72.3.

INTRODUCTION

Amides can be easily converted into thioamides by a novel method.'* 4 '' Since relatively few 1 3 C NMR data of thioamides are known from the literaturen and since recently a detailed NMR investigation of N,N-dialkyl amidea' hadbeen

performed, we felt prompted also to study the "C NMR spectra of thecorrespond- ing thioamides. Compared to amides, thioamides possess an even higher barrier to rotation around the C-N bond (see for instance 5). It is therefore to be ex-

pected that the carbon atoms of the alkyl chains e y n and anti to the thiocarbo- nyl group give rise to separate eete of signals at r o o m temperature, provided their chemical shifts are sufficiently different. It was one aim of this study

to unambigously assign the signals of the carbons to the syn and antichainsand thus gain information on the steric effect of the thiocarbonyl group on13Cchem-

ical shifts.

RESULTS

The chemical shifts of the N,N-dialkyl thioamides in C D 0 3 are listed in Table 1, the solvent shifts ACDCL3 c,D, pounds in Table 2. Table 3 gives "C chemical shifts and carbon fluorine coup-

ling constants of some N,N-dialkyl trifluorothioacetamidee and acetamides. The

assignment of the carbons was accomplished by the following methods.The a-car-

(6(CDCA3) - 6(C,&)) of selected model com-

*Part X X V . H.J.Meyer F.C.V.Larsson, S.-0.Lawesson and J.H.Bowie, Bull.Soc.

**Author to whom correspondence should be addressed Chim.Belg. a (1978j

- 525 -

bons canbe distinguished by selective proton decoupling in CDCL, solution,since the a-protons syn to the C=S group absorb at lower field than thecorresponding anti This assignment of the a-protons was verified by experiments with the shift reagent Eu(fod)3 in the case of N,N-diethyl thioformamide and

-acetamide.Forthethiaformamides, the syn-a-carbons absorb at higher field than the anti-a-carbons. This is the same situation as in the case of theformamides.

The syn-a-carbons in the higher thioamides, however, absorb at lower fieldthan the anti-a-carbons. For the assignment of the P , y, and 6 carbons, the corres- ponding proton signals had to be assigned at high field (8.46 T) in C6D, solu- tion with the aid of homonuclear decoupling. Illustrative proton datashown in Scheme 1.

Scheme 1. PROTON CHEMICAL SHIFTS IN C6D,

The corresponding carbon signals were then connected by heteronuclear decoup- ling with the proton signals. The assignments obtained in C,D, solution can be

transferred to C D a 3 as solvent since the solvent shifts of the carbon signals are small compared with the shift differences of corresponding carbons in the syn and the anti chain. The solvent shifts can, in turn, however, be used for

the assignment of closely spaced signals. The assignment procedure outlined a- bove was carried out for a selected number of compounds. The results couldeasi-

ly be adapted to the remainder of the compounds. These assignments gave thefol- lowing results: The P-carbons resonate at lower field, the y and 6 carbons at higher field in the anti-N-alkyl-chain. This is the same situation as in the case of the amides.' In some instances, the assignments of the carbonswerever- ified with experiments with Yb(fod),. The assignment of the UI and W - 1 carbons in the N,N-dihexyl thioacetamides rests also on these shift reagentexperiments.

DISCUSSION

The chemical shift data of the thioamides (Tables 1 and 3) can nowbe com- pared with those of the amides.' Table 4 gives the differences of the chemical shifts of the thioformamides and the formamides as well as the thiobutyramides and butyramides as representative examples.

By a least square analysis of the 13C chemical shifts of the thiocarbonyl and corresponding carbonyl carbons, the following equation was found:

- 526 -

This relation is quite accurate, the correlation coefficient being 0.998. Simi- lar relations have also been found for thioketones N ketones,' 0-substituted thioesters * esters,l' and dithioesters * S-substituted thioesters.ll An equa- tion describing the relationship between the 1 3 C chemical shifts of different types of thiocarbonyl- and carbonyl compounds has also been found byKalinowski and Kessler.B In the acid chain, apreciable downfield shifts are observedfbrthe carbons one and two bonds removed from the thiocarbonyl group. The a-carbonsat- tached to the nitrogen are also shifted downfield. Carbons further removed ex- perience upfield shifts which are especially pronounced for the 8-syn carbons. The shifts may partly be explained by different inductive effects of the thio- amide group operating through the bonds and by the considerably higher dipole

moment'' of the thioamides operating through space as compared with the amides.

Conformational differences could also play a certain rSle since the C=S

bond is longer than the C=O bond (radius of covalency 0 : 0.74 A , S: 1.04 A ) . This may lead to different equilibrium conformations of the alkyl chains.

The solvent effects ACDCA3 (Table 2) of the thioamides follow thesame gen- ce De

era1 trends as those of the amides.' The polar solvent effect differs fromthat of the amides due to the different dipole moment and the different geometry of the thioamide group, whereas the solvent effect of the farther removed carbons is essentially the same hydrocarbon solvent effect as that observed inthe am- ides.

As with the amides, the data of the open chain compounds can be used for the assignment of the signals in cyclic thioamides. Two examples are given in Scheme 2. The presence of the two rotamers, 2a and 2b, in equal amounts isq+n

borne out by the spectrum of 2 which shows different signals for the a-syn, P - and y-carbons for the two rotamers.

For 5 the assignment for the a- and P-carbons was confirmed by a selective decoupling experiment and by shift experiments with Yb(fod),.

1 198.96 C=S 32.41 CH, 198.79 C=S 32.46 CH, 1 1 ringcarbon signals: 17 ring carbon signals: a-syn P-syn y -syn a-syn P-syn y-syn a-anti P-anti y-anti 54.38 23.60 24.31* 54.10 25.67 26.48 53.07 27.75 26.29

54.04 25.76 26.37 (2) 27.84 26.17 a-anti p-anti y-anti 53.36 25.64 24.19* 28.87 (2), 28.78, 28.74, 28.59, 28.50 (21,

28.38 unassigned 25.51, 25.18, 25.08(2) 24.45, 24.36unassigned

Signals with double intensity are marked with "Assignment uncertain (2)

Scheme 2 . CHEMICAL SHIFTS OF CYCLIC THIOAMIDES IN CDC&

- 5 2 1 -

EXPERIMENTAL

General procedure for preparation and identification of the thiocarboxam- ides. 0.01 mole of carboxamide and 2 .2 g p-methoxyphenylthionophosphine sulfide (0.0055 mole) 3 in 10 d of anhydrous toluene were kept at 100 “c for 4 hrs. After cooling to room temperature, the reaction mixture was placed on a silica gel column and the thiocarboxamide eluated with a proper mixture ofether/light petroleum. Yield: 98-100 %. The thiocarboxamides were identified by IR, MS and elementary analysis. Some of them are known and for the new ones, see Table 5. IR spectra were recorded on a Beckman IR-18 spectrometer and MS were recorded on a CEC 21-104 mass spectrometer operating at 70 eV using direct inlet. Ele- mentary analyses were carried out by Novo Microanalytical Laboratory, Novo In- dustry A/S, DK-2880 Bagsvard, Denmark, supervised by Dr. Rolf E.hsler. Silica gel 60 (Merck) was used for column chromatography, mps and bps are uncorrected.

n

The IH NMR data were obtained on a Varian HA 100 and a Bruker HX 360 spec- trometer, the I3C NMR data on a Varian XL-100 equipped with a 16 K memory. The data of the alkyl carbons were obtained at a sweep width of 1500 He at 25.156 MHz and are therefore accurate to * 0.4 Hz. The probe temperature was 30 1 ‘C. The compounds were measured as 10 $ w/v solutions.

REFERENCES

1. B.S.PEDERSEN, S.SCHEIBYE, N.H.NILSSON and S.-O.LAWESSON, Bull.8oc.Chim.Belg.

2 . G.C.LEVY and G.L.NELSON, Carbon-13 Nuclear Magnetic Resonance for Organic 3 (1978) 223.

Chemists, Wiley-Interscience New York 1972, p.133, and references cited there.

0rg.Magn.Res. 3 (1976) 536.

229.

Can.J.Chem. 2 (1977) 2649.

3. C.PICCINN1-LEOPARDI, O.FABRE, D.ZIMMERMANN, J.REISSE, F.CORNEA and C.FULEA,

4. S.SCHEIBYE, B.S.PEDERSEN and S.-O.LAWESSON, Bull.Soc.Chim.Belg. 3 (1978)

5. C.PICCINN1-LEOPARDI, O.FABRE, D.ZIMMERMA”, J.REISSE, F.CORNEA and C.FULEA,

6. H.O.KALINOWSK1 and H.KESSLER, Angew.Chem. 86 (1974) 43. 7. H.O.KALINOWSK1, W.LUBOSCH and D.SEEBACH, Chem.Ber. 110 (1977) 3733. 8. H.FRITZ, P.HUG, H.SAUTER, T.WINKLER and E.LOGEMANN, 0rg.Magn.Bes. 2 (1977)

9. W.E.STEWART and T.H.SIDALL, Chem.Rev. a (1970) 517. 108.

10. W.WALTER and J.VOSS in “The Chemistry of hides”, Ed. J.Zabicky, Inter-

11. B.S.PEDERSEN, S.SCHEIBYE, K.CLAUSEN and S.-O.LAWESSON, Bull.Soc.Chim.Be1g.

12. W.WALTER and G.MAERTEN, Ann. (1963) 66. 13. R.C.NEUMAN and L.B.YOUNG, J.Phys.Chem. (1965) 2570. 14. J.VOSS and W.WALTER, Ann. (1968) 209. 15. J.WIT’TE and R.HUISGEN, Chem.Ber. (1958) 1129. 16. P.J.W.SCWIJL and L.BFUNDSMA, Rec.Trav.Chim.Pays-Bas 3 (1968) 38.

science London 1970, p. 383.

3 (1978) 293.

- 528 -

I

VI

N

W I

Tabl

e 1.

CARB

ON CH

EMIC

AL S

HIF

TS OF N

,N-D

IALK

YLTH

IOAM

IDES

IN C

DCL, FR

OM I

NTER

NAL

TMC

w-3

w-2

UJ-

1 UJ

cs

CY,

C.cg

CHO

n

Chai

n a

B Y

6 i

Thio

form

amid

es H-CS-N(CnH2n+1),

'1 s

37.29

a 45.37

s 42.33

11.21

a

50.77

14.43

2

s

49.32

19.36

11.31

3 a

58.18

21.96

11.00

s

47.52

28.06

20.20

a 56.22

30.72

19.72

4 Thio

acet

amid

es CH

,-CS

-N(C

nH2n

+1)2

1 s

44.32

a 42.28

s

47.99

11.21

a

46.69

13.17

2

s 55.36

19.27

11.28

3 a

54.33

21.43

11.24'

4 s

53.59

28.03

20.24

a 52.50

30.18

20.14

s 53.86

25.90

26.66

a 52.76

28.11

26.57

s 53.86

25.94

27.03

l2

a 52.75

28.14

26.91

6

13.81

13.60

13.84

19-7

3

31 -54

31.45

188.14

186.84

187.86

187.61

199.65

198.10

198.81

198.44

14.02

198.48

22.61

22.54

13.96

29.63

29.38

31.96

22.72

14.12

198.43

32 * 75

32-1

3

32 - 36

32.33

32.33

32.33

'5:

sp; a: an

ti;

w,i:

last

a

nd

'inner'

carb

on a

toms

in t

he am

ide

chain. =Assignment may

be

re

vers

ed.

(con

tinu

ed)

I VI

w 0

I

Table

1. CARBON CHEMICAL SHIFTS OF N,N-DIALKYLTHIOAMIDES IN CDCI, FROM INTERNAL

TMS

(cont.)

n

Chain

a B

Y 6

i

UJ-3

m-2

UJ- 1

UJ

cs

Crg

cH2

cH3

Thiopropionamides C&-CH,-CS-N(CnH2n+1).

s 47.93

11.20

a

45.86

13.69

2

s 55.29

19-25

a

53.56

21.88

11.25

3

s 53.56

28.06

20.24

13.87

a

51.71

30.67

20.18

13.75

s 53.83

25.90

26.66

31.57

a

51.98

28.60

26.61

31.48

s 53.83

25.94

27.01

l2

a

51.96

28.61

26.94

4

6 Thiobutyramides C% -CIE, -

Cq -CS-N(CnH2,+1

)a

2

s 47.87

11.24

a

46.00

13.75

s 55-27

19-37

11.27

3

a

53.69

21.94

s 53.53

28.11

20.24

13.85

4

a

51.81

30.71

20.16

13.72

s 53.80

25.96

26.66

31.57

6

a

52.09

28.62

26.60

31.45

s 53.81

26.01

27.02

l2

a

52.08

28.64

26.93

29-69

29.64

22.62

22.55

29.38

31.95

22.71

22.62

22.54

29.39

31.96

22.71

14.01

13.96

14.10

14.01

13.96

14.12

204.40

205.05

204.74

204.74

204.69

203.02

203.69

203.37

203.31

203.32

36.02

36-20

36.17

36.17

36.16

44.84

45 * 05

45.04

45-05

45.06

14.22

14.30

14.28

14.29

14.28

23.44

13.84

23.52

13.84

23.51

13.85

23.52

13.85

23.54

13.86

syn~ a: anti;

w,i

: last and 'inner'

carbon atoms in

the aide chain.

-

$

n 3

3

r I 3

v I 3

7l I 3

rl

0

>

21

U

a B

E

-

0 o - a o n w w 0 0 0 0

I I

-fc- O m 0 0 . .

r - N w o

0 - 0 0 m.5 fm.

r N

CON

0 0

r r . .

-fc- or. 0 0 . .

m m

rl- - 0

0 0 I 1

. .

0-f N O 0 0 I 1

. .

a n

0 0 N.?

nr- O W

0 0 . .

l a 5

s

m 0 a

0 n

0 0 ? -

n W rl

0 0 ?

m w

0 0 ?N.

nn o m

0 - 0 0 "N. f?

'$ m m m m

s Y P)

.rl e - N

rl 0

0

N

0 ?

W c -

0 0 ?N.

a-

0 0 ? ?

no O W

0 0 . .

m a

0

W

0 ?

n

0 I

?

a n - 0

0 0 I I

. .

c-0 N O 0 0 . .

- w

0 0 I I

??

m w CI-f

0 0 . .

m m

a

W

0 9

r

? 0

- m N - 0 0 I 1

. .

Chm r l N

0 0 I 1

. .

c--

0 0 I 1

?N.

n W

0 0 1 1

0 9

w o o r 0 0

I 1

. .

O r l

0 0 ?-f.

o m

W

\D

0 9

c-

0 ?

N N 0

n

0 9

m O

0

a a 0

\o

0 t

CON O r

0 0 I 1

. .

-a a- 0 0

I 1

. .

n- N - f

0 0 . .

m m

N c

- 531 -

I Ln

W

N

I

Table

3. CA

RBON

CH

EMIC

AL SHIFTS O

F N,N-TRIFLUOROTHIOACETAMIDES

AN

D AC

ETAM

IDES

IN CDCL, FR

OM

INT

ER

NA

L TMS.

J(C,

F) in

par

enth

eses

n

Chai

n a

P Y

6 E

5 CFa

Thio

acet

amid

es

2

S a

3 s a

4 s a

6 s a

Acet

amid

es

2

s a

3 s a

4 s

a

6 s a

48.7

8 1

5

48.0

4 [3

:8]

55.9

8 1

1

55.5

3 [3

:4l

41.6

5 42

.00

(3.4

)

48.5

8 49

.20

(3.2

)

46.8

4 47

.43

(3.4

)

10

.10

13

.72

(1.1

18.2

0 21

.93

(0.7

26.8

2 30

.61'

(0

.8

24.6

7 28

.56

(0.6

)

12.2

3 14

.11

20

.12

2

2.0

2

29.0

6 30

.88

26.9

0 28

.78

11.1

5 10

.99

20.1

9 2

0.0

0'

(0.1

)

26.5

6 26

.42

11.1

9 10

.87

20.1

4 1

9-9

0

26.5

5 26

.33

13.7

4 13

.60'

117.

59(2

79.2

)

117.

59(2

79.2

)

117.

60(2

79.2

)

22.5

8 13

*97

117.

56(2

79.3

) 22

.52'

13

.92'

116.

87(2

87.6

)

116.

82(2

88.8

)

13.7

8 1

1 6.

80(

288.

5)

13.6

6

31 -5

3

22.5

7 1

3'9

8

116.

82(2

87.5

) 31

.42

22.5

7 13

.94"

s: sy

n;

a: an

ti.

' he

tero

nucl

ear

doub

le re

sona

nce

at

2.35

T

assi

gnme

nt m

ay be r

ever

sed

VI

W

W

I

Table 4

. SH

IFT

DIFFERENCES BETWEEN

ANALOGOUS

THIOAMIDES AN

D AMIDES (CDCL,)

n

Chain

a B

Y 6

i m

-3

w-2

m

-1

UJ

c=x

CH,

CH,

C Hs

Formamides

s 5.

82

a

8.8

8

1

s 5.

67

2

a 8.

92

s

5.49

3

a 8.

98

s

5.58

a

9.01

4 Butyramides

s

7.81

a

4.00

2

s

7-7

2

a

3.99

3

s 7.

86

a 4.

02

4

s

7.85

a

4.04

6

s 7.

88

l2

a

4.04

-1.5

9 -0

.48

-1 -

25

0.

04

-1.4

1 -0

.13

-1.9

2 -0

.67

-1.7

3 -0

.45

-1.9

5 -0

.67

-1.9

1 -0

.63

-1.9

1 -0

.63

-0.0

2

0.06

-0 *

02

0

.03

-0.1

4 -0

.01

-0.0

8

-0.0

1

-0.1

3 -0

.08

-0.1

2 -0

.05

0.0

0

0.06

-0.0

3 -0

.13

-0.1

1 -0

.23

-0

.04

-0.1

2

-0.02

-0.03

o 0

25.4

9

24.6

1

25 *

03

24.8

8

30.8

3

31.0

2

30.8

4

30.7

9 -0

.02

-0

.07

0.01

30

.84

9.74

4.

53

-0.1

6

9.92

4.

58

-0.1

7

9.91

4.

58

-0.1

6

9.90

4.

54

-0.1

8

9.93

4.

60

-0.1

7

s:

sy

ni

a:

anti

w,i: last hd 'inner' carbon atoms

in the

amide

chain

Table

5. PHYSICAL AND

ANALYTICAL DATA OF NEW THIOAMIDES

I VI w

h

I

Compound

n

b.p.

(OC

/tor

r)

Analysis, calc. (found)$

C H

N

S

Thioacetamides

CHSCS-N(CnHzn+1

12

3

oil

60.38(60.25)

10.69(10.72)

8.81(8.84)

20.13(20.12)

4

(83-85/0- 1

) 64.17 (64.10)

11 .23( 11.22)

7.49(7.49)

17.11 (17.48)

6

( 117-1 18/0.1)

69.14(69.09)

11.94(11.87)

5.76(5.75)

13.17(13.42)

12

oil

75.91(75.71)

12.90(12.85)

3.41(3.41)

7.79 (7.85)

Thiopropionamides

CH~

cIE, CS-N(CnH2n+1 )

z 3

(68-7 1 /O

. 09)

62.43(62.20)

10.98(11.24)

8.09(8.10)

18.50(18.59)

4

(108-110/0.1)

65.67 (65.74)

11.44( 11.69

6.97( 6.88)

15.92( 16.20)

6

(138-140/0.2)

70.03(70.04

76.24(76.22

12

oil

Thiobutyramides

CHO (CH, )a CS-N(C,.,H~,+~

3

(77-79/0

4

(93/0.15

6

oil

12

oil

64.17(64.26

66.98(66.80

70.85(70.65

1)

12.06(12.02)

5.45(5.45)

12.45(12.63)

12.94( 12.84)

3.29(3.38)

7.53 (7.56)

11.23( 1

1.40)

7.49( 7.48)

17.1 1

( 17.32)

1 1.63( 1 1.79)

6.51 (6.57)

14.88( 14.87)

12.18(12.24)

5.17(5.19)

11.81(11.92)

12.98(12.80)

3.19(3.14)

7.29 (7.44)

m.p. 11

1 67.6 1

(67.60)

10.80( 10.95)

6.57 (6.58)

15.02

( 15.04)

69.71 (69.60)

11.20( 11.29)

5.81 (5.82)

13.28( 13.29)

m.p

. 42