■'i use pf radio-labelled sodium hydrogen sulphide-8-95. Rearrangement by
a nucleophilio mechanism (scheme 33, route A) would result in 100% introduction of radio-labelled sulphur into the thfone group of the 4H-thiopyran-4-thione (88). Rearrangement by a reductive mechanism (scheme 33, route B) would, however, repult in no incorporation of radio-labelled sulphur into the 4H-thiopyran-4-thione (88).
(2) The Mechanism of the Rearrangement of Ga-Thiathiophthenes (89) to 4H-Thiopyran-4-iThiones (88).
Ga-Thiathiophthpnes (89) were found^^'^^ to rearrange with either aqueous sodium sulphide or sodium hydrogen sulphide to the corresponding 4H-thiopyran-4-thiones (88). Two mechanisms were
p r o p o s e d ^ ^ f o r this rearrangement; a reductive cleavage of the sulphpr-sulphur bond (scheme 34, route B) giving l^he intermediate anlpn (91) which eliminates hydrpsulphide anion pn cyclisation, or a nucleophilio attack (scheme 34, route A) by hydrpsulphide anion at the 2- ( or 5-) position of the Ga-thiathiophthene ring leading to the same anion (91) which then cyclises. The latter mechanism was favoured pn the basis of substituent effects and since 2i-phenyl— Ga-thiathiophthpne and 2,4-diphenyl-6a-thiathiophthene also rearranged
89
*
^R^
R^
NaoS
1
1
— ---- >
1■--- -^
R1
Ri'
88 ^
Rl
R«
R^
a) Ph.
H
CH3
b)
H
P
.c) Ph
H
H
e) H
H
H
f) H
oa^
OH5
g) a
Ph
Hi
*95
6a,Thia-
Reaotion
Reaction 4H-Thlopyran-
ioIncorporation
ioExchange at
thiqphthene
Temperature
Time
4-one-lS“55
of 8-55
6-position
89a
60
5 min.
95a
5 . 611.2 '
89b
60
5 min'.
95b
1 4 , 6 2 9 . 2.
89
q 6 05 min.
9%)
. 18.4
5 6 . 889e
6 05 min.
95e
5 5 . 5 5 5 . 589f
20
5 min.
95f
1 5 . 1 1 5 . 189g
20
oa.lO see.
95g '
7 7 . 0 7 7 . 0Table 2 ,
R^ R3 R^ R3 <;8B s;Scheme 35 ®®
83
29
with sodium hydroxide to the corresponding 4H— thiopyranr4-thiones. The two mqchanispis have now been differentiated by the use of radio-labelled aquepus sodium aulphide-Sf"35. If the initial step in the rearrangement is a reductive cleavage of the sulphur-sulphur bond (scheme 34, route B), then ideally there would be no
incorporation of labelled sulphur into the 4H— thiopyran-4-thione (88). An initial nucleophilio attack, however, by labelled sulphide (scheme 34, rpute A) wpqld result in formation of the anion (91*) containing the iabei in th© ^-position. On cyclisation, 50% of the label would be eliminated since the anion (91*) would be in equilibrium with its
*
tautomer (92 ), Therefore, if rearrangement proceeds by a nucleophilio mechanism, 50% pf the original label wpuld appear in ring sulphur atom of the 4H-thiopyran-4*^thione (88 ),
In practise, it was found impossible to count radio-labelled 4H-thiopyran-4-thiones (88*) because of their strong colour quenching. The 4H“’thiopyran-4— thiones (88*) were therefore converted into the
colourless 4Brfhiopyran-4*pones (93 ) by the action qf mercury (II) 115
acetate in acetic acid and chloroform. Quench calibration.curves, relating tpe efficiency of counting to the external standard ratio of the scintillation counter, were prepared for each 4H-thiopyran-4-one
(93) in order to calculate the efficiency of counting in each unknown sample. The percentage incorporation of sulphur— 35 into the
4H-thiopyran-4-one? (93 ), defined by the expression
. specific activity (4H-thiopyran-4-one) x 100 % incorporation , ' spec^iftc activity ("sodium suxjhid?)--- was calculated for the rearrangement of each of the 6a-thiathiophthenes
(89a-g). Thpse results are tabulated in table 2.
The data are consistent with an initial reductive cleavage of the sulphur-sulphur bond (scheme 34, route B) since a mechanism involving an initial nucleophilio attack
(scheme
34, route A) would84
result in a minimum pf 50% incorporation of labelled suiphur into *
the 4H-thiopyran-4-pne (93 ), The rearrangement of four of the 6a-thiathiophthenes (89) afforded 4H-thippyranT4-ones (93*) with
less than 20% incorporation of labelled sulphur (tpble 2). However, the initially fprmed anion (91) is then susceptible to nucleophilio attack (scheme 35) at the unsubstituted sites (C^2 and/or C-5) leading to exchange of unlabelled sulphur for labelled sulphur
from the reaction medium. The anipn (91 ) (92 ) then cyclises eliminating 50% pf thp label incorporated by exchange. Exchange of both the 1- and 6#sulphur atoms is possible for the anions (91) derived from Ga-thiathiophthene (89e), 3,4-dimethyl-6a-thiathiophthene (89f), and 3,4— diphpnyl-Ga-thiathiophthene (89g). Therefore, both the 1- and 6- sulphur atoms in the anfons (91e), (91f), and (91g)
undergo 55.3%, 15,1%, and 77,0% exchange respectively. The substituent f in the 2-positipn of 4mmethyl-2^phenyl-Ga-thiathiophthene (89a),
2Tt^butyl^6a^thiathiophthene (89b), and 8-phenyl-Gq-thiathiophthene (89c) effectively blopks this position so that only the 6-sulphur atom in the anions (91a), (91b), and (91c) can exchange wfth
labelled sulphide from the surrounding medium. Thus, the G-sulphur atom in the anions (91a), (91b), and (91c) undergoes 11,2%, 29,2%, and 36.8% exchange respectively. On cyclisation, 50% pf this label is eliminated, A qualitative agreement with this mechanism is shown between the electronic effects of substituents and the
percent exchange of the 6-sulphur atom in the anipng (91) (scheme 35). The anion (91e) derived from 6a-thiathipphthene (89o) is taken as the reference with 55.3% exchange at the G-gulphur atom. The
positive inductive effect of a methyl substituent in the 4-position of the anion (91) is to increase the electron density at the 5-position. This position is therefore deactivated towards n u d p o p h i l i c exchange when compared with the corresponding position of the anfon (9le).
The anions (91a) an*) (91f) derived from 4*m^ethyl-2-phenyl«jGa-thiàthiophf-
85
then© (89a) and 8,4-dimethyl-Ga-thiathiophthehe, (89f) undergo only 11,2% apd 15.1% exchange respectively at the G-sulphur atom. A phenyl group in the 4-position withdraws electrons thus making the 5«position much reactive towards nucleophilio exchange since the negative charge of the incoming labelled sulphide anion can be delocalised into the phenyl ring (94). Thus, the anion
(9 1g) derived from 3,4-diphenyl-Ga-thiathiophthene (89g) undergoes
77.0% exchange at fhe 6-sulphur gtom under much milder conditions than was used for the rearrangement of other Ga-thiathiophthenes