Fluorinated phosphorus compounds part 8. The reactions of bis(fluoroalkyl) phosphorochloridates with sulfur nucleophiles

Article abstract of DOI:10.1016/S0022-1139(02)00239-7

The reactivity of bis (fluoroalkyl)phosphorochloridates to nucleophiles is summarised. Previous data and the results described here indicate that reactivities decrease in the order: amines > alcohols > thiols. The synthesis of CF₃CH₂OP(O)(SEt)₂ in 30% yield was accomplished by treating CF₃CH_OP(O)Cl₂ with two molar equivalents of EtSH and Et₃N in ether. The chloridates (CF₃CH₂O)₂P(O)Cl and (C₂F₅CH₂O)2-P(O)Cl did not react with MeSH in ether at -78 °C or when heated with Pb(SMe)₂ in benzene. Ethanethiol and propanethiol reacted with fluorinated chloridates in the presence of triethylamine to give thiolates (R_FO)₂P(O)SR in 13-41% yield where R_F was CF₃CH₂, C₂F₅CH₂, C₃F₇CH₂ or (CF₃)₂CH and R was Et or n-Pr. Similarly, reaction of phosphorobromidates (R_FCH₂O)₂P(O)Br, made by brominating the corresponding bis(fluoroalkyl) H-phosphonates, with benzenethiol gave derivatives (R_FCH₂O)₂P(O)SPh in 43 and 46% yield where R_F was CF₃ and C₂F₅, respectively. Treatment of the chloridothiolate Cl(EtO)P(O)SMe, prepared in two steps from triethyl phosphite, with flouroalcohols and triethylamine in ether gave species R_FO(EtO)P(O)SMe in 62-74% yield where R_F was CF₃CH₂, C₂F₅CH₂, C₃F₇CH₂ or (CF₃)₂CH. The reactions of bis(trifluoroethyl) phosphorochloridate with 2-mercaptoethanol, 3-mercaptopropanol and ethane-1,2-dithiol gave several unexpected products whose structures were tentatively assigned.

Full text of DOI:10.1016/S0022-1139(02)00239-7

Journal of Fluorine Chemistry 119 (2003) 161±171
Fluorinated phosphorus compounds
Part 8. The reactions of bis(¯uoroalkyl) phosphorochloridates
with sulfur nucleophiles
Christopher M. Timperley*,Sally A. Saunders,
Josef Szpalek,Matthew J. Waters
Defence Science and Technology Laboratory, Detection Department, Chemical and Biological Sciences,
Porton Down, Salisbury, Wiltshire SP4 0JQ, UK
Received 10 July 2002; received in revised form 19 September 2002; accepted 24 September 2002
Abstract
The reactivity of bis(¯uoroalkyl) phosphorochloridates to nucleophiles is summarised. Previous data and the results described here indicate
that reactivities decrease in the order: amines > alcohols > thiols. The synthesis of CF3CH2OP(O)(SEt)2 in 30% yield was accomplished by
treating CF3CH2OP(O)Cl2 with two molar equivalents of EtSH and Et3N in ether. The chloridates (CF3CH2O)2P(O)Cl and (C2F5CH2O)2-
P(O)Cl did not react with MeSH in ether at À78 8C or when heated with Pb(SMe)2 in benzene. Ethanethiol and propanethiol reacted with
¯uorinated chloridates in the presence of triethylamine to give thiolates (RFO)2P(O)SR in 13±41% yield where RF was CF3CH2, C2F5CH2,
C3F7CH2 or (CF3)2CH and R was Et or n-Pr. Similarly,reaction of phosphorobromidates (R FCH2O)2P(O)Br,made by brominating the
corresponding bis(¯uoroalkyl) H-phosphonates,with benzenethiol gave derivatives (R FCH2O)2P(O)SPh in 43 and 46% yield where RF was
CF3 and C2F5,respectively. Treatment of the chloridothiolate Cl(EtO)P(O)SMe,prepared in two steps from triethyl phosphite,with
¯uoroalcohols and triethylamine in ether gave species RFO(EtO)P(O)SMe in 62±74% yield where RF was CF3CH2, C2F5CH2, C3F7CH2 or
(CF3)2CH. The reactions of bis(tri¯uoroethyl) phosphorochloridate with 2-mercaptoethanol,3-mercaptopropanol and ethane-1,2-dithiol gave
several unexpected products whose structures were tentatively assigned.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: O-Alkyl O-¯uoroalkyl S-alkyl phosphorothiolate; Bis(¯uoroalkyl) phosphorobromidate; Bis(¯uoroalkyl) phosphorochloridate; O,O-bis(¯uor-
oalkyl) S-alkyl phosphorothiolate; O-Fluoroalkyl S,S-dialkyl phosphorothiolate
1. Introduction
New research opportunities emerged once it was realised
In Part 6,phosphorus trichloride was shown to react with
tert-butanol and two molar equivalents of a ¯uoroalcohol to
give bis(¯uoroalkyl) H-phosphonates A which underwent
chlorination to yield the phosphorochloridates B [1]. These
compounds are colourless liquids or low-melting solids that
can be stored in a refrigerator for many months without
degradation. The route permitted the preparation of signi®-
cant quantities of the pure chloridates for the ®rst time.
that the chemistry of the ¯uorinated phosphorochloridates
might parallel,and in places diverge from,that of conven-
tional phosphorochloridates. Poly¯uoro-alkoxy groups are
larger than alkoxy groups and more electronegative: the
phosphorus atom of bis(¯uoroalkyl) phosphorochloridates
(RFO)2P(O)Cl is more hindered and more electrophilic than
that of dialkyl phosphorochloridates (RO)2P(O)Cl [2]. Both
classes of chloridate undergo reactions typical of electro-
philes,the chlorine atom being displaced easily by a range
of nucleophiles. This process is termed phosphorylation
[3].
The mechanism of phosphorylation has been studied
extensively and is generally interpreted as a bimolecular
substitution reaction proceeding at the phosphorus atom
(SN2P process) [4]. Nucleophilic attack on the dialkyl
phosphorochloridate C produces the trigonal bipyramidal
intermediate D. The nucleophile adopts an apical position
* Corresponding author. Tel.: ‡44-1980-613566;
fax: ‡44-1980-613834.
E-mail address: cmtimperley@dstl.gov.uk (C.M. Timperley).
0022-1139/02/$ ± see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 2 ) 0 0 2 3 9 - 7

162
C.M. Timperley et al. / Journal of Fluorine Chemistry 119 (2003) 161±171
and the leaving group departs from an apical position [5],
yielding the tetrahedral product E.
The rate of substitution depends on the size and electro-
negativity of the alkoxy groups in the phosphorochloridate.
Small or electronegative alkoxy groups increase the rate,
large or electropositive groups slow it down. Less is known
about the comparative reactivities of nucleophiles,although
enough data are available to draw some conclusions [6,7].
The best picture is gleaned from the behaviour of diisopro-
pyl phosphorochloridate to nucleophiles: the ÀreactivitiÀes of
anionsdecreaseintheorderFÀ > EtOÀ > PhO > PhS [8],
n-butylamine reacts three times faster than water (N- to
O-phosphorylation ratio 14:1) [9] and ethanolamine reacts
mainly at the amino group (N- to O-phosphorylation ratio
23:1) [10]. The reactivity order does not change if the
chloridate has electronegative substituents: an equimolar
mixture of diphenyl phosphorochloridate, n-butanol and
n-butylamine in the presence of triethylamine resulted in
exclusive N-phosphorylation [11]. Phosphoryl dichloro-
¯uoride Cl2P(O)F gave the diesters (RO)2P(O)F in 45±
93% yield on treatment with excess ethanol,2-¯uoroethanol,
n- or i-propanol,cyclohexanol or 2-methylcyclohexanol
[12]. Phenol,a weaker nucleophile,did not react unless
N,N-dimethylaniline was employed as base [12]. No reac-
tion occurred with ethanethiol,but substitution did take
place in the presence of N,N-dimethylaniline to give
(EtS)2P(O)F [12].
It can be concluded that,regardless of the electronic
character of the alkoxy group/s,the phosphorus atom of
phosphorochloridates behaves as a hard acid.1 It reacts
preferentially with hard bases (nucleophiles in which the
donor atom is of high electronegativity,low polarisability
and dif®cult to oxidise,i.e. F À,RNH 2, R2NH,RO À),rather
than with soft bases (nucleophiles in which the donor atom is
of low electronegativity,high polarisability and easy to
oxidise,i.e. R À,RS À,CN À).
For bimolecular nucleophilic substitution reactions,basi-
city data are often available and can be used as a guide to
nucleophilicity provided like is being compared with like.
Thus,if the attacking atom is the same,then the two should
run reasonably parallel,and the stronger the base the more
powerful the nucleophile (e.g. EtOÀ > PhOÀ). For a given
phosphorochloridate,a general rule is that the reactivity of
nucleophiles decreases in the order: ¯uoride ion > primary
and secondary amines > aromatic amines > aliphatic
Scheme 1.
alcohols > aromatic alcohols > aliphatic thiols > aromatic
thiols.
Previous papers in this series have con®rmed that bis-
(¯uoroalkyl) phosphorochloridates obey this rule. The most
complete set of data is obtained from knowledge of the
reactions of (CF3CH2O)2P(O)Cl. Displacement of the chlor-
ine atom by hard nucleophiles such as ¯uoride [1],azide [2],
primary and secondary amines [2,15],methoxyamine [2],
¯uoroalkylamines [16],alcohols and ¯uoroalcohols [15,17]
has been demonstrated. Displacement by soft nucleophiles,
with the exception of a few Grignard reagents [18],has not
yet been explored. The reactions of sulfur nucleophiles with
¯uorinated phosphorus chloridates have been neglected and
only two phosphonates [19] and a phosphinate [20] appear to
have been made this way (Scheme 1).
The possibilities presented by the introduction of ¯uorine
into phosphorus±sulfur compounds are vast. Some generic
classes of compound are shown. Only one compound of
class F is known: (EtO)2P(O)SCH2CH2F from alkylation
of (EtO)2P(O)SNa with BrCH2CH2F in hot ethanol [21].
Two compounds of class G are known: (FCH2CH2O)2-
P(S)OC6H4NO2-p,from treatment of the chloridothioate
with para-nitrophenol and triethylamine in ether,and
(FCH2CH2O)2P(S)OEt from heating the mixed phosphite
with sulfur [21]. Ten compounds belonging to class H are
known. They comprise the acids [H(CF2)nCH2O]2P(S)SH
where n is 2 and 4,made by ¯uoroalcoholysis of phosphorus
pentasul®de [22,23],and eight derivatives (HCF 2CF2-
CH2O)2P(S)SR,made by treating the sodium or potassium
salt of the thioacid with various alkyl halides [24,25].
1 For discussion of the concept of hard or soft acids and bases refer to the
classic paper by Pearson [13]. A useful review of its application to multi-
centre reactions,with reference to phosphorus chemistry,has also been
published [14].

C.M. Timperley et al. / Journal of Fluorine Chemistry 119 (2003) 161±171
163
Molecules belonging to class I have not been made yet.
2.2. Attempted syntheses of thiolates of structure J
Those of class J that are known have the structure
(HCF2CF2CH2O)2P(O)SR where R is methyl,ethyl,propyl,
butyl, sec-butyl,pentyl or benzyl [26]. Three members of
class K have been reported: FCH2CH2O(EtO)P(O)SEt [21]
and isomers HCF2CF2CH2O(MeO)P(O)SEt and HCF2CF2-
CH2O(EtO)P(O)SMe,but it is unclear whether the last two
were obtained pure [27,28]. In this paper,we describe the
reactions of thiol nucleophiles with a selection of phosphor-
ochloridates to give some new compounds belonging to
classes I±K.2
Bis(tri¯uoroethyl) phosphorochloridate and bis(penta-
¯uoropropyl) phosphorochloridate did not react with
methanethiol in ether in the presence of triethylamine. No
precipitate was observed and the chloridates were recovered
unchanged.
2. Results and discussion
With methanol instead of methanethiol,reaction occurred
instantly and methyl esters were isolated in good yield (these
experiments will be reported in a subsequent paper). Here,
thiols are much less reactive than alcohols,but exact com-
parison between the two types of nucleophile is dif®cult.
Ambiguity arises from the fact that thiols are more acidic
(the pKa for MeSH is 10.3 [31] while thatÀof MeOH is 15.1
[32]). Consequently,the thiolate ion RS is always more
likely to be present than the alkoxide ion ROÀ,and thiolate
ions are more nucleophilic than unionised thiols.
A disadvantage of methanethiol,besides its stench,is its
low volatility (bp 6 8C). To circumvent this,it was converted
into its lead salt. Some lead thiolates were reported in
1971 by Shaw and Woods [33] but the methanethiolate
was missing. A good method for preparing it is given in
Section 4.3. Methanethiol was bubbled into a solution of
lead (II) acetate in aqueous ethanol. The thiolate precipitated
as a yellow solid (Eq. (1)).
2.1. Synthesis of the first dithiolate of structure I
Few phosphoryl compounds containing one tri¯uor-
oethoxy group are known. All are derived from tri¯uoroethyl
phosphorodichloridate. They include the phosphoramidates
CF3CH2OP(O)R2 where R equals NMe2,NMeEt,NEt 2 [15],
NHC6H5 and NHC6H4CH3-p [29],and the phosphates CF 3-
CH2OP(O)(ORF)2 where RF equals CH2CF2CF2H,CH 2C2F5,
CH2C3F7 [17] and C6H4F-m [29]. We made the ®rst sulfur
analogue by treatment of tri¯uoroethyl phosphorochloridate
1 in ether with two molar equivalents of ethanethiol and
triethylamine (the reaction was much slower than that of
primary aminessuch as ethylamine[15] in agreement with the
general rules of reactivity discussed in the previous section).
Dithiolate 2 was isolated in 85% purity by bulb-to-bulb
distillation under reduced pressure. The distillate was further
puri®ed by chromatography over silica gel and obtained as
an analytically pure colourless liquid. The isolated yield was
low as a consequence of the additional puri®cation step.
PbꢀOAc† ‡ 2 MeSH H!2O PbꢀSMe† ‡ 2 AcOH
(1)
2
2
EtOH
Lead alkylthiolates transfer alkylthio groups to sulfuryl
chloride [34],carboxylic acid chlorides [35],chlorotrialk-
ylsilanes [36±38],phosphorus trichloride or tribromide [39],
phosphorus oxychloride POCl3 or phosphorus thiochloride
PSCl3. Treatment of the latter with 1.5 molar equivalents of
lead alkylthiolate in boiling benzene produced (RS)3P=O or
(RS)3P=S with some conversion of the lead reagent to the
dialkyl disul®de [40]. Experiments with dialkyl phosphoro-
chloridates have not been conducted. No change occurred
when diethyl phosphorochloridate,bis(tri¯uoroethyl) phos-
phorochloridate or bis(penta¯uoropropyl) phosphorochlor-
idate were heated under re¯ux with a suspension of lead
methanethiolate in benzene.
The phosphorus chemical shift of compound 2 appears at
59.2 ppm,down®eld of that for the perprotio analogue
(EtS)2P(O)OEt which appears at 53.5 ppm [30].
2 The nomenclature of phosphorus±sulfur compounds can be confusing
and the names used throughout the text were chosen for clarity. The
materials described in this paper are derivatives of dithiophosphoric acid
HOP(O)(SH)2 or thiophosphoric acid (HO)2P(O)SH. The structures of
these acids is complicated by tautomeric equilibria between the O=P±SH
and HO±P=S forms. The position of the sulfur atoms is only defined
precisely when all the hydrogen atoms are replaced by alkyl groups,and
even then,under certain conditions,thiono (P=S) to thiolo (P±S)
rearrangement can occur. Compounds with one sulfur atom are classed
as phosphorothionates if they have a P=S bond or as phosphorothiolates if
they have a P±S bond. Using these rules,names for each class of
compound are as follows: F, O,O-dialkyl S-(fluoroalkyl) phosphor-
othiolates; G, O,O-bis(fluoroalkyl) O-alkyl phosphorothionates; H,
O,O-bis(fluoroalkyl) S-alkyl phosphorodithioates; I, O-(fluoroalkyl)
S,S-dialkyl phosphorodithiolates; J, O,O-bis(fluoroalkyl) S-alkyl phos-
phorothiolates; K, O-alkyl O-(fluoroalkyl) S-alkyl phosphorothiolates.
The reason for their inertness is unclear. The lead salt
was not inactive as some reacted with methylphosphonic

164
C.M. Timperley et al. / Journal of Fluorine Chemistry 119 (2003) 161±171
Table 1
dichloride MeP(O)Cl2 to give the disubstituted product
MeP(O)(SMe)2. The latter was made for studies of the
fragmentation of phosphorus compounds in an ion trap mass
spectrometer [41] and details will appear elsewhere.
An inability to obtain compounds (RFO)2P(O)SMe from
methanethiol or its lead salt is surprising as homologues
were made from higher alkanethiols (see Section 2.3).
Approaches worth studying,but outside the scope of this
Experimental data for phosphorothiolates of structure (RFO)2P(O)SR
Compound
RF
R
Yield (%)
bp (8C/mmHg)a
3a
3b
3c
3d
4a
4b
4c
4d
CF3CH2
Et
19
13
41
28
19
21
37
21
44/0.05b
43/0.03
53/0.02
35/0.03
50/0.04c
53/0.03
43/0.02
38/0.03
paper,include treatment of the dichloridate Cl P(O)SMe
2
C2F5CH2
C3F7CH2
(CF3)2CH
CF3CH2
Et
[42] with ¯uoroalcohols in the presence of tertiary amine,a
process that works well for alcohols [43],and alkylation of
thioacids; [H(CF2)2CH2O]2P(O)SMe and derivatives have
been made by treating the sodium or potassium salts of the
thioacid [H(CF2)2CH2O]2P(O)SH with alkyl iodides [24,25].
Et
Et
n-Pr
n-Pr
n-Pr
n-Pr
C2F5CH2
C3F7CH2
(CF3)2CH
a Approximate oven temperature for bulb-to-bulb distillations.
b Unfluorinated analogue (EtO)2P(O)SEt is a liquid with bp 80 8C/0.5
2.3. Successful syntheses of aliphatic thiolates
of structure J
mmHg [45].
c Unfluorinated analogue (EtO)2P(O)SPr is a liquid with bp 70 8C/0.3
mmHg [46].
Ethanethiol and propanethiol reacted with bis(¯uor-
oalkyl) phosphorochloridates in ether in the presence of
triethylamine to afford phosphorothiolates 3a±d and 4a±d as
colourless liquids.3 They were puri®ed by bulb-to-bulb
distillation. Yields and boiling points for the phosphorothio-
lates appear in Table 1.
bromine [1]. We extended this methodology and obtained
bis(penta¯uoropropyl) phosphorobromidate 5 as a colourless
liquid (bp 88 8C/1 mmHg).
Spectroscopic data for thiolates 3a±d and 4a±d appear in
Table 2. They have phosphorus chemical shifts around 30±
35 ppm,a region diagnostic for dialkyl phosphorothiolates
[26,51,52]. The shift for (CF3CH2O)2P(O)SEt 3a appears at
30.7 ppm,down®eld of that for its perprotio analouge
(CH3CH2O)2P(O)SEt which appears at 26.4 ppm [30]. In
the infrared spectra,the phosphoryl stretch for un¯uorinated
dialkyl phosphorothiolates appears between 1270 and
1245 cmÀ1. The ¯uorinated compounds gave strong C±F
stretching bands between 1300 and 1000 cmÀ1 which pre-
vented assignment of the P=O frequencies.
The chemistry of bis(¯uoroalkyl) phosphorobromidates
has not been charted and ¯uoroalkyl phosphorothiolates
with arylthio groups are unknown. Treatment of the phos-
phorobromidates with benzenethiol in ether in the presence
of triethylamine gave compounds 6a±b. The former 6a, a
solid (mp 35±36 8C),was isolated by ¯ash chromatography. 4
The latter 6b,a liquid (bp 96 8C/1 mmHg),was puri®ed by
bulb-to-bulb distillation. They have phosphorus chemical
shifts around 25 ppm; a singlet appears at 25.3 ppm for
compound 6a,more down®eld than that for the perprotio
analogue (EtO)2P(O)SPh which appears at 22 ppm [30,54].
Their synthesis illustrates the potential of bis(¯uoroalkyl)
phosphorobromidates as phosphorylating agents.
2.4. Syntheses of aromatic thiolates of structure J
In Part 6,we described the synthesis of bis(tri¯uoroethyl)
phosphorobromidate from the corresponding phosphite and
3 Unfluorinated analogues are generally prepared differently. The
perprotio analogue of 3a, (EtO)2P(O)SEt, also a distillable liquid, can
be prepared in 56% yield by treating an ethanolic solution of diethyl
sodium phosphite (EtO)2PONa with sulfur then ethyl bromide [44]. It
has also been made in 74 and 71% yield by reacting the same salt with
diethyl disulfide or ethyl phenyl disulfide in tetrahydrofuran [45], in
77% yield by reacting triethyl phosphite with diethyl disulfide [46] and
in 70% yield by isomerising the thionate (EtO)3P=S at 180±185 8C for
23 h [47]. A particularly convenient route involves the Arbusov
reaction between triethyl phosphite and ethyl thiocyanate, which
proceeds smoothly on warming, and gives the product in 90±91% yield
and the easily-removed by-product, ethyl cyanide [48,49]. Ethyl
sulfenyl chloride can be used instead of ethyl thiocyanate, but less
effectively (76% yield) [50]. Many unfluorinated compounds of
formula (RO)2P(O)SR0 can be obtained by such methods. Their
application to the synthesis of fluoroalkyl-substituted phosphorothio-
lates warrants examination.
4 The perprotio analogue of 6a, (EtO)2P(O)SPh, is a liquid. It has been
made in 50, 70 and 92% yield by the Arbusov reaction of triethyl
phosphite with phenyl 2,4-dinitrophenyl disulfide in xylene, diphenyl
disulfide in benzene, and pentachlorophenyl phenyl disulfide in ether
[46]. It was also obtained in 67% yield by treating diethyl sodium
phosphite (EtO)2PONa in benzene with diphenyl disulfide [53].
Purification entailed chromatography on Florisil [46] or distillation
(bp 95 8C/1 mmHg) [53].

Table 2
Spectroscopic data for bis(fluoroalkyl) S-alkyl phosphorothiolates (RFO)2P(O)SR 3a±d and 4a±d (NMR data measured in CDCl3)
Compound 1H NMR d, J (Hz)
13C NMR d, J (Hz)
19F NMR d
31P NMR d IR n (cmÀ1
)
Elemental analysis (%)
3a
3b
4.45 (4H,m,OCH 2),2.95 (2H,dq, J ˆ 15 122.3 (dq, J ˆ 11 and 277,CF 3), À74.6 (6F,t, J ˆ 6,CF 3) 30.7a
1456,1419,1296,1174,
1063,964,874,659
Calc. for C6H9F6O3PS (Mw 306): C 23.5,
and 7,SCH 2),1.42 (3H,t, J ˆ 7,CH
)
62.3 (dq, J ˆ 38 and 6,OCH 2),
25.5 (d, J ˆ 4,SCH 2),
H 2.9,F 37.3. Found: C 24.1,H 3.1,F 37.5
3
15.9 (d, J ˆ 7,CH
)
3
4.49 (4H,m,OCH 2),2.95 (2H,dq, J ˆ 15 125±108 (complex m,CF and
À123.7 (4F,m,CF 2),
30.7
1458,1354,1280,1203,
1157,1111,1055,1024,
935,872,721,620
Calc. for C8H9F10O3PS (Mw 406): C 23.6,
H 2.2,F 46.8. Found: C 23.8,H 2.1,F 47.1
2
and 7,SCH 2),1.42 (3H,t, J ˆ 7,CH
)
CF3),62.2 (dt, J ˆ 29 and 6,
OCH2),26 (d, J ˆ 5,SCH 2),
À82.5 (6F,m, J ˆ 287,
3
118 and 35,CF
)
3
15.9 (d, J ˆ 6,CH
)
3
3c
5.19 (4H,m,OCH 2),3.03 (2H,dq, J ˆ 15 125±115 (complex m,C 3F7),
À126.5 (4F,m,CF 2),
71.5 (m,OCH 2),25.7 (d, J ˆ 5, À120.4 (4F,m,CF 2),
SCH2),15.9 (d, J ˆ 8,CH À79.9 (6F,m,CF
35.3
35.3
1457,1356,1228,1184,
1130,1066,1014,966,
926,868,760,729
Not obtainedb
Calc. for C10H9F14O3PS (Mw 506): C 23.7,
H 1.8,F 52.6. Found: C 23.5,H 1.6,F 52.8
and 7,SCH 2),1.42 (3H,t, J ˆ 7,CH
)
3
)
)
3
3
3d
5.15 (2H,dsep, J ˆ 6 each,CH),
3.02 (2H,dt, J ˆ 17 and 7,SCH 2),
117 (dq, J ˆ 7 and 277,CF 3),
À72.7 (3F,br t,CF 3),
Not obtainedb
71.2 (dsep, J ˆ 6 and 28,OCH), À73.1 (3F,br s,CF
26.3 (d, J ˆ 5,SCH 2),16.5 (d,
)
3
1.42 (3H,t, J ˆ 7,CH )
3
J ˆ 8,CH
)
3
4a
4b
4c
4d
4.41 (4H,m,OCH 2),2.91 (2H,dt,
J ˆ 15,7,SCH 2),1.74 (2H,sextet,
123.4 (dq, J ˆ 11 and 277,CF 3), À74.0 (6F,t, J ˆ 9,CF
63.9 (dq, J ˆ 38 and 6,OCH 2),
)
31.1a
31.3
31.1
35.7
1458,1419,1294,1259,
1173,1095,1061,962,
874,659
Calc. for C7H11F6O3PS (Mw 320): C 26.3,
H 3.4,F 35.6. Found: C 26.4,H 3.7,F 35.2
3
J ˆ 7,CH ),1.05 (3H,t, J ˆ 7,CH )
33.3 (d, J ˆ 4,SCH 2),23.8 (d,
2
3
J ˆ 6,CH 2),13.7 (s,CH
)
3
4.5 (4H,m,OCH 2),2.93 (2H,dt,
J ˆ 15 and 7,SCH 2),1.71 (2H,sextet,
J ˆ 7,CH ),1.06 (3H,t, J ˆ 7,CH )
122±108 (complex m,C 2F5),
62.5 (dt, J ˆ 29 and 5,OCH 2),
33.5 (d, J ˆ 4,SCH 2),24.1 (d,
À123.4 (4F,m,CF 2),
À82.5 (6F,m,CF
1459,1269,1203,1157,
1111,1026,935,870,
721,621
Calc. for C9H11F10O3PS (Mw 420): C 25.7,
H 2.6,F 45.2. Found: 25.9,H 2.8,F 45.5
)
3
2
3
J ˆ 6,CH 2),12.5 (s,CH
)
3
4.53 (4H,m,OCH 2),2.93 (2H,dt,
J ˆ 14 and 7,SCH 2),1.75 (2H,sextet,
J ˆ 7,CH ),1.04 (3H,t, J ˆ 7,CH )
124±110 (m,C 3F7),63.8 (m,
OCH2),33.2 (d, J ˆ 4,SCH 2),
24.1 (d, J ˆ 7,CH 2),12.6 (s,
CH3)
À126.7 (4F,m,CF 2),
À120.0 (4F,m,CF 2),
1460,1356,1228,1184,
1130,1066,1014,966,
926,868
Calc. For C11H11F14O3PS (Mw 520): C 25.4,
H 2.1,F 51.2. Found: C 25.6,H 2.4,F 51.3
À80.1 (6F,m,CF
)
3
2
3
5.17 (2H,dsep, J ˆ 6 each,CH),
2.96 (2H,dt, J ˆ 16 and 7,SCH 2),
120 (dq, J ˆ 7 and 277,CF 3),
72 (dsep, J ˆ 6 and 28,OCH),
33.3 (d, J ˆ 4,SCH 2),23.6 (d,
À72.7 (3F,br t,CF 3),
À73.1 (3F,br s,CF
Not obtainedb
Not obtainedb
)
3
1.77 (2H,sextet, J ˆ 7,CH 2),1.04 (3H,t,
J ˆ 7,CH )
J ˆ 7,CH 2),12.7 (s,CH
)
3
3
a The phosphorus chemical shifts of compounds 3a and 4a,namely (CF 3CH2O)2P(O)SEt and (CF3CH2O)2P(O)SPr,appear downfield of those of their perprotio analogues (EtO) 2P(O)SEt and (EtO)2P(O)SPr
which feature at 26.4 and 26.5 ppm,respectively [30].
b Compound only 90% pure by 31P NMR analysis.

166
C.M. Timperley et al. / Journal of Fluorine Chemistry 119 (2003) 161±171
Experiments to investigate the interaction of bis(¯uor-
oalkyl) phosphorohalidates with penta¯uorobenzenethiol
did not proceed as expected: derivatives of structure
(RFCH2O)2P(O)SC6F5 could not be isolated. Bis(tri¯uor-
oethyl) phosphorobromidate and equimolar amounts of
penta¯uorobenzenethiol and triethylamine produced only
traces of triethylamine hydrobromide on mixing. After
heating under re¯ux for 48 h,the situation did not improve
and gas chromatography±mass spectrometry (GC±MS)
analysis showed the mixture to comprise unreacted bromi-
date and thiol,and an unknown of m/z 380. This latter
was not isolated,but was presumed to be sul®de 8 from
substitution of one molecule of penta¯uorobenzenethiol by
another.
It is reasonable to assume para orientation in light of
data for attack of nucleophiles on substituted penta¯uor-
obenzenes [55,56] despite de®cient knowledge of the
directional effect of the SH group. Neither penta¯uoroben-
zenethiol nor sul®de 8 reacted with the bromidate under
the conditions studied,contrasting with benzenethiol that
reacted at the phosphorus atom. The difference is mainly
electronic in origin and attributable to the greater basicity
of benzenethiol and in the case of penta¯uorobenzene-
thiol,its ability to self-condense under basic conditions
[57,58].
Scheme 2.
groups was examined. Two molar equivalents of chloridate
were treated with a molar equivalent of 2-mercaptoethanol,
3-mercaptopropanol or ethane-1,2-dithiol in ether, in the
presence of two molar equivalents of triethylamine and a
catalytic quantity of 4-dimethylaminopyridine. The antici-
pated bis-substitution products 12 did not form.
2.5. Synthesis of thiolates of structure K
The synthesis of compounds of general formula
(RFO)ROP(O)SR0 was accomplished in three steps. The
strategy involved introducing the alkylthio group ®rst
and incorporating the ¯uoroester group last. Arbusov
reaction of triethyl phosphite with methyl thiocyanate
yielded phosphorothiolate
9 that was transformed
into chloridothiolate 10 by heating with phosphorus
oxychloride. The chloridothiolate,on treatment with ¯uor-
oalcohols and triethylamine,gave compounds 11a±d
(Scheme 2). They were puri®ed by chromatography or
short-path distillation and were obtained as colourless
liquids.
Spectroscopic data for compounds 11a±d appear in
Table 3. They contain a chiral phosphorus atom. No attempt
was made to resolve the racemic mixtures.
1,2-Mercaptoethanol and 1,3-mercaptopropanol gave
three tentative productsÐphosphoric acid 13,phosphate
14 and pyrophosphate 15Ðas indicated by GC±MS analysis
(Table 4). Ethane-1,2-dithiol gave three products: phos-
phate 14 and two pyrophosphates differing in the bridging
atom (oxygen 15 or sulfur 16). The percentage of each
was calculated by integration of its peak relative to the
other components and is approximate: some volatile pro-
ducts may have escaped detection. We failed to separate
the product mixtures by chromatography or distillation.
The mechanism of reaction is obscure and merits further
investigation.
2.6. Reactions of bis(trifluoroethyl) phosphorochloridate
with bis-nucleophiles
The behaviour of bis(tri¯uoroethyl) phosphorochloridate
towards bis-nucleophiles containing one or more thiol

Table 3
Spectroscopic data for O-ethyl O-fluoroalkyl S-methyl phosphorothiolates RFO(EtO)P(O)SMe 11a±d (NMR data measured in CDCl3)
Compound 1H NMR d, J (Hz)
13C NMR d, J (Hz)
19F NMR d, J (Hz)
À74.6 (3F,t,
31P NMR d IR n (cmÀ1
)
Elemental analysis (%)
11a
11b
4.43 (2H,m,OCH 2CF3),4.23 (2H,m,
122.8 (dq, J ˆ 11 and 277,CF 3),
64.6 (d, J ˆ 6,OCH 2),62.7 (dq,
J ˆ 38 and 4,O CH2CF3),15.9 (d,
29.0a
1421,1394,1290,1257,
1173,1090,1024,964,
860,841,777,660,
611,582
Calc. for C5H10F3O3PS (Mw 238):
C 25.2,H 4.2,F 23.9. Found: C 25.2,
H 4.4,F 24.2
OCH2),2.31 (3H,d, J ˆ 16,SCH 3),
J ˆ 10,CF
)
3
1.41 (3H,t, J ˆ 7,CH )
3
J ˆ 7,SCH 3),12.2 (d, J ˆ 4,CH )
3
4.48 (2H,m,OCH 2C2F5),4.25 (2H,m,
118.5 (tq, J ˆ 287 and 34,CF 3),
111.8 (dq, J ˆ 10 and 256,CF 2),
64.7 (d, J ˆ 6,OCH 2),61.7 (dt,
J ˆ 29 and 4,O CH2C2F5),15.7 (d,
À123.5 (2F,m,CF 2),
À82.5 (3F,m,CF
29.1
1446,1394,1354,1265,
1203,1155,1111,1078,
1020,970,852,773,719,
657,621
Calc. For C6H10F5O3PS (Mw 288):
C 25.0,H 3.5,F 33.0. Found: C 25.1,
H 3.4,F 32.7
OCH2),2.33 (3H,d, J ˆ 16,SCH 3),
)
3
1.39 (3H,t, J ˆ 7,CH )
3
J ˆ 7,SCH 3),12.1 (d, J ˆ 4,CH )
3
11c
11d
4.53 (2H,m,OCH 2C3F7),4.26 (2H,m,
OCH2),2.32 (3H,d, J ˆ 16,SCH 3),
120±105 (complex m,C 3F7),64.7 (d, À126.5 (2F,m,CF 2),
29.3
1444,1394,1356,1327,
1230,1184,1132,1090,
1030,1014,966,924,
852,759,727,611,584
Calc. For C7H10F7O3PS (Mw 338):
C 24.9,H 3.0,F 39.3. Found: C 25.1,
H 2.7,F 39.1
J ˆ 6,OCH 2),61.9 (dt, J ˆ 28
and 4,O CH2C3F7),15.9 (d,
À120.5 (2F,m,CF 2),
À80.0 (3F,m,CF
1.41 (3H,t, J ˆ 7,CH )
)
3
3
J ˆ 6,SCH 3),12.1 (d, J ˆ 5,CH )
3
5.23 (1H,dsep, J ˆ 6 each,OCH),
120.6 (dq, J ˆ 7 and 280,CF 3),
À73.5 (3F,`q', J ˆ 8, 31.3
1383,1296,1234,1201,
1113,1026,972,901,
877,775,734,688,602
Calc. For C6H9F6O3PS (Mw 306):
C 23.5,H 2.9,F 37.3. Found: C 23.8,
H 3.2,F 37.3
4.28 (2H,dq, J ˆ 7,OCH 2),2.36 (3H,d, 70.4 (dsep, J ˆ 6 and 35,OCH),
CF3) and À73.6 (3F,
b
J ˆ 17,SCH 3),1.42 (3H,t, J ˆ 7,CH
)
65.5 (d, J ˆ 7,OCH),15.7 (d,
`q', J ˆ 8,CF
)
3
3
J ˆ 7,SCH 3),12.1 (d, J ˆ 5,CH )
3
a The phosphorus chemical shift of compound 11a,CF 3CH2O(EtO)P(O)SMe,is only slightly downfield of that of the perprotio analogue (EtO) 2P(O)SMe which appears at 28.6 ppm [30]. One fluoroethoxy
group hardly affects the position of the shift,yet two fluoroethoxy groups have a more profound influence (refer to Table 2,footnote a).
b Compound 11d,(CF 3)2CHO(EtO)P(O)SMe,contains two magnetically non-equivalent CF groups due to the chiral phosphorus centre: the trifluoromethyl resonances appear as slightly overlapping
3
quartets.

168
C.M. Timperley et al. / Journal of Fluorine Chemistry 119 (2003) 161±171
Table 4
Tentative products of reactions of some bis-nucleophiles with bis-(2,2,2-trifluoroethyl) phosphorochloridate
Nucleophile
Possible products
HOCH2CH2SH (%)
HOCH2(CH2)2SH (%)
HSCH2CH2SH (%)
17
20
±
8
10
24
75
70
38
±
±
38
3. Conclusion
are recorded as follows: chemical shifts in ppm from refer-
ence on the d scale,integration,multiplicity (s: singlet,d:
doublet,t: triplet,q: quartet,m: multiplet and sep: septet; br:
broad),coupling constant ( J/Hz) and assignment. IR spectra
were recorded as liquid ®lms on a Nicolet SP210 instrument
using Omnic software. Reaction mixtures were monitored
by gas chromatography±mass spectrometry (GC±MS)
using a Finnigan MAT GCQ instrument with chemical
ionisation (CI) using methane as reagent gas. Molecular
masses of pure products were con®rmed with methane
positive CI data (70 eV). All compounds containing sulfur
appeared as one spot by TLC and were >98% pure by
multinuclear NMR and GC±MS analyses,unless stated
otherwise.
Thiols react less ef®ciently with bis(¯uoroalkyl) phos-
phorochloridates than alcohols or amines. Although it is
possible to prepare compounds of structure RFOP(O)(SR)2
and (RFO)2P(O)SR in modest quantities from phosphoro-
halidates,better routes need to be developed. Reactions of
chloridates already containing the RS±P(O) grouping are
more ef®cient; ¯uoroalcoholysis of MeS(EtO)P(O)Cl gave
derivatives MeS(EtO)P(O)ORF in 62±74% yield. Reactions
of bis-nucleophiles containing thiol groups with bis(tri¯uor-
oethyl) phosphorochloridate gave complex mixtures. The
chemistry of ¯uoroalkyl phosphoryl compounds containing
sulfur groups should mature once high-yielding synthetic
routes become available.
4.1. Synthesis of S,S-diethyl O-(2,2,2-trifluoroethyl)
phosphorothiolate (2)
4. Experimental details
A solution of ethanethiol (1.49 g,24 mmol) and triethy-
lamine (3.34 ml,24 mmol) in ether (10 ml) was added
dropwise by cannula to a stirred solution of 2,2,2-tri¯uor-
oethyl phosphorochloridate (2.6 g,12 mmol) in ether
(30 ml) at 0±5 8C. After addition,the mixture was allowed
to warm to room temperature. After 14 h,an aliquot was
withdrawn for analysis by GC±MS. The reaction was 90%
complete. The precipitate was ®ltered off and the ®ltrate
concentrated. Bulb-to-bulb distillation of the residue (oven
temperature 45 8C at 0.015 mmHg) gave a liquid that was
85% pure by phosphorus NMR spectroscopy. The liquid was
subsequently chromatographed on silica gel,eluting with
12:1 hexane±acetone,to give the title compound as a colour-
less liquid (0.97 g,30%). Rf 0.48. 1H NMR: d ˆ 4:4 (2H,m,
OCH2),2.97 (4H,dq, J ˆ 15 and 7 Hz,SCH 2),1.42 (6H,t,
J ˆ 7 Hz,CH 3). 13C NMR: d ˆ 122:6 (dq, J ˆ 11 and
277 Hz,CF 3),62.4 (dq, J ˆ 38 and 7 Hz,OCH 2),26.7
(d, J ˆ 4 Hz,SCH ),15.4 (d, J ˆ 6 Hz,CH ). 19F NMR:
2,2,2-Tri¯uoroethyl phosphorodichloridate [15],bis-
(¯uoroalkyl) phosphorochloridates, bis(2,2,2-tri¯uoroethyl)
phosphorobromidate and bis(2,2,3,3,3-penta¯uoropropyl)
H-phosphonate [1] were obtained in high purity using pre-
viously reported methods. All reagents were of commercial
quality: alkanethiols and lead (II) acetate trihydrate were
purchased from Aldrich (Gillingham,UK) and ¯uoroalco-
hols from Apollo Scienti®c Ltd. (Derbyshire,UK). They
were used as received. Anhydrous solvents were used in all
experiments. Thin layer chromatography (TLC) plates,
Ê
MK6F silica gel 60 A (2:5 cm  7:5 cm,layer thickness
250 mg),were obtained from Whatman (Maidstone,UK).
Spots were visualised with iodine vapour. Silica gel for ¯ash
chromatography was from BDH Laboratory Supplies
(Poole,UK). NMR spectra were obtained on a JEOL
Lambda 500 instrument (operating at 500 MHz for 1H,
125 MHz for 13C,470 MHz for 19F,and 202 MHz for 31P
spectra) or a JEOL Lambda 300 instrument (operating at
2
3
d ˆ À74:2 (3F,t, J ˆ 8 Hz,CF ). 31P NMR: d ˆ 59:2. IR
3
1
300 MHz for H,75 MHz for 13C,282 MHz for 19F,and
(®lm): n ˆ 1452,1417,1379,1284,1230 (P=O),1171,
121.5 MHz for 31P spectra) as solutions in CDCl3,with
internal reference SiMe4 for 1H and 13C,external CFCl 3 for
19F and external (MeO)3P (d 140 ppm) for 31P spectra. Data
1068,962,850,657,602 cm
À1. HRMS: calculated
‡
C6H12F3O2PS2 268.248 ([M-HF] ˆ 248.242),found
248.211 (error 0.8).

C.M. Timperley et al. / Journal of Fluorine Chemistry 119 (2003) 161±171
169
4.2. Attempted reaction of bis(fluoroalkyl)
phosphorochloridates with methanethiol
trated to give a liquid that was puri®ed by bulb-to-bulb
distillation under reduced pressure. Boiling points appear in
Table 1 and spectroscopic data in Table 2.
A round-bottomed ¯ask was equipped with a T-adaptor
and a dry ice condenser whose outlet was ®tted with a guard
tube containing anhydrous calcium chloride. The ¯ask
was charged with a solution of bis(¯uoroalkyl) phosphoro-
chloridate (4 mmol) and triethylamine (4 mmol) in ether
(20 ml). The ¯ask and the condenser were cooled to À78 8C
(dry ice/acetone) and methanethiol was passed through the
T-adaptor. Lique®ed methanethiol was allowed to condense
into the reaction mixture until it was clear that excess
had been added. The gas ¯ow was stopped and the ¯ask
warmed to room temperature (the condenser containing dry
ice remained at À78 8C). Once the ¯ask reached room
temperature,the dry ice in the cold ®nger was allowed to
evaporate. The reaction mixture was left to stand for 12 h.
No precipitate formed and analysis by GC-MS indicated that
no reaction had taken place. Removal of solvent gave the
starting chloridates.
4.6. Preparation of bis(pentafluoropropyl)
phosphorobromidate (5)
A solution of bromine (4.62 g,28.9 mmol) in dichloro-
methane (20 ml) was added dropwise to a stirred solution
of bis(2,2,3,3,3-penta¯uoropropyl) H-phosphonate (10 g,
28.9 mmol) in dichloromethane (30 ml) at 0±5 8C. The
added bromine decolourised rapidly. After addition the
mixture was allowed to warm to room temperature and left
for 12 h. The solvent was removed. Distillation of the
residue under reduced pressure gave the title compound
as a colourless liquid (10.71 g,87%); bp 88 8C/1 mmHg and
1
46 8C/0.1 mmHg. H NMR: d ˆ 4:56 (4H,m,OCH 2). 13C
NMR: d ˆ 116 (tq, J ˆ 34 and 286 Hz,CF ),109.4 (dq,
3
J ˆ 8 and 256 Hz,CF 2),63.7 (dt, J ˆ 6 and 29 Hz,OCH 2).
19F NMR: d ˆ À123:9 (4F,m,CF ), À83.2 (6F,m,CF ). 31
P
2
3
NMR: d ˆ À8:9. IR (®lm): n ˆ 1377,1356,1304 (P=O)À, 1
4.3. Preparation of lead methanethiolate
1269,1205,1163,1126,1111,1031,935,889 cm
HRMS: calculated C6H4BrF10O3P 424.953 ([M-HF]
404.947),found 404.932 (error 1.2).
.
ˆ
‡
Lead (II) acetate trihydrate (22.8 g,60 mmol) was sus-
pended in ethanol (200 ml) maintained at 50 8C. Deionised
water (ca. 25 ml) was added and the suspension stirred until
the solid dissolved. Methanethiol was bubbled through the
solution until a yellow precipitate formed. This was ®ltered
off,washed with ethanol,and dried under high vacuum
(17.4 g,96%); mp 128 8C (dec.).
4.7. Preparation of O,O-bis(trifluoroethyl) S-phenyl
phosphorothiolate (6a)
A solution of benzenethiol (0.68 g,6.18 mmol) and
triethylamine (0.86 ml,6.18 mmol) in ether (10 ml) was
added dropwise by cannula to a stirred solution of bis-
(2,2,2-tri¯uoroethyl) phosphorobromidate (2 g, 6.18 mmol)
in ether (40 ml) at 0±5 8C. An instant precipitate of triethy-
lamine hydrobromide formed. After addition the mixture
was allowed to warm to room temperature and was left for
2 h. The precipitate was removed by ®ltration. Concentra-
tion of the ®ltrate gave a semi-solid residue. Chromatogra-
phy on silica gel,eluting with 4:1 hexane±acetone,gave the
title compound as a white solid (0.95 g,43%); mp 35±36 8C.
1H NMR: d ˆ 7:61À7:42 (5H,m,phenyl),4.37 (4H,m,
OCH2). 13C NMR: d ˆ 151:17 (d, J ˆ 8 Hz,phenyl ipso C),
135.5 (d, J ˆ 5 Hz,phenyl ortho C),130.3 (d, J ˆ 3 Hz,
phenyl meta C),129.9 (d, J ˆ 3 Hz,phenyl para C),121.2
4.4. Attempted reactions of phosphorochloridates
with lead methanethiolate
Lead methanethiolate (1.08 g,3.6 mmol) was added
in one portion to a solution of phosphorochloridate
(7.1 mmol) in benzene (50 ml) at room temperature. The
reaction mixture was heated under re¯ux for 2 h. The
yellow thiolate salt discoloured and went slightly grey.
Experiments were carried out with bis(tri¯uoroethyl)
phosphorochloridate,bis(penta¯uoropropyl) phosphoro-
chloridate and diethyl phosphorochloridate. No reaction
occurred as shown by TLC,GC±MS and multinuclear
NMR analyses.
(dq, J ˆ 11 and 277 Hz,CF ),63.5 (dq, J ˆ 38 and 6 Hz,
3
OCH2). 19F NMR: d ˆ À74:6 (6F,t, J ˆ 8 Hz,CF ). 31P
3
4.5. General procedure or O,O-bis(fluoroalkyl) S-alkyl
phosphorothiolates (3a±d) and (4a±d)
NMR d ˆ 25:3. IR (KBr disc): n ˆ 2252,1581,1475,1454,
1442,1417,1296,1259,1174,1095,1063,962,910,
877,845,818,746,737 cm
À1. HRMS calculated C10H9-
F6O3PS 354.201 ([M-HF] ˆ 334.195),found 334.201
‡
A solution of ethanethiol or propanethiol (4 mmol) and
triethylamine (0.56 ml,4 mmol) in ether (10 ml) was added
dropwise by cannula to a stirred solution of bis(¯uoroalkyl)
phosphorochloridate (4 mmol) in ether (25 ml) at 0±5 8C.
After addition,the mixture was warmed to room temperature
and left for 14 h before a portion was analysed by GC±MS.
When product predominated,the precipitate was removed
using silicone-treated ®lter paper. The ®ltrate was concen-
(error 1.8).
4.8. Preparation of O,O-bis(pentafluoropropyl) S-phenyl
phosphorothiolate (6b)
A solution of benzenethiol (0.51 g,4.64 mmol) and
triethylamine (0.65 g,4.64 mmol) in ether (10 ml) was added

170
C.M. Timperley et al. / Journal of Fluorine Chemistry 119 (2003) 161±171
Table 5
dropwise by cannula to a stirred solution of bis(2,2,3,3,3-
penta¯uoropropyl) phosphorobromidate (1.97 g,4.64 mmol)
in ether (40 ml) at 0±5 8C. An instant precipitate of triethy-
lamine hydrobromide formed. After addition the mixture
was allowed to warm to room temperature and was left for
24 h. The precipitate was removed by ®ltration. Concentra-
tion of the ®ltrate gave a liquid that was distilled under
reduced pressure using a Kugelrohr apparatus. The title
compound was obtained as a colourless liquid (0.98 g,
Experimental data for phosphorothiolates of structure (RFO)EtOP(O)SMe
Compound
Chromatography
solventa
Retention
factor
bp (8C/mmHg)
11a
11b
11c
11d
3:1 hexane±acetone
3:1 hexane±acetone
6:1 hexane±acetone
±
0.35
0.46
0.42
±
±
±
±
35/0.02b
a Chromatography plates developed with iodine vapour.
b Approximate oven temperature for bulb-to-bulb distillation.
1
46%); bp 96 8C/1 mmHg. H NMR: d ˆ 7:62À7:35 (5H,
m,phenyl),4.44 (4H,m,OCH 2). 13C NMR: d ˆ 151:1 (d,
J ˆ 8 Hz,phenyl ipso C),135.5 (d, J ˆ 5 Hz,phenyl ortho
C),130.3 (d, J ˆ 3 Hz,phenyl meta C),129.9 (d, J ˆ 3 Hz,
phenyl para C),118.1 (tq, J ˆ 34 and 285 Hz,CF 3),
4.11. General method for O-ethyl O-(fluoroalkyl) S-methyl
phosphorothiolates (11a±d)
111.3 (tq, J ˆ 9 and 256 Hz,CF ),62.7 (dq, J ˆ 29 and
2
6 Hz,OCH 2). 19F NMR: d ˆ À123:6 (4F,m,CF
2),
À82.6 (6F,m,CF 3). 31P NMR: d ˆ 25:5. IR (KBr disc):
A solution of ¯uoroalcohol (15 mmol) and triethylamine
(2.09 ml,15 mmol) in ether (10 ml) was added dropwise by
cannula to a stirred solution of O-ethyl S-methyl phosphor-
ochloridothiolate (2.61 g,15 mmol) in ether (15 ml) at 0±
5 8C. After addition,the mixture was allowed to warm to
room temperature. Within 1 h,a thick precipitate of triethy-
lamine hydrochloride formed. The precipitate was ®ltered
off,the ®lter cake washed with ether (2 Â 10 ml) and the
combined washings concentrated. Chromatography of the
residue on silica gel,eluting with solvent systems listed in
Table 5,gave the title compounds as colourless liquids.
n ˆ 2254,1442,1354,1267,1209,1159,1124,1065,
1026,908,876,837,735 cm À1. HRMS calculated C12H9-
‡
F10O3PS 454.215 ([M-HF] ˆ 434.209),found 434.202
(error 0.3).
4.9. Preparation of O,O-diethyl S-methyl
phosphorothiolate (9)
Triethyl phosphite (166 g,1 mol) and methyl thiocyanate
(73 g,1 mol) were heated under re¯ux for 1 h. Analysis by
TLC and GC±MS showed excellent conversion to the pro-
duct. Distillation under reduced pressure gave the title
compound as a colourless liquid (162 g,88%); bp 90 8C/
0.6 mmHg. Purity 95% (determined by phosphorus NMR
and GC±MS analyses). 1H NMR: d ˆ 4:18 (4H,m,OCH 2),
2.28 (3H,d, J ˆ 15 Hz,SCH 3),1.39 (6H,t, J ˆ 7 Hz,CH 3).
13C NMR: d ˆ 63:4 (d, J ˆ 6 Hz,OCH 2),15.9 (d,
J ˆ 7 Hz,SCH 3),12.2 (d, J ˆ 5 Hz,CH 3). 31P NMR:
4.12. Reactions of bis(2,2,2-trifluoroethyl)
phosphorochloridate with bis-nucleophiles
A solution of 2-mercaptoethanol,3-mercaptoethanol or
ethane-1,2-dithiol (4 mmol) and triethylamine (1.12 ml,
8 mmol) in ether (25 ml) was added dropwise by cannula
to a stirred solution of bis(2,2,2-tri¯uoroethyl) phosphoro-
chloridate (2.24 g,8 mmol) in ether (25 ml) at 0±5 8C. After
addition,a catalytic amount of 4-dimethylaminopyridine
was added and the mixture was allowed to warm to room
temperature. After 12 h,an aliquot of the reaction mixture
was analysed by GC±MS. The products are discussed in
Section 2.6. Attempts to separate them by fractionation
under reduced pressure or by chromatography on silica
gel failed.
d ˆ 27:4. IR (®lm): n ˆ 2983,2918,2848,1392,1253
À1
(P=O),1163,1097,1018,972,793 cm
.
4.10. Preparation of O-ethyl S-methyl
phosphorochloridothiolate (10)
A solution of phosphorus oxychloride (29.2 g,0.19 mol)
in chloroform (30 ml) was added in one portion to a solution
of O,O-diethyl S-methyl phosphorothiolate (35 g,0.19 mol)
in chloroform (30 ml). The mixture was heated under
re¯ux and monitored by GC±MS. After 36 h,the reaction
would not progress further. Removal of the solvent and
fractionation of the residue under reduced pressure gave the
pure title compound (29.8 g,90%); bp 104 8C/12 mmHg.
1H NMR: d ˆ 4:35 (2H,m,OCH 2),2.5 (3H,d, J ˆ 19 Hz,
SCH3),1.44 (3H,t, J ˆ 7 Hz, CH3). 13C NMR: d ˆ 66:0 (d,
Acknowledgements
Many thanks to Steve Marriott and Ian Holden for obtain-
ing the IR and NMR spectra,and to the Ministry of Defence
UK for funding the work.
References
J ˆ 9 Hz, OCH2),15.7 (d, J ˆ 8 Hz,SCH ),13.5 (d, J ˆ
3
5 Hz, CH ). 31P NMR: d ˆ 36:0. IR (®lm): n ˆ 2985,
3
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