Anomalous reaction of ethyl bromofluoro- and difluoro-acetates with dialkylphosphonites

Article abstract of DOI:10.1080/10426500801968110

The Michaelis-Arbuzov reaction of ethyl α-bromo-α-fluoro- and α, α-difluoro-acetates with dialkyl phenylphosphonites leads to the formation of unusual products including a fluorophosphinate. The reaction of ethyl bromofluoracetate with diisopropyl- and dimethyl-phenylphosphonites furnishes a complex mixture of eight and five compounds respectively. Five different compounds are obtained when ethyl bromodifluoroacetate is reacted with diisopropyl phenylphosphonite. Dimethyl phenylphosphonite yields three compounds when heated with bromochloromethane. The probable mechanism of formation of the compounds and their mass spectral characterization using GC-MS, tandem MS-MS and DART techniques are presented in this paper. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500801968110

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Phosphorus, Sulfur, and Silicon
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Anomalous Reaction of
Ethyl Bromofluoro- and
Difluoro-Acetates with
Dialkylphosphonites
H. D. Durst a , D. K. Rohrbaugh a , P. Smith b , J.
M. Nilles b , T. Connell b , J. A. Laramee b & S.
Munavalli b
a U. S. Army Edgewood Chemical and Biological
Center , Aberdeen Proving Ground, Maryland, USA
b SAIC , Aberdeen Proving Ground, Maryland, USA
Published online: 10 Oct 2008.
To cite this article: H. D. Durst , D. K. Rohrbaugh , P. Smith , J. M. Nilles , T. Connell ,
J. A. Laramee & S. Munavalli (2008) Anomalous Reaction of Ethyl Bromofluoro- and
Difluoro-Acetates with Dialkylphosphonites, Phosphorus, Sulfur, and Silicon and the
Related Elements, 183:11, 2655-2668
To link to this article: http://dx.doi.org/10.1080/10426500801968110
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Phosphorus, Sulfur, and Silicon, 183:2655–2668, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500801968110
Anomalous Reaction of Ethyl Bromofluoro- and
Difluoro-Acetates with Dialkylphosphonites
H. D. Durst,1 D. K. Rohrbaugh,1 P. Smith,2 J. M. Nilles,2
T. Connell,2 J. A. Laramee,2 and S. Munavalli2
1U. S. Army Edgewood Chemical and Biological Center, Aberdeen
Proving Ground, Maryland, USA
2SAIC, Aberdeen Proving Ground, Maryland, USA
The Michaelis–Arbuzov reaction of ethyl α-bromo-α-fluoro- and α, α-difluoro-
acetates with dialkyl phenylphosphonites leads to the formation of unusual prod-
ucts including a fluorophosphinate. The reaction of ethyl bromofluoracetate with
diisopropyl- and dimethyl-phenylphosphonites furnishes a complex mixture of eight
and five compounds respectively. Five different compounds are obtained when ethyl
bromodifluoroacetate is reacted with diisopropyl phenylphosphonite. Dimethyl
phenylphosphonite yields three compounds when heated with bromochloromethane.
The probable mechanism of formation of the compounds and their mass spectral
characterization using GC-MS, tandem MS-MS and DARTTM techniques are pre-
sented in this paper.
Keywords α-fluoro- and difluoro-esters; DART mass spectrometry; dialkylphosphonites;
free radical Arbuzov reaction; GC-MS; MS-MS; Michaelis–Arbuzov reaction
INTRODUCTION
The Michaelis–Arbuzov reaction is regarded as one of the most im-
portant reactions employed in the synthesis of organophosphorus com-
pounds containing the phosphoryl (P O) bond.1a–1f Though organic
halides are generally employed in this reaction, alkyl and aryl radi-
cals have been shown to react with trivalent phosphorus esters to fur-
nish the expected products.2 Thus, photolysis of triethylphosphite has
been found to generate O- and P-centered as well as ethyl radicals.3
The phenyl radical has been stated to be more electrophilic than alkyl
radicals.4a In fact, the following order of electronegativity has been de-
scribed: t-butoxy > phenyl > methyl > cyclohexyl.4b In view of the above,
Received 3 December 2007; accepted 15 January 2008.
Address correspondence to S. Munavalli, SAIC, P. O. Box 68, Aberdeen Proving
Ground, MD 21010, USA. E-mail: shekar.munavalli@US.army.mil
2655

2656
H. D. Durst et al.
the rapid, irreversible reaction of the in situ generated phenyl radicals
with trialkyl phosphites to yield phenyl dialkylphosphonates, does not
seem to be surprising.4c
Fluorine-containing organic halides have been stated to furnish
unexpected Arbuzov products. Thus, the reaction of pentafluoroethyl
ethyl pentanone with trimethyl phosphite yielded methoxy-perfluoro-2-
pentene and dimethyl fluorophosphononate,5a while perfluoropropenyl
ketone gave trialkyl (perfluoroethenylcarbonyl)fluorophosphonate.
Perfluoropropene has been reported to give perfluoropropenyl
phosphinofluoridate.5b–5c The proposed mechanism involves the ab-
straction of the α-fluorine by phosphorus. It should be stated here that
tris-silyloxyphosphites also undergo the normal Arbuzov reaction with
perfluoroalkenes and fluoroalkyl halides respectively.6
Since the Arbuzov reaction of diialkylphosphonites is the primary
process for the preparation of unsymmetrical phosphoryl derivatives,
the reaction of diisopropyl phenylphosphonite with ethyl bromofluoro-
and bromo difluoro-acetates has been examined and found to furnish
unexpected products. The Arbuzov reaction of the substrate with bro-
mofluoromethane at ambient temperature appears to be very sluggish.
This communication describes the identification of the various com-
pounds thus formed using GC-MS, high resolution tandem MS-MS and
DARTTM-mass spectrometric techniques and the probable mechanism
of their formation.
RESULTS AND DISCUSSION
The facile formation of phosphonium salts from the reaction of tri-
alkyl and triarylphosphines with bromofluoro acetic acid esters and
their subsequent use in the Wittig reaction have been reported.7
[(Carbethoxy)fluoromethyl] diethylphosphonate has been obtained
from the Michaelis–Becker reaction of diethyl sodiophosphonate with
ethyl bromo-fluoroacetate.8a The Arbuzov reaction of fluorine con-
taining organic halides has been reported to yield unexpected flu-
orinated phosphorus products. Thus, the reaction of α, β-dichloro-
ω-iodofluoroalkenes with triethylphosphite has been shown to yield
products corresponding to dechlorination, as well as α-(phosphoryl-ω-
iodo,α, α-perfluoroalkene.8b The same substrate when reacted with per-
fluroisobutylene at −70◦C gave diethyl-(perfluoroisobutenyl)fluropho-
sphonate via the migration of fluorine from carbon to phosphorus.8c
This unusual reaction of fluorinated reactants has been attributed to
the enhancement of the activity of the terminal fluorine by the dou-
ble bond and the increased affinity between fluorine and phosphorus.
The reaction of perfluorovinyl iodide with tris-isopropylphosphite gave

Ethyl Bromofluoro- and Difluoro-Acetates
2657
1,2-difluoro-1-iodo-diisopropylphosphnate (cis and trans).8d However,
with two equivalents of the phosphinate, trans difluoroethylene bis-
phosphoic acid tetra-isopropyl ester was obtained along with the pre-
viously mentioned compounds. Triethylphosphite has been observed
to react with ethyl bromofluoroacetate at 145◦C to give the expected
[(carbethoxy)-fluoromethyl] diisopropyl-phosphonate.8e The influence
of the bond strength and steric and configurational constraints and
considerations on the stability of the phosphoranyl radicals has been
examined in the free radical catalyzed reactions.7a The size of the alkoxy
group attached to the P-atom appears to control the rate of the Arbuzov
reaction.9b
Since virtually no report on the Vibrational Circular Dichroism
(VCD) studies of the phosphoryl group (P O) has appeared, it was
considered interesting to examine the VCD of substituted chiral P O
group containing compounds and to examine the overall effect of the
substituents on the absorption frequencies of the P O group. The P O
linkage is very stable and strong and its dissociation energy has been
reported to be between 120∼140 kcal/mol.10 The infrared stretching
frequencies of F3P O and CH3P O have been reported to be 1418
cm−1 and 1170 cm−1, respectively.10a This clearly demonstrates that
the substituents do exert considerable influence on the P O absorption
frequencies.
As stated earlier, the compounds containing phosphoryl group (P O)
are usually obtained via the classical Michaelis–Arbuzov reaction cat-
alyzed by alkyl halides1 and also through the oxidation of the respective
precursors.2 In continuation of our interest in developing methodology
to permit the synthesis of optically active and/ or pro-chiral phosphorus
compounds, the reaction of dialkyl phenyl phosphonites with activated
halides such as (bromo)(chloro)methane and ethyl α-bromo-α-fluoro-
and α-bromo-α, α-difluoroacetates has been examined and found to fur-
nish unexpected products.
A mixture containing stoichiometric amounts of diisopropyl phenyl-
phosphonite (1) and ethyl α-bromo-α-fluoroacetate (2) was heated
with stirring under nitrogen at 85–90◦C for 4 h. The GC-MS anal-
ysis of the reaction product permitted the characterization of the
following compounds: (1) ethyl α-bromo-α-fluoroacetate (2); (2) fluoro
isopropyl phenylphosphinate (3); (3) Hydrogen isopropyl phenylphos-
phinate (4), (4) diisopropyl phenylphosphonate (5); (5) (carbethoxy) iso-
propyl phenyl-phosphinate (6); (6) (carbethoxyfluoromethyl) isopropyl
phenylphosphinate (7); (8) diphenyl carbethoxyphosphinate (8); (9) di-
isopropyl phenyl [(carbethoxyfluoromethyl) pyrophosphate (9) and (10)
isomer of 9, namely diisopropyl phenyl [(carbethoxyfluoromethyl) py-
rophosphate (10).

2658
H. D. Durst et al.
FIGURE 1 Structures of compounds cited in Table I.
Figure 1 lists all the components formed during the free radical cat-
alyzed Michaelis-Arbuzov reaction of diidopropyl phenylphosphonite
(1) with ethyl bromofluoroacetate (2). The major product of the reaction
is [(carbethoxy)(fluromethyl)] isopropyl phenylphosiphinate (7, 46.8%)
and the relative proportions of the remaining compounds are given in
the experimental part. The diastereomers have been shown with wavy
lines. Compound 4 can also arise from 7 via the loss of [:CFCO2C2H5]
entity from the intermediate 7 (Figure 2). The formation of the phos-
phonates from the phosphonites via oxidation of the latter is apparent.
Compounds 4 and 5 must have been formed either during the course
of the reaction or on the hot chromatographic column from their pre-
cursor molecules. This inference stands supported by precedents.11 Im-
purities present in the starting material have been reported to lead
the Arbuzov products even in the absence of organic halides.11a−b The
reaction has also been found to occur without any catalysts around
240◦C.11c Phosphinites [R2POR] have been reported to undergo isomer-
ization to phosphine oxides even in the absence of the catalysts.11d The
formation of the fluoroisopropylphenylphosphinate (3) is quite remi-
niscent of the formation of the P F bond containing products from
methylphosphite.5a In compound 2, the fluorine is certainly activated
by the presence of the neighboring Br and CO2C2H5 groups. When the
fluorine gets abstracted from 2 via the free radical process, it leaves
behind a radical intermediate 11, which loses the CHBr moiety to give
a carbethoxy radical. A similar fate can be envisaged for the radical
intermediate 12 from the homolytic fission of 2 by splitting off Br. Car-
bethoxy isopropyl phenylphosphinate (6) arises from the free radical re-
action of the substrate (1) with carbethoxy radical to form intermediate
13, followed by the free radical catalyzed Arbuzov reaction. Compound

Ethyl Bromofluoro- and Difluoro-Acetates
2659
FIGURE 2 Probable mechanism of formation of compounds cited in Fig. 1.
7, is the expected reaction product of the Arbuzov reaction. Compounds
1 and 12 react to form radical intermediate 14, which subsequently
undergoes rearrangement to yield 7 in the presence of Br. (cf. Figure
2).
The characterization of compound 8, namely (diphenyl) isopropyl-
phosphinate, required additional confirmation, although its molecular
weight and GC-MS breakdown pattern did indicate the structure as-
signed to it. Additional supportive evidence was obtained from DART
mass spectrometry and tandem MS-MS (cf. Table II). The former per-
mitted the trapping of the ion corresponding to this compound and then
examining its breakdown behavior in detail.
It is interesting to note that the proposed cleavage of the phenyl group
attached to phosphorus derives support from two precedents. Firstly,

2660
H. D. Durst et al.
TABLE I Mass Spectral Fragmentation of Compounds 1 Through 10
(Fig. 1)
1. Diisopropyl phneylphosphonite (1): M+ = 226, r.t = 7. 35 min. ); 21 1 (M-CH3);
184 (M -C3H6); 167 (M-OC3H7); 142 [C6H5P(O)H(OH); 100%]; 125 (142-OH); 107
(HP(O)OC3H7); 96 (HP(O)OCH3); 78 (C6H6); 65 (HP(O)OH); 51 (C4H3) and 43 C3H7).
2. Ethyl α-bromo-α-fluoroacetate (2)*: M+ = 184, 139 (C2HBrFO or M-CH3-CO); 120
(C2HBrCO); 111 [M-CO2C2H5), 100%]; 105 (M-Br); 93 (141-CHO-F); 79 (Br); 73
(CO2C2H5); 60 (C2HFO); 49 (CH2FO) and 41 (C2HO).
3. Fluoro-isopropylphenylphosphinate (3): M+ = 202, 187 (M-CH3); 161[M-C3H5),
100%]; 143 (M-OC3H7); 94 (C2H7O2P); 77 (C6H5); 51 (C4H3) and 41(C3H5).
4. Hydrogen isopropyl phneylphosphinate (4): M+ =184, 183 (M-H); 169 (M-CH3);
143 [M -(C3H5), 100%]; 125 (M-OC3H7); 78 (C6H6); 65 (HP(O)OH); 51 (C4H3) and 43
C3H7).
5. Diisopropyl phneylphosphonate (5): M+ = 242; 201 [M-(C3H5); 183 (M-OC3H7);
159 [201 -(C3H6), 100%]; 141 [159-H2O or C6H5P(O)OH]; 94 (C2H7O2P); 77 (C6H5);
65 (HP(O)OH); 63 (P02);51(C4H3)and41(C3H5).
6. Carbethoxy isopropyl phneylphosphinate (6): M+ = 256; 255 (M-H); 214
(M-C3H6) ; 183 (M-CO2C2H5); 169 (183-CH2); 159 (C6H8PO3); 141 [C6H6PO2 or
159-H2O), 100%]; 124 (141 -OH); 77 (C6H5); 65 (HP(O)OH); 51 (C4H3) and41(C3H5).
7. (Carbethoxy-fluoromethyl) isopropyl phenylphosphinate (7): M+ = 288, 287
(M-H); 273 (M-CH3); 259 (M-C2H5); 246 (M-C3H6) ; 229 (M-OC3H7); 217 (246-C2H5);
201 (217-O); 183 (M-CHFCO2C2H5); 169 (183-CH2); 159 (C6H8PO3); 141 [C6H6PO2),
100%]; 125 (141-O); 109 (C2H3O2P); 91 (C7H7 or C2H4O2P); 77 (C6H5); 65 (H2PO2);
51 (C4H3) and 41(C3H5).
8. Diphenyl isopropylphosphinate (8): M+ = 260; 245 (M-CH3); 219 [M-C3H5),
100%]; 201 (M-OC3H7); 183 (M-C6H5); 141 [C6H5P(O)OH or 219-C6H6]; 125
[C6H5P(O)H]; 105 (183-C6H5 -H); 94 (C2H702P); 77 (C6H5); 51 (C4H3) and 41(C3H5).
9. 1, 2-Diisopropyl-l-phenyl-2-[(carbethoxy(fluoromethyl)]pyrophosphate (9):
M+ = 396; 381 (M-CH3); 355 (M-C3H5); 339 (355-O); 312 (355-C3H7); 295 (312-OH);
277 (M-C6H5-C3H6); 249 (277-C2H4 or CO); 235 (312-C6H5); 221 (235-CH2); 205
(221-O); 159 (C6H8PO ; 141 [C6H6P02), 100%]; 125 [C6H5P(O)H]; 107 [P(O)HOC3H7];
77 (C6H5); 63 (PO2) and41(C3H5).
10. 1, 2-Diisopropyl-l-phenyl-2-[(carbethoxy(fluoromethyl)]pyrophosphate (10):
M+ = 396. Isomer of 9 and its’ mass spectral fragmentation is very similar to 9 except
four minor peaks, appearing at m/e= 234, 248, 313 and 354 in the mass spectrum of
10 appear at m/e = 235, 249, 312 and 355 of 9.
∗All Br and Cl containing compounds showed their corresponding isotope peaks.
TABLE II MS-MS Fragmentation of Compounds 8 and 9
1. Diphenyl isopropylphosphinate (8): M+ = 261 (M+H); 243 (M-CH4 .H); 218
[M-C3H5, 100%]; 201 (M-OC3H7); 182 (M-C6H5); 141 [218-CgHj]; 77 (C6H5) and 52
(C4H4 or P(O)CH3).
2. 1, 2-Disopropyl-l-phenyl-2-(carbethoxyfluoromethyl) pyrophosphate (9):
M+ = 397 (M+H); 355 (M-C3H5); 313 (355-C3H6, 100%); 294 (312-H2O); 283 (355-C
O2C2H5). 264 (283-F); 235 (312-C6H5); 205 (235-OCH2); 159 (C6H8PO3); 141
[C6H5P(O)OH]; 125 [C6H5P(O)H]; 91 (C2H4O2P). 79 (C6H7) and 65 (PH2O2).

Ethyl Bromofluoro- and Difluoro-Acetates
2661
the reaction of n-bromopropane with triphenylphosphine has been re-
ported to give diphenyl n-propylphosphine oxide via the oxidation of
the hydroxyl group attached to phosphorus.12a Secondly, the reduction
of triphenyl-phosphinealkylidene (the Wittig reagent) with LiAlH4 pro-
ceeds with the reduction of the double bond, followed by the fission of
the bond between the phenyl group and the phosphorus atom.12b–12d
We must rationalize the formation of the two diastereomers, 9 and 10.
Compound 5 can lose the propylene entity to form isopropyl phenylphos-
phinic acid 15, the hydrogen of which then gets abstracted by Br.-radical
to yield the phospphoranyl radical intermediate (16), which in turn at-
tacks 7. The concomitant fission of the P-C6H5 bond leads to the di-
astereomers, 9 and 10 (cf. Figure 2). The presence of the phosphoranyl
radical similar to 16 has been previously invoked.13 The assignment of
the structure to the isomers squarely rests on the presence of the ions
corresponding to the loss of the two isopropyl entities, phenyl fragment,
and CHFCO2C2H5 moiety from the parent molecule. Figure 2 describes
the probable mechanism of the formation of the compounds cited in Fig-
ure 1 and Tables I and IA give the mass spectral fragmentation of the
compounds cited in Figure 1.
The reaction of diisopropyl phenylphosphonite (1) with ethyl α-
bromo-α, α -difluoroacetate (17) was carried in an analogous manner ex-
cept that compound 2 was replaced with 17 (Figure 3). The routine pro-
cessing of the reaction product, followed by the GC-analysis indicated
the presence of 6 components. The GC-MS analysis and a careful anal-
ysis of the mass spectral fragmentation patterns permitted the identifi-
cation of the following compounds: (1) ethyl α-bromo-α, α-fluoroacetate
(17); (1) (fluoro) isopropyl phenylphosphinate (3); (3) hydrogen isopropyl
phenylphosphinate (4); (4) ethyl isopropyl phenylphosphonate (18);
(5) diisopropyl phenyl-phosphonate (5); and (6) (carbethoxy) isopropyl
FIGURE 3 Structures of compounds cited in Table II.

2662
H. D. Durst et al.
FIGURE 4 Genesis of ethyl isopropyloxy phenylphosphinate (18).
phenylphosphinate (6). The origin of all but one compound, namely 18,
arising from this reaction has been previously rationalized.
It can be surmised that the source of the ethyl moiety is the car-
bethoxy radical (cf. Figure 4). This carbethoxy intermediate can lose
CO2 and generate the C2H5-radical, which then goes on to react with 1
and to form the radical intermediate 19, which finally furnishes com-
pound 18 (cf. Figure 4). Or compound 6 itself undergoes metathesis los-
ing CO2 and yielding 18. Interestingly compounds 3, 4, 5, and 6 are also
formed during the Arbuzov reaction of diisopropyl phenylphosphinate
(1) with ethyl bromofluroacetate (2), as well as with ethyl bromodiflu-
oroacetate (17). The expected product from the reaction of 1 with 17,
[(carbethoxy)(difluoromethyl)] isopropylphenylphosphinate was not de-
tected at all.
The reaction of dimethyl phenylphosphonite (20) with ethyl α-
bromo-α-fluoroacetate (2) was carried in an analogous manner. The
usual processing of the reaction product furnished a mixture con-
taining five compounds. The GC-MS analysis enabled the identifi-
cation of the following compounds; (1) ethyl α-bromo-α-fluoroacetate
(2) dimethyl phenylphosphonite (20)); (3) dimethyl phenylphospho-
nate (21); (4) [(carbethoxy)(fluoromethyl)] methyl phenylphosphinate
(22); and (5) a stereoisomer of 22, namely [(carbethoxy)-(fluoromethyl)]
methyl phenylphosphinate (23). The mass spectral fragmentation of
these compounds is described in Table III. Compound 21 certainly arises
from the oxidation of the substrate (20) under the reaction conditions.
What is interesting is the presence of the isomers, 22 and 23 (Figure 5).
Their formation can be ascribed to the steric bulk of the alkoxy group
attached to the phosphorus atom. The formation of the diastereomers

Ethyl Bromofluoro- and Difluoro-Acetates
2663
TABLE III Mass Spectral Fragmentation of Compounds Cited in
Figs. 3, 5, and 6
1. Ethyl-α-bromo, α-fluoroacetate (2): See Table 1.
2. Ethyl isopropyl phenylphosphinate (18): M+ = 228, 215 (M-CH3); 199 (M-C2H5);
187 (M -C3H5, 99%); 169 (M-OC3H7); 159 (187-C2H4, 95%); 141 ((C6H5)P(O)(OH),
100%); 94 [PH2(0)(OC2H5)]; 77 (C6H5) and 43 (C3H7).
3. Dimethyl phenylphosphonite (20): M+ = 170, 169 (M-H, 79%); 155 (M-CH3,
100%); 140 (M-OCH2); 125 [C6H5P(O)H]; 109 [P(O)(OCH3)2]; 91 (C7H7); 77 (C6H5);
63 (PO2) and 51 (C4H3).
4. Dimethyl phenylphosphonate (21): M+ = 186 (78%); 185 (M-H, 100%); 171
(M-CH3); 156 (M-OCH2); 155 (M-OCH3); 141 (155-CH2); 124 (141-OH); 91 (C7H7); 77
(C6H5); 63 (PO2) and 51 (C4H3).
5. [(Carbethoxy)(fluoromethyl)] methyl phenylphosphinate (22): M+ = 260; 231
(M-C2H5); 215 (M-OC2H5); 173 [C6H5P(O)F(OCH2)] 155 (M-CHFCO2C2H5, 100%);
141 [C6H5P(0)(OH)]; 125 [C6H5P(O)H]; 109 [P(O)(OCH3)2]; 91 (C7H7); 77 (C6H5); 63
(PO2), 51 (C4H3) and 43 (C2H3O or C2F).
6. [(Carbethoxy)(fluoromethyl)] methyl phenylphosphinate (23): M+ = 260;
stereomer of 22. The mass spectral fragmentation of 23 is identical with that of
compound 22.
7. (Chloromethyl) methyl phenylphosphinate (25): M+ = 204; 169 (M-Cl); 155
(M-CH2C1, 100%); 139 (169-OCH2); 125 [C6H5P(O)H]; 77 (C6H5); 65 (PH2O2) and 51
(C4H3).
8. Hydrogen methyl phenylphosphinate (26): M+ = 156; 155 (M-H, 100%); 141
M-CH3); 126 (M-OCH2); 91 (C7H7); 79 (M-C6H5); 65 (PH2O2) and 51 (C4H3).
22 and 23 is directly attributable to the classical Michaelis-Arbuzov
reaction. This inference stands supported by a precedence.9b
The reaction of dimethyl phenylphosphonite (20) with bro-
mochloromethane (24) is very sluggish at best at ambient temperature.
Even after several days, only trace amounts of 25 was detected by GC-
MS. This type of compounds are routinely formed during the course of
the said reaction.1f
In view of the low boiling point of (bromo)(chloro)methane
(24), the reaction of dimethyl phenylphosphonite (20) with (bromo)
FIGURE 5 Structures of compounds cited in Table II.

2664
H. D. Durst et al.
FIGURE 6 Structures of compounds cited in Table II.
(chloro)methane (24) was carried out by stirring a mixture con-
taining stoichiometric amounts dimethyl phenylphosphonite (20) and
(bromo)(chloro)methane (24) under nitrogen for 2 days at 40◦C
with a reflux condenser attached to the reaction flask. After the
volatile organics were removed under house vacuum, the residue
on gas-chromatographic analysis indicated the presence of four
components. The GC-MS analysis of the reaction product permit-
ted the characterization of the following compounds (cf. Figure
6): (1) (chloromethyl) methyl phenylphosphinate (25); (2) dimethyl
phenylphosphonite (20); (3) dimethyl phenylphosphonate (21) and (4)
hydrogen methyl phenylphosphinate (26). The formation of 26 from
25 is explained in Figure 6 (cf. broken line). Compound 25 is the
expected product of the Arbuzov reaction of dimethyl phenylphos-
phonite (20) with bromochloromethane (24). Hydrogen phenylphos-
pinate (26) arises from the splitting off of the carbene (:CHCl) from
25.
In summary, the observed formation of anomalous products appears
to be a consequence of the use of dialkylphosphonites instead of tri-
alkylphosphites and to the steric bulk of the alkoxy group attached
to the phosphorus atom. The isopropoxy moiety being bulkier than the
methoxy group hinders the attack by the bulky free radicals on the phos-
phorus atom. It is because of the problems associated with the direct
synthesis of α-fluorophosphonates, alternate methods for introducing
fluorine into the α-position have been developed.14
EXPERIMENTAL
EI mass spectra were obtained using a model 5973i GC/MSD (Ag-
ilent Technologies, Wilmington, DE) equipped with a 30 m × 0.25
mm HP-5ms capillary column (0.25 µm film). The carrier gas was
helium at 1.1 mL/min (constant flow), injection temperature was
250◦C, transfer line temperature was 280◦C, electron energy was 70
eV, and the oven was programmed from 60◦C to 280◦C at 15◦C/min

Ethyl Bromofluoro- and Difluoro-Acetates
2665
with a 10 min hold at 280◦C. The mass range was scanned from
45–500 daltons at 1.66 scans/sec. Injection was in the split (50:1)
mode.
CI mass spectra were obtained using a model TSQ-7000 GC/MS/MS
(ThermoFisher, San Jose, CA) equipped with a 30 m × 0.25 mm HP-
5ms capillary column (0.25 µm film). The carrier gas was helium at 1
mL/min, injection temperature was 250◦C, transfer line temperature
was 250◦C, electron energy was 200 eV, and the oven was programmed
from 60◦C to 270◦C at 15◦C/min with a 14 min hold at 270◦C. Methane
(UHP grade) was used as the CI reagent gas at 3500 mT. The mass
range was scanned from 60–500 daltons at 0.7 s/scan. Injection was in
the split (50:1) mode.
DARTTM Tass Spectral Technique
The sample was also analyzed by DARTTM (Direct Analysis in Real
Time) using a JEOL AccuTOF mass spectrometer. Approximately 100
nanograms of sample were applied to a glass rod and introduced to the
DARTTM ion source. Mass spectra were generated over the mass range
of 100 to 450 Da. Formulae were confirmed by exact mass measurement
to an accuracy of 0.001 Da.
Electrospray Ionization Tandem Mass Spectrometry
The sample was also analyzed by Electrospray Ionization tandem mass
spectrometry using a Finigan TSQuantum triple quadrupole mass spec-
trometer operated in positive ion mode. The sample was introduced
using Flow Injection Analysis, a 50% aqueous methanol solution was
continuously infused into the ESI source at 100 ul/min, and 5 ul injec-
tions of a solution of the sample in acetone were made with a Finnigan
Surveyor autosampler into the solvent stream. ESI mass spectra were
obtained over the mass range 50−600 Da., using Q1 operated at slightly
better than unit resolution with a scan time of 1s. Product Ion mass
spectra were obtained by selecting the parent ion in Q1 using slightly
better than unit resolution, and fragmenting the ions in Q2 using Ar-
gon as the collision gas and an energy of 15eV, and mass analyzing the
fragment ions with Q3 operated at slightly better than unit resolution
and scanning from 50 Da. to just above the mass of the parent ion, with
a scan time of 1 s.

2666
H. D. Durst et al.
Reaction of Diisopropyl phenylphosphonite (1) with Ethyl
α-Bromo-α -Fluoroacetate (2)
A
mixture containing stoichiometric amounts of diisopropyl
phenylphosphonite (1) and ethyl α-bromo-α-fluoroacetate (2) was
heated with stirring under nitrogen at 85−90◦C for 4 h. The reaction
mixture was cooled to room temperature; the volatile organics were
removed under house vacuum and the residue on gas-chromatographic
analysis showed it to contain seven components. The GC-MS analysis
of the reaction product permitted the characterization of the following
compounds: (1) ethyl α-bromo-α-fluoroacetate (2, M+ = 184, r.t. =
2.59 min, 4.7%); (2) fluoro isopropyl phenylphosphinate (3, M+ = 202,
r.t. = 6.84 min, 2.1%); (3) Hydrogen isopropyl phenylphosphinate (4,
M+ = 184, r.t. = 7.92 min, 3.9%); (4) diisopropyl phenylphosphonate
(5, M+ = 242, r.t. = 8.61 min, 28.7%); (5) (carbethoxy) isopropyl
phenylphosphinate (6, M+ = 256, r.t. = 10.30 min, 7.6%);(6) [(car-
bethoxy)(fluoromethyl)] isopropyl phenyl-phosphinate (7, M+ = 288,
r.t. = 11.00 min, 46.8%); (8) diphenyl isopropyl-phosphinate (8, M+
=
260, r.t. = 11.91 min, 0.5%); (9) diisopropyl phenyl (carbethoxyflu-
oromethyl) pyrophosphate (9, M+ = 396, r.t. = 15.66 min, 2.3%)
and (10) isomer of 9, namely diisopropyl phenyl (carbethoxyfluo-
romethyl) pyrophosphate (10, M+ = 396, r.t. = 15.72 min, 3.3%). The
mass spectral fragmentation of compounds cited above is given in
Table I.
Reaction of Diisopropyl Phenylphosphonite (1) with Eethyl
α-Bromo-α, α -Difluoroacetate (17)
The reaction of diisopropyl phenylphosphonite (1) with ethyl α-bromo-
α, α-fluoroacetate (17) was carried our in an analogous manner except
that compound 2 was replaced with 17. The routine processing of the
reaction product, followed by the GC-analysis indicated the presence
of 6 components. The GC-MS analysis and the mass spectral fragmen-
tation patterns enabled the identification of the following compounds:
(1) ethyl α-bromo-α, α -fluoroacetate (17, M+ = 202, r. t. = 2.58 min,
5.5%); (1) (fluoro) isopropyl phenylphosphinate (3, M+ = 202, r. t. =
8.49 min, 18.8%); (3) hydrogen isopropyl phenylphosphinate (4, M+
=
184, r. t. = 9.57 min, 11.1%); (4) ethyl isopropyl phenylphosphonate
(18, M+ = 228, r. t. = 10.15 min, 1.8%); (5) diisopropyl phenylphos-
phonate (5, M+ = 242, r. t. = 10.27 min, 44.8%); and (6) (carbethoxy)
isopropyl phenylphosphinate (6, M+ = 256, r. t. = 11.95 min, 18.1%)
(Figure 3).

Ethyl Bromofluoro- and Difluoro-Acetates
2667
Reaction of Dimethyl phenylphosphonite (20) with Ethyl
α-Bromo-α-Fluoroacetate (2)
This reaction was carried in an analogous manner except that diiso-
propyl phenylphosphonite (1) was replaced by dimethyl phenylphos-
phonite (20) (Figure 5). The usual processing of the reaction product
furnished a mixture containing five compounds. The GC-MS analy-
sis enabled the identification of the following compounds; (1) ethyl
α-bromo-α-fluoroacetate (2, M+ = 184, r.t. = 2.59 min, 11.2%);(2)
dimethyl phenylphosphonite (20, M+ = 170, r.t. = 7.38 min, 63.0%)); (3)
dimethyl phenylphosphonate (21, M+ = 186, r.t. = 7.47 min, 12.1%));
(4) [(carbethoxy)(fluoromethyl)] methyl phenylphosphinate (22, M+
=
260, r.t. = 10.53 min, 6.0%); and (5) a stereoisomer of 22, namely [(car-
bethoxy)(fluoromethyl) methyl phenylphosphinate (23, M+ = 260, r.t. =
10.6 min, 7.9%). The mass spectral breakdown of the above compounds
is described in Table II.
Reaction of Dimethyl phenylphosphonite (20) with
(Bromo)(Chloro)-Methane (24)
In view of the low boiling point of (bromo)(chloro)methane (24), a mix-
ture containing stochiometric amounts dimethyl phenyl-phosphonite
(20) and (bromo)(chloro)methane (24) was stirred under nitrogen for
several days at ambient temperature. After the volatile organics, were
removed under house vacuum and the residue on gas-chromatographic
analysis indicated the presence of four components. The GC-MS anal-
ysis of the reaction product permitted the characterization of the fol-
lowing compounds: (1) hydrogen methyl phenylphosphinate (26, M+
156, r.t. = 7.06 min, 3.2%); (2) dimethyl phenylphosphonite (20, M+
170, r.t. = 7.45 min, 82.6%); (3) dimethyl phenylphosphonate (21, M+
=
=
=
186, r.t. = 7.53 min, 13.9%) and (4) (chloromethyl) methyl phenylphos-
phinate (25, M+ = 204, r.t. = 9.17 min, 0.4%) (Figure 6).
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