On the reaction of bis(phosphothioyl)disulfanes with hydroxamic acids, part I: Ionic versus radical reaction pathways

Article abstract of DOI:10.1002/hc.20423

Among sodium N-alkyl-4-chlorobenzohydroxamates treated with bis(phosphothioyl)disulfanes >P(S)SSP(S)< (where >P(S) is phosphorothioyl, phosphonothioyl, and phosphinothioyl), only the N-methyl one yields quantitatively the respective O-phosphothioyl derivatives exhibiting complete inversion of configuration at phosphorus in a reaction whose products are inert toward dithiophosphate arising in the reaction. For branched N-alkyl benzohydroxamates, products of a SET process predominated. The mechanism of the title reaction is discussed.

Full text of DOI:10.1002/hc.20423

Heteroatom Chemistry
Volume 19, Number 3, 2008
On the Reaction of Bis(phosphothioyl)disul-
fanes with Hydroxamic Acids, Part I: Ionic
versus Radical Reaction Pathways
Witold Przychodzen´ and Jaroslꢀ aw Chojnacki
Faculty of Chemistry, Gdan´sk University of Technology, Narutowicza 11/12, 80952 Gdan´sk, Poland
Received 21 April 2007; revised 2 November 2007
the only one representative of disulfanes 1 among
ABSTRACT: Among sodium N-alkyl-4-chlorobenzo-
commercial organophosphorus pesticides in use.
hydroxamates treated with bis(phosphothioyl)disul-
Chemical properties of bis(phosphothioyl)disul-
fanes >P(S)SSP(S)< (where >P(S) is phosphoroth-
fanes 1 are not nearly as well documented as those
ioyl, phosphonothioyl, and phosphinothioyl), only the
of other phosphothioyl derivatives, but it is known
N-methyl one yields quantitatively the respective O-
that in 1, like in other phosphorus pseudohalo-
phosphothioyl derivatives exhibiting complete inver-
gens, the reactive disulfane unit exhibits strong
sion of configuration at phosphorus in a reaction
sulfur cationoid properties. The S S bond is read-
whose products are inert toward dithiophosphate aris-
ily cleft by nucleophiles [6] and metal species [7]
ing in the reaction. For branched N-alkyl benzo-
with formation of stable dithioacid anion or its
hydroxamates, products of a SET process predom-
metal complexes, respectively. Amines, cyanide, and
inated. The mechanism of the title reaction is dis-
organometallic compounds react in this manner. It
ꢀ
C
cussed. 2008 Wiley Periodicals, Inc. Heteroatom Chem
should be emphasized that this mechanism is not ex-
clusive. In situ generated dithioacid anion or an ex-
ternal nucleophile can dealkylate the disulfane when
19:271–282, 2008; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20423
an alkoxy group is attached to the phosphorus. Thus,
primary amines are able to dealkylate both methoxy-
and isopropoxy-substituted disulfanes 1.
INTRODUCTION
Disulfanes 1 have found wide practical application
and are involved in some important technical pro-
cesses. They are used as stabilizers for polymer com-
positions [1], vulcanization accelerators [2], antiox-
idant and antiwear additives in engine lubricant oil
additives [3], and as highly effective sulfurizating
agents [4] in organic synthesis. Some of them are
physiologically active compounds with both insec-
ticidal and fungicidal activity [5]. Phostex—a mix-
ture of bis(dialkoxyphosphinethioyl)disulfanes—is
There is still a pressing need to develop ef-
fective methods for detoxification of neurotoxic
organophosphorus compounds. The reaction with
supernucleophiles is one of the most frequently
studied. For the first time, it was found that ben-
zohydroxamic acids accelerate the hydrolysis of
diisopropyl fluorophosphates (DFP) and isopropyl
methylphosphonofluoridate (sarin) by the factor of
100 and even more at higher pH [8]. Also other
phosphoric acid derivatives (mainly esters) hydroly-
sis mediated by hydroxamate 2 was investigated ex-
cept for bis(phosphothioyl)disulfanes 1. It was pos-
tulated that the corresponding O-phosphorylated
hydroxamic acids are the primary products of
hydroxamate-catalyzed hydrolysis, but they were
never detected or isolated from aqueous media [9].
Correspondence to: Witold Przychodzen´; e-mail: witold@chem.
pg.gda.pl.
Contract grant sponsor: Polish Ministry of Education and
Science.
Contract grant number: 1T09A 07830.
2008 Wiley Periodicals, Inc.
c
ꢀ
271

272 Przychodzen´ and Chojnacki
TABLE 1 Disulfanes 1 Used in the Reaction with Hydroxa-
mates 2
According to HSAB theory, a hydroxamate an-
ion 2, being a hard base, should react preferably
with a hard electrophilic phosphorus atom of disul-
fane 1 rather than with a soft sulfur atom. On the
other hand, O-phosphothioylated hydroxamic acids
3, that is, the potential products of hydroxamate at-
tack on phosphorus in 1, are an unexplored class of
compounds. Only one patent deals with the prepa-
ration of N-methyl-N-diethoxyphosphinthioyloxy
acetamide starting from N-chloro-N-methylacet-
amide in moderate yield [10]. Recently, we iso-
lated N-isopropyl-N-[methoxy)(4-methoxyphenyl)-
phosphinothioyloxy]benzamide from the reaction
mixture of the corresponding hydroxamic acid and
Lawesson’s reagent (LR) [11].
The reactivity of hydroxamic acid mixed anhy-
drides exemplified by 3 toward nucleophiles can be
complex and should depend not only on the rel-
ative electrophilicity of both centers (localized at
nitrogen or phosphorus atoms) and on steric hin-
drance but also on the acidity of the leaving group
and on the nature of the nucleophile. For exam-
ple, the sulfur nucleophile attack at the nitrogen
atom of 3 gives products with a weak N S bond.
On the other hand, O-thioacylated hydroxamic acids
are known to undergo rearrangement to unstable
S-acylthiolobenzamides, which decompose further
to benzamides [12]. O-Phosphothioylated hydrox-
amic acids 3 are structural analogs of the corre-
sponding O-(thio)acylated and O-sulfonylated hy-
droxamic acids. It would, therefore, be interesting
to compare their chemical properties.
Compound
Y1
Y2
δ
P
(ppm)
1a
1b
1c
1d
1e
1f
OiPr
Ph
OiPr
Ph
OMe
82.7
62.2
92.8, 93.0
85.8
86.1
88.7
72.2, 74.2
87.7
Ansa
Ans
Ans
Ans
Ans
Ans
OiPr
(–)-O-Menthyl
>C(CH2O)2
NHiPr
1g
1h
N(iPr)2
aAns = 4-Methoxyphenyl.
It was observed that bis(phosphonothioyl)disul-
fanes 1c–h were more labile than the correspond-
ing bis[phosphoro(ino)thioyl]disulfanes 1a, 1b and
slowly lost sulfur during their storage. The na-
ture of this behavior is not clear yet. In addition,
it was found that repeated crystallization might
cause transesterification. When 1e was recrystal-
lized three times from isopropanol, it quantitatively
transformed into 1d.
Disulfanes 1 were treated with benzohydroxa-
mate salts 2 in THF at room temperature. Using
tertiary amines or nonnucleophilic amidines (DBU)
as bases should be avoided because they do not
fully deprotonate the starting hydroxamic acid and
are not inert toward the disulfanes 1 under study.
Therefore, it was observed that disulfanes 1a and 1b
The purpose of this paper is to report a new
reaction of various disulfanes 1 with N-alkyl-4-
chlorobenzohydroxamates 2. Effects of chemical
structure and reaction conditions have been studied.
Some preliminary results concerning the reactivity
of O-phosphothioylated hydroxamic acids 3 as sole
products of the title reaction are also presented.
RESULTS AND DISCUSSION
To investigate the effect of substituents at the phos-
phorus atom, a series of disulfanes 1a–h, derivatives
of phosphoro-, phosphono-, and phosphinodithioic
acids, have been prepared (Table 1). 4-Methoxy-
phenylphosphonodithioic acid derivatives (1e, 1g,
1h) are new compounds and have been fully char-
acterized. 1e was isolated as a pure (SP, SP) di-
astereomer. The X-ray crystal structure analysis
(Fig. 1) of compound 1e shows that the geome-
try and absolute configuration at both phosphorus
atoms are the same as that of a related bis[(–)-
menthyloxyphenylphosphinothioyl]disulfane [13].
˚
FIGURE 1 X-ray structure of 1e. Selected bond lengths (A)
and angles (◦): P(1)–S(1) 1.9353(5), P(1)–S(2) 2.112596),
S(2)–S(3) 2.0786(5), P(1)–O(2) 1.585(1), P(1)–C(5) 1.795(1),
S(1)–P(1)–S(2) 105.16(2), S(3)–S(2)–P(1) 104.44(2), S(1)–
P(1)–S(2)–S(3) 161.74(2), P(1)–S(2)–S(3)–P(2) –112.68(2).
Heteroatom Chemistry DOI 10.1002/hc

On the Reaction of Bis(phosphothioyl)disulfanes with Hydroxamic Acids, Part I: Ionic versus Radical Reaction Pathways 273
TABLE 2 Products of the Reaction of Disulfanes 1 with
Hydroxamates 2
3a(Yield)
P
Other Products
(Yield)
Entry
δ (ppm)
4 δ (ppm)
P
1
2
3
4
5
6
3aa (92) 70.0
3ab (89) 94.2
3ac (82) 97.7
3ad (95) 94.0
3ae (90) 93.7
3af (100)b
4a 109.8
4b 62.7
4c 111.4
4d 110.6
4e 111.2
–
–
5 (12)
–
–
3afꢁ (98)c
96.0/103.3
7
8
9
3ag (91) 88.2
4g 72.8
-
4a 109.8
–
–
3ah (nd)d -
3ba (30) 72.9
1a (28); 9b (7);
10b (8); 11 (3)
1e (12); 9b (9);
10b (10)
10
3be (35)
4e 110.0
94.2 and 96.2
FIGURE 2 X-ray structure of 3ae. Selected bond lengths
11
3ca (nd)d -
4a 109.8
9c (9); 10c (30)
◦
˚
(A) and torsion angles ( ): P(1)–S(1) 1.9169(8), P(1)–
O(1) 1.576(1), P(1)–O(2) 1.648(2), N(1)–O(2) 1.420(2),
C(24)–O(3) 1.229(3), O(2)–N(1)–C(24)–O(3) –179.4(2),
C(25)–N(1)–C(24)-O(3) –7.4(4), C(20)–C(21)–C(24)–O(3), –
32.5(3).
aThe two letters in the designation for 3 refer first to the identity of R
and second to the identity of Y1 and Y2.
bDetermined by 31P NMR.
cAfter quenching with CH3I.
dNot detectable after 6 h.
that the product /SP/–3ae (Fig. 2) was formed with
a complete inversion of configuration. Therefore,
the reaction has an ionic character and proceeds
via an SN2P mechanism at the phosphorus atom.
CCDC-635363 (for 1e) and CCDC-635364 (for 3e)
contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data request/cif.
In all the reactions under study, phospho-
dithioate salts 4 and sulfur always accompany the
main product 3 (Scheme 1). According to a pro-
posed reaction mechanism (Scheme 2), hydroxam-
ate 2 could attack both electrophilic centers, that is,
the phosphorus and sulfur atoms.
It should be noted that the attempts to detect
the presence of (phosphothioyl)disulfane anion 6a
failed. Immediately after mixing the reagents, an
additional resonance at δP 83.2 ppm (2% of 1a in-
tensity) was observed, but quenching with methyl
iodide gave only the signal of the corresponding
phosphorodithioic acid O,O-diisopropyl S-methyl
ester 7 (δP 92.0 ppm) in place of the signal of 4a.
Therefore, it is clear that the signal at δP 83.2 ppm
cannot correspond to (phosphothioyl)disulfane an-
ion 6a due to its expected high nucleophilicity, but
rather to an additional by-product, likely with the
“NOSP” unit (8a).
underwent fast decomposition upon DBU action in
chloroform solution (browning). 31P NMR analysis
confirmed the formation of DBU salts of the cor-
responding phosphodithioic acids besides uniden-
tified phosphorus products. Hence, the best re-
sults (total consumption of 1) were achieved if
sodium hydroxamate 2a was generated by the use
of NaH and was taken in the excess as a solu-
tion or as a solid (Table 2, entries 1–7). The reac-
tion was completed in 20 min using 2 equivalents
of 2a. Disulfanes 1a, 1b, and 1d–g afforded prod-
ucts 3 in nearly quantitative yield. In the case of
1c (entry 3) by-product, namely O,S-dimethyl (4-
methoxyphenyl)phosphonodithioate 5 (δP 99.8 ppm)
was isolated in 12% yield. Its formation was proba-
bly resulted from dealkylation of 3ac by phospho-
nodithioate salt 4c arising in the reaction, but the
presence of the corresponding dealkylation product
was not confirmed experimentally because of its in-
stability. It is interesting that the presence of the
acidic hydrogen atom and the nitrogen atom in disul-
fane 1 structure does not influence the course of the
reaction. It is obvious that the negative charge at
the nitrogen atom in 1g should repel the attacking 2
and lone electron pairs at the nitrogen in 1g and 1h
decrease the electrophilic character of the phospho-
rus center. But both these electron effects playing
substantial role in 1g and 1h seem to have no im-
portance in this particular reaction, and the total
inertness of 1h is likely due to steric factors.
Performed experiments clearly indicate that only
N-methyl hydroxamate 2a gives products 3 quanti-
tatively. 2b produces 3 with lower yields (30%–35%),
and 2c does not yield any detectable amounts of 3.
A deep green coloration appears immediately after
The reaction was also studied using optically
pure disulfane /SP, SP/–1e. X-ray analysis showed
Heteroatom Chemistry DOI 10.1002/hc

274 Przychodzen´ and Chojnacki
SCHEME 1
mixing hydroxamate 2c, and disulfanes 1 indicates
the formation of acylaminoxyl radical 2cꢁ, which was
detected by EPR. As is seen from Fig. 3, EPR spec-
trum of the above-mentioned reaction mixture con-
sists of a broad and intense three-line signal with
parameters correspond to radical 2cꢁ (aN = 0.79 mT,
g = 2.0068). Its linewidth does not exclude the pres-
ence of other transient species such as benzoyl, phos-
phothyil, or aminoxyl radicals, besides the most per-
sistent acylaminoxyl 2cꢁ that was still observed even
after 20 h. During the course of the reaction, the
coloration turns blue due to the formation of 2-
methyl-2-nitrosopropane and remains unchanged. It
indicates that 2-methyl-2-nitrosopropane is not an
efficient trap for above-mentioned radicals.
Isolation of N-alkyl-4-chlorobenzamides (9b,
9c), N-alkyl-N,O-bis(4-chlorobenzoyl)hydroxylam-
ines (10b, 10c), and O-(4-chlorobenzoyl)acetoxime
11 (Table 2, entries 9–11) provides additional,
strong evidence for radical intermediates and a
SET pathway. Therefore, it is reasonable to assume
that an electron transfer from hydroxamate 2
FIGURE 3 (a) EPR spectrum of acylaminoxyl radical 2cꢁ
spontaneously formed from 2c in THF solution (17 × 10−3 M)
exposed to air; (b) broad and strong EPR signals obtained
immediately after treating 2c with disulfane 1a; (c) and (d) the
decrease of intensity of the triplet observed after 25 min and
20 h, respectively, following disulfane addition.
SCHEME 2
Heteroatom Chemistry DOI 10.1002/hc

On the Reaction of Bis(phosphothioyl)disulfanes with Hydroxamic Acids, Part I: Ionic versus Radical Reaction Pathways 275
SCHEME 3
affords the corresponding bis(phosphoyl)disulfane
radical anion [>P(S)SSP(S)P<]− 1ꢁ and N-
alkylacylaminoxyl 2ꢁ. 2ꢁ undergoes
dispro-
a mixed ionic radical, and a pure radical mechanism
exist for the reaction of 1 with 2a, 2b, and 2c,
respectively.
a
portionation to yield hydroxamate 2b and
N-acylnitrone 11ꢁ or cleaves into 2-methyl-
2-nitrosopropane and acyl radical. Next, subse-
quent self-reactions lead to N-acyloxybenzamides
10 [14]. Isomerization of 11ꢁ and its reaction with
acetoxime give O-(4-chlorobenzoyl)acetoxime 11
exclusively. Benzamides 9b and 9c are presumably
Obviously, this contrasting behavior of hydrox-
amates 2 under investigation is caused by their oxi-
dation potential differences and the steric hindrance
around the oxygen atom. Among N-alkyl benzohy-
droxamates, the most crowded N-tert-butyl one 2c
has the lowest oxidation potential (according to the
literature data Eox = +0.25, [15], −0.77 and −0.88 V
[16] versus Fc/Fc+ for N-methyl, N-i-Pr, and N-t-Bu
benzohydroxamate, respectively).
In the previous report, we found that phospho-
rodithioates 4 caused the N O bond cleavage in
O-thioacylohydroxyloamines [17]. Additional exper-
iments showed that 3a did not react with phospho-
dithioate salts 4a at all (31P NMR analysis). Likewise,
no intramolecular nucleophilic substitution (on a
nitrogen or phosphorus atom) occurred if the ad-
ditional phosphodithioate was tethered in the struc-
ture of 3af (the formation of 3af was as a result of the
cyclic disulfane 1f opening) (Scheme 4). 31P NMR
spectrum of the reaction mixture (entry 6) contained
only two signals of 3afꢁ. Its derivative, S-methyl ester
3afꢁ, was isolated in quantitative yield after treating
the above-mentioned reaction mixture with methyl
iodide.
formed from the corresponding
8 precursors,
because it is well known that acylaminoxyl radicals
do not decompose into amides, and in addition
we found that derivatives 10 are stable and are
not cleaved by nucleophilic 4a (4 days at room
temperature). Bis(phosphothioyl)disulfane radical
anion 1ꢁ splits into a thyil radical (dimerizes to
1) and an anion 4 (Scheme 3). The recovery of a
diastereomeric mixture of 1e (Fig. 4; Table 2, entry
10) in the reaction of optically pure 1e with 2b,
which exhibits the considerably decreased optical
rotation value (from +228.6 to +2.5) and isolation
of 3be as two diastereomers in a 2:1 ratio, confirms
unambiguously the participation of thyil radicals in
the reaction under investigation.
Therefore, on the basis on the structure of the
identified products, it can be deduced that an ionic,
Heteroatom Chemistry DOI 10.1002/hc

276 Przychodzen´ and Chojnacki
FIGURE 4 31P NMR spectra of disulfane 1e: (a) optically pure form; (b) diastereomeric mixture obtained by oxidation of 4e
with iodine; (c) product isolated in the reaction of 2c with 1e.
On the other hand, it was expected that
N-phosphorothioyl thiolbenzamide 13 could be
formed from N-methyl-O-tosyl-4-chlorobenzohy-
droxamic acid 12 as a product of nucleophilic sub-
stitution at the nitrogen atom by phosphodithioate
salt 4a. But attempts to detect the corresponding
13 failed (5 min, the NMR tube reaction). The re-
action lead only to one phosphorus product, that is,
disulfane 1a (81%) accompanied by benzamide 9a
(80%), triethylammonium tosylate, and unreacted
phosphodithioate salt 4a. According to the proposed
mechanism (Scheme 5), this reaction must run with
SCHEME 4
13 intermediacy, but based only on these results it
is difficult to establish its ionic or radical character.
The experiment described above showed that the to-
sylate in 12 and the phosphodithioate in 13 were
much better leaving groups than the phosphothioate
in 3aa and 4-chlorobenzoate in 10.
It was also found that, unlike O-thioacyl hydrox-
amic acids derivatives (vide supra), product 3aa was
not prone to isomerization to S-phosphoyl deriva-
tive 3aaꢁ and subsequent homolysis leading to benza-
mide 9a (chloroformic solution, 60◦C, 4 days). This
might appear surprising at first, as the energetic bal-
ance of such transformation seems to be more ad-
vantageous (ꢀGP=S → P=O > ꢀGC=S → C=O).
Comparison of the X-ray structure of 3ae
(Fig. 2) with that of the corresponding N-methyl-4-
methylbenzohydroxamic acid [18] and 1e (Fig. 1) re-
vealed some significant differences in bond lengths.
In compound 3ae, the N O bond is longer (1% rel-
ative to hydroxamic acid), the P O bond is shorter
˚
(4.5% relative to 1e) as well as the P S bond (1.917A)
(1% relative to 1e), which length is similar to that
found for phosphothioyl chlorides [19]. Thus, the
resulting data may suggest enhanced reactivity of
Heteroatom Chemistry DOI 10.1002/hc

On the Reaction of Bis(phosphothioyl)disulfanes with Hydroxamic Acids, Part I: Ionic versus Radical Reaction Pathways 277
corresponding benzamides 9b–c [27] are known
compounds and were prepared by acylation of the re-
spective N-alkylhydroxylamine or alkylamine with 4-
chlorobenzoyl chloride. Diisopropylphosphorochlo-
ridothioate was obtained according to the described
procedure [28].
Authentic samples of N-alkyl-4-chloro-N-(4-
chlorobenzyloxy)benzamides 10b and 10c [29]
were obtained from the reaction between the
corresponding benzohydroxamic acid and 4-
chlorobenzoyl chloride. Authentic sample of O-(4-
chlorobenzoyl)acetoxime 11 was prepared from ace-
SCHEME 5
toxime.
O-phosphothioylhydroxamic acids 3 toward nucle-
ophilic attack.
Bis[isopropoxy(4-methoxyphenyl)phosphinothio-
yl)disulfane (1d). Yield 61%. White crystals from
CONCLUSIONS
ethyl acetate–hexanes. Melting point (mp) 118–
1
120◦C. H NMR, δ: 1.34 and 1.44 (2 × d, J = 6.5 Hz,
In summary, with a set of disulfanes 1 as substrates,
it was shown that the reaction demonstrated good
generality only for N-methyl benzohydroxamate 2a.
For branched N-alkyl benzohydroxamates 2b and
2c, products of a SET process predominated. It was
shown that O-phosphothioylated hydroxamic acids
3 neither react with phosphodithioate salts 4 arising
in the reaction (in contrast to O-tosyl derivative 12)
nor isomerize into labile N S derivatives (in contrast
to O-thioacyl derivatives).
6H, CH3C), 3.83 (s, 3H, OCH3), 4.98 (dspt, J = 10
and 6.5 Hz 1H, CHC), 6.67 (dd, J = 3.9 and 8.8 Hz,
2H, H-3/5), 7.55 (dd, J = 8.8 and 14.2 Hz, 2H, H-2/6)
ppm. 13C NMR, δ: 23.66, 23.70, 24.14, 24.16 (CH3C),
55.2 (OCH3), 72.16 (d, J = 6.5 Hz, CHCH3), 113.3 (d,
J = 17 Hz, C-3/5), 123.3 (d, J = 132 Hz, C-1), 133.2
(d, J = 14 Hz, C-2/6), 162.7 (C-4) ppm. 31P NMR, δ:
85.8 ppm (lit. [11] δP: 85.8 and 89.2 ppm).
(RP , RP )-bis[(–)-menthyloxy(4-methoxyphenyl)-
phosphinothioyl)disulfane (1e). To a suspension of
LR (0.505 g, 1.25 mmol) in THF (8 mL), (–)menthol
(0.39 g, 2.5 mmol) was added in one portion. After
15 min, to a clear solution tert-butyl amine (0.26 mL,
2.5 mmol) was added dropwise with cooling. Next,
thus formed tert-butylammonium salt was treated
EXPERIMENTAL
General Remarks
All NMR spectra were recorded on a Varian Unity
500 Plus spectrometer operating at 500 MHz (1H),
202.4 MHz (31P), and 125.7 MHz (13C) in CDCl3.
Mass spectra were measured with an AMD-604
double-focusing mass spectrometer (the EI method)
and a MARINER (ESI-TOF) PerSeptive Biosystems
spectrometer (the ESI method). EPR spectra of
thoroughly degassed solutions (17 × 10−3 M) of the
reactants were recorded on a Varian E4 spectrom-
eter. The g values were measured using DPPH as
reference (g = 2.0036). The TLC analysis was per-
formed on aluminum foil plates precoated with
silica gel (60F 254, Merck). Silica gel, 230–400
mesh (Merck AG, Darmstadt, Germany), was used
for column chromatography. THF was distilled
from potassium/benzophenone ketyl. Commercial
LR (Lancaster Synthesis, Lancashire, England) was
recrystallized from chlorobenzene prior to use.
Disulfanes 1a [20], 1b [21], 1c [22], 1d [22], and
1e were obtained from the corresponding phos-
phodithioate salts by using the reported method
[23]. N-Methyl- [24], N-isopropyl- [25], N-tert-
butyl-4-chlorobenzohydroxamic acid [26], and the
with an iodine solution in THF (0.16 g in 2 mL). 31
P
NMR analysis showed that the crude product 1e was
obtained as a mixture of three diastereoisomers (1e
δ 86.1, 1eꢁ δ 88.0, and 1eꢁꢁ δ 89.91 and 92.8) in 3:1:1
ratio. Removal of the solvent and crystallization
from ethanol afforded 0.36 g (42%) of the major
(RP, RP)−diastereoisomer 1e as white needles. mp
124–126◦C. [α]2D0 = +228.6 (c= 0.84 in CH2Cl2). 1H
NMR, δ: 0.70 (d, 3H), 0.83 (d, 3H), 0.92 (m, 1H), 1.01
(d, 3H), 1.07 (m, 1H), 1.37 (q, 1H), 1.45 (t, 1H), 1.52
(m, 1H), 1.70 (m, 2H), 1.88 (dt, 1 H), 2.45 (m, 1H),
3.88 (s, OCH3, 3H), 4.65 (dq, J = 4.5 and 10 Hz, 1H,
CHO), 6.72 (dd, J = 3.9 and 8.8 Hz, 2H, H-3/5), 7.57
(dd, J = 8.8 and 14.0 Hz, 2H, H-2/6) ppm. 13C NMR,
δ: 16.2, 21.3, 22.4, 23.2, 25.7, 31.9, 34.3, 42.5, 48.8,
48.9, 55.50, and 55.3 (OCH3), 79.6 (d, J = 7.7 Hz,
OCH), 113.7 (d, J = 16 Hz, C-3/5), 124.5 (d, J = 133
Hz, C-1), 133.5 (d, J = 13 Hz, C-2/6), 162.9 (C-4)
ppm. 31P NMR, δ: 86.1 ppm. HRMS (ESI): Calcd
for C34H52O4P2S4Na [M + Na+]: 737.2116; found
737.20961.
Heteroatom Chemistry DOI 10.1002/hc

278 Przychodzen´ and Chojnacki
Bis[isopropylamino(4-methoxyphenyl)phosphin-
othioyl)disulfane (1g). Oxidation of isopropylam-
monium isopropylamido(4-methoxyphenyl)phos-
phonodithioate [30] with an iodine solution in THF
and subsequent column chromatography in chloro-
form afforded 1g as a mixture of two nonseparable
diastereoisomers in a 66:34 ratio. Yield 19%. mp
the mixture was refluxed for 1.5 h and next disul-
fane 1 (0.25 mmol) was added in one portion at
room temperature. After 20 min, the reaction was
completed as judged by TLC and the mixture was
concentrated in vacuo. The residue was subjected
directly to column chromatography. Elution with
chloroform afforded elemental sulfur as the first
fraction, and next the pure 3 was collected. In
the reaction of 1c with 2a (entry 3), the second
fraction was compound 5, namely O,S-dimethyl(4-
methoxyphenyl)phosphonodithioate [11] (yield:
1
117–121◦C. H NMR, δ: 1.12 and 1.43 (2 × d, 6H,
minor), 1.18 and 1.30 (2 × d, 6H, major), 3.11 (t,
J = 8.8 Hz, NH, 1H, minor), 3.19 (t, J = 8.8 Hz,
NH, 1H, major), 3.52 (tspt, J = 6.5 and 10 Hz, 1H,
minor), 3.66 (tspt, J = 6.5 and 10 Hz, 1H, major),
3.85 (s, OCH3, 3H, major), 3.89 (s, OCH3, minor),
6.80 (dd, J = 3.3 and 8.8 Hz, 2H, H-3/5, major), 7.00
(dd, J = 3.0 and 8.8 Hz, 2H, H-3/5, major), 7.85 (dd,
J = 8.8 and 13.7 Hz, 2H, H-2/6, major), 7.98 (dd,
J = 8.8 and 13.7 Hz, 2H, H-2/6, minor) ppm. 13C
NMR, δ: 21.7 (broad, CH3, minor), 25.4 and 25.6
(CH3, major), 45.1 (CH, major), 45.3 (CH, minor),
55.6 (OCH3, major), 55.8 (OCH3, minor), 114.0 (d,
J = 15 Hz, C-3/5, major), 114.3 (d, J = 15 Hz, C-3/5,
minor), 125.2 (d, J = 113 Hz, C-1, major), 125.9 (d,
J = 115 Hz, C-1, minor), 133.5 (d, J = 13 Hz, C-2/6,
major), 133.8 (d, J = 14 Hz, C-2/6, minor), 163.2
(C-4, major), 163.4 (C-4, minor) ppm. 31P NMR, δ:
72.2 (major) and 74.2 ppm (minor). HRMS (ESI):
Calcd for C20H30N2O2P2S4Na [M + Na+]: 543.05576;
found 543.05683.
1
0.015 g, 12%; H NMR, δ: 2.18 (d, J = 15.0 Hz, 3H,
SCH3), 3.82 (d, 3H, J = 15.1 Hz, POCH3), 3.99 (s,
3H, ArOCH3), 6.99 (dd, J = 3.4 and 8.8 Hz, 2H,
H-3ꢁ/5ꢁ), 7.89 (dd, J = 8.8 and 13.7 Hz, 2H, H-2ꢁ/6ꢁ)
ppm; 31P NMR, δ: 99.8 ppm).
In the reaction of 1f with 2a (entry 6) after
16 h, the crude mixture was treated with methyl io-
dide (0.009 mL, 0.138 mmol) and the corresponding
S-methyl ester 3afꢁ was isolated as a mixture of two
diastereomers, which separation was not successful.
N-Methyl-N-diisopropoxyphosphinothioyloxy-4-
chlorobenzamide (3aa). Yield 0.042 g (92%). A
1
colorless oil. H NMR, δ: 1.27 and 1.31 (2 × d, J = 6
Hz 12H, CH3CH), 3.49 (s, 3H, NCH3), 4.71 (dspt,
J = 6.5 and 10 Hz, 2H, OCH), 7.40 (d, J = 8.8 Hz, 2H,
ArH), 7.63 (d, J = 8.8 Hz, 2H, ArH) ppm. 13C NMR,
δ: 23.5, 23.60, 23.65, and 23.7 (CH3), 40.3 (NCH3),
75.2 (d, J = 6 Hz, CH), 128.7 (C-3/5), 130.4 (C-2/6),
132.5 (C-1), 137.5 (C-4), 170.9 (C O) ppm. 31P NMR,
δ: 70.05 ppm. MS (EI), m/z (%): 365 (3) M+, 185 (2)
[M-P(S)(OiPr)2]+, 168 (3) [M-OP(S)(OiPr)2]+, 139
(100) ArC O+, 111 (13) ClC6H+5 . HRMS (EI): Calcd
for C14H21NO4PS35Cl: 365.06175; found 365.06189.
Bis[diisopropylamino(4-methoxyphenyl)phosphi-
nothioyl)disulfane (1h). Prepared as above from
LR and diisopropylamine and obtained as a mixture
of three diastereoisomers (1h δP 87.7, 1hꢁ δP 86.9
and 87.9, 1hꢁꢁ δP 89.4 and 89.5) in 13:15:1 ratio.
Crystallization from ethanol afforded (12%) of
one diastereoisomer 1hꢁ as white powder. MP
1
113–115◦C. H NMR, δ: 1.15 (d, 3H), 1.23 (d, 3H),
N-Methyl-N-diisopropoxyphosphinothioyloxy-4-
3.72 (d spt, J = 6.5 and 12.7 Hz, 2H), 3.73 (s,
OCH3, 3H), 6.49 (dd, J = 3 and 8.3 Hz, 2H, H-3/5),
7.86 (dd, J = 8.3 and 14.6 Hz, 2H, H-2/6) ppm.
13C NMR, δ: 23.3 (CH3), 23.6 (CH3), 49.0 (CH),
55.3 (OCH3), 112.9 (d, J = 17 Hz, C-3/5), 127.3 (d,
J = 111 Hz, C-1), 134.6 (d, J = 14 Hz, C-2/6), 162.0
(C-4). 31P NMR, δ: 87.7 ppm. HRMS (ESI): Calcd
for C26H42N2O2P2S4Na [M + Na+]: 627.14966; found
627.15275.
chlorobenzamide (3aa) from Diisopropylphos-
phorochloridothioate. To
a stirred solution of
N-methyl-4-chlorobenzohydroxamic acid (0.19
g, 1 mmol) and DBU (0.165 mL, 1.1 mmol) in
CH2Cl2 (5 mL), diisopropylphosphorochloridoth-
ioate (0.22 g, 1 mmol) in CH2Cl2 (2 mL) was added
dropwise at –10◦C. After 2 h, the reaction mixture
was concentrated in vacuo and the residue was
subjected to column chromatography (chloroform)
to yield 0.30 g (82%) of 3aa.
N-Methyl-O-phosphothioylbenzohydroxamic
Acids (3aa–3ag)
N-Methyl-N-diphenylphosphiothioyloxy-4-chloro-
benzamide (3ab). Yield 0.045 g (89%). A color-
less oil. 1H NMR, δ: 3.46 (s, 3H, NCH3), 7.27 (d,
J = 8.8 Hz, 2H, ArH), 7.40 (d, J = 8.8 Hz, 2H, H–),
7.44 (2 × t, 4H, H-4ꢁ), 7.53 (t, 2H), 7.90 (dd, J = 8
and 13.7 Hz, 4H, H-2ꢁ) ppm. 13C NMR, δ: 42.2
(NCH3), 128.6 (d, J = 13.7 Hz, C-3ꢁ/5ꢁ), 128.8 (C-3/5),
General Procedure. To a stirred solution of
N-methyl-4-chlorobenzohydroxamic acid (0.058 g,
0.313 mmol) in THF (5 mL), NaH (0.01 g, 0.39
mmol) was added and the mixture was stirred
under argon. When hydrogen evolution was ceased,
Heteroatom Chemistry DOI 10.1002/hc

On the Reaction of Bis(phosphothioyl)disulfanes with Hydroxamic Acids, Part I: Ionic versus Radical Reaction Pathways 279
130.3 (C-2/6), 131.9 (C-1), 132.1 (d, J = 11.4 Hz,
C-2ꢁ/6ꢁ), 132.5 (d, J = 91 Hz, C-1ꢁ), 132.8 (d, J = 3
Hz, C-4ꢁ), 137.5 (C-4), 171.7 (C O) ppm. 31P NMR,
δ: 94.2 ppm. MS (EI), m/z (%): 401 (0.5) M+, 234
(17) [Ph2P(S)OH]+, 217 (95) [Ph2P(S)]+, 168 (24)
[M-OP(S)Ph2]+, 139 (100) ArC O+, 111 (43) ClC6H+5 .
HRMS: Calcd for C20H17NO2PS35Cl 401.04062;
found 401.03906.
1H), 2.24 (m, 1H), 3.50 (s, NCH3), 3.85 (s, OCH3,
3H), 4.51 (dq, J = 4.4 and 10.7 Hz, 1H), 6.85 (dd,
J = 3.4 and 8.8 Hz, 2H, H-3/5), 7.27 (d, J = 8.3 Hz,
2H, ArH), 7.43 (d, J = 8.3 Hz, 2H, ArH), 7.67 (dd,
J = 8.8 and 13.7 Hz, 2H, H-2/6) ppm. 13C NMR, δ:
16.1, 21.3, 22.1, 23.0, 25.5, 31.7, 34.2, 40.9 (NCH3),
42.9, 48.6, 48.7, 55.6 (OCH3), 81.0 (d, J = 7.6 Hz,
OCH), 113.7 (d, J = 16 Hz, C-3ꢁ/5ꢁ), 124.2 (d, J = 153
Hz, C-1ꢁ), 128.4 (C-3/5), 130.4 (C-2/6), 132.3 (C-1ꢁ),
133.8 (d, J = 14 Hz, C-2ꢁ/6ꢁ), 137.2 (C-4), 163.4 (d,
J = 3 Hz, C-4ꢁ), 170.9 (C O) ppm. 31P NMR, δ: 93.8
ppm. MS (EI), m/z (%): 493 (1) [M – 15]+, 341
(3) [AnsP(S)OMenOH]+, 171 (40) [AnsP(S)+1]+,
139 (76) ArC O+, 111 (30) ClC6H+4 . HRMS (ESI):
Calcd for C25H33NO4PS35ClNa [M + Na+]: 532.14487;
found 532.1474.
N-Methyl-N-[methoxy)(4-methoxyphenyl)phosphi-
nothioyloxy]-4-chlorobenzamide
(3ac). Yield
0.079 g (82%). A colorless oil. 1H NMR, δ: 3.36
(s, 3H, NCH3), 3.78 (d, J = 14.1 Hz, 3H, POCH3),
3.85 (s, 3H, OCH3), 6.89 (dd, J = 3.4 and 8.8 Hz,
2H, H-3ꢁ/5ꢁ), 7.30 (d, J = 8.3 Hz, 2H, ArH), 7.47 (d,
J = 8.3 Hz, 2H, ArH), 7.72 (dd, J = 8.8 and 13.7 Hz,
2H, H-2ꢁ/6ꢁ) ppm. 13C NMR, δ: 40.6 (NCH3), 53.9 (d,
J = 6 Hz, POCH3), 55.7 (OCH3), 114.0 (d, J = 17 Hz,
C-3ꢁ/5ꢁ), 121.9 (d, J = 156 Hz, C-1ꢁ), 128.6 (C-3/5),
130.3 (C-2/6), 132.2 (C-1), 133.8 (d, J = 13 Hz,
C-2ꢁ/6ꢁ), 137.4 (C-4), 163.6 (d, J = 3 Hz, C-4ꢁ), 170.7
(C O) ppm. 31P NMR, δ: 97.7 ppm. MS (EI), m/z (%):
385 (3) M+, 218 (9) [AnsP(S)(OMe)OH]+, 201 (100)
[AnsP(S)OMe]+, 185 (11) [M-P(S)(OiPr)2]+, 168
(9) [M-OP(S)(OiPr)2]+, 139 (46) ArC O+, 111 (18)
ClC6H+5 . HRMS (EI): Calcd for C16H17NO4PS35Cl:
385.03045; found 385.02983.
O-{3-[(4-Methoxyphenyl)methylsulfanylphosphi-
nothioyloxy]-2,2-dimethylpropyl}, Oꢁ -(N-methyl-4-chl
orobenzamido)-4-(methoxyphenyl)phosphonothioic
Acid (3afꢁ). Obtained as a mixture of two dias-
teroisomers in 53/47 ratio with 98% yield. 1H NMR,
δ: 0.97, 0.99, 1.00, and 1.02 (4 × s, 6H), 2.05 (d,
J = 14.6 Hz, 1.41H, SCH3), 2.17 (d, J = 15.1 Hz,
1.59H, SCH3), 3.29 (s, 1.41H, NCH3), 3.37 (s, 1.59H,
NCH3), 3.76, 3.82, 3.98, 4.03, 4.11 (8 × dd, 4H,
OCH2), 3.83, 3.85, 3.86, 3.87 (4 × s, OCH3, 6H), 6.86,
6.91, 6.93, 6.98 (4 × dd, J = 3.4 and 8.8 Hz, 4H,
H-3/5), 7.27 (d, J = 8.8 Hz, 1.41H, ArH), 7.31 (d,
J = 8.8 Hz, 1.59H, ArH), 7.45 (d, J = 8.8 Hz, 1.41H,
ArH), 7.49 (d, J = 8.3 Hz, 1.59H, ArH), 7.72–7.89
(4 × dd, J = 8.8 and 13.7 Hz, 4H, H-2/6) ppm. 13C
NMR, δ: 15.4 (d, J = 3 Hz, SCH3), 21.7, 21.8 (C-3),
36.4 (2 × d, J = 8.4 Hz, C-2), 40.6 and 40.8 (NCH3),
55.7 (OCH3), 69.2 and 69.6 (2 × d, J = 6.9 Hz, OC),
71.3 and 71.8 (2 × d, J = 6.9 Hz, OC), 114.1 and
114.2 (2 × d, J = 16 Hz, C-3ꢁ/5ꢁ), 122.0 and 122.2
(2 × d, J = 156 Hz, C-1ꢁ), 125.65 and 125.71 (2 × d,
J = 128 Hz, C-1ꢁ), 128.6 and 128.7 (C-3/5), 130.37
and 130.41 (C-2/6), 132.9 and 133.0 (C-1), 133.8 and
133.9 (2 × d, J = 14 Hz, C-2ꢁ/6ꢁ), 137.36 and 137.42
(C-4), 163.0 and 163.6 (2 × s, C-4ꢁ), 170.77 and
170.81 (C O) ppm. 31P NMR, δ: 95.7 and 96.2 (PO2),
97.3 and 97.8 (POS) ppm. HRMS (ESI): Calcd for
C28H34NO6P2S3ClNa [M + Na+]: 696.06043; found
696.06283.
N-Methyl-N-[isopropoxy)(4-methoxyphenyl)phos-
phinothioyloxy]-4-chlorobenzamide
(3ad). Yield
0.049 g (95%). A colorless oil. 1H NMR, δ: 1.24
and 1.38 (2 × d, J = 6.5 Hz, 6H, CH3C), 3.44 (s,
3H, NCH3), 3.85 (s, 3H, OCH3), 4.89 (dspt, J = 6.5
and 11 Hz, 1H, CHC), 6.88 (dd, J = 3.4 and 8.3 Hz,
2H, H-3ꢁ/5ꢁ), 7.30 (d, J = 8.3 Hz, 2H, ArH), 7.48 (d,
J = 8.3 Hz, 2H, ArH), 7.69 (dd, J = 8.3 and 14.1 Hz,
2H, H-2ꢁ/6ꢁ) ppm. 13C NMR, δ: 23.84, 23.88, 24.03,
24.06 (CH3C), 40.5 (NCH3), 55.7 (OCH3), 73.8 (d,
J = 6.5 Hz, CHCH3), 113.8 (d, J = 16 Hz, C-3ꢁ/5ꢁ),
123.4 (d, J = 155 Hz, C-1ꢁ), 128.5 (C-3/5), 130.4
(C-2/6), 132.4 (C-1), 133.7 (d, J = 14 Hz, C-2ꢁ/6ꢁ),
137.2 (C-4), 163.5 (C-4ꢁ), 170.7 (C O) ppm. 31P NMR,
δ: 94.0 ppm. MS (EI), m/z (%): 413 (0.5) M+, 246 (6)
[AnsP(S)OiPrOH]+, 229 (28) [AnsP(S)OiPr]+, 187
(100) [AnsP(S)OH]+, 171 (30) [AnsP(S)+1]+, 139
(89) ArC O+, 111 (37) ClC6H+4 . HRMS (EI): Calcd
for C18H21NO4PS35Cl: 413.06175; found 413.06054.
N-Methyl-N-[isopropylamino(4-methoxyphenyl)-
(SP )-N-Methyl-N-[(–)-menthyloxy(4-methoxyphe-
nyl)phosphinothioyloxy] 4-chlorobenzamide (3ae).
Yield 0.057 g (90%). White crystals from ace-
tonitrile. MP 105–107◦C. [α]2D0 = –29.3◦ (c= 0.58 in
CH2Cl2).1H NMR, δ: 0.80 (d, 3H), 0.82 (m, 1H), 0.89
(d, 3H), 0.94 (d, 3H), 0.96 (m, 1H), 1.04 (m, 1H),
1.36 (m, 1H), 1.45 (t, 1H), 1.66 (m, 2H), 1.88 (m,
phosphinothioyloxy]-4-chlorobenzamide
(3ag).
Yield 0.094 g (91%). White crystals from ethyl
1
acetate–hexanes. MP 143–144◦C. H NMR, δ: 1.10
and 1.11 (2 × d, J = 6.5 Hz, 6H, CH3C), 3.28 (br s,
1H, NH), 3.49 (s, 3H, NCH3), 3.66 (d spt, 1H, CH),
3.86 (s, 3H, OCH3), 6.95 (dd, J = 3.4 and 8.6 Hz, 2H,
H-3ꢁ/5ꢁ), 7.40 (d, J = 8.3 Hz, 2H, ArH), 7.56 (d, J = 8.8
Heteroatom Chemistry DOI 10.1002/hc

280 Przychodzen´ and Chojnacki
Hz, 2H, ArH), 7.91 (dd, J = 8.6 and 13.5 Hz, 2H,
H-2ꢁ/6ꢁ) ppm. 13C NMR, δ: 25.5–25.7 (4 × s, CH3C),
42.5 (CH), 45.0 (NCH3), 55.7 (OCH3), 114.0 (d,
J = 16 Hz, C-3ꢁ/5ꢁ), 125.4 (d, J = 145 Hz, C-1ꢁ), 129.0
(C-3/5), 130.0 (C-2/6), 132.5 (C-1), 133.4 (d, J = 13
Hz, C-2ꢁ/6ꢁ), 137.6 (C-4), 163.1 (C-4ꢁ), 171.2 (C O)
ppm. 31P NMR, δ: δP: 88.2 ppm. MS (EI), m/z (%):
354 (1) [M-NHiPr]+, 228 (100) [AnsP(S)NHiPr]+,
186 (25) [AnsP(S)OH]+, 1+69 (6) [AnsP(S)]+, 139 (33)
ArC O+, 111 (13) ClC6H4 . HRMS (ESI): Calcd for
C18H22N2O3PSClNa [M + Na+]: 435.06750; found
435.06832.
7.46 (d, J = 8.8 Hz, 2H, ArH), 8.02 (d, J = 8.8 Hz,
2H, ArH) ppm. 13C NMR, δ: 17.4 and 22.3 (CH3),
127.9 (C-1), 129.1 (CH), 131.2 (CH), 139.9 (C-4),
163.3 (C N), 165.1(C O) ppm. HRMS (EI): Calcd
for C10H10NO2Cl: 211.04001; found 211.04013.
Reaction between 1e and N-Isopropyl-4-chloro-
benzohydroxamic Acid Sodium Salt (2b)
To a stirred solution of 2b (0.42 g, 1.78 mmol) in THF
(10 mL), 1e (0.60 g, 0.89 mmol) was added in one
portion. After 16 h, the solvent was stripped off under
vacuum and the residue was chromatographed with
chloroform to provide 1e (0.07 g, 12%) with [α]2D0
+2.5◦ (c= 0.86 in CH2Cl2), 3be (0.17 g, 35%), 10b
(0.03 g, 10%), and 9b (0.015 g, 9%).
Reaction between 1a and N-Isopropyl-4-chloro-
benzohydroxamic Acid Sodium Salt (2b)
To a stirred solution of 2b (0.42 g, 1.78 mmol)
in THF (10 mL), 1a (0.39 g, 0.89 mmol) was
added in one portion. After 16 h the solvent was
stripped off under vacuum and the residue was
chromatographed with chloroform to provide: 1a
(0.12 g, 28%), 3ba (0.11 g, 30%), two nonpo-
lar compounds, namely N-isopropyl-4-chloro-N-(4-
chlorobenzyloxy)benzamide 10b (0.023 g, 8%), N-
isopropyl-4-chlorobenzamide 9b (0.012 g, 7%) and
O-(4-chlorobenzoyl)acetoxime 11 (0.005 g, 3%).
Characterization of N-Isopropyl-N-[(–)-menthyl-
oxy(4-methoxyphenyl)phosphinothioyloxy]-4-chloro-
benzamide (3be). A colorless oil. [α]2D0 = –23.0◦
(c= 2.86 in CH2Cl2); 1H NMR, δ: 0.56–2.10 (complex
multiplets, 18H), 2.33 (m, 0.67H), 2.44 (m, 0.33H),
3.87 (s, 3H, OCH3), 4.12 (2 × spt, NCH, 1H), 4.55
(dq, J = 4.4 and 10.7 Hz, 0.33H), 4.71 (dq, J = 4.4
and 10.7 Hz, 0.67H), 6.92 (dd, J = 3.4 and 8.8 Hz,
1.34H, H-3/5), 6.93 (dd, J = 3.4 and 8.8 Hz, 0.66H,
H-3/5), 7.35 (d, J = 8.8 Hz, 1.34H, ArH), 7.37 (d,
J = 8.8 Hz, 0.66H, ArH), 7.53 (d, J = 8.8 Hz, 1.34H,
ArH), 7.56 (d, J = 8.8 Hz, 0.66H, ArH), 7.88 (dd,
J = 8.8 and 13.7 Hz, 1.34H, H-2/6), 7.93 (dd, J = 8.8
and 13.7 Hz, 0.66H, H-2/6) ppm. 31P NMR, δ: 94.2
and 96.2 ppm (intensity ratio: 2.2:1). HRMS (ESI):
Calcd for C27H37NO4PS35ClNa [M + Na+]: 560.17617;
found 560.17867.
Characterization of N-Isopropyl-N-diisopropoxy-
phosphinothioyloxy-4-chlorobenzamide
(3ba). A
1
colorless oil. H NMR, δ: 1.30 (d, J = 6.5 Hz, 6H),
1.36 (d, 6.5 Hz, 6H), 2.38 (d, 6.5 Hz, 6H), 4.14
(spt, 1H, NCH), 4.86 (dspt, J = 6 Hz, J = 10 Hz,
2H, OCH), 7.42 (d, J = 8.8 Hz, 2H, ArH), 7.63
(d, J = 8.8 Hz, 2H, ArH) ppm. 13C NMR, δ: 19.9
(NCCH3), 23.60, 23.65, 23.68, and 23.71 (CH3), 56.4
(NCCH3), 74.8 (d, J = 6 Hz, OCH), 129.1 (C-3/5),
130.0 (C-2/6), 133.2 (C-1), 137.9 (C-4), 172.2 (C O)
ppm. 31P NMR, δ: 72.9 ppm. HRMS (ESI): Calcd for
C16H25NO4PS35ClNa [M + Na+]: 416.08227; found
416.08415.
Reaction between 1a and N-tert-butyl-4-chloro-
benzohydroxamic Acid Sodium Salt (2c)
To a stirred solution of sodium N-tert-butyl-4-
chlorobenzohydroxamate 2c (0.25 g, 1 mmol)
in THF (4 mL) 1a (0.22 g, 0.5 mmol) was
Characterization of N-Isopropyl-4-chloro-N-(4-
chlorobenzyloxy)benzamide (10b). 1H NMR, δ: 1.29
(d, J = 6.5 Hz, 6H), 4.68 (spt, 1H, NCH), 7.34
(d, J = 8.8 Hz, 2H, ArH), 7.44 (d, J = 8.8 Hz,
2H, ArH), 7.56 (d, J = 8.8 Hz, 2H, ArH), 7.94
(d, J = 8.8 Hz, 2H, ArH) ppm. 13C NMR, δ: 19.9
(CH3), 52.7 (NCCH3), 125.5, 128.9 (CH), 129.2 (CH),
129.4 (CH), 131.5 (CH), 132.8, 137.3, 141.1, 164.0
(C O), 169.1(C O) ppm. HRMS (EI): Calcd for
C17H15NO3Cl2: 351.04290; found 351.04304.
added in one portion. Immediately
a
deep
green coloration appeared due to aminoxyl for-
mation. After 16 h, the solvent was stripped
off under vacuum and the residue was chro-
matographed with chloroform to provide two non-
polar compounds, namely N-tert-butyl-4-chloro-N-
(4-chlorobenzyloxy)benzamide 10c (0.055 g, 30%)
and N-tert-butyl-4-chlorobenzamide 9c (0.01 g, 9%).
Characterization of N-tert-butyl-4-chloro-N-(4-
chlorobenzyloxy)benzamide (10c). 1H NMR, δ: 1.59
(s, 9H), 7.24 (d, J = 8.3 Hz, 2H, ArH), 7.40 (d,
J = 8.3 Hz, 2H, ArH), 7.50 (d, J = 8.3 Hz, 2H, ArH),
7.78 (d, J = 8.3 Hz, 2H, ArH) ppm. 13C NMR, δ: 27.9
Characterization of O-(4-Chlorobenzoyl)aceto-
xime (11). White flakes from ethyl acetate–hexanes.
1
MP 89–90◦C. H NMR, δ: 2.13 and 2.14 (2 × s, 6H),
Heteroatom Chemistry DOI 10.1002/hc

On the Reaction of Bis(phosphothioyl)disulfanes with Hydroxamic Acids, Part I: Ionic versus Radical Reaction Pathways 281
(NCCH3), 63.6 (NCCH3), 125.1 (C H), 128.4 (C H),
129.0 (C H), 129.5 (C H), 131.2 (C H), 134.6 (C-1),
136.5, 141.2, 164.9 (C O), 170.6 (C O) ppm.
Crystal data for 1e [7]: C34H52O4P2S4, M = 719.94,
orthorhombic, a = 11.8388(4), b= 17.4852(5), c =
◦
◦
◦
˚
18.1602(5) A, α = 90 , β = 90 , γ = 90 , U = 3761.4(2)
3
˚
A , T = 120(2) K, space group P212121, Z = 4,
−3
˚
Characterization of N-tert-butyl-4-chlorobenza-
mide (9c). 1H NMR, δ: 1.49 (s, 9H), 7.40 (d,
J = 8.3 Hz, 2H, ArH), 7.68 (d, J = 8.3 Hz, 2H, ArH)
ppm.
Dc = 1.262 g cm , Mo Kα (λ 1 = 0.71073 A),
34,051 reflections measured, 10947 unique, R(I >
2σ(I)) = 0.0337, Rw(all reflections) = 0.0858. Abso-
lute structure parameter (Flack parameter) –0.03(4).
Crystal Data for 3ae [7]: C25H33ClNO4PS, M =
510.03, monoclinic, a = 7.2401(3), b= 13.9561(6),
N-Methyl-N-tosyloxy-4-chlorobenzamide (12)
◦
◦
◦
˚
c= 12.9788(5) A, α = 90 , β = 90.667(3) , γ = 90 ,
3
˚
To a stirred solution of 2 (0.371g, 2 mmol) in CH2Cl2
(5 mL), NaH (0.053 g, 2.2 mmol) was added. When
hydrogen evolution was ceased, the mixture was re-
fluxed under argon atmosphere for 1.5 h and next
tosyl chloride (0.381 g, 2 mmol) in CH2Cl2 (3 mL)
was added dropwise at –5◦C. After 16 h, the reac-
tion mixture was evaporated and chromatographed
on silica gel with ethyl acetate–n-hexane (1:7) to pro-
vide 0.61 g (90%) of 12 as white solid (mp 88–90◦C).
1H NMR, δ: 2.38 (s, 3H, ArCH3), 3.53 (s, 3H, NCH3),
7.15 (d, J = 8.5 Hz, 2H, ArH), 7.21 (d, J = 8.8 Hz, 2H,
ArH), 7.26 (d, J = 8.8 Hz, 2H, ArH), 7.54 (d, J = 8.8
Hz, 2H, ArH) ppm. 13C NMR, δ: 22.0 (ArCH3), 40.2
(NCH3), 128.4 (C H), 129.3 (C H), 130.0 (C H),
130.2 (C H), 130.3, 131.0, 137.7, 146.7, 170.1 (C O)
ppm. MS (EI), m/z (%): 339 (4) M+, 168 (3) Ar-
CON (CH3)+, 155 (19) ArSO+2 , 139 (100) ArC O+,
111 (18) ClC6H4+, 91 (17) C7H+7 . HRMS (EI): Calcd
for C15H14NO4S35Cl: 339.03321; found 339.03203.
U = 1311.34(9) A , T = 120(2) K, space group P21,
−3
˚
Z = 2, Dc = 1.292 g cm , Mo Kα (λ = 0.71073 A),
7341 reflections measured, 4108 unique, R(I >
2.00σ(I)) = 0.034, Rw(all reflections) = 0.0865. Abso-
lute structure parameter (Flack parameter) 0.15(6).
ACKNOWLEDGMENTS
We are grateful to Dr. B. Ciesielski (Medical Univer-
sity of Gdan`sk) for recording EPR spectra.
REFERENCES
[1] Kopacki, A. F.; Horodecky, J. US Patent 3,549,588,
1970; Chem Abstr 74: 64973 (1971).
[2] Biswas, T.; Naskar, N.; Basu, D. K. J Appl Polym Sci
1995, 58, 981–993.
[3] (a) Al-Malaika, S.; Coker, M.; Smith, P. J.; Scott, J. J
Appl Polym Sci 1992, 44, 1297–1305; (b) Barnes, A.
M.; Bartle, K. D.; Thibon, V. R. A. Tribol Int 2001, 34,
389–395.
Reaction between N-Methyl-N-tosyloxy-4-chloro-
benzamide (12) and Triethylammonium Diiso-
propoxyphosphinodithioate (4a). In CDCl3: A solu-
tion of 12 (0.068g, 0.2 mmol) and triethylammo-
nium diisopropoxyphosphinodithiate 4a (0.063 g,
0.2 mmol, 1 equiv.) in deuteriochloroform (0.7 mL)
was placed in and NMR tube. 31P NMR spectra
recorded after 5 min and 1.5 h contained only two
signals (intensity ratio 1:4), which corresponds to 1a
(δP 82.6 ppm) and diisopropoxyphosphinodithioate
4a (δP108.9 ppm), respectively.
In THF: A solution of 12 (0.136 g, 0.2 mmol)
and 4a (0.252 g, 0.8 mmol, 2 equiv.) in THF (3 mL)
was stirred for 1.5 h at room temperature. 31P NMR
analysis showed that 1a/4a ratio was raised to 6.
The deposited crystals of triethylammonium tosy-
late were filtered off [1H NMR, δ: 1.28 (t, J = 6.5 Hz,
9H), 2.32 (s, 3H, ArCH3), 3.09 (dq, J = 6.5 and 5 Hz,
6H), 7.13 (d, J = 8.5 Hz, 2H, ArH), 7.72 (d, J = 8.8
Hz, 2H, ArH), 10.3 (br s, 1H, NH) ppm], and the sol-
vent was stripped under vacuum. The residue was
chromatographed in chloroform to afford 1a (0.138
g, 81%), unreacted 12 (0.010 g, 7%), and benzamide
9a (0.054 g, 80%).
[4] Stec, W. J.; Uznan`ski, B.; Wilk, A.; Hirschbein, B. L.;
Fearon, K. L.; Bergot, B. J. Tetrahedron Lett 1993,
34, 5317–5320.
[5] Chen, W.; Tian, M. Gaodeng Xuexiao Huaxue Xuebao
1988, 9, 525–528; Chem Abstr 111:7504 (1989).
[6] Khaskin, B. A. Usp Khim 1984, 53, 1325–1351.
[7] Haiduc, I.; Goh, L. Y. Coord Chem Rev 2002, 224,
151–170.
[8] Hackley, A. B. E.; Plapinger, R.; Stolberg, M.;
Wagner-Jauregg, T. J Am Chem Soc 1955, 77, 3651–
3653.
[9] Behrman, E. J.; Biallas, M. J.; Brass, H. J.; Edwards,
J. O.; Isaks, M. J Org Chem 1970, 35, 3069–3075.
[10] Yoshida, M.; Maeda, T. JP 26393, 1964; Chem Abstr
62:10371f (1965).
[11] Przychodzen´, W. Eur J Org Chem 2005, 2002–2014.
[12] Ankers, W. B.; Brown, C.; Hudson, R. F.; Lawson,
A. J. J Chem Soc Chem Commun 1972, 935–936.
[13] Lꢀ opusinski, A.; Lꢀ uczak, L.; Michalski, J.; Koziolꢀ, A.
E.; Gdaniec, M. J Chem Soc Chem Commun 1991,
889–890.
[14] Griller, D.; Perkins, M. J. J Am Chem Soc 1980, 102,
1354–1357.
[15] Bordwell, F. G.; Fried, H. E.; Hughes, D. L.; Lynch,
T.-Y.; Satish, A. V.; Whang, Y. E. J Org Chem 1990,
55, 3330–3336.
[16] Bordwell, F. G.; Liu, W.-Z. J Am Chem Soc 1996, 118,
10819–10823.
Heteroatom Chemistry DOI 10.1002/hc

282 Przychodzen´ and Chojnacki
[17] Doszczak, L.; Przychodzen´, W.; Witt, D.; Rachon, J. J
Chem Soc, Perkin Trans 2 2002, 1747–1751.
[18] Dietrich, A.; Powell, D. R.; Eng-Wilmot, D. L.;
Hossain, M. B.; van der Helm, D. Acta Crystallogr
Sect C 1990, 46, 816–821.
[19] Khan, A. A.; Wismach, C.; Jones, P. G.; Streubel, R.
Dalton Trans 2003, 2483–2487.
[24] Banks, M. R.; Hudson, R. F. J Chem Soc, Perkin Trans
2 1986, 1211–1216.
[25] Przychodzen´, W. Heteroat Chem 2006, 17, 676–684.
[26] Uchida, Y.; Kozuka, S. Bull Chem Soc Jpn 1984, 57,
2011–2012.
[27] O’Connor, Ch. J.; Martin, W. R.; Calvert, D. J. Aust J
Chem 1981, 34, 2297–2305.
[20] Zemlyanskii, N. I.; Prib, O. A.; Drach, B. S. Zh Obsch
Khim 1961, 31, 880–803.
[21] Kuchen, W.; Mayatepek, H. Chem Ber 1968, 101,
3454–3466.
[22] Gray, I. P.; Slawin, A. M. Z.; Woolins, J. D. New J
Chem 2004, 28, 1383–1389.
[23] Przychodzen´, W. Phosphorus Sulfur Silicon Relat
Elem 2004, 179, 1621–1633.
[28] Omelan´czuk, J.; Kielbasin´ski, P.; Michalski, J.;
Mikolajczyk, J.; Mikolajczyk, M.; Skowron´ska, A.
Tetrahedron 1975, 31, 2809–2814.
[29] Smith, J.; Tedder, J. M. J Chem Soc, Perkin Trans 2
1987, 895–896.
[30] Aragoni, M. C.; Arca, M.; Demartin, F.; Devillanova,
F. A.; Graiff, C.; Isaia, F.; Lippolis, V.; Tiripicchio, A.;
Verani, G. Eur J Inorg Chem 2000, 2239–2244.
Heteroatom Chemistry DOI 10.1002/hc