Synthesis of thiohydroxamic acids and thiohydroximic acid derivatives

Article abstract of DOI:10.1021/jo500080x

An improved and expanded preparation of thiohydroxamic acids is reported along with a one-pot conversion of these compounds to novel thiohydroximic acid derivatives. A variety of aryl, heteroaryl, and alkyl substituents are well tolerated to provide a rap

Full text of DOI:10.1021/jo500080x

Note
pubs.acs.org/joc
Synthesis of Thiohydroxamic Acids and Thiohydroximic Acid
Derivatives
Berenice C. Lemercier and Joshua G. Pierce*
́
́
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States
S
* Supporting Information
ABSTRACT: An improved and expanded preparation of thiohydroxamic
acids is reported along with a one-pot conversion of these compounds
to novel thiohydroximic acid derivatives. A variety of aryl, heteroaryl, and
alkyl substituents are well tolerated to provide a rapid approach to alkene-
functionalized thiohydroximic acids that serve as potentially useful building
blocks for organic synthesis.
hiohydroxamic acids are unusual molecules with four dif-
T
ferent types of atoms in close proximity (C-sp2, N, O,
and S), which gives them a wide range of reactivity and makes
them very N-acidic: the average pKa of thiohydroxamic acids
is 4.2−5.6.1 Therefore they are excellent bidentate chelators,
and this property has been exploited in the study of metal ions.2
Thiohydroxamic acids exist in equilibrium between their thione
and thiol forms (Figure 1a). The thiohydroxamic tautomers are
Figure 2. Synthesis of thiohydroxamic acids.
There are three main methods for the synthesis of thio-
hydroxamic acids in the literature (Figure 2).7 Given the broad
availability of hydroxamic acids,8 thionation with Lawesson’s
reagent or P2S5 appears to be the most straightforward way of
accessing thiohydroxamic acids; however, this method works
well only with O-protected hydroxamic acids and yields com-
plex mixtures with other hydroxamic acids.9 Another method to
prepare thiohydroxamic acids is thioacylation of hydroxylamine
derivatives. Dithiocarboxylic esters,10 their salts,2b and thio-
nocarboxylic acid esters1 have been used with variable success
to make thiohydroxamic acids. These thioacylating agents
are often made from dithiocarboxylic acids and thus are not
Figure 1. (a) Tautomers of thiohydroxamic acids. (b) Naturally
occurring thiohydroxamic and thiohydroximic acids.
equally stable in the gas phase, and the thione form is more
stable in the solution and solid phases.3 Naturally occurring
thiohydroxamic acids are rare, but some simple thiohydrox-
amate metal chelates have antibacterial properties (Figure 1b).4
In contrast, naturally occurring thiohydroximic acid derivatives
are frequently observed, exemplified by O-sulfonyl S-glucosyl
thiohydroximates, known as glucosinolates, which are isocyanate
precursors in plants.5 The most common synthetic thiohy-
droxamic acids are the O-acyl thiohydroxamic acids known as
Barton esters that are widely used as radical precursors.6
Received: January 13, 2014
Published: February 20, 2014
© 2014 American Chemical Society
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Note
broadly commercially available and are unstable to storage and
handling. Modern thioacylating agents have been introduced
that are easier to access, handle, and store;11 unfortunately,
these reagents are not easily employed for the preparation of
unsubstituted thiohydroxamic acids because they create by-
products that can be difficult to remove from the acidic
thiohydroxamic acid products. The final method to synthesize
thiohydroxamic acids is the addition of sulfur nucleophiles to
N-hydroxyimidoyl chlorides or nitrile oxides.12 This is also the
method of choice to synthetically access thiohydroximic acids
from the glucosinolate family and Barton esters.13 Despite the
availability of synthetic methods to access thiohydroxamic acids,
their synthesis and use in synthetic chemistry is rare, with the
exception of Barton’s esters. Indeed, they are plagued with a
bad reputation of decomposing and rearranging through Lossen
or Beckmann rearrangements before any useful reaction can
occur.
We chose to revisit and expand the previously described
addition of sulfur nucleophiles to N-hydroxyimidoyl chlorides
to access a variety of unknown N-unsubstituted thiohydroxamic
acids and S-allyl thiohydroximic acid derivatives.12 We targeted
this subclass of thiohydroximic acid derivatives since they bear
functional groups that can potentially be employed as reactive
handles for their application in heterocycle synthesis. As a
starting point to evaluate the potential of this approach we
targeted benzothiohydroxamic acid (4a, Scheme 1). Freshly
report for the addition of sodium sulfide to di-ortho-substituted
arylimidoyl chlorides.12a Optimization of this method was
achieved through a significant reduction in the equivalents of
sodium sulfide, the addition of an amine base, and the use of
hydrochloric acid for reaction quenching. Accordingly, under
our optimized conditions, sodium sulfide (3 equiv) was added
to N-hydroxyimidoyl chloride 3a (1 equiv) in the presence of
triethylamine (1 equiv) to generate thiohydroxamic acid 4a in
92% yield after extraction of the acidified water layer. With a
high yielding synthesis of thiohydroxamic acid 4a in hand, we
explored the one-pot conversion to activated thiohydroximic
acid derivatives. Thiohydroxamic acid 4a was S-alkylated with
allyl chloride 5 in the presence of catalytic tetrabutylammonium
iodide (TBAI) followed by treatment with pentafluorobenzoyl
chloride (6) to obtain thiohydroximic acid 7a in 72% yield
(55% over 4 steps, 2 purifications) (Scheme 1).
With this optimized route we were able to synthesize a
series of thiohydroxamic acids (4a−g) in 21−76% yield over
three steps and only one purification from the corresponding
aldehyde (Table 1). Aryl (4a−c), heteroaryl (4d,e), and alkyl
Table 1. Substrate Scope of Thiohydroxamic Acid Formation
Scheme 1. Optimized Synthesis of Thiohydroxamic and
Thiohydroximic Acids
(4f,g) substituted oximes were well tolerated in the reaction,
providing an expanded substrate scope for this transformation.
The variance in yield for these reactions stems from the varying
stability of the intermediate nitrile oxides (generated in situ
from the N-hydroxyimidoyl chlorides) as these intermediates
can readily undergo dimerization and other decomposition
pathways.12
We next sought to convert the thiohydroxamic acids to a
variety of S-alkyl-O-acyl derivatives via the one-pot alkylation/
acylation approach. Acylation of the oxygen effectively weakens
the N−O bond, allowing for the potential application of these
derivatives in transition metal mediated and radical reactions.15
Employing this method a series of thiohydroximic acid deriv-
atives (7a−w) were prepared in 30% to quantitative yield
(6−76% overall over four steps, Table 2). Electron-rich and
electron-deficient alkenes performed well in the transforma-
tion as well as mono- and disubstituted alkenes. Additionally,
the acylation could be accomplished with pentafluorobenzoyl
distilled benzaldehyde (1a) was treated with hydroxylamine
hydrochloride to provide oxime 2 in 87% yield. After aqueous
workup, the pure oxime 2 was chlorinated with NCS in DMF
to provide the N-hydroxyimidoyl chloride 3a in 95% yield.
With 3a in hand we initially explored the addition of allylthiol
reagents to the N-hydroxyimidoyl chlorides; however, in all
cases cycloaddition between the alkene and the in situ
generated nitrile oxide was the predominant reaction product.14
To circumvent this issue we modified and expanded an isolated
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stable to storage at room temperature for months without
decomposition.
Table 2. Substrate Scope of Thiohydroximic Acid Derivative
Formation
In conclusion, we have optimized a procedure for the pre-
paration of N-unsubstituted thiohydroxamic acids and devel-
oped a one-pot preparation of thiohydroximic acid derivatives.
A variety of functional groups are well tolerated, and products
bearing alkene groups and activated N-O bonds are readily
prepared. These thiohydroximic acid products are function-
alized to undergo a variety of further organic transformations
and serve as new heteroatom building blocks for synthesis.
EXPERIMENTAL SECTION
■
General Information. THF was purified using an alumina
filtration system. Aldehydes were purchased from a commercial
chemical company and used as received.
Reactions were monitored by TLC analysis (precoated silica gel
60 F254 plates, 250 mm layer thickness), and visualization was
accomplished with a 254 nm UV light and by staining with a KMnO4
solution (1.5 g of KMnO4, 10 g of K2CO3, and 1.25 mL of a 10%
NaOH solution in 200 mL of water). Reactions were also monitored
by LC−MS (2.6 mm C18 50 × 2.10 mm column). Flash chro-
matography on SiO2 was used to purify the crude reaction mixtures
and performed on a flash system utilizing prepacked cartridges and
linear gradients.
Melting points were determined using a capillary melting point
apparatus. Infrared spectra were determined on a FT/IR spectrometer.
1H, 13C, and 19F NMR spectra were obtained on a 400 MHz instru-
ment in CDCl3 unless otherwise noted. Chemical shifts were reported
in parts per million with the residual solvent peak used as an internal
1
1
standard (CDCl3 = 7.26 ppm for H and 77.16 ppm for 13C). H
NMR spectra were run at 300 or 400 MHz and are tabulated as
follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet,
q = quartet, m = multiplet, bs = broad singlet, dt = doublet of triplet,
tt = triplet of triplet), number of protons, and coupling constant(s).
13C NMR spectra were run at 100 MHz using a proton-decoupled
pulse sequence with a d1 of 0 s unless otherwise noted and are
tabulated by observed peak. CS and CO peaks are reported only
for selected products (due to tautomers). Extended delay times and
multiday experiments were required to observe these peaks on 50+ mg
quantities. 19F NMR spectra were run at 376 MHz and are tabulated as
follows: chemical shift, multiplicity (m = multiplet, tt = triplet of
triplet), number of fluorines, and coupling constant(s). High-
resolution mass spectra were obtained on an ion trap mass
spectrometer using heated electrospray ionization (HESI).
N-Hydroxythiophene-2-carbimidoyl Chloride (3d). General
Protocol A. To thiophene-2-carbaldehyde oxime (0.50 g, 3.9 mmol)
in DMF (3.9 mL) at 0 °C was added 1/5 portion of NCS (0.56 g,
4.1 mmol), and the reaction mixture was stirred at 0 °C for 1 h. The
remaining of the NCS was added portion wise over 1 h while the
temperature was slowly warmed to rt. The reaction mixture was stirred
at rt for 2 h, poured into iced water (16 mL), and extracted with
EtOAc, and the organic layer was separated, washed with water, dried
(MgSO4), and concentrated in vacuo. The residue was purified by flash
chromatography on SiO2 (hexanes/EtOAc, 0 to 12%) to yield 0.46 g
a
Isolated yield. BzF = pentafluorobenzoyl; Bz = benzoyl; Ac = acetyl;
Cbz = carboxybenzyl.
1
(72%) of 3d (mixture of two isomers) as a yellow solid: H NMR
(7a−l, 7s−w), benzoyl (7m,n), acetyl (7o), nitrobenzoyl (7p),
carboxybenzyl (7q), and carboxymethyl (7r) groups in high
yield. In all cases variation in yield is reflective of the thio-
hydroxamic acid formation (Table 1) as the alkylation/acylation
steps proceed in moderate to high yield over two steps. It is
important to note that the reaction products are readily
purified via silica gel flash chromatography and have been
(400 MHz) δ 7.82 (bs, 1 H), 7.58 (d, 0.1 H, J = 4.8 Hz, minor), 7.54
(dd, 1 H, J = 3.8, 1.2 Hz, major), 7.38 (dd, 1 H, J = 5.1, 1.3 Hz, major),
7.31 (d, 0.1 H, J = 4.0 Hz, minor), 7.06 (dd, 1 H, J = 5.1, 3.8 Hz,
major), 6.88 (d, 0.1 H, J = 4.1 Hz, minor); 13C NMR δ 135.3, 135.2,
130.0, 128.9, 127.3; IR (film) 3298, 3100, 1624, 1582, 1000, 838 cm−1;
HRMS m/z calcd for C5H5ClNOS [M + H]+ 161.9775, found
161.9774.
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N-Hydroxy-4-methoxybenzothioamide (4b). According to general
protocol C, N-hydroxy-4-methoxybenzimidoyl chloride 3b17 (0.10 g,
0.54 mmol), Et3N (0.075 mL, 0.54 mmol), and Na2S (0.39 g, 1.6
mmol) afforded 0.40 g (41%) of 4b as a yellow solid after extraction:
1H NMR (400 MHz) δ 7.67 (d, 2 H, J = 8.8 Hz), 6.93 (d, 2 H, J =
8.8 Hz), 3.85 (s, 3 H); 13C NMR δ 162.4, 128.5, 127.6, 114.2, 55.6
(CS not visible under experimental conditions); IR (film) 3136,
3004, 2884, 1600, 1396, 1174, 964, 838 cm−1; ESIMS m/z 182 [M −
H]−; HRMS m/z calcd for C8H10NO2S [M + H]+ 184.0427, found
184.0425; mp = 96−98 °C.
N-Hydroxythiazole-4-carbimidoyl Chloride (3e). General
Protocol B. To a stirred solution of thiazole-4-carbaldehyde (0.50 g,
4.5 mmol) in EtOH (8.7 mL) was added hydroxylamine hydrochloride
(0.34 g, 4.8 mmol) followed by pyridine (0.39 mL, 4.8 mmol). The
reaction mixture was stirred for 2 h at rt, quenched with satd aq
NH4Cl, and extracted with EtOAc. The organic layer was separated,
dried (MgSO4), and concentrated in vacuo to yield 0.53 g (95%) of
thiazole-4-carbaldehyde oxime as a yellow solid (mixture of isomers)
1
after extraction: H NMR (400 MHz) δ 8.88 (d, 1 H, J = 1.8 Hz,
major), 8.85 (d, 0.7 H, J = 2.0 Hz, minor), 8.36 (d, 0.7 H, J = 2.0 Hz,
minor), 8.34 (s, 1 H, major), 7.86 (s, 0.7 H, minor), 7.63 (d, 1 H, J =
2.0 Hz, major); 13C NMR (d1 = 1 s) δ 153.9, 152.2, 149.6, 146.3,
144.5, 140.6, 124.9, 118.4; IR (film) 3208, 3076, 2920, 2854, 1636,
1510, 976, 820 cm−1; ESIMS m/z 129 [M + H]+; HRMS m/z calcd for
C4H5N2OS [M + H]+ 129.0117, found 129.0119; mp = 115−122 °C.
According to general protocol A, thiazole-4-carbaldehyde oxime
(0.52 g, 4.1 mmol) and NCS (0.58 g, 4.3 mmol) in DMF (4.1 mL)
for 4 h afforded 0.36 g (54%) of 3e as a white crystalline solid after
filtration: 1H NMR (DMSO-d6, 400 MHz) δ 12.46 (s, 1 H), 9.18 (dd,
1 H, J = 2.0, 1.0 Hz), 8.15 (dd, 1 H, J = 2.0, 1.0 Hz); 13C NMR
(DMSO-d6) δ 155.6, 148.4, 131.0, 121.1; IR (film) 3300, 3070, 1537,
997, 808 cm−1; ESIMS m/z 163 [M + H]+; HRMS m/z calcd for
C4H4ClN2OS [M + H]+ 162.9727, found 162.9727; mp > 175 °C.
4-Bromo-N-hydroxybenzothioamide (4c). According to general
protocol C, 4-bromo-N-hydroxybenzimidoyl chloride 3c18 (0.43 g,
1.8 mmol), Et3N (0.25 mL, 1.8 mmol), and Na2S (1.3 g, 5.5 mmol)
afforded 0.13 g (32%) of 4c as a yellow solid after extraction: 1H NMR
(400 MHz) δ 7.57 (s, 4 H); 13C NMR δ 133.9, 132.2, 128.3, 125.8
(CS not visible under experimental conditions); IR (film) 3148,
3028, 1588, 826 cm−1; ESIMS m/z 230, 232 [M − H]−; HRMS m/z
calcd for C7H5BrNOS [M − H]− 229.9273, found 229.9273; mp =
106−110 °C.
N-Hydroxythiophene-2-carbothioamide (4d). According to gen-
eral protocol C, N-hydroxythiophene-2-carbimidoyl chloride 3d19
(0.32 g, 2.0 mmol), Et3N (0.27 mL, 2.0 mmol), and Na2S (1.5 g, 5.9
mmol) afforded 0.24 g (77%) of 4d as a brown oil (two tautomers)
after extraction: 1H NMR (400 MHz) δ 7.66−7.61 (m, 0.6 H, minor),
7.48−7.43 (m, 2 H, major), 7.14 (dd, 0.3 H, J = 5.0, 3.8 Hz, minor),
7.08−7.06 (m, 1 H, major); 13C NMR δ 138.3, 129.8, 127.8, 126.9
(CS not visible under experimental conditions); IR (film) 3454,
3328, 3094, 2220, 1648, 1588, 718 cm−1; ESIMS m/z 158 [M − H]−;
HRMS m/z calcd for C5H4NOS2 [M − H]− 157.9729, found
157.9729.
N-Hydroxy-3-phenylpropanimidoyl Chloride (3g). According to
general protocol B, 3-phenylpropanal oxime (0.40 g,
2.7 mmol) and NCS (0.38 g, 2.8 mmol) in DMF (2.7 mL) for 1 h
afforded 0.42 g (86%) of 3g (mixture of isomers) as a pale yellow oil
after purification by chromatography on SiO2 (hexanes/EtOAc,
0 to 20%): 1H NMR (400 MHz) δ 7.45 (s, 1 H), 7.34−7.27
(m, 2.4 H, major and minor), 7.25−7.19 (m, 3 H, major), 7.09−7.06
(m, 0.6 H, minor), 2.97 (dd, 2 H, J = 8.9, 6.3 Hz, major), 2.84−2.79
(m, 2 H, major), 2.61 (t, 0.4 H, J = 7.2 Hz, minor), 2.47−2.42
(m, 0.4 H, minor); 13C NMR δ 141.3, 139.7, 128.7, 128.5, 126.6, 38.6,
32.6; IR (film) 3298, 3028, 2932, 1636, 1492, 1456, 952, 688 cm−1;
HRMS m/z calcd for C9H11ClNO [M + H]+ 184.0524, found
184.0524.
N-Hydroxythiazole-4-carbothioamide (4e). According to general
protocol C, N-hydroxythiazole-4-carbimidoyl chloride 3e (0.33 g,
2.0 mmol), Et3N (0.28 mL, 2.0 mmol), and Na2S (1.5 g, 6.1 mmol)
afforded 0.21 g (66%) of 4e as an off white crystalline solid after
1
extraction: H NMR (400 MHz) δ 8.90 (d, 1 H, J = 2.1 Hz), 8.34
(d, 1 H, J = 2.1 Hz); 13C NMR δ 154.1, 150.3, 125.2 (CS not
visible under experimental conditions); IR (film) 3173, 3093, 1566,
682 cm−1; ESIMS m/z 159 [M − H]−; HRMS m/z calcd for
C4H5N2OS2 [M + H]+ 160.9838, found 160.9835; mp = 102−104 °C.
N-Hydroxybenzothioamide (4a). General Protocol C. To a stirred
solution of N-hydroxybenzimidoyl chloride 3a16 (2.00 g, 12.9 mmol)
in Et2O (172 mL) was added an aqueous solution of Na2S (9.26 g,
38.6 mmol) followed by Et3N (1.79 mL, 12.9 mmol). The reaction
mixture was stirred for 1 h and poured into a separatory funnel. The
Et2O was separated from the aqueous, which was acidified to pH = 2
with 5 M HCl, extracted with dichloromethane, dried (MgSO4), and
concentrated in vacuo to yield 1.71 g (87%) of 4a as a green solid:
1H NMR (400 MHz) δ 8.17 (bs, 2 H), 7.69−7.64 (m,
2 H), 7.52−7.38 (m, 3 H); 13C NMR δ 171.5, 135.3, 131.5, 129.1,
127.0; IR (film) 3177, 3061, 2572, 1556, 960, 691 cm−1; ESIMS m/z
152 [M − H]−; HRMS m/z calcd for C7H8NOS [M + H]+ 154.0321,
found 154.0321; mp = 39−40 °C.
N-Hydroxycyclopropanecarbothioamide (4f). According to gen-
eral protocol C, N-hydroxycyclopropanecarbimidoyl chloride 3f
(0.16 g, 1.3 mmol), Et3N (0.18 mL, 1.3 mmol), and Na2S (0.95 g,
4.0 mmol) afforded 0.071 g (46%) of 4f as a yellow solid (two
tautomers) after extraction: 1H NMR (400 MHz) δ 1.80−1.72
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(m, 1 H, major), 1.37−1.30 (m, 0.6 H, minor), 1.39−1.24 (m, 2 H,
major), 1.11−1.06 (m, 1.4 H, minor), 1.06−0.96 (m, 3.7 H, major and
minor); 13C NMR δ 18.8, 10.4, 7.3 (CS not visible under
experimental conditions); IR (film) 3508, 3190, 2920, 1378 cm−1;
ESIMS m/z 116 [M − H]−; HRMS m/z calcd for C4H6NOS [M −
H]− 116.0165, found 116.0161; mp = 111−112 °C.
3-Methylbut-2-en-1-yl N-((Perfluorobenzoyl)oxy)benzi-
midothioate (7b). According to general protocol D, N-hydroxyben-
zothioamide 4a (0.200 g, 1.31 mmol), 1-bromo-3-methyl-2-butene
(0.160 g, 1.31 mmol), Et3N (0.182 mL, 1.31 mmol), TBAI (49.0 mg,
0.131 mmol), Et3N (0.219 mL, 1.57 mmol), and pentafluorobenzoyl
chloride (0.228 mL, 1.57 mmol) in Et2O (13.1 mL) at rt afforded
0.493 g 91%) of 7b as a off-white solid after purification by chroma-
N-Hydroxy-3-phenylpropanethioamide (4g). According to general
protocol C, N-hydroxy-3-phenylpropanimidoyl chloride 3g (0.40 g,
2.2 mmol), Et3N (0.31 mL, 2.2 mmol), and Na2S (1.6 g, 6.6 mmol)
afforded 0.15 g (37%) of 4g as a yellow solid (4:1 mixture of
1
tography on SiO2 (hexanes/EtOAc, 0 to 10%): H NMR (300 MHz)
1
tautomers) after extraction: H NMR (400 MHz) δ 7.36−7.28 (m,
δ 7.53−7.45 (m, 5 H), 5.05−4.99 (m, 1 H), 3.21 (d, 2 H, J = 7.8 Hz),
1.65 (s, 3 H), 1.41 (s, 3 H); 13C NMR δ 169.1, 138.7, 131.6, 130.8,
129.0, 117.6, 31.3, 25.7, 17.7 (CO not visible under experimental
conditions); 19F NMR δ −136.8−136.9 (m, 2 F), −147.9−148.0 (m,
1 F), −160.2−160.4 (m, 2 F); IR (film) 3058, 3034, 1768, 1654, 1546,
1504, 1426, 1324, 1186, 1000, 910, 862 cm−1; ESIMS m/z 416 [M +
H]+; HRMS m/z calcd for C19H14F5NO2SNa [M + Na]+ 438.0558,
found 438.0552; mp = 71−73 °C.
2.5 H, major and minor), 7.25−7.18 (m, 4 H, major and minor), 3.06
(t, 2 H, J = 7.5 Hz, major), 2.97 (t, 0.5 H, J = 7.5 Hz, minor), 2.84−
2.81 (m, 2 H, major), 2.63 (t, 0.5 H, J = 7.4 Hz, minor); 13C NMR
(d1 = 1 s) δ 139.8, 128.8, 128.5, 126.8, 41.1, 34.2, CS not visible
under experimental conditions; IR (film) 3316, 3190, 3064, 2920,
2566, 1450, 1366, 700 cm−1; ESIMS m/z 180 [M − H]−; HRMS m/z
calcd for C9H10NOS [M − H]− 180.0489, found 180.0480; mp =
45−48 °C.
General Protocol D: One-Pot Allylation and Acylation of
Thiohydroxamic Acids. To a stirred solution of thiohydroxamic
acid (1 equiv) in Et2O or THF (0.1 M) was added allyl bromide or
chloride derivative (1 equiv), tetrabutylammonium iodide (TBAI)
(0.1 equiv), and Et3N (1 equiv). The reaction mixture was stirred at
rt or 60 °C for 1.5−3 h, then Et3N (1.2 equiv) and acylating agent
(1.2 equiv) were added at rt, and the reaction mixture was stirred
for 30 min. After completion the reaction was quenched with 10%
aqueous solution of Na2S2O3, stirred for 15 min, and extracted with
EtOAc, and the organic layer was separated, washed with NaHCO3,
water and brine, dried (MgSO4), and concentrated in vacuo. The
residue was purified by chromatography on SiO2 to yield the pure
product.
2-Bromoallyl N-(Perfluorobenzoyl)oxybenzimidothioate (7c).
According to general protocol D, N-hydroxybenzothioamide 4a
(0.200 g, 1.31 mmol), 2,3-dibromopropene (0.153 g, 1.31 mmol),
Et3N (182 μL, 1.31 mmol), TBAI (48.7 mg, 0.131 mmol), Et3N
(219 μL, 1.57 mmol), and pentafluorobenzoyl chloride (230 μL,
1.57 mmol) in Et2O (13.0 mL) at rt afforded 0.362 g (60%) of 7c as a
white solid after purification by chromatography on SiO2 (hexanes/
1
EtOAc, 0 to 15%): H NMR (400 MHz) δ 7.54−7.46 (m, 5 H), 5.47
(s, 1 H), 5.43 (d, 1 H, J = 2.3 Hz), 3.57−3.56 (m, 2 H); 13C NMR δ
166.9, 131.2, 130.4, 129.3, 129.1, 127.2, 120.5, 42.0 (CO not visible
under the experimental conditions); 19F NMR δ −136.7−136.6 (m,
2 F), −147.4−145.5 (m, 1 F), −160.0−160.1 (m, 2 F); IR (film) 3060,
2919, 1766, 1652, 1625, 1504, 1420, 1326, 1189, 1004, 914, 864 cm−1;
ESIMS m/z 466, 468 [M + H]+; HRMS m/z calcd for
C17H9BrF5NO2SNa [M + Na]+ 487.9350, found 487.9348; mp =
45−46 °C.
2-Methylallyl N-(Perfluorobenzoyl)oxybenzimidothioate (7a).
According to general protocol D, N-hydroxybenzothioamide 4a (0.751 g,
4.90 mmol), 3-chloro-2-methyl-1-propene (505 μL, 4.90 mmol), Et3N
(684 μL, 4.90 mmol), TBAI (183 mg, 0.490 mmol), Et3N (820 μL,
5.88 mmol), and pentafluorobenzoyl chloride (864 μL, 5.88 mmol) in
THF (49.0 mL) at 60 °C afforded 1.41 g (72%) of 7a as a yellow solid
after purification by chromatography on SiO2 (hexanes/EtOAc, 0 to
7%): 1H NMR (400 MHz) δ 7.51−7.46 (m, 5 H), 4.76 (s, 1 H), 4.55
(s, 1 H), 3.20 (s, 2 H), 1.68 (s, 3 H); 13C NMR δ 168.7, 156.2, 139.5,
131.0, 130.9, 129.2, 128.9, 115.4, 39.8, 21.2; 19F NMR δ −136.8−
136.9 (m, 2 F), −147.8−147.9 (m, 1 F), −160.1−160.3 (m, 2 F); IR
(film) 3052, 2920, 1762, 1648, 1522, 1492, 1414, 1330, 1198, 1000,
916, 874 cm−1; ESIMS m/z 402 [M + H]+; HRMS m/z calcd
for C18H12F5NO2SNa [M + Na]+ 424.0401, found 424.0399; mp =
60−61 °C.
Methyl 2-((((((Perfluorobenzoyl)oxy)imino)(phenyl)methyl)thio)-
methyl)acrylate (7d). According to general protocol D, N-hydroxy-
benzothioamide 4a (0.10 g, 0.65 mmol), methyl 2-(bromomethyl)-
acrylate (82 μL, 0.65 mmol), Et3N (91 μL, 0.65 mmol), TBAI (24 mg,
0.065 mmol), Et3N (0.11 mL, 0.78 mmol), and pentafluorobenzoyl
chloride (0.11 mL, 0.78 mmol) in Et2O (6.5 mL) at rt afforded 0.24 g
(83%) of 7d as a white solid after purification by chromato-
1
graphy on SiO2 (hexanes/EtOAc, 0 to 25%): H NMR (400 MHz)
2325
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Note
δ 7.52−7.46 (m, 5 H), 6.14 (s, 1 H), 5.26 (d, 1 H, J = 0.7 Hz), 3.74
(s, 3 H), 3.51 (d, 2 H, J = 0.9 Hz); 13C NMR δ 168.0, 165.7, 135.5,
131.1, 130.8, 129.3, 129.0, 128.6, 52.4, 33.4 (CO not visible
under the experimental conditions); 19F NMR δ −136.7−136.8 (m,
2 F), −147.7 (tt, 1 F, J = 21.0, 4.9 Hz), −160.1−160.3 (m, 2 F); IR
(film) 3064, 3004, 2962, 1768, 1726, 1648, 1522, 1498, 1420, 1198,
1006, 916, 868, 742 cm−1; ESIMS m/z 446 [M + H]+; HRMS m/z
calcd for C19H12F5NO4SNa [M + Na]+ 468.0299, found 468.0299;
mp = 49−50 °C.
(2E)-Methyl 4-(((((Perfluorobenzoyl)oxy)imino)(phenyl)methyl)-
thio)but-2-enoate (7g). According to general protocol D, N-hydroxy-
benzothioamide 4a (0.10 g, 0.65 mmol), methyl 4-bromocrotonate
(90 μL, 0.65 mmol), Et3N (91 μL, 0.65 mmol), TBAI (24 mg,
0.065 mmol), Et3N (0.11 mL, 0.78 mmol), and pentafluorobenzoyl
chloride (0.11 mL, 0.78 mmol) in Et2O (6.5 mL) at rt afforded 0.24 g
(81%) of 7g as a off-white solid after purification by chromatography
1
on SiO2 (hexanes/EtOAc, 0 to 30%): H NMR (300 MHz) δ 7.53−
7.48 (m, 5 H), 6.63 (dt, 1 H, J = 15.6, 7.2 Hz), 5.47 (d, 1 H, J = 15.5
Hz), 3.71 (s, 3 H), 3.37 (dd, 2 H, J = 7.1, 1.3 Hz); 13C NMR δ 167.0,
165.9, 141.2, 131.3, 130.6, 129.1, 124.1, 51.9, 33.5 (CO not visible
under the experimental conditions); 19F NMR δ −136.6−136.7 (m,
2 F), −147.5 (tt, 1 F, J = 21.2, 5.4 Hz), −160.0−160.2 (m, 2 F); IR
(film) 3064, 2998, 2956, 1762, 1648, 1504, 1438, 1324, 1192, 1000,
910, 862 cm−1; ESIMS m/z 446 [M + H]+; HRMS m/z calcd for
C19H12F5NO4SNa [M + Na]+ 468.0299, found 468.0301; mp = 67−
68 °C.
(E)-2-Methylbut-2-en-1-yl N-(Perfluorobenzoyl)oxy-
benzimidothioate (7e). According to general protocol D, N-
hydroxybenzothioamide 4a (0.10 g, 0.65 mmol), (E)-1-bromo-2-
methylbut-2-ene20 (0.20 g, 0.65 mmol), Et3N (91 μL, 0.65 mmol),
TBAI (65 mg, 0.065 mmol), Et3N (0.11 mL, 0.78 mmol), and
pentafluorobenzoyl chloride (0.11 mL, 0.78 mmol) in Et2O (6.5 mL)
at rt afforded 0.24 g (88%) of 7e as a white solid after purification by
chromatography on SiO2 (hexanes/EtOAc, 0 to 10%): 1H NMR
(300 MHz) δ 7.50−7.46 (m, 5 H), 4.99−4.92 (m, 1 H), 3.20 (s,
2 H), 1.59−1.58 (m, 3 H), 1.49−1.46 (m, 3 H); 13C NMR (d1 = 5 s)
δ 169.0, 156.3, 131.4, 130.8, 129.6, 129.2, 128.8, 124.9, 42.3, 14.8,
13.7; 19F NMR δ −136.9−136.9 (m, 2 F), −148.0 (tt, 1 F, J = 21.2,
5.1 Hz), −160.2−160.4 (m, 2 F); IR (film) 3058, 3022, 2926, 1762,
1648, 1504, 1426, 1324, 1000, 910, 862 cm−1; ESIMS m/z 416 [M +
H]+; HRMS m/z calcd for C19H14F5NO2SNa [M + Na]+ 438.0558,
found 438.0558; mp = 66−67 °C.
Cinnamyl N-(Perfluorobenzoyl)oxybenzimidothioate (7h).
According to general protocol D, N-hydroxybenzothioamide 4a
(0.10 g, 0.65 mmol), cinnamyl bromide (0.10 mL, 0.65 mmol),
Et3N (91 μL, 0.65 mmol), TBAI (24 mg, 0.065 mmol), Et3N
(0.11 mL, 0.78 mmol), and pentafluorobenzoyl chloride (0.11 mL,
0.78 mmol) in Et2O (6.5 mL) at rt afforded 0.26 g (85%) of 7g as a
white solid after purification by chromatography on SiO2 (hexanes/
EtOAc, 0 to 7%): 1H NMR (300 MHz) δ 7.54−7.48 (m, 5 H), 7.29−
7.19 (m, 5 H), 5.96−5.93 (m, 2 H), 3.44−3.42 (m, 2 H); 13C NMR δ
168.2, 136.0, 134.2, 131.2, 131.0, 129.2, 129.0, 128.7, 128.2, 126.5,
123.0, 35.6 (CO not visible under the experimental conditions); 19F
NMR δ −136.8−136.7 (m, 2 F), −147.7−147.8 (m, 1 F), −160.3−
160.1 (m, 2 F); IR (film) 3056, 3028, 2920, 1768, 1654, 1498, 1414,
1318, 1084, 1000, 916, 862 cm−1; ESIMS m/z 464 [M + H]+; HRMS
m/z calcd for C23H14F5NO2SNa [M + Na]+ 486.0558, found
486.0560; mp = 124−125 °C.
2-Fluoroallyl N-(Perfluorobenzoyl)oxybenzimidothioate (7f).
According to general protocol D, N-hydroxybenzothioamide 4a
(0.300 g, 1.96 mmol), 2-fluoro-3-(methylsulfonyl)prop-1-ene21
(0.302 g, 1.96 mmol), Et3N (273 μL, 1.96 mmol), TBAI (73.1 mg,
0.196 mmol), Et3N (328 μL, 2.35 mmol), and pentafluorobenzoyl
chloride (342 μL, 2.45 mmol) in Et2O (6.50 mL) at rt afforded 0.230 g
(29%) of 7f as a yellow solid after purification by chromatography on
1
SiO2 (hexanes/EtOAc, 0 to 15%): H NMR (400 MHz) δ 7.55−7.47
(m, 5 H), 4.57 (dd, 1 H, J = 15.5, 3.4 Hz), 4.11 (dd, 1 H, J = 47.2, 3.4
1
Hz), 3.34 (d, 2 H, J = 15.5 Hz); 13C NMR δ 167.0, 160.1 (d, JC−F
=
2
257.1 Hz), 131.2, 130.4, 129.3, 129.1, 93.9 (d, JC−F = 18.6 Hz), 33.2
2
(d, JC−F = 31.3 Hz) (CO not visible under the experimental
conditions); 19F NMR δ −98.9−99.2 (m, 1 F), −136.6−139.9 (m,
2 F), −147.4−147.5 (m, 1 F), −160.0−160.2 (m, 2 F); IR (film) 3064,
3016, 2932, 1768, 1678, 1654, 1498, 1444, 1330, 1186, 1000, 916,
868 cm−1; ESIMS m/z 406 [M + H]+; HRMS m/z calcd for
C17H9F6NO2SNa [M + Na]+ 428.0150, found 428.0151; mp =
45−49 °C.
2-(Trifluoromethyl)allyl N-(Perfluorobenzoyl)oxybenzi-
midothioate (7i). According to general protocol D, N-hydroxybenzo-
thioamide 4a (0.150 g, 0.979 mmol), 2-bromomethyl-3,3,3-trifluo-
ropropene (0.185 g, 0.979 mmol), Et3N (135 μL, 0.979 mmol), TBAI
(36.7 mg, 0.0979 mmol), Et3N (164 μL, 1.17 mmol), and penta-
fluorobenzoyl chloride (171 μL, 1.17 mmol) in Et2O (9.80 mL) at
2326
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Note
rt afforded 0.358 g (80%) of 7i as a yellow oil after purification by
1
chromatography on SiO2 (hexanes/EtOAc, 0 to 10%): H NMR
(400 MHz) δ 7.53−7.47 (m, 5 H), 5.77 (s, 1 H), 5.41−5.40 (m,
1 H), 3.39 (s, 2 H); 13C NMR δ 166.9, 133.9, 133.6, 131.3, 130.3,
129.1, 124.0, 122.5, 121.3, 30.9 (CO not visible under the experi-
mental conditions); 19F NMR δ −68.3 (s, 3 F), −136.7−136.8 (m,
2 F), −147.3−147.5 (m, 1 F), −160.0−160.2 (m, 2 F); IR (film)
3064, 2926, 1768, 1702, 1648, 1504, 1420, 1270, 1192, 1126, 1006,
916, 868 cm−1; HRMS m/z calcd for C18H9F8NO2SNa [M + Na]+
478.0119, found 478.0115.
(E)-7-Methylocta-2,6-dien-1-yl N-((Perfluorobenzoyl)oxy)-
benzimidothioate (7l). According to general protocol D, N-
hydroxybenzothioamide 4a (0.200 g, 1.31 mmol), geranyl bromide
(270 μL, 1.31 mmol), Et3N (182 μL, 1.31 mmol), TBAI (48.7 mg,
0.130 mmol), Et3N (219 μL, 1.57 mmol), and pentafluorobenzoyl
chloride (228 μL, 1.57 mmol) in Et2O (13.1 mL) at rt afforded 0.450
g (71%) of 7l as a white solid after purification by chromatography
1
on SiO2 (hexanes/EtOAc, 0 to 7%): H NMR (400 MHz) δ 7.52−
7.46 (m, 5 H), 5.04−4.99 (m, 2 H), 3.22 (d, 2 H, J = 7.8 Hz), 2.02−
1.92 (m, 4 H), 1.66 (s, 3 H), 1.57 (s, 3 H), 1.41 (s, 3 H); 13C NMR δ
169.1, 142.2, 132.1, 131.6, 130.8, 129.0, 123.6, 117.4, 39.5, 31.2,
26.3, 25.8, 17.8, 16.1 (CO not visible under the experimental
conditions); 19F NMR δ −136.8−136.9 (m, 2 F), −147.9−148.1 (m,
1 F), −160.2−160.4 (m, 2 F); IR (film) 3064, 3028, 2920, 1768,
1648, 1540, 1504, 1420, 1324, 1186, 1000, 916, 856 cm−1; ESIMS
m/z 484 [M + H]+; HRMS m/z calcd for C24H23F5NO2S [M + H]+
484.1364, found 484.1358; mp = 42−44 °C.
Allyl N-(Perfluorobenzoyl)oxybenzimidothioate (7j). According to
general protocol D, N-hydroxybenzothioamide 4a (0.200 g, 1.31 mmol),
allyl bromide (116 μL, 1.31 mmol), Et3N (182 μL, 1.31 mmol), TBAI
(48.7 mg, 0.130 mmol), Et3N (219 μL, 1.57 mmol), and penta-
fluorobenzoyl chloride (230 μL, 1.57 mmol) in Et2O (13.0 mL) at rt
afforded 0.391 g (77%) of 7j as a white solid after purification by
chromatography on SiO2 (hexanes/EtOAc, 0 to 10%): 1H NMR (400
MHz) δ 7.52−7.45 (m, 5 H), 5.67−5.57 (m, 1 H), 5.03−5.00 (m,
1 H), 4.89−4.84 (m, 1 H), 3.26−3.23 (m, 2 H); 13C NMR δ 168.3,
132.0, 131.1, 131.0, 129.2, 128.9, 119.3, 35.7 (CO not visible under
the experimental conditions); 19F NMR δ −136.8−136.7 (m, 2 F),
−147.8−147.7 (m, 1 F), −160.3−160.1 (m, 2 F); IR (film) 3082,
3064, 2932, 1762, 1654, 1510, 1426, 1324, 1192, 1006, 916, 862 cm−1;
ESIMS m/z 388 [M + H]+; HRMS m/z calcd for C17H10F5NO2SNa
[M + Na]+ 410.0245, found 410.0243; mp = 65−66 °C.
2-Methylallyl N-Benzoyloxybenzimidothioate (7m). According to
general protocol D, N-hydroxybenzothioamide 4a (0.619 g, 4.04
mmol), 3-chloro-2-methyl-1-propene (416 μL, 4.04 mmol), Et3N
(564 μL, 4.04 mmol), TBAI (0.151 g, 0.400 mmol), Et3N (676 μL,
4.85 mmol), and benzoyl chloride (569 μL, 4.85 mmol) in THF
(40.4 mL) at 60 °C afforded 0.455 g (36%) of 7m as a white solid after
purification by chromatography on SiO2 (hexanes/EtOAc, 0 to 15%):
1H NMR (400 MHz) δ 8.20−8.17 (m, 2 H), 7.64−7.60 (m, 1 H),
7.54−7.51 (m, 4 H), 1.71 (s, 3 H), 7.49−7.47 (m, 3 H), 4.77−4.76
(m, 1 H), 4.60 (s, 1 H), 3.23 (s, 2 H); 13C NMR δ 166.4, 163.5, 139.9,
133.6, 131.7, 130.5, 130.0, 129.4, 128.9, 128.7, 115.2, 39.6, 21.3; IR
(film) 3058, 2932, 1732, 1534, 1438, 1228, 964, 850, 760 cm−1;
ESIMS m/z 312 [M + H]+; HRMS m/z calcd for C18H17NO2SNa
[M + Na]+ 334.0872, found 334.0872; mp = 80−81 °C.
Cyclohex-1-en-1-ylmethyl N-((Perfluorobenzoyl)oxy)benzi-
midothioate (7k). According to general protocol D, N-hydroxybenzo-
thioamide 4a (0.200 g, 1.31 mmol), 1-(bromomethyl)cyclohex-1-
ene22 (116 μL, 1.31 mmol), Et3N (183 μL, 1.31 mmol), TBAI (48.7
mg, 0.130 mmol), Et3N (219 μL, 1.57 mmol), and pentafluor-
obenzoyl chloride (228 μL, 1.57 mmol) in Et2O (13.0 mL) at rt
afforded 0.523 g (91%) of 7k as a white solid after purification by
chromatography on SiO2 (hexanes/EtOAc, 0 to 10%): 1H NMR
(400 MHz) δ 7.50−7.43 (m, 5 H), 5.19 (s, 1 H), 3.15 (s, 1 H), 1.87
(s, 4 H), 1.59−1.55 (m, 2 H), 1.50−1.46 (m, 2 H); 13C NMR
δ 169.1, 131.8, 131.3, 130.7, 129.2, 128.8, 127.2, 40.5, 27.1, 25.3,
22.6, 22.0 (CO not visible under the experiment conditions); 19F
NMR δ −136.8−136.9 (m, 2 F), −147.9−148.1 (m, 1 F), −160.2−
160.3 (m, 2 F); IR (film) 3058, 2932, 1762, 1648, 1540, 1522, 1504,
1420, 1324, 1192, 1000, 916, 856 cm−1; ESIMS m/z 442 [M + H]+;
HRMS m/z calcd for C21H17F5NO2S [M + H]+ 442.0895, found
442.0886; mp = 52−56 °C.
Allyl N-Benzoyloxybenzimidothioate (7n). According to general
protocol D, N-hydroxybenzothioamide 4a (0.200 g, 1.31 mmol), allyl
bromide (116 μL, 1.31 mmol), Et3N (182 μL, 1.31 mmol), TBAI
(48.7 mg, 0.0131 mmol), Et3N (219 μL, 1.57 mmol), and benzoyl
chloride (184 μL, 1.57 mmol) in Et2O (13.0 mL) at rt afforded 0.336 g
(87%) of 7n as a white solid after purification by chromatography on
1
SiO2 (hexanes/EtOAc, 0 to 15%): H NMR (400 MHz) δ 8.19−8.17
(m, 2 H), 7.64−7.60 (m, 1 H), 7.54−7.47 (m, 7 H), 5.70−5.61 (m,
1 H), 5.04−5.01 (m, 1 H), 4.92−4.87 (m, 1 H), 3.29−3.26 (m, 2 H);
13C NMR δ 166.0, 163.4, 133.6, 132.4, 131.7, 130.6, 130.0, 129.3,
128.9, 128.8, 128.7, 119.0, 35.5; IR (film) 3064, 3010, 2920, 1738,
1600, 1576, 1534, 1444, 1234, 970, 850, 712 cm−1; ESIMS m/z 298
2327
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Note
[M + H]+; HRMS m/z calcd for C17H15NO2SNa [M + Na]+ 320.0716,
found 320.0717; mp = 88−89 °C.
General Protocol E: Acylation of Thiohydroximic Acids. To a
stirred solution of N-hydroxybenzothioamide 4a (0.708 g, 4.62 mmol)
in Et2O (46.2 mL) were added allyl bromide (412 μL, 4.62 mmol),
tetrabutylammonium iodide (TBAI) (0.172 g, 0.462 mmol), and Et3N
(645 μL, 4.62 mmol). The reaction mixture was stirred at rt for 1.5 h,
quenched with water, and extracted with EtOAc, and the organic layer
was separated, washed with a 10% aqueous solution of Na2S2O3 until
the yellow color disappeared, then washed with brine, dried (MgSO4),
and concentrated in vacuo. The residue was purified by chromatog-
raphy on SiO2 (hexanes/EtOAc, 0 to 20%) to yield 0.770 g (86%) of
allyl N-hydroxybenzimidothioate as a colorless oil: 1H NMR (400
MHz) δ 9.46 (bs, 1 H), 7.52−7.49 (m, 2 H), 7.43−7.40 (m, 3 H),
5.73−5.63 (m, 1 H), 4.98−4.96 (m, 1 H), 4.89−4.84 (m, 1 H), 3.30−
3.28 (m, 2 H); 13C NMR δ 155.4, 133.4, 133.1, 129.9, 128.8, 128.7,
128.7, 118.3, 34.9; IR (film) 3220, 3082, 2980, 1636, 1588, 1492, 1444,
928, 760, 694 cm−1; ESIMS m/z 194 [M + H]+; HRMS m/z calcd for
C10H12NOS [M + H]+ 194.06341, found 194.06359.
To a solution of thiohydroximic acid (1 equiv) in DCM (0.1 M)
at 0 °C were added Et3N (1.2 equiv) or pyridine (1.1 equiv) and
acylating agent (1.2 eq or 1.1 equiv), and the reaction mixture
was stirred for 30 min to 1.5 h. After completion the reaction was
quenched with water and extracted with DCM; the organic layer was
separated, washed with brine, and dried (MgSO4); and the solvent was
removed in vacuo to yield the pure product or the residue was purified
by chromatography on SiO2.
Allyl N-((Benzyloxy)carbonyl)oxybenzimidothioate (7q). Accord-
ing to general protocol E, allyl N-hydroxybenzimidothioate (0.10 g,
0.52 mmol), pyridine (46 μL, 0.57 mmol), and benzyl chloroformate
(83 μL, 0.57 mmol) in DCM (5.2 mL) afforded 0.18 g (quant) of 7q
as a white solid after purification by chromatography on SiO2
1
(hexanes/EtOAc, 0 to 20%): H NMR (400 MHz) δ 7.49−7.36 (m,
10 H), 5.67−5.57 (m, 1 H), 5.30 (s, 2 H), 5.00−4.97 (m, 1 H), 4.88−
4.82 (m, 1 H), 3.26−3.24 (m, 2 H); 13C NMR δ 164.7, 153.6, 134.9,
132.3, 131.6, 130.7, 129.2, 128.9, 128.8, 125.7, 119.0, 70.5, 35.6; IR
(film) 3064, 3034, 2933, 1780, 1636, 1378, 1240, 1222, 946, 868,
844 cm−1; ESIMS m/z 328 [M + H]+; HRMS m/z calcd for
C18H17NO3SNa [M + Na]+ 350.0821, found 350.0822; mp = 7
6−78 °C.
Allyl N-(Methoxycarbonyl)oxybenzimidothioate (7r). According
to general protocol E, allyl N-hydroxybenzimidothioate (0.11 g,
0.54 mmol), pyridine (48 μL, 0.60 mmol), and methyl chloroformate
(47 μL, 0.60 mmol) in DCM (5.2 mL) afforded 0.13 g (94%) of 7r as
a colorless oil: 1H NMR (400 MHz) δ 7.47−7.44 (m, 5 H), 5.69−5.58
(m, 1 H), 5.01−4.98 (m, 1 H), 4.89−4.84 (m, 1 H), 3.86 (s, 3 H),
3.27−3.24 (m, 2 H); 13C NMR δ 164.7, 154.1, 132.3, 131.5, 130.7,
129.2, 128.8, 119.0, 55.6, 35.5; IR (film) 3076, 3056, 2950, 1780, 1635,
1558, 1492, 1438, 1234, 916, 880, 772 cm−1; ESIMS m/z 252 [M +
H]+; HRMS m/z calcd for C12H13NO3SNa [M + Na]+ 274.0508,
found 274.0508.
Allyl N-Acetoxybenzimidothioate (7o). According to general
protocol E, allyl N-hydroxybenzimidothioate (0.10 g, 0.52 mmol),
Et3N (87 μL, 0.62 mmol), and acetic anhydride (59 μL, 0.62 mmol)
1
in DCM (5.2 mL) afforded 0.13 g (quant) of 7o as a yellow oil: H
NMR (400 MHz) δ 7.46−7.44 (m, 5 H), 5.69−5.59 (m, 1 H), 5.02−
4.99 (m, 1 H), 4.90−4.85 (m, 1 H), 3.25−3.23 (m, 2 H), 2.25 (s,
3 H); 13C NMR δ 168.8, 164.8, 132.4, 131.8, 130.6, 129.2, 128.8,
119.0, 35.5, 19.6; IR (film) 3076, 3058, 2926, 1768, 1636, 1552,
1198, 1000, 904, 862, 706 cm−1; ESIMS m/z 236 [M + H]+; HRMS
m/z calcd for C12H13NO2SNa [M + Na]+ 258.0559, found 258.0558.
3-Methylbut-2-en-1-yl N-((Perfluorobenzoyl)oxy)-3-phenylpropa-
nimidothioate (7s). According to general protocol D, N-hydroxy-3-
phenylpropanethioamide 4g (0.14 g, 0.77 mmol), 1-bromo-3-methyl-
2-butene (94 μL, 0.77 mmol), Et3N (0.11 mL, 0.77 mmol), TBAI
(29 mg, 0.077 mmol), Et3N (0.13 mL, 0.93 mmol), and penta-
fluorobenzoyl chloride (0.14 mL, 0.93 mmol) in Et2O (7.7 mL) at rt
afforded 0.22 g (65%) of 7s as a white solid after purification by
chromatography on SiO2 (hexanes/EtOAc, 0 to 12%): 1H NMR (400
MHz) δ 7.35−7.31 (m, 2 H), 7.26−7.23 (m, 3 H), 5.22−5.18 (m,
1 H), 3.53 (d, 2 H, J = 7.7 Hz), 3.09−3.05 (m, 2 H), 2.93−2.89 (m,
2 H), 1.74 (s, 3 H), 1.65 (s, 3 H); 13C NMR δ 168.5, 140.2, 139.4,
128.8, 128.5, 126.8, 117.0, 35.2, 33.7, 29.0, 25.8, 18.1 (CO not
visible under the experimental conditions); 19F NMR δ −136.9−137.0
(m, 2 F), −148.1−148.2 (m, 1 F), −160.3−160.4 (m, 2 F); IR (film)
3058, 3028, 2932, 1756, 1654, 1606, 1504, 1420, 1198, 1144, 1006,
886, 838 cm−1; ESIMS m/z 444 [M + H]+; HRMS m/z calcd for
C21H19F5NO2S [M + H]+ 444.1051, found 444.1047; mp = 90−91 °C.
Allyl N-(4-Nitrobenzoyl)oxybenzimidothioate (7p). According to
general protocol E, allyl N-hydroxybenzimidothioate (0.10 g, 0.52
mmol), Et3N (87 μL, 0.62 mmol), and 4-nitrobenzoyl chloride (0.12 g,
0.62 mmol) in DCM (5.2 mL) afforded 0.18 g (quant) of 7p as a
white solid after purification by chromatography on SiO2 (hexanes/
1
EtOAc, 0 to 20%): H NMR (400 MHz) δ 8.35 (s, 4 H), 7.51−7.49
(m, 5 H), 5.71−5.61 (m, 1 H), 5.06−5.03 (m, 1 H), 4.92−4.87 (m, 1
H), 3.30−3.28 (m, 2 H); 13C NMR δ 167.6, 161.6, 150.9, 134.4, 131.3,
131.1, 130.9, 129.2, 128.9, 123.9, 119.3, 35.6; IR (film) 3082, 3058,
2980, 1756, 1606, 1522, 1486, 1402, 1348, 1252, 976, 928, 862 cm−1;
ESIMS m/z 343 [M + H]+; HRMS m/z calcd for C17H14N2O4SNa
[M + Na]+ 365.0567, found 365.0568; mp = 96−97 °C.
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Note
1
10%): H NMR (400 MHz) δ 7.52 (dd, 1 H, J = 5.1, 1.2 Hz), 7.50
(dd, 1 H, J = 3.7, 1.2 Hz), 7.13 (dd, 1 H, J = 5.1, 3.7 Hz), 5.16−5.11
(m, 1 H), 3.56 (d, 2 H, J = 7.8 Hz), 1.69 (s, 3 H), 1.54 (s, 3 H); 13C
NMR δ 161.1, 139.2, 133.3, 131.2, 130.2, 127.8, 117.6, 32.4, 25.8, 17.8
(CO not visible under the experimental conditions); IR (film) 3112,
2968, 2914, 1768, 1648, 1522, 1504, 1420, 1330, 1180, 1000, 838, 784
cm−1; ESIMS m/z 422 [M + H]+; HRMS m/z calcd for
C17H12F5NO2S2Na [M + Na]+ 444.0122, found 444.0114.
3-Methylbut-2-en-1-yl N-((Perfluorobenzoyl)oxy)cyclo-
propanecarbimidothioate (7t). According to general protocol D,
N-hydroxycyclopropanecarbothioamide 4f (65 mg, 0.55 mmol),
1-bromo-3-methyl-2-butene (68 μL, 0.55 mmol), Et3N (77 μL, 0.55
mmol), TBAI (21 mg, 0.055 mmol), Et3N (93 μL, 0.67 mmol), and
pentafluorobenzoyl chloride (97 μL, 0.67 mmol) in Et2O (5.5 mL) at
rt afforded 55 mg (26%) of 7t as an orange oil after purification by
chromatography on SiO2 (hexanes/EtOAc, 0 to 10%): 1H NMR
(400 MHz) δ 5.29−5.24 (m, 1 H), 3.73 (d, 2 H, J = 7.7 Hz), 1.80−
1.73 (m, 1 H), 1.77 (s, 3 H), 1.71 (s, 3 H), 1.20−1.16 (m, 2 H), 1.02−
1.00 (m, 2 H); 13C NMR δ 170.5, 138.9, 117.5, 28.9, 25.9, 18.0, 13.9,
7.6 (CO not visible under the experimental conditions); 19F NMR
δ −137.0−137.1 (m, 2 F), −148.3−148.4 (m, 1 F), −160.3−160.5 (m,
2 F); IR (film) 2974, 2920, 1768, 1654, 1558, 1510, 1426, 1324, 1192,
934, 874 cm−1; ESIMS m/z 380 [M + H]+; HRMS m/z calcd for
C16H14F5NO2SNa [M + Na]+ 402.0558, found 402.0557.
3-Methylbut-2-en-1-yl N-((Perfluorobenzoyl)oxy)thiazole-4-carbi-
midothioate (7w). According to general protocol D, N-hydroxythia-
zole-4-carbothioamide 4e (0.106 g, 0.662 mmol), 1-bromo-3-methyl-
2-butene (81.0 μL, 0.662 mmol), Et3N (92.0 μL, 0.662 mmol), TBAI
(24.6 mg, 66.1 μmol), Et3N (0.111 mL, 0.794 mmol), and
pentafluorobenzoyl chloride (0.115 mL, 0.794 mmol) in Et2O (6.60
mL) at rt afforded 0.187 g (67%) of 7w as a pink crystalline solid after
purification by chromatography on SiO2 (hexanes/EtOAc,
1
0 to 15%): H NMR (400 MHz) δ 8.93 (dd, 1 H, J = 2.1, 1.0 Hz),
7.88 (dd, 1 H, J = 2.1, 1.0 Hz), 5.06−5.02 (m, 1 H), 3.54 (d, 2 H, J =
7.8 Hz), 1.66 (s, 3 H), 1.54 (s, 3 H); 13C NMR δ 163.3, 153.9,
147.4, 139.1, 122.1, 117.5, 30.6, 25.8, 25.7 (CO not visible under
the experimental conditions); 19F NMR δ −136.6−136.6 (m, 2 F),
−147.5−147.7 (m, 1 F), −160.0−160.2 (m, 2 F); IR (film) 3104,
2978, 2921, 1761, 1652, 1497, 1193, 1094, 934, 900, 859 cm−1; ESIMS
m/z 423 [M + H]+; HRMS m/z calcd for C16H12F5N2O2S2 [M + H]+
423.0255, found 423.0243; mp = 69−71 °C.
ASSOCIATED CONTENT
Cinnamyl 4-Bromo-N-((perfluorobenzoyl)oxy)benzimidothioate
(7u). According to general protocol D, 4-bromo-N-hydroxybenzo-
thioamide 4c (0.250 g, 1.08 mmol), cinnamyl bromide (0.164 mL,
1 . 0 8 m m o l ) , E t 3 N ( 0 . 1 5 0 m L , 1 . 0 8 m m o l ) ,
TBAI (40.2 mg, 0.108 mmol), Et3N (0.180 mL, 1.29 mmol), and
pentafluorobenzoyl chloride (0.188 mL, 1.29 mmol) in Et2O (10.8
mL) at rt afforded 0.275 g (47%) of 7u as a off-white solid after
purification by chromatography on SiO2 (hexanes/EtOAc, 0 to 10%):
1H NMR (400 MHz) δ 7.62 (d, 2 H, J = 8.4 Hz), 7.40 (d, 2 H, J = 8.4
■
S
* Supporting Information
1H NMR and 13C NMR spectra. This material is available free
of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: jgpierce@ncsu.edu.
■
Hz), 7.32−7.29 (m, 2 H), 7.23−7.21 (m, 3 H), 6.01−5.91 (m, 2 H),
3.45 (d, 2 H, J = 6.1 Hz); 13C NMR δ 167.1, 135.8, 134.4, 132.3,
130.7, 130.2, 128.8, 128.3, 126.5, 125.6, 122.7, 35.7 (CO not visible
under the experimental conditions); IR (film) 3088, 3064, 2926, 1762,
1654, 1588, 1498, 1414, 1318, 1192, 1000, 916, 862 cm−1; HRMS m/z
calcd for C23H14BrF5NO2S [M + H]+ 541.9843, found 541.9847; mp =
122−124 °C.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge North Carolina State University for
generous start-up support, and acknowledgement is made to
the Donors of the American Chemical Society Petroleum
Research Fund for partial support of this research. Mass spectra
were obtained at the Mass Spectrometry Laboratory at North
Carolina State University.
REFERENCES
■
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