A convenient method for the preparation of functionalized N-acylsulfenamides from primary amides

Article abstract of DOI:10.1080/10426507.2015.1065258

We have developed a convenient method for the synthesis of functionalized N-acylsulfenamides under mild conditions and in moderate to good yields. The designed method is based on the reaction of (5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-yl)-disulfanyl derivatives with nitrogen nucleophiles generated from primary amides or imides and sodium hydride. The developed method allows for the preparation of N-acylsulfenamides bearing additional hydroxyl, carboxyl, or amino functionalities.

Full text of DOI:10.1080/10426507.2015.1065258

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
A convenient method for the preparation of
functionalized N-acylsulfenamides from primary
amides.
Mateusz Musiejuk & Dariusz Witt
To cite this article: Mateusz Musiejuk & Dariusz Witt (2015): A convenient method for the
preparation of functionalized N-acylsulfenamides from primary amides., Phosphorus, Sulfur,
and Silicon and the Related Elements, DOI: 10.1080/10426507.2015.1065258
To link to this article: http://dx.doi.org/10.1080/10426507.2015.1065258
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Date: 03 December 2015, At: 22:03

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Functionalized N-acylsulfenamides from primary amides
A convenient method for the preparation of functionalized N-acylsulfenamides from
primary amides.
Mateusz Musiejuk and Dariusz Witt*
Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology,
Narutowicza 11/12, 80-233 Gdansk, Poland Fax +48(58)3472694
*Corresponding Author E-mail: chemwitt@pg.gda.pl
Key words
sulfenamide, thiols, amide, phthalimide, phosphorodithioic acid
Abstract
We have developed a convenient method for the synthesis of functionalized N-acylsulfenamides
under mild conditions and in moderate to good yields. The designed method is based on the
reaction of (5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-yl)-disulfanyl derivatives with
nitrogen nucleophiles generated from primary amides or imides and sodium hydride. The
developed method allows for the preparation of N-acylsulfenamides bearing additional hydroxyl,
carboxyl, or amino functionalities.
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Introduction
Sulfenamides are a class of compounds containing a trivalent nitrogen bonded to a divalent
sulfur. A number of practical applications have been found for these stable and reactive
sulfenylating reagents in industry, including their use as pesticides,1,2 rubber vulcanization
accelerators1,3 and prodrugs in medicinal chemistry.1,4 The interesting chiroptical properties of
sulfenamides, based on the S-N bond, have also been studied.5 Sulfenamides are also useful as
synthetic reagents. For instance, S-phenyl sulfenamides have been used as a source of aminyl,6
amidyl,7 and thioaminyl8 radicals. Sulfenamides have been also involved in the insertion
reactions.9 Sulfenamides have been produced as intermediates in the synthesis of disulfanes,10
chiral amines11 and amino acids.12 S,N-diaryl sulfenamides have been utilized as a source of
electrophilic arylthio units,13 and methanesulfenamide has been used in the preparation of
inversely fused bicyclic -lactams.14
Although sulfenamides are quite useful functionally, their formation is generally limited to rather
harsh methods that may not be compatible with other functional groups within the molecule. The
synthesis of sulfenamides has been reviewed15 recently. The most common methods for the
synthesis of sulfenamides are based on the reaction of an amine or metal amide with sulfenic
acid derivatives, RSX, where X may be a halogen, phthalimide, alkoxy group, or sulfur-bearing
functionality.1 Other methods involve the reaction of thiols and amines in the presence of
oxidizing reagents16 or the reaction of disulfides and amines in the presence of silver or mercuric
salts.17 Recently, sulfenamides have been obtained through the reaction of amines with glycosyl
thioacetates in the presence of diethyl bromomalonate,18 3-phenylsulfenyl-2-(N-
cyanoimino)thiazolidine,19 S-[2-(3-oxo-1,2-benzisothiazolinyl)]-2-mercaptobenzoates20 and N-
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(1-alkenylthio)phthalimides,21 respectively. Sulfenamides can also be prepared by the copper-
catalyzed coupling of amines with diaryl disulfides22 or arylthiols.23 The literature refers to
sulfenamides as R1-S-NR2 in which R1 and R can be H, alkyl or aryl groups, whereas when one
of the nitrogen R groups is an acyl group refers to them as being N-acylsulfenamides or N-
(thioalkyl or aryl)amides. The most common methods for obtaining N-acylsulfenamides include
the reaction of amides with N-sulfenylbenzimidazoles,24 sulfenyl chlorides25,26 and thermolysis
of N-acetyliminodialkylsulfuranes.27 Several methods to construct cyclic N-acylsulfenamides
have been reported. These methods are based on the condensation of 2-(chlorocarbamoyl)-
phenylsulfenyl chlorides with amines,28 CuI-mediated reaction of 2-halo-arylamides and sulfur
powder,29 and intramolecular dehydrogenative cyclization.30
The major disadvantages of most of the above procedures include the thermal and moisture
sensitivities of the sulfenylating reagents and their high reactivity toward nucleophilic substrates
such as hydroxy and active methylene groups, as well as toward multiple bonds. These
considerations prevent the synthesis of N-acylsulfenamides with these reactive functionalities.
As a way to overcome these limitations, we designed a new method for the preparation of N-
acylsulfenamides from 5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinane-2-disulfanyl derivatives
1. The electrophilic properties of the disulfanyl derivatives 1 of phosphorodithioic acid have
been previously used to produce functionalized unsymmetrical molecules such as dialkyl
disulfanes,31 alkyl-aryl disulfanes,32 ‘bioresistant’ disulfanes,33 unsymmetrical disulfanes of L-
cysteine and L-cystine,34 and diaryl disulfanes.35 The disulfanyl derivatives 1 have also been
conveniently used for the preparation of α-sulfenylated carbonyl compounds,36 functionalized
phosphorothioates37 and symmetrical38 and unsymmetrical39 trisulfanes.
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Results and Discussion
The limitations of the known methods for preparing functionalized N-acylsulfenamides have
encouraged us to develop a new synthetic strategy. Our idea is based on the reaction of
electrophilic disulfanyl derivatives of phosphorodithioic acid 1 with a nucleophilic nitrogen-
centered anion generated from an amide or imide and sodium hydride (Scheme 1 and Table 1).
As the data in Table 1 demonstrate, the sulfenylation reaction of primary amides 2a-c and
phthalimide 2d with disulfanyl derivatives 1a and 1b proceeds efficiently in very high yield (75-
95%). This indicates that the presence of the unprotected hydroxy group did not greatly impact
the sulfenylation process. However, reactions of compound 1c (R1 = Ph) with benzamide 2a and
trimethylacetamide 2c provided N-acylsulfenamides 3i and 3j in 31% and 43% yield,
respectively. In these cases, the formation of N-acylsulfenamides 3i and 3j was hampered by the
formation of diphenyl disulfide (isolated in 58% and 50% yield, respectively). The presence of a
carboxylic acid ester group was not tolerated under the developed conditions. The reaction of
disulfanyl compound 1d with nicotinamide 2b and trimethylacetamide 2c produced
corresponding N-acylsulfenamides 3k and 3l in poor yield (12-20%). However, the starting
material 1d was consumed, most likely via side reactions, such as ester condensation and/or -
sulfenation,36 which are responsible for the low yields of N-acylsulfenamides 3k and 3l. The
formation of N-acylsulfenamides with an additional amino group was most challenging, as both
hydrogens from the primary amino group had to be replaced by protective groups to avoid
undesired sulfenylation. We selected compound 1e, in which the amino functionality was
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protected by two Boc groups. The reaction of disulfanyl derivative 1e with nicotinamide 2b and
trimethylacetamide 2c produced corresponding N-acylsulfenamides 3m and 3n in moderate
yields (43-64%). However, NMR data analysis for compounds 3m and 3n revealed the removal
of one Boc group from the protected amino group. The 2.4-fold excess of amide 2 that is
required for high conversion of the reaction also appears to be responsible for the removal of one
Boc group.
To demonstrate the scope and limitations of this new N-acylsulfenamide formation reaction, we
reacted secondary amides 2e–g with sulfenylating reagent 1a. The 2.4 equivalents of the nitrogen
nucleophile anion were generated by means of sodium hydride in tetrahydrofuran from amides
2e-g, respectively. Then, treatment with disulfane derivative 1a at room temperature for 16 hours
afforded unexpected products 4 and 5 (Scheme 2). The results are summarized in Table 2.
The reaction of secondary amides 2e-g with disulfanyl derivative 1a produced
didodecyldisulfane 4 and the disulfane of phosphorodithioic acid 5 in very high yields (Table 2,
entry 1-3). Moreover, acetanilide 2e, N-benzoylaniline 2f and N-methylbenzamide 2g were
recovered in 99, 97 and 96% yield, respectively. We also performed the reaction of compound 1a
with 20 mol% of 2g (Table 2, entry 4). We were able to isolate disulfane 4 (62%) and 5 (52%),
as well as starting materials 2g (95%) and 1a (34%). This indicates that the amide anion is able
to catalyze the formation of symmetrical disulfanes 4 and 5 from 1a. Detailed mechanistic
studies are in progress. Nevertheless, the secondary amides cannot be converted into
corresponding N-acylsulfenamides 3 by means of disulfanyl derivatives 1 under the developed
conditions.
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Conclusions
A convenient method has been developed for the preparation of functionalized N-
acylsulfenamides 3 bearing hydroxy, ethyl ester, or tert-butoxycarbonylamino groups. Reactions
of 1 with a variety of primary amides 2 in the presence of sodium hydride in tetrahydrofuran at
room temperature were generally complete within 16 h and gave functionalized N-
acylsulfenamides 3 in moderate or very good yields after purification. The simplicity and the
presence of additional functional groups make this method one of the most attractive approaches
for the preparation of functionalized N-acylsulfenamides.
Experimental
Benzamide, nicotinamide, trimethylacetamide, phthalimide, and NaH (60% in mineral oil) are
commercially available from Aldrich. 1-[(5,5-Dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-
yl)disulfanyl]dodecane (1a),37a 11-[(5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-
yl)disulfanyl]undecan-1-ol (1b),37a [(5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-
yl)disulfanyl]benzene (1c),35 ethyl 11-[(5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-
yl)disulfanyl]undecanoate (1d),24a 11-[(5,5-Dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-
yl)disulfanyl]-N,N-di-(tert-butoxycarbonyl)undecylamine (1e)40 were synthesized by described
procedures. THF was dried and distilled by standard procedures. Melting points are uncorrected.
NMR spectra were recorded on a Varian Gemini 500 MHz or 200 MHz spectrometer. The
residual solvent peak was used as internal reference (CDCl3: = 7.26 for 1H, = 77.0 for 13C); 31P
NMR used an external standard as reference (85% H3PO4: = 0). ESI-MS spectra were recorded
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on a Mariner PerSeptve Biosystem. Column chromatography was performed with silica gel 60
(230–400 mesh, Merck). Preparative TLC chromatography was performed with silica gel
Polygram SIL G/UV254 (Macherey-Nagel). Petroleum ether = PE.
Synthesis of N-acylsulfenamides (3)
General Procedure
A solution of carbonyl compound 2a–d (2.4 mmol) in anhyd THF (5 mL) was added dropwise to
a suspension of NaH (0.1 g, 2.5 mmol) in anhyd THF (15 mL) at r.t. under an N2 atmosphere.
When the evolution of H2 had ceased, a soln of 1 (1.0 mmol) in anhyd THF (5 mL) was added.
The mixture was stirred at r.t. for 16 h and evaporated under vacuum. The residue was dissolved
in EtOAc (50 mL), washed with sat. aq NH4Cl, dried (MgSO4), filtered, and concentrated. The
products were purified by column chromatography (Table 1). All experiments were performed in
1.0 mmol scale of 1. Additional characterization details are provided in the Supplemental
Materials.
N-(1-dodecylthio)benzamide (3a)
White solid, mp 43–46 oC; Rf = 0.3 (hexanes–CH2Cl2, 1:1); yield 264 mg (82%).
1H NMR (200 MHz; CDCl3):  = 0.89 (t, J = 6.4 Hz, 3H, CH3), 1.25–1.50 (m, 18H, CH2); 1.55–
1.75 (m, 2H, CH2-C-S), 2.86 (t, J = 7.3 Hz, 2H, CH2S), 6.90 (brs, 1H, NH), 7.40–7.60 (m, 3H,
Ar), 7.72–7.85 (m, 2H, Ar).
13C NMR (50 MHz, CDCl3):  = 14.0, 22.6, 27.8, 28.5, 28.6, 29.0, 29.1, 29.3, 29.4, 29.5, 31.8,
39.2, 127.4, 128.5, 131.9, 133.7, 169.5.
HRMS (ESI): m/z [M + H]+ calcd for C19H32NOS: 322.2205; found: 322.2221.
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N-(1-dodecylthio)nicotinamide (3b)
White solid, mp 53–55 oC; Rf = 0.28 (hexanes–CH2Cl2, 1:1); yield 287 mg (89%).
1H NMR (500 MHz; CDCl3):  = 0.86 (t, J = 6.8 Hz, 3H, CH3), 1.20–1.38 (m, 16H, CH2), 1.39–
1.45 (m, 2H, CH2), 1.62 (quint, J = 7.6 Hz, 2H, CH2-C-S), 2.86 (t, J = 7.6 Hz, 2H, CH2S), 7.42–
7.50 (m, 1H, Ar), 7.50 (brs, 1H, NH), 8.21 (d, J = 7.8 Hz, 1H, Ar), 8.76 (brs, 1H, Ar), 9.10 (brs,
1H, Ar).
13C NMR (50 MHz, CDCl3):  = 14.0, 22.6, 27.8, 28.5, 29.1, 29.2, 29.4, 29.5, 31.8, 38.7, 123.5,
129.7, 135.6, 148.3, 152.4, 168.2.
HRMS (ESI): m/z [M + H]+ calcd for C18H31N2OS: 323.2157; found: 323.2163.
N-(1-dodecylthio)trimethylacetamide (3c)
White solid, mp 40–42 oC; Rf = 0.3 (PE–CH2Cl2, 1:1); yield 242 mg (80%).
1H NMR (200 MHz; CDCl3):  = 0.87 (t, J = 6.4 Hz, 3H, CH3), 1.18–1.40 (m, CH2, 18H), 1.24
(s, 9H, tBu), 1.45-1.70 (m, 2H, CH2), 2.72 (t, J = 7.4 Hz, 2H, CH2S), 6.38 (brs, 1H, NH).
13C NMR (50 MHz, CDCl3):  = 14.1, 22.6, 27.6, 27.7, 28.6, 29.2, 29.3, 29.4, 29.5, 29.6, 31.9,
38.4, 39.7, 180.1.
HRMS (ESI): m/z [M + H]+ calcd for C17H36NOS: 302.2518; found: 302.2527.
N-(1-dodecylthio)phthalimide (3d)
White solid, mp 61–63 oC; hexanes–CH2Cl2, 1:1, then CHCl3; Rf = 0.25 (CHCl3); yield 327 mg
(94%).
1H NMR (200 MHz; CDCl3):  = 0.86 (t, J = 6.5 Hz, 3H, CH3), 1.10–1.50 (m, 18H, CH2); 1.50–
1.70 (m, 2H, CH2-C-S), 2.87 (t, J = 7.3 Hz, 2H, CH2S), 7.73–7.84 (m, 2H, Ar), 7.87–7.98 (m,
2H, Ar).
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13C NMR (50 MHz, CDCl3):  = 14.0, 22.6, 28.1, 28.4, 29.0, 29.2, 29.3, 29.4, 29.5, 31.8, 38.6,
123.8, 132.0, 134.5, 168.5.
HRMS (ESI): m/z [M + H]+ calcd for C20H30NO2S: 348.1997; found: 348.2004.
N-(11-hydroxy-1-undecylthio)benzamide (3e)
White solid, mp 46–48 oC; Rf = 0.27 (EtOAc–CH2Cl2, 1:6); yield 243 mg (75%).
1H NMR (200 MHz; CDCl3):  = 1.20–1.50 (m, 15H, OH, CH2), 1.50– 1.75 (m, 4H, CH2), 2.84
(t, J = 7.3 Hz, 2H, SCH2), 3.63 (t, J = 6.5 Hz, 2H, CH2O), 6.97 (brs, 1H, NH), 7.40–7.60 (m, 3H,
Ph), 7.75–7.86 (m, 2H, Ph).
13C NMR (50 MHz, CDCl3):  = 25.6, 27.7, 28.5, 29.1, 29.3, 29.3, 29.4, 32.6, 38.7, 62.9, 127.4,
128.5, 131.9, 133.7, 169.7.
HRMS (ESI): m/z [M + Na]+ calcd for C18H29NNaO2S: 346.1817; found: 346.1811.
N-(11-hydroxy-1-undecylthio)nicotinamide (3f)
White solid, mp 59–61 oC; Rf = 0.3 (EtOAc–CH2Cl2, 1:2); yield 308 mg (95%).
1H NMR (200 MHz; CDCl3):  = 1.20–1.50 (m, 14H, CH2), 1.50–1.75 (m, 4H, CH2), 2.87 (t, J =
7.3 Hz, 2H, CH2S), 3.37 (brs, 1H, OH), 3.65 (t, J = 6.5 Hz, 2H, CH2O), 7.46–7.60 (m, 1H, Ar),
7.77 (brs, 1H, NH), 8.26-8.40 (m, 1H, Ar), 8.72-8.85 (m, 1H, Ar) 9.17 (brs, 1H, Ar).
13C NMR (50 MHz, CDCl3):  = 25.6, 27.7, 28.4, 29.0, 29.2, 29.3, 32.6, 38.6, 62.7, 123.6, 129.8,
136.1, 148.1, 152.1, 168.1.
HRMS (ESI): m/z [M + H]+ calcd for C17H29N2O2S: 325.1950; found: 325.1961.
N-(11-hydroxy-1-undecylthio)trimethylacatamide (3g)
Waxy solid, mp 39–41 oC; Rf = 0.3 (EtOAc–CH2Cl2, 1:6); 246 mg (81%).
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1H NMR (200 MHz; CDCl3):  = 1.22 (s, 9H, tBu), 1.20–1.48 (m, 15H, OH, CH2), 1.48-1.66 (m,
4H, CH2), 2.72 (t, J = 7.2 Hz, 2H, SCH2), 3.64 (t, J = 6.5 Hz, 2H, CH2O); 6.39 (brs, 1H, NH).
13C NMR (50 MHz, CDCl3):  = 25.6, 27.4, 27.5, 28.4, 29.0, 29.2, 29.4, 32.6, 38.2, 39.6, 62.7,
180.3.
HRMS (ESI): m/z [M + Na]+ calcd for C16H33NNaO2S: 326.2130; found: 326.2143.
N-(11-hydroxy-1-undecylthio)phthalimide (3h)
White solid, mp 47–49 oC; Rf = 0.28 (EtOAc–CH2Cl2, 1:3); yield 329 mg (94%).
1H NMR (200 MHz; CDCl3):  = 1.20–1.50 (m, 14H, CH2), 1.50–1.75 (m, 4H, CH2), 2.87 (t, J =
7.3 Hz, 2H, CH2S), 3.37 (brs, 1H, OH), 3.65 (t, J = 6.5 Hz, 2H, CH2O), 7.73–7.84 (m, 2H, Ar),
7.87–7.98 (m, 2H, Ar).
13C NMR (50 MHz, CDCl3):  = 25.6, 27.7, 28.4, 29.0, 29.1, 29.2, 29.3, 32.6, 38.6, 62.7, 123.8,
132.0, 134.5, 168.5.
HRMS (ESI): m/z [M + Na]+ calcd for C19H27NNaO3S: 372.1609; found: 372.1598.
N-(phenylthio)benzamide (3i)
Yellowish solid, mp 113–115 oC; Rf = 0.30 (CH2Cl2); yield 71 mg (31%).
1H NMR (200 MHz; CDCl3):  = 7.15 – 7.65 (m, 9H, NH, Ar), 7.86 (d, J = 8.2 Hz, 2H, Ar).
13C NMR (200 MHz, CDCl3):  = 125,55; 126.8, 127.6, 128.7, 132.4, 134.1, 139.0, 170.1.
HRMS (ESI): m/z [M + H]+ calcd for C13H12NOS: 230.0640; found: 230.0644.
N-(phenylothio)trimethylacetamide (3j)
Yellowish solid, mp 98–100 oC; Rf = 0.35 (CH2Cl2); yield 90 mg (43%).
1H NMR (200 MHz; CDCl3): = 1.30 (s, 9H, tBu), 6.86 (brs, 1H, NH), 7.10-7.40 (m, 5H, Ph).
13C NMR (50 MHz, CDCl3):  = 27.7, 39.9, 124.9, 126.6, 128.9, 139.0, 179.8.
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HRMS (ESI): m/z [M + H]+ calcd for C11H16NOS: 210.0953; found: 210.0949.
N-(10-Ethoxycarbonyl-1-decylthio)nicotinamide (3k)
Yellowish oil; Rf = 0.3 (EtOAc–CH2Cl2, 2:1); yield 44 mg (12%).
1H NMR (200 MHz; CDCl3): = 1.05 – 1.50 (m, 15H, CH2, CH3), 1.50-1.80 (m, 4H, CH2), 2.30
(t, J = 7.0 Hz, 2H, CH2CO), 2.84 (t, J = 7.4 Hz, 2H, CH2S), 4.12 (q, J = 7.2 Hz, 2H, OCH2),
7.30-7.50 (m, 1H, Ar), 7.51 (brs, 1H, NH), 8.10-8.20 (m, 1H, Ar), 8.70-8.80 (m, 1H, Ar), 9.00-
9.10 (m, 1H, Ar).
13C NMR (50 MHz, CDCl3): = 14.0, 23.4, 25.2, 27.3, 27.8, 29.1, 29.2, 29.3, 30.5, 32.3, 38.7,
60.1, 123.8, 128.9, 135.9, 148.4, 152.5, 169.8, 172.1.
HRMS (ESI): m/z [M + H]+ calcd for C19H31N2O3S: 367.2055; found: 367.2064.
N-(10-Ethoxycarbonyl-1-decylthio)trimethylacetamide (3l)
Yellowish oil; Rf = 0.3 (EtOAc–CH2Cl2, 1:25); yield 69 mg (20%).
1H NMR (200 MHz; CDCl3): = 1.05 – 1.40 (m, 15H, CH2, CH3), 1.50 (s, 9H, tBu), 1.55 – 1.80
(m, 4H, CH2), 2.30 (t, J = 7.0 Hz, 2H, CH2CO), 2.83 (t, J = 7.4 Hz, 2H, CH2S), 4.11 (q, J = 7.2
Hz, 2H, OCH2), 7.00 (brs, 1H, NH).
13C NMR (50 MHz, CDCl3): = 14.0, 23.4, 27.3, 27.8, 29.1, 29.2, 29.3, 29.5, 30.5, 32.3, 38.6,
39.7, 60.2, 172.1, 180.1.
HRMS (ESI): m/z [M + Na]+ calcd for C18H35NNaO3S: 368.2235; found: 368.2228.
N-(11-(N-tert-butoxycarbonylamino)-1-undecylthio)nicotinamide (3m)
Yellowish oil; EtOAc–CH2Cl2, 1:5 then EtOAc–CH2Cl2, 1:1;Rf = 0.27 (EtOAc–CH2Cl2, 1:1);
yield 182 mg (43%).
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1H NMR (200 MHz; CDCl3): = 1.10 – 1.40 (m, 14H, CH2); 1.44 (s, 9H, Boc), 1.50-1.80 (m,
4H, CH2), 2.88 (t, J = 7.2 Hz, 2H, SCH2), 3.09 (q, J = 6.3 Hz, 2H, CH2N), 4.50 (brs, 1H,
NHBoc); 7.30-7.55 (m, 2H, S-NH, Ar), 8.23 (d, J = 7.9 Hz, 1H, Ar), 8.78 (brs, 1H, Ar), 9.11
(brs, 1H, Ar).
13C NMR (50 MHz, CDCl3): = 23.4, 27.3, 27.8, 28.4, 28.6, 29.2, 29.3, 29.5, 30.5, 32.3, 38.7,
41.3, 70.6, 123.7, 128.8, 135.8, 148.3, 152.4, 156.3, 169.4.
HRMS (ESI): m/z [M + H]+ calcd for C22H38N3O3S: 424.2634; found: 424.2642.
N-(11-(N-tert-butoxycarbonylamino)-1-undecylthio)trimethylacetamide (3n)
Yellowish oil; Rf = 0.25 (PE–CH2Cl2, 1:2); yield 258 mg (64%).
1H NMR (200 MHz; CDCl3): = 1.10 – 1.40 (m, 14H, CH2); 1.44 (s, 9H, tBu), 1.50 (s, 9H,
Boc), 1.50-1.80 (m, 4H, CH2), 2.88 (t, J = 7.2 Hz, 2H, S-CH2), 3.00-3.20 (m, 2H, CH2N), 4.50
(brs, 1H, NHBoc); 7.0 (brs, 1H, S-NH).
13C NMR (50 MHz, CDCl3): = 23.4, 27.3, 27.8, 28.4, 28.6, 29.1, 29.2, 29.3, 29.5, 30.5, 32.3,
38.6, 39.7, 41.2, 70.6, 156.3, 180.1.
HRMS (ESI): m/z [M + Na]+ calcd for C21H42N2NaO3S: 425.2814; found: 425.2825.
Acknowledgment
We gratefully acknowledge the National Science Centre for financial support (grant no.
2013/09/B/ST5/01261).
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Table 1 Synthesis of N-acylsulfenamides 3 a
R1 = (CH2)11Me R1 = (CH2)11OH R1 = Ph R1 = (CH2)10CO2Et R1 = (CH2)11N(R3)Boc
R3 = Boc 1e
1a
1b
1c
1d
R2 = Ph 2a
R2 = 3-pyridyl 2b 3b (89)
R2 = t-Bu 2c
3a (82)
3e (75)
3f (95)
3g (81)
3h (94)
3i (31)b
-
-
-
3k (12)
R3 = H 3m, (43)
R3 = H 3n, (64)
3c (80)
3j (43)c 3l (20)
Phthalimide 2d
3d (94)
-
-
-
b
a The yield (%) of the isolated product is reported in parentheses. The formation of (PhS)2 was observed (58%).
c The formation of (PhS)2 was observed (50%).
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Table 2 Reaction of secondary amides with disulfane 1a
Entry
R1
R2
4 yield (%)a
5 yield (%)a
2
1
Me
Ph
90
78
2e
2
3
Ph
Ph
Ph
95
97
82
81
2f
Me
2g
4b
Ph
Me
62
52
2g
a The yield of the isolated product. b The 20 mol% of 2g was used.
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Scheme 1
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Scheme 2
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