S-Thioacyldithiophosphates in the synthesis of thiohydroxamic acids and O-thioacylhydroxylamines

Article abstract of DOI:10.1055/s-2002-31957

S-Thioacyldithiophosphates proved to be excellent thioacylating agents. They are easily available from carboxylic acids. Due to their low reactivity towards oxygen nucleophiles and high reactivity towards nitrogen ones they found application in the synthe

Full text of DOI:10.1055/s-2002-31957

PAPER
1047
S-Thioacyldithiophosphates in the Synthesis of Thiohydroxamic Acids and
O-Thioacylhydroxylamines
S
ynthesis of Th
e
iohydroxam
s
ic
A
cids
z
and
O
-
Thio
e
acylhydrox
k
ylamines Doszczak,* Janusz Rachon*
Department of Organic Chemistry, Faculty of Chemistry, Technical University of Gda sk, ul. Narutowicza 11/12, 80-952 Gda sk; Poland
E-mail: Rachon@chem.pg.gda.pl
Received 15 February 2002
acid transformation to thiohydroxamic acids based on O-
Abstract: S-Thioacyldithiophosphates proved to be excellent thio-
acetylation of the hydroxamic acid, followed by thion-
ation of the O-acetyl derivative with Lawessons’ reagent,
followed by deprotection of the hydroxy group. However,
acylating agents. They are easily available from carboxylic acids.
Due to their low reactivity towards oxygen nucleophiles and high
reactivity towards nitrogen ones they found application in the syn-
thesis of thiohydroxamic acids directly from hydroxylamines with- this multi-step procedure does not guarantee high yields
out protection on the hydroxy group. However, in cases of steric
(10–50%).
hindrance O-thioacyl hydroxylamines are formed and can be isolat-
ed with high yield.
A second approach to the synthesis of thioacyl derivatives
is based on preparing an active derivative of thiocarboxy-
Key words: thiohydroxamic acids, hydroxylamines, acylations,
lic acid and the reaction of nucleophiles with the thus ob-
phosphates, chemoselectivity
tained thioacylating agent.2,9–13 However, there is a
shortage of stable and easily available thioacylating re-
agents (especially because most of them can only be pre-
Thiohydroxamic acids (being thioacyl derivatives of hy-
pared from dithiocarboxylic acids, which scarcely are
droxylamines) are a class of compounds containing sig-
commercial reagents and are hard to obtain or to handle in
nificantly different neighboring atoms, ie nitrogen,
pure form). In the chemical literature many methods of
oxygen, sulfur, and a carbon atom in sp2 hybridization.
thioacylation of hydroxylamines have been described,
The specific bond system causes thiohydroxamic acids to
however most of them require protection of the hydroxy
be excellent double dentate ligands capable of complex-
group in hydroxylamine. Consequently overall yields
ing cations of different metals. These bioligands are being
were low.1
used in nature for transport of numerous cations. They are
also used in analytical chemistry for the quantitative de-
We have recently described14 a convenient method for the
conversion of carboxylic acids into thioacyl dithiophos-
phates 6, excellent thioacylating reagents (see Scheme 1).
The method is based on isomerisation of acyl dithophos-
phates 3 to O-thioacyl monothiophosphates 4. The mix-
ture of isomers 3 and 4 treated with dithiophosphoric acid
yields S-thioacyl dithiophosphates 6 exclusively. These
reagents are easy to obtain, and they do not have to be iso-
lated prior to thioacylation, although in many cases isola-
tion is simple and provides stable crystalline reagents. The
title compounds react much faster with nitrogen or sulfur
nucleophiles than with oxygen ones. This can be applied
to direct synthesis of hydroxythioamides and hydroxy-
dithioesters. Here we would like to present the application
of our method to the synthesis of thiohydroxamic acids by
direct thioacylation of N-alkylhydroxylamines (without
protection of hydroxy group).
termination of numerous metals. Moreover, in the past 25
years O-acyl derivatives of thiohydroxamic acids have
found wide application as a source of efficiently generated
carbon, sulfur, nitrogen, or phosphorus radicals. The de-
rivatives of thiohydroxamic acids and their metal com-
plexes are widespread in nature and already have found
application in medicine and technology.1
Thioacyl derivatives might be obtained using two main
approaches. One is a step by step method based on the
synthesis of acyl derivatives and their subsequent thion-
ation with thionating agents such as diphosphorus deca-
sulfide or Lawessons’ reagent.2–4 However, although
hydroxamic acids (being acyl derivatives of hydroxy-
lamines) are easily available, their direct sulfuration with
diphosphorus decasulfide yields complicated mixture of
products, whereas the expected thiohydroxamic acids are
present in only small quantities.5,6 Moreover, recently
Przychodzen7 has shown that in the reaction of N-alkylhy-
droxamic acids with Lawessons’ Reagent, thiohydroxam-
ic acids, amides, and thioamides are formed. Hence, direct
formation of hydroxamic acids cannot be classified as a
good synthetic method for thiohydroxamic acids. On the
other hand Rzepa8 et al. proposed a method of hydroxamic
Studying the scope and limitations of the new thioacyla-
tion method, we treated S-thioacyl dithiophosphates 6
with N-alkylhydroxylamines in the presence of triethy-
lamine in chloroform (Scheme 2). From such a reaction
mixture we isolated N-alkyl thiohydroxamic acids with
moderate to very good yields. The results of this set of ex-
periments are collected in Table 1.
Our method of thioacylation is very simple: thioacyl
dithiophosphate is added to the solution or suspension of
a nucleophile with one equivalent of a base (e.g. triethy-
lamine). In most cases the reaction is finished immediate-
Synthesis 2002, No. 8, 04 06 2002. Article Identifier:
1437-210X,E;2002,0,08,1047,1052,ftx,en;P00502SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1048
L. Doszczak, J. Rachon
PAPER
Scheme 1 Conversion of carboxylic acids into thioacylating reagents and their reaction with nucleophiles.
facilitates obtaining the crude product free of dithiophos-
phates and other strongly polar compounds.
As one can see from the data collected in Table 1, the
method is efficient, and sterically hindered N-tertbutylhy-
droxylamine and N-phenetylhydroxylamine are also ef-
fectively thioacylated (Table 1, entries 10d,g,h,k,l).
Moreover, S-thiopivaloyl dithiophosphate (6a) as well as
bifunctional 5-methoxycarbonylthiopentanoyl dithio-
phosphate (6d) appeared to be good thioacylating agents
(Table 1, entries 10a,i–l).
Scheme 2 Reaction of S-thioacyl dithiophosphates 6 with N-alkyl-
Table 1 Synthesis of Thiohydroxamic Acids 10
However, we found that S-thiopivaloyl dithiophosphate
(6a), as well as thiobenzoyl dithiophosphate 6b treated
with hydroxylamines possessing a bulky substituent or
two substituents on the nitrogen atom (N-tertbutylhydrox-
ylamine, N-phenethylhydroxylamine, N-hydroxylmor-
pholine, N-isopropylbenzhydroxamic acid) in the
presence of triethylamine yield O-thioacylhydroxy-
lamines 11 efficiently (Scheme 3, Table 2).
Entry
10a
10b
10c
10d
10e
10f
R
R
Yield (%)
71
t-Bu
Me
Ph
Me
68
Ph
i-Pr
73
Ph
CH(Me)Ph
Me
72
Pr
83
Pr
i-Pr
80
10g
10h
10i
Pr
CH(Me)Ph
t-Bu
77
Pr
57
MeOCO(CH2)4
MeOCO(CH2)4
MeOCO(CH2)4
MeOCO(CH2)4
Me
91
10j
i-Pr
91
Scheme 3 Reaction of S-thioacyl dithiophosphates 6 with N-alkyl-
hydroxylamines 9 possessing bulky or two substituents
10k
10l
CH(Me)Ph
t-Bu
94
Table 2 Synthesis of O-Thioacylhydroxylamines 11
82
Entry
11m
11n
11o
R
R
R
H
H
Yield (%)
t-Bu
t-Bu
t-Bu
t-Bu
Ph
t-Bu
96
95
71
95a
74
ly. Subsequent washing with water, drying and solvent
evaporation yields crude product 10.
CH(Me)Ph
CH2CH2OCH2CH2
i-Pr
It is important to mention that formation of water-soluble
trialkylammonium phosphates 8 during thioacylation with
thioacyl dithiophosphates is generally an advantage, be-
cause it simplifies isolation of the product. However,
when obtaining water-soluble products it can be trouble-
some to isolate the product by water extraction. Then fil-
tering the reaction mixture through a short pad of silica gel
11p
11r
PhCO
H
t-Bu
a DBU was applied as a base instead of Et3N; reaction time 24 h
Synthesis 2002, No. 8, 1047–1052 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Thiohydroxamic Acids and O-Thioacylhydroxylamines
1049
1H NMR (CDCl3): = 7.97 (2 H, d, J = 7.8), 7.64 (1 H, t, J = 7.3),
7.49 (2 H, t, J = 7.3), 4.38 (2 H, dd, JH–H = 10.7, JP–H = 3.9), 4.02 (2
H, dd, JH–H = 10.7, JP–H = 25.9), 1.38 (3 H, s), 0.93 (3 H, s).
13C NMR (CDCl3): = 185.97, 136.61, 134.91, 129.18, 128.62,
79.1 (d, JP–C = 9.9), 32.73 (d, JP–C = 7.6), 22.79, 20.99.
31P NMR (CDCl3): = 69.1.
HRMS: m/z Calcd for C12H15O3PS2 (M+): 302.02002. Found:
Hydroxylamines are known as ambident nucleophiles but
the results of our previous experiments showed very poor
reactivity of thioacyl dithiophosphates 6 towards oxygen
nucleophiles. Reversed reactivity observed in this set of
experiments can be explained by supernucleophilic prop-
erties of oxygen in hydroxylamines comparing to com-
mon alcohols as well as the lower thermodynamic
stability of the N-thioacylated product due to steric hin-
drance compared to the O-thioacylated product (see also
base-catalyzed isomerization of sterically hindered hy-
droxamic acids to O-acyl hydroxylamines15,16 and papers
of Lobo17–21 et al. on N- and O-acylation of hydroxy-
lamines with different acylating agents).
302.01975.
Butyryl 2-(5,5-Dimethyl-2-thiono-1,3,2-dioxaphosphorinanyl)
Sulfide (3c)
Yield: 92%; mp 98–99 ºC.
IR (KBr): 1744 (C=O), 1043 (POC), 988 (POC), 678 (P=S) cm–1.
1H NMR (CDCl3): = 4.24 (2 H, dd, JH–H = 10.3, JP–H = 3.9), 3.95
(2 H, dd, JH–H = 10.3, JP–H = 25.4), 2.72 (2 H, dt, JH–H = 7.3,
In conclusion we have elaborated a very simple strategy
of thioacylation with the use of thioacyl dithiophosphates.
The thioacylation of hydroxylamines generally yields
thiohydroxamic acids. However, in cases of higher steric
hindrance or N,N-disubstituted hydroxylamines, O-thioa-
cyl hydroxylamines are formed and can be isolated with
high yield. It is important to mention that both kinds of
products are hardly available using other methods. More-
over, to our best knowledge, O-thioacyl hydroxylamines
have not yet been described in chemical literature.
J
P–H = 1.9), 1.71 (2 H, tq, J1, J2 = 7.3), 1.32 (3 H, s), 0.97 (3 H, t,
JH–H = 7.3), 0.91 (3 H, s).
13C NMR (CDCl3): = 192.72 (d, JP–C = 3.5), 78.81 (d, JP–C = 9.6),
48.72 (d, JP–C = 2.5), 32.69 (d, JP–C = 7.1), 22.66, 20.98, 18.78,
13.55.
31P NMR (CDCl3): = 70.1.
HRMS: m/z Calcd for C9H17O3PS2 (M+): 268.03568. Found:
268.03562.
5-Carbomethoxypentanoyl 2-(5,5-Dimethyl-2-thiono-1,3,2-di-
oxaphosphorinanyl) Sulfide (3d)
Yield: 100%; mp ~ 25 ºC.
IR (KBr): 1734 (C=O), 1046 (POC), 995 (POC), 679 (P=S) cm–1.
1H NMR (CDCl3): = 4.25 (2 H, dd, JH–H = 11, JP–H = 4.8), 3.97 (2
H, dd, JH–H = 11, JP–H = 25.3), 2.79 (2 H, dt, J1 = 7, J2 = 1.5), 3.67
(3 H, s), 2.34 (2 H, t, J = 7), 1.7 (4 H, m), 1.33 (3 H, s), 0.92 (3 H, s).
13C NMR (CDCl3): = 192.2 (d, JP–C = 3.4), 173.47, 78.69 (d,
JP–C = 10.3), 51.64, 46.26 (d, JP–C = 3.4), 33.55, 32.52 (d, JP–
C = 6.8), 24.35, 23.99, 22.48, 20.79.
All reactions were carried out under an argon atmosphere in anhyd
solvents (benzene and THF dried over benzophenone ketyl, CH2Cl2
dried over CaH2, CHCl3 dried over P2O5 hexane and cyclohexane
dried over potassium). Chromatography was carried out on Silica
Gel 60 (0.15–0.3 mm) Machery Nagel NMR was preformed on
Vaarian Gemini 500 MHz (all J values are given in Hz); IR on a
Bruker IFS66 (liquids from film and solids from KBr tablet); MS
were acquired on a MASPEC II system [II32/99D9] in EI mode and
if necessary liquid SIMS technique was applied.
31P NMR (CDCl3): = 69.2.
HRMS (LSIMS): m/z Calcd for C12H22O5PS2 (M + H+): 341.06463.
Acyl 2-(5,5-Dimethyl-2-thiono-1,3,2-dioxaphosphorinanyl) Sul-
fides 3; General Procedure
AcCl (3 mmol) was added to a solution of 5,5-dimethyl-2-thiolo-2-
thiono-1,3,2-dioxaphosphorinane (2) (0.594 g, 3 mmol) in benzene
(10 mL). Subsequently, Et3N (0.303 g, 3 mmol) or pyridine (0.237
g, 3 mmol) was added dropwise to the ice-cold solution. Immediate-
ly Et3N HCl precipitated. After 15 min the reaction mixture was fil-
tered through a short pad of silica gel. After solvent evaporation
pure product was obtained.
Found: 341.06308.
Thioacyl 2-(5,5-Dimethyl-2-thiono-1,3,2-dioxaphosphorinanyl)
Sulfides 6; Typical Procedure
The solution of acyl 2-(5,5-dimethyl-2-thiono-1,3,2-dioxaphospho-
rinanyl) sulphide 3 (5 mmol) and 5,5-dimethyl-2-thiolo-2-thiono-
1,3,2-dioxaphosphorinane (2) (1.98 g, 10 mmol) in benzene
(35 mL) was heated under reflux for 2–4 h (until the starting mate-
rial disappeared completely). Subsequently phosphoric thioacids
were removed by washing with aq Na2CO3 and then H2O. Next, the
organic layer was dried (MgSO4) and the solvent was evaporated.
The crude product was used for thioacylation without further puri-
fication, or if necessary was purified by means of silica gel chroma-
tography or crystallization.
Pivaloyl 2-(5,5-Dimethyl-2-thiono-1,3,2-dioxaphosphorinanyl)
Sulfide (3a)
Yield: 96%; mp 112–113 ºC.
IR (KBr): 1703 (C=O), 1046 (POC), 997 (POC), 686 (P=S) cm–1.
1H NMR (CDCl3): = 4.23 (2 H, dd, JH–H = 11, JP–H = 4.8), 3.95 (2
H, dd, JH–H = 11, JP–H = 25.3), 1.31 (3 H, s), 1.26 (9 H, s), 0.91 (3 H,
s).
Thiopivaloyl 2-(5,5-Dimethyl-2-thiono-1,3,2-dioxaphosphor-
inanyl) Sulfide (6a)
Reaction time: 4 h. Before washing with aq NaHCO3, the reaction
mixture was diluted with CHCl3, because the product started to pre-
cipitate. Crystallization from benzene.
13C NMR (CDCl3): = 199.7, 78.77 (d, JP–C = 9.9), 49.45, 32.69 (d,
JP–C = 7.4), 27.23, 22.7, 21.03.
31P NMR (CDCl3): = 70.8.
HRMS: m/z Calcd for C10H19O3PS2: 282.05132. Found: 282.05046.
Yield: 95%; mp 153–154 ºC.
IR (KBr): 1209 (C=S), 1045 (POC), 992 (POC), 678 (P=S) cm–1.
1H NMR (CDCl3): = 4.19 (2 H, d, JH–H = 10.7, JP–H = 3.9), 3.94 (2
H, dd, JH–H = 10.7, JP–H = 25.9), 1.45 (9 H, s), 1.34 (3 H, s), 0.89 (3
H, s).
Benzoyl 2-(5,5-Dimethyl-2-thiono-1,3,2-dioxaphosphorinanyl)
Sulfide (3b)
Yield: 98%; mp 114–115 ºC.
IR (KBr): 1679 (C=O), 1591, 1579, 1474, 1447 (C=CAr), 1043
(POC), 985 (POC), 668 (P=S) cm–1.
Synthesis 2002, No. 8, 1047–1052 ISSN 0039-7881 © Thieme Stuttgart · New York

1050
L. Doszczak, J. Rachon
PAPER
13C NMR (CDCl3):
P150C = 10.1), 32.61 (d, JP–C = 7.1), 31.29, 22.62 (d, JP–C = 4.2),
20.99.
= 241.86 (d, JP–C = 4.2), 78.67 (d,
N-(1-Phenylethyl)thiobenzhydroxamic Acid (10d)
Extraction.
J
N-Methyl-N-thiobutyrylhydroxylamine (10e)
31P NMR (CDCl3): = 70.7.
HRMS: m/z Calcd for C10H19O2PS3 (M+): 298.02853. Found:
298.02848.
N-Methylhydroxylamine hydrochloride was used and crude thio-
butyryl 2-(5,5-dimethyl-2-thiono-1,3,2-dioxaphosphorinanyl) sulf-
ide (6c); eluent: benzene–hexane, 1:1.
Thiobenzoyl 2-(5,5-Dimethyl-2-thiono-1,3,2-dioxaphosphorin-
anyl) Sulfide (6b)
Reaction time: 2 h; eluent: benzene; yield 94%; mp 95–97 ºC.
N-Isopropyl-N-thiobutyrylhydroxylamine (10f)
N-Isopropylhydroxylamine oxalate was used and crude thiobutyryl
2-(5,5-dimethyl-2-thiono-1,3,2-dioxaphosphorinanyl) sulfide (6c);
extraction.
IR (KBr): 1181 (C=S), 1587, 1479, 1442 (C=CAr), 1042 (POC), 985
(POC), 678 (P=S) cm–1.
N-(1-Phenylethyl)-N-thiobutyrylhydroxylamine (10g)
Crude thiobutyryl 2-(5,5-dimethyl-2-thiono-1,3,2-dioxaphosphor-
inanyl) sulfide (6c) was used; eluent: benzene–hexane, 1:2.
1H NMR (CDCl3): = 8.04 (2 H, d, J = 8.3), 7.59 (1 H, t, J = 7.8),
7.4 (2 H, t, J = 7.8), 4.29 (2 H, dd, JH–H = 10.7, JP–H = 3.4), 3.98 (2
H, dd, JH–H = 10.7, JP–H = 25.9), 1.37 (3 H, s), 0.9 (3 H, s).
13C NMR (CDCl3): = 219.44, 145.56 (d, JP–C = 5.5), 133.6,
128.73, 127.32, 78.91 (d, JP–C = 9.6), 32.65 (d, JP–C = 7.3), 22.64,
20.96.
N-tert-Butyl-N-thiobutyrylhydroxylamine (10h)
Crude thiobutyryl 2-(5,5-dimethyl-2-thiono-1,3,2-dioxaphosphor-
inanyl) sulfide (6c) was used; extraction.
31P NMR (CDCl3): = 68.6.
HRMS: m/z Calcd for C12H15O2PS3 (M+): 317.99718. Found:
N-(5-Carbomethoxythiopentanoyl)-N-methylhydroxylamine
(10i)
N-Methylhydroxylamine hydrochloride was used and crude 5-
carbomethoxythiopentanoyl 2-(5,5-dimethyl-2-thiono-1,3,2-diox-
aphosphorinanyl) sulfide (6d); eluent: CH2Cl2.
317.99997.
Thioacylation of Hydroxylamines with Thioacyl 2-(5,5-Dime-
thyl-2-thiono-1,3,2-dioxaphosphorinanyl) Sulfides (6); General
Procedure
N-(5-Carbomethoxythiopentanoyl)-N-isopropylhydroxy-
lamine (10j)
N-Isopropylhydroxylamine oxalate was used and crude 5-carb-
To the solution of hydroxylamine (or suspension of hydroxylamine
hydrochloride or oxalate) (1 mmol) in CHCl3 (2 mL), Et3N (1, 2 or
3 mmol, respectively) was added. Next, the solution of thioacyl 2-
(5,5-dimethyl-2-thiono-1,3,2-dioxaphosphorinanyl) sulfide (1
mmol) in CHCl3 (4 mL) was added dropwise. [If the thioacyl dithio-
phosphate was crude (after only washing with aq NaHCO3), then a
25% excess was used.] After 15 min, the reaction mixture was fil-
tered through a short pad of silica gel. After solvent removal residue
was purified by means of either:
omethoxythiopentanoyl
2-(5,5-dimethyl-2-thiono-1,3,2-dioxa-
phosphorinanyl) sulfide (6d); eluent: CH2Cl2.
N-(1-Phenylethyl)-N-(5-carbomethoxythiopentanoyl)hydroxy-
lamine (10k)
Crude 5-carbomethoxythiopentanoyl 2-(5,5-dimethyl-2-thiono-
1,3,2-dioxaphosphorinanyl) sulfide (6d) was used; eluent: CH2Cl2.
1) chromatography; or
N-tert-Butyl-N-(5-carbomethoxythiopentanoyl)hydroxylamine
(10l)
Crude 5-carbomethoxythiopentanoyl 2-(5,5-dimethyl-2-thiono-
1,3,2-dioxaphosphorinanyl) sulfide (6d) was used; eluent: CH2Cl2.
2) extraction (only for thiohydroxamic acids): the residue was dilut-
ed with CHCl3 and extracted with 1 M aq NaOH. Next the water lay-
er was acidified with 6 M aq HCl and extracted with CHCl3. The
resulting organic layer was dried (MgSO4). Solvent evaporation
yielded pure product.
N-tert-Butyl-O-thiopivaloylhydroxylamine (11n)
For chromatography of thiohydroxamic acids, low metal content
silica gel is beneficial. Thus, silica gel was washed with aq sodium
EDTA, MeOH and dried on a rotary evaporator.
Eluent: CHCl3.
N-(1-Phenylethyl)-O-thiopivaloylhydroxylamine (11o)
Eluent: CHCl3.
NMR, MS and IR data for N-thioacyl and O-thioacyl hydroxy-
lamines 10, 11 are collected in Table 3.
O-Thiopivaloyl-N-hydroxymorpholine (11p)
Eluent: CHCl3.
N-Methyl-N-thiopivaloylhydroxamic Acid (10a)
N-Methylhydroxylamine hydrochloride was used; instead of
CHCl3, CH2Cl2 was the solvent; eluent: CHCl3.
N-Benzoyl-N-isopropyl-O-thiopivaloylhydroxylamine (11r)
Instead of Et3N, 1,8-diazabicyclo[5.4.0]undec-7-ene was used; the
reaction was carried out in darkness (reaction flask covered tightly
with aluminum foil) due to the photochemical instability of the
product; reaction time: 24 h; eluent: benzene.
N-Methylthiobenzhydroxamic Acid (10b)
N-Methylhydroxylamine hydrochloride was used; eluent:
t-BuOMe–hexane, 10:3.
N-tert-Butyl-O-thiobenzoylhydroxylamine (11s)
Eluent: benzene–cyclohexane, 1:1.
N-Isopropylothiobenzhydroxamic Acid (10c)
N-Isopropylhydroxylamine oxalate was used; eluent: benzene.
Synthesis 2002, No. 8, 1047–1052 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Thiohydroxamic Acids and O-Thioacylhydroxylamines
1051
Table 3 Analytical Data for Compounds 10, 11
Entry
1H NMR (CDCl3, 500 MHz)
, J (Hz)
13C NMR (CDCl3,
125 MHz)
HRMS (EI),
M observed
(calculated)
Molecular
Formula
IR (NaCl, film)
(cm–1)
10aa
11.39 (1 H, s), 3.72 (3 H, s),
1.38 (9 H, s)
192.72, 41.74, 40.22,
30.45
147.07199
(147.07179)
C6H13NOS
3298 (OH), 2963,
2874 (CH), 1221
(C=S)
10b
10c
10d
11 (1 H, br s), 7 (5 H, m), 3.4 (3
H, s)22
9.75 (1 H, s), 6.9 (5 H, s), 4.15
(1 H, m), 1.2 (6 H, d, J = 6)7
10.95 (1 H, br s), 7.39 (10 H,
m), 5.43 (1 H, q, J = 6.9), 1.77 130.05, 128.91, 128.53,
(3 H, d, J = 6.9)
182.35, 138.26, 138.45,
257.08752
(257.08744)
C15H15NOS
C5H11NOS
C7H15NOS
C12H17NOS
3334 (OH), 3030,
2983, 2937 (CH),
1205 (C=S)
126.91, 126.88, 62.26,
18.86
10e
10f
10g
10.82 (1 H, s), 3.56 (3 H, s),
184.45, 40.74, 38.53,
133.05652
(133.05614)
3280 (OH), 2965,
2934, 2874 (CH),
1214 (C=S)
2.67 (2 H, t, J = 7.8), 1.78 (2 H, 22.27, 13.82
tq, J1 = J2 = 7.8), 0.97 (3 H, t,
J = 7.8),
10.75 (1 H, br s), 4.56 (1 H,
sept, J = 6.5), 2.68 (2 H, m),
1.69 (2 H, m), 1.36 (6 H, d,
J = 6.5), 0.96 (3 H, t, J = 7.7)
182.59, 54.14, 40.85,
22.88, 20.42, 14.13
161.08715
(161.08744)
3271 (OH), 2967,
2936, 2874 (CH),
1211 (C=S)
11.7 (1 H, br s), 7.15 (5 H, m), 184.4, 138.7, 129.1, 126.6, 223.10398
5.03 (1 H, q, J = 7.3) 2.4 (2 H, 60.9, 40.7, 22.7, 19.5, 14.0 (223.10309)
m), 1.55 (5 H, m), 0.67 (3 H, t,
3278 (OH), 2965,
2932, 2873 (CH),
1210 (C=S)
J = 7.3)
10h
10i
11.36 (1 H, s), 2.83 (2 H, m),
1.85 (2 H, m), 1.61 (9 H, s), 0.98 24.31, 14.24
(3 H, t, J = 7.4)
185.24, 67.22, 41.7, 30.4, 175.10290
C8H17NOS
C8H15NO3S
3306 (OH), 2965,
2933, 2874 (CH),
1224 (C=S)
(175.10309)
10.77 (1 H, s), 3.65 (3 H, s),
3.59 (3 H, s), 2.69 (2 H, t,
J = 7.8), 2.34 (2 H, t, J = 7.3),
1.79 (2 H, m), 1.69 (2 H, m)
183.89, 173.94, 51.82,
205.07790
38.56, 38.37, 33.78, 28.12, (205.07727)
24.45
2950, 2868, (CH),
1735 (C=O), 1199
(C=S), 1045, 995
(CO)
10j
10k
10l
10.77 (1 H, s), 4.56 (1 H, sept, 181.84, 173.88, 53.97,
233.10811
C10H19NO3S
3294 (OH), 2979,
2949, 2872 (CH),
1737 (C=O), 1237
(C=S), 1037 (CO)
J = 6.3), 3.65 (3 H, s), 2.75 (2
H, t, J = 7.8), 2.35 (2 H, t,
51.83, 38.24, 33.78, 28.52, (233.10857)
24.54, 20.19
J = 7.3), 1.77 (2 H, m), 1.71 (2
H, m), 1.39 (6 H, d, J = 6.3)
10.88 (1 H, br s), 7.35 (5 H, m), 183.89, 173.9, 138.66,
5.55 (1 H, q, J = 6.8), 3.65 (3 H, 129.15, 128.6, 126.59, 61, (296.13204)
s), 2.75 (2 H, m), 2.32 (2 H, t, 51.84, 38.25, 33.77, 28.51,
J = 7.3), 1.77 (2 H, m), 1.67 (2 24.55, 19.56
H, m), 1.8 (3 H, d, J = 6.8)
296.13164
C15H22NO3S (M+ 3285 (OH), 2949,
H)c
2870 (CH), 1736
(C=O), 1235 (C=S),
1027, 977 (CO)
11.34 (1 H, s), 3.65 (3 H, s),
184.42, 173.94, 67.05,
247.12472
C11H21NO3S
3302 (OH) 2986,
2950, 2871 (CH),
1737 (C=O), 1203
(C=S), 1027 (CO)
2.87 (2 H, t, J = 7.8), 2.35 (2 H, 51.82, 39.2, 33.91, 30.16, (247.12422)
t, J = 7.3), 1.86 (2 H, m), 1.7 (2 30.02, 24.73
H, m), 1.62 (9 H, s)
11mb
11n
2.9 (1 H, s), 1.22 (9 H, s), 1.08 211.73, 55.2, 45.15, 28.76, 189.11926
C6H13NOS
C13H19NOS
3298 (NH), 2968,
2934, 2907, 2870
(CH), 1204 (C=S)
(9 H, s)
27.1
(147.07179)
7.3 (5 H, m), 3.92 (1 H, q), 3.25 213, 144.5, 128.9, 127.6,
(1 H, br s), 1.45 (3 H, d), 1.2 (9 60.88, 45.31, 27.15, 23.6
H, s)
237.11825
(237.11873)
3309 (OH), 2967,
2931 (CH), 1118
(C=S)
Synthesis 2002, No. 8, 1047–1052 ISSN 0039-7881 © Thieme Stuttgart · New York

1052
L. Doszczak, J. Rachon
PAPER
Table 3 Analytical Data for Compounds 10, 11 (continued)
Entry
11o
1H NMR (CDCl3, 500 MHz)
, J (Hz)
13C NMR (CDCl3,
125 MHz)
HRMS (EI),
M observed
(calculated)
Molecular
Formula
IR (NaCl, film)
(cm–1)
3.59 (4 H, m), 3.16 (4 H, m), 1.1 212.35, 68.22, 54.41,
(9 H, s)
203.09856
(203.09800)
C9H17NO2S
C15H21NO2S
2988, 2966, 2930,
2860 (CH), 1186
(C=S), 1048 (CO)
45.51, 27.07
11p
7.57 (2 H, dt, J1 = 7, J2 = 1.5),
227.33, 170.44, 134.86,
279.12955
(279.12930)
2975, 2933 (CH),
1672 (C=O), 1176
(C=S)
7.44 (1 H, tt, J1 = 7.3, J2 = 1.5), 131.02, 128.42, 127.8,
7.38 (2 H, tt, J1 = 7.3, J2 = 1.5), 54.22 46.93, 30.03, 20.43,
4.54 (1 H, m), 1.32 (3 H, d, 6.6), 19.54
1.31 (9 H, s), 1.25 (3 H, d, J = 7)
11r
7.91 (2 H, d, J = 7.3), 7.58 (1 H, 197.4, 135.49, 133.75,
t, J = 7.8), 7.46 (2 H, t, J = 7.8), 129.03, 126.89, 55.66,
209.08758
(209.08744)
C11H15NOS
3304 (NH), 2968
(CH), 1207 (C=S)
3.17 (1 H, br s), 1.19 (9 H, s)
29.02
a All thiohydroxamic acids gave a positive Fe3+ test.
b All O-thioacylhydroxylamines gave negative Fe3+ test.
c LSIMS method.
(10) Hoeg-Jensen, T.; Olsen, C.; Holm, A. J. Org. Chem. 1994,
59, 1257.
(11) Katritzky, A. R.; Moutou, J.; Yang, Z. Synthesis 1995, 1497.
(12) Kato, S.; Hattori, E.; Sato, H.; Mizuta, M.; Ishida, M. Z.
Naturforsch. B 1981, 86, 783.
Acknowledgements
We gratefully acknowledge the Polish State Committee for Scienti-
fic Research for financial support (Grant No. 3 T09A 061 16).
(13) Kato, S.; Shibahashi, H.; Katada, T.; Tagaki, T.; Noda, I.;
Mizuta, M.; Goto, M. Lieb. Ann. Chem. 1982, 1229.
(14) Doszczak, L.; Rachon, J. J. Chem. Soc. Chem. Commun.
2000, 2093.
(15) Boche, G.; Bosold, F.; Schroder, S. Angew. Chem. Int. Ed.
Engl. 1988, 27, 973.
(16) Bitner, S. Tetrahedron Lett. 1965, 95.
(17) Prabhakar, S.; Lobo, A. M.; Marques, M. M. Tetrahedron
Lett. 1982, 23, 1391.
(18) Lobo, A. M.; Marques, M. M.; Prabhakar, S.; Rzepa, H. S. J.
Org. Chem. 1987, 52, 2925.
(19) Ferreira, L. M.; Lobo, A. M.; Prabhakar, S.; Marcelo-Curto,
M. J.; Rzepa, H. S.; Yi, M. Y. J. Chem. Soc., Chem.
Commun. 1991, 1127.
(20) Lobo, A. M.; Marques, M. M.; Prabhakar, S.; Rzepa, H. S. J.
Chem. Soc., Chem. Commun. 1985, 1113.
(21) Ferreira, L. M.; Lobo, A. M.; Prabhakar, S.; Teixeira, A. C.
Tetrahedron 1999, 55, 3541.
(22) Murray, K. S.; Newman, P. J.; Gatehouse, B. M.; Taylor, D.
Aust. J. Chem. 1978, 31, 983.
References
(1) Chimiak, A.; Przychodzen, W.; Rachon, J. Heteroatom
Chem., 2002, 13, 169.
(2) Scheithauer, S.; Mayer, R. In Thio- and Dithiocarboxylic
Acids and Their Derivatives, Vol. 4; Senning, A., Ed.;
Thieme: Stuttgart, 1979.
(3) Cherkasov, R. A.; Kutyriev, G. A.; Pudovik, A. N.
Tetrahedron 1985, 41, 2567.
(4) Cava, M. P.; Levinson, M. I. Tetrahedron 1985, 41, 5061.
(5) Ito, Y.; Umino, K.; Sekguchi, T.; Miyagishima, T.; Egawa,
Y. J. Antibiot. 1971, 24, 131.
(6) Black, D. St. C.; Ooi, K. L. Aust. J. Chem. 1988, 41, 47.
(7) Przychodzen, W.; Chimiak, A. Phosphorus, Sulfur, Silicon
Relat. Elem. 1998, 143, 77.
(8) Prabhakar, S.; Lobo, A. M.; Santos, M. A.; Rzepa, H. S.
Synthesis 1984, 829.
(9) Zacharie, B.; Sauve, G.; Penney, C. Tetrahedron 1993, 49,
10489.
Synthesis 2002, No. 8, 1047–1052 ISSN 0039-7881 © Thieme Stuttgart · New York