Applications of dithioacetals in ester synthesis

Article abstract of DOI:10.1080/00397910802654641

The α-oxoketene dithioacetals are simple synthetic intermediates widely utilized and implicated for the synthesis of a variety of heterocyclic compounds other than alicyclic and aromatic compounds. They act as 1,3-electrophilic three-carbon synthons. The

Full text of DOI:10.1080/00397910802654641

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Applications of Dithioacetals in
Ester Synthesis
Ashish Kumar Tewari a & Priyanka Srivastava a
a Faculty of Science, Department of Chemistry ,
Banaras Hindu University , Varanasi, India
Published online: 14 Jul 2009.
To cite this article: Ashish Kumar Tewari & Priyanka Srivastava (2009) Applications of
Dithioacetals in Ester Synthesis, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:16, 2837-2842, DOI:
10.1080/00397910802654641
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Synthetic Communications1, 39: 2837–2842, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802654641
Applications of Dithioacetals in Ester Synthesis
Ashish Kumar Tewari and Priyanka Srivastava
Faculty of Science, Department of Chemistry, Banaras Hindu University,
Varanasi, India
Abstract: The a-oxoketene dithioacetals are simple synthetic intermediates widely
utilized and implicated for the synthesis of a variety of heterocyclic compounds
other than alicyclic and aromatic compounds. They act as 1,3-electrophilic
three-carbon synthons. The a-oxoketene dithioacetal of pyrazolone derivatives
can be efficiently converted through a base-catalyzed alcoholysis into the corres-
ponding ester in a single one-step reaction with good yield of pure products. In
this article, we summarize recent direct conversion of a-oxoketene dithioacetals
to highly desirable esters. The overall process is an example of intramolecular
rearrangement of bonds. Characterization and identification of all synthesized
1
compounds were assigned through H NMR and mass spectroscopy.
Keywords: S,O-Acetal, alcoholysis, cyclocondensation, a-oxoketene dithioacetal,
synthons, thiomethyl
The a-oxoketene dithioacetals[1–3] can be considered masked b-ketoesters
that have ambient electrophilicity at 1,3-carbon centers as a result of
the presence of bisalkylthio groups, which can be converted into ester
functionality when desired.[1a]
Conversion of a-oxoketene dithioacetals into the corresponding
a,b-unsaturated ester involves reduction of ketones with NaBH4 followed
by BF3 ꢀ OEt2-mediated alcoholysis. As a part of our interest in the chem-
istry[4] of a-oxoketene dithioacetals, we developed a one-pot method for
synthesis of ester using a-oxoketene dithioacetals as intermediates.[5–8]
(See Fig. 1)
Received September 29, 2008.
Address correspondence to Ashish Kumar Tewari, Department of Chemistry,
Faculty of Science, Banaras Hindu University, Varanasi 221 005, India. E-mail:
tashish2002@yahoo.com
2837

2838
A. K. Tewari and P. Srivastava
Figure 1. Conversion of a-oxoketene dithioacetals into the corresponding
a,b-unsaturated ester.
Scheme 1. One-pot synthesis of ester using a-oxoketene dithioacetals.
Compound 4 was converted into 4-(bis-methylsulfanylmethylene)-5-
methyl-2-phenyl-2,4-dihydropyrazol-3-one 5a[9] and 4-(bis-ethylsulfanyl-
methylene)-5-methyl-2-phenyl-2,4-dihydropyrazol-3-one 5b by the route
shown in Scheme 1. Thus, 4 was treated with carbon disulfide and methyl
iodide to give a mixture of 5a and 5b in the presence of Sodium hydroxide
(NaOH)=Potassium hydroxide (KOH). (See Scheme 1)
Compound 5a was reacted with sodium ethoxide with overall
yield of 70–90% in the presence of suitable alcohols to give 7, 8, and 9.
(Scheme 2)
It is interesting to note that reaction of 5a with NaOEt in dimethyl
formamide (DMF) or CH3CN as a solvent gave compound 10.
In conclusion, we have developed an efficient one-step method to
prepare different 4-substituted pyrazole-esters under simple reaction
conditions. This method features a short reaction time and good yields
of pure products.
EXPERIMENTAL
Unless otherwise noted, all materials were used as received from a com-
mercial supplier without further purification. All anhydrous reactions were
performed using oven-dried glassware, and all solvents were dried before

Applications of Dithioacetals in Ester Synthesis
2839
Scheme 2. Role of a-oxoketene dithioacetals in ester synthesis.
preceding with the reactions. Reactions were monitored using silica-gel G
thin-layer chromatography (TLC) plates and their spots were visualized
under an ultraviolet (UV) lamp or by iodine vapors. Melting points were
taken in an electrically heated instrument and are uncorrected.
Synthesis of 4(Bis-methylsulfanyl-methylene)-5-methyl-2-phenyl-2,4-
dihydropyrazol-3-one (5a)
A mixture of 3-methyl-1-phenyl pyrazol-5-one (172.4 mmol, 30 g) and CS2
(172.4 mmol, 10.40 ml) was dissolved in anhydrous DMF and slowly added
to a mixture of anhydrous K2CO3 (431.0 mmol, 59.48 g), DMF (20 ml), and
C6H6 (40 ml) at 0ꢁC. After 5 h, CH3I (344.8 mmol, 21.46 ml) in 10 ml C6H6
was added dropwise. After 6 h, the solvent was removed, and the residue was
dissolved in CHCl3 (800 ml), washed with water (2 ꢂ 100 ml), and dried over
anhydrous sodium sulfate. The mixture was concentrated to give a dark
orange-red viscous solution, which was purified on silica gel using ethyl acet-
ate and hexane as an eluent to give 5a in 40.54g (84.58%). Mp¼ 46–48ꢁC;

2840
A. K. Tewari and P. Srivastava
1H NMR [300 MHz, CDCl3, 25ꢁC, Si(CH3)4]: d 2.51 (s, 3H, CH3); d 2.689 (s,
3H, SCH3); d 2.751 (s, 3H, SCH3); d 7.122–7.985 (m, 5H, Ar-H) (Ja ¼ 8.4;
Jb ¼ 7.5, 7.8; Jc ¼ 6.9, 7.2 Hz).
Synthesis of 4(Bis-ethylsulfanyl-methylene)-5-methyl-2-phenyl-2,4-
dihydropyrazol-3-one (5b)
A mixture of 3-methyl-1-phenyl pyrazol-5-one (5.7 mmol, 1 g) and CS2
(5.7 mmol, 0.34 ml) were dissolved in anhydrous DMF and slowly added
to a mixture of anhydrous K2CO3 (14.2 mmol, 1.95 g), DMF (20 ml), and
C6H6 (40 ml) at 0ꢁC. After 5 h, C2H5I (11.4 mmol, 0.91 ml) in 10 ml C6H6
was added dropwise. After 6 h, solvent was removed, and the residue was
dissolved in CHCl3 (800 ml), washed with water (2 ꢂ 100 ml), and dried over
anhydrous sodium sulfate. The mixture was concentrated to give a dark
orange-red viscous solution, which was purified on silica gel using ethyl acet-
ate and hexane as an eluent to give 13b in 1.32g (75.42%). Mp¼ 40–42ꢁC;
1H NMR [300 MHz, CDCl3, 25ꢁC, Si(CH3)4]: d 2.52 (s, 3H, CH3); d 1.31–
1.44 (double t, 3H, CH2CH3 ꢂ 2) (J ¼ 7.5, 7.2, 8.1, 7.5, 7.5 Hz); d 3.17–
3.34 (double q, 4H, CH2CH3 ꢂ 2) (J ¼ 7.5, 7.5, 7.2, 7.5, 7.2, 7.2 Hz);
d 7.12–7.98 (m, 5H, Ar-H) (Ja ¼ 7.8; Jb ¼ 7.8; Jc ¼ 7.2, 7.2 Hz).
Synthesis of 5-Hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic
Acid Methyl Ester (7)
Compound 5a (3.5 mmol, 1 g) was added to a solution of NaOC2H5
(7.0 mmol, 0.47 g) in 10 ml dry methanol, followed by heating under
reflux for 2 h. Concentrated HCl was added until it became acidic,
followed by water. Then the precipitate was filtered and washed with
water. Mp ¼ 138–140ꢁC; yield ¼ 0.8 g (95.86%); 1H NMR [300 MHz,
CDCl3, 25ꢁC, Si(CH3)4]: d 2.40 (s, 3H, CH3); d 3.92 (s, 3H, OCH3);
d 7.26–7.79 (m, 5H, Ar-H) (Ja ¼ 8.1; Jb ¼ 7.2; Jc ¼ 7.5, 9.3 Hz); d 9.99
(broad s, 1H, O-H); MS (m=z) Mþ 233.
Synthesis of 5-Hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic
Acid Ethyl Ester (8)
Compound 5a (3.5 mmol, 1 g) was added to a solution of NaOC2H5
(7.0 mmol, 0.47 g) in 10 ml dry ethanol, followed by heating under reflux
for 2 h. Concentrated HCl was added until it became acidic, followed by
water. Then the precipitate was filtered and washed with water. Mp ¼ 95–
1
97ꢁC; yield ¼ 0.74 g (83.63%); H NMR [300 MHz, CDCl3, 25ꢁC,

Applications of Dithioacetals in Ester Synthesis
2841
Si(CH3)4]: d 1.383–1.425 (t, 3H, CH2CH3) (J ¼ 5.7, 6.9 Hz); d 2.412
(s, 3H, CH3); d 4.351–4.417 (q, 2H, CH2CH3) (J ¼ 6.9, 5.7, 7.2 Hz);
d 7.265–7.796 (m, 5H, Ar-H) (Ja ¼ 7.8; Jb ¼ 6.9; Jc ¼ 6.9, 8.4 Hz);
d 10.081 (broad s, 1H, O-H); MS (m=z) Mþ 247.
Synthesis of 5-Hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic
Acid Isopropyl Ester (9)
Compound 5a (3.5 mmol, 1 g) was added to a solution of NaOC2H5
(7.0 mmol, 0.47 g) in 10 ml dry ethanol, followed by heating under reflux
for 2 h. Concentrated HCl was added until the mixture became acidic,
followed by water. Then the precipitate was filtered and washed with
water. Mp ¼ 58–60ꢁC; yield ¼ 0.70 g (74.85%); 1H NMR [300 MHz,
CDCl3, 25ꢁC, Si(CH3)4]: d 1.370–1.391 (d, 6H, CH3 ꢂ 2) (J ¼ 6.3 Hz);
d 2.405 (s, 3H, CH3); d 5.217–5.300 (p, 1H, CH) (J ¼ 6.0, 6.6, 6.0,
6.3 Hz); d 7.261–7.787 (m, 5H, Ar-H) (Ja ¼ 7.5; Jb ¼ 5.4; Jc ¼ 7.2,
8.1 Hz); d 10.132 (broad s, 1H, O-H); MS (m=z) Mþ 261.
Synthesis of 3,3-Bis-methylsulfanyl-2-[1-(phenyl-hydrazono)-ethyl]-
acrylic Acid Ethyl Ester (10)
Compound 5a (0.5 g, 7.0 mmol) was added to a solution of anhydrous
NaOC2H5 (0.24 g, 1.4 mmol) in 10 ml acetonitrile or 20 ml DMF,
followed by heating under reflux for 6 h or stirring at room temperature
for 24 h. Concentrated HCl was added until the mixture became acidic,
followed by water. The precipitate was filtered and washed with water.
Mp ¼ 98–100ꢁC; yield ¼ 3.3 g (56.70%); 1H NMR [300 MHz, CDCl3,
25ꢁC, Si(CH3)4]: d 1.40 (s, 3H, CH3); d 2.41 (s, 3H, CH3); d 2.52
(s, 3H, SCH3); d 4.34–4.41 (q, 2H, OCH2CH3); d 7.25–7.79 (m, 5H,
Ar-H); d 10.08 (broad s, 1H, NH).
ACKNOWLEDGMENT
The authors gratefully acknowledge the Department of Science and
Technology, New Delhi, for financial assistance through the Young
Scientist Program.
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