Preparation of new tert-butyl substituted coumarins, thiocoumarins and dithiocoumarins

Article abstract of DOI:10.1080/10426500701340949

6-tert-Butyl-4-methyl- and 6,8-di-tert-butyl-4-methylcoumarin were prepared from tert-butylphenols and diketene via the corresponding aryl acetoacetates. 6-tert-Butyl-4-methyl-thiocoumarin (6) was obtained from 6-tert-butylthiophenol. Thionation with Lawesson's or Davy's reagent led to the related thion- and dithiocoumarins. The structures were proved by NMR spectroscopy and an X-ray structure analysis of 6.

Full text of DOI:10.1080/10426500701340949

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Preparation of New tert-
Butyl Substituted Coumarins,
Thiocoumarins and
Dithiocoumarins
Jürgen Voss a , Ronald Edler a & Gunadi Adiwidjaja b
a University of Hamburg, Department of Chemistry,
Organic Chemistry, Hamburg, Germany
b University of Hamburg, Department of
Geosciences, Hamburg, Germany
Version of record first published: 15 Jun 2007.
To cite this article: Jürgen Voss , Ronald Edler & Gunadi Adiwidjaja (2007):
Preparation of New tert-Butyl Substituted Coumarins, Thiocoumarins and
Dithiocoumarins, Phosphorus, Sulfur, and Silicon and the Related Elements, 182:8,
1893-1905
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Phosphorus, Sulfur, and Silicon, 182:1893–1905, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701340949
Preparation of New tert-Butyl Substituted Coumarins,
Thiocoumarins and Dithiocoumarins
¨
Jurgen Voss
Ronald Edler
University of Hamburg, Department of Chemistry, Organic Chemistry,
Hamburg, Germany
Gunadi Adiwidjaja
University of Hamburg, Department of Geosciences, Hamburg,
Germany
6-tert-Butyl-4-methyl- and 6,8-di-tert-butyl-4-methylcoumarin were prepared from
tert-butylphenols and diketene via the corresponding aryl acetoacetates. 6-tert-
Butyl-4-methyl-thiocoumarin (6) was obtained from 6-tert-butylthiophenol. Thion-
ation with LAWESSON’s or DAVY’s reagent led to the related thion- and dithio-
coumarins. The structures were proved by NMR spectroscopy and an X-ray structure
analysis of 6.
Keywords Coumarins; dithiocoumarins; keto-enol tautomerism; thiocoumarins; X-ray
structure
INTRODUCTION
Within the context of our studies on the EPR spectra of ester,1 thioester,2
and, in particular, of dithiopyrone3 radical anions, we became inter-
ested in the preparation and investigation of the corresponding benzo-
anellated compounds, i.e., the coumarins (2H-1-benzopyran-2-ones)
and thiocoumarins (2H-1-benzothiopyran-2-ones). In order to simplify
the expected complexity of the EPR spectra and in consideration of an
unequivocal experimental assignment of the proton hyperfine structure
coupling constants,3 we needed tert-butyl derivatives. A preliminary
Received August 14, 2006; accepted February 23, 2007.
The University of Hamburg and the Fonds der Chemischen Industrie are gratefully
acknowledged for their financial support. We thank Prof. Dr. U. Behrens, Hamburg, for
his help concerning the X-ray structure.
Address correspondence to Ju¨rgen Voss, University of Hamburg, Department of Chem-
istry, Organic Chemistry, Martin-Luther-King-Platz 6, Hamburg D-20146, Germany.
E-mail: juergen.voss@chemie.uni-hamburg.de
1893

1894
J. Voss et al.
study4 had shown that coumarin radical anions are only persistent
enough as to give resolved EPR spectra if they are substituted with
a methyl group in the 4-position. We describe here the synthesis of
4-methyl-coumarins with tert-butyl substituents in the benzene ring
and of the corresponding thio derivatives. Our EPR results have been
published elsewhere.5
RESULTS AND DISCUSSION
We obtained 6-tert-butyl-4-methylcoumarin (5a) from commer-
cially available 4-tert-butylphenol (1a) and 4-methylene-2-oxetanone
(diketene) via the β-keto-ester 3a with an overall yield of 44% using
6
1
the general method of LACEY (Scheme 1). According to its H NMR
spectrum, 3a consisted of a 2:1 mixture of the keto and enol tautomers
(Scheme 2).
SCHEME 1 (1): NEt3, CHCl3; (2): H2SO4, 75% or AlCl3, CS2; (3): LR or DR,
toluene.
SCHEME 2 Keto-Enol-Tautomerism of 3a, 3b, 4, 11a, and 11b (X = O, S).

Coumarins, Thiocoumarins and Dithiocoumarins
1895
The 13C NMR signals were assigned by comparison of the experi-
mentally observed shifts with the theoretical ones (Table I). The lat-
ter were calculated from data for 4-methylcoumarin, thiolcoumarin,
thioncoumarin and dithiocoumarin,7 and the increments of a tert-butyl
substituent.8
Thionation of 5a with 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadi-
phosphetane 1,3-disulfide (LAWESSON’s reagent, LR)9,10 gave a 84%
yield of the thioncoumarin 7a (Scheme 1).
The base-catalyzed reaction of 2,4-di-tert-butylphenol (1b) with
diketene led to the β-ketoester 3b, again as a 2:1 mixture of the keto-
enol tautomers (Scheme 2). Obviously due to steric hindrance, the yield
was only 37%. Cyclodehydration with sulfuric acid gave a very small
amount (5% yield) of the desired 6,8-di-tert-butyl-4-methylcoumarin
(5b). In this case, dealkylation was observed. Under the strongly acidic
conditions, 3a (2.3%) was formed as byproduct. Furthermore, ester
cleavage with formation of 1b took place.
The thionation of 5b to 7b was achieved with 45% yield by using 2,4-
bis(methylthio)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, the so-called
DAVY’s reagent (DR),11 which is more reactive than LR. It produces even
dithioesters on reaction with carboxylic acids. No dithiocoumarin was
formed from 5b, however.
An analogous synthesis12,13 of the thiocoumarine 6 required 4-tert-
butylthiophenol (2) as starting material. The preparation of arenethi-
ols by reduction of arenesulfonyl chlorides with lithium alanate is de-
scribed in the literature.14 In our hands, however, the use of the much
cheaper zinc dust in sulfuric acid as the reductive reagent15,16 turned
out to give a higher yield of 2. The reaction of 2 with diketene led to the
β-keto-thioester 4. As one would expect according to the literature,12,13
4, as well as the acetothioacetates 11a and 11b, also exist as mixtures
(ca. 2:1) of the keto and the enol tautomers (Scheme 2). Cyclization un-
der dehydration of 4 with aluminum trichloride eventually led to the
thiocoumarin 6 (Scheme 1). The very low yield of only 4.5% is obvi-
ously due to a rapid decomposition of 6 under the rather harsh reaction
conditions.
According to the NMR spectra of 6, no dealkylation or migration of
the tert-butyl substituent had occurred, which could have happened
in the presence of the strong LEWIS-acid aluminum trichloride.17 The
correct structure of 6 and, in particular, the 6-position of the tert-
butyl substituent, was corroborated by an X-ray structure analysis
(Figure 1). The bicyclic thiocoumarin skeleton of the molecule does not
deviate significantly from planarity. The relevant bond lengths and an-
gles (see the legend of Figure 1) exhibit the expected values and are

1896

Coumarins, Thiocoumarins and Dithiocoumarins
1897
FIGURE 1 ORTEP view of the thiocoumarin 6. Thermal ellipsoids are drawn
at the 50% probability level. Hydrogen atoms are not shown. Relevant func-
tional bond lengths (pm): S–C-2: 175.9, S–C-8a: 173.9, C-2–O: 122.4, C-2–C-3:
144.6, C-3–C-4: 133.6, C-4–C-4a: 146.5, C-4a–C-8a: 140.4; and bond angles (◦):
C-2–S–C-8a: 105.0, S–C-2–O: 117.5, S–C-2–C-3: 118.1, O–C-2–C-3: 124.4, C-2–
C-3–C-4: 128.5.
in reasonable agreement with values found for the related 6-methyl-4-
morpholinomethyl-thiocoumarin.18
The thiocoumarin 6 was readily transformed into the corresponding
dithiocoumarin 8 with 62% yield by use of LR.
The di-tert-butylthiophenols 10a19 and 10b19 can be obtained
from 1-bromo-2,4-di-tert-butylbenzene (9a)20 and 1-bromo-3,5-di-tert-
butylbenzene (9b),21 respectively, by GRIGNARD reaction with elemental
sulfur and reduction of the intermediate disulfide with lithium alanate.
Both thiophenols reacted with diketene to form the corresponding S-
aryl acetothioacetates 11a and 11b (Scheme 3). An intramolecular cy-
clization of 11a and 11b with aluminum trichloride under formation of
the thiocoumarins 12a or 12b could, however, not be achieved (Scheme
3). Instead, a tert-butyl substituent was split off from 11a to form 4,
and ester cleavage led to 2. The thioester 11b was completely unreac-
tive because the cyclization is sterically hindered due to the tert-butyl
substituents in the two ortho-positions of 11b. The thioester 11b was
recovered unchanged from the reaction mixture.
When we tried to prepare 3,6-di-tert-butylcoumarin (14a) from 4-tert-
butylphenol (1a) and the known ethyl 2-tert-butylacetoacetate (13)22,23
only 5a and 5b instead of 14a were formed as products via cleavage
(5a) or rearrangement (5b) of a tert-butyl group (Scheme 4). An attempt

1898
J. Voss et al.
SCHEME 3 (1): 1. Mg, THF, 2. S8, 3. LiAlH4; (2): NEt3,CH2Cl2; (3): AlCl3, CS2.
to prepare 3,6,8-tri-tert-butylcoumarin (14b) from 1b and 13 was also
unsuccessful. Again, only a low yield of 5b was formed in this case.
EXPERIMENTAL
Melting points (m.p., uncorrected) were determined with a Leitz-
Heiztischmikroskop. Boiling points (b.p.) were determined during dis-
tillation. Thin layer chromatography (TLC) was performed on Al
foils coated with SiO2 F254 (Merck, Darmstadt). The spots were de-
tected by the extinction of the fluorescence or by spraying with the
iodine/sodium azide reagent.24 Column chromatography (CC) was
performed on Kieselgel 60, (Merck, Darmstadt), 0.063–0.200 mm

Coumarins, Thiocoumarins and Dithiocoumarins
1899
SCHEME 4 (1): H2SO4 or AlCl3, CS2.
(70–230 mesh). Eluents [CH2Cl2, petroleum ether (PE)] were distilled
prior to use. Solvents were purified and dried by standard laboratory
procedures.25 Removal of solvents was performed in a vacuum rotatory
evaporator.
IR spectra were measured as KBr pellets or films on Perkin-Elmer
spectrometers 297 and 399.
NMR spectra were measured in CDCl3 on Varian T60 (60 MHz for 1H)
or Bruker WM 400 (400 MHz for 1H, 100.62 MHz for 13C) spectrometers.
The 13C NMR data are compiled in Table I. Chemical shifts δ are related
to SiMe4 (δ = 0.00 ppm) as internal standard. Coupling constants J are
given in Hz.
Mass spectra were measured on a Varian MAT CH 7 spectrometer
at 70 eV.
X-Ray Structure Analysis
The crystal data of 6 and a summary of the experimental details are
given in Table II. Data collection was performed with a CAD 4 SDP
(Enraf Nonius) diffractometer with graphite-monochromated Cu-Kα,
˚
(Ni-filter, 1.54184 A) in the θ/2θ scan mode at 298 K. The structure
was solved by the direct method MULTAN.26 All non-hydrogen atoms
were localized. After refinement of these parameters the hydrogen
atoms were localized by differential FOURIER-synthesis.27 The final
refinement was performed by least squares methods. An experimental
correction for absorption28 was performed in addition to the usual
LORENTZ-correction for polarization. Crystallographic data of 6 have
been deposited with the Cambridge Crystallographic Data Centre as a
supplementary publication No. CCDC-612426. Copies of the data can
be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 IEZ, UK [Fax: (international) +44-1223/336-033;
E-mail: deposit@ccdc.cam.uk].

1900
J. Voss et al.
TABLE II Crystal Data and
Structure Refinement for 6
Compound
Empirical formula
Formula weight
C14H16OS
232.35
Crystal system
Space group
a = b [pm]
c [pm]
Tetragonal
P41212
916.6 (1)
2937.4 (2)
2468 106
8
V [pm3]
Z
–3
ρcalcd. [g cm
µ [cm
]
1.32
21.05
–1
]
F(000)
992
2/60
0, 7/ 0, 8/0, 32
1777
θ-limits [◦]
h/k/l-Limits
Reflections collected (I > 3σI)
Number of parameters
210
R-Index
Rw-Index (w = σI
0.038
0.039
–2
)
4-tert-Butylphenyl 3-Oxobutanoate (3a)
4-tert-Butylphenol (1a, 100 g, 0.67 mol) was dissolved in CHCl3
(150 mL). NEt3 (5 drops) was added and the solution was heated to
55◦C. Freshly distilled diketene was dropped in within 1 h and the re-
action mixture was heated to 55◦C for another 1.5 h. The solvent was
removed and the residue was recrystallized from PE to yield 3a (143 g,
91%) as colorless crystals, m.p. 40.5–41.5◦C. IR: ν 3060, 2970 (s), 2870,
1760 (s, C=O), 1715 (s, C=O), 1660 (C=C), 1620 (C=C), 1600, 1500,
1
1400, 1360, 1305, 1260, 1100, 1015, 920, 840, 550 cm−1. H NMR (60
MHz); ketone: δ 1.22 [s, 9H, C(CH3)3], 1.90 (s, 3H, CH3), 3.48 (s, 2H,
CH2), 7.03 (m, 4H, Har); enol: δ 1.22 [s, 9H, C(CH3)3], 2.17 (s, 3H, CH3),
5.10 (s, 1H, 2-H), 7.03 (bs, 4H, Har), 9.60 (bs, 1H, OH). Anal. calcd. for
C14H18O3 (234.30): C, 71.77; H, 7.74; Found: C, 71.70; H, 7.59.
6-tert-Butyl-4-methylcoumarin (5a)
The ester 3a (100 g, 0.43 mol) was dissolved in 75% H2SO4 (300 mL)
and stirred at 20◦C for 24 h. The reaction mixture was poured into
H2O (1 L) and repeatedly extracted with diethyl ether. The extract was
washed with dilute aqueous KOH and H2O and dried over Na2SO4. The
solvent was removed and the residue was washed with icy-cold PE and
then recrystallized from PE to give 5a (45 g, 48%) as long, colorless
needles, m. p. 120.5–121◦C. IR: ν 3050, 2960, 2870, 1720 (s, C O), 1620
(C C), 1600 (C C), 1570, 1490, 1380, 1270, 1220, 1180, 1065, 1000, 920

Coumarins, Thiocoumarins and Dithiocoumarins
1901
(s), 895, 880 (s), 640 cm−1. 1H NMR (400 MHz): δ 1.34 [s, 9H, C(CH3)3],
2.44 (d, 4 JH,CH3 = 0.7 Hz, 3H, CH3), 6.22 (q, 4 JH,CH3 = 0.7 Hz, 1H, 3-H),
7.22 (d, 3 JH7,H8 = 6.7 Hz, 1H, 8-H), 7.57 (m, 2H, 7-H, 8-H). MS (70 eV)
m/z (%) = 216 (18) [M+], 202 (14), 201 (100) [M+− CH3], 173 (22), 161
(12), 145 (11), 28 (59). Anal. calcd. for C14H16O2 (216.28): C, 77.75; H,
7.46; Found: C, 77.82; H, 7.40.
6-tert-Butyl-4-methylthionocoumarin (7a)
The coumarin 5a (10.0 g, 46.0 mmol) and LR (18.6 g, 46.0 mmol) were
refluxed in toluene (200 mL) for 2.5 h. The toluene was removed and the
residue was extracted with hot EtOH/H2O (1:1). After drying and re-
moval of the solvent, a residue (9.5 g, m. p. 125–126◦C) containing 2% of
S8 according to its elemental analysis was obtained. Column chromatog-
raphy (PE) and subsequent recrystallization (EtOH/H2O, 1:1) gave pure
7a (9.0 g, 84%) as bright yellow crystals, m. p. 127–128◦C. IR: ν 3060,
3040, 2960 (s), 2900, 2860, 1605 (s, C=C), 1560 (s), 1280, 1255 (s), 1150
(s), 1120, 1100 (s), 1065, 980, 820 (s) cm−1. 1H NMR (400 MHz): δ 1.34
[s, 9H, C(CH3)3], 2.37 (d, 4 J
= 0.7 Hz, 3H, CH3), 7.11 (q, 4 J
=
H,CH3
H,CH3
0.7 Hz, 1H, 3-H), 7.35 (d, 3 J
= 6.7 Hz, 1H, 8-H), 7.59 (d, 4 J
=
H7,H8
H5,H7
1.3 Hz, 1H, 5-H), 7.63 (dd, 3 J
Anal. calcd. for C14H16OS (232.35): C, 72.37; H, 6.94, S, 13.80; Found:
C, 72.56; H, 6.98; S, 13.65.
= 6.7 Hz, 4 J
= 1.3 Hz, 1H, 7-H).
H7,H8
H5,H7
4-tert-Butylthiophenol (2)15,16
Ice (720 g) and conc. H2SO4 (1.30 L) were mixed in a three-necked
round-bottomed flask equipped with a high-performance reflux-cooler
and a mechanical stirrer. Under cooling with an ice/NaCl mixture
and vigorous stirring, powdered 4-tert-butylbenzenesulfonyl chloride29
(79.1 g, 0.34 mol) and subsequently, as quickly as possible, Zn dust (120
g, 1.83 mol) were added. After stirring at 0◦C for 1 h, subsequent reflux-
ing for 3.5 h, and cooling, the reaction mixture was repeatedly extracted
with diethyl ether. The extracts were dried over K2CO3, and the solvent
was removed. Distillation of the residue gave 2 (48.1 g, 85%) as a col-
orless liquid, b.p. 55◦C/0.3 Torr. IR: ν 3080, 3020, 2960 (s), 2860, 2560
(SH), 1500 (s), 1480, 1460, 1360, 1265, 1200, 1120 (s), 1010, 920, 820
(s), 740, 720 cm−1. 1H NMR (60 MHz): δ 1.20 [s, 9H, C(CH3)3], 3.17 (s,
1H, SH), 7.02 (m, 4H, Har).
S-4-tert-Butylphenyl 3-Oxobutanethioate (4)
Thiophenol 2 (9.0 g, 54 mmol) was dissolved in dry CH2Cl2 (200 mL).
Freshly distilled diketene (4.56 g, 54 mmol) and NEt3 (3 drops) were
added, and the solution was stirred at 20◦C for 12 h. A quantitative

1902
J. Voss et al.
yield of 4 was obtained on removal of the solvent. Purification by CC
(CH2Cl2) gave 4 (12.0 g, 89%) as a colorless liquid. IR: ν 2960 (s), 2900,
2870, 1720 (s, C=O), 1695 (s, C=O), 1620 (s, C=C), 1490, 1400, 1360,
1265, 1190, 1155, 1080, 1010, 970, 855 cm−1. 1H NMR (60 MHz); ketone:
δ 1.28 [s, 9H, C(CH3)3], 2.13 (s, 3H, CH3), 3.63 (s, 2H, CH2), 7.30 (m,
4H, Har); enol: δ 1.28 [s, 9H, C(CH3)3], 1.83 (s, 3H, CH3), 5.42 (s, 1H,
2-H), 7.30 (m, 4H, Har), 11.4 (bs, 1H, OH).
6-tert-Butyl-4-methyl-thiocoumarin (6)
The thioester 4 (5.0 g, 20 mmol) was added to a suspension of AlCl3
(20 g) in dry CS2 (20 mL). The mixture was refluxed for 7 h. After cooling,
it was poured into icy-cold H2O and repeatedly extracted with diethyl
ether. The ether was removed, and the residue was chromatographed
(CH2Cl2). Recrystallization (2×) from CH2Cl2 gave pure 6 (0.21 g, 4.5%)
as colorless crystals, m.p. 94–95◦C. IR: ν 3050, 2960, 2900, 2860, 1620
(s, C=O), 1580, 1530, 1470, 1370, 1260, 1220, 900, 820 cm−1. 1H NMR
(400 MHz): δ 1.37 [s, 9H, C(CH3)3], 2.52 (d, 4 J
= 0.7 Hz, 3H, CH3),
= 6.7 Hz, 1H, 8-H),
CH3,H
6.43 (q, 4 J
= 0.7 Hz, 1H, 3-H), 7.29 (d, 3 J
CH3,H
H7,H8
7.46 (dd, 3 J
= 6.7 Hz, 4 J
= 1.7 Hz, 1H, 7-H), 7.75 (d, 4 J
=
H7,H8
H5,H7
H5,H7
1.7 Hz, 1H, 5-H). MS (70 eV) m/z (%) = 234 (4), 232 (59) [M+], 217 (53)
[M+− CH3], 204 (30) [M+− CO], 189 (100) [M+− CO – CH3], 161 (25),
149 (25), 147 (13), 115 (11), 81 (12), 80 (11). Anal. calcd. for C14H16OS
(232.35): C, 72.37; H, 6.94; S, 13.80; Found: C, 72.33; H, 7.03; S, 13.97.
6-tert-Butyl-4-methyl-dithiocoumarin (8)
The thiocoumarin 6 (0.60 mg, 2.60 mmol) and LR (1.12 g, 2.70 mmol)
were refluxed in toluene under stirring for 2 h. The toluene was re-
moved, and the residue was extracted with hot EtOH/H2O (1:1). Pure
8 (0.40 g, 62%) was obtained from the extract as orange crystals, m.p.
118–119◦C. IR: ν 2965 (s), 2875, 1580 (s), 1530 (s), 1450, 1380, 1240,
1
1220 (s), 1020 (s), 995 (s), 890, 825 cm−1. H NMR (400 MHz): δ 1.34
[s, 9H, C(CH3)3], 2.45 (s, 3H, CH3), 7.30 (d, 3 J
= 6.7 Hz, 1H, 8-H),
H7,H8
7.34 (s, 1H, 3-H), 7.53 (dd, 3 J
= 6.7 Hz, 4 J
= 0.7 Hz, 1H, 7-H),
H7,H8
H5,H7
7.81 (d, 4 J
= 0.7 Hz, 1H, 5-H). MS m/z (%) = 250 (9), 248 (93) [M+],
H5,H7
235 (11), 233 (100) [M+− CH3], 204 (20), 189 (51), 161 (16), 147 (11),
115 (11). Anal. calcd. for C14H16S2 (248.41): C, 67.69; H, 6.49; S, 25.82;
Found: C, 67.59; H, 6.57; S, 25.81.
2,4-Di-tert-butylphenyl 3-Oxobutanoate (3b)
Diketene (40.7 g, 0.48 mol) was dropped into a boiling solution of 2,4-
di-tert-butylphenol (1b, 100 g, 0.48 mol) and NEt3 (5 drops) in CHCl3
(150 mL) within 1 h. The reaction mixture was refluxed for 7 h. Most of
the solvent was removed and the residue was triturated with PE. The

Coumarins, Thiocoumarins and Dithiocoumarins
1903
mixture crystallized on cooling and the solid was filtered. Recrystal-
lization from PE gave 3b (51 g, 37%), m.p. 55–56◦C. IR: ν 3060, 2960,
2870, 1760 (C=O), 1660 (C=C), 1620, 1600, 1500, 1460, 1400, 1360,
1300, 1260, 1100, 1015, 920, 840, 745 cm−1. 1H NMR (60 MHz); ketone:
δ 1.32 [s, 9H, C(CH3)3], 1.35 [s, 9H, C(CH3)3], 2.30 (s, 3H, CH3), 3.63
(s, 2H, CH2), 6.83–7.33 (m, 3H, Har); enol: δ 1.32 [s, 9H, C(CH3)3], 1.35
[s, 9H, C(CH3)3], 1.98 (s, 3H, CH3), 5.18 (s, 1H, 2-H), 7.10 (m, 3H, Har),
11.63 (bs, 1H, OH). Anal. calcd. for C18H26O3 (290.40): C, 74.45; H, 9.02;
Found: C, 75.79; H, 9.17.
6,8-Di-tert-butyl-4-methylcoumarin (5b)
Ester 3b (29 g, 0.1 mol) was slowly added to 75% H2SO4 (120 mL).
The reaction mixture was stirred at 20◦C for 24 h, then poured into
H2O (360 mL) and repeatedly extracted with diethyl ether. The extract
was washed with aqueous KOH and H2O and dried over Na2SO4. The
solvent was removed and the residue was chromatographed (CH2Cl2).
The fractions containing 5b were collected, concentrated and triturated
with a small amount of PE. On cooling to –30◦C, 5a (0.50 g, 2.3%) crys-
tallized from the solution and was removed by filtration. The solvent
was removed from the filtrate and the residue was crystallized from a
small amount of PE to yield pure 5b (1.36 g, 5%), m.p. 90–92.5◦C. IR: ν
3080, 2960 (s), 1710 (s, C=O), 1620 (C=C), 1575 (s), 1480, 1460, 1425,
1380, 1360, 1280, 1235, 1065, 1100 (s), 940 (s), 905, 880 (s), 770, 645
cm−1. 1H NMR (60 MHz): δ 1.37 [s, 9H, C(CH3)3], 1.50 [s, 9H, C(CH3)3],
2.38 (d, 4 J
= 0.7 Hz, 3H, CH3), 6.08 (q, 4 J
= 0.7 Hz, 1H, 3-H),
H,CH3
H,CH3
7.37–7.53 (AB-system, 2H, 5-H, 7-H). Anal. calcd. for C18H24O2 (272.39):
C, 79.37; H 8.88; Found: C, 79.90; H, 8.94.
6,8-Di-tert-butyl-4-methyl-thionocoumarin (7b)
Coumarin 5b (0.38 g, 1.30 mmol) and DR11 (0.74 g, 2.60 mmol) were
refluxed in toluene (5 mL) under stirring for 50 min. The solvent was
removed and the residue was purified by preparative scale TLC (2 mm
SiO2 layer, CH2Cl2) to yield 7b (0.18 g, 45%) as bright yellow crystals,
m.p. 127–128◦C. IR: ν 2980 (s), 1620 (s, C=C), 1580 (s), 1470, 1410,
1395, 1380, 1320, 1280, 1160, 1100, 890, 780 cm−1. 1H NMR (60 MHz):
δ 1.35 [s, 9H, C(CH3)3], 1.51 [s, 9H, C(CH3)3], 2.38 (s, 3H, CH3), 7.01 (s,
1H, 3-H), 7.40–7.65 (m, 2H, 5-H, 7-H).
S-2,4-Di-tert-butylphenyl 3-Oxobutanethioate (11a)
2,4-Di-tert-butylthiophenol (10a,19,20 4.0 g, 18 mmol) was dissolved
in CH2Cl2 (60 mL). Diketene (1.51 g, 18 mmol) and NEt3 (4 drops) were
added and the reaction mixture was stirred at 20◦C for 12 h. The solvent
was removed. The residue was chromatographed (CH2Cl2) to yield 11a
(4.4 g, 80%). IR: ν 3070, 2960, 1725 (C O), 1695 (C=C), 1480, 1400,

1904
J. Voss et al.
1
1360, 1280, 1240, 1195, 1080, 965, 870, 705 cm−1. H NMR (60 MHz);
ketone: δ 1.32 [s, 9H, C(CH3)3], 1.43 [s, 9H, C(CH3)3], 1.98 (s, 3H, CH3),
3.45 (s, 2H, CH2), 6.97–7.37 (m, 3H, Har); enol: δ 1.32 [s, 9H, C(CH3)3],
1.43 [s, 9H, C(CH3)3], 1.70 (s, 3H, CH3), 5.25 (s, 1H, 3-H), 7.2 (m, 3H,
Har), 11.13 (bs, 1H, OH). Anal. calcd. for C18H26O2S (306.47): C, 70.55;
H, 8.55; S, 10.46; Found: C, 71.11; H, 8.66; S, 10.45.
S-3,5-Di-tert-butylphenyl 3-Oxobutanethioate (11b)
Thioester 11b (85%) , colorless crystals, m.p. 44–45 ◦C, was prepared
from 3,5-di-tert-butylthiophenol (10b)19,21 as described for 11a. IR: ν
3070, 2970, 1725 (C O), 1695 (C=C), 1620, 1480, 1400, 1380, 1240,
1
1190, 1080, 965, 870, 705 cm−1. H NMR (60 MHz); ketone: δ 1.30 [s,
18H, C(CH3)3], 2.08 (s, 3H, CH3), 3.55 (s, 2H, CH2), 7.12–7.40 (m, 3H,
Har); enol: δ 1.30 [s, 18H, C(CH3)3], 1.83 (s, 3H, CH3), 5.37 (s, 1H, 3-H),
7.12–7.40 (m, 3H, Har), 12.07 (bs, 1H, OH). Anal. calcd. for C18H26O2S
(306.47): C, 70.55; H, 8.55; S, 10.46; Found: C, 71.15; H, 8.65; S, 10.23.
Ethyl 2-tert-Butyl-3-oxobutanoate (13)22,23
Ethyl acetoacetate (63.3 mL, 65 g, 0.50 mol) and tert-butyl alcohol
(113 mL, 88.8 g, 1.20 mol) were mixed in a 500-mL three-necked flask
under exclusion of moisture. Under cooling with ice, dry, purified (ab-
sorption flask with B2O3/H2SO4) gaseous BF3 was introduced for 5 h
(until saturation) through a glass tube, which reached about 1 cm above
the level of the liquid. The ice-bath was removed and the reaction mix-
ture was left at 20◦C for 14 h. A solution of NaOAc·3H2O (100 g) in H2O
(300 mL) was added. The product was extracted with diethyl ether (3
× 150 mL), the extract was dried over Na2SO4, and the solvent was re-
moved. Vacuum distillation by use of a spinning band column gave 19 g
(20%) of 13, b.p. 98–100◦C/20 Torr. IR: ν 2960, 2910, 2870, 1740 (C O),
1
1720 (C O), 1470, 1390, 1220, 1200, 1140, 1040, 600 cm−1. H NMR
3
(60 MHz): δ 1.05 [s, 9H, C(CH3)3], 1.20 (t, J = 7.0 Hz, 3H, CH2CH ),
3
2.15 (s, 3H, COCH3), 3.22 (s, 1H, CH), 4.10 (q, 3 J = 7.0 Hz, 2H, CH2).
Reaction of 1a and 1b with 13 (Attempted Preparation
of 14a or 14b)
An intimate mixture of 1a (32 g, 0.21 mol) and 13 (20 g, 0.107 mol)
was slowly added with stirring to 75% H2SO4 (180 mL). The mixture
was heated to 85◦C for 1 h and then poured into H2O (1 L). The solution
was repeatedly extracted with diethyl ether, the extract was washed
with aqueous KOH and H2O and dried over Na2SO4. The solvent was
removed and the residue was chromatographed (CH2Cl2). No 14a was
found. Instead, 5a (0.8 g, 3.5%) and 5b (0.1 g, 0.4%) were isolated, which
were identical with the authentic compounds.
An analogous reaction of 1b with 13 gave only 5b as product.

Coumarins, Thiocoumarins and Dithiocoumarins
1905
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