A convenient synthetic method for fluorine-containing 4- alkoxydihydrobenzo[b][1,4]diazepinols and 3H-benzo[b][1,4]diazepines by the reaction of β-trifluoroacetylketene acetals with 1,2-phenylenediamines

Article abstract of DOI:10.3987/COM-08-S(F)72

β-Trifluoroacetylketene dialkyl acetals (3 and 5) reacted easily with various 1,2-phenylenediamines to give novel 4-alkoxy-2-trifluoromethyl-2,3- dihydro-1H-benzo[b][1,4]diazepinols (6 and 8) in moderate to high yields. Dehydration of 6 and 8 proceeded th

Full text of DOI:10.3987/COM-08-S(F)72

HETEROCYCLES, Vol. 77, No. 2, 2009
983
HETEROCYCLES, Vol. 77, No. 2, 2009, pp. 983 - 990. © The Japan Institute of Heterocyclic Chemistry
Received, 29th July, 2008, Accepted, 9th September, 2008, Published online, 11th September, 2008
DOI: 10.3987/COM-08-S(F)72
A
CONVENIENT SYNTHETIC METHOD FOR FLUORINE-
CONTAINING 4-ALKOXYDIHYDROBENZO[b][1,4]DIAZEPINOLS AND
3H-BENZO[b][1,4]DIAZEPINES BY THE REACTION OF
β-TRIFLUOROACETYLKETENE ACETALS WITH 1,2-PHENYLENE-
DIAMINES
Norio Ota,a Etsuji Okada,a* Naoya Terai,a Tomomi Miyamura,a Dai Shibata,a and
Tsuneaki Sakatab
aDepartment of Chemical Science and Engineering, Graduate School of
Engineering, Kobe University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
Fax: +81(78)8036194; E-mail: okaetsu@kobe-u.ac.jp
bDepartment of Life Science, Graduate School of Science and Technology, Kobe
University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
Abstract – β-Trifluoroacetylketene dialkyl acetals (3 and 5) reacted easily with
various 1,2-phenylenediamines to give novel 4-alkoxy-2-trifluoromethyl-2,3-
dihydro-1H-benzo[b][1,4]diazepinols (6 and 8) in moderate to high yields.
Dehydration of 6 and 8 proceeded thermally under reduced pressure to afford the
corresponding fluorine-containing 3H-benzo[b][1,4]diazepines (7 and 9).
INTRODUCTION
Benzo[b][1,4]diazepines have attracted much attention as an important class of heterocycles in the field
of medicinal and agricultural chemistries.1 These compounds are widely used as powerful agents,
especially for the antipsychotic therapy.2 Very recently, we have reported the facile synthesis of novel
fluorine-containing dihydrobenzo[b][1,4]diazepinols (2),3 some of which showed remarkable
antineoplastic efficacy,4 by the reaction of β,β-bis(trifluoroacetyl)vinyl ethers (1) with various
1,2-phenylenediamines (Scheme 1). In our previous studies, it was found that ketene dithioacetals5 and
orthoacetates6 reacted with trifluoroacetic anhydride quite easily to afford the corresponding
β-trifluoroacetylated ketene S,S- and O,O-acetals, respectively, and that these acylated compounds
This paper is dedicated to Professor Emeritus Keiichiro Fukumoto on the occasion of his 75th birthday.

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HETEROCYCLES, Vol. 77, No. 2, 2009
cleanly underwent nucleophilic S-N and O-N exchange reactions7,8 with aliphatic and aromatic amines to
give β-trifluoroacetylated ketene S,N-, O,N-, and N,N-acetals. Thereafter, these β-trifluoroacetyl-
NH2
OH
H
R
CF3
N
i-BuO
COCF3
COCF3
NH2
MeCN, rt
COCF3
R
N
H
1
2
Scheme 1
ketene acetals were found to be convenient building blocks which are applicable to the syntheses of a
variety of novel fluorine-containing heterocyclic compounds by the reactions with bifunctional
nucleophiles. For instance, fluorine-containing isoxazolines, 1H-pyrazolines, and imidazolines were
easily obtained by the reactions with hydroxylamine, hydrazines, and 1,2-ethylenediamine,
respectively.9,10 Additionally, Reddy et al. reported the interesting reaction of β-trifluoroacetylketene
acetal (3) with 4,5-dimethyl-1,2-phenylenediamine under microwave irradiation to give solely
benzimidazoles (4) without any formation of benzodiazepines (Scheme 2).11 These studies and our
Me
Me
NH2
NH2
H
N
Me
Me
EtO
EtO
COCF3
N
COCF3
MW
3
4
Scheme 2
continuing interest in the synthesis of trifluoromethyl-containing benzodiazepines, a new potential
pharmacophore of antineoplastic efficacy, prompted us to explore the feasibility of the benzodiazepine-
ring construction by the non-microwave assisted cyclization reaction of β-trifluoroacetylketene acetals
with 1,2-phenylenediamines.
In this paper we wish to report the annulation reaction of
β-trifluoroacetylketene acetals (3 and 5) with various 1,2-phenylenediamines under very mild conditions
without microwave irradiation to afford the desired fluorine-containing 2,3-dihydro-1H-
benzo[b][1,4]diazepinols (6 and 8) having an alkoxy group at the C-4 position. In addition, the

HETEROCYCLES, Vol. 77, No. 2, 2009
985
thermally induced dehydration of 6 and 8 under reduced pressure leading to the formation of the
corresponding 2-alkoxy-3H-benzo[b][1,4]diazepines (7 and 9) is presented.
RESULTS AND DISCUSSION
β-Trifluoroacetylketene dimethyl acetal (5) was easily prepared in 92% yield by the acylation of trimethyl
orthoacetate with trifluoroacetic anhydride according to our method reported previously.6,12 The results
of the annulation reaction of 5 with 1,2-phenylenediamines are depicted in Scheme 3 and summarized in
Table 1. Reaction of 5 with slightly excess amounts of 1,2-phenylenediamine readily occurred at room
R1
R2
NH2
NH2
OH
H
N
CF3
R1
R2
R1
R2
CF3
N
MeO
MeO
COCF3
+
MeCN, rt, 1h
N
N
OMe
OMe
5
6a-e'
7a-e'
Scheme 3
Table 1. Reaction of β-trifluoroacetylketene dimethyl acetal (5) with 1,2-phenylene-
diamines.a
Entry
1
R1
H
R2
H
Product
6a
7a
Yield (%)b
68
5
2
3
4
5
Me
Me
6b
7b
6c
7c
63
13
78
5
Cl
Cl
COPh or H
NO2 or H
H or COPh
H or NO2
6d and 6d’c
7d and 7d’c
6e and 6e’c
7e and 7e’c
81d
2d
65d
11d
a 1.1 equiv of 1,2-phenylenediamines was used.
b Isolated yield after chromatography.
c The mixture of the two regioisomers was placed on the column. The regio-
chemistry and the ratio are not determined yet.
d Combined yield of two regioisomers.
temperature in acetonitrile to give the desired 4-methoxy-2-trifluoromethyl-2,3-dihydro-1H-
benzo[b][1,4]diazepin-2-ol (6a) in 68% yield with the formation of its dehydrated product,

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HETEROCYCLES, Vol. 77, No. 2, 2009
2-methoxy-4-trifluoromethyl-3H-benzo[b][1,4]diazepine (7a), in 5% yield (Entry 1).
Similarly,
4,5-dimethyl- and 4,5-dichloro-1,2-phenylenediamines reacted with 5 to afford the corresponding
dihydrobenzodiazepinols (6b,c) - benzodiazepines (7b,c) mixtures in high combined yields (Entries 2
and 3).
The annulation with unsymmetrical 1,2-phenylenediamines such as 4-benzoyl- and
4-nitro-1,2-phenylenediamines also proceeded cleanly to afford the mixtures of the four components, the
two regioisomers of dihydrobenzodiazepinols (6d,d’ and 6e,e’) and those of benzodiazepines (7d,d’
and 7e,e’), in excellent combined yields (Entries 4 and 5). Although the attempted separation of
mixtures of the two regioisomers was unsuccessful, all of the separation of the mixtures into 6a-e’ and
7a-e’ was easily performed by column chromatography.
These results of our approaches on the reactions of 5 with 1,2-phenylenediamines show sharp contrast
with those reported by Reddy et al (see Scheme 2).11 As shown in Scheme 3, dihydrobenzodiazepinols
(6) were obtained predominantly, together with the small amounts of the corresponding benzodiazepines
(7) under very mild conditions in the absence of microwave irradiation in acetonitrile without any
formation of the corresponding benzimidazoles (4). To verify no difference in reactivities between
dimethyl derivative (5) and diethyl one (3), we then examined the reaction of 3 with
4,5-dimethyl-1,2-phenylenediamine,
in
which
4-ethoxy
derivative
of
2,3-dihydro-1H-
benzo[b][1,4]diazepinols (8) was obtained solely in 66% yield without corresponding benzimidazoles (4) as
depicted in Scheme 4.
Me
Me
NH2
NH2
OH
H
N
CF3
Me
Me
EtO
EtO
COCF3
MeCN, rt, 1h
66%
N
OEt
8
3
Scheme 4
Next we attempted the acid-catalyzed dehydration of 2,3-dihydro-1H-benzo[b][1,4]diazepin-2-ols (6a-e’
and 8) to 3H-benzo[b][1,4]diazepines (7a-e’ and 9), but this resulted in failure to give complex mixtures.
So, we tried to carry out the present dehydration with the use of Kugelrohr distillation apparatus, namely,
by heating under reduced pressure, as depicted in Scheme 5 and summarized in Table 2. All
dihydrobenzodiazepinols (6a-e’ and 8) was thoroughly dehydrated at 110-150 °C under reduced pressure
(3 mmHg) within 1.5 h to provide the corresponding benzodiazepines (7a-e’ and 9) in high yields except
for the cases of 7a and 7e,e’ with formation of large amounts of decomposition products.

HETEROCYCLES, Vol. 77, No. 2, 2009
987
OH
H
N
CF3
OR3
R1
R2
R1
R2
CF3
N
3 mmHg, 1.5h
N
N
OR3
6a-e', 8
7a-e', 9
Scheme 5
Table 2. Dehydration of 2,3-dihydro-1H-benzo[b][1,4]diazepinols (6a-e’ and 8).
Entry
1
2
R1
H
Me
Cl
R2
H
Me
Cl
R3
Me
Me
Me
Product
Yield (%)b
24
91
75
Temp (°C)a
110
120
120
110
150
120
7a
7b
7c
3
4c
5c
6
COPh or H H or COPh Me
NO2 or H
Me
7d and 7d’d 89e
7e and 7e’d 48e
H or NO2
Me
Me
Et
9
85
a Oven temperature (3 mmHg).
b Isolated yield after distillation.
c A mixture of two regioisomers (6d,d’ or 6e,e’) was used as a starting material.
d The mixture of two regioisomers was distilled. The regiochemistry and the ratio are not determined
yet.
e Combined yield of two regioisomers.
In summary, we have developed a facile and convenient synthetic method for 4-alkoxy-2-trifluoromethyl-
2,3-dihydro-1H-benzo[b][1,4]diazepinols (6 and 8), which are not easily obtained by other methods.
Moreover, the thermal dehydration of 6 and 8 was successfully carried out under reduced pressure to give
2-alkoxy-4-trifluoromethyl-3H-benzo[b][1,4]diazepines (7 and 9). Evaluation of biological activities,
especially of antineoplastic efficacy, is now under way for novel fluorine-containing benzodiazepines
(6-9).
EXPERIMENTAL
Mps were determined on an electrothermal digital melting point apparatus and are uncorrected. The 1H
NMR spectra were recorded on a Bruker AVANCE500 spectrometer using TMS as an internal standard.
IR spectra were taken with a PerkinElmer Spectrum ONE FT-IR spectrometer. Microanalyses were
taken with a YANACO CHN-Corder MT-5 analyzer.
Synthesis of 1,1,1-trifluoro-4,4-dimethoxybut-3-en-2-one (5).12
To an ice-cooled stirred solution of 1,1,1-trimethoxyethane (4.81 g, 40 mmol) and pyridine (6.33 g, 80
mmol) in CHCl3 (40 mL) was added dropwise trifluoroacetic anhydride (16.80 g, 80 mmol) and the

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HETEROCYCLES, Vol. 77, No. 2, 2009
mixture was stirred for 3 h at rt. Then, CH2Cl2 (100 mL) was added and the whole mixture was washed
with 10 % aq. Na2CO3 (50 mL) and with water (50 mL), and dried over Na2SO4. The solvent and
1
pyridine was removed in vacuo to give 5 (6.76 g, 92%). 5: mp 67-68 °C (n-hexane-EtOAc); H NMR
(CDCl3): δ 4.98 (s, 1H, =CH), 3.98 (s, 3H, CH3), 3.92 (s, 3H, CH3); IR (KBr): 1675 (C=O) cm-1. Anal.
Calcd for C6H7F3O3: C, 39.14; H, 3.83. Found: C, 39.16; H, 3.82.
General procedure for the synthesis of 4-methoxy-2-trifluoromethyl-2,3-dihydro-1H-benzo[b][1,4]-
diazepin-2-ols (6a-e’) and 4-methoxy-2-trifluoromethyl-3H-benzo[b][1,4]diazepines (7a-e’).
To a solution of 5 (184 mg, 1.0 mmol) in MeCN (4 mL) was added 1,2-phenylenediamines (1.1 mmol)
and the mixture was stirred for 1 h at rt. The solvent was removed under reduced pressure and the crude
mixture was chromatographed on silica gel column using n-hexane-EtOAc (9:1) as eluent to give 6a-e’
and 7a-e’. In the case with 4-benzoyl-1,2-phenylenediamine, a mixture of 6d and 6d’ and a mixture of
7d and 7d’ were eluted respectively. Similarly, a mixture of 6e and 6e’ and a mixture of 7e and 7e’
were eluted respectively in the case with 4-nitro-1,2-phenylenediamine.
4-Methoxy-2-trifluoromethyl-2,3-dihydro-1H-benzo[b][1,4]diazepin-2-ol (6a): mp 126-127 °C
1
(n-hexane-EtOAc); H NMR (CDCl3): δ 7.10-6.81 (m, 4H, Harom), 4.11 (s, 1H, OH or NH), 3.91 (s, 3H,
OCH3), 3.27 (s, 1H, OH or NH), 2.82 (d, 1H, J = 14.0 Hz, CH2), 2.61 (d, 1H, J = 14.0 Hz, CH2); IR
(KBr): 3326, 3112, 1652 cm-1. Anal. Calcd for C11H11F3N2O2: C, 50.77; H, 4.26; N, 10.77. Found: C,
50.72; H, 4.43; N, 10.65.
4-Methoxy-7,8-dimethyl-2-trifluoromethyl-2,3-dihydro-1H-benzo[b][1,4]diazepin-2-ol (6b): mp
122-123 °C (n-hexane-EtOAc); 1H NMR (CDCl3): δ 6.89 (s, 1H, Harom), 6.62 (s, 1H, Harom), 4.05 (s, 1H,
OH or NH), 3.88 (s, 3H, OCH3), 3.14 (s, 1H, OH or NH), 2.81 (d, 1H, J = 14.0 Hz, CH2), 2.59 (d, 1H, J =
14.0 Hz, CH2), 2.20 (s, 3H, CH3), 2.19 (s, 3H, CH3); IR (KBr): 3321, 3082, 1652 cm-1. Anal. Calcd for
C13H15F3N2O2: C, 54.16; H, 5.24; N, 9.72. Found: C, 54.10; H, 5.01; N, 9.47.
7,8-Dichloro-4-methoxy-2-trifluoromethyl-2,3-dihydro-1H-benzo[b][1,4]diazepin-2-ol
(6c):
mp
117-118 °C (n-hexane-EtOAc); 1H NMR (CDCl3): δ 7.21 (s, 1H, Harom), 6.97 (s, 1H, Harom), 4.21 (s, 1H,
OH or NH), 3.89 (s, 3H, OCH3), 3.17 (s, 1H, OH or NH), 2.84 (d, 1H, J = 14.0 Hz, CH2), 2.63 (d, 1H, J =
14.0 Hz, CH2); IR (KBr): 3315, 3071, 1648 cm-1. Anal. Calcd for C11H9Cl2F3N2O2: C, 40.14; H, 2.76; N,
8.51. Found: C, 40.28; H, 2.74; N, 8.40.
A mixture of (2-hydroxy-4-methoxy-2-trifluoromethyl-2,3-dihydro-1H-benzo[b][1,4]diazepin-
8-yl)phenylmethanone (6d) and (2-hydroxy-4-methoxy-2-trifluoromethyl-2,3-dihydro-1H-
benzo[b][1,4]diazepin-7-yl)phenylmethanone (6d’): 1H NMR (CDCl3): δ 7.74-6.82 (m, 8H, Harom), 4.61
(s, 1H, OH or NH), 4.50 (s, 1H, OH or NH), 3.92, 3.86 (s, 3H, OCH3), 2.89 (d, 1H, J = 14.0 Hz, CH2),
2.73 (d, 1H, J = 14.0 Hz, CH2); IR (KBr): 3372, 3324, 1662, 1646 cm-1. Anal. Calcd for C18H15F3N2O3:
C, 59.34; H, 4.15; N, 7.69. Found: C, 59.49; H, 4.41; N, 8.02.

HETEROCYCLES, Vol. 77, No. 2, 2009
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A mixture of 4-methoxy-8-nitro-2-trifluoromethyl-2,3-dihydro-1H-benzo[b][1,4]diazepin-2-ol (6e)
1
and 4-methoxy-7-nitro-2-trifluoromethyl-2,3-dihydro-1H-benzo[b][1,4]diazepin-2-ol (6e’): H NMR
(CDCl3 + CD3CN): δ 8.20-7.73 (m, 2H, Harom), 7.23-7.07 (m, 1H, Harom), 5.60 (s, 1H, NH or OH), 5.50 (s,
1H, NH or OH), 4.00, 3.90 (s, 3H, OCH3), 2.89 (d, 1H, J = 14.0 Hz, CH2), 2.73 (d, 1H, J = 14.0 Hz,
CH2); IR (KBr): 3487, 3300, 3170, 1649 cm-1. Anal. Calcd for C11H10F3N3O4: C, 43.29; H, 3.30; N,
13.77. Found: C, 43.38; H, 3.33; N, 13.65.
2-Methoxy-4-trifluoromethyl-3H-benzo[b][1,4]diazepine (7a): bp (oven temperature) 110 °C / 3
mmHg; 1H NMR (CDCl3): δ 7.63-7.13 (m, 4H, Harom), 3.87 (s, 3H, OCH3), 3.10 (s, 2H, CH2); IR (KBr):
1646 cm-1. Anal. Calcd for C11H9F3N2O: C, 54.55; H, 3.75; N, 11.57. Found: C, 54.79; H, 3.71; N,
11.37.
2-Methoxy-7,8-dimethyl-4-trifluoromethyl-3H-benzo[b][1,4]diazepine (7b): bp (oven temperature)
120 °C / 3 mmHg; 1H NMR (CDCl3): δ 7.32 (s, 1H, Harom), 7.16 (s, 1H, Harom), 3.90 (s, 3H, OCH3), 3.08
(s, 2H, CH2), 2.30 (s, 6H, CH3); IR (KBr): 1648 cm-1. Anal. Calcd for C13H13F3N2O: C, 57.78; H, 4.85;
N, 10.37. Found: C, 57.96; H, 4.94; N, 10.10.
7,8-Dichloro-2-methoxy-4-trifluoromethyl-3H-benzo[b][1,4]diazepine (7c): mp 98-99 °C (n-hexane-
1
EtOAc); H NMR (CDCl3): δ 7.66 (s, 1H, Harom), 7.49 (s, 1H, Harom), 3.93 (s, 3H, OCH3), 3.16 (s, 2H,
CH2); IR (KBr): 1648 cm-1. Anal. Calcd for C11H7Cl2F3N2O: C, 42.47; H, 2.27; N, 9.01. Found: C,
42.87; H, 2.36; N, 8.68.
A mixture of (2-methoxy-4-trifluoromethyl-3H-benzo[b][1,4]diazepin-7-yl)phenylmethanone (7d)
and (4-methoxy-2-trifluoromethyl-3H-benzo[b][1,4]diazepin-7-yl)phenylmethanone (7d’): bp (oven
temperature) 140 °C / 3 mmHg; 1H NMR (CD3CN): δ 8.07-7.35 (m, 8H, Harom), 3.94, 3.91 (s, 3H, OCH3),
3.29 (s, 2H, CH2); IR (KBr): 1657, 1642 cm-1. Anal. Calcd for C18H13F3N2O2: C, 62.43; H, 3.78; N,
8.09. Found: C, 62.39; H, 3.98; N, 7.93.
A mixture of 2-methoxy-7-nitro-4-trifluoromethyl-3H-benzo[b][1,4]diazepine (7e) and 4-methoxy-
7-nitro-2-trifluoromethyl-3H-benzo[b][1,4]diazepine (7e’): bp (oven temperature) 150 °C / 3 mmHg;
1H NMR (CDCl3): δ 8.27-8.00 (m, 2H, Harom), 7.73-7.57 (m, 1H, Harom), 3.81 (br s, 3H, OCH3), 3.24 (s,
2H, CH2); IR (KBr): 1646 cm-1. Anal. Calcd for C11H8F3N3O3: C, 46.00; H, 2.81; N, 14.63. Found: C,
46.02; H, 2.98; N, 14.44.
Synthesis of 4-ethoxy-7,8-dimethyl-2-trifluoromethyl-2,3-dihydro-1H-benzo[b][1,4]diazepin-2-ol
(8).
To a solution of 36 (214mg, 1.0 mmol) in MeCN (4 mL) was added 4,5-dimethyl-1,2-phenylenediamine
(150 mg, 1.1 mmol) and the mixture was stirred for 1 h at room temperature. The solvent was removed
under reduced pressure and the crude mixture was chromatographed on silica gel column using
1
n-hexane-EtOAc (4:1) as eluent to give 8 (200 mg, 66%). 8: mp 117-118 °C (n-hexane-EtOAc); H

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HETEROCYCLES, Vol. 77, No. 2, 2009
NMR (CDCl3): δ 6.79 (s, 1H, Harom), 6.66 (s, 1H, Harom), 4.35 (s, 1H, OH or NH), 4.24 (q, 2H, J = 7.0 Hz,
CH2CH3), 4.12 (s, 1H, OH or NH), 2.71 (d, 1H, J = 14.0 Hz, CH2), 2.48 (d, 1H, J = 14.0 Hz, CH2), 2.16
(s, 6H, CH3), 1.30 (t, 3H, J = 7.0 Hz, CH2CH3); IR (KBr): 3332, 3095, 1648 cm-1. Anal. Calcd for
C14H17F3N2O2: C, 55.62; H, 5.67; N, 9.27. Found: C, 55.66; H, 5.66; N, 9.22.
General procedure for the dehydration of dihydrobenzodiazepinols (6 and 8) to benzodiazepines (7
and 9).
The dehydration of 6 and 8 was successfully carried out with the use of Kugelrohr distillation apparatus.
The conditions are as follows: oven temperature, see Table 2; heating time, 1.5 h; reduced pressure, 3
mmHg.
2-Ethoxy-7,8-dimethyl-4-trifluoromethyl-3H-benzo[b][1,4]diazepine (9): mp 82-83 °C (n-hexane-
1
EtOAc); H NMR (CDCl3): δ 7.26 (s, 1H, Harom), 7.09 (s, 1H, Harom), 4.30 (q, 2H, J = 7.0 Hz,
CH2CH3), 3.07 (s, 2H, CH2), 2.31 (s, 3H, CH3), 2.30 (s, 3H, CH3), 1.32 (t, 3H, J = 7.0 Hz, CH2CH3); IR
(KBr): 1642, 1615 cm-1. Anal. Calcd for C14H15F3N2O: C, 59.15; H, 5.32; N, 9.85. Found: C, 59.20; H,
5.36; N, 10.04.
REFERENCES
1. D. Lloyd and H. MacNab, Adv. Heterocycl. Chem., 1998, 71, 1.
2. (a) H. Schutz, ‘Benzodiazepines,’ Springer, Heidelberg, 1982. (b) R. I. Fryer, ‘Comprehensive
Heterocyclic Chemistry,’ Wiley, New York, 1991.
‘Benzodiazepines,’ Raven Press, New York, 1973.
(c) L. Randall and B. Kappel,
3. N. Ota, T. Tomoda, N. Terai, Y. Kamitori, D. Shibata, M. Médebielle, and E. Okada, Heterocycles,
2008, 76, 1205.
4. E. Okada, N. Ota, T. Tomoda, M. Fujimoto, and H. Takenaka, Jpn. Kokai Tokkyo Koho
2006-273844, 2006.
5. M. Hojo, R. Masuda, and Y. Kamitori, Tetrahedron Lett., 1976, 17, 1009.
6. M. Hojo, R. Masuda, and E. Okada, Synthesis, 1986, 1013.
7. M. Hojo, R. Masuda, E. Okada, H. Yamamoto, K. Moriomoto, and K. Okada, Synthesis, 1990, 195.
8. M. Hojo, R. Masuda, E. Okada, and Y. Mochizuki, Synthesis, 1992, 455.
9. M. A. P. Martins, C. M. P. Pereira, N. E. K. Zimmermann, W. Cunico, S. Moura, P. Beck, N.
Zanatta, and H. G. Bonacorso, J. Fluorine Chem., 2003, 123, 261.
10. B. Narsaiah, A. Sivaprasad, and R. V. Venkataratnam, J. Fluorine Chem., 1994, 66, 47.
11. A. C. S. Reddy, P. S. Rao, and R. V. Venkataratnam, Tetrahedron, 1997, 53, 5847.
12. Very recently, the synthesis of 1,1,1-trifluoro-4,4-dimethoxybut-3-en-2-one (5) was reported: M.
Lubbe, A. Bunescu, M. Sher, A. Villinger, and P. Langer, Synlett, 2008, 1862.