Reaction between tert-butyl isocyanide and 1,1,1-trifluoro-4-aryl-butane-2,4-diones. Synthesis of new trifluoromethylated furan derivatives

Article abstract of DOI:10.1016/j.jfluchem.2004.05.017

The 2:1 adducts produced in the reaction between tert-butyl isocyanide and 1,1,1-trifluoro-4-arylbutan-2,4-diones were isolated and characterized as fluorinated aminoketenimines, which undergo enolization-cyclization reactions in boiling chloroform to pro

Full text of DOI:10.1016/j.jfluchem.2004.05.017

Journal of Fluorine Chemistry 125 (2004) 1497–1500
Reaction between tert-butyl isocyanide and
1,1,1-trifluoro-4-aryl-butane-2,4-diones
Synthesis of new trifluoromethylated furan derivatives
Mohammad H. Mosslemina, Issa Yavarib,*, Mohammad Anary-Abbasinejada,
Mohammad R. Nateghia
aDepartment of Chemistry, Islamic Azad University, Yazd, Iran
bDepartment of Chemistry, Tarbiat Modarres University, P.O. Box 14115-175, Tehran, Iran
Received 14 November 2003; received in revised form 17 May 2004; accepted 21 May 2004
Available online 19 July 2004
Abstract
The 2:1 adducts produced in the reaction between tert-butyl isocyanide and 1,1,1-trifluoro-4-arylbutan-2,4-diones were isolated and
characterized as fluorinated aminoketenimines, which undergo enolization-cyclization reactions in boiling chloroform to produce new
trifluoromethylated furan derivatives.
# 2004 Elsevier B.V. All rights reserved.
Keywords: CH-acid; Trifluoromethylated furans; Aminoketenimine; 1,3-Dicarbonyl compound
1. Introduction
data. Of interest are the strong ketenimine absorption bands
at about 2090 cmꢀ1 in the IR spectra of compounds 2a–c and
a broad N–H peak at about 3300 cmꢀ1 for the alkylamino
group. The mass spectra of these 1:2 adducts exhibited fairly
weak molecular ion and/or MHþ ion peaks at appropriate m/
z values for 2 and strong molecular ion peaks for 3. Any
initial fragmentations involve the loss of t-butylamino moi-
eties and scission of the trifluoroacetyl bonds.
These trifluoromethylated aminoketenimines may be for-
mulated as having been derived from initial a,a-addition of
the CH-acid to the isocyanide and subsequent nucleophilic
addition of another molecule of the isocyanide to yield
intermediate 5, which is converted into the aminoketenimine
system 2 by proton transfer (Scheme 2).
The greatest reactivity observed for isocyanides is the
reaction of the functional group with acidic reactants [1–10].
A general feature of isocyanide reactions is the formation of
a,a-addition products, i.e. two new bonds are formed with
the terminal isocyanide carbon atom. Typical examples
include the reaction of isocyanides with protonic acids
[4–6,10]. Here, we wish to report that CH-acids such as
trifluoromethyl substituted 1,3-dicarbonyl compounds 1
react with tert-butyl isocyanide producing 1:2 adducts
(acid:isocyanide).
2. Results and discussion
Compounds 2a–c can be converted quantitatively to the
trifluoromethylated furan ring systems 3a–c upon refluxing
in chloroform for 2–5 h. However, compounds 2 do have two
alternative ways to cyclize. Since the carbonyl signal of the
The reaction of 1,1,1-trifluoro-4-arylbutan-2,4-diones (1)
with tert-butyl isocyanide leads to fluorinated aminokete-
nimines 2, which were converted quantitatively to trifluor-
omethylated furan derivatives 3 (see Scheme 1). All the
compounds are stable crystalline solids at room temperature
whose structure is fully supported by elemental analyses, IR,
1H, 13C, and 19F NMR spectroscopy and mass spectrometric
arylketone moiety at about d ¼ 180 ppm is present in the 13
C
NMR spectra of compounds 3, we conclude that the
trifluoroacyl group undergoes cyclization. It seems that
the electron-withdrawing trifluoromethy group enhances
the nucleophilic addition to the adjacent carbonyl
group. Further evidence is obtained from the mass spectra
of compounds 3, which exhibit strong peaks for the ArCO
fragments. The IR spectra of 3a–c are similar to those of the
* Corresponding author. Tel.: þ92-21-8006631; fax: þ92-21-8006544.
E-mail address: isayavar@yahoo.com (I. Yavari).
0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2004.05.017

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M.H. Mosslemin et al. / Journal of Fluorine Chemistry 125 (2004) 1497–1500
Scheme 1.
Scheme 2.
corresponding aminoketenimines except for the strong
absorption band at about 2090 cmꢀ1 which is absent in
compounds 3a–c.
The presented reaction of t-butyl isocyanide with fluori-
nated 1,3-diketones provides a simple entry into the synth-
esis of trifluoromethylated ketenimine derivatives of
potential synthetic interest. The procedure described here
may be useful as a method for the preparation of 2,3-
diaminofurans which are difficult to prepare [11].
(3 mL) was added dropwise a solution of t-butyl isocyanide
(0.33 g, 4 mmol) in CH2Cl2 (3 mL) at ꢀ5 oC over 10 min.
The reaction mixture was then allowed to warm up to room
temperature and stirred for 24 h. The solvent was removed
under reduced pressure and the residue was purified by silica
gel (Merck silica gel 60, 230–400 mesh) column chromato-
graphy using n-hexane-ethyl acetate as eluent. The solvent
was removed under reduced pressure to afford the product
which was recrystallized from ethyl acetate to yield 2a as
colorless crystals, 0.62 g, yield 80%, mp 147–149 8C.
IR (KBr) (nmax, cmꢀ1) ¼ 3340 (NH), 2070 (C¼C¼N),
1683 (C¼O).
3. Experimental
1H NMR (CDCl3) d ¼ 1.4 (9H, s, CMe3), 1.5 (9H, s,
CMe3), 4.4 (1H, q, 4JHF ¼ 9 Hz, CH), 7.2 (1H, m, CH), 7.6
(1H, br s, NH), 7.7–7.8 (2H, m, 2 CH) ppm.
Melting points were measured with an Electrothermal
9100 apparatus. Elemental analyses were performed using a
Heraeus CHN-O-Rapid analyzer. Mass spectra were
recorded with a FINNIGAN-MAT 8430 mass spectrometer
operating at an ionization potential of 70 eV. IR spectra were
recorded with a Shimadzu IR-470 spectrometer. 1H, 13C, and
19F NMR spectra were recorded with a JEOL EX-90A
13C NMR (CDCl3) d ¼ 28.5 (CMe3), 30.1 (CMe3), 51.9
1
(CMe3), 53.5 (CMe3), 116.0 (C), 123.6 (q, JFC ¼ 264 Hz,
CF3), 124.4 (CH), 125.1 (CH), 127.5 (CH), 131.2 (C), 139.4
2
(C), 153.9 (C), 171.0 (q, JFC ¼ 28 Hz, CF3–C¼O), 182.8
(C¼O) ppm.
1
19F NMR (CDCl3) d ¼ ꢀ66.74 (CF3) ppm.
MS (EI, 70 eV): m/z (ion, %) ¼ 389 (MHþ, 1), 333 (MHþ
ꢀ Me2C¼CH2, 11), 157 (31), 111 (C5H3SOþ, 46), 57
(C4H9þ, 100), 41 (C3H5þ, 48).
spectrometer at 90, 22.6 and 84.7 MHz, respectively. H,
13C and 19F NMR spectra were obtained on solution in
CDCl3 using TMS or CFCl3 as internal standard. The
triflouromethylated 1,3-dicarbonyl compounds used in this
work were purchased from Fluka (Buchs, Switzerland) and
used without further purifications.
Analytically calculated for C18H23F3N2O2S (388.5): C,
55.7; H, 6.0; N, 7.2%. Found: C, 55.4; H, 5.9; N, 7.2%.
3.1. Preparation of 2-[1-(tert-butylamino)-2-(tert-
butylimino)vinyl]-4,4,4-trifluoro-1-(2-thienyl)-butane-1,3-
dione (2a): typical procedure
3.2. 2-[1-(tert-Butylamino)-2-(tert-butylimino)vinyl]-4,4,4-
trifluoro-1-phenyl-butane-1,3-dione (2b)
Colorless crystals; yield: 0.59 g (77%), mp 150–152 8C.
IR (KBr) (nmax, cmꢀ1) ¼ 3315 (NH), 2085 (C¼C¼N),
1684 (C¼O).
To a magnetically stirred solution of 1,1,1-trifluoro-4-(2-
thienyl)-butane-2,4-dione (0.44 g, 2 mmol) in CH2Cl2

M.H. Mosslemin et al. / Journal of Fluorine Chemistry 125 (2004) 1497–1500
1499
1H NMR (CDCl3) d ¼ 1.2 (9H, s, CMe3), 1.4 (9H, s,
19F NMR (CDCl3) d ¼ ꢀ76.52 (CF3) ppm.
CMe3), 4.3 (1H, q, JHF ¼ 9 Hz, CH), 5.9 (1H, br s, NH),
MS (EI, 70 eV): m/z (ion, %) ¼ 388 (Mþ, 43), 332 (Mþ ꢀ
Me2C¼CH2, 84), 276 (45), 260 (53), 111 (C5H3SOþ, 67), 83
(24), 57 (C4H9þ, 100), 41 (C3H5þ, 81).
4
7.3–7.7 (5H, m, Ph) ppm.
13C NMR (CDCl3) d ¼ 28.3 (CMe3), 30.1 (CMe3), 51.8
(CMe3), 53.3 (CMe3), 92.2 (CH), 117.1 (C), 123.9 (q,
1JFC ¼ 265 Hz, CF3), 127.6 and 129.0 (CHmeta and CHortho),
132.8 (Cipso), 134.0 (CHpara), 154.2 (C), 177.2 (q,
2JFC ¼ 37 Hz, CF3–C¼O), 186.2 (C¼O) ppm.
Analytically calculated for C18H23F3N2O2S (388.5): C,
55.7; H, 6.0; N, 7.2%. Found: C, 55.5; H, 5.8; N, 7.2%.
3.5. [4,5-bis(tert-Butylamino)-2-(trifluoromethyl-3-furyl)]-
phenyl-methanone (3b)
19F NMR (CDCl3) d ¼ ꢀ65.81 (CF3) ppm.
MS (EI, 70 eV): m/z (ion, %) ¼ 383 (MHþ, 1), 382 (Mþ,
0.5), 326 (Mþ ꢀ Me2C¼CH2, 23), 253 (326 ꢀ Me3CNH2,
15), 227 (253 ꢀ CN, 44), 105 (C7H5Oþ, 41), 77 (C6H5þ, 29),
57 (C4H9þ, 100), 41 (C3H5þ, 76).
Pale yellow powder; yield: 0.59 g (95%), mp 145–146 8C.
IR (KBr) (nmax, cmꢀ1) ¼ 3320 and 3253 (2 NH), 1664
(C¼O).
Analytically calculated for C20H25F3N2O2 (382.4): C,
62.8; H, 6.6; N, 7.3%. Found: C, 63.0; H, 6.5; N, 7.4%.
1H NMR (CDCl3) d ¼ 1.4 (9H, s, CMe3), 1.5 (9H, s,
CMe3), 4.4 (H, br s, NH), 5.7 (H, br s, NH), 7.2–7.7 (5H, m,
Ph) ppm.
3.3. 2-[1-(tert-Butylamino)-2-(tert-butylimino)vinyl]-4,4,4-
trifluoro-1-(2-naphthyl)-butane-1,3-dione (2c)
13C NMR (CDCl3) d ¼ 28.4 and 30.2 (CMe3), 52.0 and
53.5 (CMe3), 89.7 (q, 3JFC ¼ 36 Hz, C¼C–CF3), 117.4 (C),
123.5 (q, 1JFC ¼ 265 Hz, CF3), 124.9 and 128.6 (CHortho and
CHmeta), 127.7 (CHpara), 129.2 (Cipso), 142.1 (C), 154.32(q,
2JFC ¼ 4 Hz, C–CF3), 182.4 (C¼O) ppm.
Colorless crystals; yield: 0.60 g (97%), mp 160–162 8C.
IR (KBr) (nmax, cmꢀ1) ¼ 3275 (NH), 2090 (C¼C¼N),
1684 and 1649 (C¼O).
19F NMR (CDCl3) d ¼ ꢀ75.91 (CF3) ppm.
1H NMR (CDCl3) d ¼ 1.2 (9H, s, CMe3), 1.37 (9H, s,
MS (EI, 70 eV): m/z (ion, %) ¼ 382 (Mþ, 25), 326 (27),
CMe3), 4.6 (1H, q, JHF ¼ 9 Hz, CH), 6.7 (1H, br s, NH),
227 (51), 105 (C7H5Oþ, 49), 57 (100).
4
7.4–8.3 (7H, m, naphthyl) ppm.
Analytically calculated For C20H25F3N2O5 (382.4): C,
62.8; H, 6.6; N, 7.3%. Found: C, 62.7; H, 6.6; N, 7.2%.
13C NMR (CDCl3) d ¼ 28.4 (CMe3), 30.3 (CMe3), 52.0
(CMe3), 53.5 (CMe3), 91.3 (CH), 117.9 (C), 122.5 (q,
1JFC ¼ 263 Hz, CF3), 122.8, 124.4, 126.2, 126.6, 128.2,
128.3, 128.7, 132.6 and 133.3 (naphthyl), 142.2 (C), 154.5
(C), 178.1 (q, 2JFC ¼ 35 Hz, CF3–C¼O), 188.1 (C¼O) ppm.
19F NMR (CDCl3) d ¼ ꢀ66.22 (CF3) ppm.
3.6. [4,5-bis(tert-Butylamino)-2-(trifluoromethyl-3-furyl)]-
(2-naphthyl)-methanone (3c)
Pale yellow powder; yield: 0.86 g (100%), mp 151–153 8C.
IR (KBr) (nmax, cmꢀ1) ¼ 3315 and 3235 (2 NH), 1669
(C¼O).
MS (EI, 70 eV): m/z (ion, %) ¼ 432 (Mþ, 0.5), 376 (Mþ ꢀ
Me2C¼CH2, 15), 303 (376 ꢀ Me3CNH2, 7), 277 (Mþ
155, 30), 155 (C11H7Oþ, 38), 127 (C10H7þ, 23), 57 (C4H9
100), 41 (C3H5þ, 36).
ꢀ
þ
,
1H NMR (CDCl3) d ¼ 1.4 (9H, s, CMe3), 1.5 (9H, s,
CMe3), 4.4 (H, br s, NH), 5.7 (H, br s, NH), 7.3–8.2 (7H, m,
naphthyl) ppm.
Analytically calculated for C24H27F3N2O2 (432.5): C,
66.7; H, 6.3; N, 6.5%. Found: C, 66.5; H, 6.2; N, 6.4%.
13C NMR (CDCl3) d ¼ 28.4 (CMe3), 30.3 (CMe3), 52.0
3
(CMe3), 53.5 (CMe3), 91.1 (q, JFC ¼ 36 Hz, C¼C–CF3),
1
3.4. Preparation of [4,5-bis(tert-butylamino)-2-
(trifluoromethyl-3-furyl)]-(2-thienyl)-methanone (3a):
typical procedure
123.5 (q, JFC ¼ 264 Hz, CF3), 123.8, 124.2, 126.3, 126.6,
127.7, 128.2, 128.35, 129.9, 132.6 and 133.3 (naphthyl),
2
142.2 (C), 154.5 (q, JFC ¼ 4 Hz, C–CF3), 182.6
(C¼O) ppm.
A magnetically stirred solution of 2a (0.78 g, 2 mmol) in
CHCl3 (10 mL) wasrefluxedfor5 h.The solventwasremoved
under reduced pressure and the residue was obtained as pale
yellow powder; yield: 0.75 g (98%), mp 141–143 8C.
IR (KBr) (nmax, cmꢀ1) ¼ 3435 and 3330 (2 NH), 1655
(C¼O).
19F NMR (CDCl3) d ¼ ꢀ76.33 (CF3) ppm.
MS (EI, 70 eV): m/z (ion, %) ¼ 432 (Mþ, 25), 376 (Mþ ꢀ
Me2C¼CH2, 17), 303 (376 ꢀ Me3CNH2, 5), 277 (Mþ
155, 33) 155 (C11H7Oþ, 34), 127 (C10H7þ, 23), 57 (C4H9
100), 41 (C3H5þ, 46).
ꢀ
þ
,
Analytically calculated for C24H27F3N2O2 (432.5): C,
66.7; H, 6.3; N, 6.5%. Found: C, 66.6; H, 6.2; N, 6.6%.
1H NMR (CDCl3) d ¼ 1.4 (9 H, s, CMe3), 1.5 (9H, s,
CMe3), 4.4 (H, br s, NH), 5.7 (H, br s, NH), 7.0–7.4 (3H, m, 3
CH) ppm.
References
13C NMR (CDCl3) d ¼ 28.4 (CMe3), 30.0 (CMe3), 51.8
3
(CMe3), 53.4 (CMe3), 89.9 (q, JFC ¼ 35 Hz, C¼C–CF3),
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(CH), 127.4 (CH), 130.7 (C), 139.2 (C), 153.8 (q,
2JFC ¼ 4 Hz, C–CF3), 180.5 (C¼O) ppm.

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