13C NMR of thia- or aza-substituted butyric acid derivatives

Article abstract of DOI:10.1002/1097-458X(200102)39:2<113::AID-MRC808>3.0.CO;2-B

Eight thia- or aza-substituted butyric acid derivatives were prepared and the influence of these substituents on aromatic ¹³C NMR shifts was studied. Copyright

Full text of DOI:10.1002/1097-458X(200102)39:2<113::AID-MRC808>3.0.CO;2-B

MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2001; 39: 113–114
Reference Data
13C NMR of thia- or aza-substituted butyric
acid derivatives
INTRODUCTION
For the synthesis of derivatives of (iso)thiochromanone and
isoquinolone, it was necessary to prepare appropriately substituted
phenylthia- and phenylazabutyric acids 1a–h (Scheme 1).
We report here the 13C NMR chemical shifts of these
compounds.
1
Johannes Frohlich, Fritz Sauter1 and Viktor Milata2∗
¨
1
Institute for Organic Chemistry, Technical University Wien, Getreide-
markt 9, A-1110 Vienna, Austria
2
Department of Organic Chemistry, Faculty of Chemical Technology,
EXPERIMENTAL
Slovak Technical University, Radlinske´ ho 9, SK-812 37 Bratislava, Slovak
Republic
The synthesis of thiabutyric acid derivatives has been described.1–3
In the case of 3-azabutyronitrile derivatives we applied the modified
Strecker method4 for the synthesis of the corresponding 2,2-
tetramethylene analogs according to Ref. 5
Received 30 September 1999; Revised 15 July 2000; Accepted 20 July 2000
NMR spectra were determined with a Bruker AC 200 FT-NMR
spectrometer. Chemical shifts were assigned from HETCOR spectra
and are expressed in ppm downfield from tetramethylsilane. The
sweep width was kHz, the digital resolution was 0.1 ppm and the
concentration of the samples was 30 mg of the compound in 0.5 ml
of the appropriate solvent.
Eight thia- or aza-substituted butyric acid derivatives
were prepared and the influence of these substituents on
aromatic 13C NMR shifts was studied. Copyright 2001
John Wiley & Sons, Ltd.
KEYWORDS: NMR; 13C NMR; 4-phenyl-3-thiabutyric acid
derivatives; 4-phenyl-4-thiabutyric acid derivatives;
4-phenyl-3-azabutyric acid derivatives
4-Phenyl-3-aza-2,2-tetramethylene acid derivatives I
Into a mixture of 20 mmol of N-(un)substituted benzylamine,
20 mmol of hydrochloric acid, 40 ml of of 25% ethanol, 20 mmol
of cyclopentanone and 20 ml of ethanol was dropped a solution
of 30 mmol of potassium cyanide in 10 ml of water with magnetic
stirring. After 4 days the precipitate (1e) was filtered off or the
reaction mixture (1g) was extracted with diethyl ether, dried with
ŁCorrespondence to: V. Milata, Department of Organic Chemistry, Faculty of
Chemical Technology, Slovak Technical University, Radlinske´ho 9, SK-812 37
Bratislava, Slovak Republic.
Scheme 1
Table 1. 13C chemical shifts [υ (ppm) rel. to TMS] for 4-phenyl-3-(or 4-)thia(or aza)butyric acid derivativesa
—X—Y—CR1R2R
Cipso
Cortho
129.2
Cmeta
128.6
Cpara
127.4
Other signals
—CH2 —S—CH2 —COOH, 1a
136.8
176.8 (COOH), 36.3 (PhCH2 —), 31.9
(—CH2COOH)
—S—CH2CH2 —COOH, 1b
—CH2 —S—CH2-COOMe, 1c
—S—CH2CH2 —COOMe, 1d
—CH2 —NH—C(CH2)4CN, 1e
135.0
137.0
135.0
139.2
130.1
128.9
129.8
128.5
129.0
128.3
128.8
128.3
126.6
127.0
126.3
127.3
177.1 (COOH), 34.4 (CH2COOH), 30.9
(—SCH2 —)
170.5 (COOMe), 52.0 (OMe), 36.1
(PhCH2 —), 31.8 (—CH2COOMe)
171.8 (COOMe), 51.5 (OMe), 33.9
(CH2COOMe), 28.7 (—SCH2 —)
122.9 (CN), 61.2 (N—C), 50.2
(PhCH2 —), 39.0 [C(CH2CH2)2], 23.5
[C(CH2CH2)2]
(continued overleaf)
Copyright 2001 John Wiley & Sons, Ltd.

114
Reference Data
Table 1. (continued)
—X—Y—CR1R2R
Cipso
Cortho
128.4
Cmeta
127.7
Cpara
127.0
Other signals
—CH2 —NH—C(CH2)4COOH, 1f
140.0
179.5 (COOH), 70.0 (N—C), 48.4
(PhCH2 —), 35.8 [C(CH2CH2)2], 24.2
[C(CH2CH2)2]
—CH2 —NMe—C(CH2)4CN, 1g
138.3
140.0
128.5
128.3
128.2
128.2
126.8
126.7
120.2 (CN), 68.8(N—C), 58.4 (PhCH2),
38.5 (NMe), 37.9 (C(CH2CH2)2), 23.2
[C(CH2CH2)2]
—CH2 —NMe—C(CH2)4COOH, 1hb
176.6 (COOH), 74.7 (N—C), 56.7
(PhCH2), 36.0 (NMe), 32.1
(C(CH2CH2)2), 24.8 [C(CH2CH2)2]
a υChloroform D 77.0 ppm.
b In DMSO-d6, υDMSO D 39.5 ppm.
sodium sulfate and evaporated. Hydrolysis of the nitriles to the
corresponding acids was achieved with concentrated sulfuric acid
REFERENCES
1. Petropoulos JC, McCall MA, Tarbel DS. J. Amer. Chem. Soc. 1953;
75: 1133.
2. Kiang AK, Mann FG. J. Chem. Soc. 1951; 1911.
3. Fong HO, Hardstaff WR, Kay DG, Langler RF, Morse RH, San-
doval D-N. Can. J. Chem. 1979; 57: 1206.
4. Strecker A. Justus Liebigs Ann. Chem. 1850; 75: 27.
5. Euerby MR, Waigh RD. J. Chem. Res. (M) 1982; 2417.
6. Ewing DF. Org. Magn. Reson. 1979; 12: 499.
°
at 20–100 C for 12 h, followed by work-up after neutralization and
°
filtration or extraction, drying and evaporation. 1e, 62%, 42–43 C;
°
1g, 76%, 130–140 C/0.45 Torr.
RESULTS
The 13C chemical shifts of the eight substituted 4-phenyl-3-(or 4-)
thia(or aza)butyric acids 1a–h are collected in Table 1.
Copyright 2001 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2001; 39: 113–114