Novel diamides of dipiridyldicarboxylic acid
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 4, April, 2012
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was suspended in carbon tetrachloride (300 mL), acetyl bromide
(100 mL) was added, and the mixture was refluxed with stirring
for 4 h. After cooling, the precipitate was filtered off, washed
with a solution of soda and water, and dried in air. The target
dibromide was obtained as a white powder with the temperature
of decomposition >300 С in a yield of 22 g (59%). Н NMR
(DMSOꢀd6), : 2.51 (s, 6 Н); 7.84 (d, 2 Н, J = 1.7 Hz); 7.92
(d, 2 Н, J = 1.7 Hz).
4,4´ꢀDibromoꢀ6,6´ꢀdimethylꢀ2,2´ꢀdipyridyl (9). A mixture of
4,4´ꢀdibromoꢀ6,6´ꢀdimethylꢀ2,2´ꢀdipyridyl diꢀNꢀoxide (20 g,
0.053 mol) and phosphorus tribromide (20 mL) in methylene
dichloride (150 mL) was stirred at ambient temperature for 4 h
and left to stay for 16 h. The solution was poured into ice (300 mL)
and neutralized by the addition of soda until carbon dioxide
stopped evolving. The obtained solution was extracted with meꢀ
thylene dichloride (4×50 mL). The extract was dried over anhyꢀ
drous sodium sulfate. After the solvent was evaporated, the prodꢀ
uct was obtained in a yield of 14.8 g (81%), m.p. 158—160 С.
1Н NMR (CDCl3), : 2.41 (s, 6 Н); 8.48 (d, 2 Н, J = 1.7 Hz);
8.76 (d, 2 Н, J = 1.7 Hz).
4ꢀHexylacetanilide (17). 4ꢀHexylacetophenone (40.8 g,
0.2 mol) was dissolved in acetic acid (200 mL) containing conꢀ
centrated sulfuric acid (50 mL, 92 g) at 60—70 С. Sodium azide
(0.3 mol) was introduced by small portions with vigorous stirring
avoiding too intense dinitrogen evolution (the addition took about
2 h). Stirring was continued for 3 h more under the same condiꢀ
tions. Then the mixture was poured into ice (3 L) and left to
warm to ambient temperature. The precipitate was filtered off
and washed with water containing a small amount of soda to
remove adsorbed acids. A white powder with m.p. 92—92.5 С.
(Ref. 14: 91—92 С) was obtained in a yield of 37.23 g (71%).
1Н NMR (CDCl3), : 0.98 (t, 3 Н, J = 6.7 Hz); 1.29 (m, 6 Н);
1.58 (quint, 2 Н, J = 7.5 Hz); 2.30 (s, 3 Н); 2.55 (t, 2 Н, J = 7.7 Hz);
7.12 (d, 2 Н, J = 8.2 Hz), 7.30 (br.s, 1 Н); 7.39 (d, 2 H, J = 8.2 Hz).
13С NMR (CDCl3), : 14.06, 22.58, 24.51, 28.88, 31.43, 31.70,
35.34, 119.99, 128.81, 135.45, 139.10, 168.20.
4ꢀHexylꢀNꢀethylaniline (18). A solution of 4ꢀhexylacetanilide
(26.2 g, 0.119 mol) in anhydrous tetrahydrofuran (150 mL) was
added on cooling in a water bath and stirring to a suspension of
lithium alumohydride (5.24 g, 0.138 mol) in anhydrous tetraꢀ
hydrofuran (50 mL). After the end of dihydrogen evolution, the
reaction mixture was refluxed for 6 h and left to stay for 16 h.
The reaction mixture was decomposed by the consecutive addiꢀ
tion of water (5.24 mL), a 15% solution of sodium hydroxide
(5.24 mL), and water (3×5.24 mL) with stirring and cooling in
a water bath. The precipitate was filtered off and washed with
tetrahydrofuran (3×30 mL). The solution was dried over anhyꢀ
drous calcium dichloride. Tetrahydrofuran was evaporated, and
the obtained amine was distilled in vacuo collecting the fraction
with b.p. 139—140 С (3 Torr). The target compound was obꢀ
tained as a viscous yellow liquid* in a yield of 22.8 g (93%).
1Н NMR (CDCl3), : 0.87 (t, 3 Н, J = 3.9 Hz); 1.02 (t, 3 Н,
J = 6.9 Hz); 1.28 (m, 4 Н); 1.55 (m, 2 Н); 2.64 (m, 2 Н); 2.90
(t, 2 Н, J = 5.9 Hz); 3.46 (s, 1 H); 3.58 (q, 2 Н, J = 6.9 Hz); 6.38
(d, 2 Н, J = 4.8 Hz); 6.89 (d, 2 Н, J = 4.8 Hz).
Synthesis of diamides 1—8 (general procedure). The starting
acid was refluxed in thionyl chloride (5 mL of SOCl2 per 1 g of
the acid), adding dimethylformamide (0.5 mL) for 2.5 h. Thioꢀ
nyl chloride was removed by distillation, and the remained acid
chloride was dried in a vacuum of a waterꢀjet pump and disꢀ
solved in anhydrous tetrahydrofuran (10 g of THF per 1 g of the
starting acid). The obtained solution was added with stirring in
portions to a mixture of the starting amine taken in an amount of
2.1 equivalents to the acid and in the equal volume with the
amount of triethylamine in anhydrous tetrahydrofuran (10 mL
of THF per 1 g of the amine). After the end of addition, the
obtained mixture was protected from moisture with a calcium
dichloride tube, stirred for 4—5 h at 40—50 С, and left to stay
for 16 h. The equal volume of water was added to the reaction
mixture, and the organic layer was separated. The aqueous fracꢀ
tion was three times extracted with diethyl ether. The combined
organic fractions were washed with water and dried over anhyꢀ
1
4,4´ꢀDibromoꢀ2,2´ꢀdipyridylꢀ6,6´ꢀdicarboxylic acid (13).
The starting 4,4´ꢀdibromoꢀ6,6´ꢀdimethylꢀ2,2´ꢀdipyridyl (5 g,
0.015 mol) was dissolved at 50 С in concentrated sulfuric acid
(70 mL), and chromium anhydride (7.5 g, 0.075 mol) was introꢀ
duced by portions, controlling the temperature increase not highꢀ
er than 75 С. The obtained solution was stirred for 2 h at 70 С
and poured into ice (300 mL). The precipitate formed was
filtered off, washed on the filter with water, ethanol, and diꢀ
ethyl ether, and dried in air. The target diacids was obtained
as a white powder in a yield of 4.8 g (80%), m.p. 274—275 С
1
(with decomp.). Н NMR (DMSOꢀd6), : 8.91 (br.s, 2 Н); 8.29
(br.s, 2 Н).
Synthesis of 3ꢀ and 4ꢀfluoroꢀNꢀethylanilines (14 and 15) from
substituted anilines was carried out by analogy to the procedure
for 4ꢀchloroꢀNꢀethylaniline.15 The total yields of the final prodꢀ
ucts were 43% for 3ꢀfluoroꢀNꢀethylaniline (14) and 52% for
4ꢀfluoroꢀNꢀethylaniline (15).
Compound 14, b.p. 130—134 С (25 Torr). 1Н NMR (CDCl3),
: 0.93 (t, 3 Н, J = 7.1 Hz); 2.74 (q, 2 Н, J = 7.1 Hz); 3.43 (br.s,
1 H); 6.11 (br.m, 2 Н), 6.27 (t, 1 Н, J = 8.1 Hz); 6.90 (m, 1 Н).
Compound 15, b.p. 112—114 С (25 Torr). 1Н NMR (CDCl3),
: 0.72 (t, 3 Н, J = 7.3 Hz); 2.52 (q, 2 Н, J = 7.3 Hz); 3.04 (br.s,
1 Н); 6.01 (m, 2 Н), 6.53 (t, 2 Н, J = 6.8 Hz).
4ꢀHexylacetophenone (16). Acetyl chloride (0.22 mol) was
added on cooling with ice and stirring to a suspension of AlCl3
(28 g, 0.23 mol) in CH2Cl2 (100 mL). The resulting solution
was stirred for 15 min. Hexylbenzene (32.4 g, 0.2 mol) was
added on cooling with ice and stirring. The obtained soluꢀ
tion was stirred for 2 h. After the end of stirring, the reacꢀ
tion mixture was poured into a mixture of concentrated hydroꢀ
chloric acid (200 mL) and ice (200 g). The organic fraction was
separated, and the aqueous fraction was extracted with methylꢀ
ene dichloride (2×50 mL). The combined organic extracts were
washed with water and dried over calcium dichloride. The
solvent was removed on a rotary evaporator. The residue was
distilled in vacuo, collecting the fraction with b.p. 130—132 С
(2 Torr). Target acetophenone was obtained in a yield of 33.86 g
* An increase in the amount of the used alumohydride and reꢀ
duced acetanilide does not increase the amount of isolated amine.
This is related, most likely, to the fact that an insoluble layer of
metallized amine and an amide layer poorly soluble in THF are
formed on the lithium alumohydride surface. Therefore, to obꢀ
tain larger amounts of Nꢀethylanilines, it is reasonable to carry
out several parallel reactions with the indicated loads and to
combine the obtained filtrates.
1
(83%). Н NMR (CDCl3), : 0.89 (t, 3 Н, J = 6.6 Hz); 1.37
(m, 4 Н); 1.66 (quint, 4 Н, J = 7.2 Hz); 2.52 (s, 3 Н); 2.81
(t, 2 Н, J = 7.7 Hz); 7.35 (d, 2 Н, J = 8.1 Hz) 7.95 (d, 2 Н,
J = 8.1 Hz).