Pentylpropane-1,3-diol (3 ). A solution of compound 2
2,3-Difluorophenol (7). Hydrogen peroxide (10%, 340 cm3,
1 mol) was added dropwise to a stirred solution of compound
6 (47 g, 0.3 mol) in diethyl ether (350 cm3) and heated under
reflux. The stirred mixture was heated under reflux for a
further 2.5 h, and then cooled. The ethereal layer was separated
and the aqueous layer partitioned into diethyl ether
(2×200 cm3). The combined ether extracts were washed with
aqueous sodium hydroxide (10%, 4×100 cm3) and the separ-
ated aqueous layers were acidified with 36% hydrochloric acid.
The product was partitioned from the aqueous layer into
diethyl ether (3×100 cm3) and the combined ether extracts
5
5
(59.2 g, 0.26 mol) in sodium-dried diethyl ether (50 cm3) was
added dropwise to a mixture of lithium aluminium hydride
(19.5 g, 0.52 mol) in dry diethyl ether (450 cm3) with vigorous
stirring and the mixture heated under gentle reflux. During
this period, 4×50 cm3 portions of dry diethyl ether were
added. After further heating (1 h), water (75 cm3) was added
carefully followed by sulfuric acid (20%, 350 cm3) in order to
decompose the lithium aluminium complex. The aqueous layer
was partitioned with diethyl ether (2×100 cm3) and the com-
bined ether extracts were washed with water (2×100 cm3) and
were washed with water and dried (MgSO ). The solvent was
dried (MgSO ). The solvent was removed in vacuo to give the
4
4
removed in vacuo to give an off white solid. Yield=39 g
product as a colourless oil. Yield=31 g (83%).
(100%); mp 30–32 °C.
d
(270 MHz; CDCl ; Me Si): 0.90 (3H, t, J 6.5, CH –),
H
3
4
3
d
(270 MHz; CDCl ; Me Si): 5.15 (1H, d, OH), 6.67–6.82
1.30 (8H, m, CH C H ), 1.77 (1H, m, J 4.0, –C H CHCH –),
3 4
2.74 (2H, s, –OH), 3.64 [2H, dd, J 10.5 and 7.5, –(CH OH) ],
3.82 [2H, dd, J 10.5 and 4.0, –(CH OH) ]. n
3700–3040 (bonded O–H str), 2962 (CH –, C–H asym str),
2930 (–CH –, C–H asym str), 2882 (CH –, C–H sym str),
H
3
4
8
4
8
2
(2H, ABCXY, –C H F ), 6.90–7.00 (1H, ABCXY, –C H F ).
6
3 2
6 3 2
2
2
n
(CDCl film)/cm−1: 3700–3000 (bonded O–H str), 1630,
(film)/cm−1:
max
3
2
2
3
max
1535, 1513, 1492 and 1482 (CLC str), 1310 (O–H in-plane
def ), 1255, 1182 (C–O str), 1025, 910, 736 and 700 (1,2,3-
trisub, o.o.p.d.). m/z: 130 [M]+.
2
2
3
2866 (–CH –, C–H sym str), 1470 (CH – asym, -CH – sci,
C–H def ), 1381 (O–H in-plane def ), 1035 (C–O str). m/z: 128
3
2
2,3-Difluoro-1-pentoxybenzene (8 ). A solution of 1-bromo-
[M−H O]+, 110, 98.
5
2
pentane (30.5 g, 0.2 mol) in acetone (50 cm3) was added
dropwise to a stirred mixture of compound 7 (26 g, 0.2 mol)
and potassium carbonate (55.5 g, 0.4 mol) in acetone
(200 cm3) at room temperature. The stirred mixture was heated
under reflux (48 h) (i.e. until GLC analysis revealed complete
reaction) and the crude product was extracted into diethyl
ether (2×200 cm3) and dried (Na SO ). The solvent was
removed in vacuo and the pure product obtained by distillation
under reduced pressure as a colourless liquid. Yield=37 g
(92%); bp 75–78 °C/0.6 mmHg.
2-(4-Bromophenyl)-5-pentyl-1,3-dioxane (4 ). A mixture of
5
compound 3 (31 g, 0.21 mol), 4-bromobenzaldehyde (38.8 g,
5
0.21 mol) and toluene-4-sulfonic acid (0.11 g, 0.6 mmol) in
dry toluene (200 cm3) was heated under reflux (3 h) using a
Dean and Stark trap to remove water as it was produced. On
cooling to room temperature, the mixture was poured into
aqueous sodium hydrogen carbonate solution (5%, 70 cm3)
and the separated organic layer was washed with aqueous
sodium hydrogen carbonate solution (5%, 2×60 cm3), water
2
4
d
(270 MHz; CDCl ; Me Si): 0.93 (3H, t, J 7.0, CH –),
H
3
4
3
(2×60 cm3) and dried (MgSO ). The solvent was removed
1.43 (4H, m, CH C H –), 1.83 (2H, qn, J 7.0, –CH CH O–),
3 2
4.03 (2H, t, J 6.5, –CH O–), 6.74 (2H, ABCXY, –C H F ),
6.96 (1H, ABCXY, –C H F ). n
(CH –, C–H asym str), 2942 (–CH –, C–H asym str), 2882
(CH –, C–H sym str), 2872 (–CH –, C-H sym str), 1624, 1517
and 1487 (CLC str), 1473 (CH – asym, –CH – sci, C–H def ),
1322, 1294, 1257 (aryl–O str), 1076 (alkyl–O str), 768 and 710
4
4
2
2
in vacuo and the residue purified by crystallisation from
2
6
6 3 2
methanol to remove the cis-isomer. Yield=33.1 g (50%);
mp 76.5–77.0 °C.
(KCl disc)/cm−1: 2968
3 2
max
2
3
3
d
(270 MHz; CDCl ; Me Si): 0.89 (3H, t, J 6.5, CH –),
H
3
4
3
2
1.09 (2H, q, J 7.0, CH CH –), 1.29 (6H, m, –CH C H –),
2.11 (1H, m, 5-H), 3.52 (2H, dd, J 11.5 and 11.5, Ha), 4.22
(2H, dd, J 11.5 and 4.5, He), 5.36 (1H, s, 2-H), 7.35 (2H,
3
2
2 3 6
3
2
(1,2,3-trisub, C–H o.o.p.d.). m/z: 200 [M]+, 130.
AA∞BB∞, –C H –), 7.49 (2H, AA∞BB∞, –C H –). n
(KBr
6
4
6
4
max
2
disc)/cm−1: 2964 (CH –, C–H asym str), 2936 (–CH –, C–H
2,3-Difluoro-4-pentoxyphenylboronic acid (9 ). Quantities. n-
3
5
Butyllithium (20 cm3, 10.0 M in hexanes, 0.2 mol), compound
asym str), 2868 (CH –, –CH –, C–H sym str), 1600 and 1490
3
2
8 (37 g, 0.19 mol) and triisopropyl borate (70 g, 0.38 mol).
(CLC str), 1470 (CH – asym, –CH – sci, C–H def ), 1387
5
3
2
The experimental procedure was as described previously for
(CH –, C–H sym def ), 1168, 1132, 1088, 1073, 1026 and 1014
3
the preparation of compound 6. Yield=45 g (100%).
(C–O str), 982, 805 (1,4-disub, C–H o.o.p.d.). m/z: 314 [M]+,
d
(270 MHz; CDCl ; Me Si): 0.94 (3H, t, J 6.5, CH –),
312 [M]+, 185, 183, 157, 155.
H
3
4
3
1.42 (4H, m, –C H –), 1.84 (2H, qn, J 7.0, –CH CH O–),
3.15 [2H, br, –B(OH) ], 4.07 (2H, t, J 6.5, –CH O–), 6.77
(1H, ABXY, –C H F –), 7.44 (1H, ABXY, –C H F –). n
2
4
2
2
2
2
2,3-Difluorophenylboronic acid (6). n-Butyllithium (30 cm3,
10.0 M in hexanes, 0.3 mol) was added dropwise to a stirred,
cooled (−78 °C) solution of 1,2-difluorobenzene (34.5 g,
0.3 mol) in dry THF (350 cm3) under an atmosphere of dry
nitrogen. The reaction mixture was stirred (2.5 h), then a
previously cooled (−78 °C) solution of triisopropyl borate
(113 g, 0.6 mol) in dry THF (200 cm3) was added dropwise
at −78 °C. The reaction mixture was allowed to warm to
room temperature overnight then stirred (1 h) with hydro-
chloric acid (10%, 300 cm3). The product was partitioned into
diethyl ether (2×300 cm3), and the combined ether extracts
6
2 2
6
2 2
max
3
(KBr disc)/cm−1: 3700–3000 (bonded O–H str), 2960 (CH –,
C–H asym str), 2940 (–CH –, C–H asym str), 2880 (CH –,
2
3
C–H sym str), 2868 (–CH –, C–H sym str), 1630 and 1520
(CLC str), 1470 (CH – asym, –CH – sci, C–H def ), 1365
(B–O str), 1306, 1222 (aryl–O str), 1084 and 1030 (alkyl–O
str), 908, 820 (1,4-disub, C–H o.o.p.d.), 790, 747. m/z:
(180 °C): 678 [M]+−trimer, 468, (120 °C): 244 [M]+, 174, 130.
2
3
2
1-(2,3-Difluorophenyl)pentan-1-ol (10 ). n-Butyllithium
5
(50 cm3, 10.0 M in hexanes, 0.5 mol) was added dropwise to
were washed with water and dried (MgSO ). The solvent was
a stirred and cooled (−78 °C) solution of 1,2-difluorobenzene
(57 g, 0.5 mol) in dry THF (600 cm3) under an atmosphere
of dry nitrogen. The mixture was maintained under these
conditions (3 h), then a solution of pentanal (43.1 g, 0.5 mol)
in dry THF (50 cm3) was added dropwise at −78 °C. The
temperature of the reaction mixture was allowed to reach
room temperature overnight. An aqueous solution of
ammonium chloride (27 g in 160 cm3 water) was added and
the product was extracted into diethyl ether (2×150 cm3).
4
removed in vacuo to yield colourless crystals. Yield=47 g
(100%).
d (270 MHz; CDCl ; Me Si): 5.10 [2H, d, J 5.5, –B(OH) ],
H
3
6
4
3 2
2
7.15 (1H, ABCXY, –C H F ), 7.27 (1H, ABCXY, –C H F ),
6 3 2
7.57 (1H, ABCXY, –C H F ).
n
(KCl disc)/cm−1:
6
3 2
max
3700–3000 (bonded O–H str), 1628, 1588 and 1472 (CLC str),
1360 (B–O str), 1270, 1048, 908, 796 and 734 (1,2,3-trisub,
C–H o.o.p.d.). m/z: 158 [M]+, 140, 114.
J. Mater. Chem., 1999, 9, 1669–1677
1671