Simplified ketimine preparation

Article abstract of DOI:10.1080/00397910802663410

An extremely simple method for preparing imines from aryl and alkylaryl ketones and a variety of amines is presented. The process involves the diffusion of the appropriate amine vapor from one arm of an H-tube into the other arm containing the ketone. Most reactions are quantitative, and, in many cases, there is no real work-up or purification required.

Full text of DOI:10.1080/00397910802663410

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Simplified Ketimine
Preparation
Neeranat Thienthong a , Ylva E. Bergman a & Patrick
Perlmutter a
a School of Chemistry, Monash University, Victoria,
Australia
Published online: 26 Jun 2009.
To cite this article: Neeranat Thienthong , Ylva E. Bergman & Patrick Perlmutter
(2009): Simplified Ketimine Preparation, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 39:15, 2683-2693
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Synthetic Communications1, 39: 2683–2693, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802663410
Simplified Ketimine Preparation
Neeranat Thienthong, Ylva E. Bergman, and Patrick Perlmutter
School of Chemistry, Monash University, Victoria, Australia
Abstract: An extremely simple method for preparing imines from aryl and
alkylaryl ketones and a variety of amines is presented. The process involves the
diffusion of the appropriate amine vapor from one arm of an H-tube into the
other arm containing the ketone. Most reactions are quantitative, and, in many
cases, there is no real work-up or purification required.
Keywords: Green chemistry, ketimine, solvent-free
INTRODUCTION
Ketimines can be prepared by the condensation of the appropriate amine
and ketone under a variety of conditions. For primary imines, these
conditions include the use of a large excess of ammonia,[1] ammonia in
alcoholic solvent,[2] in dimethylformamide (DMF)[3] or toluene[4] with
Lewis-acid catalysis, liquid ammonia,[5] and ammonia in formamide[6]
or tetrahydrofuran (THF)[7] in combination with high pressure. Second-
ary imines, on the other hand, have been prepared by mixing various
ketones and amines in aromatic[8] or chlorinated solvents[9] under reflux
or under the influence of a Lewis acid.[10] Other conditions involve the
use of alcoholic solvents in combination with Dean–Starke[11] apparatus
and solvent-free conditions under high temperature.[12]
We[13] and others[14] have recently reported solvent-free processes for
preparing primary[13] and secondary[14] imines. These methods involve
the in situ generation of ammonia or primary amine from an ammonium
Received September 26, 2008.
Address correspondence to Patrick Perlmutter, School of Chemistry, Monash
University, P. O. Box 23, Melbourne 3800, Victoria, Australia. E-mail: Patrick.
Perlmutter@sci.monash.edu.au
2683

2684
N. Thienthong, Y. E. Bergman, and P. Perlmutter
Scheme 1. Preparation of amines 3a–p.
salt and a base. We now report a new, highly efficient method for imine
formation that involves delivery of the requisite amine as a vapor (see
Scheme 1).
RESULTS AND DISCUSSION
In the experimental setup, shown in Fig. 1, neat ketone is placed in one
arm of an H-tube and either an aqueous solution of an amine or simply
a neat amine is placed in the other. The vapors from the amine or amine
solution then diffuse through the ketone, reacting to form the corre-
sponding imine. In some cases, conversion of the starting ketone to imine
Figure 1. H-tube.

Simplified Ketimine Preparation
2685
can be monitored visually because the ketone is colorless and the product
imine is yellow.
The results from this study are displayed in Table 1. Most of the
reactions were allowed to run to completion. Also, in most cases, no
purification was necessary. For those few cases where the conversion
was less then 100%, the balance of material was unreacted ketone, which
could be removed by column chromatography.
Some important trends appeared from this study. First, as before,[13]
the 2-hydroxy group is essential for the reaction to proceed. Ketones
lacking this substituent (entries 4, 6, and 8) cannot be converted to the
corresponding imine under the same conditions as for substituted
ketones. However, by adding a small amount of dry methanol to the
ketone, the imine is formed in quantitative yields. The faster reaction rate
Table 1. Formation of imines
Temp. Time Conv.
(%)
Entry
R1
R2 Ketone R3a Imine (ꢀC) (h)
1
2
2-Hydroxyphenyl 2-Pyridyl 1a
2-Pyridyl 1b
H
H
3a
3b
20
20
40
90
100
80
2-Hydroxy-5-
bromophenyl
3
4
5
6
7
8
9
2-Hydroxyphenyl 2-Pyridyl 1a
Phenyl 2-Pyridyl 1c
2-Hydroxyphenyl Phenyl
Phenyl Phenyl
2-Hydroxyphenyl Methyl
Me
Me
Me
Me
Me
Me
Me
3c
3d
3e
3f
20
20
20
20
20
20
20
3
24
48
42
20
108
24
100
100b
100
1d
1e
1f
15b,c
3g
3h
3i
100
75b,c
100
Phenyl
2-Hydroxy-5-
bromophenyl
Methyl 1g
2-Pyridyl 1b
10 2-Hydroxy-4-
methoxyphenyl
11 2-Hydroxyphenyl 2-Pyridyl 1a
Phenyl
1h
Me
3j
20
23
100
iPr
iPr
3k
3l
20
20
15
15
100
100
12 2-Hydroxy-5-
bromophenyl
2-Pyridyl 1b
13 2-Hydroxy-4-
methoxyphenyl
14 2-Hydroxyphenyl 2-Pyridyl 1a
Phenyl 1h
iPr
3m
3n
20
15
70
Bn
55
55
18
6
days
14
100
70
15 2-Hydroxyphenyl Phenyl 1d R-(þ)-a- 3o
MeBn
16 2-Hydroxyphenyl 2-Pyridyl 1a R-(þ)-a- 3p
55
75c
MeBn
days
aAqueous amine solution was used for R¼H, Me.
bSmall amount of dry methanol was added to the ketone.
cProduct not purified.

2686
N. Thienthong, Y. E. Bergman, and P. Perlmutter
(compare entries 3 versus 4, 5 versus 6, and 7 versus 8) for the 2-hydroxy
compounds is presumably due to activation through intramolecular
hydrogen bonding of the carbonyl group with the phenolic hydroxy
group.
Employing low-boiling liquid amines, for example, iso-propylamine (bp
31.7ꢀC), led to efficient conversion at rates comparable to those for aq.
MeNH2 (compare entries 9 and 11 with, respectively, entries 12 and 13).
Non volatile amines such as benzylamine (bp 184–185ꢀC) and methylbenzy-
lamine (bp 181–183ꢀC) required warming (55ꢀC) of the neat liquid amine to
increase its vapor pressure. Benzylamine gave complete conversion under
these conditions at a rate comparable to the rate for a volatile amine (com-
pare entry 14 with entry 11). The more hindered a-methylbenzylamine
required a significantly longer reaction time (compare entry 16 with 14).
EXPERIMENTAL
General
Melting points (mp) were measured on a Kofler hotstage and are uncor-
rected. Proton NMR (1H NMR) spectra were recorded at 300 MHz on a
Varian Mercury spectrometer, 300 MHz on a Bruker DPX 300 spectro-
meter, or 400 MHz on a Bruker Advance DRX 400 spectrometer. The
1H NMR spectra data refer to deuteriochloroform solution (CDCl3)
using solvent proton shift as an internal standard at 7.26 ppm. Carbon
NMR (13C NMR) spectra were recorded at 75 MHz on a Varian Mercury
spectrometry or at 100 MHz on a Bruker Advance DRX 400 spectro-
meter and are referenced using the solvent carbon shift as an internal
standard at 77.36 for 300 MHz and 77.00 ppm for the 400 MHz spectro-
meter. Chemical shifts were recorded on the d scale in parts per million
(ppm). Infrared (IR) spectra were recorded on a Perkin-Elmer 1600 Series
or Equinox IFS 55 Fourier transform spectrophotometer (cmꢁ1
scale) and refer to thin films of liquids (neat) between NaCl plates. The
intensities of each frequency (nmax) are expressed as s (strong), m
(medium), or w (weak), prefixed by b (broad) where appropriate. Low-
resolution mass spectra (MS) were recorded on a micromass platform
spectrometer (QMS, quadrupole mass electrospray). High-resolution
mass spectra (HRMS) for accurate mass determinations were recorded
on a Bruker BioApex 47e Fourier transform mass spectrometer fitted
with an Analytica electrospray source using NaI for accurate mass cali-
bration (accuracy <5 ppm). Column chromatography was carried out
on silica gel 60 (0.040–0.063 mm, Merck No. 9385). Anhydrous methanol
(MeOH) was freshly distilled from magnesium methoxide under a nitrogen

Simplified Ketimine Preparation
2687
atmosphere prior to use. Most of the chemicals were purchased from
Aldrich Chemical Company and used as received. 2-Hydroxybenzophe-
none (99%), methylamine (40% w=w aq. solution) and isopropylamine
(99 þ %) were purchased from Lancaster.
Typical Procedure
On one side of an H-tube, the described ketone was added, and to the
other side, aqueous amine solution or neat amine was added. The tube
was sealed immediately with a rubber seal stopper, and the reaction was
1
monitored by H NMR spectrometry. The excess ammonia or amine
gas was removed under reduced pressure to give the corresponding
imine.
2-[Imino(pyridin-2-yl)methyl]phenol (3a)
Imine (3a) was prepared according to the general method from ketone
(1a) (50 mg, 0.25 mmol) and 40% aq. NH4OH solution (3 mL). The
yellow-brown liquid ketone (1a) was converted to a yellow solid in
48 h with 100% conversion. The excess of ammonia gas and water
was removed under reduced pressure to give the title compound (3a)
as a yellow solid (49 mg, 100%). Mp 112ꢀC. 1H NMR (300 MHz,
CDCl3) d 6.79 (t, J ¼ 7.5 Hz, 1H), 7.07 (d, J ¼ 8.1 Hz, 1H), 7.36 (m,
2H), 7.44 (dd, J ¼ 4.8, 7.8 Hz, 1H), 7.52 (bd, J ¼ 7.8 Hz, 1H), 7.83 (t,
J ¼ 7.8 Hz, 1H), 8.77 (bd, J ¼ 4.8 Hz, 1H), 10.04 (s, 1H, NH), 14.20
(s, 1H, OH). 13C NMR (75 MHz, CDCl3) d 118.14, 118.74, 123.47,
125.15, 131.56, 133.65, 136.92, 150.71, 155.14, 163.62, 178.06. IR (neat)
nmax 3281w, 3059w, 1607s, 1584m, 1498m, 1267m, 1150m, 914m, 752s
cmꢁ1. Ms calc. (found) for C12H10N2Oþ (M þ Hþ): m=z 199.2 (199.0,
100%). HRMS calc. (found) for C12H10N2Oþ (M þ Hþ): m=z
199.0793 (199.0867).
4-Bromo-2-[imino(pyridin-2-yl)methyl]phenol (3b)
Employing the general method, after 48 h, the yellow liquid ketone (1b)
was converted to a yellow solid imine with 100% conversion. The excess
methylamine was removed under reduced pressure and the residue was
purified by flash chromatography to give the title compound (3b) as a
yellow solid. Mp 64–65ꢀC. 1H NMR (300 MHz, CDCl3) d 6.97 (d,
J ¼ 8.1 Hz, 1H), 7.48 (m, 3H), 7.52 (d, J ¼ 7.8 Hz, 1H), 7.87 (dt, J ¼ 2.1,
7.8 Hz, 1H), 8.78 (d, J ¼ 4.5 Hz, 1H). 13C NMR (75 MHz, CDCl3)

2688
N. Thienthong, Y. E. Bergman, and P. Perlmutter
d 109.54, 118.99, 120.72, 123.27, 125.40, 133.49, 136.29, 137.20, 150.72,
154.29, 162.56, 176.96. IR (neat) nmax 2924w, 1627m, 1520m, 1472w,
1435w, 1241m, 1120m, 796s cmꢁ1. Ms calc. (found) for C12H10BrN2Oþ
(M þ Hþ): m=z 277.1 (277.1, 279.2, 100%). HRMS calc. (found) for
C12H10BrN2Oþ (M þ Hþ): m=z 276.9976 (276.9973).
2-[(Methylimino)(pyridin-2-yl)methyl]phenol (3c)
Employing the general method, imine (3c) was prepared from ketone (1a)
(50 mg, 0.25 mmol) and 40% methylamine aq. solution (2 mL). After 3.5 h,
the yellow solid of the ketone was converted to an orange oil of (3c) with
100% conversion. The excess methylamine was removed under reduced pres-
sure to give the title compound (3c) as a yellow solid (53 mg, 100%). Mp
1
77–78ꢀC. H NMR (400 MHz, CDCl3) d 3.17 (s, 3H), 6.63 (t, J ¼ 7.3 Hz,
1H), 6.67 (dd, J ¼ 2.1, 7.9Hz, 1H), 6.98 (dd, J¼ 0.4, 8.3 Hz, 1H), 7.24
(dd, J ¼ 2.1, 6.7 Hz, 1H), 7.27 (dt, J ¼ 1.1, 7.7 Hz, 1H), 7.41 (dd, J ¼ 4.9,
7.7 Hz, 1H), 7.86 (dt, J ¼ 1.8, 7.7 Hz, 1H), 8.80 (d, J ¼ 4.9 Hz, 1H). 13C
NMR (100 MHz, CDCl3) d 38.32, 117.38, 118.02, 119.07, 123.12, 123.67,
130.56, 132.29, 136.55, 150.26, 152.78, 163.23, 172.91. IR (neat) nmax
1610s, 1578m, 1496m, 1450m, 1334m, 1306m, 1260m, 1005m, 755s cmꢁ1
.
Ms calc. (found) for C14H14NOþ (M þ Hþ): m=z 212.2 (212.0, 100%).
HRMS calc. (found) for C14H14NOþ (M þ Hþ): m=z 212.1075 (212.1071).
N-[Phenyl(pyridin-2-yl)methylene]methanamine (3d)
Employing the general method, imine (3d) was prepared from ketone (1c)
(50 mg, 0.27 mmol) and 40% methylamine aq. solution (2 mL). After 17 h,
no product was obtained. Dry methanol (0.5 mL) was added to the
ketone and was left to stand at room temperature for 24 h. After 24 h,
the colorless solution changed to a yellow solution. The excess methyla-
mine and methanol were removed under reduced pressure to give the title
compound (3d) as a yellow oil (53 mg, 100%). 1H NMR (400 MHz,
CDCl3) d 3.26 (s, 3H), 3.34 (s, 3H), 7.16 (m, 3H), 7.21 (m, 4H), 7.40
(m, 8H), 7.54 (m, 2H), 7.69 (dt, J ¼ 1.8, 7.9 Hz, 1H), 7.80 (m, 2H), 8.60
(dd, J ¼ 0.9, 4.9 Hz, 1H), 8.77 (dd, J ¼ 0.9, 4.9 Hz, 1H). 13C NMR
(100 MHz, CDCl3) d 41.48, 42.07, 123.07, 123.43, 123.66, 124.24,
128.28, 128.31, 128.46, 128.73, 128.81, 130.29, 136.12, 136.57, 136.62,
139.12, 149.53, 150.42, 155.91, 157.55, 168.11, 169.89. IR (neat) nmax
3056w, 1665s, 1632w, 1581m, 1567w, 1466w, 1447m, 1433m, 1319s,
1283s, 1246m, 1162m, 994m, 940m cmꢁ1. Ms calc. (found) for
C13H13Nþ2 (M þ Hþ): m=z 197.2 (197.2, 60%, 455.5, 100%). HRMS calc.
(found) for C13H13Nþ2 (M þ Hþ): m=z 197.1073 (197.1074).

Simplified Ketimine Preparation
2689
2-[(Methylimino)(phenyl)methyl]phenol (3e)
Employing the general method, imine (3e) was prepared from ketone (1d)
(50 mg, 0.25 mmol) and 40% methylamine aq. solution (2 mL). After 48 h,
the pale yellow solid ketone was converted to a yellow oil (3e) with 100%
conversion. The excess methylamine was removed under reduced pres-
1
sure to give the title compound (3e) as a yellow oil (53 mg, 100%). H
NMR (400 MHz, CDCl3) d 3.16 (s, 3H), 7.20 (m, 2H), 7.51 (m, 3H),
6.62 (dt, J ¼ 1.2, 7.6 Hz, 1H), 6.80 (dd, J ¼ 1.7, 7.9 Hz, 1H), 6.98 (dd,
J ¼ 0.9, 7.8 Hz, 1H), 7.26 (dt, J ¼ 1.7, 7.6 Hz, 1H). 13C NMR
(100 MHz, CDCl3) d 38.19, 117.04, 118.28, 119.74, 127.40, 128.83,
129.08, 131.33, 132.44, 133.64, 164.01, 175.58. IR (neat) nmax 3054m,
2924m, 1610s, 1586s, 1498m, 1453m, 1310m, 1262m, 1149m, 1041m,
753s cmꢁ1. Ms calc. (found) for C13H13N2Oþ (M þ Hþ): m=z 213.2
(213.3, 100%). HRMS calc. (found) for C13H13N2Oþ (M þ Hþ): m=z
213.1028 (213.1028).
2-[1-(Methylimino)ethyl)phenol] (3g)
Employing the general method, imine (3g) was prepared from ketone (1f)
(200 mL, 0.17 mmol) and 40% methylamine aq. solution (2 mL). The
colorless liquid ketone was converted to a yellow liquid of imine (3g)
within 35 min with 33% conversion. After 20 h, the yellow liquid solidified
to a yellow solid corresponding to 3g with 100% conversion. The excess
methylamine was removed under reduced pressure to give the title com-
1
pound (3g) as a yellow solid (25 mg, 100%). Mp 68–69ꢀC. H NMR
(400 MHz, CDCl3) d 2.33 (s, 3H), 3.33 (s, 3H) 6.73 (dt, J ¼ 1.2, 7.6 Hz,
1H), 6.92 (d, J ¼ 8.3 Hz, 1H), 7.27 (dt, J ¼ 8.3 Hz, 1H), 7.49 (dd,
J ¼ 1.5, 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 14.05, 35.85,
116.84, 119.26, 119.56, 128.21, 132.95, 165.45, 173.48. IR (neat) nmax
3368w, 1617s, 1503m, 1453m, 1317m, 1010m, 767m cmꢁ1. Ms calc.
(found) for C9H12NOþ (M þ Hþ): m=z 150.1 (244, 100%). HRMS calc.
(found) for C9H12NOþ (M þ Hþ): m=z 150.0919 (150.1510).
4-Bromo-2-[(methylimino)(pyridin-2-yl)methyl]phenol (3i)
Employing the general method, imine (3i) was prepared from ketone (1b)
(55 mg, 0.19 mmol) and 40% methylamine aq. solution (2 mL). After 24 h,
the yellow solid was converted to an orange liquid corresponding to 3i
with 100% conversion. The excess methylamine was removed under
reduced pressure to give the title compound (3i) as a yellow oil (57 mg,
1
100%). H NMR (400 MHz, CDCl3) d 3.13 (s, 3H), 6.72 (d, J ¼ 2.4 Hz,

2690
N. Thienthong, Y. E. Bergman, and P. Perlmutter
1H), 6.84 (d, J ¼ 8.8 Hz, 1H), 7.24 (dt, J ¼ 1.0, 7.7 Hz, 1H), 7.29 (dd,
J ¼ 2.4, 8.8 Hz, 1H), 7.40 (dd, J ¼ 4.8, 7.7 Hz, 1H), 7.85 (dt, J ¼ 1.7,
7.7 Hz, 1H), 8.76 (d, J ¼ 4.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) d
38.33, 108.88, 120.20, 120.28, 123.18, 124.17, 132.68, 135.15, 136.92,
150.52, 151.79, 162.69, 172.02. IR (neat) nmax 1616s, 1585s, 1567m,
1475s, 1430w, 1402w, 1386w, 1332m, 1291s, 1256m, 1012w, 824s, cmꢁ1
.
Ms calc. (found) for C13H12BrN2Oþ (M þ Hþ): m=z 291.1 (291.2.
293.2, 100%). HRMS calc. (found) for C13H12BrN2Oþ (M þ Hþ): m=z
291.0133 (291.0124, 293.0145).
5-Methoxy-2-[(methylimino)(phenyl)methyl]phenol (3j)
Employing the general method, imine (3j) was prepared from ketone
(1h) (50 mg, 0.22 mmol) and 40% methylamine aq. solution (2 mL).
After 8 h, the pale yellow solid ketone was converted to a yellow solid
corresponding to 3j with 80% conversion. After 23 h, 3j was obtained
with 100% conversion. The excess methylamine was removed under
reduced pressure to give the title compound (3j) as a yellow solid
1
(52 mg, 100%). Mp 95–96ꢀC. H NMR (400 MHz, CDCl3) d 3.05 (s,
3H), 3.79 (s, 3H), 6.06 (dd, J ¼ 2.5, 9.0 Hz, 1H), 6.36 (d, J ¼ 2.5 Hz,
1H), 6.60 (dt, J ¼ 9.0 Hz, 1H), 7.20 (m, 2H), 7.48 (m, 3H). 13C NMR
(100 MHz, CDCl3) d 35.44, 55.27, 102.24, 105.62, 112.27, 127.58,
128.83, 129.41, 132.82, 164.61, 172.05, 174.56. IR (neat) nmax 2853m,
1597s, 1547s, 1444w, 1347w, 1285m, 1212m, 1165m, 1109m, 1031m,
708m cmꢁ1. Ms calc. (found) for C15H16NOþ2 (M þ Hþ): m=z 242.3
(242.3, 100%). HRMS calc. (found) for C15H16NOþ2 (M þ Hþ): m=z
242.1181 (242.1170).
2-[(Isopropylimino)(pyridin-2-yl)methyl]phenol (3k)
Employing the general method, imine (3k) was prepared from ketone (1a)
(25 mg, 0.12 mmol) and isopropylamine (2 mL). After 15 h, the yellow
solid was converted to an orange liquid (3k) with 100% conversion. The
excess isopropylamine was removed under reduced pressure to give the
1
title compound (3k) as a yellow oil (30 mg, 100%). H NMR (400 MHz,
CDCl3) d 1.28 (d, J ¼ 6.2 Hz, 6H) 3.17 (sep, J ¼ 6.2 Hz, 1H), 6.65 (m,
2H), 6.98 (d, J ¼ 8.3 Hz, 1H), 7.26 (m, 1H), 7.28 (dt, J ¼ 1.2, 7.7 Hz,
1H), 7.41 (dd, J ¼ 4.9, 7.7 Hz, 1H), 7.86 (dt, J ¼ 1.8, 7.7 Hz, 1H), 8.80
(d, J ¼ 4.9 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 24.37, 52.34, 117.75,
118.28, 119.39, 123.24, 123.91, 131.04, 132.52, 136.71, 150.42, 153.60,
163.58, 169.51. IR (neat) nmax 2968m, 2924m, 1610s, 1584m, 1499m,
1455m, 1427w, 1305w, 1260m, 1151m, 752s cmꢁ1. Ms calc. (found) for

Simplified Ketimine Preparation
2691
C15H17N2Oþ (M þ Hþ): m=z 241.3 (241.0), 100%). HRMS calc. (found)
for C15H17N2Oþ (M þ Hþ): m=z 241.1341 (241.1366).
4-Bromo-2-[(isopropylimino)(pyridin-2-yl)methyl]phenol (3l)
Employing the general method, imine (3l) was prepared from ketone (1b)
(25 mg, 0.09 mmol) and isopropylamine (2 mL). After 15 h, the yellow
solid was converted to an orange solid (3l) with 100% conversion. The
excess isopropylamine was removed under reduced pressure to give the
1
title compound (3l) as a yellow solid (28 mg, 100%). Mp 145–146ꢀC. H
NMR (400 MHz, CDCl3) d 1.22 (d, J ¼ 6.3 Hz, 6H), 3.42 (sep, J ¼ 6.2 Hz,
1H), 6.68 (d, J ¼ 2.5 Hz, 1H), 6.87 (d, J ¼ 8.8 Hz, 1H), 7.28 (dt, J ¼ 1.0,
7.7 Hz, 1H), 7.33 (dd, J ¼ 2.4, 8.9 Hz, 1H), 7.44 (dd, J ¼ 4.8, 7.7 Hz,
1H), 7.87 (dt, J ¼ 1.7, 7.7 Hz, 1H), 8.79 (d, J ¼ 4.8 Hz, 1H). 13C NMR
(100 MHz, CDCl3) d 24.28, 52.49, 109.22, 120.42, 120.63, 123.23,
124.32, 133.12, 135.34, 136.99, 152.67, 162.97, 168.65. IR (neat) nmax
2968m, 2923m, 2853w, 1612s, 1582s, 1565s, 1479s, 1427m, 1381m,
1289s, 1151m, 828m cmꢁ1. Ms calc. (found) for C15H16BrN2Oþ
(M þ Hþ): m=z 319.2 (319.1, 321.1 100%). HRMS calc. (found) for
C15H16BrN2Oþ (M þ Hþ): m=z 319.0441 (319.0446, 321.0427).
2-[(Isopropylimino)(phenyl)methyl]-5-methoxyphenol (3m)
Employing the general method, imine (3m) was prepared from ketone (1h)
(25 mg, 0.01 mmol) and isopropylamine (2 mL). After 15 h, the pale yellow
solid was converted to a yellow solid (3m) with 70% conversion. The resi-
due was purified by flash chromatography to give the title compound (3m)
as a yellow solid (15 mg, 50%). Mp 88–89ꢀC. 1H NMR (400 MHz, CDCl3)
d 1.21 (d, J ¼ 6.4 Hz, 6H), 3.49 (sep, J ¼ 6.2 Hz, 1H), 3.77 (s, 3H), 6.08 (dd,
J ¼ 2.6, 9.0 Hz, 1H), 6.37 (d, J ¼ 2.5 Hz, 1H), 6.55 (dt, J ¼ 9.0 Hz, 1H),
7.23 (m, 2H), 7.49 (m, 3H). 13C NMR (100 MHz, CDCl3) d 24.30,
50.20, 55.52, 102.38, 105.70, 112.56, 127.66, 128.94, 129.43, 133.16,
133.51, 164.55, 171.37, 171.41. IR (neat) nmax 3054w, 1606s, 1518w,
1443w, 128þ3m, 1265m, 1211m, 1111m cmꢁ1. Ms calc. (found) for
C17H20NO2 (M þ Hþ): m=z 270.3 (270.1, 100%). HRMS calc. (found)
for C17H20NO2þ (M þ Hþ): m=z 270.1494 (270.1497).
2-[(Benzylimino)(pyridin-2-yl)methyl]phenol (3n)
Employing the general method, imine (3n) was prepared from ketone (1a)
(100 mg, 0.50 mmol) and benzylamine (1 mL). After 24 h, the reaction

2692
N. Thienthong, Y. E. Bergman, and P. Perlmutter
mixture showed no product. The benzylamine was warmed to 55ꢀC and
left to stand at this temperature for 18 h. After 18 h, the yellow solid was
converted to a dark yellow solid (3n) with 100% conversion. The excess
benzylamine was removed under reduced pressure to give the title com-
1
pound (3n) as a yellow solid (144 mg, 100%). Mp 83–84ꢀC. H NMR
(400 MHz, CDCl3) d 4.54 (s, 2H), 6.69 (m, 2H), 7.00 (d, J ¼ 8.3 Hz, 1H),
7.28 (m, 7H), 7.43 (dd, J ¼ 4.9, 7.7 Hz, 1H), 7.86 (dt, J ¼ 1.7, 7.7 Hz, 1H),
8.83 (d, J ¼ 4.9 Hz, 1H). 13C NMR (100 MHz, CDCl3) d 55.59, 117.76,
118.02, 119.25, 123.21, 123.88, 127.16, 127.62, 128.65, 131.00, 132.60,
136.63, 136.68, 138.76, 150.42, 153.60, 163.58, 169.51. IR (neat) nmax
3061w, 1609s, 1584m, 1469w, 1452w, 1334w, 1259w, 1153w, 750s cmꢁ1
.
Ms calc. (found) for C20H17NOþ (M þ Hþ): m=z 289.3 (289.2, 100%).
HRMS calc. (found) for C20H17NOþ (M þ Hþ): m=z 289.1456 (289.1337).
(R)-2-[Phenyl-(1-phenylethylimino)methyl]phenol (3o)
Employing the general method, imine (3o) was prepared from ketone (1d)
(100 mg, 0.50 mmol) and R-(þ)-a-methylbenzylamine (3 mL). After 24 h,
the reaction mixture showed no product. The amine solution was warmed
to 55ꢀC and left to stand at this temperature for 6 days. The excess amine
was removed under reduced pressure to give a yellow residue. The residue
was purified by flash chromatography to give the title compound (3o) as
a yellow solid (113 mg, 70%). Mp 130–132ꢀC (lit.[15] 128–130ꢀC). 1H
NMR (400 MHz, CDCl3) d 1.53 (d, J ¼ 6.6 Hz, 3H) 4.51 (q, J ¼ 6.6 Hz,
1H), 6.63 (dt, J ¼ 1.2, 7.2 Hz, 1H), 7.76 (dd, J ¼ 1.7, 8.0 Hz, 1H), 6.99
(m, 2H), 7.21–7.33 (m, 8H), 7.42–7.56 (m, 3H). Ms calc. (found) for
C21H19NOþ (M þ Hþ): m=z 302.1 (301.15, 100%). HRMS calc. (found)
for C21H19NOþ (M þ Hþ): m=z 302.1549 (301.1469).
CONCLUSION
In summary, we have developed a simplified method for converting
ketones to ketimines under very mild conditions. The process also max-
imizes the incorporation of all materials used in the process into the final
product as well as minimizes the generation of solvent waste.
ACKNOWLEDGMENTS
This project was supported in part by the Australian Research Council
Centre for Green Chemistry. N. T. is grateful to Monash University
for scholarship support.

Simplified Ketimine Preparation
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