Catalytic amination of aldehydes to amides

Article abstract of DOI:10.1002/1099-0690(200102)2001:3<523::AID-EJOC523>3.0.CO;2-Z

Aldehydes react in a disproportionation reaction in the presence of rhodium catalysts to yield amines and amides. By adding N-methylmorpholine N-oxide as an oxidant in the presence of catalytic amounts of rhodium, the oxidative amination of aldehydes proceeds selectively to give the corresponding amide. Both aliphatic and aromatic aldehydes react with secondary amines to yield carboxylic acid amides in good to excellent yields.

Full text of DOI:10.1002/1099-0690(200102)2001:3<523::AID-EJOC523>3.0.CO;2-Z

FULL PAPER
Catalytic Amination of Aldehydes to Amides
Annegret Tillack,[a] Ivo Rudloff,[a] and Matthias Beller*[a]
Keywords: Amination / Aldehydes / Rhodium / Catalysis / Oxidation / Amides
Aldehydes react in a disproportionation reaction in the pres-
ence of rhodium catalysts to yield amines and amides. By
adding N-methylmorpholine N-oxide as an oxidant in the
presence of catalytic amounts of rhodium, the oxidative am-
ination of aldehydes proceeds selectively to give the corres-
ponding amide. Both aliphatic and aromatic aldehydes react
with secondary amines to yield carboxylic acid amides in
good to excellent yields.
Introduction
tion, we studied the reaction of benzaldehyde with styrene
and morpholine in the presence of catalytic amounts of
[Rh(COD)2]BF4 in THF at 100 °C. Surprisingly, we ob-
served N-benzylmorpholine and N-benzoylmorpholine as
major products, making it clear that styrene did not take
part in this reaction. Therefore we investigated the reaction
of benzaldehyde and morpholine (Scheme 2) more closely.
Aromatic and aliphatic amides are of significant import-
ance in organic chemistry as integral parts of polymers, nat-
ural products, and pharmaceuticals. In general, amides are
synthesized from amines and activated carboxylic acid de-
rivatives with the same oxidation level as the resulting prod-
uct.[1] Another attractive method is the aminocarbonylation
of olefins with carbon monoxide and amines in the presence
of late transition metal catalysts.[2] An alternative approach,
from economically attractive and available starting mat-
erials, is the direct oxidative amination of aldehydes. So far,
only a few examples of this type of process have been re-
ported. Among them the palladium- and ruthenium-cata-
lyzed transformations of aldehydes to amides are the only
transition metal-catalyzed variants known.[3] The palla-
dium-catalyzed reaction, however, requires the use of a stoi-
chiometric amount of aryl bromide as the oxidant, and the
ruthenium-catalyzed reaction proceeds with only moderate
yields. Similarly, oxidative amidations require the use of a
stoichiometric or excess amount of transition metal.[4]
Recently, we have discovered new types of oxidative ami-
nations of olefins with amines to give enamines
(Scheme 1).[5]
Scheme 2
N-benzoylmorpholine was obtained in 52% yield, from
benzaldehyde (4.40 mmol), morpholine (2.20 mmol),
[Rh(COD)2]BF4 (0.055 mmol), and PPh3 (0.11 mmol). In
addition 15% of N-benzylmorpholine and small amounts
(Ͻ 2%) of benzyl alcohol and benzyl benzoate were isol-
ated. This new type of disproportionation reaction requires
the presence of a cationic rhodium catalyst. In the absence
of rhodium or in the presence of [Rh(COD)Cl]2·2PPh3, no
amide formation was observed. Instead, the 2:1-addition
product
of
morpholine
and
benzaldehyde
PhCH[N(CH2CH2)2O]2 could be detected. Variation of the
ratio of benzaldehyde to morpholine showed that the amide
yield increased up to 65% with an increasing amount of
benzaldehyde (Table 1, entries 1Ϫ3). Using toluene as the
solvent similar reactions were observed, although N-benzyl-
morpholine and N-benzoylmorpholine were produced in
equal amounts (Table 1, entries 4Ϫ6).
As shown in Table 1, other secondary amines (e.g. piper-
idine, N-methyl-N-butylamine) as well as other aliphatic
and aromatic aldehydes (e.g. o-tolylaldehyde, p-fluoro-
benzaldehyde, p-methoxy-benzaldehyde, and cyclohex-
anecarbaldehyde) undergo similar disproportionation reac-
tions albeit in lower yields. Primary amines such as aniline
and n-butylamine give exclusively the corresponding imines.
With regards to the mechanism of the rhodium-catalyzed
oxidative amination of aldehydes, we propose that the
amine and aldehyde react to form the corresponding amino
alcohol (Scheme 3). This amino alcohol may coordinate to
the rhodium(I) complex. This coordination is preferred for
cationic rhodium complexes rather than the formation of
Scheme 1
The key factor for success in this reaction is the use of a
cationic rhodium catalyst. Here we report for the first time
a rhodium-catalyzed oxidative amination of aldehydes to
give various aliphatic and aromatic amides in good to excel-
lent yields.
Results and Discussion
In order to develop a new domino sequence consisting of
oxidative amination of olefins and subsequent aldol reac-
[a]
Institut für Organische Katalyseforschung an der Universität
Rostock e.V.,
Buchbinderstr. 5Ϫ6, 18055 Rostock, Germany
Fax: (internat.) ϩ49-381/466-9324
E-mail: Matthias.Beller@ifok.uni-rostock.de
Eur. J. Org. Chem. 2001, 523Ϫ528
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0203Ϫ0523 $ 17.50ϩ.50/0
523

A. Tillack, I. Rudloff, M. Beller
FULL PAPER
[a]
Table 1. Reaction of aldehydes with amines catalyzed by [Rh(COD)2]BF4·2PPh3
[a]
General conditions: 4.40 mmol aldehyde, 2.20 mmol amine (or as described in the table), 0.055 mmol [Rh(COD)2]BF4 (2.5 mol-%),
[b]
0.11 mmol PPh3, 20 h. Ϫ The yield was determined by GC using an internal standard (hexadecane).
halide bridged complexes. Dehydrogenation of the amino
This mechanism explains all of the observed products as
alcohol yields the corresponding amide and a rhodium(III) well as the necessity to use cationic rhodium complexes. In
dihydride complex, which reduces the aldehyde to the cor- order to make the oxidative amination of aldehydes more
responding alcohol, or the aminal to the amine.
useful for synthetic applications, the reduction of aldehyde
to alcohol, and side-reactions of the alcohol have to be
avoided. We thought that the addition of N-methylmorpho-
line N-oxide would result in the regeneration of a cata-
lytically active rhodium dehydrogenation catalyst. In addi-
tion, the use of a base as co-catalyst should increase the
rate of the dehydrogenation step. Indeed, the reaction of
benzaldehyde (4.40 mmol), morpholine (2.20 mmol), N-
methylmorpholine N-oxide (2.20 mmol), [Rh(COD)2]BF4
(0.055 mmol), and potassium carbonate (0.22 mmol) in
THF at 100 °C proceeds much more selectively: N-benzoyl-
morpholine is obtained in Ͼ99% yield! After some optim-
ization work, piperidine and methyl-n-butylamine yielded
N-benzoylpiperidine and N-benzoyl-N-methyl-N-n-bu-
tylamine in 96% and 94% respectively (Table 2, entries 11
and 17); primary amines, however, gave exclusively the cor-
responding imines (Table 2, entry 19).
In all of these reactions, only traces of benzylamines were
detected. Catalytic amounts of potassium carbonate (0.1
Scheme 3
524
Eur. J. Org. Chem. 2001, 523Ϫ528

Catalytic Amination of Aldehydes to Amides
FULL PAPER
Table 2. Reaction of benzaldehyde with different amines catalyzed by [Rh(COD)2]BF4 in the presence of N-methylmorpholine N-oxide/
[a]
K2CO3
[a]
General conditions: 4.40 mmol aldehyde, 2.20 mmol amine (or as described in the table), 0.055 mmol [Rh(COD)2]BF4 (2.5 mol-%),
[b]
2.20 mmol N-methylmorpholine N-oxide, 0.22 mmol K2CO3. Ϫ The yield was determined by GC using an internal standard (hexade-
cane). Ϫ 1 mol-% catalyst. Ϫ 2.20 mmol K2CO3.
[c]
[d]
equiv.) are sufficient for an improved transformation of al- amide are obtained at 100 °C in THF. Otherwise, significant
dehydes to amides. Using a stoichiometric or excess amount amounts of the N-(cyclohexylmethyl)morpholine were pro-
of potassium carbonate did not increase the yield of the duced.
amide any further. In general an excess of the aldehyde is
All attempts to react n-octanal with morpholine gave α-
used in order to obtain the highest yields of amide, but in octylidenomorpholine and octanoylmorpholine. Satisfact-
the case of piperidine an excess of amine is necessary to get ory yields of the desired amide were obtained by using an
optimum results with benzaldehyde.
excess of morpholine.
In addition to benzaldehyde, o-tolylaldehyde and p-
In conclusion, we have developed a new rhodium-cata-
fluorobenzaldehyde were converted into amides with mor- lyzed oxidative amination of aldehydes. By variation of the
pholine in excellent yields (94Ϫ100%, Table 3). Using p- amine/aldehyde ratio, good to excellent yields of dial-
fluorobenzaldehyde, nucleophilic aromatic substitution of kylamides are obtained. The new method makes use of ubi-
the p-fluoro substituent was observed as a side-reaction. quitously available starting materials and is the most effici-
The yield of N-(4-fluorobenzoyl)morpholine was mainly in- ent procedure to synthesize amides from aldehydes known
fluenced by the reaction temperature. The highest yields to date.
were realized at 100 °C in THF. In toluene at higher tem-
peratures, a considerable amount of 4-morpholinobenzal-
dehyde was formed.
Experimental Section
Under standard conditions the less activated p-methoxy-
benzaldehyde provided only moderate yields of the amide.
Remarkably, an excess of morpholine did not give the ex-
pected aminal, but a higher yield of the amide. Cyclohex-
anecarbaldehyde also provided a better yield of the amide
General: All operations were carried out under an inert atmosphere
of argon. Toluene and THF were freshly distilled from sodium tet-
raethylaluminate under argon prior to use. Amines were distilled
from CaH2. Aldehydes were dried over 4 A molecular sieves and
distilled before use. Triphenylphosphane, N-methylmorpholine N-
˚
if an excess of morpholine was used. The best yields of oxide, and potassium carbonate were purchased from Aldrich.
Eur. J. Org. Chem. 2001, 523Ϫ528 525

A. Tillack, I. Rudloff, M. Beller
FULL PAPER
Table 3. Reactions of different aldehydes with morpholine catalyzed by [Rh(COD)2]BF4 in the presence of N-methylmorpholine N-oxide/
[a]
K2CO3
[a] All reactions were carried out with 4.40 mmol aldehyde, 2.20 mmol amine (or as described in the Table), 2.20 mmol N-methylmorpho-
[b]
line N-oxide, 0.22 mmol potassium carbonate, and 2.5 mol-% [Rh(COD)2]BF4. Ϫ The yield was determined by GC using an internal
standard (hexadecane).
[Rh(COD2)]BF4 was prepared according to literature procedures.[6]
Spectra were recorded on: NMR: Bruker ARX 400; CHCl3/CDCl3 The amines were obtained after column chromatography (eluent:
were dried over MgSO4 and the solvent was removed in vacuo.
as internal reference; δ in ppm, J in Hz. Ϫ FT IR: Nicolet Magna
550. Ϫ MS: AMD 402. Ϫ M.p.: Büchi 535 apparatus; uncorrected
values. Ϫ GC analysis: HP 6890 gas chromatograph using a HP-1
capillary column.
chloroform/methanol ϭ 100:1).
Catalytic Reaction with Oxidant (Method B): The Rh complex
(0.055 mmol), K2CO3 (0.22 mmol), and N-methylmorpholine N-
oxide (2.20 mmol) were suspended in the corresponding solvent
(5 mL). Amine and aldehyde were then added at room temperature
as described in Table 2 and 3. The reaction mixture was heated in
a pressure tube (8Ϫ20 h) at 100 °C (or 140 °C). Both the work up
and purification were carried out according to method A.
General Procedure for the Reaction of Amines with Aldehydes. —
Catalytic Reaction without Oxidant (Method A): The Rh complex
(0.055 mmol) and triphenylphosphane (0.11 mmol) were suspended
in the corresponding solvent (5 mL). Amine and aldehyde were
then added at room temperature as described in Table 1. The reac-
tion mixture was heated in a pressure tube for 20 h at 100 °C in
THF, or at 140 °C in toluene. The yield of products was determined
by gas chromatography with hexadecane as the internal standard.
The solvent was then removed in vacuo and the residue was dis-
solved in CH2Cl2 (20 mL) and extracted three times with HCl (5%).
The amide was isolated from the oily residue of the organic phase
N-Benzylmorpholine:[7] Method A, colorless oil, yield (GC): 42%.
1
Ϫ H NMR (400 MHz, CDCl3): δ ϭ 2.44 (t, 4 H, NCH2), 3.49 (s,
2 H, CH2), 3.70 (t, 4 H, OCH2), 7.31Ϫ7.34 (m, 5 H, Ph). Ϫ 13C
NMR (100 MHz, CDCl3): δ ϭ 53.5 (2 NCH2), 63.4 (CH2), 66.4 (2
OCH2), 127.1, 128.2, 129.1 (CH, Ph), 137.7 (C, Ph). Ϫ MS (EI):
m/z (%) ϭ 177 (13) [Mϩ], 176 (100), 100 (25), 91 (23) [{PhCH2}ϩ].
by column chromatography (eluent: chloroform/methanol
100:1).
ϭ
N-Benzoylmorpholine:[8] Method B, colorless solid, m.p. 72 °C,
yield (GC): 100%. Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 3.22Ϫ3.96
(m, 8 H, CH2), 7.4 (m, 5 H, Ph). Ϫ 13C NMR (100 MHz, CDCl3):
δ ϭ 42.5, 48.0 (NCH2), 66.7 (2 OCH2), 127.0, 128.4, 129.7 (CH,
Ph), 135.2 (C, Ph), 170.3 (CO). Ϫ MS (EI): m/z (%) ϭ 191 (21)
In order to isolate the amine, the combined aqueous HCl phases
were neutralized by the addition of NaOH (to pH ϭ 9) and then
extracted three times with CH2Cl2. The combined organic layers
526
Eur. J. Org. Chem. 2001, 523Ϫ528

Catalytic Amination of Aldehydes to Amides
FULL PAPER
[Mϩ], 190 (39), 105 (100) [{PhCO}ϩ], 86 (12), 77 (53). Ϫ FT IR
Ph), 155.6 (C, Ph), 190.9 (CHO). Ϫ MS (CI, isobutane): m/z (%):
(KBr): ν˜ ϭ 1634 (CϭO) cmϪ1
.
192 (100) [(MH)ϩ].
N-Benzylpiperidine:[9] Method A, colorless oil, yield (GC): 34%. Ϫ
1H NMR (400 MHz, CDCl3):
1.38Ϫ1.47 (m, H,
N-(4-Methoxybenzyl)morpholine:[16] Method A, colorless oil, yield
δ
ϭ
2
(GC): 38%. Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 2.40 (t, 3J ϭ
3
NCH2CH2CH2), 1.57 (m, 4 H, NCH2CH2), 2.37 (m, 4 H, NCH2), 4.4 Hz, 4 H, 2 ϫ CH2), 3.43 (s, 3 H, CH3), 3.68 (t, J ϭ 4.4 Hz, 4
3.47 (s, 2 H, NCH2), 7.29Ϫ7.34 (m, 5 H, Ph). Ϫ 13C NMR
H, 2 ϫ CH2), 3.78 (s, 2 H, CH2), 6.85, 7.23 (m, 4 H, Ph). Ϫ 13C
(100 MHz, CDCl3): δ ϭ 24.4 (NCH2CH2CH2), 26.0 (NCH2CH2), NMR (100 MHz, CDCl3): δ ϭ 54.0 (2 NCH2), 55.7 (CH3), 63.3
54.4 (NCH2), 126.8, 128.0, 129.2 (CH, Ph), 138.6 (C, Ph). Ϫ MS (CH2), 67.5 (2 OCH2), 114.0, 130.2 (CH, Ph), 130.8 (C, Ph), 159.2
(EI): m/z (%) ϭ 175 (72) [Mϩ], 174 (70), 98 (58), 91 (100)
(COCH3). Ϫ MS (CI, isobutane): m/z (%) ϭ 207 (44) [(MH)ϩ], 121
(100), 86 (18).
[{PhCH2}ϩ], 84 (53).
N-Benzoylpiperidine:[10] Method B, colorless oil, yield (GC): 96%.
N-(4-Methoxybenzoyl)morpholine:[3a] Method B, white solid, m.p.
1
Ϫ
1H NMR (400 MHz, CDCl3):
δ
ϭ
1.50 (br m,
2
H, 42 °C, yield (GC): 84%. Ϫ H NMR (400 MHz, CDCl3): δ ϭ 3.6
NCH2CH2CH2), 1.66 (br m, 4 H, NCH2CH2), 3.32 (br m, 2 H, (br d, 8 H, 4 CH2), 3.8 (s, 3 H, CH3), 6.8, 7.3 (m, 4 H, Ph). Ϫ 13C
NCH2), 3.69 (br m, 2 H, NCH2), 7.37 (m, 5 H, Ph). Ϫ 13C NMR NMR (100 MHz, CDCl3): δ ϭ 54.4 (CH3), 65.9 (4 CH2), 112.8,
(100 MHz, CDCl3): δ ϭ 24.5 (NCH2CH2CH2), 25.6 and 26.5
(NCH2CH2), 43.0 and 48.7 (NCH2), 126.7, 128.3, 129.3 (CH, Ph), isobutane): m/z (%) ϭ 222 (100) [(MH)ϩ], 135 (16). Ϫ FT IR
136.4 (C, Ph), 170.2 (CO). Ϫ MS (EI): m/z (%) ϭ 189 (38) [Mϩ],
(KBr): ν˜ ϭ 2963, 2921, 2854 (CH2), 1635 (CϭO), 1514, 1456,
188 (100), 105 (78) [{PhCO}ϩ], 84 (6), 77 (43). Ϫ FT IR (neat): 1428 cmϪ1
126.3, 128.2, (Ph), 159.9 (COCH3) 169.4 (CO). ϪMS (CI,
.
ν˜ ϭ 1632 (CϭO) cmϪ1
.
N-(Cyclohexylmethyl)morpholine:[17] Method A, colorless oil, yield
N-Benzyl-N-butyl-N-methylamine:[11] Method A, colorless oil, yield
(GC): 54%. Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 0.80 (m, 2 H, H-
(GC): 23%. Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 0.91 (t, 3 H, 4), 1.00Ϫ1.20 (m, 4 H, H-3), 1.40 (m, J1,2 ϭ 7.3 Hz, 1 H, H-1),
3
3
CH3), 1.34 (m, 2 H, NCH2CH2CH2), 1.51 (m, 2 H, NCH2CH2), 1.58Ϫ1.72 (m, 4 H, H-2), 2.04 (d, 2 H, CH2), 2.30 (t, J ϭ 4.4 Hz,
2.18 (s, 3 H, NCH3), 2.37 (t, 2 H, NCH2), 3.48 (s, 2 H, PhCH2), 4 H, 2 NCH2), 3.60 (t, 4 H, 2 OCH2). Ϫ 13C NMR (100 MHz,
7.30Ϫ7.33 (m, 5 H, Ph). Ϫ 13C NMR (100 MHz, CDCl3): δ ϭ 14.0 CDCl3): δ ϭ 26.5 (C-3), 27.2 (C-4), 32.3 (C-2), 35.0 (C-1), 54.6 (2
(CH3), 20.6 (NCH2CH2CH2), 29.6 (NCH2CH2), 42.2 (NCH3), 57.3
NCH2), 66.5 (CH2), 67.4 (2 OCH2). Ϫ MS (CI, isobutane): m/z
(NCH2), 62.3 (PhCH2), 126.8, 128.1, 129.0 (CH, Ph), 139.3 (C, Ph). (%) ϭ 184 (100) [(MH)ϩ], 100 (92) [M Ϫ C6H11ϩ].
Ϫ MS (CI, isobutane): m/z (%) ϭ 177 (14) [Mϩ], 176 (100), 162
N-(Cyclohexylcarbonyl)morpholine:[18] Method B, white solid, m.p.
86 °C (diethyl ether), yield (GC): 58%. Ϫ 1H NMR (400 MHz,
CDCl3): δ ϭ 1.15Ϫ1.26 (m, 4 H, H-3), 1.45 (m, 2 H, H-4),
(7), 134 (15), 120 (28), 91(76) [{PhCH2}ϩ].
N-Benzoyl-N-butyl-N-methylamine:[12] Method B, colorless oil,
yield (GC): 94%. Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 0.74 and 1.60Ϫ1.76 (m, 4 H, H-2), 2.36 (m, 1 H, H-1), 3.40Ϫ3.60 (m, 8 H,
0.93 (t, 3 H, CH3), 1.10 and 1.36 (m, 2 H, NCH2CH2CH2), 1.46
2 NCH2, 2 OCH2). Ϫ 13C NMR (100 MHz, CDCl3): δ ϭ 26.2 (C-
and 1.59 (m, 2 H, NCH2CH2), 2.87 and 3.01 (s, 3 H, NCH3), 3.17 3, C-4), 29.7 (C-2), 40.7 (C-1), 42.3, 46.3 (2 NCH2), 67.3, 67.5 (2
and 3.48 (t, 2 H, NCH2), 7. 32 (m, 5 H, Ph). Ϫ 13C NMR OCH2), 175.1 (CO). Ϫ MS (CI, isobutane): m/z (%) ϭ (198) (100)
ϩ
Ϫ1
˜
(100 MHz, CDCl3): δ ϭ 13.4 and 13.7 (CH3), 19.4 and 19.9 [(MH) ]. Ϫ FT IR (KBr): ν ϭ 1636 (CϭO), 1444, 1360 cm
.
(NCH2CH2CH2), 28.9 and 30.1 (NCH2CH2), 32.5 and 37.2
N-(2-Methylbenzyl)morpholine:[16] Method A, colorless oil, yield
(GC): 22%. Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 2.30 (s, 3 H,
CH3), 2.38 (t, 3J ϭ 4.4 Hz, 4 H, 2 NCH2), 3.39 (s, 2 H, CH2), 3.62
(t, 4 H, 2 OCH2), 7.05Ϫ7.15 (m, 4 H, Ph). Ϫ 13C NMR (100 MHz,
CDCl3): δ ϭ 53.9 (2 NCH2), 63.0 (CH2), 67.4 (2 OCH2), 125.9,
127.6, 130.3, 130.7, 136.4 (CH, Ph), 138.0 (C, Ph). Ϫ MS (CI,
(NCH3), 47.0 and 50.8 (NCH2), 126.4, 126.6, 128.1, 129.0 (CH,
Ph), 136.6 (C, Ph), 171.0 and 171.7 (CO). Ϫ MS (EI): m/z (%) ϭ
191 (10) [Mϩ], 105 (100) [{PhCO}ϩ], 77 (37). Ϫ FT IR (neat): ν˜ ϭ
1634 (CϭO) cmϪ1
.
N-(4-Fluorobenzyl)morpholine:[13] Method A, colorless oil, yield
(GC): 6%. Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 2.35 (t, 3J ϭ isobutane): m/z (%) ϭ 192 (100) [(MH)ϩ], 105 (14).
4.6 Hz, 4 H, 2 NCH2), 3.39 (s, 2 H, CH2), 3.65 (t, 4 H, 2 OCH2),
N-(2-Methylbenzoyl)morpholine:[19] Method B, white solid, m.p.
43Ϫ44 °C, yield (GC): 100%. Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ
2.24 (s, 3 H, CH3), 3.17 (m, 2 H, NCH2), 3.51 (m, 2 H, NCH2),
6.95, 7.20 (4 H, Ph). Ϫ 13C NMR (100 MHz, CDCl3): δ ϭ 53.9 (2
NCH2), 63.0 (CH2), 67.4 (2 OCH2), 115.4, 115.6, 131.0, 131.1 (CH,
Ph), 133.9 (C, Ph), 163.7 (CF). Ϫ MS (CI, isobutane): m/z (%) ϭ
196 (100) [(MH)ϩ], 164 (10), 109 (30).
3
3.74 (m, J ϭ 4.8 Hz, 4 H, 2 OCH2), 7.0Ϫ7.5 (m, 4 H, Ph). Ϫ 13C
NMR (100 MHz, CDCl3): δ ϭ 19.4 (CH3), 42.3 (2 NCH2), 47.7 (2
OCH2), 126.2, 126.4, 129.5, 130.9, 134.6 (CH, Ph), 136.1 (C, Ph),
N-(4-Fluorobenzoyl)morpholine:[14] Method B, pale yellow oil, yield
1
(GC): 94%. Ϫ H NMR (400 MHz, CDCl3): δ ϭ 2.95 (m, br, 8 H, 170.0 (CO). Ϫ MS (EI): m/z (%) ϭ 205 (20) [Mϩ], 119 (100), 91
4 CH2), 7.0, 7.5 (4 H, Ph). Ϫ 13C NMR (100 MHz, CDCl3): δ ϭ (46). Ϫ FT IR (KBr): ν ϭ 2964, 2920, 2855 (CH2), 1637 (CϭO),
˜
67.3 (4 CH2), 116.0, 116.2, 129.8, 129.9 (CH, Ph), 131.7 (C, Ph),
165.2 (CF), 169.9 (CO). Ϫ MS (CI, isobutane): m/z (%) ϭ 210 (100)
[(MH)ϩ], 123 (18). Ϫ FT IR (KBr): ν˜ ϭ 2962, 2923, 2855 (CH2),
1490, 1430 cmϪ1
.
N-Octanoylmorpholine:[20] Method B, colorless oil, yield (GC):
61%. Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 0.86 (t, 3 H, CH3), 1.29
1636 (CϭO), 1510, 1457, 1436 cmϪ1
.
3
(m, 8 H, 4 CH2), 1.60 (m, J ϭ 7.6 Hz, 2 H, CH2), 2.29 (t, 2 H,
4-Morpholinobenzaldehyde:[15] Method A (140 °C, toluene, alde-
hyde/amine ϭ 2:1), pale yellow solid, m.p. 66 °C (EtOH), yield
CH2), 3.45 (t, 2 H, NCH2), 3.57Ϫ3.67 (m, 3J ϭ 4.6 Hz, 6 H, NCH2,
2 OCH2). Ϫ 13C NMR (100 MHz, CDCl3): δ ϭ 13.1 (CH3), 21.6,
(GC): 30%. Ϫ 1H NMR (400 MHz, CDCl3): δ ϭ 3.25 (t, 3J ϭ 24.3, 28.1, 30.7, 32.1 (CH2), 40.8, 45.0 (2 NCH2), 65.7, 66.0 (2
3
4.4 Hz, 4 H, 2 ϫ CH2), 3.79 (t, J ϭ 4.4 Hz, 4 H, 2 ϫ CH2), 6.82, OCH2), 170.9 (CO). Ϫ MS (EI): m/z (%) ϭ 213 (12) [Mϩ], 142
7.69 (m, 4 H, Ph), 9.70 (CHO). Ϫ 13C NMR (100 MHz, CDCl3): (28), 129 (100). Ϫ FT IR (KBr): ν˜ ϭ 2961, 2845 (CH2), 1653 (Cϭ
δ ϭ 47.7 (2 ϫ NCH2), 66.9 (2 ϫ OCH2), 113.9, 128.1, 132.2 (CH, O), 1430, 1116 cmϪ1
.
Eur. J. Org. Chem. 2001, 523Ϫ528
527

A. Tillack, I. Rudloff, M. Beller
FULL PAPER
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