Synthesis and reactivity of alkenyl- and alkynyl-substituted β,β-dihalo-and?β,β,β-trichloroamines

Article abstract of DOI:10.1016/j.tet.2009.01.034

β,β-Dihalo- and β,β,β-trichloroamines, obtained by Lewis acid-promoted Petasis-type reaction of α,α-dichlorinated and α,α,α-trichlorinated imines or reduction of α,α-dihaloaldimines, were subjected to a reactivity study and turned out to be remarkably sta

Full text of DOI:10.1016/j.tet.2009.01.034

Tetrahedron 65 (2009) 1957–1966
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and reactivity of alkenyl- and alkynyl-substituted
b,b-dihalo-and b,b,b-trichloroamines
,
a
b
b
Kourosch Abbaspour Tehrani a , Sara Stas , Bart Lucas , Norbert De Kimpe
*
a Faculty of Sciences, Department of Applied Biological Sciences and Engineering, Laboratory for Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium
b Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, B-9000 Ghent, Belgium
a r t i c l e i n f o
a b s t r a c t
Article history:
b
,
b
-Dihalo- and
dichlorinated and
a reactivity study and turned out to be remarkably stable compounds. In general, only the bases KOtBu
and NaOMe cause a 1,2-dehydrochlorination with formation of unsaturated -chloroimines or un-
saturated -dichloroimines. Hydrolysis of the -chloroimines with aqueous oxalic acid resulted in the
formation of the corresponding unsaturated -chloroketones. The reaction of simple -dihaloamines
with NaOMe and KOtBu generated 2-haloprop-2-enylmines and 2,2-dimethoxypropylamines.
Ó 2009 Elsevier Ltd. All rights reserved.
b
,
b
a
,
b
-trichloroamines, obtained by Lewis acid-promoted Petasis-type reaction of
a,a-
Received 25 November 2008
Received in revised form 5 January 2009
Accepted 7 January 2009
,a
,a
-trichlorinated imines or reduction of -dihaloaldimines, were subjected to
a,a
a
Available online 14 January 2009
a
,a
a
a
b,b
Keywords:
Boron
a
b
-Chloroimines
-Halogenated amines
Petasis
1. Introduction
Because of the high specificity and the very limited choice
of the existing syntheses for -trichloroamines it was decided
to extend the Lewis acid-promoted borono-Mannich reaction to
-trichloroaldimines. Moreover, because of the rather limited
b,b,b
Recently, a new Petasis reaction with
a,a-dichlorinated aldi-
mines or
a-fluoroaldimines and potassium alkenyltrifluoroborates
a,a,a
or potassium alkynyltrifluoroborates under Lewis acid promotion
access to acyclic polychlorinated amines in general, almost
no studies have appeared on their reactivity.16 Therefore, the
previously obtained dichlorinated secondary propargylamines
was described.1–3 This reaction led to the formation of functional-
ized b,b-dichloroamines 6 and 7.
There have been not many reports about the synthesis of acyclic
-dichloroamines. A free radical process for the addition of
and allylamines1 and the envisaged
b,b,b-trichloroamines were
b
,b
subjected to a wide variety of bases and nucleophiles in order
to investigate their synthetic potential. It was expected that the
N-chlorodialkylamines across various olefins in order to obtain
dichloroamines has been described.4–7 Another, more convenient
method reported the synthesis of -chloroamines by reduction of
-chloro-, -dichloro- and
-trichloroimines8 and reduction
of -chloro-
-fluorocarboxylic amides9 by borane–methyl sulfide
complex. A convenient entry into -trichloroamines consisted
of the reduction of -trichloroimines by means of sodium
cyanoborohydride in methanol in the presence of acetic acid.10
Equally, syntheses of acyclic -trichloroamines have not been
extensively explored. The oldest reported method for the prepara-
b,b-
b
-chloro atom could participate in directed elimination and/or
substitution reactions. Moreover, the presence of an unsaturated
system (alkenyl- or alkynyl group) in -position of the amino
b
a
a
,
a
a,
a,
a
a
a
a
group could allow further rearrangements.
b,b,g
a,a,b
2. Results and discussion
b,b,b
Recently, we described the Lewis acid-promoted Mannich-type
reaction as an extension of the classic Petasis reaction with potas-
sium 2-phenylvinyl- and phenylethynyltrifluoroborates 2 as boron
tion of b,b,b-trichloroamines concerns the reaction of trichloroacetic
acid with imines.11,12 Other methods are based on the addition of
aniline across ethyl 4,4,4-trichloro-2-cyano-2-butenoate.13,14 A third
components and
a,a-dichloroaldimines 1 as imine components
(Scheme 1).1 In a first step the electrophilic organodifluoroborane 3,
generated in situ by reaction between the corresponding organo-
trifluoroborate 2 and BF3$OEt2, formed a nitrogen–boron complex 4
entry to b,b,b-trichloroamines consists of the reaction of carbon tet-
rachloride or (trichloromethyl)benzene with phenyl(dialkylamino)
acetonitriles under phase transfer catalysis.15
with the
a,a-dichloroimine. This complexation facilitates the
transfer of the alkenyl or alkynyl group to the imino carbon atom.
Therefore, it was expected that the same Lewis acid-promoted
* Corresponding author. Tel.: þ32 (0)26293292; fax: þ32 (0)26293304.
E-mail address: kourosch.abbaspour.tehrani@vub.ac.be (K. Abbaspour Tehrani).
borono-Mannich reaction with
a,a,a-trichloroaldimines would
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.034

1958
K. Abbaspour Tehrani et al. / Tetrahedron 65 (2009) 1957–1966
R2BF3K (2)
F
F
BF OEt
.
- KBF4
3
2
R1
B
R1
F2B
R1
R2
R1
R2
aqueous
NaOH
N
R2
N
N
HN
R2BF2 (3)
R2 = CH=CHPh : CH2Cl2/HFIP (9/1)
H
H
Cl Cl
Cl Cl
Cl Cl
Cl Cl
R
2 = CCPh : CH2Cl2
rt, 18 h
6 R2 = CH=CHPh (62 - 74%)
CPh (72 - 83%)
5
1
4
7 R2 =
C
R1 = Ph, Bn, tBu, iPr, nPr, Allyl, Et, Me
R
2 = CH=CHPh,
C
CPh (72 - 83% )
Scheme 1. Lewis acid-promoted Mannich-type reaction with
a,a-dichloroaldimines.
proceed as well, if not better, because of the even higher electron-
withdrawing properties of the trichloromethyl group.
product was present, which could be identified by 1H NMR as
-chloroimine 11a by the characteristic appearance of a quadruplet
a
Indeed, this modified Petasis-type reaction of
a,
a,
a-tri-
at 4.69 ppm (CDCl3). The reaction was continued with fresh silica
and after 4 days only half of product 7a remained. Silica was added
one more time, and after a total contact time of 10 days between
chloroaldimines17,18 8 with styryl or phenylethynyltrifluoroborates
in the presence of BF3$OEt2 afforded the corresponding N-alkyl-
(4,4,4-trichloro-1-phenylbut-1-en-3-yl)amines
9
and N-alkyl-
b,b-dichloroamine and silica gel, only 18 mol % of the starting
(4,4,4-trichloro-1-phenylbut-1-yn-3-yl)amines 10 in good yields
(Table 1). When the less reactive styryltrifluoroborate was used,
1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) was added as cosolvent, to
improve the yield.1 In general, these trichloroamines could be
simply purified by high vacuum evaporation to remove traces of
substrate 7a was present in the mixture. After a final filtration and
evaporation of the solvents a yield of 70% could be calculated for
a-chloroimine 11a, taking into account the 82 mol % purity.
Apparently, under the influence of silica gel, -dichloroamines
b,b
undergo a 1,2-elimination of HCl to generate the corresponding
Table 1
Lewis acid-promoted Mannich-type reaction with
a
,
a
,
a
-trichloroaldimines
1 equiv
BF3K
1 equiv
BF3K
R
2a
HN
2b
R
R
HN
Cl3C
N
1 equiv BF OEt
.
1 equiv BF OEt
3 2
Cl3C
.
3
2
Cl3C
H
CH2Cl2, rt, 18 h
CH2Cl2/HFIP (9/1)
rt, 18 h
8
9
10
R (8)
Yielda of 9 (%)
Yielda of 10 (%)
tBu (8a)
iPr (8b)
nPr (8c)
Allyl (8d)
79 (9a)
61 (9b)
55 (9c)
61 (9d)
76 (10a)
68 (10b)
68 (10c)
65 (10d)
a
Yields after high vacuum evaporation (purity >95%).
styrene, phenylacetylene or starting imine, leaving the products in
purities of over 95%.
Attempted purification of the obtained Mannich products (9 and
10) by flash chromatography on silica gel resulted in considerable
loss of product (up to 60 mass % of the product degraded on the
column). A comparable decrease in yield was noticed by purifying
b
-chloroenamines, which then tautomerize into
a
-chloroimines.
The latter compounds are known to be hydrolytically unstable and
can usually not be purified by flash chromatography on silica gel;
this explains the abovementioned decrease in yield.
In order to perform the dehydrohalogenation of 6 and 7 in a more
controlled manner, their reactivity towards different bases was in-
vestigated. When N-alkyl-(4,4-dichloro-1-phenylpent-1-en-3-yl)
amines 6 and N-alkyl-(4,4-dichloro-1-phenylpent-1-yn-3-yl)amines
7 were reacted with 2–3 equiv of n-propylamine, Et3N, NaH or
MeMgCl either at 0 ꢀC, room temperature or under reflux, no reaction
b,
b
-dichloroamines 6 or 7 on silica gel. Therefore, the influence of
silica gel on -dichloroamine 7a was examined more closely. The
b,b
Mannich product 7a was dissolved in EtOAc/Hexane and stirred
with an excess of silica gel (Table 2). After 1 day, a trace of side
took place. Treatment of b,b-dichloroamines 6 and 7 with stronger
bases like LDA or n-BuLi (2 equiv) under an inert atmosphere at 0 ꢀC
always resulted in complete degradation of the starting material.
Despite these negative results, there is one precedent in the literature
in which N-(2,2-dichloro-1-phenylpropyl)aniline is converted in an
Table 2
Influence of SiO2 on
b
,
b
-dichloroamines
Ph
Cl Cl
Cl
Ph
Ph
Cl Cl
HN
SiO2
a
-chloroimine upon reaction with MeLi.16,19
+
EtOAc/Hexane
(5/95), rt
The use of potassium tert-butoxide to synthesize vinyl chlorides
HN
N
or alkynes from geminally chlorinated alkyl ethers has been already
reported by Tennyson and Romo.20 When KOtBu in THF was added
to N-alkyl-(4,4-dichloro-1-phenylpent-1-yn-3-yl)amines 7, com-
7a
7a
11a
Number of days
(reaction time)
Ratio of amine 7a/imine 11a (mol %)a
plete conversion into the corresponding
a-chloroimines 11 oc-
curred already with only 1.2 equiv of KOtBu. Yields fluctuated
around 80–95% (purity >90%), depending on the amount of KOtBu
added and the reaction time. Highest yields were obtained by
adding 2 equiv of KOtBu in THF under reflux for 2 h. As evidenced by
1
4
10
95/5
50/50
18/82
a
Compound 7a (0.5 mmol) is mixed every time with 2 g fresh SiO2.

K. Abbaspour Tehrani et al. / Tetrahedron 65 (2009) 1957–1966
1959
1H NMR spectroscopy,
a
-chloroketimines 11 were obtained as one
12 varied between 23% and 85%. With a N-n-propyl substituent,
geometrical isomer, i.e., E with respect to the imino function
(Scheme 2), which parallels similar results in the literature.18
For N-alkyl-(4,4-dichloro-1-phenylpent-1-en-3-yl)amines 6 the
results strongly depended on the nitrogen substituent, the amount
of KOtBu added and the reaction conditions (time and tempera-
ture), but conversion was almost never complete (Table 3). Yields of
complete conversion to a-chloroimine 12a was achieved when
three or more equivalents of KOtBu were used (purity >90%) (en-
tries 2, 3). In the case of an N-isopropyl substituent (entries 4–8),
the more equivalents of base used, the higher the conversion rate,
but a complete conversion to the a-chloroimine 12b could not be
accomplished. For sterical reasons ketimine 12b existed exclusively
as the Z-isomer.18
Ph
At first sight, the presence of a MeCHCl moiety in 11 and 12
would suggest an initial deprotonation of the CHN by tert-butoxide,
probably favoured by the presence of an alkynyl or alkenyl sub-
stituent, followed by loss of a chloride anion, and final tautomeri-
Ph
Cl Cl
HN
Cl
2 equiv KOtBu, THF
reflux, 2 h
N
R
R
zation of the b-chloroenamine 13 (route a). Since the reaction also
7a R = nPr
7b R = iPr
11a (95%)
11b (89%)
went to completion with only 1.2 equiv of KOtBu, first the amine
should be deprotonated. In accordance with the literature, intra-
molecular nucleophilic substitution occurs with formation of an
intermediate 2-chloroaziridine 14, which ionizes to give an aziri-
nium chloride 15.16,19 Rearrangement of this azirinium chloride by
a 1,2-hydride shift might then result in an isomeric azirinium ion 18
Scheme 2.
Table 3
Dehydrochlorination of N-alkyl-(4,4-dichloro-1-phenylpent-1-en-3-yl)amines 6
Cl
Cl Cl
or its isomeric ring opened form, i.e., an
a-imino carbenium ion 19
KOtBu
and consecutive attack of chloride at the carbenium ion finally af-
THF
HN
N
fords the
isomeric
a
-chloroketimine 11 or 12 (Scheme 3). No traces of the
R
R
a
-chloroketimine 17 have ever been observed.
6
12
A
short-path high vacuum distillation (0.01 mmHg) was
attempted to purify the obtained -chlorinated imines 11 and 12.
a
Entry
R
Reaction
Conversion:
ratio 6/12 (%)
Ratio
E/Z 12
Yield of
conditionsa
12 (%)c
Unfortunately, these imines were not stable under these conditions
and afforded only black tars. Efforts made to purify the chlorinated
imines by flash chromatography on neutral alumina (Al2O3) were
unsuccessful.
1
2
3
nPr (6a)
nPr (6a)
nPr (6a)
2 equiv KOtBu,
THF, reflux, 2 h
3 equiv KOtBu,
THF, reflux, 2 h
4 equiv KOtBu,
THF, 0 ꢀC, 30 min,
rt 18 h
62/38
0/100
0/100
20/80b
50/50b
50/50b
30 (12a)
85 (12a)
75 (12a)
The use of NaOMe in methanol also resulted in the
dehydrochlorination of N-alkyl-(4,4-dichloro-1-phenylpent-1-yn-
3-yl)amines 7 (0.5 mmol). However, yields and purities of the
4
5
6
iPr (6b)
iPr (6b)
iPr (6b)
2 equiv KOtBu,
THF, reflux, 2 h
3 equiv KOtBu,
THF, reflux, 2 h
4 equiv KOtBu,
THF, 0 ꢀC, 30 min,
rt 18 h
65/35
56/44
73/27
0/100
0/100
0/100
32 (12b)
36 (12b)
23 (12b)
corresponding a
-chloroimines 11 were lower than with KOtBu as
base. N-Alkyl-(4,4-dichloro-1-phenylpent-1-en-3-yl)amines 6 did
not react with NaOMe in methanol. Probably, methoxide was not
basic enough to deprotonate the nitrogen atom of amines 6.
In general, the synthesized
a ,b
-chloro-a0 0-unsaturated keti-
mines 11 and 12 were unstable compounds and could only be
stored for a few days under argon at ꢁ4 ꢀC before degradation
started. Analogous 1-aza-1,3-butadienes, i.e., N-unsubstituted
7
8
9
iPr (6b)
iPr (6b)
iPr (6b)
4 equiv KOtBu,
THF, reflux, 2 h
5 equiv KOtBu,
THF, reflux, 2 h
10 equiv KOtBu,
THF, reflux, 2 h
20/80
10/90
0/100
0/100
d
71 (12b)
82 (12b)
d
a,
a,
a
-trifluoromethyl-a0
,b
0-unsaturated imines, have also been
-chlori-
reported as unstable compounds.21 On the other hand,
a
Complete
degradation
nated imines are valuable substrates in synthetic organic chemis-
a
Reactions were carried out on 0.5 mmol scale.
Determined by 1H NMR spectroscopy in benzene-d6.
Determined by 1H NMR spectroscopy.
try.22 Because syntheses of -chloro-a0 0-unsaturated ketones are
a ,b
b
c
23–25
rare
and publications about other
a , -
-halogeno-a0 b0
Cl Cl
Cl
Cl
R2
R2
R2
Cl-
KOtBu
route b
R2
R2
X
N
R1
HN
N
NR1
NR1
R1
R1
6 R2 = CH=CHPh
7 R2 = C CPh
15
16
17
14
route a
Cl
R2
Cl
Cl-
R2
R2
R1
R2
N
N
N
R1
HN
R1
R1
18
19
11
12
13
Scheme 3. Proposed mechanism for the formation of the a-chloroketimine.

1960
K. Abbaspour Tehrani et al. / Tetrahedron 65 (2009) 1957–1966
unsaturated ketones (
are also scarce, efforts were made to hydrolyze the
a
-fluoroketones,26–29
a
-bromoketones30–34
-chloroimines
11 and 12 to the corresponding ketones. In general, hydrolysis of
chlorinated ketimines into the corresponding -chloroketones can
)
Cl
3 equiv KOtBu, THF
Cl3C
HN
Ph
Ph
Ph
a
reflux, 3 h (87%)
Cl
a
-
or
N
5 equiv NaOEt, EtOH (2N)
reflux, 3 h (79%)
a
be carried out via aqueous acid hydrolysis with hydrochloric acid or
oxalic acid.35 Hydrolysis of imine 11a with 4 N hydrochloric acid
afforded a mixture of 89 mol % (E)-, 9 mol % (Z)-1,4-dichloro-
1-phenylpent-1-en-3-one (20) and 2 mol % 1-pentyn-3-one 21.
Both stereoisomers were separated by flash chromatography on
9a
23
Cl
Ph
3 equiv KOtBu, THF
Cl3C
Cl
reflux, 3 h
HN
N
silica gel. b-Chlorovinylketones 20 are formed by addition of hy-
drogen chloride to the alkyne moiety of the alkynyl ketone 21
10a
24 (84%)
(Scheme 4).36
Scheme 6.
Cl
in this reaction. Since it has been shown that the reduction of N-
alkyl-(2,2-dichloropropylidene)amines 25 with lithium aluminium
Cl
O
Ph
hydride leads to 1,2-disubstituted aziridines,40
a,a-dichloroimines
Ph
Cl Cl
Cl
Ph
(E)-20 (33%)
25 were treated with 2 equiv of sodium cyanoborohydride in the
presence of 1 equiv of acetic acid in methanol, thus affording 2,2-
dichloropropylamines 26a–c in high purity after vacuum distilla-
tion (Scheme 7).
aq. HCl (4N)
rt
N
Cl
O
Ph
11a
21 (trace)
In order to investigate the dehydrochlorination of N-tert-butyl-
(2,2-dichloropropyl)amine (26b) different concentrations of so-
dium methoxide in methanol were added and the reaction mixture
was refluxed overnight. In all cases, varying amounts of starting
material 26b, N-tert-butyl-(2-chloroprop-2-enyl)amine (27),
N-tert-butyl-(2,2-dimethoxypropyl)amine (28) and 2-methoxy-
propen-2-enylamine (29) were formed. The presence of the
O
Cl
(Z)-20 (4%)
Scheme 4.
On the other hand, a-chloroketimine 12b could be hydrolyzed to
the corresponding ketone 22 either by reaction with aqueous hy-
drogen chloride37 (65%) or with oxalic acid (71%) (Scheme 5). This
method thus constitutes a valuable alternative for the synthesis of
,b
-chloro-a0 0-unsaturated ketones in good yields and only three
a-amino ketoacetal 28 can be interpreted as resulting from a 2-
chloroaziridine 30, which is converted into the azirinium in-
termediate 31.41 Methoxide addition across the iminium bond of 31
would then generate a 2-methoxyaziridine 32, which after ring
a
steps starting from a,a-dichloroimines 1 (Petasis-type reaction, 1,2-
dehydrochlorination with KOtBu and hydrolysis with oxalic acid).
opening and a second methoxide addition finally leads to a-amino
ketoacetal 28 (Scheme 8).
By using more dilute concentrations of sodium methoxide in
methanol (0.5 M), more N-tert-butyl-(2,2-dimethoxypropyl)amine
(28) was formed at the expense of N-tert-butyl-(2-chloroprop-2-
enyl)amine (27). All attempts to separate compounds 28 and 27 by
vacuum distillation failed. In an attempt to drive the reaction to-
wards one single end product, 2,2-dichloropropylamine 26b was
reacted with an excess of concentrated sodium methoxide in
methanol (10 equiv, 10 M). In this case, the formation of 2,2-
dimethoxypropylamine (28) was accompanied by significant
amounts of its elimination product 2-methoxypropen-2-enylamine
(29) in a 65/35 ratio (GC).
2 equiv (COOH)2.2H2O
Cl
Cl
H2O/CH2Cl2 (1/1)
reflux, 2 h (71%)
Ph
Ph
or
O
N
4N HCl/CH2Cl2 (1/1)
rt, 1 h (65%)
12b
22
Scheme 5. Hydrolysis of
a
-chloroimines into a-chloroketones.
The reaction of N-4-methoxyphenyl-(4,4,4-trifluoro-1-phenyl-
but-1-yn-3-yl)amine with sodium hydroxide in THF to give the
corresponding difluoroimine, has been reported.38,39 In view of this
result, the same reaction was attempted using N-alkyl-(4,4,4-tri-
chloro-1-phenylbut-1-en- and -yn-3-yl)amines 9a and 10a.
Treatment of N-tert-butyl-(4,4,4-trichloro-1-phenylbut-1-yn-3-
yl)amine (10a) with NaOH (4–5 equiv 0.5–3 N NaOH, acetone, rt to
reflux, 2–18 h) afforded in all cases only starting material. By using
stronger bases like KOtBu in THF or sodium ethoxide in ethanol,
Since the reaction of
b,
b-dichlorinated amines with potassium
tert-butoxide furnished
a-chloroimines, 2,2-dichloropropylamine
26b was also subjected to a reaction with KOtBu. The overnight
reaction of 26b with 2 equiv of KOtBu in refluxing THF, however, did
not lead to N-(2-chloropropylidene)-tert-butylamine but furnished
a 1/3 mixture (GC) of starting material 26b and N-(2-chloroprop-2-
enyl)-tert-butylamine (27). The same reaction with 5 equiv of
KOtBu in tert-butanol at room temperature gave rise to complete
degradation.
the expected a,a-dichloroimine 23 was formed in good yields but
with a disappointing purity of 85% (NMR). Several efforts to purify
imines 23 by high vacuum distillation were unsuccessful due to
extensive degradation. Interestingly, no further reactions of 23
with sodium ethoxide to N-2-(1,1-diethoxyalkylidene)amine
were observed.37 The conversion of N-tert-butyl-(4,4,4-trichloro-1-
2 equiv NaCNBH3, MeOH
Cl Cl
Cl Cl
R2
1 equiv HOAc
H
phenylbut-1-en-3-yl)amine (10a) to the corresponding
a,a-
R2
rt, 16 h
dichloroimine 24 could also be achieved using KOtBu in THF
(Scheme 6). Dichloromethyl imine 24 was obtained with a purity
of more than 95%.
N
HN
R1
R1
25a R1 = i-Pr, R2 = Me
25b R1 = t-Bu, R2 = Me
25c R1 = cHex, R2 = Me
26a (89%)
26b (72%)
26c (62%)
In view of the rather unexpected results obtained in the re-
actions of
b
,b
-dichloro- and
tert-butoxide, less functionalized
b
,
b
,
b
-trichloroamines with potassium
-dihaloamines were evaluated
b,b
Scheme 7.

K. Abbaspour Tehrani et al. / Tetrahedron 65 (2009) 1957–1966
1961
Cl
OMe
HN
Cl Cl
MeO OMe
H
N
10 equiv. NaOMe, MeOH (2M)
reflux, 24 h
H
N
26b
+
+
+
HN
26b
27
29
28
Ratio: 41/52/3/5
MeO
H
N
N
N
N
Cl
MeO
30
31
32
33
Scheme 8.
It was expected that the brominated analogue of 26b, i.e., N-tert-
butyl-(2,2-dibromopropyl)amine (36) would be a better substrate
for the preparation of N-(2-bromoprop-2-enyl)-tert-butylamine.
The dibromination of N-(propylidene)-tert-butylamine (34) could
KOtBu in tetrahydrofuran resulted in 2-haloprop-2-enylamines and
2,2-dimethoxypropylamines.
4. Experimental part
4.1. General
43
easily be effected by means of N-bromosuccinimide in CCl4 or
cyclohexane. It must be stressed that analogous brominations of N-
(propylidene)propylamine only led to complex reaction mixtures
even when the reaction was performed at room temperature. N-
tert-Butyl-(2,2-dibromopropyl)amine (36) was obtained by re-
GC–MS analyses were performed using an Intersience GC 8000
series gas chromatograph with a ECÔ-5 column (length: 30 m,
internal diameter: 0.32 mm, film thickness: 0.25 mm). Products are
duction of a,a-dibromoaldimine 35 with sodium cyanoborohydride
injected in a split injector (250 ꢀC); the inert carrier gas is helium.
Mass spectra were measured with a Fisons Instruments MD 800
using electron impact (70 eV) as ionization method. HRMS-data
were obtained with a VGQuattro II mass spectrometer (positive ion
mode). Under standard measurement conditions the sample was
dissolved in CH3CN/H2O (1:1) containing 0.1% TFA. In order to avoid
eventual hydrolysis, the imines 8 were dissolved in CH3CN/MeOH
(1:1). High resolution 1H NMR (250 MHz) and 13C NMR (62.9 MHz)
spectra were recorded in CDCl3 or DMSO-d6 on a Bruker Avance
DRX 250 spectrometer. Chemical shifts are reported in parts per
million downfield from TMS. 13C NMR assignments were made
using DEPT, HMQC and HMBC spectra. Infrared spectra were
recorded with an Avatar 370 FT-IR apparatus (Thermo Nicolet).
in methanol. In general, N-tert-butyl-(2,2-dibromopropyl)amine
(36) showed higher reactivity towards NaOMe and KOtBu. With
sodium methoxide in methanol complete conversions were effec-
ted and varying ratios of N-tert-butyl-(2,2-dimethoxypropyl)amine
(28), N-(2-bromoprop-2-enyl)-tert-butylamine (37) and N-tert-
butylpropargylamine were obtained. The extra elimination step of
HBr from 37 could be avoided by using 5 equivalents of NaOMe in
methanol at 35 ꢀC. In this case, N-(2-bromoprop-2-enyl)-tert-
butylamine (37) was obtained in 40% yield after vacuum distillation
(Scheme 9). N-tert-Butyl-(2-haloprop-2-enyl)amines 27 and 37
have been prepared previously by reaction of 2,3-dihalopropene
with tert-butylamine.41
2 equiv NaCNBH3
Br
Br Br
Br Br
1 equiv HOAc
MeOH, rt, 16 h
5 equiv NaOMe, MeOH (4M)
35 °C, 16 h
2.2 equiv NBS
H
H
CCl4, 16h, rt
(85%)
N
N
HN
HN
cyclohexane,
16 h,70 °C
(80%)
34
35
36 (85%)
37 (40%)
Scheme 9.
3. Conclusion
Unless otherwise stated, the IR-spectra were recorded using the
attenuated total reflection technology. Flash chromatography was
In summary, we have successfully extended the Lewis acid-
promoted Mannich-type reaction of aldimines with potassium
performed using Merck silica (diameter 40–63 mm). TLC-analysis
was performed on glass backed plates (Merck) coated with 0.2 mm
silica with UV-indicator 60 F254. Preparative HPLC was performed
using a Gilson HPLC (332 PUMP) and a Gilson UV-detector (UV/VIS-
156) with a reversed phase Discovery BIO wide pore C18 column
organotrifluoroborates to the use of
a,a,a-trichloro-acetaldimines.
In addition to the obtained -trichloroamines, the formerly
b,b,b
prepared dichlorinated secondary propargylamines and allyl-
amines were reacted with several bases. When KOtBu was used, 1,2-
(length: 25 cm, internal diameter: 21.2 mm, particle size: 10
mm)
dehydrochlorinations took place, leading to
and 12, which could be hydrolyzed into the corresponding
chloroketones 20 and 22 in aqueous oxalic acid or hydrochloric
a
-chloroketimines 11
using a MeCN/H2O gradient containing 0.1% TFA. b,b-Dichloro-
a
-
amines 6 and 7 were obtained as described before.1
acid/CH2Cl2 two-phase system, respectively. Treatment of
b,b,b-
trichloroamines 9 and 10 with NaOEt in ethanol or with KOtBu in
4.2. Synthesis of N-alkyl-(2,2,2-trichloroethylidene)amines 8
tetrahydrofuran also resulted in the formation of the corresponding
a
,
a
-dichloroketimines 23 and 24. On the other hand, the reaction of
The synthesis of N-alkyl-(2,2,2-trichloroethylidene)amines 8
was performed according to the literature procedures.17,18 All
simple 2,2-dihalopropylamines with NaOMe in methanol and

1962
K. Abbaspour Tehrani et al. / Tetrahedron 65 (2009) 1957–1966
reactions have been performed starting from 0.15 mol of
acetaldehyde.
4.3.1. N-tert-Butyl-(4,4,4-trichloro-1-phenylbut-1-en-3-yl)-
amine (9a)
Yield: 964 mg (79%), light brown oil. 1H NMR (250 MHz, CDCl3):
4.2.1. N-(2,2,2-Trichloroethyliden)-tert-butylamine17 (8a)
For the sake of completeness full spectral data are given here.
Yield: 17.3 g (57%), light-yellow liquid, bp¼67 ꢀC/22 mmHg. 1H
d
7.35–7.14 (5H, m, aromate), 6.57 (1H, d, J¼15.9 Hz, CHCHCarom.quat.),
6.11 (1H, dd, J¼15.9, 8.0 Hz, CHCHCarom.quat.), 3.89 (1H, dd, J¼8.0, 0.3 Hz,
CCl3CH), 1.10 (9H, s, NC(CH3)3). 13C NMR (62.90 MHz, CDCl3):
135.3
d
NMR (500 MHz, CDCl3):
13C NMR (62.90 MHz, CDCl3):
(NC(CH3)3), 29.2 (NC(CH3)3). IR (ATR, cmꢁ1):
d
7.63 (1H, s, HCN), 1.29 (9H, s, NC(CH3)3).
(Carom.quat.),134.3 (CHCHCarom.quat.),127.6 (Carom.ortho),127.3 (Carom.para),
126.8 (CHCHCarom.quat.), 125.5 (Carom.meta), 103.8 (CCl3), 70.0 (CCl3CH),
d
152.0 (CN), 95.5 (CCl3), 57.7
1680, 1653 (C]N).
n
50.8 (C(CH3)3), 29.5 (C(CH3)3). IR (ATR, cmꢁ1):
n 1495, 1448 (C]C
MS (70 eV, m/z (%)): 208 ([Mþ7]þ, 2), 206 ([Mþ5]þ, 19), 204
([Mþ3]þ, 37), 202 ([MþHþ], 34), 188 (54), 186 (43), 168 (48), 166
(42), 152 (66), 150 (71), 138 (51), 136 (45), 116 (48), 97 (41), 95 (51),
84 (50), 77 (46), 57 (100).
aromate),1365,1271 (CH]CH). MS (70 eV, m/z (%)): 312 ([Mþ7]þ, 0.1),
310 ([Mþ5]þ, 0.4), 308 ([Mþ3]þ,1), 306 (MþHþ, 2), 235 (45), 233 (40),
197 (100), 188 (97), 177 (61), 162 (100), 143 (81), 127 (99), 119 (44), 115
(100),102 (95), 91 (59), 89 (45), 86 (54), 73 (46), 65 (49), 63 (57), 57 (87),
51 (53). HRMS (ESI): m/z calcd for C14H18Cl3NþH: 306.0583; found:
306.0521.
4.2.2. N-(2,2,2-Trichloroethyliden)isopropylamine (8b)
Yield: 13.5 g (48%), colourless liquid, bp¼33 ꢀC/17 mmHg. 1H
NMR (250 MHz, CDCl3):
d
7.75 (1H, s, HCN), 3.68 (1H, septet,
4.3.2. N-(4,4,4-Trichloro-1-phenylbut-1-en-3-yl)iso-
propylamine (9b)
J¼6.3 Hz, NCH(CH3)2), 1.26 (6H, d, J¼6.3 Hz, NCH(CH3)2). 13C NMR
(62.90 MHz, CDCl3):
d
154.5 (CN), 94.2 (CCl3), 59.2 (NCH(CH3)2),
Yield: 710 mg (61%), yellow oil. 1H NMR (250 MHz, CDCl3):
23.3 (NCH(CH3)2). IR (ATR, cmꢁ1):
n
1666 (C]N). MS (70 eV, m/z
d
7.38–7.17 (5H, m, aromate), 6.58 (1H, d, J¼15.8 Hz, CHCHCarom.quat.),
(%)): 194 ([Mþ7]þ, trace), 192 ([Mþ5]þ, 0.5), 190 ([Mþ3]þ, 3), 188
([MþHþ], 4),154 (13),152 (19),136 (13),122 (14), 97 (11), 95 (16), 81
(12), 70 (100), 63 (17), 60 (16).
6.09 (1H, dd, J¼15.8, 8.2 Hz, CHCHCarom.quat.), 3.77 (1H, d, J¼8.2 Hz,
CCl3CHNH), 2.92 (1H, septet, J¼6.3 Hz, NHCH(CH3)2), 1.39 (1H, br
s, NH), 1.06 and 1.04 (2ꢂ3H, 2ꢂd, J¼6.3 Hz, NHCH(CH3)2). 13C NMR
(62.90 MHz, CDCl3):
d 135.0 (Carom.quat.), 134.4 (CH]CHCarom.quat.),
4.2.3. N-(2,2,2-Trichloroethyliden)propylamine (8c)
127.7 (Carom.ortho), 127.2 (Carom.para), 125.7 (Carom.meta), 124.1
Yield: 7.6 g (27%), yellow liquid; bp¼40 ꢀC/18 mmHg. 1H NMR
(CH]CHCarom.quat.), 103.5 (CCl3), 73.1 (CCl3CHNH), 45.7
(250 MHz, CDCl3):
d
7.75 (1H, t, J¼1.3 Hz, HCN), 3.60 (2H, td, J¼7.2,
(NHCH(CH3)2), 23.0, 21.3 (NHCH(CH3)2). IR (ATR, cmꢁ1):
n 1496,1474,
1.3 Hz, NCH2CH2CH3), 1.74 (2H, sextet, J¼7.2 Hz, NCH2CH2CH3), 0.95
1447 (C]C aromate), 1382, 1369 (HC]CH). MS (70 eV, m/z (%)): 298
([Mþ7]þ, trace), 296 ([Mþ5]þ, trace), 294 ([Mþ3]þ, trace), 292
(MþHþ, 0.1), 174 (100), 162 (7), 161 (5), 143 (4), 132 (4), 131 (4), 130
(4),129 (4),128 (5),127 (8),126 (7),117 (3),116 (4),115 (24), 91 (7), 77
(5). HRMS (ESI): m/z calcd for C13H16Cl3NþH: 292.0427; found:
292.0496.
(3H, t, J¼7.2 Hz, NCH2CH2CH3). 13C NMR (62.90 MHz, CDCl3):
d 156.7
(CN), 94.0 (CCl3), 60.4 (NCH2CH2CH3), 23.2 (NCH2CH2CH3), 11.5
(NCH2CH2CH3). IR (ATR, cmꢁ1):
n 1668 (C]N). MS (70 eV, m/z (%)):
194 ([Mþ7]þ, trace),192 ([Mþ5]þ,1),190 ([Mþ3]þ, 3),188 ([MþHþ],
4), 160 (13), 158 (13), 154 (12), 152 (18), 124 (11), 123 (13), 122 (22),
95 (20), 70 (100), 60 (21), 51 (17).
4.3.3. N-(4,4,4-Trichloro-1-phenylbut-1-en-3-yl)-
n-propylamine (9c)
4.2.4. N-(2,2,2-Trichloroethylidene)-2-propenylamine (8d)
Yield: 2.77 g (10%), colourless liquid, bp¼44 ꢀC/20 mmHg. 1H
Yield: 640 mg (55%), yellow oil. 1H NMR (250 MHz, CDCl3):
NMR (250 MHz, CDCl3):
d
7.77 (1H, s, HC]N), 6.04–5.96 (1H, m,
d
7.44–7.12 (5H, m, aromate), 6.61 (1H, d, J¼15.7 Hz, CHCHCarom.quat.),
CH2CH]CH2), 5.27–5.25 (2H, m, CH2CH]CH2), 4.28 (2H, dd, J¼5.6,
1.3 Hz, CH2CH]CH2). 13C NMR (62.90 MHz, CDCl3):
157.5 (C]N),
133.4 (CH2CH]CH2), 117.9 (CH2CH]CH2), 94.0 (CCl3), 60.3
6.08 (1H, dd, J¼15.7, 8.2 Hz, CHCHCarom.quat.), 3.73 (1H, d, J¼8.2 Hz,
CCl3CHNH), 2.76–2.55 (2H, m, NHCH2CH2), 1.56–1.43 (2H, m,
NHCH2CH2), 0.87 (3H, t, J¼7.3 Hz, NHCH2CH2CH3). 13C NMR
d
(CH2CH]CH2). IR (ATR, cmꢁ1):
n
1665 (C]N), 1419, 1347, 1311
(62.90 MHz, CDCl3): d 135.0 (CHCHCarom.quat.), 127.7 (Carom.ortho),
(CH]CH2). MS (70 eV, m/z (%)): 192 ([Mþ7]þ, trace), 190 ([Mþ5]þ,
0.3), 188 ([Mþ3]þ, 1), 186 ([MþHþ], 2), 150 (12), 124 (11), 122 (31),
119 (10), 117 (14), 95 (18), 82 (13), 68 (100), 60 (20), 51 (19).
127.3 (Carom.para), 126.1 (Carom.quat.), 125.7 (Carom.meta), 123.7
(CHCHCarom.quat.), 102.3 (CCl3), 75.3 (CCl3CHNH), 48.7 (NHCH2CH2),
22.1 (NHCH2CH2),10.6 (NHCH2CH2CH3). IR (ATR, cmꢁ1):
n 1495,1448
(C]C aromate), 1380, 1300 (CH]CH). MS (70 eV, m/z (%)): 298
([Mþ7]þ, trace), 296 ([Mþ5]þ, trace), 294 ([Mþ3]þ, trace), 292
(MþHþ, trace), 197 (5), 174 (100), 163 (5), 162 (11), 161 (8), 143 (6),
142 (5),132 (34),130 (7),129 (5),128 (6),127 (12),126 (7),116 (7),115
(41), 102 (4), 91 (6), 77 (7), 76 (5). HRMS (ESI): m/z calcd for
C13H16Cl3NþH: 292.0427; found: 292.0465.
4.3. Synthesis of
procedure
b,b,b-trichloroamines 9 and 10: general
To a stirred solution of
b,b,b-trichloroaldimine 8 (1 equiv,
4 mmol) in CH2Cl2 (8 mL) was added the potassium trifluoroborate
2a or 2b (1 equiv, 4 mmol, 840 mg 2a or 832 mg 2b) in one portion,
followed by BF3$Et2O (1 equiv, 4 mmol, 568 mg). The reaction
mixture was stirred for 18 h at room temperature and poured into
aqueous NaOH (0.5 M, 8 mL). After isolation of the organic layer, the
aqueous phase was washed with CH2Cl2 (8 mL, 8 mL, 4 mL, 4 mL).
The organic fractions were dried (MgSO4) and concentrated under
reduced pressure. In order to remove traces of starting material,
styrene or phenylacetylene the crude reaction mixture was treated
under high vacuum (50 ꢀC, 0.01 mmHg) during 1–2 h. The reactions
with trifluoroborate 2a were carried out in CH2Cl2/HFIP (9/1)
4.3.4. N-(4,4,4-Trichloro-1-phenylbut-1-en-3-yl)-2-
propenylamine (9d)
Yield: 705 mg (61%), yellow oil. 1H NMR (250 MHz, CDCl3):
d
7.44–7.12 (5H, m, aromate), 6.60 (1H, d, J¼15.8 Hz, CHCHCarom.quat.),
6.06 (1H, dd, J¼15.8, 8.2 Hz, CHCHCarom.quat.), 5.92–5.77 (1H, m,
NHCH2CH]CH2), 5.22–5.07 (2H, m, NHCH2CH]CH2), 3.79 (1H, d,
J¼8.2 Hz, CCl3CH), 3.44 (1H, ddt, J¼14.1, 5.3, 6.7 Hz, NHC(H)
HCH]CH2), 3.26 (1H, ddt, J¼14.1, 1.5,1.2 Hz, NHCH(H)CH]CH2),1.67
(1H, br s, NH). 13C NMR (62.90 MHz, CDCl3):
d 135.4 (NHCH2CH]
CH2), 135.1 (CHCHCarom.quat.), 134.9 (Carom.quat.), 127.7 (Carom.ortho),
127.3 (Carom.para), 125.7 (Carom.meta), 123.2 (CHCHCarom.quat.), 116.1
(8 mL). The yields described below for b,b,b-trichloroamines 9 and
10 are the yields after high vacuum evaporation and purities are
>95%. Analytically pure samples were obtained by a preparative
HPLC on a C18 column with MeCN/water gradient as eluent.
(NHCH2CH]CH2), 102.1
(CCl3),
74.0
(CCl3CHNH),
49.0
(NHCH2CH]CH2). IR (ATR, cmꢁ1):
n 1461,1495,1448 (C]C aromate),
1258 (CH]CH). MS (70 eV, m/z (%)): 296 ([Mþ7]þ, trace), 294

K. Abbaspour Tehrani et al. / Tetrahedron 65 (2009) 1957–1966
1963
([Mþ5]þ, trace), 292 ([Mþ3]þ, trace), 290 (MþHþ, trace), 172 (100),
162 (5), 130 (8), 129 (9), 128 (8), 127 (11), 126 (5), 117 (6), 116 (7), 115
(25), 102 (5), 91 (16), 77 (7), 76 (5), 51 (4). HRMS (ESI): m/z calcd for
C13H14Cl3NþH: 290.0270; found 290.0228.
([Mþ7]þ, trace), 292 ([Mþ5]þ, trace), 290 ([Mþ3]þ, 0.1), 288
(MþHþ, 0.1), 198 (5), 197 (4), 196 (13), 170 (100), 161 (6), 160 (6), 152
(4), 151 (4), 149 (10), 141 (6), 140 (4), 129 (4), 128 (31), 127 (23), 126
(25), 115 (14), 114 (15), 113 (11), 103 (7), 102 (12), 91 (7), 84 (5), 77
(6), 76 (7), 75 (6), 74 (9), 63 (5), 62 (6), 51 (5), 50 (4). HRMS (ESI): m/z
calcd for C13H12Cl3NþH: 288.0114; found 288.0145.
4.3.5. N-tert-Butyl-(4,4,4-trichloro-1-phenylbut-1-yn-3-yl)-
amine (10a)
Yield: 921 mg (76%), light brown oil. 1H NMR (250 MHz, CDCl3):
4.4. Synthesis of
a-chloroimines 11 and 12 and a,a-
d
7.39–7.33 (2H, m, CHarom.ortho), 7.26–7.15 (3H, m, CHarom.metaþpara),
4.15 (1H, s, CCl3CHNH), 1.18 (9H, s, C(CH3)3). 13C NMR (62.90 MHz,
CDCl3): 130.6 (Carom.ortho), 127.6 (Carom.para), 127.3 (Carom.meta), 121.3
(Carom.quat.), 101.8 (CCl3), 86.7 (C^CCarom.quat.), 84.9 (C^CCarom.quat.),
61.7 (CCl3CHNH), 50.8 (C(CH3)3), 28.8 (C(CH3)3). IR (ATR, cmꢁ1):
dichloroimines 23 and 24: general procedure
d
To a solution of b,b-dichloroamine 6 or 7 or b,b,b-trichloro-
amine (9 or 10) (0.5 mmol) in dry THF (10 mL), KOtBu was added
in one portion at room temperature. The mixture was heated
under reflux for 2 h before it was quenched with 10 mL water.
After extraction with CH2Cl2 (20 mL, 20 mL, 10 mL), the organic
layers were combined and dried over MgSO4. Filtration and con-
centration under reduced pressure resulted in the corresponding
n
1490, 1443 (C]C aromate). IR (NaCl, cmꢁ1):
n 2226 (C^C). MS
(70 eV, m/z (%)): 310 ([Mþ7]þ, trace), 308 ([Mþ5]þ, trace), 306
([Mþ3]þ, trace), 304 (MþHþ, 0.1), 198 (11), 196 (32), 186 (89), 170
(19), 130 (100), 102 (15), 57 (35). HRMS (ESI): m/z calcd for
C14H16Cl3NþH: 304.0427; found 304.0459.
a
-chloroimine 11 or 12 or a,a-dichloroimine 23 or 24. The amount
of KOtBu differs, depending on the product, which is synthesized.
Reactions were performed on a 0.5 mmol scale, unless otherwise
stated.
4.3.6. N-(4,4,4-Trichloro-1-phenylbut-1-yn-3-yl)-
isoproylamine (10b)
Yield: 786 mg (68%), yellow oil. 1H NMR (250 MHz, CDCl3):
d
7.49–7.42 (2H, m, CHarom.ortho), 7.38–7.25 (3H, m, CHarom.metaþpara),
4.4.1. (E)-N-(4-Chloro-1-phenylpent-1-yn-3-ylidene)-
propylamine (11a)
4.24 (1H, s, CCl3CHNH), 3.24 (1H, septet, J¼6.2 Hz, NHCH(CH3)2),
1.68 (1H, br s, NH), 1.22 and 1.15 (2ꢂ3H, 2ꢂd, J¼6.2 Hz,
Amount of KOtBu used: 2 equiv. Yield: 111 mg (95%), dark yellow
NHCH(CH3)2). 13C NMR (62.90 MHz, CDCl3):
d
131.8 (Carom.ortho),
oil. 1H NMR (250 MHz, CDCl3):
d 7.58–7.53 (2H, m, CHarom.ortho),
128.8 (Carom.para), 128.3 (Carom.meta), 122.2 (Carom.quat.), 101.8 (CCl3),
7.41–7.32 (3H, m, CHarom.metaþpara), 4.69 (1H, q, J¼6.8 Hz, CH3CHCl),
3.68 (2H, t, J¼6.8 Hz, NCH2CH2CH3), 1.78 (3H, d, J¼6.8 Hz, CH3CHCl),
1.78–1.65 (2H, m, NCH2CH2CH3), 0.97 (3H, t, J¼7.4 Hz,
NCH2CH2CH3). Following signals for the Z-imine could be distin-
86.3 (C^CCarom.quat.), 85.5 (C^CCarom.quat.), 66.1 (CCl3CHNH), 48.0
(NHCH(CH3)2), 23.9 and 22.3 (NHCH(CH3)2). IR (ATR, cmꢁ1):
n 2222
(C^C), 1490, 1473, 1443 (C]C aromate). MS (70 eV, m/z (%)): 296
([Mþ7]þ, trace), 294 ([Mþ5]þ, trace), 292 ([Mþ3]þ, trace), 290
(MþHþ, 0.1), 198 (6), 197 (6), 196 (19), 172 (100), 161 (4), 160 (6), 156
(6), 130 (76), 128 (5), 127 (5), 126 (9), 125 (7), 114 (7), 113 (8), 103
(10), 102 (17), 77 (7), 76 (6), 74 (6), 62 (5). HRMS (ESI): m/z calcd for
C13H14Cl3NþH: 290.0270; found 290.0233.
guished in the E/Z mixture. 1H NMR (250 MHz, CDCl3):
d 7.64–7.24
(5H, m, aromate), 7.10 (1H, d, J¼16.8 Hz, CH]CHCarom.quat.), 6.87
(1H, d, J¼16.8 Hz, CH]CHCarom.quat.), 4.51 (1H, q, J¼6.7 Hz,
CH3CHCl), 3.42 (2H, t, J¼7.1 Hz, NCH2CH2CH3), 1.71 (3H, d, J¼6.7 Hz,
CH3CHCl), 1.68–1.59 (2H, m, NCH2CH2CH3), 0.94 (3H, t, J¼7.4 Hz,
NCH2CH2CH3). 13C NMR (62.90 MHz, CDCl3):
d 153.5 (CN), 132.2
4.3.7. N-(4,4,4-Trichloro-1-phenylbut-1-yn-3-yl)propylamine (10c)
(Carom.ortho), 129.8 (Carom.para), 128.5 (Carom.meta), 121.2 (Carom.quat.),
98.5 (C^CCarom.quat.), 79.6 (C^CCarom.quat.), 60.0 (CHCl), 57.6
(NCH2CH2CH3), 23.5 (NCH2CH2CH3), 22.5 (CH3CHCl), 12.0
Yield: 786 mg (68%), orange oil. 1H NMR (250 MHz, CDCl3):
d
7.50–7.43 (2H, m, CHarom.ortho), 7.38–7.26 (3H, m, CHarom.metaþpara),
4.24 (1H, s, CCl3CHNH), 3.07–2.96 and 2.89–2.74 (2H, 2ꢂm (AB),
NHCH2CH2), 1.77 (1H, br s, NH), 1.68–1.51 (2H, m, NHCH2CH2CH3),
0.99 (3H, t, J¼7.4 Hz, NHCH2CH2CH3). 13C NMR (62.90 MHz, CDCl3):
(NCH2CH2CH3). IR (ATR, cmꢁ1):
n 2205 (C^C), 1655 (C]N), 1489,
1443 (C]C aromate). MS (70 eV, m/z (%)): 236 ([Mþ3]þ, 0.5), 235
([Mþ2]þ,1), 234 (MþHþ, 2), 233 (Mþ, 2),198 (33),170 (69),141 (30),
139 (31), 127 (100), 115 (50).
d
131.9 (Carom.ortho), 128.8 (Carom.para), 128.3 (Carom.meta), 122.1
(Carom.quat.), 101.8 (CCl3), 86.7 (C^CCarom.quat.), 84.9 (C^CCarom.quat.),
68.1 (CCl3CHNH), 50.3 (NHCH2CH2), 23.1 (NHCH2CH2), 11.6
4.4.2. (E)-N-(4-Chloro-1-phenylpent-1-yn-3-ylidene)-
isopropylamine (11b)
(NHCH2CH2CH3). IR (ATR, cmꢁ1):
n 2227 (C^C), 1490, 1459, 1443
(C]C aromate). MS (70 eV, m/z (%)): 296 ([Mþ7]þ, trace), 294
([Mþ5]þ, trace), 292 ([Mþ3]þ, trace), 290 (MþHþ, 0.1), 198 (5), 197
(4), 196 (15), 172 (100), 161 (4), 160 (5), 149 (5), 130 (35), 127 (4), 126
(9), 115 (5), 114 (7), 113 (7), 103 (8), 102 (10), 77 (5), 76 (5), 74 (4).
HRMS (ESI): m/z calcd for C13H14Cl3NþH: 290.0270; found
290.0265.
Amount of KOtBu used: 2 equiv. Yield: 104 mg (89%), dark yel-
low oil. 1H NMR (250 MHz, CDCl3):
d 7.56–7.53 (2H, m, CHarom.ortho),
7.40–7.37 (3H, m, CHarom.metaþpara), 4.65 (1H, q, J¼6.8 Hz, CH3CHCl),
4.09 (1H, septet, J¼6.2 Hz, NCH(CH3)2), 1.76 (3H, d, J¼6.8 Hz,
CH3CHCl), 1.22 and 1.20 (2ꢂ3H, 2ꢂd, J¼6.2 Hz, NCH(CH3)2).
13C NMR (62.90 MHz, CDCl3): 151.3 (CN), 132.3 (Carom.ortho), 129.8
(Carom.para), 128.5 (Carom.meta), 121.3 (Carom.quat.), 98.1 (C^CCarom.quat.),
79.3 (C^CCarom.quat.), 60.1 (CHCl), 55.7 (NCH(CH3)2), 23.2 and 23.1
4.3.8. N-(4,4,4-Trichloro-1-phenylbut-1-yn-3-yl)-2-
propenylamine (10d)
(NCH(CH3)2), 22.5 (CH3CHCl). IR (ATR, cmꢁ1):
n 2205 (C^C), 1604
Yield: 746 mg (65%), orange oil. 1H NMR (250 MHz, CDCl3):
(C]N), 1489, 1443 (C]C aromate). MS (70 eV, m/z (%)): 236
([Mþ3]þ, 2), 235 ([Mþ2]þ, 3), 234 (MþHþ, 10), 233 (Mþ, 8), 198 (46),
182 (30), 170 (41), 142 (30), 141 (31), 139 (38), 128 (100), 115 (36), 77
(33), 63 (32).
d
7.50–7.42 (2H, m, CHarom.ortho), 7.37–7.25 (3H, m, CHarom.metaþpara),
6.04–5.88 (1H, m, NHCH2CH]CH2), 5.38–5.12 (2H, m,
NHCH2CH]CH2), 4.28 (1H, s, CCl3CHNH), 3.69 (1H, ddt, J¼14.1, 5.6,
6.6 Hz, NHC(H)HCH]CH2), 3.53 (1H, ddt, J¼14.1, 1.5, 1.2 Hz,
NHCH(H)CH]CH2), 1.93 (1H, br s, NH). 13C NMR (62.90 MHz,
CDCl3): 135.6 (NHCH2CH]CH2), 131.9 (Carom.ortho), 128.9 (Carom.para),
128.4 (Carom.meta), 122.0 (Carom.quat.), 117.6 (NHCH2CH]CH2), 101.5
(CCl3), 86.9 (C^CCarom.quat.), 84.5 (C^CCarom.quat.), 67.0 (CCl3CHNH),
4.4.3. N-(4-Chloro-1-phenylpent-1-en-3-ylidene)-
propylamine (12a)
Amount of KOtBu used: 3 equiv. Yield: 100 mg (85%), dark yellow
oil.1H NMR (250 MHz, CDCl3):
d7.64–7.24 (5H, m, aromate), 7.10 (1H, d,
50.6 (NHCH2CH]CH2). IR (ATR, cmꢁ1):
1443 (C]C aromate), 1287 (CH]CH). MS (70 eV, m/z (%)): 294
n
2226 (C^C), 1490, 1460,
J¼16.8 Hz, CHCHCarom.quat.), 6.87 (1H, d, J¼16.8 Hz, CHCHCarom.quat.),
4.95 (1H, q, J¼6.7 Hz, CH3CHCl), 3.55 (2H, t, J¼7.1 Hz, NCH2CH2CH3),

1964
K. Abbaspour Tehrani et al. / Tetrahedron 65 (2009) 1957–1966
1.74 (3H, d, J¼6.7 Hz, CH3CHCl), 1.76–1.66 (2H, m, NCH2CH2CH3), 0.97
(3H, t, J¼7.4 Hz, NCH2CH2CH3). 13C NMR (62.90 MHz, CDCl3): 164.2
(CN), 137.3 (CHCHCarom.quat.), 128.8 (Carom.ortho), 128.6 (Carom.para), 127.2
(Carom.meta), 123.2 (Carom.quat.), 117.6 (CH]CHCarom.quat.), 57.4 (CHCl),
53.4 (NCH2CH2CH3), 24.2 (NCH2CH2CH3), 22.2 (CH3CHCl), 12.0
temperature. The reaction was diluted in EtOAc (18 mL), washed
with water (18 mL) and brine (18 mL), dried over MgSO4, filtered and
concentrated in vacuo. Purification by flash chromatography
(EtOAc/cHex (5/95), Rf¼0.22) afforded 22 (65%, 32 mg) as a yellow oil.
1H NMR (250 MHz, CDCl3):
d
7.76 (1H, d, J¼15.9 Hz,
(NCH2CH2CH3). IR (ATR, cmꢁ1):
(C]C aromate), 1376 (CH]CH).
n
1629 (C]N), 1494, 1449
CHCHCarom.quat.), 7.62–7.58 (2H, m, CHarom.ortho), 7.46–7.40 (3H,
CHarom.metaþpara), 7.09 (1H, d, J¼15.9 Hz, CHCHCarom.quat.), 4.59
(1H, q, J¼6.8 Hz, CHCl), 1.70 (3H, d, J¼6.8 Hz, CH3). 13C NMR
4.4.4. (Z)-N-(4-Chloro-1-phenylpent-1-en-3-ylidene)-
isopropylamine (12b)
(62.90 MHz, CDCl3): d 193.7 (C]O), 145.2 (CHCHCarom.quat.), 134.2
(Carom.quat.), 131.0 (Carom.para), 129.0 (Carom.ortho), 128.6 (Carom.meta),
Amount of KOtBu used: 5 equiv. Yield: 96 mg (82%), dark yellow
oil. In the crude reaction mixture 10 mol % starting material was
present. Following signals could be distinguished in the NMR
121.1 (CHCHCarom.quat.), 57.8 (CHCl), 20.2 (CH3). IR (NaCl, cmꢁ1):
n
1671, 1692 (CO), 1607, 1575 (C]C aromate), 1495, 1449 (HC]CH).
MS (70 eV, m/z (%)): 196 ([Mþ2]þ, 0.7), 194 (Mþ, 4), 133 (8), 131
(100), 115 (4), 103 (87), 91 (6), 77 (53), 76 (5), 74 (6), 66 (3), 63
(16), 51 (34). HRMS (ESI): m/z calcd for C11H11ClOþH: 195.0577;
found 195.0523.
spectra of this mixture. 1H NMR (250 MHz, CDCl3):
d 7.51–7.27 (5H,
m, aromate), 7.08 (1H, d, J¼16.8 Hz, CHCHCarom.quat.), 6.85 (1H, d,
J¼16.8 Hz, CHCHCarom.quat.), 4.89 (1H, q, J¼6.8 Hz, CH3CHCl), 4.00
(1H, septet, J¼6.2 Hz, NCH(CH3)2), 1.73 (3H, d, J¼6.8 Hz, CH3CHCl),
1.19 and 1.18 (2ꢂ3H, 2ꢂd, J¼6.2 Hz, NCH(CH3)2). 13C NMR
(62.90 MHz, CDCl3): 162.1 (C]N), 137.0 (CHCHCarom.quat.), 128.8
(Carom.ortho), 128.6 (Carom.para), 127.2 (Carom.meta), 123.7 (Carom.quat.),
117.6 (CHCHCarom.quat.), 58.1 (CHCl), 50.6 (NCH(CH3)2), 23.7 and 23.6
4.5.2. (E)- and (Z)-1,4-Dichloro-1-phenylpent-1-en-3-one (20)
(E)-N-(4-Chloro-1-phenylpent-1-yn-3-ylidene)propylamine
(11a) (0.39 mmol, 92 mg) was cooled to 0 ꢀC and treated with
1.4 mL 4 N HCl. After 1 h stirring at room temperature the reaction
was diluted with EtOAc (14 mL), washed with water (14 mL) and
brine (14 mL), dried over MgSO4, filtered and concentrated in
vacuo. Purification by flash chromatography (EtOAC/nHex (1/9))
afforded (E)-20 (Rf¼0.28, 33%, 38 mg) and (Z)-20 (Rf¼0.32, 4%,
5 mg) as yellow oils (about 95% pure), which were contaminated
with very small amounts of 4-chloro-1-phenyl-1-pentyn-3-one
(20).
(NCH(CH3)2), 22.3 (CH3CHCl). IR (ATR, cmꢁ1):
n 1630 (C]N), 1494,
1448 (C]C aromate),1376,1362 (CH]CH). MS (70 eV, m/z (%)): 238
([Mþ3]þ, 2), 237 ([Mþ2]þ, 14), 236 (MþHþ, 7), 235 (Mþ, 30), 200
(60),184 (30),143 (32),141 (30),128 (100), 115 (35), 96 (49), 91 (34),
65 (30), 58 (34).
4.4.5. N-(4,4-Dichloro-1-phenylbut-1-en-3-ylidene)-tert-butyl
amine (23)
Yield: 118 mg (87%), about 85% pure, brown oil. 1H NMR
4.5.2.1. (E)-1,4-Dichloro-1-phenylpent-1-en-3-one ((E)-20). 1H NMR
(250 MHz, CDCl3):
d
7.50–7.15 (5H, m, aromate), 6.98 (1H, d,
(250 MHz, CDCl3): d 7.77–7.70 (2H, m, CHarom.ortho), 7.49–7.40 (3H,
J¼15.8 Hz, CHCHCarom.quat.), 6.81 (1H, d, J¼15.8 Hz, CHCHCarom.quat.),
6.21 (1H, s, CHCl2), 1.29 (9H, s, C(CH3)3). Sample was not pure
enough for further analysis.
m, CHarom.metaþpara), 7.18 (1H, s, CHCquat.), 4.53 (1H, q, J¼6.8 Hz,
CHCl), 1.69 (3H, d, J¼6.8 Hz, CH3). 13C NMR (62.90 MHz, CDCl3):
d
191.7 (CO), 147.4 (Carom.quat.), 137.3 (Cquat.Cl), 131.2 (Carom.para),
128.7 (Carom.meta), 127.5 (Carom.ortho), 118.9 (COCHCCl), 59.2 (CHCl),
20.1 (CH3). IR (NaCl, cmꢁ1):
1697 (CO), 1587, 1574 (C]C aromate),
4.4.6. N-(4,4-Dichloro-1-phenylbut-1-yn-3-ylidene)-tert-butyl
amine (24)
n
1490, 1445 (HC]CH). MS (70 eV, m/z (%)): 232 ([Mþ4]þ, trace), 230
([Mþ2]þ, 0.3), 228 (Mþ, 1), 168 (22), 167 (15), 165 (100), 137 (13),
130 (6), 129 (7), 103 (41),102 (34), 77 (10), 76 (11), 75 (9), 64 (13), 63
(9), 51 (11), 50 (11). HRMS (ESI): m/z calcd for C11H10Cl2OþH:
229.0187; found 229.0145.
Yield: 113 mg (84%), brown oil. 1H NMR (250 MHz, CDCl3):
d
7.51–7.48 (2H, m, CHarom.ortho), 7.36–7.22 (3H, m, CHarom.metaþpara),
6.08 (1H, s, CHCl2), 1.36 (9H, s, NC(CH3)3). 13C NMR (62.90 MHz,
CDCl3): 145.6 (CN), 131.0 (Carom.ortho), 129.1 (Carom.para), 127.6
d
(Carom.meta), 120.0 (Carom.quat.), 99.0 (C^CCarom.quat.), 78.8 (C^C
Carom.quat.), 73.4 (CHCl2), 56.3 (C(CH3)3), 28.0 (C(CH3)3). IR (ATR,
4.5.2.2. (Z)-1,4-Dichloro-1-phenylpent-1-en-3-one ((Z)-20). 1H NMR
(250 MHz, CDCl3): d 7.65–7.61 (2H, m, CHarom.ortho), 7.48–7.38 (3H,
cmꢁ1):
n
2199 (C^C), 1607 (C]N), 1489, 1443 (C]C aromate). MS
(70 eV, m/z (%)): 272 ([Mþ5]þ, 0.5), 271 ([Mþ4]þ, 1), 270 ([Mþ3]þ,
2), 269 ([Mþ2]þ, 2), 268 (MþHþ, 3), 267 (Mþ, 3), 184 (72), 161 (32),
149 (69), 126 (100), 113 (42), 100 (30), 85 (31), 83 (33), 76 (58), 74
(37), 63 (32), 57 (87).
m, CHarom.metaþpara), 6.89 (1H, s, CHCquat.), 4.30 (1H, q, J¼6.8 Hz,
CHCl), 1.57 (3H, d, J¼6.8 Hz, CH3). 13C NMR (62.90 MHz, CDCl3):
d
191.7 (CO), 147.4 (Carom.quat.), 137.3 (Cquat.Cl), 131.2 (Carom.para),
128.7 (Carom.meta), 127.5 (Carom.ortho), 118.9 (COCHCCl), 59.2 (CHCl),
20.1 (CH3). IR (NaCl, cmꢁ1):
1697 (CO), 1587, 1574 (C]C aromate),
n
4.5. Synthesis of
procedure
a
-chloroketones 20 and 22: general
1490, 1445 (HC]CH). MS (70 eV, m/z (%)): 232 ([Mþ4]þ, trace), 230
([Mþ2]þ, 0.3), 228 (Mþ, 1), 168 (22), 167 (16), 165 (100), 137 (15),
130 (4), 129 (5), 103 (36), 102 (34), 78 (4), 77 (9), 76 (11), 74 (10), 63
(20), 51 (10), 50 (10). HRMS (ESI): m/z calcd for C11H10Cl2OþH:
229.0187; found 229.0122. Following signals of 4-chloro-1-phe-
nylpent-1-yn-3-one (21) could be distinguished in the NMR spec-
trum of the crude reaction mixture. 1H NMR (250 MHz, CDCl3):
A solution of 0.25 mmol of
a-chloroimine 11 or 12 in CH2Cl2
(5 mL) was added to a solution of 0.25 mmol oxalic acid in water
(5 mL). After 2 h of reflux, the organic layer was separated and the
water layer was extracted with CH2Cl2 (5 mL, 5 mL, 3 mL). The
CH2Cl2-extracts were dried over MgSO4, filtered and the solvent
evaporated in vacuo.
d
7.50–7.30 (5H, m, aromate), 4.53 (1H, q, J¼6.8 Hz, CHCl), 1.77 (3H,
d, J¼6.8 Hz, CH3). MS (70 eV, m/z (%)): 194 ([Mþ2]þ, trace), 192 (Mþ,
0.4), 158 (0.4), 157 (0.20), 131 (3), 129 (100), 103 (1), 101 (8), 99 (1),
78 (2), 77 (2), 76 (8), 74 (12), 64 (2), 63 (3), 62 (1), 51 (5), 50 (4).
4.5.1. 4-Chloro-1-phenylpent-1-en-3-one (22)
Hydrolysis
of
N-(4-chloro-1-phenylpent-1-en-3-ylidene)
isopropylamine (12a) (0.25 mmol, 59 mg) with oxalic acid fur-
nished 4-chloro-1-phenylpent-1-en-3-one (22) in 71% yield
(34 mg, yellow oil). Alternatively this product may be obtained by
hydrolyzing N-(4-chloro-1-phenylpent-1-en-3-ylidene)isopropyl-
amine (0.5 mmol, 118 mg) with 2 mL of 4 N HCl for 1 h at room
4.6. Reduction of N-(2,2-dihalopropylidene)amines 25:
synthesis of 2,2-dihalopropylamines 26: typical procedure
The following experiment is representative for the synthesis of
compounds 26a–cand 36. To a solution of N-(2,2-dichloropropylidene)-

K. Abbaspour Tehrani et al. / Tetrahedron 65 (2009) 1957–1966
1965
tert-butylamine (0.46 g, 2.5 mmol) in dry methanol (5 mL) was added
acetic acid (0.15 g, 2.5 mmol). At 0 ꢀC and sodium cyanoborohydride
(0.33 g, 5 mmol) was added portionwise under vigorous stirring. After
overnight reaction at room temperature the reaction mixture was
poured into aqueous NaOH (01 M, 40 mL) and extracted with CH2Cl2
(3ꢂ10 mL). The organic layers were combined and dried over MgSO4.
Filtration and concentration under reduced pressure, followed by vac-
uum distillation (bp 79–81 ꢀC/25 mmHg, lit.7 73 ꢀC/35 mmHg) fur-
nished N-tert-butyl-(2,2-dichloropropyl)amine (25b) (72%, 0.33 g) as
a colourless oil.
fraction 56–64 ꢀC/15 mmHg (0.61 g) consisted of a 7/3 mixture of N-
(2-chloroprop-2-enyl)-tert-butylamine
and
N-tert-butyl-(2,2-
dimethoxypropyl)amine (1H NMR). Analytically pure samples of 27
and 28 were obtained by preparative gas chromatography.
4.7.1. N-(2-Chloroprop-2-enyl)-tert-butylamine (27)
1H NMR (270 MHz, CDCl3):
d
5.42 (1H, d, J¼0.7 Hz, CH(H)), 5.26
(1H, d, J¼0.7 Hz, CH(H)), 3.36 (2H, s, CH2N), 1.4 (1H, br s, NH), 1.13
(9H, s, C(CH3)3). 13C NMR (68 MHz, CDCl3):
141.6 (CCl), 110.9
(]CH2), 49.7 (CH2N), 48.6 (C(CH3)3), 28.3 (C(CH3)3). IR (NaCl,
d
cmꢁ1):
n NH not visible, 1639 (C]C). MS (70 eV, m/z (%)): 149
4.6.1. N-tert-Butyl-(2,2-dichloropropyl)amine (26b)
([Mþ2]þ, trace), 147 (Mþ, 1), 134 (40), 132 (100), 96 (9), 77 (5), 75
1H NMR (270 MHz, CDCl3):
d
3.12 (2H, s, CH2), 2.14 (3H, s,
CH3CCl2), 1.45 (1H, br s, NH), 1.11 (9H, s, C(CH3)3). 13C NMR (68 MHz,
CDCl3): 90.9 (CCl2), 58.1 (CH2), 50.2 (C(CH3)3), 34.3 (CH3CCl2), 29.2
(C(CH3)3). IR (NaCl, cmꢁ1):
3340 (NH), 2965, 1479, 1455, 1364. MS
(7), 58 (7), 57 (7), 56 (10).
d
4.7.2. N-tert-Butyl-(2,2-dimethoxypropyl)amine (28)
n
1H NMR (270 MHz, CDCl3):
d
3.21 (6H, s, C(OCH3)2), 2.65 (2H, s,
CH2), 1.36 (3H, s, CH3C(OCH3)2), NH was not visible, 1.09 (9H, s,
C(CH3)3). 13C NMR (68 MHz, CDCl3):
101.5 (C(OCH3)2), 49.9
(C(CH3)3), 48.1 (OCH3), 46.7 (CH2), 29.0 (C(CH3)3), 20.5
(70 eV, m/z (%)): 187 ([Mþ4]þ, trace), 185 ([Mþ2]þ, 1), 185 (Mþ, 2),
172 (8), 170 (40), 168 (66), 134 (50), 132 (72), 96 (13), 94 (15), 92
(44), 86 (87), 58 (39), 57 (100), 56 (40), 55 (15). HRMS (ESI): m/z
calcd for C7H15Cl2NþH: 184.0660; found 184.0643.
d
(CH3CC(OCH3)2). IR (NaCl, cmꢁ1):
n NH not visible, 2965, 1232. MS
(70 eV, m/z (%)): no Mþ, 129 (17), 127 (15), 114 (23), 99 (12), 97 (11),
89 (12), 86 (18), 85 (29), 59 (29), 57 (100). In the 1H NMR spectrum
of compound 28 following signals of tert-butyl-(2-methoxypropen-
2-enyl)amine (29) could be distinguished. 1H NMR (270 MHz,
4.6.2. N-(2,2-Dichloropropyl)isopropylamine (26a)
Scale of the experiment: 45 mmol. Yield: 6.81 g (89%), colourless
oil. Bp 54 ꢀC/15 mmHg.
1H NMR (270 MHz, CDCl3):
d
3.16 (2H, s, CH2), 2.91 (1H, sep-
CDCl3):
d
4.08 (1H, d, J¼1.8 Hz, CH(H)), 3.96 (1H, d, J¼0.7 Hz, CH(H)),
tet, J¼6.3 Hz, (CH3)2CH), 2.15 (3H, s, CH3CCl2),1.48 (1H, br s, NH),1.09
3.57 (3H, s, OCH3), 3.19 (2H, s, CH2N), NH not visible, 1.12 (9H, s,
C(CH3)3). MS (70 eV, m/z (%)): 143 (6), 128 (100), 96 (51), 86 (11), 72
(10), 59 (10), 58 (10), 57 (21).
(6H, d, J¼6.3 Hz, (CH3)2CH). 13C NMR (68 MHz, CDCl3):
d 90.3 (CCl2),
62.1 (CH2), 48.6 (CH), 34.5 (CH3CCl2), 23.0 (CH(CH3)2). IR (NaCl,
cmꢁ1):
n 3328 (NH), 2965, 1468, 1446, 1381. MS (70 eV, m/z (%)): 171
([Mþ2]þ, trace), 169 (Mþ, 1), 158 (2), 156 (8), 154 (17), 134 (11), 120
(15), 118 (25), 94 (12), 92 (20), 84 (9), 72 (100), 56 (15). HRMS (ESI):
m/z calcd for C6H13Cl2NþH: 170.0503; found 170.0516.
4.8. Reaction of N-tert-butyl-(2,2-dibromopropyl)amine (36)
with sodium methoxide and potassium tert-butoxide
This procedure is analogous to the procedure for the preparation
of 27 and 28. The crude reaction mixture was obtained by reaction
of 6.5 mmol of 36 with sodium methoxide in methanol (8.13 mL,
4 M) at 35 ꢀC during 18 h. Short path distillation gave N-(2-bro-
moprop-2-enyl)-tert-butylamine (37) as a light-yellow oil. Bp 82–
88 ꢀC/25 mmHg (lit.42 103–105 ꢀC/90 mmHg). Yield: 0.56 g (40%).
4.6.3. N-Cyclohexyl-(2,2-dichloropropyl)amine (26c)
Scale of the experiment: 35 mmol. Yield: 4.56 g (62%), colourless
oil. Bp 108–116 ꢀC/15 mmHg.
1H NMR (270 MHz, CDCl3):
d
3.19 (2H, s, CH2N), 2.51 (1H, tꢂt,
J¼10.0, 3.6 Hz, NCH), 2.14 (3H, s, CH3), 1.9–1.10 (10H, m, (CH2)5). 13
C
NMR (68 MHz, CDCl3):
d
80.9 (CCl2), 62.1 (CH2N), 56.9 (CH), 34.8
1H NMR (270 MHz, CDCl3):
(1H, d, J¼1.0 Hz, CH(H)), 3.43 (2H, s, CH2N), 1.13 (9H, s, C(CH3)3), NH
was not visible. 13C NMR (68 MHz, CDCl3):
134.0 (CBr), 116.5
d
5.88 (1H, d, J¼1.0 Hz, CH(H)), 5.50
(CH3), 34.0 (2ꢂCH2), 26.3 ((CH2)2CH2(CH2)2), 25.2 (2ꢂCH2). IR
(NaCl, cmꢁ1):
n
2928, 2854,1458,1371, NH not visible. MS (70 eV, m/z
d
(%)): 211 ([Mþ2]þ, trace), 209 (Mþ, 1), 176 (2), 174 (4), 168 (16), 166
(22), 138 (14), 112 (100), 83 (24), 56 (11), 55 (19). HRMS (ESI): m/z
calcd for C9H17Cl2NþH: 210.0816; found 210.0838.
(]CH2), 51.5 (CH2N), 50.6 (C(CH3)3), 29.1 (C(CH3)3). IR (NaCl, cmꢁ1):
n
3315 (NH), 1635 (C]C). MS (70 eV, m/z (%)): 193 ([Mþ2]þ, 1), 191
(Mþ), 178 (98), 176 (100), 121 (4), 119 (4), 97 (22), 96 (9), 82 (13), 58
(8), 57 (8), 56 (9). HRMS (ESI): m/z calcd for C7H14BrNþH: 192.0388;
found 192.0363.
4.6.4. N-tert-Butyl-(2,2-dibromopropyl)amine (36)
Scale of the experiment: 20 mmol. Yield: 4.64 g (85%), yellow
oil. Bp 82–85 ꢀC/10 mmHg.
A solution of 2,2-dibromopropylamine (36) (0.27 g, 1 mmol) in
dry THF (2 mL) was reacted with KOtBu (0.25 g, 2.2 mmol) during
3 h under reflux. After aqueous workup (20 mL) and extraction
with CH2Cl2 (3ꢂ5 mL) the combined organic phases were dried
over MgSO4, filtered and concentrated in vacuo. This crude reaction
mixture contained 67% of N-tert-butylpropargylamine as measured
by capillary GC. Despite the fact that this crude product could not be
further purified, following significant signals could be distin-
guished in the NMR spectra. These data differ slightly from those
reported in literature, probably due to solvent related shifts.44 1H
1H NMR (270 MHz, CDCl3):
d
3.22 (2H, s, CH2), 2.50 (3H, s,
CH3CBr2),1.13 (9H, s, C(CH3)3), NH was not visible.13C NMR (68 MHz,
CDCl3): 70.6 (CCl2), 60.8 (CH2), 50.6 (C(CH3)3), 38.1 (CH3CCl2), 29.7
(C(CH3)3). IR (NaCl, cmꢁ1):
3335 (NH), 2978, 2867,1481,1446,1390,
d
n
1366. MS (70 eV, m/z (%)): 273 ([Mþ2]þ, trace), 256 (18), 258 (9), 260
(19),176 (33),178 (30),138 (34),136 (32), 98 (26), 97 (27), 86 (44), 82
(14), 58 (42), 57 (100), 56 (19). HRMS (ESI): m/z calcd for
C7H15Br2NþH: 271.9649; found 271.9670.
NMR (270 MHz, CDCl3):
d
3.38 (2H, d, J¼2.6 Hz, CH2), 2.21 (1H, t,
4.7. Reaction of N-tert-butyl-(2,2-dichloropropyl)amine 26b
with sodium methoxide
J¼2.6 Hz, CH), 1.13 (9H, s, C(CH3)3), NH was not visible. 13C NMR
(68 MHz, CDCl3): d 83.2 (^CCH2), 70.4 (CH), 50.5 (C(CH3)3), 47.8
(CH2), 28.5 (C(CH3)3). MS (70 eV, m/z (%)): 111 (5), 97 (14), 96 (100),
A solution of sodium methoxide in methanol (2 M, 50 mL) was
added to N-tert-butyl-(2,2-dichloropropyl)amine (1.84 g, 10 mmol).
This reaction mixturewas stirred overnight under reflux, poured out
in water (150 mL) and extracted with dichloromethane (3ꢂ50 mL).
After drying over MgSO4, filtration and concentration under reduced
pressure the residue was subjected to vacuum distillation. The
81 (7), 80 (7), 70 (9), 58 (9), 57 (7), 56 (7), 55 (7), 54 (9).
Acknowledgements
S.S. is a research assistant of the Fund for Scientific Research-
Flanders (Belgium).

1966
K. Abbaspour Tehrani et al. / Tetrahedron 65 (2009) 1957–1966
23. (a) Raina, S.; Singh, V. K. Tetrahedron 1995, 51, 2467–2476; (b) Giubellina, N.;
References and notes
Aelterman, W.; De Kimpe, N. Pure Appl. Chem. 2003, 75, 1433–1442.
24. Satoh, T.; Nakamura, A.; Iriuchijima, A.; Hayashi, Y.; Kubota, K. i. Tetrahedron
2001, 57, 9689–9696.
25. Livingston, R.; Cox, L. R.; Odermatt, S.; Diederich, F. Helv. Chim. Acta 2002, 85,
3052–3077.
1. Stas, S.; Abbaspour Tehrani, K. Tetrahedron 2007, 63, 8921–8931.
2. Konev, A. S.; Stas, S.; Novikov, M. S.; Khlebnikov, A. F.; Abbaspour Tehrani, K.
Tetrahedron 2007, 64, 117–123.
3. Stas, S.; Abbaspour Tehrani, K. Tetrahedron 2008, 64, 3457–3463.
4. Neale, R. S.; Hinman, R. L. J. Am. Chem. Soc. 1963, 85, 2666–2667.
5. Neale, R. S. J. Am. Chem. Soc. 1964, 86, 5340–5342.
26. Linderman, R. J.; Lonikar, M. S. J. Org. Chem. 1988, 53, 6013–6022.
27. Coutrot, P.; Grison, C. Tetrahedron Lett. 1988, 29, 2655–2658.
28. Davis, F. A.; Kasu, P. V. N. Tetrahedron Lett. 1998, 39, 6135–6138.
29. Martins, M. A. P.; Emmerich, D. J.; Pereira, C. M. P.; Cunico, W.; Rossato, M.;
Zanatta, N.; Bonacorso, H. G. Tetrahedron Lett. 2004, 45, 4935–4938.
30. Himbert, G.; Henn, L. Tetrahedron Lett. 1981, 22, 2637–2640.
31. Kowalski, C. J.; Haque, M. S. J. Org. Chem. 1985, 50, 5140–5142.
32. Rankin, T.; Tykwinski, R. R. Org. Lett. 2003, 5, 213–216.
33. Kavala, V.; Naik, S.; Patel, B. K. J. Org. Chem. 2005, 70, 4267–4271.
34. Goud, P. M.; Sheri, A.; Desai, P. V.; Watkins, E. B.; Tekwani, B.; Sabnis, Y.; Gut, J.;
Rosenthal, P. J.; Avery, M. A. Med. Chem. Res. 2005, 14, 74–105.
35. Stevens, C.; De Kimpe, N. Org. Prep. Proced. Int. 1990, 22, 589–595.
36. Mangelinckx, S.; Rooryck, S.; Jacobs, J.; De Kimpe, N. Tetrahedron Lett. 2007, 48,
6535–6538.
6. Neale, R. S. Tetrahedron Lett. 1966, 5, 483–488.
7. Neale, R. S.; Marcus, N. L. J. Org. Chem. 1968, 33, 3457–3460.
8. De Kimpe, N.; Stevens, C. Tetrahedron 1991, 47, 3407–3416.
9. Verniest, G.; Colpaert, F.; Van Hende, E.; De Kimpe, N. J. Org. Chem. 2007, 72,
8569–8572.
10. D’hooghe, M.; De Meulenaer, B.; De Kimpe, N. Synlett 2008, 2437–2442.
11. Lukasiewicz, A. Tetrahedron 1964, 20, 1–12.
12. Wichert-Tur, Z. Pol. J. Chem. 1997, 71, 739–746.
13. Brower, F.; Burkett, H. J. Am. Chem. Soc. 1953, 75, 1082–1084.
14. Gaudemar-Bardone, F.; Mladenova, M.; Gaudemar, M. Synthesis 1988, 611–614.
´
15. Ma˛kosza, M.; Kwast, A.; Kwast, E.; Jonczyk, A. J. Org. Chem. 1985, 50, 3722–3727.
16. De Kimpe, N.; Verhe´,R.;DeBuyck,L.;Schamp,N.Bull. Soc. Chim. Belg.1983,92, 233–239.
17. Verhe,
37. De Kimpe, N.; Schamp, N. Bull. Soc. Chim. Belg. 1974, 83, 507–514.
38. Magueur, G.; Crousse, B.; Bonnet-Delpon, D. Tetrahedron Lett. 2005, 46,
2219–2221.
´
R.; De Kimpe, N.; De Buyck, L.; Tilley, M.; Schamp, N. Bull. Soc. Chim. Belg.
1977, 86, 879–885.
18. De Kimpe, N.; Verhe´, R.;De Buyck, L.; Moens, L.; Schamp, N. Synthesis1982, 43–46.
19. De Kimpe, N.; Verhe´, R.; De Buyck, L.; Schamp, N. J. Org. Chem.1980, 45, 5319–5325.
20. Tennyson, R.; Romo, D. J. Org. Chem. 2000, 65, 7248–7252.
21. Palacios, F.; Ochoa de Retana, A. M.; Pascual, S.; Oyarzabal, J. J. Org. Chem. 2004,
69, 8767–8774.
39. Magueur, G.; Crousse, B.; Bonnet-Delpon, D. Eur. J. Org. Chem. 2008, 1527–1534.
40. DeKimpe, N.; Verhe´, R.;DeBuyck,L.;Schamp,N. Synth. Commun.1975, 5, 269–274.
41. De Kimpe, N.; Stanoeva, E. Synthesis 1994, 695–697.
42. Bottini, A. T.; King, B. J.; Olsen, R. E. J. Org. Chem. 1963, 28, 3241–3243.
43. De Kimpe, N.; De Corte, B. Tetrahedron 1992, 48, 7345–7362.
44. Ben-Efraim, D. A. Tetrahedron 1973, 29, 4111–4125.
´
22. De Kimpe, N.; Verhe, R. In The Chemistry of
a-Haloketones, a-Haloaldehydes and a-
Haloimines; Patai, S., Rappoport, Z., Eds.; Wiley: Chichester, UK,1988; pp 394–439.