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Dehydrogenation of Secondary Amines to IminesCatalyzed by an Iridium PCP Pincer Complex
A TIffiSIS SUBMITTED TO TIffi GRADUATE DIVISION OFTHE UNNERSITY OF HAWAI'I IN PARTIAL FULFILLMENT OF
THE REQUIREMENTS FOR THE DEGREE OF
MASTER OF SCIENCE
IN
CHEMISTRY
DECEMBER 2002
By
Wei Cheng
Thesis Committee:Craig M. Jensen, Chairperson
JohnD. HeadRoger E. Cramer
TABLE OF CONTENTS
AcknowledgementsAbstractList of SchemesChapter 1: Introduction
1.1 Condensation of Aldehydes and Ketones with Amines1.2 Catalytic Imination of Ketones1.3 Oxidative Dehydrogenation of Amines
Chapter 2: Catalytic Reactions2.1 Introduction2.2 Experimental
2.2.1 Catalytic Reactions General Procedure
2.2.2 Synthesis ofAuthentic Samples ofImines2.2.3 Preparative scale synthesis ofN-butylidenebenzy1amine
2.3 Results and Discussion2.3.1 Catalytic Reactions2.3.2 Preparative scale catalytic reaction
Chapter 3: Mechanistic Studies3.1 Introduction3.2 Experimental
3.2.1 The preparation of 2,2,2' ,2' -tetramethy1dibuty1aimine
3.3 Results and Discussion3.3.1 Spectra Study
3.3.2 Results
Chapter 4: ConclusionsReferenceAppendix
11
111
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10101112121516162022222525282829323436
ACKNOWLEDGEMENTS
I would like to give my sincere thanks to my advisor, Professor Craig M. Jensen,
for his guidance and for allowing me to contribute to this project.
I would also like to thank the members of the Jensen research group, past and
present, for their help and companionship.
Many thanks go to Wesley Yoshiba for his help in obtaining NMR and mass
spectra.
ii
ABSTRACT
The PCP pincer complex, IrH2{C6H3-2,6-(pBu/2)2}, catalyzes the transfer
dehydrogenation of secondary amines. Dehydrogenation occurs across C-N bonds rather
than C-C bonds to give imines that are obtained in good to excellent yields when the
reactions are carried out in toluene solution. The regioselectivity of the dehydrogenation
of aliphatic amines is stringently controlled by stene factors while dehydrogenation of
aromatic amines leads to imine products favored thermodynamically by conjugated 1t
bonds in the aromatic system. The dehydrogenation reaction has been successfully
carried out in large scale (separable) with N-butylbenzylamine with acceptable separation
yield. The dehydrogenation of2,2,2',2'-tetramethyldibutylamine leads exclusively to
production of the corresponding imine indicating that the catalytic reaction pathway
involves the initial intermolecular oxidative addition of a N-H bond rather than a C-H
bond.
iii
LIST OF SCHEMES
Scheme Page
I. Amine Dehydrogenation with Ru-catalyst and PhIO 5
II. Catalytic dehydrogenation ofbenzyl amine 8
III. Possible Mechanismsfor the Dehydrogenation of Amines 23
IV. Synthesis of 2,2,2',2'-tetramethyldibutylaimine 26
V. Fragmentation of Imines 29
VI. Results of dehydrogenationof 2,2,2' ,2'-tetramethyldibutylaimine 31
iv
Table
I.
II.
LIST OF TABLES
Some typical bond energies
Dehydrogenation of amines using PCP pincer catalyst
v
Page
11
19
TABLE OF CONTENTS
AcknowledgementsAbstractList of SchemesChapter 1: Introduction
1.1 Condensation of Aldehydes and Ketones with Amines1.2 Catalytic Imination of Ketones1.3 Oxidative Dehydrogenation of Amines
Chapter 2: Catalytic Reactions2.1 Introduction2.2 Experimental
2.2.1 Catalytic Reactions General Procedure2.2.2 Synthesis of Authentic Samples ofImines
2.2.3 Preparative scale synthesis ofN-butylidenebenzylamine
2.3 Results and Discussion2.3.1 Catalytic Reactions
2.3.2 Preparative scale catalytic reaction
Chapter 3: Mechanistic Studies3.1 Introduction3.2 Experimental
3.2.1 The preparation of 2,2,2' ,2' -tetramethyldibutylaimine
3.3 Results and Discussion3.3.1 Spectra Study3.3.2 Results
Chapter 4: ConclusionsReference
11
III
IV
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101011121215161620222225252828293234
Acknowledgements
11
Abstract
The PCP pincer complex, IrHz{C6H3-2,6-(PBu'z)z}, catalyzes the transfer
dehydrogenation of secondary amines. Dehydrogenation occurs across C-N bonds rather
than C-C bonds to give imines that are obtained in good to excellent yields when the
reactions are carried out in toluene solution. The regioseleetivity of the dehydrogenation
of aliphatic amines is stringently controlled by steric factors while dehydrogenation of
aromatic amines leads to imine products favored thermodynamically by conjugated 1t
bonds in the aromatic system. The dehydrogenation reaction has been successfully
carried out in large scale (separable) with N-butylbenzylamine with acceptable separation
yield. The dehydrogenation of2,2,2',2'-tetramethyldibutylamine leads exclusively to
production of the corresponding imine indicating that the catalytic reaction pathway
involves the initial intermolecular oxidative addition of a N-H bond rather than a C-H
bond.
iii
LIST OF SCHEMES
Scheme Page
I. Amine Dehydrogenation with Ru-catalyst and PhIO 5
II. Catalytic dehydrogenation of benzyl amine 8
III. Possible Mechanismsfor the Dehydrogenation of Amines 23
IV. Synthesis of 2,2,2',2'-tetramethyldibutylaimine 26
V. Fragmentation oflmines 29
VI. Results of dehydrogenationof 2,2,2',2'-tetramethyldibutylaimine 31
IV
Table
I.
II.
LIST OF TABLES
Some typical bond energies
Dehydrogenation of amines using PCP pincer catalyst
v
Page
11
19
Chapter 1
Introduction
Imines are one of the basic building blocks of modem organic chemistry. For
example, the enantioselective hydrogenation ofimines is an important way to produce
optically active amines. [1) The C=N group in imines occurs in many organic
molecules of fundamental importance and biochemical activities. Imines also playa
pivotal role in chemical transformations as diverse as the synthesis of azaaromatic
heterocycles [2] and the biosynthesis of amino acids. [3] Imines are also intermediates
for reactions like the Strecker Synthesis. [4] There are generally three ways to
synthesize imines, the condensation of aldehydes and ketones with amines, the
catalytic imination ofketones and the catalytic dehydrogenation of amines.
1.1 Condensation ofAldehydes and Ketones with Amines
The preparation ofbasic aldimines is very simple. The condensation of
aliphatic aldehydes with aliphatic primary or secondary amines forms the
corresponding hnines. To gain higher yield, the water formed in the reaction must be
removed to push the equilibrium. This can be accomplished by distillation, using
R R
"" ""C=O + R -NH2 ----J..~ C=N-R +H 20 (1)'/ ./R R
1
azeotrope-forming solvent or using molecular sieves. [5]
However, the preparation of imines becomes progressively more difficult as
one passes from aldehydes to ketones and as one employs aromatic, rather than
aliphatic reactants. Sometimes the preparation of imines could become more
problematic when:
1. One or both ofthe reactants of the condensation are aromatic, especially in the case
of aromatic ketones. Higher reaction temperatures are needed as well as longer
reaction times. In most of the cases, the yield is very low. [5]
2. The imines from primary aldehydes undergo very easily aldol-type condensations
under acidic condition to form polymers. [5]
3. For the amines and aldehydes with low boiling points, i.e., N
benzylidenemethylamine, critical conditions are required. For example, temperature as
low as -40°C, under argon/nitrogen, thick-walled flask equipped with Solv-Seal joints.
In such cases, the yield of the reaction is quite low. [6J
1.2 Catalytic Imination of Ketones
Over 120 years ago, Schiff showed that aldimine formation from aromatic
amines is base-catalyzed. [7J For the most difficult case, ketimines bearing two or more
aromatic groups, Reddelien found that a combination ofproton and Lewis acids
proved to be an effective iminating catalyst. [8J The use of acidic or basic catalysis,
however, coupled with the slower rates ofketiminations, can lead to extensive side
reactions, such as aldol condensations or competitive IA-additions to ct,B-unsaturated
2
ketones. Under Reddelien's conditions of imination, for example, acetophenone and
aniline produce a large proportion ofdypnone anil while chalcone yields only one
conjugate adduct:
oII
Ph-C-Me
1
ZnCI2, heat
Ph H
"'c=c! Ph
M / "'C=N/e / ._
Ph2
(2)
3
oPhNH
2Ph", H2 II .
Z Cl h • Me /C-C-C-Phn 2, eatPhNH
4
(3)
In more recent work, TiCl4 has been used to promote the formation of
ketimines from substituted cyclohexanones. [9] Employment of a molar equivalent of
n-Bu2SnCh has been suggested for the same purpose. [9J Likewise, ZnCh has shown to
catalyze the preparation ofketimines from ketones and N,N-bis(trimethylsilyl)-
amines. [10] Other indirect routes to ketimines include the reactions of ketones with
iminophosphoranes, ofN-di-aikylaluminoimines with primary amines, and of <;t-
iminophosphonium methylides with aldehydes. [II] However, in these syntheses of
ketimines, the former Lewis acid catalyzed methods do not resolve the issue of
possible side reactions, and the latter indirect methods involve multi-step processes.
John Eisch's group tried to find a potent iminating agent for both aldehydes and
ketones, which would selectively and irreversibly attack the carbonyl group and
minimize the condensation reactions. The dialuminum salt of a primary amine was
3
found to be an attractive reagent, since reaction with a ketone would irreversibly form
a highly stable dialuminoxane, as shown in reaction 4. The imination agent a, bis
(didethylaluminum) phenylimide proved capable ofiminating
R R" a: R"=Ph E=Et" ••
R"N(AlEzh + /C=O b: R=Ph E=C\-' /C=N"" + E2AI-O-AIE2 (4)R' R' R"
Ketones. However, the conversions were only modest at lower temperatures and at
higher temperatures the residual Et-Al groups tend to eliminate ethylene. The resulting
Al-H bonds then caused a competing reduction of the ketone. To obviate this
difficulty, an analogous iminating reagent b, bis(dichloroaluminium) phenylimide, was
prepared. This reagent proved capable of converting aldehydes and a variety of
aliphatic and aromatic ketones into ketimines in generally high yields within a reaction
temperature range of 25-65 DC. However, modest amounts of aldol condensation still
were observed. However, the yield was higher than Reddelien's method. [12]
1.3 Oxidative Dehydrogenation of Amines
Another major method to synthesize imines is through oxidative
dehydrogenation ofamines, which is also widespread in biochemistry (e.g. by various
amine oxidase enzymes). The common oxidation of amines may lead to variety of
products, including nitriles, nitro species and carbonyl compounds formed by cleavage
reactions of highly reactive imine species formed in the oxidation. By contrast,
however, the oxidation of amines coordinated to metal centers leads quantitatively to
4
the dehydrogenated product. [13] Limited numbers of systems for the catalytic
production of imines through the dehydrogenation of amines have been developed.
However, they are not widely employed due to low yields, unsatisfactory product
selectivity and/or high request catalyst loading.
Gilabert found PhIO, either alone or, better, in conjunction with RuCh(PPh3)3
is efficient for dehydrogenation of secondary, activated amines to imines. The Ru- .
catalyzed amine oxidation with PhIO could proceed via a ruthenium-amine complex
undergoing 13-hydride elimination to an imine-hydridoruthenium while PhIO acts as
hydrogen acceptor. Alternatively, the oxidation product ofRuCh(pPh3h and PhIO, a
Ru-oxo complex, could be the active catalyst, which dehydrogenates the amines and is
regenerated by the PhIO, as shown in Scheme 1.
Scheme I. Amine Dehydrogenation with Ru-catalyst and PhIO
I
oII(RU
LxRu
5
However the experiment provided no evidence in favor of these mechanisms.
The oxidation of amines to imines by PhIO in absence of catalyst started from
nucleophilic addition of the amine to the iodosyl function leading to the intermediate
which breaks down via l3-hydride elimination to imine, iodobenzene and H20, as
shown in reaction 5.
/Ph
PhI=OPhH2C-N-Ph ---.~PhHC-N ----.~ PhCH=NPh + PhI + H20
I I IH H/1"
HO Ph
The reaction gives lower yield and requires the presence ofan activating
(5)
phenyl ring or double bond in a position of the C-H bond undergoing oxidation. In the
absence of such activation the reaction does not proceed. [14] Murahashi did a similar
research by using t-butyl hydroperoxide instead ofPhIO in presence ofa ruthenium
catalyst. However, the oxidation of amines is limited to several aromatic amines and
the requirement of a strong oxidant and high catalyst loadings renders this system
unattractive and not widely employed. [15]
The Yoshiki group from Osaka University found treatment ofbenzylamine
with a catalytic amount of a binuclear copper (II) complex of7-azaindole under an
oxygen atmosphere at room temperature produced benzylidene benzylamine and
benzonitrile in good yields, as shown in equation 6.
6
~ -2e- ~Ph NH2 --.2-H-+--l·'- Ph ~NH--l (6)
However, the result of the reaction seems unpredictable since n-propylamine gave no
propionitrile but only corresponding imine under same conditions. The same catalyst
system was also tried with secondary and tertiary amines. However, the reaction with
secondary amines produced quite low yields since the reactivity of secondary amines
toward oxidation is controlled more by steric factors. The bulky structure of the
catalyst strongly hindered the coordination of the amines to the Cu metal center. While
various aliphatic tertiary amines were nearly inert in this oxidation system, N-
phenylpyrrolidine, which has relatively low ionization potential in comparison with N-
alkylpyrrolidine, reacted to give oxidative cyclo adducts and the oxygenated product,
l-phenyl-2-pyrrolidinone. [16]
The James group from University of British Columbia used trans-
[RuvI(tmp)(OhJ to dehydrogenate primary and secondary amines. Primary amines
with -eH2NH2 functionality were oxidized to nitriles in 100% yields, having water as
the coproduct; the intermediate imines (-CH=NH) are presumably readily
dehydrogenated. Primary and secondary amines with ~-H gave imines in moderate to
low yield, and sometimes other products presumably resulting from imine
decomposition (particularly from hydrolysis). No oxidation of tertiary amines (e.g.
pyridine) was detected. Possible reaction steps are proposed in Scheme II.
7
Scheme II. Catalytic dehydrogenation ofbenzyl amine
PhC==N
t--HzO
disp. PhCHzNHz -_\::--------l..~ PhCH=NH
[RuIV(tmp)(O)]2
ill@j
[RuII(tmp)] __P_h_C_H.:..zNH---=z,--... [RuII(tmp)(PhCHzNHzh]3 4
The initial step involves a two-electron oxidation ofbenzylamine to N-
benzylidenemaine by 1, which is then reduced to the monooxo species 2. Complex 2 is
known to disproportionate in solution to reform 1 and the species 3, which is
previously reported to be very reactive toward Oz. Complex 1 or possibly species 2
presumably effects the second dehydrogenation ofthe imine to the nitrile. Complex 4
must be formed via a competitive reaction ofthe amine with 3. The fact that the
catalytic system uses Oz from air to oxidize the amines and forms water as a byproduct
affects the dehydrogenation of secondary amines to imines, since it limits the reaction
only to imines (products) or amines (reactants) which are not sensitive to air and
water. [17]
8
We found that the existing documented methods of imine synthesis are not
satisfactory. The condensation of aldehydes/ketones with amines is limited to aliphatic
aldehydes with aliphatic amines. Catalytic imination ofketones is always
accompanied by side reactions like aldol condensation. Oxidative dehydrogenation of
amines has promising potential. However, the yield is moderate to low and most ofall,
all the reactions are carried out in catalytic scale, no practical scale reactions are ever
tried. It is ofour interest to find an efficient way to synthesize imines through
dehydrogenation of amines with our iridium PCP pincer complex catalyst.
9
Chapter 2
Catalytic Reactions
2.1 Introduction
Recently, the iridium PCP pincer complex, IrH2{C6H3-2,6-(pBut~h}, 1, has
been found to be a highly efficient and robust catalyst for the transfer dehydrogenation
of aliphatic C-H bonds ofcycloalkanes, [I8J linear alkanes, [191 ethylbenzene, and
tetrahydrofuran. [20] It is also reported to efficiently dehydrogenate alcohols and diols
to different forms ofproducts, aldehydes, ketones and cyclic unsaturated ketones. [21] It
was therefore of our interest to investigate whether this reactivity could be extended to
amines. The fact that oxidative dehydrogenation of amines uses oxygen as the oxidant
and forms water as byproduct limits the reactions to amines/imines insensitive to air
and water. The PCP pincer catalyst uses tbe (t-butyl ethylene) as the acceptor of
hydrogen for the dehydrogenation and thus gets rid of this limitation.
The problem is both C-C bond and N-C bond are eligible to dehydrogenation.
It is hard to decide whether the oxidative dehydrogenation will occur at the C-C or N
C bonds, which could lead to completely different products. Calculation ofthe bond
energy shows that the amines' dehydrogenation is found to be more
thermodynamically favored than the alkanes' dehydrogenation. The large energy
difference of C-N and C=N ( 77 kcal/mol comparing with 63 kcal/mol between C-C
10
and C=C) and the low bond energy ofN-H ( 93 kcal/mol comparing with 99.2
kcal/mol of C-H ) make the amine dehydrogenation more favorable.
Table 1. Some typical bond energies·
* :CRC Handbook of ChemIstry and PhYSICS, 55 EdItIOn.
Bond Type C-H N-H C-C C=C C-N C=N
Bond Energy (Kcal/mol) 99.2 93 83 146 70 147
. .
2.2 Experimental
All manipulations were carried out using standard Schlenk and glovebox
techniques under purified argon. Solvents were degassed and dried using standard
procedures. The amines were purchased from Aldrich Chemicals Co. and used without
further purification. The complex 1 was synthesized by literature methods. [8c] The lH
NMR spectra were recorded on a Varian Unity Inova 400 spectrometer. Chemical
shifts are reported in ppm down field of TMS using the solvent as internal standard
(CDC!), 8 7.26). 13C spectra were recorded with complete proton decoupling and are
reported in ppm downfield ofTMS with the solvent as an internal standard (CDC!),
877.0). Gas chromatographic analyses were performed with a Hewlett Packard 5890
instrument with a HP 5980A flame ionization detector and HP-l capillary column
(25.0 m). Gas chromatographic-mass spectral analyses were carried using a HP 5890
SERIES II instrument with a 5971A mass selective detector and HP-l capillary
column (25.0 m).
11
2.2.1 Catalytic Reactions General Procedure
200°C+ (7)
Solutions of the substrates (0.26 nunol), tbe (0.20 ml, 1.53 nunol) and 4 ml of
toluene were charged with 1 (22mg, 0.037 nunol) in sealed Schlenk tubes in a
Vacuum Atmospheres glovebox under argon. The tubes were then fully inunersed in a
constant temperature bath at 200 °c for the prescribed reaction times. After this time
the tubes are allowed to cool down to room temperature. The products were identified
by GCIMS analysis upon comparison to synthesized samples of authentic compounds.
Product yields were calculated from the ratio of the integrated intensities of signals
produced by the products and those of the toluene solvent after weighting the data by a
predetermined relative molar response factor.
2.2.2 Synthesis of Authentic Samples ofImines
Method 1:
+
12
(8)
0.2 mole amine was put in a 100ml round bottom flask in ice-water bath. 0.2
mole aldehyde was added dropwise over a 2-hour period. After addition, keep stirring
for 15 minutes. 0.4 mole KOH was added to the reaction mixture, which was stirred
for another 15 minutes. The reaction mixture was stored in the refrigerator overnight
and then filtered. Separation will be needed if two layers were present. Another 0.05
mole KOH was added and the product was distilled, under vacuum in the case of high
boiling point imines.
Method 2:
+p-Ts-OH •
R
"c=N-R"R'/
(9)
0.2 mole amine, 0.2 mole ketone, 25 mg ofp-Ts-OH, 50 ml of anhydrous
toluene were added to a 250ml round bottom flask. Then the mixture was heated to
reflux and Dean-Stark Separator was used to collect 3.6ml H20. The product was
distilled, under vacuum in the case of high boiling point imines.
N-butylidenebutylamine:
Follow Method 1. Bp: 135-139 0 C. IH NMR (400.00 MHz, CDCh): /)7.584 (t,
CH=N), 3.317 (t, CH2-N), 2.1 84(m, CH2-C=N), 1.533 (m, CH2), 1.283 (m, CH2),
0.887 (m, CHl). llC NMR (100.5 MHz, CDCh) /)164.752 (s, CH=N), 60.988 (s, CH2-
N), 37.637 (s, CH2), 32.796 (s, CH2), 20.228(s, CH2), 19.418(s, CH2), 13.753(s, CHl),
13
13.667(s, CH3). MS (M/z): [Mt 127, [M-C3H7t 84, [M-CJf9t 70, [M-CH3t 112,
[M-C4H7Nt 57.
N-isobutylideneisobutylamine:
Follow Method 1. Bp: 121-125 °C. IH NMR (400.00 MHz, CDCh): I) 7.444
(d, CH=N), 3.160 (d, CHz-N), 2.427(m, CH-C=N), 1.877 (m, CH-C-N), 1.069 (d,
CH3), 0.872 (d, CH3). l3C NMR (100.5 MHz, CDCh) I) 169.741 (s, CH=N), 69.385 (s,
CH2-N), 33.962 (s, CH-C=N), 29.099 (s, CH-C-N), 20.445(s, CH3), 19.449(s, CH3).
MS (M/z): [Mt 127, [M-C3H7t 84, [M-C4H9t 70, [M-C4H7Nt 57.
N-ethyldenecycIohexylamine:
Follow Method 1. Bp: 147-151 DC. IH NMR (400.00 MHz, CDCh): I) 7.706
(m, CH=N), 2.898 (m, CH-N), 1.916(d, CH3), 1.762 (m, CH2), 1.626 (m, CH2), 1.451
(m, CH2), 1.257 (m, CH2), 1.178 (m, CH2). l3C NMR (100.5 MHz, CDCh) I) 158.131
(s, CH=N), 69.466 (s, CHz-N), 34.291 (s, CH3), 25.506 (d, CH2), 24.787 (s, CH2),
22.158 (s, CH2). MS (M/z): [Mt 125, [M-CH3t 110, [M-C2HSt 96, [M-C3H7t 82.
N-butylidenebenzylamine:
Follow Method 1. Bp: 60-63 °c /2-3mmHg. IH NMR (400.00 MHz, CDCh):
I) 7.787 (t, CH=N), 7.329 (m, CJIs), 4.572(s, CH2-N), 2.305 (m, CH2), 1.614 (m,
CH2), 0.976 (m, CH3). l3 C NMR (100.5 MHz, CDCh) I) 166.166 (s, CH:=N), 128 (m,
C6HS), 65.036 (s, CH2-N), 37.816 (s, CH2), 19.368 (s, CH2), 13.744(s, CH3). MS
(M/z): [Mt 161, [M-CJH7t 118, [M-C4H9t 104, [M-C2HSt 132.
N-benzylidenebenzylamine:
14
Follow Method 1. Bp: 82-85 0 C 12-3mmHg. IH NMR (400.00 MHz, CDCb):
Ii 8.412 (s, CH=N), 7.809 (m, C6Hs), 7.354 (m, C6HS), 4.843 (m, CHz). l3C NMR
(100.5 MHz, CDCb) Ii 161.975 (s, CH=N), 128 (m, C6HS), 65.021 (s, CH2-N). MS
(MIz): [Mt 195, [M-C6Hst 117, [M-C7H6Nt 91.
N-isopropylidenebenzylamine:
Follow Method 2. Bp: 58-60 0 C 12-3mmHg. lH NMR (400.00 MHz, CDCh):
Ii 8.306 (t, CH=N), 7.407 (m, C6HS), 3.541(m, CH-N), 1.276 (m, CH3). l3C NMR
(100.5 MHz, CDCb) Ii 158.318 (s, CH=N), 130 (m, C~s), 61.662 (s, CH-N), 24.115
(s, CH3). MS (MIz): [Mt 147, [M-CH3t 132, [M-C3H7t 104, [M-C3H9Nt 89.
2.2.3 Preparative scale synthesis ofN-butylidenebenzylamine
A solution of the N-butylbenzylamine (0.5 ml), tbe (0.10 ml) and 5 ml of
toluene was charged with 1 (25 mg) in a sealed Schlenk tube in a Vacuum
Atmospheres glovebox under argon. The tube was then fully immersed in a constant
temperature bath at 200 °c for 5 days. After this time, the reaction mixture was cooled
to room temperature and concentrated to about 0.4 m!. The product was then separated
by column chromatography (Davisil1M 100-200 mesh silica gel) by eluting with a
mixture of ethyl acetate, triethylamine and hexane (1: 1:20 by volume). The product
fraction was collected and concentrated under vacuum. The isolated product (yield)
was identified as N-butylidenebenzylamine by MS and NMR (IH and l3C) analysis
upon comparison to an authentic sample. lH NMR (400.00 MHz, CDCb): Ii 7.787 (t,
CH=N), 7.329 (m, C6Hs), 4.572(s, CHz-N), 2.305 (m, CHz), 1.614 (m, CHz), 0.976 (m,
15
CH3). 13C NMR (100.5 MHz, CDC!)) 0 166.166 (s, CH=N), 128 (m, C6Hs), 65.036 (s,
CH2-N), 37.816 (s, CH2), 19.368 (s, CH2), 13.744(s, CH3). MS (M/z): [Mt 160, [M
C3H7t 118.
2.3 Results and Discussion
2.3.1 Catalytic Reactions
Recently we have shown that the iridium PCP pincer complex 1 can be used as
an efficient and robust catalyst for the dehydrogenation of a variety of aliphatic C-H
bonds. We have now found that 1 also catalyzes the elimination of hydrogen from
saturated amines. However, dehydrogenation occurs across the C-N bond rather than
at the C-H bond to give imines as seen in equation 7 (page 12). This reactivity is
highly sensitive to steric constraints at the metal center and we have observed
remarkable regioseJectivity in the dehydrogenation of asymmetric secondary amines.
Primary and tertiary amines have been proved to be inert towards the dehydrogenation
reaction since there is no place for a C=N double bond in tertiary amines.
The catalytic activity was initially screened using solutions consisting ofthe
saturated amine, and the hydrogen acceptor, tbe. The orange solutions were sealed in
tubes under argon and fully immersed in an oil bath at 200 °c for 18 hours. The
solution became red upon heating and gradually changed color to yellow-orange
during the reaction period. Gas chromatographic analysis ofthe reaction mixtures
showed the substrates were converted to the corresponding imines with greater than
99% selectivity. However, only 1-% yields were obtained in preliminary experiments
16
with the neat reaction mixture even upon longer reaction times and increased catalyst
loading. It was found that further catalytic activity could be obtained from 1 upon its
isolation from the reaction mixture. Thus catalytic activity ceases after -1000
turnovers not as the result of complex degradation rather because an inhibiting
concentration of the imine product is attained. This observation is consistent with the
established pattern ofproduct inhibition that has uniformly been found to limit
dehydrogenation reactions catalyzed by 1. [22J We previously found that in case of
alcohol dehydrogenation, this problem was eliminated upon dilution of the catalytic
system with toluene. [11] In order to obtain synthetic useful yields, it seemed necessary
to try dilutions with amines. This strategy turned out to be successful with secondary
amines and the good to excellent yields seen in Table I were obtained in reactions
carried out in diluted toluene solution for 3 days at 200 °C.
Table 2 summarizes the results of the dehydrogenation experiments in which
toluene solutions of the amines, pincer complex 1, and tbe were heated for 3 days at
200 °C. Mass spectra of the products were obtained by GC-MS analysis·ofthe
reaction mixtures. However, it should be noted that the catalytic efficiency is greatly
diminished in these high yield reactions. Even at 200°C, a reaction time of 3 days is
required to reach the optimal yields and the turnover numbers are nearly two orders of
magnitude lower than those obtained in the reactions with neat amines.
It was found that the dehydrogenation of asymmetric secondary amines occurs
across the most sterically accessible C-N bond with greater than 99% regioselectivity.
The most successful example of steric control over the dehydrogenation of amines is
the dehydrogenation ofN-ethylcyclohexylamine which gives exclusively N-
17
cyclohexylacetadimine. It is believed that the regioselectivity ofthe dehydrogenation
originated from the nature of the pincer complex 1. The bulky tert-butyl groups on the
phosphorus greatly hinder the incoming of a large group toward the Ir metaL
However, electronic factors were found to exert great influence on the regioselectivity
of the reaction too, especially for aromatic amine substrates. The reactions of
substrates 5-7 give exclusively benzaIdimines. Benzaldimines are much more stable
thermodynamically than the alternative aldimines due to the big conjugated 1t system
formed while the nonnal aldimines are very reactive in the nature. However, we can
still see the affect of the steric control in the reactions of substrates 5-7. Substrate 6 is
extremely unreactive and thus has the lowest yield because ofthe hindrance ofthe
isopropyl group, comparing with substrate 5 and 7. Some low-molecular-weight
secondary amines were also tried, like diethyl amine and N-ethylpropylamine. The
reactions lead to some polymerized products due to the fact that low-molecular-weight
imines are easy to polymerize under high temperatures.
18
Table 2. Dehydrogenation of amines using 1 catalyst. (J.
Item Substrate Product Yield
1 1 111 IN! 76.5%
2 ~N~ ~~ 72.3%H N .
3 o-i1~ o-N~ 94.3%
4 ~i1/('" ~N~ 38.8%
5 CYN~ (rN~ 60.0%H
6 ( r11-< ( r N-< 9.5%
7 ( ri1- <r N-
52.5%
8 <ri1~ ) <rN~) 44.0%
9 NEt) N/R N/A
a: Reaction conditions: imines (0.26 mmol), tbe (1.53 mmot), 4ml oftoluene and 1 (22mg, 0.036 mmot), at 200°Cfor 72 hours.
19
2.3.2 Preparative scale catalytic reaction
The dehydrogenation reaction has been successfully carried out in large scale
(separable) with substrate 5, N-butylbenzylamine. Details of the experiment are
covered in the experimental part on page 15. Acceptable separated yield has been
gained (32%). MS and NMR (lH and 13C) analysis upon comparison to an authentic
sample identified the isolated product (yield) as N-butylidenebenzylamine.
The preparative scale catalytic reaction was carried using similar conditions.
However, the separation of the products was the most difficult step of the preparative
scale catalytic reaction. Column chromatography was used as a common separation
procedure. The problem is that most of the imines are very reactive and easily undergo
hydrolysis under acidic conditions and unfortunately the silica gel used for column
chromatography is acidic. To avoid the hydrolysis, we found triethylamine can be
used as part of the cluting solution to control the pH of the eluting environment. Short
columns were used to shorten the time the imines stayed in the column. However, the
results are not satisfactory since most substrates we employed either still hydrolyze
under such conditions or only give low yield. N-butylbenzylamine was the only one
that was found not to hydrolyze during the separation while maintaining a relatively
high yield. The possible reason that N-butylbenzylamine is favored for the preparative
scale catalytic reaction is that it has relatively larger molecular weight and higher
boiling point. So it tends to be more stable than other imines. N-benzylbenzylamine
has molecular weight and higher boiling point than N-butylbenzylamine. However, the
catalytic reaction of it under normal condition gives lower yield and it is not
applicable for the catalytic reaction in preparative scale.
20
The preparative scale oxidative dehydrogenation reaction is not successful by
employing the PCP iridium pincer catalyst. The main reason is that the imine products
are very reactive and easy to undergo hydrolysis. Thus it makes the separation
difficult. To obtain the pure products from the reaction mixture, column
chromatography seems to be the most practical method. It is why most of the catalytic
systems employed on amine dehydrogenation can't separate the imine product.
21
Chapter 3
Mechanistic Studies
3.1 Introduction
The iridium PCP pincer complex 1 was found to catalyze the dehydrogenation
ofalkanes efficiently. [18,19] The mechanism is well studied and it is now generally
accepted that the transfer dehydrogenation of alkanes by 1, involves the initial
oxidative addition of alkane across methyl C-H bonds to the intennediate 14 electron
complex, Ir{C6H3-2,6-(PBu'2)2}, 2, which arises upon dehydrogenation of1 by t
butylethylene. [22.23] By analogy, it is possible that the amine catalytic reactions
undergo direct dehydrogenation across the C-N bond through an initial N-H or C-H
oxidative addition to 2 followed by a ~-elimination from the resulting amide ligand to
produce an imine as per the "N-H oxidative addition" or "C-H oxidative addition a to
amino group" pathways seen in Scheme III. However, previous studies of the catalytic
dehydrogenation oflinear alkanes revealed that while tenninal alkenes are the
kinetically preferred product of the reaction, they are subject to secondary catalytic
isomerization by 1 and ultimately internal alkenes are obtained. [J9] Additionally,
mechanistic studies of the palladium black catalyzed hydrolysis of tertiary amines
indicated that the reaction involves the initial aliphatic dehydrogenation of amines to
enamines that are subsequently converted to imines. [24] This raises the possibility that
22
Scheme III. Possible Mechanisms for the Dehydrogenation of Amines
H3CCH2CMe3
PBut
I ~CH2CH2Me.}-- y 3
Ir
~ I'HPBut2
PBut2
RCH2CH2NHR' / \ I
C-H OxidativeAddition
N-H OxidativeAddition
C-H OxidativeItion u to
Amino Group
PBUt2 R
I CH,}--Ir)? 'CH2NHR'
I'HPBut
2
PIBUt2 /CH2RCH
'}--Ir)? 'NHR'
\:........:( I'HPBUt2
P,BUt2 R
~~NHR',) H/r-H..PBut
2
~
1P1BUt2 pH2R
CH
,}--Ir)? "NHR'
\:........:( I'HPBut
2
PBut
RN-CHCH,R " r-!,;H H,C-CHCM" _P,BU
t2
m.V~,I" · I/'v
C
....PBJ%;~ PBJ,H " j H"'r-
H
\171f' N-
R' PB '
\\ Ii "'" Ir-H PB ' ",II ~I IU2 R'H .. /
PsJ, I,I/'CH CI'H 2 HzR
PBut2
'"w
the dehydrogenation of secondary amine with PCP pincer complex 1 also involves an
initial aliphatic dehydrogenation ofamines to enamines that undergo subsequent
catalytic tautomerization to imines. Thus the alternative "C-H oxidative addition"
pathway mechanism seen in Scheme III must also be considered. In all, N-H oxidative
addition is thermodynamically favored as shown by the theoretical calculation ofbond
energies while the bulky structure of the PCP pincer complex prefers the less crowded
site, which is usually the C-H site and thus kinetically select C-H oxidative addition.
Both of the N-H and C-H pathways start from the removal of the H on iridium
pincer complex 1. The hydrogen acceptor, tbe, takes two H atom from the PCP pincer
complex and turns it into a 14 electron intermediate 2. In the N-H pathway N-H
oxidative addition occurs followed by ~ elimination. A TJ 2-Ir-(C=N) complex is
formed. Then the imine leaves and the catalyst returns to its original l6e structure. In
the C-H pathway, C-H oxidative addition occurs followed by /3 elimination. A TJ2-Jr
(C=C) complex is fonned. Then H migrates to the 2-C. After several migration
elimination steps, TJ2-Ir-C=N complex is formed. Then the imine leaves and the
catalyst returns to its original l6-electron structure.
24
3.2 Experimental
3.2.1 The preparation of 2,2,2',2'-tetramethy1dibutylamine
A special amine compound was designed to examine the catalytic dehydration
of secondary amines. This compound is 2,2,2',2'-tetramethyldibutylaimine. The
preparative procedure of2,2,2',2'-tetramethyldibutylaimine is shown as in scheme IV.
Steps:
a) 2,2-dimethylbutyric acid 2 (29.0g, 0.25mol) was added to thionyl chloride (48.0g,
OAOmI) in a flask at 23°C under stirring. Reaction started at once and hydrogen
chloride was released. The addition rate was controlled to keep a steady reaction
and the reaction mixture was warmed at 40 °c for 4 hrs. The reaction mixture was
distilled and the fraction at 128-131 °c was collected. The yield of2,2-dimethyl
butyryl chloride 3 as a colorless to yellowish liquid was 25.0g, 85% yield.
b) To an ice-cooled aqueous solution of ammonium hydroxide (150ml) was dropwise
added 2,2-dimethylbutyryl chloride 3 (23.0g, 0.17mol). The addition was
controlled to keep the reaction temperature below 15°C and the reaction mixture
was stirred another hour after addition. The reaction mixture was filt\lred, and the
crystals were washed with ice-cooled water and were air-dried. The yield of2,2
dimethylbutyramide 4 as white crystals was 15.6g, 80% yield.
25
Scheme IV. Synthesis of2,2,2',2'-tetramethyldibutylamine
~OH a
o
o
CIb
o
d~NH2
c) To a suspension of lithium aluminum hydride (4.40g, O.12mol) in anhydrous ether
(20OmI) was added a solution of2,2-dimethylbutyrarnide (13.0g, O.l13mol) in the
same solvent (200ml). The addition was controlled at such a rate that the reaction
mixture refluxed gently. After addition the reaction mixture was warmed to reflux
for 48h. The reaction mixture was cooled in an ice bath and water was gradually
added to decompose the hydride resulting in a sandy suspension. The mixture was
filtered and the filter cake was washed with ether thoroughly. The filtrate and
washes were combined, dried over anhydrous magnesium sulfate and distilled. The
fraction of 2,2-dimethylbutylamine 5 was collected at 104-105 °C as a colorless
liquid in 43%, 4.90g yield.
26
d) To a solution of2,2-dimethylbutylamine 5 (2.80g, O,028mol) and triethylamine
(7.OmI, 0.050mol) in anhydrous methylene chloride (2OmI) was added a solution
of2,2-dimethylbutyryl chloride 3 (4.20g, 0.03 Imol) in the same solvent (20ml) at
oDC under stirring. The reaction mixture was stirred another hour at 0 DC and
overnight at 23 DC after addition. The reaction mixture was washed with water, 5%
sodium bicarbonate, 2N hydrochloric acid, and dried over anhydrous magnesium
sulfate. Removal of the solvent gave a brownish liquid, N-2,2-dimethylbutyl-Z,Z
dimethylbutyramide 6 in 88% yield (4.90g). The amide was used for·the next
reduction without further purification.
e) To a suspension oflithium aluminum hydride (836mg, 22mmol) in anhydrous
ether (5OmI) was dropwise added a solution ofN-Z,Z-dimethylbutyl-Z,Z
dimethylbutyramide (4.0g, ZOmmol) in the same solvent (50ml). The reaction
mixture was warmed to reflux gently for 48h after addition. The reaction mixture
was cooled in an ice bath and water was added gradually to decompose the hydride
resulting in a sandy suspension. The mixture was filtered and the solid was washed
with ether thoroughly. The filtrate and washes were combined, dried over
anhydrous magnesium sulfate and distilled. The fraction of Z' ,Z' ,Z,Z
tetramethyldibutyJamine was collected at 194-198 DC as a colorless liquid in 41 %
yield (1.5Zg).
MS and NMR (1 H and DC) analysis identified the isolated product as Z,Z,Z',
Z' -tetramethyldibutylaimine. IH NMR (400.00 MHz, CDCh): 0 Z.313 (s, CH2-N),
I.Z5Z (m, CH2), 0.835 (s, CHJ), 0.803 (m, CHJ). 13C NMR (100.5 MHz, CDCh) 0
27
61.301 (s, CHz-N), 34.296 (s, CHz), 32.422 (s, CHz), 25.131(s, CHJ), 8.301(s, CH3).
MS (m/z): [Mt 185, [M-CsHllt 114, [M-CJII4Nt 85, [M-CH3t 170, [M-CzH5t
156.
3.3 Results and Discussion
3.3.1 Spectra Study
Throughout our study of imines published in the last 20 years, no systematic
study was found of the mass spectra ofimines and there is no published MS pattern
for the imines. It is " g,'eat opportunity for us to investigate the mass-spectral behavior
of imines here since we have synthesized plenty of authentic imines during our study
ofthe transfer dehydrogenation of amines. It is very useful to know the general mass
spectral pattern and NMR behavior ofimines and therefore we can identifY imines
with mass spectra and NMR.
The characteri stic peaks in I H NMR and l3C NMR of imines are the peaks of
carbon nitrogen double bond. In lH NMR, the peak of the H on the C=N bond is
shown in the range ofa7.4-8.5 ppm. Aliphatic imines tend to have H-C=N peak
around a7.5 ppm, while aromatic imines with the C=N bond conjugated with the
aromatic ring have the hydrogen in H-C=N more shielded by electrons and tend to be
in the lower field over a8 ppm. In 13C NMR, the C peak of the C=N double bond
ranges from Ii 158-170 ppm.
The most typical fragmentation in the Mass Spectrum ofimines is the cleavage
of the C-C bond at the a position to the C of the N=C double bond and this will
28
generate the peaks of the highest abundance, as shown in Scheme V-1. Another
typical fragmentation is like 2 in Scheme V, the cleavage of the C-N bond, which
generates two fragments. Molecular ions are usually of low or negligible abundance
for aliphatic imincs while aromatic imines usually have molecular ion peaks of
medium abundance.
Scheme V. Fragmentation ofImines
3.3.2 Results
-R'
H
1+R ............ -:::::-C
N
+
1
2
In order to distinguish between the pathways involving initial aliphatic vs.
direct amino dehydrogenation, we examined the dehydrogenation of 2,2,2' ,2'-
tetramethyldibutylaimine, 2. If2 underwent dehydrogenation across the ierminal ethyl
C-C bond to give the cnamine product seen in Scheme VI, the presence ofa
quaternary carbon in the aliphatic chain would prevent secondary internalization of the
unsaturation via sequential hydride migration and l3-elimination. The transfer
dehydrogenation of 2 was carried out under the standard conditions employed in the
29
previous chapter. GC/MS analysis of the reaction mixture indicated that only one
product was produced whose mass spectrum is identified as N-2,2-dimethylbutyl-2,2
dimethyl-3-butanalimine. The mass spectrum of the imine is distinct from that
expected for the cnamine as it contains a peak at rnIz 98 corresponding to a
[N=CHCMe2C2Hs]' fragment. The presence of an internal unsaturation is also
indicated by the presence ofmlz 156, [M-C2H5t peak, rather than [M-C2~tpeak.
The rnIz 112, [M-CI-I2CMe2C2Hs]' peak is the most intense in the spectrum. Thus the
lack ofa rnIz 114, [M-CH2CMe2CH=CHzt peak clearly indicates the lack ofa distal
unsaturation. Additionally, the production of the imine was confirmed by NMR
spectroscopy from the reaction mixture en vacuo. The lH NMR spectrum contained a
distinctive signal at a7.47 ppm that can readily be assigned to the alpha hydrogen of a
dialkyl imine and the l3C NMR spectrum contained the expected resonance at 171.3
ppm for the imine carbon. Therefore, it appears that the reaction pathway involves
direct amino ralher than initial aliphatic dehydrogenation, as shown in scheme V. This
conclusion is consistent with the observation that the catalytic system is completely
ineffective with triethylamine.
30
Scheme VI. Results of dehydrogenation 0[2,2,2',2'-
tetramethyldibutylaimine
+ 'B/u
PBU'2
C-R oxidativeaddition
N-R oxidativeadditon
~- - - ---- - ----- -----------"'----------,,,,,,
31
Chapter 4
Conclusions
The previous studies of the iridium PCP pincer complex 1 shows that it is a
highly efficient and robust catalyst for the transfer dehydrogenation of the aliphatic C
H bonds ofalkanes [8-10] and alcohols [11]. Our work with the PCP complex 1 extends
the catalysis of the dehydrogenation to secondary amines. Although our initial studies
indicated that the catalytic systems became product inhibited after <10% conversion
of amines to imines, good to excellent yields have been obtained upon dilution of the
catalytic system with toluene. The dehydrogenation reaction has been successfully
carried out in large scale (separable) with N-butylbenzylamine with acceptable
separated yield. However, large-scale reactions with other imines was unsuccessful
since the hydrolysis of the imine products makes the separation ofproducts
impossible. The practicality of the system for organic synthesis is questionable in view
ofthe high catalyst loading that is required. The regioselectivity of the
dehydrogenation of aliphatic amines is stringently controlled by steric factors while
dehydrogenation of aromatic amines leads to imine products favored
thermodynamicalIy due to the presence ofa conjugated 1t system. It is widely accepted
that the transfer dchydrogenation ofalkanes by 1 is believed to undergo the oxidative
addition of alkane across thc C-H bond to the intermediate 14-electron complex 2.
However, there ,Ire three possible pathways for the dehydrogenation of amines,
through N-H associative addition, C-H oxidative addition a to amino group or through
32
aliphatic oxidative addition. A special amine, 2,2,2',2'-tetramethyldibutylamine 3, has
been designed and synthesized. After examining the reaction of amine 3 with our
pincer catalyst system, the product was found to be exclusively the corresponding
imine. Thus the catalytic transfer dehydrogenation ofamines with the PCP pincer
complex 1 are sllOwn to undergo the N-H associative addition pathway. The lack of
reactivity with tCltiary amines also indicates that the catalytic reaction pathway
involves the initial intermolecular oxidative addition of an N-H rather than a C-H
bond.
33
Reference:
[1] R. Noyori, Asymmetric Catalysis In Organic Synthesis, John Wiley & Sons, 1994.
[2] lA. Joule, G.F. Smith, Heterocyclic Chemistry, 2nd ed., Van Nostrand Reinhold,
New York, 1978, p 74-80.
[3] E. E. Snell, A. E. Braunstein, E. S. Severin, Y. M. Torchinsky, Pyridoxal
Catalysis: Enzymes and Model Systems, Wiley, New York, 1968.
[4] G. M. Loudon, Organic Chemistry, 3rd ed., 1995.
[5] S. Patai, The chemistry o/the carbon-nitrogen double bond, interscience
publishers, 1970.
[6] J. N. Coalter, J. C. Huffman, K. G. Caulton, Organometallics, 2000,19, P 3569
3578.
[7] H. Schiff, A1111. Chelll. Pharm., 1864-5,131, P 118.
[8] G. Reddelien, Ber. Dish. Chem. Ges., 1913,46,2721.
[9] (a) H. Weingarten,.T. P. Chupp, W. A. J. White, J. Org. Chem., 1967,32,6246; (b)
C. Stein, B. Dejcso, J. C. Pommier, Synth. Commun., 1982, 12,495.
[10] N. Duffaut,.J. P.Dupin, Bull. Soc. Chim. Fr., 1966,3205.
[11] (a) H. Y. Oshida, T. Ogata, Synthesis, 1977,626; (b) H. Tani, N. J. Oguni,
Polymer Sci., 1965, B3, 123.
[12] l J. Eisch, R. Sanchez, J Org. Chem., 1986,51,1848-1852.
[13] F. R. Keene, Coordination Chemistry Reviews, 1999, 187,121-149.
[14] P. Muller, D. M. Gilabcrt, Tetrahedron, vol. 44, No. 23,7171-7175.
34
[15] S. Murahashi, T. Naota, H. Taki, J. Chem. Soc., Chem. Commun., 1985,613-614.
[16] S. Minikat~l, Y. Ohshil1la, A. Takemiya, I. Ryu, M. Komatsu, Y. Ohshiro,
ChemistryLettcrs, 1997,311-312.
[17] A. J. Bailey, B. R. James, Chem. Commun., 19962343-2344.
[18] (a) M.Gupta, C. Hagen, W. C. Kaska, R. Flesher, C. M. Jensen, J. Chem. Soc.
Chem. Commull., 19%,2083; (b) W. Xu, G. P. Rosini, M. Gupta, C. M. Jensen, W. C.
Kaska, K. KrOllgh-Jespcrsen, A. S. Goldman, J. Chem. Soc. Chem. Commun., 1997,
2273; (c) M. Gupta, C. Hagen, W. C. Kaska, R. Cramer, C. M. Jensen, J. Am. Chem.
Soc., 1997, 119, 840.
[19] F. Liu, E. D. Pak, B. Singh, C. M. Jensen, J. Am. Chem. Soc., 1999,121,4086.
[20] M. Gupta, W. C. Kaska, C. M. Jensen, J. Chem. Soc. Chem. Commun., 1997,461.
[21] D. Morales-Morales, R. Redon, Z. Wong, D. W. Lee, K. Magnuson; C. M.
Jensen, Can. J. Gcm., 200l, 79, 879.
[22] C. M. Jensen, Chem. Soc., Chem. Commun., 1999,2443.
[23] (a) S. Q. Nill, M. B. Hall, J. Am. Chem. Soc., 1999, 121, 3992; (b) K. Krough
Jespersen, M. C~erw, M. Kanelberge, A. S. Goldman, J. Chem.I1if. Comput. Sci.,
2001,20,1144
[24] S. Muralmhi, T. Watanabe, J. Am. Chem. Soc., 1979, 101, 7429.
3S
Appendix: Spectra for Selected Compounds
36
GCMS for 2,2,2' ,2'-tetramethyldibutylaimine
i\.bundilnCE!1100000 ~
Scan 1161 (17.006 min): DIMUTSTA.D1 j 4
laoaaoo
900000
800000
700000
600000
500000
400000
300000
200000rj~,
100000
80706050o 1,..~"'"T.,..,.ll4T'~""f4-~"'"T.,:.).l)..,.T'~::"-rr-~';"i-''.;.'.jJ,..,...,.~I~~~':c';rc-~",TL',-',-~" ~"""--r~'-;"'j...-~.,...,.~l,..."
100 110 120 130 140 150 160 170 180
GCMS for 2,2,2' ,2'-tetrametbyldibutylaimine from catalytic reaction
~N~
Abundanc~ Sean 1055 115.858 min) : DlMUTBUT.D1 2
100000
90000
80000
70000
60000
50000 84
4000056
30000 1';.r:,
20000 5 9tl
10000
'dil'llJ
~r, II ,'j" II 124 ii,'0
50 60 70 80 90 100 110 120 130 140 150 160 170 180
IH NMR for 2,2,2',2'-retramethyldibutylairnine in catalytic reaction
I d I, , , , , , ,
11 ", • , • • • 3 2 1 -, pp.
"c NMR for 2,2.2·.2'-tetramethyldibutylaimine in catalytic reaction
I1
,n, ,u,
,H'
,'01
,..
E
")5
~ I•~ .."l .
~ :
~1\I
I j,
4' 20 pp•
'H NMR for 2,2,2',2'-tetramethyldibutylaimine
"C NMR for 2,2,2',2' -tetramethyldibutylaimine
,.. po.
•II
J
.. l. , ,. .,.., , , , ,., " .. " •• 3' " 1G ppm
GeMS for Authentic N-ethyldenecyclohexylamine
o-N"
GeMS for N-ethyldenecyclohexylamine from catalytic reaction
Abundance Scan 262 (6.538 min): CLYET-l.D: 'II
60000
50000.2
55 %
40000
30000
6920000
Iu
tOOOO
"1
[II ~
,,~LcII 1'/ 'I" II 'I' III 91j I ,
040 45 50 55 60 65 70 75 80 85 90 95 tOO 105 UO US 120 125 130
IH NMR for Authentic N-ethyldenecyclohexylamine
o-N~
•
~iI
J
I L ~~J"'", , ,
7 • , 4 3 PO'
" C NMR for Authenlic N-ethyldenecyclohexylamine
I r
•
i 1I
,lS.
,lS' '31
,I"
,11.
,'"
,"
,••
,"
,.. ,"
,.. " pp.
GeMS for Authentic N-isobutylideneisobutylamine
Scan 17 (3.728 min): DIISOBU.O84
57
5
7"
~
4
I1
50 60 70 80 90 100
I!
nO 120 1)0 140
GeMS for N-isoootylideneisoootyJamine /lorn calalytic reaction
Abundance
2500000
2000000
1500000
10DOOOO
500000
57
5S
Scan 19 (3.753 min): OIISOBU1.0
40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125
I H NMR fer Authentic N-isebutyiideneisebutylamine
"c NMR for Authentic N-isobutylideneisobutylamine
-~..jJ
" .,' I
i.... ,
'70
" ..". 151 ".
, ., • L
'"~ '20 11. '00 " ••
1
" .. 50 .. 30
II
po.
GeMS for Authentic N-butylidenebutylamine
Abundance
3500000
3000000
2500000
2000000
1500000
1000000
57
70
Scan 198 (5.802 min): OIBUTYL.D8
--~.,I1
500000 99
1I,,51r~·9
Q/j II 77 nl! Ike 9' J0') , L'. ,65 15 90 90 95 100 105 110 115 120 125 130.5 50 55 60 10 95
GeMS for N.butylidenebutylamine from catalytic reaction
~~
Abundance
4000
3500
3000
2500
2000
1500
1000
500
Sean 31S (9.681 min): DIBUTYL9.D8
91
57
70
56"l'j
'i I ,/r '[ 'I" If I I. , . , . , . , , I I, , I.5 50 55 60 65 10 75 90 95 90 95 100 105 110 115 120
I H NMR for Authentic N-butylidenebutylamine
1 PPIIz3••II ~ ~
~l • '-- '---, i ,
"C NMR for Authentic N-butylidenebutylamine
~~
~!
1!
~j1 I I
~ ~! of..:
I
.1. .•,." ~,
'60
.l
'41 '20 '"
.1
•• ...•L •••• .l J J hI. ,I
41
GCMS for Authentic N·isopropylidenebenzylamine
Abunddllce
1600000
1400000
1200000
1000000
800000
600000
400000
200000
Scan 1140 t16.683 min): 5ENISOPS.D
105
n
"q
'IIIII
I,'I, lui
i :
Ii. I, II II i i·' . i , I
70 80,
50 60 90 100 110 120 130 140 150
.~
IJ
GCMS for N.isopropylidenebenzylamine from catalytic ~tion
Abundance SCAn 819 (16.494 min); BEHZI$Ot.O90000 1 ,
80000
70000
60000
50000
40000 Iil(lS
30000
200009177
10000 'II .'. II It II:tll IIII IiI to' Ii.,
t·.! I . I0
50 60 70 80 90 100 110 120 130 140 150
IH NMR for Authentic N-isopropylidenebenzylamine
~N-<
•'.
!j
" •,•
,•
,•
,4
,, ,2 pp.
"e NMR for Authentic N.isopropylidenebenzylllllline
•;I;11
ii!
I
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i 11
, ,, , , ,155 151 14' 14' 13. 13. pp.
=
i
GCMS for N-butylideMbenzylamine from eatalytic reaction
Abundance Scan 1339 (21.514 min): BENZBUT1.D1 8
91
10' 1328'
l ~,II
77
81~",1 I'i IllJI ' i'i ~ ',1 \ :'!
"v', ,
60000
50000
40000
30000
20000
10000
o50 60 70 80 90 100 110 120 130 140 150 160
I HNMR for Authentic N-butylidenebenzylarnine
"c NMR for Authentic N-butylidenebenzylamine
-~
•Ij
1 1~
1,
I• •- .. .
r II
..=~--
Iii;
1;
II!
1L
, , , , , , ,1" 150 141 130 1Z1 111 111 .. ,
••,
10,.. ,
50,
41 30
GeMS fur Authentic N-benzylidenebenzylamine
Abundance
350000
Scan 2286 (32.288 min): DIBENZS2.D1
300000
250000
200000 1150000
100000;';C"'
GeMS fur N-beIlzylidenebenzylamine from eatalytic reaction
Abundance10000
Scan 1927 (32.306 min): DIBENZYl.D1
9000
8000
1000
6000
5000
4000
3000]'"1'-,
2000
100065 117
801060500lr.,.~,J,..,-.,...,.,..jJ,J.,..,.,,~.,l,-.,~~lJ.L,-.,l,-.,-rl-"""'~>J.h-~~~....,-~....,-~....,-...,.l,....,-~-r;-~-r;-,...jlj..,.,
90 1.00 110 120 130 140 150 160 170 180 190 200
IH NMR for Authentic N-benzylidenebenzylamine
1
( ~·"'-,---r----r-,-r--~~~,~··- ..... -,-...,...._-,-----.-----r-.-.---....--,--.-~~~..,........-.,.----r-___,.__ - T~-,---...,....--.---,------r-- y--,
11 9 1!I ., 6 S 4 3
"e NMR for Authentic N-benzylidenebenzylamine
pp.
~
iiI I
: .'f I
I
,---, -"r ,- -r··,----,,,,--·r------r r"-16. 151 141
·,·_·,............---T -'--1-'" .~.-,.. ( ,--,..-,-...,...·-T-'- ,--,---·~--r---r-"T"-··r-... '(._,
13' 12. 111 1" 91 4.-'-'"1......
78 pp.