250 Yadav et al.
Asian J. Chem.
R2NH
2
Montmoriil
onite K-10
EXPERIMENTAL
General procedure for the synthesis of enamines using
58
Dehydration
in situ
59 Montmorillonite clay: To montmorillonite (1 g) was added
60 ketone (1 mmol) and amine (5-6 mmol) and the mixture was
61 mixed. The solid mass was then irradiated in a domestic or
62 automated microwave oven for 4-5 min at 50-60 ºC. The time
63 of reaction was specified in Table-1. For domestic microwave
64 reactions, it was necessary to control the temperature of the
65 reaction by keeping a beaker of 200 mL of water. After the
66 reaction, the solid mass as washed with dichloromethane (20
67 mL) and it was then evaporated to obtain enamines. These
68 enamines are used as such for next alkylation and acylation
69 reactions.
N
MWI (300W)
1-5 min
O
NR2
3
R M
R
1
Scheme-I: Montmorillonote K-10 catalysed microwave induced synthesis
of enamine
It is observed that pyrrolidine was much more reactive 112
with cyclic ketone in comparison to piperidine and morpholine 113
(Tables 1-3. Piperidine have comparable reactivity like pyrro- 114
lidine while morpholine was found less reactive towards the 115
cyclic ketone and took slightly longer time to complete the 116
reaction (Table-3).
117
RESULTS AND DISCUSSION
The ring size and substitution pattern of cyclic ketone 118
was also found that have an influence on the reactivity of the 119
ketone towards base. Cyclopentanone was found more reactive 120
in endocyclic enamine formation (entry 1b, Table-1). It is also 121
noticed that the formation of endocyclic enamine and their 122
diastereomeric ratio in case of β-tetralone (1g-i) is greatly influe- 123
nced by the substituents in benzene nucleus. The title endocyclic 124
enamine (3g-i) is formed exclusively under our stated protocols. 125
Any β-unsaturated endocyclic enamine is obtained during the 126
course of reaction. The probable reason might be the electronic 127
effect of benzene nucleus and the substituents in the ring. Insta- 128
lling the endocyclic double bond with respect to benzylic posi- 129
tion could be the driving force for this reaction. This probably 130
due the conjugation effect, which stabilized the products greatly. 131
The methoxy group in aromatic nucleus make the reaction 132
slower because the weak electron donating effects slightly reduce 133
the electrophilic character through neutralizing the positive 134
charge on carbon atom in carbonyl group, which resulted in 135
70
Solid surface-mediated reactions or surface-bound reagents
71 are used to study several organic reactions. There are a number
72 of factors that need to address when such a reaction is performed.
73 The pH of the solid surface is very crucial. Solid surfaces can
74 act as Lewis acids or bases during the reactions. The most common
75 solid used in laboratory experiment are different forms of clay
76 of which montmorillonite is our choice. For examples, synt-
77 hesis of β-lactams, nitration of aromatic hydrocarbons and
78 functionalized aromatic compounds, nitration of hormones and
79 β-lactams, de-protection of oximes, oxidation of allylic and
80 benzylic alcohols glycosylations of alcohols and synthesis of
81 pyrroles were performed by montmorillonite-induced reactions
82 [18]. Different forms of silica gel, florisil, molecular sieves
83 and alumina were also used. Some of the reactions were perfor-
84 med in a domestic and automated microwave oven.
85
The cause of rate acceleration by montmorillonite in the
86 presence of microwave was not investigated. The inner cavity
87 of clay is responsible for binding the reactants and accommo-
88 dates water. The synthesis of enamines was usually carried
89 out by the condensation of carbonyl compounds with secondary
90 amine in presence of dehydrating agents like acid or base at
91 high temperature. Under this condition, ketones were transformed
92 into corresponding enamines. In this study, we describe the
93 montmorillonite K-10-catalyzed synthesis of enamines.
the retardation of reactivity of carbonyl groups.
136
In both α- and β-unsubstituted tetralones (1d and 1g) was 137
found more reactive and under goes facile reaction with pyrro- 138
lidine to offer the excellent yield of title endocyclic enamine 139
(3d and 3g) within shorter reaction time. While methoxy 140
substituent in α and β-tetralone (1d-f and 1h-i) took longer to 141
complete with comparatively lower yield.After the successful 142
synthesis of various cyclic enamines, next attention was focussed 143
to perform the synthetic reaction of another useful class of 144
enamine with piperidine as nucleophilic counter having the 145
94
Ketone 1 (1mmol) and 2º amines 2 (5-6 mmol) were taken
95 in to microwave vial and 1 g of montmorillonite K-10 clay
96 was added to it. The vial was placed in automatic microwave
97 reactor and allowed to irradiate for 2-7 min. This reaction produced
98 enamine 3 (Scheme-I). The cyclodehydration takes place to
99 afford the enamine 3 in good to excellent yield. The driving
100 force of this reaction is microwave heating and the acidic nature
101 of the montmorillonite K-10 clay. It was observed that crude
102 ketone and secondary amine give the reaction with very low
103 yield under the stated condition. In present investigations, no
104 solvents and neat pyrrolidine were used in excess to execute
105 the reaction.
same electrophilic carbonyl compounds.
146
Various enamines with piperidine was sucessfully synth- 147
esized with montmorillonite K-10 catalyzed reaction under 148
microwave irradiation yeilding excellent yields (Table-2). 149
Similarly, using morpholine base, enamies were also 150
synthesized successfully in very good yields (Table-3).
151
Conclusion
152
A montmorillonite-supported reactions for the synthesis 153
of enamines using ketones and 2º amines (pyrrolidines, piperi- 154
dine and morpholine) are successfully demonstrated. This 155
reaction produces excellent yields of enamines and this method 156
allows the isolation of the products very easily. This method 157
may find application in the synthesis of products that can be 158
formed through dehydration as one of the major pathways. 159
106
The reaction course greatly depends on the structure, substi-
107 tuent and the ring size of cyclic ketone. The reaction rate and
108 the reactivity of pyrrolidine with ketone eventually depends
109 on the basicity of cyclic amine, which measured and quantify
110 from the pka value of its conjugate acid, which revealed that
111 higher the value of pka of conjugate acid, stronger the base.
Yadav, Ram Naresh
