A simple amide protecting group: synthesis of oligoamides of Nylon 6
Gerald M. Brooke,*a S. Mohammeda and Mark C. Whitingb
a Chemistry Department, Science Laboratories, South Road, Durham, UK DH1 3LE
b School of Chemistry, University of Bristol, Cantock’s Close, Bristol, UK BS8 1TS
The 4-methoxybenzyl group (R) in amide groups NR(CNO)
renders all intermediates in the synthesis of oligomers of
Nylon 6 soluble in common solvents and is readily removed
in boiling trifluoroacetic acid.
The best science is carried out on pure compounds. Recently,
the preparation of some monodisperse linear long-chain alkanes
was described,3 materials of interest for relating their properties
as models to those of commercial polythene, a polydisperse
substance; the folding of the molecular chains in these
compounds is of particular interest.4 The study of pure
oligoamides of the Nylon family is expected to provide even
more insights into the nature of the chain-folding process since
both amide and alkyl folds are possible.
Wallace Carothers described the first use of a disecondary
diamine to introduce ‘rubberiness’ into a polyamide in an early
patent—the preparation of poly(N,N’-dimethylpentamethyl-
enesuccinamide),
{N(Me)(CH2)5N(Me)(CNO)(CH2)2)-
(CNO)]n};1 the hydrogen-bonding properties due to the
NH(CNO) group, which confer many of the desirable properties
of Nylons, were lost from the point of view of normal use at that
time, textiles. Soon afterwards, other workers investigated the
use of N,NA-dialkyl derivatives of 1,6-hexamethylenediamine
(alkyl = methyl, ethyl, isobutyl and benzyl) for incorporation
into alkyl Nylon 6,10 polymer,2 but very little has been
published since in this area. The most noticeable physical
property affected in these polymers compared with the non-
alkylated materials was a marked increase in solubility in
common organic solvents.
We have exploited the lack of inter-chain hydrogen-bonding
in N-alkylated amides to make soluble intermediates which
were purified by chromatography on silica to produce pure
‘end-capped’ Nylon 6 oligomers. These compounds have been
made previously,5 but their purity could not be monitored.
While relatively little work has been carried out on amide
protecting groups,6 we have now discovered that the
4-methoxybenzyl group in an amide [N(CH2C6H4OMe-
4)(CNO)] is an excellent protecting group, conferring solubility
in common solvents† on all derivatives, and being readily
removed by boiling TFA. Scheme 1 shows the initial formation
of the partially protected ethyl ester of acid 1 and its final
protection to give the N-Boc derivative 2, the starting material
for an iterative synthesis. The first protected amide linkage in 4
was formed from 3 and 1 by a method used in peptide
chemistry.7 The Boc group in 4 was removed by TFA at room
temperature and the chain-doubling reaction repeated succes-
sively to give first the fully protected dimer 5 (n = 2), then the
tetramer 5 (n = 4) etc. up to the hexadecamer 5 (n = 16).
Individual ‘end-capped’ amides were obtained by deprotection
of the N-terminus in 5, followed by propanoylation to give 6,
and conversion of the ethoxycarbonyl terminus to the propyla-
mide derivative 7.‡ Finally, removal of the amide protecting
group gave ‘end-capped’ oligomers 8 (n = 2, 4, 8 and 16) of
Nylon 6.§ The purity of the intermediates, formed in high
yielding reactions, could be monitored by HPLC and their
structures confirmed by 1H NMR spectroscopy. The final end-
capped Nylon 6 oligomers 8 were found to be soluble in
CD3CO2D at 80 °C, which enabled the complete confirmation
of their structures to be carried out by 1H NMR spectroscopy at
500 MHz. Currently, we are employing similar methodology for
the synthesis of oligomers of Nylon 6,6 and Nylon 4,6.
The 4-methoxybenzyl group as a protecting group on
nitrogen in an amide not only renders the parent molecule more
soluble (the property exploited in this work); it also removes a
potentially acidic hydrogen which could be incompatible in
further types of reaction. It would then assume the role of a
classical protecting group, and could be introduced into a
NH(CNO) bond via treatment with LDA–4-methoxybenzyl
bromide.
i, ii
HRN
CO2Et
H2N
CO2Et
1
iii
BocN
CO2Et
R
2
v
iv
NH
R
COEt
O
BocN
R
COH
O
1
3
vi
BocN
C
O
N
COEt
O
R
R
4
repetition
of steps
above
Boc
N
R
C
O
OEt
n
5
v
H
N
R
C
O
OEt
n
EtCO
N
R
C
OEt
n
vii
O
6
7
viii
EtCO
NHPr
N
R
C
O
NHPr
Footnotes and References
n
* E-mail: g.m.brooke@durham.ac.uk
EtCO
N
H
C
v
† Binary mixtures of appropriate solvents for chromatography were selected
from the following: CH2Cl2, MeOH, EtOAc, Et2O and light petroleum (bp
40–60 °C).
‡ All the intermediates 2–7 in Scheme 1 were viscous liquids/gums;
compound 1 was a liquid, bp 148–151 °C/0.01 mm Hg.
§ An unidentified solid precipitated during the final deprotection of the
amide groups in 7. The TFA was removed in vacuo and the residue was
O
n
8 (n = 2, 4, 8 and 16)
R = 4-MeOC6H4CH2
Scheme 1 Reagents and conditions: i, 4-MeOC6H4CHO; ii, NaBH4; iii,
Boc2O; iv, NaOH, the H+; v, TFA, 25 °C; vi, DCC, 1-hydroxybenzotriazole;
vii, EtCOCl; viii, PrNH2, KCN(cat.); ix, TFA, reflux
Chem. Commun., 1997
1511
Brooke, Gerald M.
