Chemistry Reference
In-Depth Information
Tris(hydroxymethyl)acrylamidomethane [THAM] [18-20] and its protected
acetonide [CH
2
¼
CHCONHC[(CH
2
O)
2
CMe
2
](CH
2
OH)] [21] have been synthesized
and utilized in the creation of hyperbranched materials [22] or glucose-based
surfactants [22].
3.2.2 Methanetricarboxylate-Based
Trialkyl methanetricarboxylates were readily prepared by treating dialkyl mal-
onate with alkyl chloroformate in basic conditions [23-25]; the sodium salt can be
isolated and subsequently C-alkylated using a primary alkyl halide (R
0
X) or equiv-
alent leaving group to generate R
0
C(CO
2
R)
3
. Hydrolysis leads to the initial tris-acid,
R
0
C(CO
2
H)
3
, which easily loses carbon dioxide [26] generating the free monoacid,
R
0
CH
2
CO
2
H; whereas, reduction (BH
3
-THF) gave the corresponding triol R
0
C-
(CH
2
OH)
3
. Subsequent extension of this triol can be accomplished by the following
sequence of simple transformations: ClCH
2
CO
2
H, MeOH/H
þ
, LAH, TsCl giving
R
0
C(CH
2
OCH
2
CH
2
OTs)
3
. Whereas, nucleophilic substitution of the terminal leaving
group of R
0
C(CH
2
OCH
2
CH
2
OTs)
3
is a facile process. Treatment of the intermediate
ester R
0
C(CH
2
OCH
2
CO
2
Me)
3
with TRIS (see above) easily creates a new amide bond
and access to R
0
C[CH
2
OCH
2
CONHC(CH
2
OH)
3
]
3
via initial transesterification, that
is,
R
0
C[CH
2
OCH
2
CO
2
CH
2
C(NH
2
)(CH
2
OH)
2
]
3
>
, followed by a facile intramo-
lecular rearrangement to the desired amide product [4].
<
3.2.3 Nitromethane-Based
