Page 175 - Academic Press Encyclopedia of Physical Science and Technology 3rd Organic Chemistry

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Encyclopedia of Physical Science and Technology EN007F-314 July 6, 2001 16:59

Heterocyclic Chemistry 331

1,3-Dipolar cycloaddition reactions are similar to COOH
COOMe
Diels–Alder reactions, both proceeding through a cyclic 1. ∆
transition state of six pi electrons, but differ in that + O 2. acid
three atoms supply the four-electron unit (in contrast
to four atoms in a Diels–Alder reaction). Consequently, synthesis of naphthalene-1-carboxylic acid
a five-membered ring results. Many cycloadditions,
including 1,3-dipolar cycloaddition reactions, proceed Alpha-pyrone, on photolysis, yields the highly reactive
with high stereocontrol. Sometimes the heterocyclic ring cyclobutadiene.
can be cleaved to give acyclic compounds of defined
stereochemistry. hν
+ CO 2
O O
C 6 H 5
heat C 6 H 5 LiAlH 4 C 6 H 5 preparation of cyclobutadiene
+ N
_ O N OH NH 2
O
Some alpha-pyrones can act as dienes, affording poly-
substituted benzenes.
Four-membered heterocycles are often synthesized by
[2 + 2]cycloadditions. An important example is the reac-
tion of ketenes with imines to give beta-lactams. MeOOC COOMe MeOOC
180 °C
+
O O COOMe
O
O COOMe
R 1 NR 1 COOMe
C N
+ cycloaddition of an α-pyrone
C R 3 R 2
R R R 2 R 3 R R
[2 + 2] cycloaddition route to β-lactams Certain cyclic sulfones extrude sulfur dioxide when
treated with N,N-dimethylaminofulvene, affording inky-
3-Substituted furans can be prepared by means of a pho- blue azulenes.
tolytic cycloaddition. Many other [2 + 2]cycloadditions
O
giving heterocycles are known.
+ O S R R
HO NMe 2
COOR
R R
COOR
H COOR hν p-TsOH synthesis of an azulene
+ O
O O O O
Heterocyclic rings can be used to protect functionality.
synthesis of 3-substituted furans
Thus, the formation of cyclic ketals can be used to protect
either ketones or aldehydes, or 1,2-diols.
F. Use of Heterocycles in Synthesis 3 3
R 1 HO R p-TsOH R 1 O R
The following examples show how heterocycles can be O +
R 2 H 3 O + R 2
used to prepare molecules that often cannot be readily HO O
synthesized by other routes. Thus, alkyl halides (R X) are protection of functionality as a cyclic acetal

converted into alpha-substituted aldehydes via dihydro-
1,3-oxazine intermediates. Deprotection occurs under mildly acidic aqueous con-
ditions. The Gabriel phthalimide synthesis enables alkyl
H halides to be converted to primary amines. The action of
2
O R X O 1. NaBH 4 2
R ammonia itself on alkyl halides produces a mixture of
_ R 2 2. H 2 O O
N N
R 1 amines and quaternary salts.
R 1 R 1
synthesis of aldehydes using dihydro-1,3-oxazines
O O
COOH
_ + RI H 2 O RNH 2 +
Certain furans readily undergo Diels–Alder reactions to N K N R
COOH
form adducts that can eliminate water to give substituted O O
benzenes,andincertaincasesbenzenegivesnaphthalenes. use of phthalimides in the Gabriel synthesis