Noncovalent solid-phase organic synthesis
Encyclopedia
Noncovalent solid-phase organic synthesis or NC-SPOS is a form of Solid-phase synthesis
whereby the organic substrate is bonded to the solid phase not by a covalent bond
but by other chemical interactions. This bond may consist of an induced dipole interaction between a hydrophobic matrix and a hydrophobic anchor. As long as the reaction medium is hydrophilic (polar) in nature the anchor will remain on the solid phase. Switching to a nonpolar solvent releases the organic substrate containing the anchor.
In one experimental setup the hydrophobic matrix is RP silica gel (C18) and the anchor is acridone
. Acridone
is N-alkylated and the terminal alkene
group is converted into an aldehyde
by ozonolysis
. This compound is bonded to RP silica gel and this system is subjected to a tandem sequence of organic reactions. The first reaction is a Barbier reaction
with propargylic bromide in water (green chemistry
) and the second reaction is a Sonogashira coupling
. Substrates may vary in these sequences and in this way a chemical library
of new compounds can be realized.
The phosphorus ligand in the Sonogashira coupling
with phenyliodine is the water soluble TPPTS ligand
Solid-phase synthesis
In chemistry, solid-phase synthesis is a method in which molecules are bound on a bead and synthesized step-by-step in a reactant solution; compared with normal synthesis in a liquid state, it is easier to remove excess reactant or byproduct from the product. In this method, building blocks are...
whereby the organic substrate is bonded to the solid phase not by a covalent bond
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....
but by other chemical interactions. This bond may consist of an induced dipole interaction between a hydrophobic matrix and a hydrophobic anchor. As long as the reaction medium is hydrophilic (polar) in nature the anchor will remain on the solid phase. Switching to a nonpolar solvent releases the organic substrate containing the anchor.
In one experimental setup the hydrophobic matrix is RP silica gel (C18) and the anchor is acridone
Acridone
Acridone is an organic compound based on the acridine skeleton, with a carbonyl group at the 9 position. It may be synthesized by the self-condensation of N-phenylanthranilic acid.-Derivatives:...
. Acridone
Acridone
Acridone is an organic compound based on the acridine skeleton, with a carbonyl group at the 9 position. It may be synthesized by the self-condensation of N-phenylanthranilic acid.-Derivatives:...
is N-alkylated and the terminal alkene
Alkene
In organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
group is converted into an aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
by ozonolysis
Ozonolysis
Ozonolysis is the cleavage of an alkene or alkyne with ozone to form organic compounds in which the multiple carbon–carbon bond has been replaced by a double bond to oxygen...
. This compound is bonded to RP silica gel and this system is subjected to a tandem sequence of organic reactions. The first reaction is a Barbier reaction
Barbier reaction
The Barbier reaction is an organic reaction between an alkyl halide and a carbonyl group as an electrophilic substrate in the presence of magnesium, aluminium, zinc, indium, tin or its salts. The reaction product is a primary, secondary or tertiary alcohol...
with propargylic bromide in water (green chemistry
Green chemistry
Green chemistry, also called sustainable chemistry, is a philosophy of chemical research and engineering that encourages the design of products and processes that minimize the use and generation of hazardous substances...
) and the second reaction is a Sonogashira coupling
Sonogashira coupling
In organic chemistry, a Sonogashira coupling is a coupling reaction of terminal alkynes with aryl or vinyl halides. This reaction was first reported by Kenkichi Sonogashira and Nobue Hagihara in 1975.-Catalyst:...
. Substrates may vary in these sequences and in this way a chemical library
Chemical library
A chemical library or compound library is a collection of stored chemicals usually used ultimately in high-throughput screening or industrial manufacture. The chemical library can consist in simple terms of a series of stored chemicals...
of new compounds can be realized.
Sonogashira coupling
In organic chemistry, a Sonogashira coupling is a coupling reaction of terminal alkynes with aryl or vinyl halides. This reaction was first reported by Kenkichi Sonogashira and Nobue Hagihara in 1975.-Catalyst:...
with phenyliodine is the water soluble TPPTS ligand