Noncovalent solid-phase organic synthesis or NC-SPOS is a form of
Solid-phase synthesis
In chemistry, solid-phase synthesis is a method in which molecules are covalently bound on a solid support material and synthesised step-by-step in a single reaction vessel utilising selective protecting group chemistry. Benefits compared with no ...
whereby the organic substrate is bonded to the solid phase not by a
covalent bond
A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atoms ...
but by other chemical interactions. This bond may consist of an
induced dipole interaction
In molecular physics, the van der Waals force is a distance-dependent interaction between atoms or molecules. Unlike ionic or covalent bonds, these attractions do not result from a chemical electronic bond; they are comparatively weak and the ...
between a
hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, th ...
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 (C
18) and the anchor is
acridone
Acridone is an organic compound based on the acridine skeleton, with a carbonyl group at the ''9'' position. It is a yellow solid.
Synthesis and structure
The molecule is planar. Optical spectra reveal that the keto tautomer predominates in the ga ...
.
Acridone
Acridone is an organic compound based on the acridine skeleton, with a carbonyl group at the ''9'' position. It is a yellow solid.
Synthesis and structure
The molecule is planar. Optical spectra reveal that the keto tautomer predominates in the ga ...
is N-alkylated and the terminal
alkene
In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond.
Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
group is converted into an
aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
by
ozonolysis
In organic chemistry, ozonolysis is an organic reaction where the unsaturated bonds of alkenes (), alkynes (), or azo compounds () are cleaved with ozone (). Alkenes and alkynes form organic compounds in which the multiple carbon–carbon bond ...
. 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
The Barbier reaction is an organometallic reaction between an alkyl halide (chloride, bromide, iodide), a carbonyl group and a metal. The reaction can be performed using magnesium, aluminium, zinc, indium, tin, samarium, barium or their salts. Th ...
with propargylic bromide in water (
green chemistry
Green chemistry, also called sustainable chemistry, is an area of chemistry and chemical engineering focused on the design of products and processes that minimize or eliminate the use and generation of hazardous substances. While environmental che ...
) and the second reaction is a
Sonogashira coupling
The Sonogashira reaction is a cross-coupling reaction used in organic synthesis to form carbon–carbon bonds. It employs a palladium catalyst as well as copper co-catalyst to form a carbon–carbon bond between a terminal alkyne and an aryl or vi ...
. Substrates may vary in these sequences and in this way a
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. Each chemic ...
of new compounds can be realized.
{{center,
The phosphorus ligand in the Sonogashira coupling
The Sonogashira reaction is a cross-coupling reaction used in organic synthesis to form carbon–carbon bonds. It employs a palladium catalyst as well as copper co-catalyst to form a carbon–carbon bond between a terminal alkyne and an aryl or vi ...
with phenyliodine is the water-soluble TPPTS ligand
References
Solid-phase synthesis