Cyclization

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In chemical syntheses, cyclization (also called cyclization or ring closure ) refers to the formation of a cyclic, i.e. ring-shaped compound from unsaturated starting materials. The reaction can take place intra- or intermolecularly with the formation of pure, saturated or unsaturated, carbon rings or heterocycles .

If a further ring is built on an existing ring or ring system, this is called annulation . The cyclization leads to rings that have between three and about sixteen members. A cyclization can be initiated photochemically , thermally or catalytically , especially by transition metal catalysis .

Intramolecular ring closure

The intramolecular ring closure can take place as an electrocyclic ring closure reaction or it can be brought about by condensation reactions . The ring-closing metathesis is another method for the synthesis of cyclic compounds. An example of an electrocyclic ring closure is the isomerization of 1,3-butadiene to cyclobutene , for a ring closure under condensation conditions the Dieckmann condensation .

Synthesis of cyclobutene

Whether an intramolecular ring closure is easy or difficult to achieve depends not least on the size of the ring systems formed. Rings with 5–6 ring links are particularly easy to access, as these systems have the lowest ring tension .

Cyclodi- and oligomerization

By organometallic complex catalysis, 1,3-butadiene can be cyclodimerized to 1,5-cyclooctadiene . Cyclotrimerization to 1,5,9-cyclododecatriene is also possible. Cyclizing four molecules is called cyclotetramization, with more than four molecules one speaks of cyclooligomerization.

The synthesis of heterocycles is also possible through organometallic complex catalysis. Benzonitrile can be cyclized to triphenyl-substituted triazine by means of iron carbonyl complexes .

Intermolecular ring closures can take place as cycloadditions or as cyclocondensations. One of the best-known cycloadditions is the Diels-Alder reaction , while the Knorrsche pyrrole synthesis is an example of a cyclocondensation.

[n + m] cyclizations

The [n + m] cyclizations include the Diels-Alder reactions. These are [4 + 2] cycloadditions in which two different starting materials, such as 2,4-hexadiene with maleic acid dimethyl ester , provide 4 or 2 π electrons for the cyclization to the cyclohexene derivative.

The Paternò-Büchi reaction is a photochemical [2 + 2] cycloaddition named after Emanuele Paternò and George Hermann Büchi for the formation of four-membered oxetane rings from a carbonyl component and an alkene.

1, n-dipolar cycloadditions

1,3- dipolar molecules such as ozone , azides , diazoalkanes, nitrile oxides, nitrile imines, nitrones can add to unsaturated compounds such as alkenes or alkynes with ring closure. Intramolecular 1,4-dipolar cycloaddition of alkenyl-substituted 3,6-dihydro-6-oxo-1-pyrimidinium-4-olates leads to heterotricycles.

Cyclization of peptides and proteins

The ring closure saturates the open ends of the amino acid chains ( peptides and proteins ), giving them greater stability . The ends are usually not linked directly, but rather via a short chain of suitably selected amino acids. The physiological activity of the molecule can thus be roughly maintained while the stability is increased.

Individual evidence

  1. Katharina Johannes, Martin Watzke, Jürgen Martens : Synthesis of α, β-unsaturated caprolactams starting from heterocyclic imines. In: Journal of Heterocyclic Chemistry. Vol. 47, No. 3, 2010, pp. 697-702, doi : 10.1002 / jhet.381 .
  2. Hans-Jürgen Arpe: Industrial organic chemistry. Important preliminary and intermediate products. 6th, completely revised edition. Wiley-VCH, Weinheim 2007, ISBN 978-3-527-31540-6 .
  3. Clive W. Bird: The synthesis of heterocyclic compounds via transition metal intermediates. In: Journal of Organometallic Chemistry. Vol. 47, No. 2, 1973, pp. 281-309, doi : 10.1016 / S0022-328X (00) 81739-8 .
  4. ^ The Mechanism of the Paterno-Buchi Reaction and its Application in the Organic Synthesis Review
  5. Ivan Ernest: Binding, Structure and Reaction Mechanisms in Organic Chemistry. Springer, Vienna et al. 1972, ISBN 3-211-81060-9 , pp. 349-350.
  6. Hans Gotthardt, Martin Riegels: Heterotricycles by intramolecular 1,4-dipolar cycloaddition of alkenyl-substituted 3,6-dihydro-6-oxo-1-pyrimidinium-4-olates. In: Chemical Reports . Vol. 121, No. 6, 1988, pp. 1143-1146, doi : 10.1002 / cber.19881210620 .
  7. J. Deeg: Ring closure in proteins . In: Spectrum of Science , January 2010, p. 12