Library Catalogue

Library Catalogue

  • external user (warningwarning)
  • Log in as
  • About the Catalogue

    Union Catalogue of Agricultural Libraries in the Netherlands

    The WUR Library Catalogue contains bibliographic data on books and periodicals held by the libraries of Wageningen University and Research Centre and some 15 associated libraries. Holding data are added to each record.

    Subjects covered include Agrotechnology, Food and Food Production, Plant and Animal Sciences, Soil Science, Geo-information, Landscape and Spatial Planning, Water and Climate, Ecosystem Studies, Economics and Society.

    The joint collections of the participating libraries cover a substantial part of the internationally available scientific literature in these disciplines.

    As far as Dutch scientific literature in these fields is concerned, coverage can be considered near 100%, including much of the so-called "grey literature".

    All titles are entered in their original language. Keywords are added to facilitate subject searching.

    The database is updated every day and now contains over 830.000 records.

Record number 104731
Title Cinesubstitutie en broomverplaatsing bij inwerking van kaliumamide op 4-gesubstitueerde halogeenpyridinen
show extra info.
P. Vrijhof
Author(s) Vrijhof, P.
Publisher Wageningen : Veenman
Publication year 1974
Description 90 p ill
Notes Proefschrift Wageningen
Ook verschenen als handelsuitgave
Tutors Hertog, Prof. Dr. H.J. den
Graduation date 1974-02-08
Dissertation no. 578
Author abstract show abstract

A survey is given of investigations on the reactions of halogeno-azahetarenes in strongly basic media, especially towards potassium amide and lithium piperidide, which were found to comprise direct and cine substitutions, ring openings and ring transformations, halogen migrations and several other processes. In this connection we studied reactions of 4-substituted halogenopyridines with potassium amide, involving cine substitutions and halogen migrations (chapter 1).

Reaction procedures and methods of analysis applied are described in chapter 2.

First we investigated the amination of 3-bromo-4-ethoxypyridine, a substrate previously supposed to be converted at -33° into 2-amino-4-ethoxypyridine, 4-ethoxypyridine and 2-amino-5-bromo-4-ethoxypyridine via a mechanism involving 4-ethoxy-2,3-didehydropyridine as an intermediate and a bromine migration (PIETERSE and DEN HERTOG, 1962). By varying reaction conditions and applying 2H-labelling it was established that 3-bromo-4-ethoxypyridine is transformed into 4-ethoxypyridine and 3,5-dibromo-4-ethoxypyridine by an intermolecular trans-bromination, that 4-ethoxypyridine is formed at the same time by potassium-bromine exchange and that 2(=6)-amino-4-ethoxypyridine does not originate from a didehydropyridine derivative as an intermediate but results from an abnormal-addition-elimination reaction (AE a ) starting with an attack on the nucleus at C-6 by the amide ion. In a base-catalyzed reaction the 3,5-dibromo derivative is converted into 2,5-dibromo-4-ethoxypyridine, which at -33° is aminated to yield 2-amino-5- bromo-4-ethoxypyridine.

Action of potassium amide on 3-bromo-2,4-diethoxypyridine results in a bromine shift to C-5 and subsequent formation of 2,4-diethoxypyridine, 6-amino-2,4- diethoxypyridine and 6-amino-3-bromo-2,4-diethoxypyridine (chapter 3).

Variation of the substituent at C-4 and the halogen atom at C-3 gave the following results.

3-Chloro-4-ethoxypyridine is converted into 4-amino-3-chloropyridine (AE-mechanism). The 3-iodo derivative yields 4-ethoxypyridine and 3-amino-4-ethoxypyridine at -33° whereas at -75° only deiodination takes place.

3-Chloro-, 3-bromo- and 3-iodo-4-piperidinopyridine give the 3-amino derivative according to the S N Ar 2 - or AE-mechanism, this strongly temperature dependent process being favoured by the voluminosity of the substituent. Evidence for a nucleophilic substitution via radical anions as a side-reaction is obtained in the conversion of 3-iodo- into 3-amino-4-piperidinopyridine. Only 3-bromo-4-piperidinopyridine yields the 2-amino compound through the AE a -pathway with initial attack of the amide ion at C-2 and C-6. Dehalogenation was found to occur in the aminations of 3-bromo- and 3-iodo-4-piperidino pyridine (potassium-halogen exchange).

3-Bromo-4-(4'-pyridyl)pyridine containing a -I, -M substituent is rapidly transformed into 2-amino- and 3-amino-4-(4'-pyridyl)pyridine and into debrominated material. In a mixture of liquid ammonia and ether some 2-bromo-4-(4'- pyridyl)pyridine is formed together with 4-(4'-pyridyl)pyridine; a result indicating that possibly in both media bromine migration takes place, in liquid ammonia followed by a rapid amination.

3-Bromo-4-cyanopyridine, the second compound with a -I, -M group studied, yields 4-aminopyridine, 3-bromo-4-aminopyridine, 3,5-dibromo-4-aminopyridine and 2-bromo-4-aminopyridine. Thus in this case bromine migrations occur and subsequently replacements of the cyano by the amino group (chapter 4).

In connection with the results described above the reactivities of dibromo- and tribromo-4-ethoxypyridines in liquid ammonia and in a mixture of liquid ammonia and ether were studied.

In liquid ammonia 2,3-dibromo-4-ethoxypyridine yields 2,5-dibromo-4-ethoxypyridine and 2-amino-5-bromo-4-ethoxypyridine; 2,5-dibromo-4-ethoxypyridine also gives 2-amino-5-bromo-4-ethoxypyridine, while 3,5-dibromo-4-ethoxypyridine is converted into the 2,5-dibromo- and 2-amino-5-bromo derivative as well, together with substances resulting from side and subsequent reactions. It is supposed that all the reactions start with the abstraction of the most acidic proton. The formed carbanion then abstracts a bromonium ion from a molecule of the starting material yielding 2,3,5-tribromo-4-ethoxypyridine and the anion of the 2- or 5-bromo derivative. From these products by a second migration of a bromonium ion 2,5-dibromo-4-ethoxypyridyl-3-anion and the starting substance are obtained.

In the mixture of liquid ammonia and ether the same disproportionation products are formed. In this medium however, they react independently according to different routes. Thus 2,3-dibromo- and 2,5-dibromo-4-ethoxypyridine give mixtures of 2-amino-4-ethoxypyridine, 2,6-dibromo-4-ethoxypyridine and 2,3,6-tribromo-4-ethoxypyridine of the same composition, whereas 3,5-dibromo-4-ethoxypyridine is converted into 3-bromo-4-ethoxypyridine as main product, together with 2,3,6-tribromo-4-ethoxypyridine.

2,3,5-Tribromo-4-ethoxypyridine is transformed in both media into 2,3,6-tribromo-4-ethoxypyridine and in liquid ammonia also debrominated to 2,5-dibromo-4-ethoxypyridine.

In order to check the validity of the mechanisms proposed several experiments were carried out, viz. the action of potassium amide on mixtures of two substrates. The results are in good agreement with the schemes given and corroborate the introduced reaction mechanisms. Although in nearly all the reactions studied the bromine migration is an intermolecular process, there is an indication of an intramolecular transformation in the isomerization of 3,5-dibromo-6-deutero-4-ethoxypyridine into 2,5-dibromo-6-deutero-4-ethoxypyridine of nearly the same deuterium content.

The above was an incentive to investigate the base-catalyzed bromine shift in bromo-chloro-4-ethoxypyridines in both media. The reaction of 3-bromo-2-chloro-4-ethoxypyridine proceeds analogously to that of 2,3-dibromo-4-ethoxypyridine. 2-Bromo-3-chloro-4-ethoxypyridine was found to be the only example of a substrate from which a bromonium ion is abstracted from C-2 in the pyridine nucleus, producing 3-chloro-4-ethoxypyridine and 2,6-dibromo-3-chloro-4-ethoxypyridine. From 3-bromo-5-chloro-4-ethoxypyridine together with the last-mentioned products 2-bromo-5-chloro-4-ethoxypyridine is formed.

Finally it is emphasized that several isomerizations described may be used for the synthesis of compounds otherwise not easily accessible (chapter 5).

Online full textINTERNET
On paper FORUM ; STACKS ; NN08202,578
FORUM ; STACKS ; NN08200,578
Keyword(s) (cab) chemical reactions / halogens / pyridines
Categories Organic Chemistry
Publication type PhD thesis
Language Dutch; Flemish
There are no comments yet. You can post the first one!
Post a comment

To support researchers to publish their research Open Access, deals have been negotiated with various publishers. Depending on the deal, a discount is provided for the author on the Article Processing Charges that need to be paid by the author to publish an article Open Access. A discount of 100% means that (after approval) the author does not have to pay Article Processing Charges.

For the approval of an Open Access deal for an article, the corresponding author of this article must be affiliated with Wageningen University & Research.

Please log in to use this service. Login as Wageningen University & Research user or guest user in upper right hand corner of this page.