General reactions with hydroxyl group



Here we shall consider 3-tropanol as a standard compound.

01. Upon oxidation with cromic acid tropine first forms Tropinone. 

The reaction further proceeds to give ecgoninic acid or N-methyl succinimide. 

With halogens oxidation occurs yielding 2,2,4,4-tetrahalo Tropinone. 

Tropine burns in air. 


02. Sodium or potassium reacts upon Tropine forming tropoxide. 

The product is stronger base than water. Hence it is not stable in water.

Strong bases such as metal hydrides or metal amides also react with Tropine to give tropoxide. 


03. Tropine reacts upon Grignard reagents giving alkane.

04.It reacts with carboxylic acids in presence of mineral acids to produce esters. 

Acid anhydrides can be used for better yield. 

Acyl halides give the best yield with a vigorous reaction. 


05. With Lucas reagent it gives tropnyl halides. 

It also reacts with phosphorus halides or thionyl halides giving tropyl halides. Thionyl chloride should be used for a clear product since SO2 and HCl are both gases. 


For 3-bromo tropane, HBr + conc. sulfuric acid is used, and for 3-iodo tropane simply HI is refluxed with tropine.


06.  Tropine reacts with aldehydes or ketones in presence of dry HCl to form acetals or ketals. 

It reacts with acetylene in presence of Hg compounds to yield acetals. 

07. Phosgene reacts with Tropine in an inert solvent (e.g. benzene) at low temperature to yield tropyl chloroformate. 

When phosgene is heated with excess of Tropine in presence of pyridine, the product is tropyl carbonate. 

08. Tropine can be methylated (also alkylated) by dimethyl sulphate or dimethyl carbonate. 

09. HNO3 and H2SO4 react with Tropine to produce tropanyl nitrate and tropanyl bisulphate. 

The bisulphate compounds thus produced reacts further to give a variety of products upon reaction conditions.

 

a. When heated alone 

b. When H2SO4 in excess 

c. When Tropine in excess 

10. Tropine combine with phenylisocyanate to form N-Phenyl substituted urethan. 

These types of compounds are crystalline solids and may be used to characterize Tropine, Scopine or other hydroxy Tropane.

 

11. On exhaustive methylation it yields tropilidene (cyclohepttriene). 

12. By action of conc. Nitric acid at low temperature tropanyl nitrate is formed. 

 

Urea is added to destroy any nitrous acid formed.

 

13. By the action of nitrous acid on tropine, tropanyl nitrate is formed. 

 

14. In presence of Lewis acids diazomethane reacts with tropine. 

 

15. Tropanyl borates are prepared by the reaction of tropine with boric acid. 

 

Tropanyl phosphates are obtained by the reaction of phosphorus oxychlorides in pyridine. 




General reactions with ketone group



Here we'll consider 3-tropinone as a standard_

01. Hydrogen cyanide adds on tropinone.


The hydrogen of tropinone cyanohydrin either in basic or acid solution will convert the nitrile group to carboxylic acid.


This α-hydroxy acid contains one more carbon than tropinone.

 

02. Tropinone react with grignard reagents to form compley adducts.


These upon hydrolysis with acid yields alcohol.


03. In the presence of acidic (or basic) catalyst, tropinone react with alcohols to form ketals.


Dry HCl catalyzes the forward reaction, while aqueous HCl catalyzes the reverse reaction. The above equilibria lie far to the left and are unfavorable to the formation of ketal. But equilibria are tiled to right by removing water produced during the reaction, ketal is prepared in satisfactory yield. This is done by the addition of orthoformic ester.


In presence of acids, however the product is enol ether.


With glycol in presence of acid it produces a cyclic ketal.


It is sometimes necessary to protect or mask the keto group in tropinone to prevent it from reacting during the course of a transformation of other functional group in the molecule. Ketals are useful for these purposes and tropinone can be regenerated by acid hydrolysis.


04. Tropinone reacts with thiols or thioalcohols more rapidly than with alcohols to form tropinone mercaptol.


The thioketal is regenerated to acid hydrolysis but can be readily converted to Tropinone when hydrolyzed in presence of HgCl2-CdCOmixtures.

Refluxing tropinone mercaptol with ethanol in presence of freshly prepared raney Ni replaces the thiol group by hydrogen.


Thiols readily undergo desulphurisation.


05. NH3 derivatives that contains primary amine group G-NH2, add to the carbonyl group of tropinone to form unstable intermediates. These immediately lose a molecule of water to yield respective condensation product.


G stands for the general group bonded to –NH2 group in the NH3 derivative.


These products are crystalline solids having sharp melting point. For this reason they are frequently employed for the identification of Tropinone. The semicarbazone product has a high melting point than oxime or phenylhydrazone. However 2, 4-Dinitrophenylhydrazine can also be used.


When tropinone oxime is heated with acetic anhydride


Tropinone also reacts with N-substituted hydroxylamines to form nitrones.


The nitrone readily undergo 1, 3 addition reaction.


Oximes and hydrazones regenarate the carbonyl compound when refluxed with dilute HCl acid. Regeneration from phenylhydrazones by this method is usually difficult. One fairly successful method is by exchange of the phenylhydrazino group with another oxo compound, e.g. piruvic acid. The most satisfactory method, however, appears to be the use of acetylacetone in faintly acid solution (Ried et al., 1962), the product is 3, 5-dimethyl-1-phenylpyrazole.


 06. When tropinone is treated with nitrous acid, the half oxime is formed.


07. Tropinone condenses with chloroform in the presence of KOH.


08. Tropinone reacts with sodium or sodamide in ethereal solution.


09. Tropinone has two α-carbons. Thus tropinone in presence of Ba(OH)2 establishes the following equilibrium.


The equilibrium lies almost completely on the left; but the yield can may be increased by boiling in a soxhlet with solid Ba(OH)2. Other possible products are


10.  Tropinone condenses with arometic aldehydes or ketones in presence of dilute alkali.


11. Tropinone reacts with hydrazoic acid in presence of concentrated sulfuric acid giving a amide.


12. When hydrazones or semicarbazones are heated with sodium in ethanol at 180°C, N2 is eliminated and tropane is formed.


Because of α-carbon the reaction is only successful when DMSO is used as a solvent and very strong base is used (like potassium t-butoxide).

 

13. With secondary amine tropinone forms enamine.


Primary amines also form enamines.


However, in this case enamine-imine tautomerism is possible and the equilibrium lies virtually completely on the imine side, and consequently the enamine cannot be isolated.


15. Tropinone reacts with PCl5 to form 2, 2-dichlorotropane. The yield is poor.



16. Cl2 or Br2 replaces one or more α-hydrogen atoms from tropinone.


17. Tropone is prepared from tropinone by a Hofmann elimination and a bromination.


18. Reduction: See preparation of tropine

 

19. Ecgonine can be prepared from tropinone by the action of sodium and carbon dioxide.




Reactions with secondary amine group



We shall consider nortropane as a standard here_

01.  On action of acid chlorides these gives N, N-disubstituted amides.


02. With acids these gives ditropanylammonium salts.


03. With alkyl halides these gives 4° salts.


04. With hypochlorus acid these gives N-chloroamines.


05. With grignard reagents alkane is formed


06. With nitrous acid it forms oily nitrosoamines. (Libermann reaction)


07. On oxidation with KMnO4 these gives ditropanylhydrazines.




Reactions with tertiary amine group


We shall consider tropane as a standard here_

01. Compounds of these series react with alkyl halides giving a tetraammonium salt. Thus,


When tetraammonium salt is treated with AgOH it gives tetraammonium hydroxides.


02. When oxidized with H2O2 these gives N-Oxide.


03. With acids these forms tritropanylammonium salts.


04. With nitrous acid these gives salts.