Different Schiff Bases-Structure, Importance and Classification

Abstract

Schiff bases are a vast group of compounds characterized by the presence of a double bond linking carbon and nitrogen atoms, the versatility of which is generated in the many ways to combine a variety of alkyl or aryl substituents. Compounds of this type are both found in nature and synthesized in the laboratory. For years, Schiff bases have been greatly inspiring to many chemists and biochemists. In this article, we attempt to present a new take on this group of compounds, underlining of the importance of various types of Schiff bases. Among the different types of compounds that can be classified as Schiff bases, we chose hydrazides, dihydrazides, hydrazones and mixed derivatives such as hydrazide-hydrazones. For these compounds, we presented the elements of their structure that allow them to be classified as Schiff bases. While hydrazones are typical examples of Schiff bases, including hydrazides among them may be surprising for some. In their case, this is possible due to the amide-iminol tautomerism. The carbon-nitrogen double bond present in the iminol tautomer is a typical element found in Schiff bases. In addition to the characteristics of the structure of these selected derivatives, and sometimes their classification, we presented selected literature items which, in our opinion, represent their importance in various fields well.

Keywords: Schiff bases; dihydrazides; hydrazides; hydrazide–hydrazones; hydrazones.

Figure 1

The specific structure fragment characteristic of Schiff bases, where R₁, R₂ and R₃ are alkyl or (more often) aryl groups. R₁ or/and R₂ may also be hydrogen atoms.

Figure 2

Examples of Schiff bases—the imine fragments are framed [12].

Figure 3

An example of the formation of intra-molecular hydrogen bonds by Schiff bases in keto-enol equilibrium together with resonance structures of the corresponding forms (R and R₁ = alkyl groups) [34].

Figure 4

A moiety characteristic of hydrazides, where R is -C(=O)- or -(O=)S(=O)-.

Figure 5

The equilibrium of amide-iminol tautomers of carbonyl hydrazides [66].

Figure 6

Nomenclature in Newman’s projection depending on the value of the torsion angle [76].

Figure 7

Examples of isomeric equilibria of E (left) and Z (right) hydrazides. The Z isomer dominates when the folding of the molecule allows for the formation of multiple hydrogen bonds [64].

Figure 8

Isonicotinic acid hydrazide (isonidazid).

Figure 9

Enzymatic activation of isonidazid or its derivative (where R is H, an alkyl or aryl substituent), resulting in the formation of a hydrazyl and ultimately acyl radical and a diazene derivative [80].

Figure 10

Isonidazid derivatives: (a) N′-(propan-2-yl)-4-pyridinecarboxylic acid hydrazide and (b) N′-benzyl-4-pyridine carboxylic acid hydrazide [82].

Figure 11

Examples of monosubstituted, hydrazides of (a) aminobenzoic acid, (b) luciferin, (c) 1-hydroksy-2-naphthoic acid, (d) 1-hydroxyanthracene-2-carboxylic acid, exhibiting chemiluminescence. The -NH₂ substituent in the Markush structure (a) can assume “ortho” and “meta” positions without losing its chemiluminescent properties [92].

Figure 12

Biotin hydrazide.

Figure 13

Carbidopa-N-amino-α-methyl-3-hydroxy-L-tyrosine.

Figure 14

Synthesis of hydrazine and hydrazide derivatives of 3-formylchromone. Hydrazine derivatives of 3-formylchromone: 1: R2=R5=F, R3=R4=R6=H; 3: R4=CF3, R2=R3=R5=R6=H; 4: R3=R5=CF3, R2=R4=R6=H; 6: R2=R3=R5=R6=F, R4=H; 7: R2=CH3, R5=F, R3=R4=R6=H; 8: R2=R4=R6=F, R3=R5=H; 9: R2=R3=R4=R5=R6= F, 10: R2=CF3, R3=R4=R5=R6=H.

Figure 15

Structure characteristic for carbonyl hydrazides, where R is an alkyl or aryl substituent.

Figure 16

Basic structure of sulfonyl hydrazides, where R is an aryl group.

Figure 17

Peptide (left) and aza-peptide (right), where R is a side chain.

Figure 18

Aza-peptide (left) and azatide (right), where R, R₁ and R₂ are side chains—hydrazide bonds are framed.

Figure 19

Structure of hydrazine acid, where R₁ and R₂ may be a hydrogen atom, an alkyl group or an aryl group.

Figure 20

Resonance forms of the M–C–O bond [55].

Figure 21

Tetra- and pentacarbonyl hydrazinecarbonyl complexes and their oxidation product carbonyl hydrazid (R₁, R₂, R₃ and R₄ are an alkyl group) [107].

Figure 22

The basic structure of dihydrazides, where R and R₁ is an alkyl, aryl, or hydrogen group.

Figure 23

Structure of 3-aminophthalic acid hydrazide (luminol) [92].

Figure 24

Amide-iminol tautomerism of luminol [92].

Figure 25

The basic structure of hydrazones, where R is an alkyl or aryl group.

Figure 26

The imine–enamine tautomerization of hydrazones.

Figure 27

A complex of two hydrazone ligands and one nickel(II) ion [131]. R1 and R2 are substituents as described in Table 1.

Figure 28

Basic structure of the sulfonyl hydrazone, where R and R₁ are alkyl or aryl groups.

Figure 29

The basic structure of a hydrazide–hydrazone, where R and R₁ are either alkyl or an aryl groups.

Figure 30

Hydrazide–hydrazone derivative of biphenyl-4-carboxylic acid, where R = NO₂, -Cl or -Br [135].

Figure 31

Structure of the 2r, 4c-diaryl-3-azabicyclo [3.3.1] nonan-9-one-4-methyl-1,2,3-thiadiazole-5-carbonyl hydrazide–hydrazone [136].

Figure 32

Derivative of 2,6-difluorobenzoic acid and 6-bromoindole—hydrazide–hydrazone with anti-cancer properties [77].

Figure 33

New hydrazide–hydrazones of lactic acid with antibacterial activity.

Figure 34

Quinoline derivative with significant antibacterial properties.

Figure 35

Indol-2-one derivative with antibacterial activity.

Figure 36

N-substituted indole derivative with antibacterial properties.

Figure 37

N-(2-Thiouracil-5-oyl)hydrazone derivative with antibacterial activity.

Figure 38

4-Methyl-1,2,3-thiadiazole-carboxylic acid hydrazide derivative active against a panel of bacterial strains.

Figure 39

Pyrazine derivative with antitubercular properties.