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Raoof and Sadiq Iraqi Journal of Science, 2022, Vol. 63, No. 12, pp: 5086-5105
DOI: 10.24996/ijs.2022.63.12.1
_________________________________
* Email: amaalsameer74@gmail.com 5086
Mannich Bases: Synthesis, Pharmacological Activity, and Applications: A
Review
Sura S. Raoof 1*, Amaal S. Sadiq2
1Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
Department of chemistry, College of Science for woman, University of Baghdad, Al-Jadiriya, Baghdad, Iraq
Received: 6//202 Accepted: //2022 Published: 30/1/2022
Abstract
The Mannich reaction is one of the most important types of organic chemistry
fundamental reactions. It is a crucial stage in the production of various medicines,
natural goods, and industrial chemicals. Chemists' imaginations have always been
piqued because of this. In general, the Mannich reactions can be used as part of a
tandem reaction sequence to produce complex target molecules in an elegant and
often easy manner. The following article examines and summarizes methods for
synthesizing Mannich derivatives, in addition to offering a survey of recent
advancements in several fields’ applications of the Mannich reaction, such as
biological applications, antimicrobial activity, anticancer activity, anti-inflammation
and antioxidant activity, antimalarial activity, anti-viral activity, and so on. We also
go over how mannich base is used in industry and agriculture.
Keywords: Applications, Synthesis, Mannich bases, Biological Activity
ISSN: 0067-2904
Raoof and Sadiq Iraqi Journal of Science, 2022, Vol. 63, No. 12, pp: 5086-5105
1. Introduction
Mannich reactions are more flexible than other reactions. As a result, they have long
piqued the interest of chemists [1]. The Mannich reaction's final products are Mannich bases,
which are beta-amino ketones carrying compounds [2-4]. Aminomethylations, also known as
Mannich reactions, are condensations with three components where the substrate is RH (a
molecule with a hydrogen atom that is active) that combines with formaldehyde and an amine
to generate Mannich base[5]. The R-H substrates used in Mannich reactions could come from
various structurally diverse types of molecules. Because the substrate's active hydrogen atom
is on a carbon atom or a heteroatom that can be bonded to sulfur, nitrogen, oxygen, or
phosphorus, aminomethylation can produce the C-, S-, N-, O-, and P-Mannich reactions,
respectively[6]. For the production of compounds containing nitrogen, the Mannich method is
frequently utilized[7]. The chemistry of the Mannich base has attracted a lot of attention
recently. Mannich bases have had antifungal[8], antibacterial[9,10], anti-HIV[11],
antiviral[12,13], antimicrobial[14], and anticancer[15] properties. On the surfaces of the
polymer industry, they are also used as paints and active substances. Due to their
anticonvulsant characteristics, Mannich reactions are reported as potential biological agents.
They can also be used in other situations such as antituberculars[16], vasorelaxing[17].
Antimalarial[18], anticonvulsant[19], analgesic[20], drugs, biological[21] and
pharmacological activity[22,23]. Other uses include agrochemicals such as plant growth
regulators[24], contact with enzymes involved in antioxidant processes, suppression of
mitochondrial respiration[25,26], suppression of the enzyme topoisomerase [27,28], and
tubulin polymerization.
Mannich reaction mechanism
In the 1960s, research focused on the chemistry of Mannich bases, which were considered
active intermediates that could be easily converted into a range of mixtures with uses in a
variety of industries. The discussion over the mechanism of the Mannich reaction lasted quite
a while, and from that point on, it was proposed that the reaction has two mechanisms, as
indicated by the reaction conditions[29].
A. In acidic medium
In the reaction of amine with formaldehyde in the acidic medium, the active hydrogen
atom in certain chemical compounds is replaced by the methyl amine group (Scheme 1) [30]
Scheme 1 - The mechanism of the Mannich reaction in acidic medium
B. In alkaline medium
Mannich bases could be formed in the alkaline medium by the nucleophilic addition of
amines to the carbonyl group of aldehydes before adding an enolizable carbonyl compound
(Scheme 2) [31]
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Scheme 2 - The mechanism of the Mannich reaction in alkaline medium
Biological activity and applications of Mannich bases
The enormous curiosity in the chemistry of the Mannich reaction has largely fueled the
realities that follow:
1- Anti-microbial activity
The antibacterial activity of a novel Mannich reaction chain containing 4-amino-3-(N-
phthalimidomethyl)-1,2,4-triazole-5-thione 5a–h (Scheme 3) was tested against several gram-
positive and gram-negative bacteria and parasite species. According to the findings,
levofloxacin, a traditional treatment, and Mannich base 5h showed nearly equivalent actions
against K. pneumonia and E. coli. Among the examined compounds, the greatest activity was
found in the Mannich reaction with electron-donating substituents (hydroxyl and methoxy) on
the phenyl ring (5b and 5h) or halogens on the phenyl ring (5e and 5f). The Mannich base
with the 2-hydroxy group had the greatest level of antifungal efficacy against Candida
albicans. The findings also show how the inclusion of a morpholine ring in heterocyclic
particles increases antibacterial activity [32].
N
O
O
C
H2
COOH H2NH
N CSH
N NH2
+
N
O
O
C
H2N
NHN
NH2
S
N
O
O
C
H2N
NHN
NS
HC R
N
O
O
C
H2N
NN
S
N
HC R
NO
Fusti on at 145 0C
R-CHO, AcOH, ref lux
HCHO
morphloine
ethanol
12
3
(4a-i)
(5a-h)
4a, 5a = phenyl
4b, 5b = 2-hydroxyphenyl
4c, 5c = 3-pyridyl
4e, 5e = 4-chlorophemy l
4f , 5f = 4-bromophnyl
4g, 5g = 4-pyridyl
4h, 5h = 4-methoxyphe nyl
4i = 4-fluorophenyl
Scheme 3 - Synthesis of compounds 5a–h by Mannich reaction
The corresponding compounds 6a-6e were produced at high yields by reacting substituted
benzaldehyde and morpholine or methyl amine with acetanilide. Using matching streptomycin
as standards, the researchers discovered the novel heterocyclic Mannich bases. They were
examined for antibacterial activity against E. coli using the cup and plate technique. All the
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titled compounds showed good antimicrobial activities. Specifically, compounds 6a and 6b
possessed very good antimicrobial efficacy against Bacillus and Escherichia coli [33].
Figure 1: Structures of compounds 6a-6e
The antibacterial efficacy of aminoalkylated-2-naphthols 7-29 (Scheme 4) was put to the
test against a group of gram-positive (MRSA, S. aureus, and Enterococcus fecalis) and gram-
negative (two strains of P. aeruginosa, Escherichia coli, Citrobacter freundii, K. pneumonia,
Enterobacter cloacae, and Proteus vulgaris) and gram-negative, with amoxicillin as a
reference. Mannich bases 7-30 had little effect on gram-negative bacteria, but several
aminoalkylated-2-naphthols demonstrated promise against gram-positive bacteria. The kind of
aryl moiety added to the Mannich base framework by the aldehyde component used in amino
alkylation is shown to regulate antibacterial efficacy in this series of molecules [34].
Scheme 4 - Aminoalkylated-2-naphthols 7-30
2-Naphthol 1 was amino alkylated in the Mannich reaction using 2-carboxaldehyde
thiophene as the aldehyde reagent and 1H-benzotriazole as the amine reagent (Scheme 5). The
antibacterial action of this new group of Mannich reactions [31-38] versus the original list of
bacteria showed that they were all passive against gram-negative bacteria but active against
gram-positive bacteria at varying stages. Candidates 34 and 38, which have hydrophobic
moieties in this part of the molecule, are inert against E. fecalis, suggesting that the nature of
the various amino moieties in the structure of these Mannich bases induces some selectivity.
The most active compounds in this system against S. aureus were Mannich bases 36 and 37,
which were created from 5-bromothiophene-2-carboxaldehyde as the aldehyde component
and piperidines as amine reagents. All the candidates showed anti-MRSA activity. When the
thiophene ring is replaced with bromine, the antibacterial efficacy of Mannich bases 36 and
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37 does not appear to differ, much from that of their unsubstituted equivalents, 15 and 16,
respectively [34].
Scheme 5 - Novel heterocyclic Mannich bases
Secondary amines, benzimidazoles, and formaldehyde are used to make new N-Mannich
bases (Figure 2). The examined compounds 39 and 40 exhibited different anti-biofilm features
and were microbicidal, being active against a wide spectrum of Gram-negative and Gram-
positive bacterial strains both in adherent and planktonic states, endorsing their potential in
the development of novel anti-microbial and anti-biofilm agents. The presence of nucleophilic
groups inside the molecule, like CH3 or OH, is linked to the compounds' microbicidal activity.
As a result, the compounds of OH in both types, benzimidazole and Mannich bases, had the
greatest microbicidal and anti-biofilm effects. The molecule's planarity and symmetry both
provide substantial support for its antibacterial activity[35].
Figure 2: N-Mannich bases for benzimidazole
Microwave helped from benzaldehyde, thiomorpholine, and benzamide, acetamide,
carbamide(urea)/nicotinamide yielded good production of Mannich bases such as N-
((thiomorpholino)phenyl methyl)benzamide (41), N-((thiomorpholino)phenyl methyl)
acetamide (42), 1-N-(phenyl(thiomorpholino)methyl)carbamide (43) and N-(phenyl
(thiomorpholino)methyl)nicotinamide (44) (Figure 3). All the bacterial and fungal strains
tested were active against total chemicals. The compounds (41-44) Mannich bases are
moderately active or very efficient against fungal and bacterial strains when used as typical
antibacterial medications. N-(Phenyl(thiomorpholino)methyl)acetamide (42) has superior
antibacterial and antifungal activity against Pseudomonas aeruginosa, Staphylococcus aureus,
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and Escherichia coli compared to other Mannich bases. The compound N-
((thiomorpholino)phenylmethyl)carbamide (43) has excellent activity against Candida
albicans, Penicillium species, and Aspergillus niger in parallel with other Mannich bases. The
procedure has several advantages, including being a green chemical approach, having a
simple handling method, having a short reaction time, having an easy experimental setup, and
using a cheap and environmentally benign kind of catalyst[36].
Figure 3:Structure of [41-44]
Various N-Mannich reactions of heterocyclic 1,3,4-thiadiazoles 47-52 (a-c) were designed
and synthesized (Scheme 6), and their antimicrobial and anti-inflammatory effects were tested
in vitro. Compounds 47b and 48a had the strongest antibacterial efficiency against S. aureus,
whereas compounds 47a and 47b had the highest antibacterial activity efficiency against B.
subtilis. It was discovered that compound 3b had prime antibacterial efficacy against both
microorganisms. When compared to the common antibiotic ciprofloxacin, the compounds
47c, 51c, and 52c exhibited extremely similar actions against the pathogen E.coli. The
pipiridine ring is thought to be required in Mannich for antibacterial action against gram-
negative E. coli. The most potent compound against K. pneumoniae was found to be
compound 3a. The cup-plate method was used to assess the synthesized compounds'
antifungal efficacy in vitro. The compounds 47a, 48a, 49a, and 52a were found to be the most
effective against the fungus A. niger in the study. In Mannich base compounds, the structural
dimethylamine group is required for antifungal action against A. niger. The compounds 48a,
48b, 49c, 50b, 52a, and 52c exhibited outstanding action against the fungus C. albicans
compared to the conventional medicine Fluconazole. The anti-inflammatory efficacy of the
randomly selected compounds was assessed in albino rats using the carrageen-induced rat
paw oedema model and the standard medication, diclofenac sodium. The experiment lasted 2
hours, with intervals of 0.5, 1.0, and 2.0 hours. When compared to normal medicine, the
compounds 47a, 48b, 51b, and 52c of fluconazole have a stronger anti-inflammatory effect.
To summarize the chemical 51b entire performance, it showed good anti-inflammatory
pharmacological efficacy. The chemical 51b has more unsaturated hydrocarbons in its
structure than the Schiff base, which has high lipophilic characteristics due to the electron-
rich morpholine ring in the Mannich base[37].
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Scheme 6 - A graphic representation of the produced title compounds
In the formation of formaldehyde, norbornene methanol interacts with secondary
amines(Figure 5), yielding new norbornene-containing Mannich bases(53). The chemicals
created have high antibacterial and antifungal action against organisms such as Klebsiella
pneumoniae, Staphylococcus aureus, Candida albicans, albicans yeast-like fungus, and
Escherichia coli, which outperform reference agents in clinical practice (ethanol, furacilinum,
rivanol, chloramine, and phenol). The compounds' lowest inhibitory and bactericidal
concentrations were specified. At very low concentrations, the chemicals are effective against
bacteria and fungi (S. aureus, E. coli, and C. albicans) [38].
Figure 5: Norbornene-containing Mannich bases
2- Anti-inflammation and antioxidant activity
A chain of five new Mannich bases of dehydrozingerone (DHZ) derivatives (54a-e) was
synthesized successfully and evaluated for their anti-inflammatory activity. To assess
antioxidant and anti-inflammatory activity, inhibition of denaturation of heat-induced albumin
and the free radical DPPH method are used, respectively. All of the produced compounds
(54a-e) demonstrated antioxidant and anti-inflammatory activity. Compound 54c contained
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the N-methylpiperazine moiety, which has the best anti-inflammatory efficacy. The efficacy
was identical to that of diclofenac sodium 54e contains a dimethylamine moiety, which has
the best antioxidant activity. When compared to quercetin as a reference, the molecule
demonstrated moderate activity. The antioxidant efficacy of Mannich base derivatives of
DHZ compounds was often much better than that of DHZ[39].
Figure 6: Synthesis of dehydrozingerone (DHZ) derivatives using Mannich reaction
The corresponding compounds 55a-55c were synthesized by reacting substituted
benzimidazole, aldehydes, and an active hydrogen molecule (Figure 7); they were tested for
anti-inflammatory and analgesic properties. Analgesic and anti-inflammatory efficiency. All
compounds possess very good analgesic and anti-inflammatory efficiency[40].
Figure 7 : Mannich bases with a 2-substituted benzimidazole moiety
A chain of mono-carbonyl analogs of curcumin (AMACs), including the morpholine
Mannich[(2E,6E)-2-(4-hydroxy-3-[morpholin-4-yl-)methyl]phenylmethylidene)-6(phenyl
methylidene)cyclohexane-1-one)] was synthesized (Scheme 7). The antioxidant and anti-
inflammatory properties of the title and the original compounds were determined using the
2,2-diphenyl-2-picrylhydrazyl (DPPH) technique free radicals and the technique of
denaturation of proteins, respectively. Of the tested compounds, only compound 57d had
similar antioxidant efficacy as to cyclovalone. All the AMACs exhibited lower anti-
inflammatory activity compared to cyclovalone. Despite this, compounds 58c and 58d had
potent anti-inflammatory action that was nearly identical to cyclovalone and conventional
diclofenac sodium [41].
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Scheme 7- The title compounds' structures and synthesis routes
Based on α-mangostin and γ-mangostin (C-4 and C-4/C-5) aminomethyl derivatives
synthesized, several new mangostin derivatives have been developed, demonstrating the
feasibility of C-4 and C-4/C-5 placement of -mangostins and -mangostins 1,2 using the
Mannich process. Furthermore, new aminomethyl derivatives [61-69].The chelating capacity
of the study compounds was shown to have a strong positive association with RSA. The
addition of substituents in positions C-4 and C-4/C-5 scores significantly; all synthesized
compounds show a lessening in hemolytic activity, while the C-4-CH2NMe2-group includes
compounds with the highest cytotoxicity against RBCs compared to other mangostin
derivatives. In AOA, mangostin 70 and its fundamental components 71-73 appeared to be
significantly more dominant than mangostin 1 and its derivatives 62-69 for all factors studied.
At low concentrations, Mannich bases 62, 63, and 66-17 protect RBCs from mammalian acute
oxidative stress better than mangostins and -mangostins 1, 2. The findings propose that
additional research into the pharmacological characteristics of produced C-4 and C-4/C-5-
aminomethyl derivatives could yield beneficial results (Schemes 8 and 9)[42].
Raoof and Sadiq Iraqi Journal of Science, 2022, Vol. 63, No. 12, pp: 5086-5105
Schemes 9 - Synthesis of C-4/C-5-aminomethylated derivatives of ?-mangostin. Reagents and
conditions: (a) 2.2 eq. HCHO/morpholine or azepane, PhH, reflux, 45-75 minutes; (b) 2.7 eq.
CH2(NMe2)2, PhH, room temerature, 60 min minutes
3- Anti-cancer activity
Lawsone has been used to successfully synthesize novel Mannich reactions that are
effective against a wide range of parasites and cancer cell lines. The anti-proliferative action
is determined by the N-alkyl chain's length. Whereas N-tetradecyl and N-dodecyl derivatives
74a and 74b outperformed N-heptyl compound 1, N-hexadecyl derivative 74c had the highest
efficiency. The dodecyl derivative 74a was obtained with maximum efficiency from the N-
hexadecyl 74c and the N-heptyl derivative 1 in the panc-1 cancer cells in the pancreas and the
vinblastine-resistant cervical carcinoma KBV1 (Vbl). Compounds 74a-c significantly
increased the production of reactive oxygen species (ROS) in cancer cells. In general, the 2-
pyridylmethylamine and benzyl compounds were less active. The reason for compound [74a-
c]'s unusually strong activity in PC-3 prostate cancer cells that are negative for androgen
receptors remains unknown. Compound 74c, as well, has an anti-parasitic effect, which was
linked to a significant distortion of T.B. Brucei parasites’ microtubule cytoskeleton.
Furthermore, 74c's significantly stronger activity in cells of E. histolytica compared to the
anti-parasitic medication metronidazole encourages additional research into 74c and its linked
analogs in this area of tropical disorders. The novel lawsone Mannich reactions (74a-c)
demonstrate to be appealing multi-targeted curative filters for the treatment of tumors and
parasite turmoil (Scheme 10), owing to their ease of manufacture [43].
Scheme 10 - New lawsone derivatives
The docking consequences of Mannich bases and tamoxifen with estrogen receptor protein
(PDB ID 2YAT) and their interactions with the dynamic site of an objective protein are given
in Figures 8-14. In this study, tamoxifen was utilized as a standard ligand for the comparison
of docked compound results. Tamoxifen triphenylethylene is an estrogen receptor agonist. It
Raoof and Sadiq Iraqi Journal of Science, 2022, Vol. 63, No. 12, pp: 5086-5105
has "estrogenic and antiestrogenic activities" depending on the target tissue. It is strongly
antiestrogenic on the mammary epithelium, so it is used in both the prevention and treatment
of cell-pernicious growth. "It is proestrogenic on the uterine epithelium," thus the current
debate about its safety in cancer prevention, especially since an increased rate of endometrial
cancer has been discovered and is being treated systematically in women with tamoxifen.
Tamoxifen's CDOCKER value of 7.62965 kcal/mol. This implies that tamoxifen has shown
lower binding affinity with the 2YAT protein compared with our compounds. There is no
hydrogen bond required between tamoxifen and the receptor. There was only one Pi-Pi
interaction between the phenyl ring of tamoxifen and His524. Moreover, several electrostatic
and Van der Waals interactions are included to increase the binding affinity of tamoxifen. The
docking outcomes of compounds with active-site amino acids at the 2YAT receptor showed
better binding interactions. The affinity of N-(diphenylamino)methyl acetamide was
discovered to be four times greater than standard. One strong hydrogen bond (distance 1.98
Å) connects the ketone group of the N-(diphenylamino)methyl acetamide atom to the Arg 394
residue [44].
Figure 8: Interaction details of N-(diphenylamino)methyl acetamide with active-site amino
acids of 2YAT receptor
Figure 9: Linteraction details of N-(diphenylamino)methyl acrylamide with active-site amino
acids of 2YAT receptor
Figure 10: Interaction details of N-morpholino(phenyl)methyl acetamide with active-site
amino acids of 2YAT receptor
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Figure 11: Interaction details of morpholino(phenyl)methyl] benzamide (MBB) with active-
site amino acids of 2YAT receptor
Figure 12: Interaction details of N-phenyl(pyrrolidin-1-yl)methyl acetamide with active-site
amino acids of 2 YAT receptor
Figure 13: Interaction details of N-phenyl(pyrrolidin-1-yl)methyl benzamide (PBB) with
active-site amino acids of 2YAT receptor
Figure 14 : Interaction details of tamoxifen with active-site amino acids of 2YAT receptor
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An original chain of kaempferol Mannich compounds was obtained by combining the
Mannich reaction with the substituted amine (Scheme 11). The amino methylation of
kaempferol occurred primarily in positions [C-6 and C-8] of the A-ring. For the main
substitution reaction, the experiential and computational results point to a hydrogen bond-
assisted SN2 mechanism. An anti-proliferative test on HeLa, HCC1954, and SK-OV-3 are
three human cancer cell lines that have already been studied. The number of chemicals
studied displayed intermediate to powerful cytotoxicity in opposition to the three cells of
cancer; compound 75e, which is identical to the control sample cisplatin, had specific anti-
proliferative action against HeLa cells. Kaempferol molecules and their lanthanide
compounds emit blue-green fluorescence depending on the solution conditions (neutral,
acidic, or alkaline). These findings are predictable to aid future research into the synthesis and
implementation of various nitrogen-containing flavone derivatives, particularly with primary
amines[45].
Scheme 11 - Preparation of kaempferol derivatives
4- Anti-malarial activity
The in vitro activity of the new antimalarial Mannich bases (2-hydroxy-1,4-
naphthoquinone-4-hydroxyaniline hybrid) was developed, produced, and assessed (Scheme
15). The measured dosage (1 mg/mL), was significantly lower than that of the reference
treatment, chloroquine (0.1 mg/mL). All of the synthesized compounds showed in vitro
efficacy versus antimalarial chloroquine-sensitive descent (P. Falciparum RKL-2) compounds
with morpholinyl 76f (IC50 is 0.391 g/mL) and propyl 76a (IC50 is 0.453 g/mL)
substitutions. On the other hand, they are far more effective than the rest of the manufactured
analogues. Compound 76f (IC50 is 0.993 g/mL) was reported to be more efficient against the
resistant strain (RKL-9) of plasmodium falciparum than compound 5a (IC50 is 2.92 g/mL).
These chemicals were also less effective against the resistant strain than chloroquine (IC50 is
0.299 g/mL). Compounds with the least saturated heterocyclic moiety (morpholinyl, 76f) or
alkyl groups (n-propyl, 76a, and isopropyl, 76b) show a more powerful antimalarial efficacy
than those substituted for bulky aryl (phenyl, 76e) or alkyl (diisopropyl, 76c, and n-butyl,
76d) moieties. Furthermore, because all the compounds showed promising drug-like
properties, it appeared that a plausible link between drug-likeness and antimalarial activity
existed [46].
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Figure 15 :Synthesis of compounds 5a-5f
The Mannich reaction was used to successfully add secondary amines to the chalcone
compounds (Scheme 12), and the spectroscopic investigation confirmed this. The antimalarial
efficacy of the created compounds was examined in vitro versus the Plasmodium falciparum
3D7 strain (sensitive CQ); all of the compounds showed high activity. Molecular docking was
used to analyze the interactions with the binding site of the created compounds in place of the
wild type (plasmodium falciparum dihydrofolate reductase thymidylate synthase (Pf-DHFR-
TS), PDB ID: IJ3I), and quadruple mutant (PDB ID: IJ3K and Pf-DHFR-TS). Together, the
wild and mutant Pf-DHFR kinds form various hydrogen bonds and interactions with the side
chains of Cys15, Asp54, Ala16, Leu164, Tyr170, and Met55 and exhibit acceptable drug-like
behavior that is beneficial to membrane permeability. According to the molecular docking
results, compound 78b has the lowest energy and the maximum number of hydrogen bonds,
indicating that it has the best antimalarial activity[47].
Scheme 12 - Reagents and conditions of synthesis
5- Anti-viral activity
A unique chain of N and O-Mannich bases of diaryl-dihydropyrimidines was synthesized
utilizing conventional and microwave methods, synthesized, and tested against various viral
strains (Scheme 13), reagents, and conditions of synthesis. An intermediate chalcone was used
to add the aromatic groups at 4 and 6-positions right away, and the title compounds were
created by combining the chalcone with ciprofloxacin's piperidinyl ring. Some chemicals
exhibit strong antiviral activities against certain virus strains. Hepatitis B (EC50 = 1; SI =
300), cowpox (EC50 = 15.1; SI = 19.9), and vaccinia (EC50 = 20.9; SI = 14.4) were the three
virus strains against which compound 81f demonstrated activity. Compound 81a showed
significant restrained action versus influenza A (H1N1) California strain EC50-0.52M; SI-94,
which was equivalent to ribavirin EC50-5.1M; SI-63 (48).
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Scheme 13 - Reagents and conditions of synthesis
6- In the field of agriculture
Mannich reaction synergy with phenolation pre-treatment was applied to amination
biorefinery technological lignin to improve a modern, lignin-based, highly effective nitrogen
fertilizer (Scheme 14): reagents and conditions of synthesis. Following that, a leaching
experiment in a soil column was used to study the nitrogen emission from aminated lignin's
action in the soil. The number of active sites in lignin increased significantly after
phenolation, from 2.91 mmol/g to 8.26 mmol/g, according to the findings. Furthermore, in
this study, the amount of nitrogen in aminated lignin was significantly dependent on the type
of amination reagent rather than the number of reactants. Lignin that has been amined and
contains a higher quantity of nitrogen (10.13 %) and a low C/N rate (6.08) may be produced
under ideal conditions. Furthermore, with the APL that was created in this study, the
mechanism through which nitrogen is released into the soil is perfect, which is notable. As a
result, it has been thought that these aminated lignin derivatives 83 might be utilized to make
a variety of lignin-based, high-efficiency nitrogen fertilizers[49]
Scheme 14: Chemosynthesis scheme of the aminated lignin with high nitrogen content (A)
The phenolation of lignin; (B) The Mannich reaction of phenolated lignin under alkaline
condition.
7- In the field of industry
The iron corrosion inhibitors N,N'-dimethylenephosphonyl aminopropylmethylsilanol
(DPMS) and N,N'-dimethylenephosphonyl aminopropyl dimethylsilanol (DPDS) were
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produced using a simple Mannich technique (Scheme 15), reagents and conditions of
synthesis. N,N'-dimethylenephosphonyl propyl amine (DPPA) was too well chosen to be
examined with the help of these two silanes to investigate the relationships between corrosion
inhibition characteristics and molecular configuration. The number of phosphonyl groups in
each of these three compounds is the same, but the number of hydrolysis groups is different.
Electrochemical methods were used to evaluate the iron's corrosion inhibition characteristics
in sulfuric acid solutions. The effect of these three inhibitors on iron corrosion grew at first
and then declined when the concentration reached its highest value, according to
electrochemical data. The chemical evaluation of the absorption operation was based on the
equilibrium constant and standard Gibbs free energy. Furthermore, DPMS outperformed
DPDS and DPPA in terms of corrosion inhibition. To explain the differences between these
three inhibitors, a concept of their organization on the surface of the iron was proposed [50].
Scheme 15 - On the oxidized ionophore (a) DPPA, (b) DPDS, and (c) DPMS molecules self-
assemble and reinforce each other
A corrosion inhibitor was created with nitrogen atoms, and a conjugated link was found in
this compound. (Scheme 16). Reagents and conditions of synthesis, and the final product was
dubbed multi-Mannich base (MBT 84) because it was synthesized under the optimal
circumstances of the orthogonal test results. In a solution of CO2-saturated steel with a [3 wt%
NaCl] concentration, the corrosion inhibitor has an inhibitory effect, which was investigated.
The corrosion rate was 0.0446 mm/a with a 90.4% corrosion inhibition rate. MBT is a
blended corrosion inhibitor that primarily demonstrates cathode suppression capacity,
according to electrochemical and adsorption theory studies. The Langmuir adsorption
isotherm governs the MBT adsorption on the surface of steel sheets. It can self-adsorb on the
roof of N80 steel sheets, giving it a good corrosion inhibitor. An atomic force microscope was
used to characterize the surface of the N80 steel sheets (AFM). The results show that the
MBT-added N80 steel sheet differs considerably from the blank control group; the steel
sheet's surface is rather smooth, showing "that MBT forms an effective protective film on the
N80 steel's surface", preventing the steel sheet from rusting[51].
Raoof and Sadiq Iraqi Journal of Science, 2022, Vol. 63, No. 12, pp: 5086-5105
Scheme 16 - The synthesis of MBT (84)
8. Conclusion
Mannich bases and their derivatives are shown to have robust and diversified actions, as
explained by the structure of the work described in this paper. This review examined several
biological functions of Mannich base derivatives in the current scenario. Mannich bases, it
might be inferred, offer tremendous biological potential that has yet to be realized. In addition
to endorsing the researchers' efforts to develop new Mannich bases bearing heterocyclic
compounds in order to be widely used for industrial and agricultural purposes.
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