“CESIUM CARBONATE as a mediated inorganic base in some

organic transformations”

Seminar submitted to
Faculty of Pharmacy
The Maharaja Sayajirao University of Baroda

Guided by Submitted by
Dr. Prashant murumkar Poonam. P. Jamwal

Faculty of Pharmacy
The Maharaja Sayajirao University of Baroda
Vadodara-390001

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 INDEX

SR.NO. DESCRIPTION PAGE

NO.
1 Introduction 3

2 Chemical properties 4

3 Applications of cesium carbonate in organic synthesis 6

4 Conclusions 37
IN
T R
O 5 References 38 D
U C
TI O
N
Caesium is a metal denoted as Cs in the periodic table with the atomic number of 55.
• It is one of the most reactive metal.
• It is found in the s-block which is because the outermost electron of Caesium is in s-orbital.
• Caesium is a soft, shiny-gold alkali metal which is having a melting point of 28.5 °Celsius
(83.3 °Fahrenheit), which is one of five rudimentary metals that can become liquid at room
temperature.
The Discovery of Caesium:
• Chemists such as Robert Bunsen and Gustav Kirchhoff who discovered cesium in 1860
when investigating the spectrum in mineral water.
• The name designated from the Latin word "caesius", which denotes "sky blue".
• This defines to the color of the line that the spectrum the chemists saw when they were
discovering the spectrum.

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• This later on tipped them of a new element caesium.
Possessions of Caesium:
• Samples of cesium are kept in sealed containers, under an inert liquid or gas or in a vacuum.
The element is highly reactive that it would react with water and air.
• Cesium instinctively ignites in air which describes that it is pyrophoric in nature.
• It is the one of the supreme alkaline of all the elements and oxidizes explosively with water
to give rise to caesium hydroxide (CsOH), which is a strong base in nature.
• Allen scale of electronegativity indicates cesium as the most electronegative element.
• It is drawn into fine wires because of its softer-ductile character.
• Cesium-133 is the only one isotope of cesium that occurs naturally. Although there are
numerous radioactive isotopes that has been produced.
• Caesium atom has an electron resonance frequency of 9,192,631,770 cycles per second.

Natural abundance of Caesium:

• Cesium is anticipated to be occurred at a large quantity of 1 to 3 parts per million on the

Earth's crust, which is an average occurrence for a chemical element.

• It is fundamentally found in the minerals of Pollucite and Lepidolite. Pollucite is a mineral

that occurs in excessive quantities at Bernic Lake which is in Canada and also in USA which
are the sources the element is formulated. Though it is commercially produced as a by-
product of lithium production.

Chemical Properties: -

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There are many base catalysts, such as alkali carbonates, hydroxides and fluorides. One
of the most important alkali carbonates is cesium carbonate. It has acquired considerable
attention nowadays in organic synthesis due to some unique properties of cesium ions, such
as its large cationic radius and the ease of its solvation in numerous organic solvents. The Cs+
ion is more deshielded.
cesium carbonate is a well-balanced base that is considered a mild base, and this unique
feature is highly essential for selective deprotonation as well as its suitability for the base
catalysed reactions, in which it has basic character weaker than hydroxides or alkoxides and
stronger than other carbonates.

[1] Blum has reported the effect of cesium ions in organic synthesis; these ions are different
than the other alkali metals in composition.
This unique potential distribution, due to neighbour and next neighbour interactions,
described by these surfaces, accounts for the performance of cesium ions both in terms of
synthetic efficiency and structure modelling ability.

[2] Dijstra et al. reported an assessment of the causes of the cesium effect.
The experiments indicate that cesium salts, in particular, the carboxylates, are nearly or
completely dissociated in free ions or solvent-separated ion pairs in dipolar aprotic solvents
like dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) solvate cations more
effectively than anions.

[3] Ostrowicki et al. reported a review on the effect of cesium ions (CsF, Cs 2CO3 and CsOH)
on the ring closer reactions in order to synthesize medio- and macrocyclic compounds.

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The use of CsOH in the C–C bond formation reactions improved the yields of the products as
compared to the use of NaOH. Cs2CO3 was used in the C–N bond formation reactions
(synthesis of aza maerocycles), which lead to higher yields in case of the synthesis of large
rings.
The use of cesium salts of aromatic carboxylic acids is effective in the formation of C–O
ether bonds, in which the products were obtained in good yields.
Cesium salts have been also used in different concentrations in the synthesis of heteroaryl,
arene and aliphatic lactones as well as C–S bond formation reactions.

[4] Galli has also reported a review on the cesium ion effect in the synthesis of macrocyclic
compounds, these experimental results arise from nucleophilic displacement reactions run
in dipolar aprotic solvents such as DMF with anionic nucleophiles, generated in situ from the
parent acid by an alkali metal (M) carbonate as the heterogeneous base.
The effect of cesium salts on the intermolecular, intramolecular and cyclization reactions was
also reported.

Applications of cesium carbonate in organic synthesis

Alkylation and arylation of carbon, nitrogen, oxygen and sulfur
1) Alkylation of ketones and amides with primary alcohols

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The α-alkylation of ketones and amides is an important transformation for C-C bond
formation and has widespread application in the synthesis of biologically active compounds.
Iridium complex bearing a functional bipyridonate ligand is a highly effective catalyst for
the α-alkylation of ketones with primary alcohols under environmentally benign and mild
conditions of Cs2CO3. The α-alkylation of acetophenone (2) with benzyl alcohol (1) was
reported by Li and coworkers as a model reaction by using a different iridium catalyst on the
reaction yields. The reaction proceeded in the presence of Cs 2CO3 (0.1 equiv per substrate) at
110 °Celsius, and performed in tert-amyl alcohol under reflux under an air atmosphere to
give the α-alkylated product 3 in different yields (Scheme 1)

Guo and coworkers have reported the α-alkylation for N, N-dimethylacetamide(4) with
benzyl alcohol(1) employing iridium catalysed complex as a precatalyst and different types
of alkali bases to form N, N-dimethyl-3-phenyl propionamide (5). the reactions were
carried out under various conditions with low yield (3%) in the case of using cesium
carbonate (Scheme 2)

2) Carbon arylation of alkyl aromatics

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Cesium carbonate has relatively high solubility in DMF and appears to act as a good base for
the abstraction of protons from alkylarenes. Alkylarenes having relatively strong electron-
withdrawing substituents or alkyl substituted heteroaromatic compounds are similarly
arylated. 4-Alkylnitrobenzenes can effectively react with aryl bromides at their benzylic
position in the presence of catalytic amounts of Pd(OAc) 2, PPh3, and Cs2CO3 as a base to give
the corresponding di-arylated product 8 (Scheme 3)

3) Arylation of heterocyclic rings

Liegault and coworkers have found that under modified conditions of Cs 2CO3, Pd(OAc)2, P(t-
Bu)2 Me and HBF4 in mesitylene, good yields of C4 arylation could be achieved. For example,
5-chloroxazole substrates bearing either an aryl or an isobutyl group at the C2 position &
direct arylation at C4 with various electron-rich and electron-poor aryl bromides to provide
the corresponding products in good yields. 5-Chloro-2-phenyloxazole (11) also participated
well in these transformations to provide the C4-arylated oxazoles in 58 % yield (Scheme 4)

4) Direct arylation and aza-benzylation

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Laha and coworkers have introduced an optimized condition for the reaction of sulfonanilide
(12), 2-bromobenzyl bromide (13) and a reagent blend consisting of Pd(OAc) 2, PPh3, and
Cs2CO3 in refluxing 1,4-dioxane for 16 h, which afforded compound 14 in good to excellent
yield (Scheme 5)

Zhou and coworkers have reported an approach for C–N and C–C bond formations by using
an electron-deficient N-benzoyloxyamine as an efficient electrophilic nitrogen source and N-
tosylhydrazone as a nucleophilic coupling partner in the formation steps in the presence of
palladium-catalyzed/Norbornene and Cs2CO3 as a base. The 1-iodo-2-methylbenzene
(15), N-benzoyloxyamine (16), and N-tosylhydrazone (17) were used as substrates for
ortho-Amination/N-tosylhydrazone insertion reaction. The reaction mechanism showed
cesium carbonate base was the main base for conversion of N-tosylhydrazone to the (1-
diazoethyl)benzene and benzoyl elimination group (Scheme 6)

5) Aza-alkylation of secondary amines

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Steven and coworkers reported that the inorganic bases that afforded good yields and better
conditions. these conditions were further improved by using cesium carbonate which effected
rapid and high yielding formation of enamides 21 from secondary amine 19 and
trichloroethane (TCA; 20; Scheme 7)

The catalyzed coupling of gem-dibromovinyl phenylacetamide (22) with nitrogen

nucleophiles such as N-tosylbenzyl amine caused indirect generation of the ynamides (23)
within 3 h. The latter (23) underwent a base-promoted intramolecular hydroamination to
afford the N-acetyl-2-amidoindole (24). this reaction was carried out in the presence of a
condition that contains 4 equivalents of Cs2CO3 in THF at 80°C (Scheme 8)

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An aryl halide can be coupled with 1-aza-15-crown-5 (25) using palladium ligand in
toluene in the presence of Cs2CO3 as a base to give good yields of N-aryl-aza crown ethers
26 (Scheme 9)

6) Aza-alkylation of bicyclic β-lactam

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N-Alkylation and N-arylation reactions by using a bicyclic β-lactam using silica supported
cesium carbonate were reported by Manisha and Kaushik. They used Silica was a solid
support for Cs2CO3 on the reaction to give the desired product. This is because of the
hygroscopic nature of Cs2CO3, which was made poorly hygroscopic by absorbing on silica.
The method provides easy work up and quantitative yield of versatile N-alkylated and N-
arylated -β- lactam in less reaction time. The N-alkylation and N-arylation of β-lactam
with alkyl and aryl bromide 27 was carried out to yield the desired alkylated and arylated
products 28 (Scheme 10)

7) Oxygen and nitrogen arylation of amino alcohols

The selectivity of N-or O-arylation can be achieved when different ligands are used via Cu-
catalyzed cross-coupling reactions. The diketone ligand (L1) causes selective formation of
the N-arylated product 29 in DMF at RT, whereas the 1,10-phenanthroline ligand (L2)
promotes selective O-arylation product 30 in toluene at 90°C. Both of the two reactions
cannot proceed without Cs2CO3 (Scheme 11)

8) Alkylation, acylation of nitrogen and sulfur in pyrimidinthiones

A reaction of alkyl or acyl halides and 1.1 equivalent of Cs2CO3 in anhydrous DMF at
room temperature afforded S-alkyl and N3-acyl derivatives. Alkyl and acyl derivatives of
3,4-dihydropyrimidin-2(1H)-thiones 32 and 33 were synthesized in the presence of Cs 2CO3
(Scheme 12)

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9) Alkylation of phosphite

The synthesis of extremely hindered phosphonates otherwise difficult to prepare using

conventional methods was achieved by using mild Cs 2CO3 and at ambient reaction
conditions. Dibenzyl phosphite 34 united with ethyl bromoacetate affording the
substituted phosphonate 35 in excellent yield (Scheme 13)

alkylation reaction was developed using an inorganic base in DMSO as a polar aprotic
solvent. Cesium carbonate was chosen as the inorganic base among other alkali carbonate
bases; the conversion percent of the alkylated product 37 increased when the concentration
of cesium carbonate increased. This may be related to cesium carbonate solubility (Scheme
14)

10) Arylation of sulfur atoms

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Palladium-catalyzed C-S bond formation firstly reported by Migita lead to other C
heteroatom bond formations. The first reaction is a pd-catalyzed coupling with an auxiliary
ligand used to speed up the reaction kinetics to form a carbon–sulfur bond and concomitant
hydrolysis of the nitrile functional group to amide. The second reaction is aromatic
nucleophilic substitution of fluorine with 2-methylimidazole promoted by cesium carbonate
(Scheme 15)

11) Intramolecular nitrogen and oxygen arylation

1,4-Benzoxazine-2-carboxylate (43a) was synthesized from the heterocyclization of methyl

3-(benzylamino)-2-(2-bromo-4-chlorophenoxy)acrylate (42) in boiling DMF containing
cesium carbonate and CuI (Scheme 16)

The C–O bond forming reaction between aryl bromides/iodides and aliphatic alcohols to
produce aromatic ethers using CuI/8-hydroxyquinoline and Cs2CO3 as a base was applied
by Kundu and Nayak. The Mannich adduct 44 underwent intramolecular etherification for
carbon–oxygen bond forming reaction between alcohols and aryl bromides to form O-
heterocycle 45 (Scheme 17)

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The diepoxide 46 underwent intramolecular cyclization reaction upon treating with excess
Cs2CO3 in methanol giving the desired two-ring system 47 (Scheme 18)

12) Alkylation reaction using aziridine ring

The enantioselective alkylation of tert-butyl indanone carboxylate 48 with aziridine
electrophiles 49a in aqueous Cs2CO3 solution and quinoline catalysts gave good yields of the
products 50. By modifying the mesityl protected aziridine 49a to the o-
(trifluoromethyl)benzenesulfonyl-substituted aziridine 49b, an increase in the reactivity with
complete conversion to alkylation adduct 50b in 48 h at 0 °C. It also exhibited excellent
enantioselectivity (94 % ee). Applying various cinchona alkaloid-derived phase-transfer
catalysts (a–d), catalyst (d) bearing the bulky adamantoyl ester was found to be the most
selective affording the alkylation adduct 50b in good yield, and in 94 % ee when the reaction
was conducted at 0 °C with 50 % aq. Cs2CO3 as the base (Scheme 19)

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13) Biaryl coupling reactions
Donati and coworkers studied the effect of Na2CO3, K2CO3and Cs2CO3 in dioxane, THF, and
DMF on biaryl coupling reactions. The selectivity of the reactions directly depends upon the
solvent polarity and the base dissociation. The use of easily dissociated cesium carbonate in
THF lead to formation of phenanthridinone 52 and/ or 53 in a significant increase in the
yields from amide 51 (Scheme 20)

Six-membered annulation reaction

1) Formation of carbon anion and six membered
The anionic sequences, the first step in a carbon–carbon bond formation through nucleophilic
substitution reaction, was performed in basic medium using different types of bases. Cs 2CO3
was used in the condensation of a methylene active compounds with unsaturated ester (54
and 56) to give the annulated esters 57 (Scheme 21)

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Cs2CO3 as an alkali base has been widely used as an excellent base for a variety of
transformations in organic synthesis. for example, in the synthesis of benzo[c]chromen-6-
one derivatives via Michael addition-intramolecular, Aldoloxidative aromatization reactions
between substituted 2-hydroxychalcone (58) and b-ketoesters (Scheme 22)

2H-Chromenes and 4H-chromenes were synthesized from the same starting material just by
choice of base. It was found that chromenes (4H, 2H) were observed when benzyl bromide
derivative 60 was treated with cesium and potassium carbonate and tetrahydrothiophene.
Using K2CO3 as a base under the optimal conditions gave the 2H-chromenes product 61 in
high yields. 4H-Chromene derivative was obtained as minor product. While on using Cs 2CO3
instead of K2CO3, the reaction proceeded to give 4H-chromene as a major product. The
experimental results: 2H-chromene was transformed into 4H-chromene easily in the presence
of Cs2CO3, but the same transformation proceeded very slowly in the presence of K 2CO3
(Scheme 23)

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Subhadip and coworkers treated 1,3-cyclohexanedione with ethyl acrylate in the presence of
different bases and solvents. Cs2CO3 in DMSO was optimal for the Michael reactions
(requiring nearly for the first step) and alkylation (requiring typically for the second step) to
yield ethyl 3-(2-((2-bromoallyl)oxy)-6-oxocyclohex-1-en-1-yl)propanoate (63) (Scheme
24)

2) Combination of Cs2CO3 with N-heterocyclic carbene organocatalysts

The combination of Cs2CO3 with N-heterocyclic carbene (NHC) organocatalysts that allow
for the development of highly selective and effective reactions. Zhu and coworkers have
treated 1,3-dicarbonyl substrates with β-ketoesters containing various ester groups and
examined the regioselectivity of the terminal groups through changing the NHC with cesium
carbonate in the formed product 65 (Scheme 25)

3) Thien-annulationandbenz-annulation
An intramolecular rearrangement initiated by Cs2CO3 gave 67. First, substituents on the
arylalkenoyl 66 with electron donating groups showed better reactivity than those with
electron-withdrawing groups. Various kinds of functional groups such as OMe, NO 2, F, Cl
and Me, were well-tolerated. Naphthyl, heteroaryl, and ferrocenyl substrates were also
productive delivering benzo[b]thiophenes 67 (Scheme 26)

17
In Scheme 27, Initially, deprotonation at one of the methylene groups of the dithiolane
moiety triggered the ring-opening reaction to generate the thiolate anion which cyclized to
form thiophene intermediate through a sequential intramolecular heteroannulation and
protonation. Subsequently, Michael addition of the anion of ethylcyanoacetate to the double
bond of II followed by protonation formed intermediate III. Deprotonation of III triggered
an intramolecular nucleophilic displacement of the thioether, VIII which underwent ester
elimination followed by oxidative aromatization to produce the desired benzo[b]thiophenes
(67)

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 4) Fused five-membered annulation reaction
Kelly and Andrew stated that the choice of base had a complex influence on both reaction
efficiency and diastereoselectivity and switching from Cs 2CO3 to other bases lowered the
diastereoselectivity of the alkylation process. Cyclization and alkylation reaction of tert-
butyl (1-methyl-4-oxocyclohexa-2,5-dien-1-yl) malonate (68) was taken as an example for
prove the influence of both Cs2CO3 and methyl iodide (Scheme 28)

for optimization of indole synthesis (71) by reaction of 2-iodoaniline with methyl

acetoacetate. It was found the best conditions and yield were use of binol as additive in the
presence of cesium carbonate as base in DMSO at 50°C for 4 h (Scheme 29)

synthesis of highly substituted cyclopentadiene-fused chromones 74 (Scheme 30) through a

palladium acetate and Cs2CO3 -catalyzed cascade sequence was reported by Wang and
coworkers.

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 Miscellaneous reactions
1) Intermolecular Stetter reactions
Dieter and coworkers reported a enantioselectivity reaction parameters by screening different
chiral triazolium-based precatalysts (NHC) and alkali cations of the carbonate base. The
reaction of benzaldehyde and chalcone 76 to form benzoin 77 was investigated and it was
found Cs2CO3 in THF led to an increased enantioselectivity (Scheme 31)

2) Aldol reactions
Aldol reaction is a powerful means of forming C–C bonds between aldehydes and ketones in
ethanol. Problems such as the substrate containing ester, halide, epoxide, and sulfonate or the
severe self- condensations of alkyl aldehydes bearing a-hydrogen atoms cannot survive such
conditions. Bo and Chunbao have used different alkali carbonate bases and different solvents
to study the optimum reaction conditions of epoxide 78 and p- nitrobenzaldehyde (79)
(Scheme 32)

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3) Suzuki coupling reactions
Bedford and coworkers prepared a series of palladium complexes to facilitate Suzuki
coupling reactions of aryl bromide (81) substrates with phenyl boronic acid (82) using
cesium carbonate as a base and dioxane as a solvent (Scheme 33)

4) Aza-Henry (or nitro-Mannich) reactions

Palomo and coworkers presented a new asymmetric aza-Henry technology with broad
substrate scope based on the use of α-amidosulfone (84) and phase-transfer catalysis (PTC).
quaternary ammonium salts and inorganic bases (e.g., Cs 2CO3, CsOH.H2O, K2CO3) to find
optimum reaction conditions for α-amidosulfone and nitromethane reaction in toluene as
solvent. Cesium hydroxide monohydrate was found to be the most efficient base and best
conversion yield and the rest yielded approximately similar conversion percents (Scheme 34)

5) Cross-coupling reaction
The cross-coupling of p-iodotoluene (89) with phenylboronic acid (87) under atmospheric
pressure of carbon monoxide (88) catalyzed by palladium complexes was reported by
Ishiyama and coworkers. The yields of 4-methylbenzophenone (90) were mostly influenced
by the base and solvent employed. The best results were obtained with dioxane and Cs 2CO3
(Scheme 35)

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The reaction of 2,2-dibromovinyl)-benzene (91) and potassium (p-tolylethynyl)- tri-
fluoroborate (92) (2 equiv.) in the presence of palladium salt and Cs 2CO3 as a base gave the
cross-coupling product (93). Kabalka and coworkers enhanced the utility of the reaction for
preparation of a variety of potassium alkynyl trifluoroborates via deprotonation of 1-
alkynes followed sequentially by transmetallation, then in situ treatment with KHF and 1,1-
dibromo-1-alkenes (Scheme 36)

Primer and coworkers discussed the role of a base in cross-coupling reactions and preparation
of alkyl derivatives 96. They reported that Cs2CO3 was the best base for maximizing
productive cross-coupling while limiting side reactions. The precise role of the base is not
defined but rate studies reveal that BF3 appears to inhibit the reaction. Its removal by an
added base allows reactions to proceed to completion (Scheme 37)

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6) Crossover transfer hydrogenation
cesium carbonate in the crossover transfer hydrogenation catalyst system
[Ir(COD)Cl]2/dppp/Cs2CO3] may be due to its action in deprotonation. It was used in the
reduction of α, β-unsaturated ester 98 into the saturated carbonyl analogs 100 (Scheme 38)

The formation of C–C/C–O biaryl coupling of benzo[d]oxazole (1,3-azole) (101) and

naphthalen-2-yl pivalate (102) took place in the presence of Ni ligand catalyst to yield the
corresponding heterobiaryl (naphthalen-2-yl benzoxazole) in good yield. The reaction was
assumed to proceed via formation of mononuclear Ni(II) complex; then, a stoichiometric
reaction between the formed complex and benzoxazole provided naphthalen-2-yl
benzoxazole (103). The rate of the reaction was accelerated by the action of Cs 2CO3 which
indicates the interference between cesium carbonate and the nickel complex in the
intermediates (Scheme 39)

7) Etherification reactions
The relatively mild conditions, short reaction times, and high product yields by using Cs 2CO3
as a base in the etherification process. For example, the use of Cs 2CO3 as a basic catalyst
improves the reaction of phenol derivatives 104 with alkyl and aryl bromides to yield
ether derivatives 105 (Scheme 40)

Cesium carbonate and DMF were considered the most favorable base and reaction medium
for synthesis of b-aryloxyl acrylates through a Wittig reagent. The importance of Cs2CO3 in
the reaction of phenol, Wittig reagent and acetyl chloride may be due to the formation of the
desired product 109 in high yield (Scheme 41)

Esterification reactions

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Cs2CO3 and DMF were considered the most favorable base and reaction medium for synthesis
of β-aryloxyl acrylates through a Wittig reagent. The importance of Cs 2CO3 in the reaction of
phenol, Wittig reagent and acetyl chloride may be due to the formation of the product 109 in
high yield (Scheme 41)

8) Esterification reactions
Although esterification was considered a simple reaction, it often involves unexpected
problems. For example, other functional groups may be sensitive to acidic or basic conditions
or the reaction time is very high. The use of alkyl halide in the reaction with carboxylic acids
110 in a polar solvent and presence of Cs 2CO3 as a base are considered for ester production
111 (Scheme 42)

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Another esterification process was reported by Qrareya and coworkers using imidazolium
salts. The salt 112 acted as a sulfating agent for the in-situ preparation of trifluoroethyl
sulfates (113) in a basic medium from Cs2CO3 at different concentrations (Scheme 43)

9) Phosphination reaction
Treatment of 1-alkynylphosphines (114) with diphenyl phosphine in the presence of
catalytic amounts of copper(I) iodide and different concentration of Cs2CO3 in DMF yielded
1,2-bis(diphenylphosphino)-alkyene derivatives (115). The product was isolated as
disulfide 116. The mechanism of the phosphination required basic medium from Cs 2CO3 to
abstract the hydrogen of the formed ligand and then attack 1-alkynyl phosphine (Scheme 44)

10)

Birding reactions
Diacetylamido-bridged p-tert-butylcalix[7]arenes (118 and 119) were synthesized regio-
selectively by a base-promoted alkylation employing Cs 2CO3 of p-tert-butylcalix[7]arene
(117) with dichloro bridging agents [ClCH2CONH(CH2)nNHCOCH2Cl, n = 2 and 3] (Scheme
45)

25
11) One-pot three-component reactions
condensation of 2-(4-methylphenylethynyl)-1H-indole (121) with epichlorohydrin (122)
and sodium azide was the main target of Arigela and coworkers. The three components
were react both in the absence and presence of base Cs2CO3, changing the nature of the
solvent from non-polar to polar and changing from traditional heating to a microwave
method. (Scheme 46)

26
The one-pot three-component reaction between bis(pinacolato)diboron (B2(pin)2) (129), α, β-
unsaturated aldehydes 126, and heterocyclic salt 127 as the NHC pre-co-catalyst and amine in
a solution containing Cs2CO3 as a base gave 1,2 as a minor product(130) and 1,4 as a major
product 131 of the selective addition to α, β-unsaturated aldehydes. However, removing the
amine and just having the NHC catalyst did not decrease the reaction rate and the 1,4
selectivity was unaffected (Scheme 47)

The synthesis of fused tetracyclic quinolones 135 was developed via a Ugi-variant reaction
and Pd-catalyzed bis-annulation in a solution of acetonitrile containing Cs2CO3 (Scheme 48)

synthesis of pyrazolo[1,2- b]phthalazine-5,10-diones (137) via the three-component

reaction of aldehydes, malononitrile and phthalhydrazide (136) is reported by Maleki and
coworkers. The main catalyst in the conversion process was the Cs2CO3 supported on
hydroxyapatite-coated Ni0.5Zn 0.5Fe2O4 (Scheme 49)

27
12) Nucleophilic substitution
The reaction of N-propyl mercaptoacetamide (138) and 3-chloro-2-nitropyridine (139)
proceeded affording the cyclized pyrido[1, 4]thiazinone (141) product in good yield. bases
such as Cs2CO3 showed good catalytic efficiency in refluxing acetonitrile. (Scheme 50)

Cs2CO3 proved to be the most powerful among bases that was tested in nucleophilic
substitution. Other alkali carbonates resulted in lower yields. Organic bases such as
triethylamine were far less effective. Catalytic amounts of Cs 2CO3 resulted in poor
conversions even with prolonged reaction. The following reaction was efficient enough to
allow multiple C–S bond formations in one pot. The dithiol 143 underwent the nucleophilic
substitution reactions with 2.4 equivalent of methyl 4-nitrobenzoate (142) and Cs2CO3 to
provide product 144 (Scheme 51)

28
Lee and coworkers have examined that the mono nucleophilic substitution reaction was
greatly increased by adding Cs2CO3 in THF at RT, and thus 2-chloro-3-phenoxy 1,4-
naphthoquinone (146) was obtained in excellent yield without any side-product from the
reaction of phenol and 2,3- dichloronaphthoquinone (145) (Scheme 52)

The selective methylation and carboxymethylation by using the electrophilic reactivity of

dimethyl carbonate (DMC) for the ambient nucleophile phenyl hydrazine were investigated
by Rosamilia and coworkers. Changing the reaction conditions, especially the basicity of the
medium, gave reaction selectivity at either or both of the nucleophilic centers. Cs 2CO3 as a
basic catalyst in the medium led to formation of both carbazates (148 and 149) and the
reaction rate progressed more slowly (Scheme 53)

The regioselective nucleophilic substitution reaction of ethyl 2-benzoyl-1-

chlorocyclopropanecarboxylate (150) and salicylic aldehyde in CH3- CN in the presence
of various bases at room temperature was investigated by Zhang and coworkers. common
inorganic bases used readily promoted the reaction and gave the desired product 151 and
Cs2CO3 was the best choice among all the bases used, and the reaction gave high yield (151)
after 2 h. (Scheme 54)

29
13) Varied reaction
The reaction of oxazolone 152 with ethyl isocyanoacetate (153) in the presence of bases and
Cu catalysts was selected for the formation of bisoxazole derivatives. when 152 was reacted
with 153 in the presence of Cs 2CO3 as base and DMF as a solvent to give 154 and/or 155.
reaction conditions for the formation of only one product oxazole 154 or bisoxazole 155 was
achieved through controlling the reaction temperature and time. (Scheme 55)

30
Intramolecular cyclization of 154–155 is much more efficient in the presence of Cu catalyst
(CuI/Cs2CO3) giving bisoxazole 155 in high yield and purity (Scheme 56)

The tandem cyclization between 2-iodobenzoic (156) acid and β-diketone 157 was
performed in the presence of CuI (10 mol%) and Cs 2CO3 (2.0 equiv) as a base in DMF to
prepare the isocoumarine 158. This condition afforded a good yield from the desired
isocoumarine. base can prompt this reaction to proceed very well, and copper salts are not
needed at all. (Scheme 57)

31
Cycloaddition reactions
1) [5 + 1] Cyclization reactions
A synthesis of aminoquinolinederivatives 161 by a Pd-catalyzed [5 + 1] cascade
annulations of isocyanides with functionalized enaminones was given by Yang and
coworkers. They are focused on the research of cascade reactions based on isocyanides to
construct different molecules as well as complex heterocycles. After screening of reaction
conditions, Cs2CO3 was found to be the best inorganic additive base for the reaction of 3-((2-
iodophenyl)amino)-5,5-dimethylcyclohex-2-enone (159) and tert-butyl isocyanide (160;
Scheme 58)

32
2) [4 + 2] Cyclization reactions
The coupling of N-heterocyclic carbenes (NHCs) and Cs2CO3 could promote a host of
reactions such as ring opening, polymerization, homoenolate formation, and trans
esterification besides the widely known benzoin condensation and Stetter reaction. The N-
heterocyclic carbene NHC-catalyzed formal [4+ 2] synthesis of spirocyclic oxindole-
dihydropyranones 164 from the reaction of α, β-unsaturated ester 162 with isatin
derivative 163 was achieved in toluene containing Cs2CO3 as a base and carbene catalyst at
20°C for 48 h. Under the basic reaction conditions, no formation of the desired product 164
was observed in the absence of an NHC. With imidazolium A as the NHC precatalyst, 164
was formed in 69 % yield (Scheme 59)

33
synthesis of 2-arylphenols were studied by He and coworkers. They used 1-phenylpenta-3,4-
dien-2-one (165) and ethyl 3-oxobutanoate (166) as substrates. They optimized that the
reaction of 165 and 166 proceeded under the promotion of an equivalent amount of Cs2CO3 to
generate ethyl 6-hydroxy-2,4- dimethyl-[1,10 -biphenyl]-3-carboxylate (167) in CH3CN at
80°C for 4 h (Scheme 60)

intermediate 170 then underwent protonolysis and isomerization to afford 171. Then, an
intramolecular cyclization of the last product happened to give the target indolyl imidazole
product 172. Cs2CO3 was the best choice leading to the desired product where the anion of
isocyanactate was initiated by Cs2CO3 (Scheme 61)

34
3) [3 + 3] Cyclization reaction
The reaction conditions for the preparation of a hydroxyl-benzoate 176 through one-pot
reactions was carried out using α-fluoro-β-ketoester 174 and chalcone 173. After screening
a series of bases and exploring the reaction temperature (70–120°C) and time (0.5–4 h), it
was found that using the equivalent amount of Cs2CO3 at 70°C for 30 min afforded (176) in
high yield. It was also found that increased reaction time or temperature caused
decarboxylation of 176 to form 3,5-disubstituted-phenol 175 (Scheme 62)

35
 2-cyclohexenone was selected as a model substrate reacting with B2pin2 as the
borylating reagent to optimize the activity of Cu 3(BTC)2 as a solid catalyst under
different conditions. The observed results are summarized in Table 1. 2-
cyclohexenone can react with B2pin2 in the presence of metallic Cu, Cu(I) or Cu(II)
salts or complexes to obtain β-ketopinacolboronates. The β-boronation of 2-
cyclohexenone did not occur either in the absence of Cu3(BTC)2 or in the absence of
cesium carbonate as a base both at room temperature or at 60 ◦C (Entries 1–2, Table
1). In contrast, the combination of Cu3(BTC)2 and cesium carbonate afforded the
desired product of 80% yield after 24 h at room temperature (Entry 3, Table 1). The
reaction was faster and afforded a higher product yield at a 60 ◦C reaction temperature
after 6 h (Entry 6, Table 1), while the relevant control experiments at 60 ◦C showed
almost no reaction (Entries 4–5, Table 1). The product yield was almost unaffected
when the reaction was carried out under inert atmosphere or using potassium
carbonate as a base (Entries 7–8, Table 1). This means that ambient oxygen is not
playing any role and that other carbonates can promote borylation equally. It was,
however, observed that the use of sodium carbonate led to a significant decrease in
the product yield (Entry 9, Table 1). A comparison of the catalytic activity under the
present conditions with either Cu(I) or Cu(II) salts or with other MOFs such as MIL-
101(Cr), MIL-53(Al), ZIF-8 showed either no products were formed or the yields
were much lower than that achieved with Cu3(BTC)2 (Entries 10–14, Table 1).

36
The crystal structure of Cu3(BTC)2 (BTC: 1,3,5-benzenetricarboxylate) contains water
molecules that are loosely bound to the coordinatively unsaturated sites around copper atoms
[50]. Initially, these coordinatively unsaturated metal sites in Cu 3(BTC)2 react with B2pin2 in
the presence of a base to afford reactive copper-boryl intermediates, which behave as the
catalytically active species. Later, these copper-boryl complexes promote the conjugate
addition to the α, β-unsaturated carbonyl compound to provide an organocopper intermediate,
which upon hydrolysis with water affords the desired product by generating a copper
hydroxide. This reacts further with B2pin2 to regenerate the active copper-boryl complex
species. This mechanistic proposal is depicted in Scheme 2.

37
 Conclusions
There are various uses and applications of cesium carbonate in organic synthesis was
reported. The mild conditions, the short reaction times, the ease of work-up procedures and
the excellent percent yields of the products encourage researchers to use cesium carbonate as
an inorganic base in many organic process.
Cu3(BTC)2 in the presence of cesium carbonate as a base is a suitable solid catalyst for
promoting the formation of β-keto organoboranes in high to moderate yields. The solid acts
as a heterogeneous catalyst and can be reused in consecutive runs without decrease in
activity. Considering the importance of functionalized organoboranes, this work represents
some significant merits by employing readily available Cu 3(BTC)2 without containing non-
noble metal as a convenient catalyst for the synthesis of β-keto organoboranes under mild
reaction conditions.

References

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Bis (Pinacolato)Diboron Catalyzed by Cu3(BTC)2 Using Cesium Carbonate as a Base.
Nanomaterials 2021, 11, 1396.

2. Ramy Rabie, Mohamed M. Hammouda, Khaled M. Elattar., Cesium carbonate as a

mediated inorganic base in some organic transformations, Res Chem Intermed 2016,
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3. A.A. Fadda, R. Rabie, Res. Chem. Intermed. 42, 771 (2016); https://goo.gl/SyWhVF

4. Yao, Q.; Lu, X.; Liu, K.; Ma, C.; Su, J.; Lin, C.; Li, D.; Dou, J.; Sun, J.; Duan, W. An
NHC-CuCl functionalized metal–organic framework for catalyzing β-boration of α, β-
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39