Chapter-1

Introduction

Chapter 1

PhD Thesis 2

1.1. Introduction

1.1.1. Carbon monoxide

Carbon monoxide (CO) is a colorless, odorless and tasteless gas which is

highly toxic to humans and animals in higher quantities [1-2]. It consists of one

carbon atom and one oxygen atom, connected by a triple bond which consists of two

covalent bonds as well as one dative covalent bond. It is the simplest Oxo carbon in

nature, and is an anhydride of formic acid [3].

Carbon monoxide is the twelfth most abundant gas in the atmosphere with

about 1.2 × 10-5% in the lower atmosphere. Worldwide, the largest source of carbon

monoxide is natural in origin, due to photochemical reactions in the troposphere

which generate about 5 x 1012 kilograms per year [4]. Other natural sources of CO

include volcanoes, forest fires, and other forms of combustion. Carbon monoxide is

produced from the partial oxidation of carbon-containing compounds, it forms when

there is not enough oxygen to produce carbon dioxide (CO2), such as when operating

a stove or an internal combustion engine in an enclosed space. In the presence of

oxygen, carbon monoxide burns with a blue flame, producing carbon dioxide.

Other than natural sources CO was also produced by daily human life. The

typical concentrations of carbon monoxide in natural and artificial environments are

given in Table 1.1.

Table 1.1. Concentration of CO in different human environment

Concentration (ppm)

Source

0.1 Atmosphere level [5] 0.5-5 Average level in homes [6] 5-15 Near properly tuned gas stoves [7] 100-200 Exhaust from automobiles in the central area of

Mexico City [8] 5,000 Home wood fire [7] 7,000 Undiluted warm car exhaust without a catalytic

converter[7]

1.1.2. Biological and physiological properties of CO

Carbon monoxide is produced naturally by the human and animal body as a

signaling molecule. Thus, carbon monoxide may have a physiological role in the body,

such as a neurotransmitter or a blood vessel relaxant [9]. Because of the role of carbon

Chapter 1

PhD Thesis 3

monoxide in the body, abnormalities in its metabolism have been linked to a variety

of diseases, including neurodegenerations, hypertension, heart failure and

inflammation. But CO has adverse effects if it is inhaled. CO forms a very strong

bond with the iron atom of hemoglobin in the blood, and once bonded cannot be

dislodged (unlike oxygen and CO2 which detach easily and reversibly). As more and

more CO is inhaled, more red blood cells get 'used up' leaving fewer and fewer

available to carry the vital oxygen to the muscles, tissues and brain of the animal. If

not treated immediately with O2 and possibly a blood transfusion, the animal would

die of asphyxiation.

1.1.3. Industrial production of CO

A major industrial source of CO is producer gas, a mixture containing mostly

carbon monoxide and nitrogen, formed by combustion of carbon in air at high

temperature when there is an excess of carbon. In an oven, air is passed through a bed

of coke. The initially produced CO2 equilibrates with the remaining hot carbon to give

CO. The final product consists of three gases, carbon monoxide, carbon dioxide, and

nitrogen in the ratio of 6:1:18. Above 800 °C, CO is the predominant product.

O2 + 2 C → 2 CO (∆H = −221 kJ/mol) (1.1)

Another source is water gas, a mixture of hydrogen and carbon monoxide

produced via the endothermic reaction of steam and carbon. The products in this case

are hydrogen (50%), carbon monoxide (40%), carbon dioxide (5%) and other gases

(5%) [10].

H2O + C → H2 + CO (∆H = +131 kJ/mol) (1.2)

Other similar synthesis gases (H2+CO) can be obtained by partial oxidation of

natural gas and other hydrocarbons. Carbon monoxide is also a byproduct of the

reduction of metal oxide ores with carbon, shown in a simplified form as follows.

MO + C → M + CO (1.3)

1.1.4. Applications of CO

CO is very important in industry, since it is a precursor to a number of

important organic chemicals (Fig.1.1). Its application includes the water-gas shift

reaction for the production of high purity hydrogen, Monsanto process for the

synthesis of acetic acid, Tennessee-Eastman acetic anhydride process, Fischer–

Chapter 1

PhD Thesis 4

Tropsch synthesis of hydrocarbons, Mond process for purification of nickel,

hydroformylation and hydroaminomethylation.

CO+H2

CH3OH

CH4

C1-Chemicals

Acetic acid

Acetic anhydride

Vinylacetate

Ethylene glycol

Homologation

Methylformate

CO2

Fine Chemicals Hydrogen or CO

Carbonylation

Hydroformylation

Fischer-Tropsch products

Methylformate

Chemicals

Gasoline Fine chemicals Olefins, Aromatics

Hydromainomethylation

Fig. 1.1. C1 building blocks

1.1.4.1. Water-gas shift reaction

The water-gas shift reaction [11] is the reaction in which carbon monoxide

reacts with water vapor to form carbon dioxide and hydrogen.

CO(g) + H2O(v) → CO2(g) + H2(g) (1.4)

The water-gas shift reaction is an important industrial reaction. It is often used

in conjunction with steam reforming of methane or other hydrocarbons, which is

important for the production of high purity hydrogen for use in ammonia synthesis.

The process is often used in two stages, stage one a high temperature shift (HTS) at

350 °C and stage two a low temperature shift (LTS) at 190–210 °C. Standard

industrial catalysts for this process are iron oxide promoted with chromium oxide for

the HTS step and copper on a mixed support composed of zinc oxide and aluminum

oxide for the LTS shift step.

Chapter 1

PhD Thesis 5

1.1.4.2. Monsanto acetic acid process

The Monsanto process is an important method for the production of acetic acid

by catalytic carbonylation of methanol. This process operates at a pressure of 30–60

atm and a temperature of 150–200 °C gave selectivity greater than 99%. The

Monsanto process has largely been superseded by the Cativa process, a similar

iridium-based process industrialized by BP Chemicals Ltd. which is more economical

and environmentally friendly [12].

1.1.4.3. Tennessee-Eastman acetic anhydride process

Acetic anhydride is produced by carbonylation of methyl acetate in a process

that was inspired by the Monsanto acetic acid synthesis [13].

CH3CO2CH3 + CO → (CH3CO)2O (1.5)

In this process lithium iodide converts methyl acetate to lithium acetate and

methyl iodide, which in turn affords through carbonylation of acetyl iodide. Acetyl

iodide reacts with acetate salts or acetic acid to give the product. Rhodium iodides and

lithium salts are employed as catalysts. The reaction is conducted under anhydrous

conditions in contrast to the Monsanto acetic acid synthesis because acetic anhydride

is not stable in aqueous medium.

1.1.4.4. Fischer–Tropsch synthesis of hydrocarbons

The Fischer–Tropsch process (or Fischer–Tropsch synthesis) is a set of

chemical reactions that convert a mixture of carbon monoxide and hydrogen into

liquid hydrocarbons [14].

(2n+1) H2 + n CO → CnH(2n+2) + n H2O (1.6)

This key process of gas to liquids technology produces a petroleum substitute,

typically from coal, natural gas, or biomass for use as synthetic lubrication oil and as

synthetic fuel. The F-T process has received intermittent attention as a source of low-

sulfur diesel fuel and to address the supply and/or cost of petroleum-derived

hydrocarbons. A variety of synthesis gas compositions can be used. For cobalt-based

catalysts the optimal H2:CO ratio is around 1.8-2.1. Iron-based catalysts stimulate the

water-gas-shift reaction and thus can tolerate significantly lower ratios. This reactivity

can be important for synthesis gas derived from coal or biomass, which tend to have

relatively low H2:CO ratios (<1).

Chapter 1

PhD Thesis 6

1.1.4.5. Mond process

The Mond Process, sometimes known as the Carbonyl process is a technique

created by Ludwig Mond in 1890 to extract and purify nickel [15]. The process was

used commercially before the end of the 19th century. It is done by converting nickel

oxides (nickel combined with oxygen) into pure nickel. This process makes use of the

fact that carbon monoxide complexes with nickel readily and reversibly to give nickel

carbonyl. No other element forms a carbonyl compound under the mild conditions

used in the process.

This process has three steps:

1. Nickel oxide is reacted with syngas at 200 °C to remove oxygen, leaving impure

nickel. Impurities include iron and cobalt.

NiO (s) + H2 (g) → Ni (s) + H2O (g) (1.7)

2. The impure nickel is reacted with excess carbon monoxide at 50-60 °C to form

nickel carbonyl.

Ni (s) + 4 CO (g) → Ni(CO)4 (g) (1.8)

3. The mixture of excess carbon monoxide and nickel carbonyl is heated to 220-

250 °C. On heating, tetracarbonyl nickel decomposes to give nickel:

Ni(CO)4 (g) → Ni (s) + 4 CO (g) (1.9)

1.1.4.6. Hydroformylation and hydroaminomethylation

The reaction between olefinic double bond and the mixture of hydrogen and

carbon monoxide (synthesis gas) leading to the formation of linear and branched

aldehydes as primary products is known as hydroformylation reaction or Oxo reaction

(Scheme 1.1). Adkins has introduced the term hydroformylation, since there is an

attack of hydrogen and formyl group (–CHO) at the unsaturated center of the carbon

chain of the alkene molecule [16]. The primary products of hydroformylation

reactions are aldehydes only. However, the formation of other Oxo products is also

known subsequent to the formation of aldehydes [17].

Chapter 1

PhD Thesis 7

Scheme 1.1. Hydroformylation reaction

Hydroaminomethylation (Scheme 1.2) is the single pot synthesis of amines

from an olefin, amine (alkyl amines, morpholine, pyrollidine etc) and syngas (H2, CO)

[18]. It is an elegant, atom economic, efficient process for the synthesis of amines. It

is the tandem reaction of hydroformylation in which the olefin reacts with CO and H2

to form aldehydes which will then react with amine to give an imine or enamine. This

will in turn get hydrogenated to the final amine. Hydroaminomethylation is closer to

applications as an intermediate for the synthesis of bulk, nylon, drugs and fine

chemicals.

Scheme 1.2. Hydroaminomethylation of olefin (R1 = R2 = R3 = H, alkyl or aryl group)

1.2. Hydroformylation: Synthesis of aldehydes

Otto Roelen in 1938 while investigating the reaction mechanism of the

Fischer–Tropsch (F–T) synthesis by addition of syngas to ethene could observe a

small amount of propanal formation which led to the discovery of hydroformylation

[19–21]. A small amount of propanal (and diethyl ketone) was formed when a mixture

of ethylene and synthesis gas was passed over a fixed bed of the catalyst containing

cobalt at 150 °C and 100 atm. He also observed that the selectivity of propanal

increased significantly when the reaction was carried out at 51 atm and 150 °C. First

real catalyst for the hydroformylation reaction was the conventional F–T catalyst.

Later it was recognized that cobalt afforded higher conversion and selectivity of

Chapter 1

PhD Thesis 8

propanal when used as a catalyst in homogeneous conditions. Hydroformylation is

one of the most important homogeneously catalyzed reactions performed in industries

along with carbonylation of methanol to acetic acid and oxidation of p–xylene to

dimethyl terephthalate (DMT). Consequently, hydroformylation of alkenes is the most

used and well–understood homogeneous catalytic reactions and is also a subject of

exhaustive review [22–38].

The hydroformylation reactions are done in homogeneous conditions and the

catalysts typically, consist of complex of transition metal atom (M), especially

platinum group metals [39, 40]. These transition metal complexes interact with CO

[41-45] and hydrogen to form metal carbonyl hydride species, which is an active

hydroformylation catalyst. Typically, complexes containing carbonyl ligands are

known as unmodified catalysts. On the other hand, introduction of tailor made ligand

to the transition metals results into modified catalysts.

The mechanism for the cobalt-catalyzed hydroformylation was proposed by

Heck and Breslow in 1960s, which is accepted as the general mechanism for Co- and

Rh-catalyzed hydroformylation at present as given in Fig. 1.2 [46]. The first step of

the mechanism is the dissociation of one carbon monoxide ligand from complex (1),

which is the catalyst precursor, leading to the formation of the hydride species

containing an empty coordination site (2). The alkene is then coordinated to complex

(2) and led to the formation of complex (3), and a migratory insertion of the alkene

into the rhodium hydride bond results in the formation of the alkyl species (4).

Subsequently, a CO inserts into the rhodium-alkyl bond resulting in the acyl species

(5) and hydrogenation, via an oxidative addition of hydrogen followed by a reductive

elimination, gives the product aldehyde (6) and regenerates the unsaturated Rh-

complex (2). Furthermore, β-hydrogen elimination of the alkyl species (4) may lead to

isomerization and the formation of less reactive internal alkenes.

Chapter 1

PhD Thesis 9

Fig. 1.2. Mechanism of hydroformylation, L = Ligand (Generally phosphine ligand)

Hydroformylation is an elegant reaction for the production of aldehydes. The

Oxo process or hydroformylation of olefins with synthesis gas (CO+H2) is the

principal route for the synthesis of C3-C15 aldehydes, which are converted to alcohols,

acids or other derivatives. By far the most important Oxo chemical is n-butanal,

followed by C6-C13 aldehydes for plasticizer alcohols, iso-butanal and C12-C18

aldehydes for detergent alcohols. Nearly all Oxo aldehydes are converted to

Chapter 1

PhD Thesis 10

derivatives in plants adjacent to the hydroformylation unit; very small volumes of

Oxo aldehydes are transported.

1.2.1. World market of Oxo products

Propene derived n-butanal and iso-butanal account for nearly 73% of world

consumption of Oxo products. High consumption volumes for both alcohol

derivatives of n-butanal (n-butanol and 2-ethylhexanol (2-EH)) will continue in the

near future. However, it is expected that the consumption of n-butanol will surpass 2-

EH consumption in 2009–2010. This is partly due to replacement of di(2-ethylhexyl)

phthalate (DEHP), the main plasticizer derived from 2-EH, with other plasticizers

derived from other plasticizer alcohols. C6-C13 plasticizer alcohols have lost market

share, primarily as a result of decreased production and consumption of C7, C9 and

C11 linear alcohols. They are expected to continue to lose market share, largely as a

result of increased production and consumption of 2-propylheptanol (2-PH), which is

derived from n-pentanal, the hydroformylation product of 1-butene. World

consumption of n-pentanal will grow at the highest rate of all Oxo chemicals, largely

as a result of the commissioning of 2-PH capacity in Europe and China starting in late

2009 and continuing into 2013. The pie chart in Fig. 1.3 shows world consumption of

Oxo chemicals.

Fig. 1.3. World consumption of Oxo chemicals 2008

Demand for Oxo chemicals in the United States is expected to grow at an

average annual rate of almost 2% during 2008-2013. The long-term prospects for Oxo

Chapter 1

PhD Thesis 11

chemicals in Western Europe improved considerably during 2005–2008, as

associations and capacity reductions resulted in improved efficiencies and capacity

utilization. The commissioning of plants for 2-PH and additional iso-nonyl alcohol

(INA) capacity helped to reduce the former dependence on 2-EH. Western European

consumption of Oxo chemicals is predicted to grow at an average annual rate of 2.0%

during 2008–2013. Japanese consumption is forecast to experience 0.9% average

annual growth during 2008–2013. Other Asian consumption, excluding Japan, is

expected to grow at 5.0% annually during the same period; China, India and Taiwan

are the main growth markets in this region. Middle Eastern consumption of Oxo

chemicals is forecast to grow significantly at an average annual rate of 4.8% during

2008–2013, albeit from a small base, largely as a result of increased n-butanol

demand for n-butyl acrylate by late 2010 [47].

1.2.2. Hydroformylation process: Stages of developments

Table 1.2. Developments in hydroformylation processes in different stages

1st Stage 2nd Stage 3rd Stage

Temperature (°C) 120-180 85-130 110-130

Pressure (bar) 200-350 15-60 40-60

Metal concentration

0.4-0.7

(cobalt, wt% of feed)

200-270

(rhodium, ppm)

200-270

(rhodium, ppm)

Ligand Absent or triphenyl

phosphine

Triphenyl

phosphine

Water soluble

ligand

Light products

(wt%)

3-13 - -

Aldehydes (wt%) 70-75 82-95 91-95

Alcohols (wt%) 6-10 5-8 5-9

Heavy ends (wt%) 4-17 - -

As far as hydroformylation catalysts are concerned, three developmental

stages for these catalysts can be visualized (Table 1.2). The first stage of

hydroformylation is exclusively for cobalt based catalytic systems. Second stage is for

the development of ligands, specially triphenyl phosphine, and the shift from cobalt to

Chapter 1

PhD Thesis 12

rhodium as the central metal. Third stage is the development of biphasic catalyst

based on rhodium by modification of ligand [33]. The various ligands used in the

different stages of development are given in Fig. 1.4

Fig. 1.4. Ligands developed at different stages of development in hydroformylation

1.2.2.1. Cobalt based processes (1st stage)

The first stage of development (Table 1.2) is the reaction with cobalt carbonyl

hydrides (HCo(CO)4) as a catalyst, with the pressure range between 200-350 bar to

avoid decomposition of the catalyst and deposition of metallic cobalt. The

temperature was adjusted according to the pressure and the concentration of the

catalyst between 120 and 180 °C to get an acceptable rate of reaction. Cobalt

processes are mostly used in the production of medium to long chain olefins, because

rhodium catalysts dominate the hydroformylation of propene. The presently applied

cobalt processes have reached a high standard of performance. Most of these

processes are pretty similar, the main difference between the cobalt processes are the

separation of product and catalyst. Three of these processes are that of BASF, Exxon

and Shell.

BASF process

The BASF hydroformylation process of propene or higher olefins occurs

under high pressure [48]. The catalyst is in the form of HCo(CO)4. This catalyst will

be separated from the liquid product by addition of oxygen and formic or acetic acid,

leading to an aqueous solution which contains the cobalt predominantly as formate or

acetate. The organic products are withdrawn in a phase separator and the cobalt

solution is concentrated afterwards and sent to the carbonyl generator. The cobalt

losses are compensated. In the reactor stirring is important to accomplish thorough

mixing of the olefins and the aqueous catalyst solution. The best selectivity to linear

aldehydes is obtained at low temperatures. The disadvantage is the process difficulty

and economic aspects of the separation and recyclability of the catalyst.

Chapter 1

PhD Thesis 13

Exxon process

The Exxon process is designed to convert olefins in the range of C6-C12.

Recovery of the catalyst is different than that of BASF process. In the Exxon process

the ‘Kuhlmann’ catalyst cycle technology is applied [49]. This involves two main

steps: the recovery of sodium carbonylate and its regenerative conversion into cobalt

carbonyl hydride. The HCo(CO)4 catalyst reacts with syngas in the reactor under

normal hydroformylation conditions. After the reaction the product mixture is treated

with aqueous alkali, to convert HCo(CO)4 to water-soluble NaCo(CO)4, which is

extracted as aqueous solution from the organic product phase. Then the catalyst is

regenerated by addition of H2SO4. The advantage of the Exxon process is that the

catalyst does not undergo decomposition and enters the reactor in its most active form.

A big disadvantage is that catalyst separation and recovery must be carried out under

CO pressure to preserve the catalyst.

Shell process

In the Shell process reactants in range of C7-C14 are converted using a

phosphine modified cobalt catalyst [50]. In this process the product mixture is

distillated, the organic products leave the distillation column at the top and the

catalyst is recovered at the bottom. Before re-entering the reactor the catalyst recycle

is upgraded with catalyst and phosphine ligand. The benefits of this process are the

high n/iso ratio, the low pressure and the direct formation of alcohols. The drawback

is the low activity of the ligand modified catalyst, which requires a large reactor

volume and difficulties associated with separation of the catalyst.

1.2.2.2. Rhodium based processes (2nd Stage)

Rhodium catalyst processes are used since the 1970s and dominate for

hydroformylation of propene. Rhodium catalysts are more expensive than cobalt

catalysts and have higher activity, but have lower activity in case of branched olefins.

The catalyst used is rhodium with triphenyl phosphine ligand. UCC, BASF and

Mitsubishi use rhodium based hydroformylation process for commercial synthesis.

UCC, BASF and Mitsubishi process

The Union Carbide Corporation (UCC) commercially applies the

hydroformylation of propene in a liquid-recycle process [51]. These plants are called

LPO (Low Pressure Oxo) plants [52]. The reaction takes place in a stainless steel

reactor where the gas and propene are introduced via a feed line and a gas-recycle.

Chapter 1

PhD Thesis 14

The catalyst is dissolved in high-boiling aldehyde condensation products. The product

mixture consists of dissolved gas, aldehydes, rhodium-phosphine complex, free

phosphine ligand and the higher-boiling aldehyde condensation products. The product

mixture passed into a separator and a flash evaporator, where the major part of inert

and unconverted reactants is taken overhead. The flashed-off gases are returned to the

reactor. The liquid stream is heated and is fed to two distillation columns in series.

The gaseous aldehydes are sent over the top and condensed and separated from the

syngas, which is recycled. At the bottom the catalyst solution is separated and

recycled in the reactor. If the feed of the process has a sufficient purity the catalyst

may last more than a year. The BASF and Mitsubishi rhodium based processes are

quite parallel to the UCC process [53, 54].

1.2.2.3. Disadvantages of cobalt and rhodium based homogeneous

hydroformylation and development of biphasic catalysts (3rd Stage)

Both cobalt and rhodium based industrial processes suffer the easy and

effective recycling of the catalyst. The separation of the catalyst and products from

the homogeneous reaction mixture, severe conditions, and low activities of catalysts

were main limitations for cobalt based processes. Development of rhodium-phosphine

catalyst gave higher activities and selectivity with lower temperature and pressure

conditions. But these systems also lack the efficient separation, regeneration and

recyclability of the catalyst.

These disadvantages led to the development of biphasic catalysts. Here the

catalyst will be in one phase (aqueous phase) and reactant and product in the other

phase (organic phase). The reaction occurs at the interface of the two phases as shown

in Fig. 1.5. Development of water soluble ligand triphenylphosphine trisulfonate

sodium salt (TPPTS) was the chief achievement in this stage. The replacement of

triphenyl phosphine with TPPTS led to the development of water soluble rhodium

complex. This complex is used in the Ruhrchemie/Rhône-Poulenc (RCH/RP) process

for hydroformylation of propene.

Chapter 1

PhD Thesis 15

Fig. 1.5. Biphasic hydroformylation of olefin using water soluble

HRhCO(TPPTS)3

Ruhrchemie/Rhône-Poulenc process

The RCH/RP (Ruhrchemie/Rhône-Poulenc) process is an example of a two

phase system. The reactor contains the aqueous catalyst and is fed with propene and

syngas, TPPTS is used as a ligand for the rhodium catalyst complex [55]. After the

reaction the crude aldehyde product is degassed and separated into the aqueous

catalyst solution and the organic aldehyde phase. The heat of the aqueous phase is

then used to produce steam in a heat exchanger. After separation the organic phase is

passed through a stripping column, where the unreacted olefins are separated and sent

back to the reactor. The product mixture is then distilled into n- and iso-butanal. The

produced steam from the reactor is used in the reboiler of the distillation unit, which is

a big advantage. This is the cleanest hydroformylation industrial process because of

the straightforward separation of the organic products from the catalyst.

However the system is limited by the solubility of organic substrates in

aqueous phase. The rate of higher olefins hydroformylation drops dramatically

because of their low solubility in water. Therefore, there is a pressing need to develop

a heterogeneous catalyst to overcome the drawbacks of homogeneous catalyst

(separation and catalyst reuse) and biphasic catalysis (solubility of the higher olefins).

Also the development of heterogeneous catalyst can help in developing flow reactors

for hydroformylation which can improve the process in industries. This lead the

Chapter 1

PhD Thesis 16

researchers to conduct research based on heterogeneous catalyst for hydroformylation

reactions.

1.3. Heterogeneous hydroformylation

Heterogeneous hydroformylation is one of the emerging research areas of last

three decades to overcome the drawbacks of recyclability associated with

homogeneous hydroformylation. In this regard the research has been progressed by

heterogenization of homogeneous catalysts into a solid support like zeolites, activated

carbon, alumina, polymers, supported dendrimers and mesoporous silica materials

(silica, MCM-41, SBA-15 etc.).

1.3.1. Heterogenization of homogeneous catalyst on zeolite materials

Zeolites are materials consisting of Si-Al framework and having uniform

channel size, high surface area, shape selectivity, thermal and chemical stability with

varied acidic and basic properties. The main advantage in the use of zeolites as a

support is the enhanced selectivity due to the well-defined pores structure.

Rhodium exchanged zeolite-X and -Y are found to be active for

hydroformylation of propene at atmospheric pressures [56]. In an another study the

rhodium phosphine complexes was in situ encapsulated in zeolite NaY and was active

for propene hydroformylation at 150 °C and 1 atm [57]. The catalysts were not stable,

but showed an enhancement in linear vs. branched products with an increased

production of alcohols compared to rhodium zeolites without phosphines.

Hydroformylation of 1-hexene by various zeolite-supported rhodium species were

reported [58]. The hydroformylation of 1-hexene was carried out at 50 and 125°C and

300 psig CO:H2 (1:1). The activity of the immobilized catalysts is affected by the type

and amount of phosphine. Chaudhari et al. reported a heterogeneous system of

catalyst made up by tethering of HRh(CO(PPh3)3 in zeolite Y using phosphotungstic

acid as tethering agent [59]. The catalyst showed excellent stability, selectivity to

aldehydes and improved activity for hydroformylation of various olefins. The catalyst

was also recyclable without loss in its activity and selectivity. In an another study by

Chaudhari et al., HRh(CO(PPh3)3 was impregnated on zeolite Y (Scheme 1.3) and

also encapsulated in zeolite Y [60]. The impregnated catalyst was leached out in the

first cycle itself where as the encapsulated catalyst was found to be efficiently active

Chapter 1

PhD Thesis 17

and recyclable. The zeolite based supports had demerits of lower pore diameter which

restricted the encapsulation of bulky complexes and also the hydroformylation of

higher olefins.

Scheme 1.3. Tethering of HRh(CO)(PPh3)3 complex to zeolite Y by phosphotungstic

acid for hydroformylation [60]

1.3.2. Heterogenization of homogeneous catalyst on activated carbon

Activated carbon support is having a very high surface area and has a

possibility of enhancement in surface chemistry. Rh supported on activated carbon of

different origins (peat, wood and coconut shell based) is reported [61]. The catalyst is

tested for ethene hydroformylation and found that the catalyst based on coconut shell

based activated carbon showed better activity and selectivity to propanal. Without any

pretreatment with H2 or CO the catalyst showed better activity. In another study,

carbon supported Ba salt of HRh(CO)(TPPTS)3 (Fig. 1.6) was used as a highly active

and stable hydroformylation catalyst [62]. The catalyst is prepared by interaction of a

carbon supported barium nitrate with an aqueous solution of HRh(CO)(TPPTS)3 and

NaTPPTS [1:6], [TPPTS = triphenylphosphine trisulfonate] to form a precipitated

Ba2+ salt of HRh(CO)(TPPTS)3 and free TPPTS-Ba3/2 where Ba2+ is adsorbed on the

carbon surface by physical adsorption. Conversion of 95% of 1-decene

hydroformylation with 89.5% aldehyde selectivity was obtained but with a lower n/iso

ratio of 0.51.

Chapter 1

PhD Thesis 18

Rh

P

CO

SO3

SO3

Ba

P

SO3

Ba

O3S

SO3

Ba

P

SO3

O3

SBa

SO3 SO3

Ba Ba

Ba

Rh

PCO

H

O3SO3S

Ba

P

O3

SBa

SO3

SO3

Ba

P

O3S O3S

O3

S

O3S

Ba

Ba

H

Fig. 1.6. Carbon supported Ba salt of HRh(CO)(TPPTS)3 [62]

De Lecea et al. have heterogenized the [Rh(µ-Cl)(COD)]2 complex (COD =

cyclooctadiene) on activated carbon and used as catalysts for the hydroformylation

of 1-octene [63]. The effects of surface chemistry of the activated carbon and the

solvent used on the activity and selectivity were investigated. In methanol, the

catalysts are selective to alcohols. The heterogenized catalyst showed conversion and

selectivity similar to its homogeneous counterpart but showed leaching of the Rh

complex. In another study, HRh(CO(PPh3)3 was impregnated by incipient wetness

Chapter 1

PhD Thesis 19

technique on to carbon nanotube [64]. The catalyst was highly active and selective

for propene hydroformylation with molar n/iso ratio of 12-13.

1.3.3. Heterogenization of homogeneous catalyst on alumina

Heterogenization of rhodium on alumina by ion-exchange and homogeneous

precipitation method is reported [65]. The supported Rh(III) is then reduced to Rh(0)

using molecular H2 or NaBH4. The catalyst was active and selective for styrene

hydroformylation but the leaching of Rh metal was prominent under

hydroformylation conditions. Nano-porous alumina synthesized through sol-gel

method was used as a support for rhodium catalyst impregnation [66]. The catalyst

showed high activity on hydroformylation of ethene. Kawi et al. synthesized a series

of alumina-supported Wilkinson’s catalyst for hydroformylation of styrene [67]. The

support was functionalized by surface amine ligands onto which PAMAM

(polyamidoamine) dendrimers were grafted followed by anchoring of Wilkinson’s

catalyst. Dendritic nanoalumina supported catalysts showed higher activity and

selectivity than that of dendritic α-alumina, β-alumina and SBA-15. The zeroth

generation dendritic nanoalumina showed higher activity while the first generation

dendritic nanoalumina showed higher regioselectivity. The higher surface area of the

support was the reason for zeroth generation catalysts for its higher activity and the

crowdedness around the metal center was the reason for lower activity of higher

generation catalysts.

1.3.4. Heterogenization of homogeneous catalyst on resins and polymers

The research for heterogenization of homogeneous complex on the resins and

other polymeric supports, in which metal complex is immobilized on resin/polymer

surface through their surface functional groups, is one of the current interest for

hydroformylation reaction. Uozumi et al., reported the synthesis and application of

rhodium phosphine complexes supported on amphiphilic resin beads of polystyrene–

poly(ethylene glycol) graft co–polymer (1% divinyl benzene (DVB) cross–linked) for

the hydroformylation of various alkenes in water [68]. The heterogeneous catalyst

showed excellent yields up to 99% for aldehydes. Hydroformylation of 1-hexene in

supercritical CO2 (scCO2) and other organic solvents was reported by Fujita et al.,

using polymer supported rhodium catalyst prepared from polystyrene bound PPh3 and

dicarbonyl acetylacetonato rhodium. The supported catalyst was reused for several

Chapter 1

PhD Thesis 20

cycles by means of simple filtration [69]. Chaudhari et al. studied the kinetics of

hydroformylation of 1-hexene using rhodium–TPPTS bounded on the surface of ion

exchange resin, amberlite IRA–93 as a catalyst [70]. Another method for synthesis of

immobilized homogeneous catalyst by addition of a bi–functional ligand followed by

a metal complex (rhodium, cobalt and platinum/tin) onto ion exchange resin

(sulfonated styrene–divinylbenzene) for hydroformylation of 1-hexene was reported

[71]. Artner et al., have reported metal doped thermosetting epoxy resins, like

triglycidyl derivative of 4–aminophenol, synthesized by polymerization reaction using

molybdenum, palladium, or rhodium complexes as initiators. These metal doped

epoxy resins were observed as highly efficient catalysts for hydroformylation reaction.

These catalysts were recovered by filtration and recycled without much loss in its

activity [72].

1.3.5. Heterogenization of homogeneous catalyst on supported dendrimers

Heterogenization of rhodium metal complexes on supported dendrimers is one

of the research interests in recent times. Dendrimers are macromolecules with

emerging applications in the area of material and biological sciences [73–75]. In

current decades, dendrimers are found to be novel materials for use in catalysis

because of their highly branched and bulky structures which can provide multiple

sites for coordination with metal complexes [76–78]. The dendrimers are generally

soluble in organic solvents, but can be separated by nano filtration from the reaction

mixture in liquid phase due to their large size. The coordination of dendrimers with

transition metal complexes may bring forth enhanced catalytic performance due to

positive dendritic effect [77]. Dendrimers being large (2 to 4 nm) tree–like molecules

with a stubborn globular shape makes them more suitable for ultrafiltration than

soluble polymers. The metal–binding groups are usually on the exteriors of

dendrimers but can also be covered within shape–selective pockets. Advantageously,

dendrimers may exhibit bidentate binding (through two donor atoms on the same

dendrimer arm) to the metal. The chelate (ring–forming) effect will then ensure the

minimum leaching of metal complex.

Chapter 1

PhD Thesis 21

Fig. 1.7. Phosphonated PAMAM-SiO2 dendrimer rhodium complexes of different

generation [79]

Alper et al. have studied supported dendrimers used to anchor the rhodium

metal complexes for hydroformylation reactions. PAMAM dendrimers were grown

over silica in successive generations and is used for the preparation of phosphonated

PAMAM-SiO2 dendrimer rhodium complexes (Fig. 1.7) for hydroformylation of

olefins [79]. The catalyst was highly active and regioselective for hydroformylation of

aryl olefins and vinyl acetate. However, the third- and fourth generation catalysts of

these type displayed low activity compared to the lower generations. This was

believed to be due to incomplete phosphonation reactions at higher generation

dendrimers arising from steric crowding and ultimately resulting in the threshold of

dendrimer growth being reached. It was supposed that extending the chain length of

each generation would relieve the steric crowding and allow for increased catalyst

loading at higher generations. This led this group to extend their work in this regard.

To extend the chain length, the ethylenediamine linker was substituted by 1,4-

diaminobutane, 1,6-diaminohexane and 1,12-diaminododecane [80]. The lengthening

of the monomeric unit of the dendrimer decreased the congestion at the surface (Fig

1.8). The hydroformylation of styrene and vinyl acetate proceeds in up to quantitative

yields, and in fine regioselectivity using these catalysts. These silica-supported

catalysts were recovered by microporous filtration using a 0.45 µm membrane filter

and are reusable for at least three cycles.

Chapter 1

PhD Thesis 22

O

O

O

Si N

O

NH

O

NH

N

N

NH

OHN

O

N

NH

O

N

NH

O

N

N

HN

O

NH

O

N

Ph2P

PPh2

Rh

Ph2P

PPh2

Rh

Ph2P

PPh2

Rh

NPh2P

Ph2P

Rh

O

HN

N

NH

ON

PHPh2

PHPh2

Rh

NH

O

N

NH

O

N

Ph2P

Ph2P

Rh

HN

O

N

Ph2P

PPh2

Rh

NH

O

N

Ph2P

PPh2

Rh

Fig. 1.8. Lengthening of the monomeric unit of the dendrimer in third generation [80]

PAMAM dendrimers were also successfully grown over periodic mesoporous

silica like MCM-41 [81]. The dendrimer generation was done on aminopropylated

MCM-41 (Scheme 1.4). This dendrimer supported on MCM-41 was then

phosphinomethylated and then formed complexation with rhodium. The catalyst was

highly active with turn over frequency (TOF) of 1800 h-1 for hydroformylation of 1-

octene. Similar kind of PAMAM dendrimers supported on davasil silica [82] and

Chapter 1

PhD Thesis 23

SBA-15 [83] etc. are reported. All these catalysts were active and selective for

hydroformylation with reusability.

Scheme 1.4. Dendrimer generation in aminopropylated MCM-41 [81]

1.3.6. Heterogenization of homogeneous catalyst on various silica materials

Various silica materials were used as an efficient support for heterogenization

of homogeneous catalyst for hydroformylation reactions. Silica materials owing to its

higher surface area and mesoporous nature have advantage of easy encapsulation of

large metal complexes and the higher pore diameter and pore volume will increase the

easy ingress and egress of reactant and products. The silica materials having a surface

area in between 250 to 1000 m2/g with high thermal stability attracted the researchers

to utilize its properties as a support for homogenous metal complexes.

Gao et al., reported the rhodium carbonyl thiolate complex tethered to

phosphine-modified Pd–SiO2 which was prepared by tethering the phosphine ligand

Ph2P(CH2)3Si(OC2H5)3 to Pd–SiO2, to give the tethered complex catalyst (Fig. 1.9)

[84]. These catalysts were active even at mild conditions of 1 bar of H2 and CO (1:1)

and at 60 oC.

Chapter 1

PhD Thesis 24

Fig. 1.9. Rhodium carbonyl thiolate complex tethered Pd–SiO2, M =Pd [84]

In another study, the hybrid PPh3–Rh/SiO2 catalyst for hydroformylation of

olefins was prepared by doping PPh3 onto the Rh/SiO2. The chemical bond of the

hybrid catalyst was formed between the PPh3 ligand and Rh metal particles on the

surface of SiO2 support [85]. The catalyst was highly active and recyclable for

hydroformylation. The results reveal that hydroformylation of olefins to aldehydes

dominantly take place on the surface of the hybrid catalyst.

P

RhHP

PRhHP

PRhHP

PRhHP

P

RhHP

PRhHP

SiO2

SiO2

P

PH

HP

PH

PH

PH

PH

PHPH

HP

P

P

P

SiO2

Rh particle

RhPh3P PPh3

H

PPh3OC

Fig. 1.10. Model of the PPh3-Rh/SiO2 catalyst [86]

Yan et al., had reported the PPh3 modified Rh/SiO2 catalyst as an active

catalyst for heterogeneous hydroformylation of propene in a fixed-bed reactor [86].

The conducted in situ FTIR studies confirmed that PPh3 molecules could be

Chapter 1

PhD Thesis 25

chemically adsorbed on the heterogeneous Rh/SiO2, and they promote the in situ

formation of HRh(CO)(PPh3)3 species and HRh(CO)2(PPh3)2 species, which are the

active catalytic species that improve the activity and selectivity of propene

hydroformylation (Fig. 1.10). The problem of metal leaching is greatly reduced by

directly fastening Rh nano-particles to the support, and Rh species are tightly bound

by the Rh–O bonds and the very strong metal–metal bonds.

Heterogeneous chiral catalysts were prepared by modifying silica-supported

rhodium (Rh/SiO2) with chiral phosphorus ligands [87]. The chirally modified

Rh/SiO2 catalysts exhibited high activity, regioselectivity, and enantioselectivity for

the asymmetric hydroformylation of styrene and vinyl acetate. Up to 72% ee and

100% selectivity of branched aldehyde for the hydroformylation of vinyl acetate were

obtained for (R)-BINAP–Rh/SiO2 catalysts. Marchetti et al., had reported SiO2

tethered rhodium complexes obtained from Rh(CO)2(acac) and 3-(mercapto)propyl-

and 3-(1-thioureido)propyl- functionalized silica gel [88]. These catalysts were used

for hydroformylation of functionalized olefins of biological interests like styrene, 1,1-

diphenylethene, 2-tosyloxystyrene, 2-benzyloxystyrene and vinyl acetate. The catalyst

showed good activity, with conversion, chemo- and regioselectivity comparable with

homogeneous catalysts. But a small extent of leaching was observed.

Supported aqueous phase catalysts (SAPC) synthesized over SiO2 was

prepared by Zhu et al. for hydroformylation of higher olefins [89]. The Rh was

supported over high surface area SiO2 and TPPTS was introduced as water soluble

ligand. The reaction was conducted in an aqueous biphasic media and the catalyst was

found to reduce the resistance of mass transfer in water/organic biphasic media for the

hydroformylation of higher olefins. The chemical coordination bonds between the

highly dispersed Rh particles and the TPPTS ligands are responsible for its high

catalytic activity for the hydroformylation of olefins.

Apart from the above SiO2 materials the research is more focused on

mesoporous silica like MCM-41, HMS, SBA-15 type materials. The highly porous

nature with high surface area and pore diameters in the range of 2 to 20 nm made

these materials as a suitable support for heterogenization. Mobile Oil Corporation

discovered the new class of mesoporous silica material called Mobile Composite

Materials like MCM-41 and MCM-48 which have been extensively studied as a

support for heterogeneous hydroformylation [90–92].

Chapter 1

PhD Thesis 26

Rh4(CO)12-derived rhodium carbonyls have been successfully anchored to

MCM-41(PPh2), MCM-41(NH2) and MCM-41(SH), which are formed, respectively,

by functionalization of silicate MCM-41 with Cl(CH2)3Si(OMe)3 plus KPPh2,

H2N(CH2)3Si(OEt)3 and HS(CH2)3Si(OMe)3, to produce MCM-41-tethered

unidentified phosphine- and amine-containing rhodium carbonyl clusters [91].

Rh4(CO)12 is mostly converted to Rh6(CO)16 on unfunctionalized MCM-41. All the

Rh4(CO)12-derived catalysts exhibited very high selectivity (>98%) for the formation

of cyclohexane carboxaldehyde in cyclohexene hydroformylation. The

unfunctionalized catalyst was leached out whereas the functionalized ones were stable

and recyclable.

Huang et al. also extended their studies and reported a Rh-complex tethered on

aminated MCM-41 as a heterogeneous catalyst for efficient hydroformylation of 1-

hexene [93], 1-octene and styrene [94]. A nitrogen-containing organosilane coupling

reagent like aminopropyl triethoxy silane, was used for the functionalization of the

MCM-41 support to obtain aminated MCM-41. The tethering of the rhodium

complexes substantially does not result in the change in the mesoporous structural

ordering of MCM-41, although the resultant materials exhibit reduced pore sizes, total

pore volumes and BET surface areas. Two sets of catalysts, tethered PPh3-free Rh-

complex and tethered PPh3-containing Rh-complexes were synthesized. For 1-hexene

and 1-octene hydroformylation, the tethered PPh3-free rhodium complex is of no

advantages in activity, selectivity and n/i aldehyde ratio over the corresponding

untethered one. But, the catalyst tethered with PPh3-containing rhodium complex had

enormous advantage in activity and selectivity over the untethered PPh3-containing

rhodium complex except for n/i aldehyde ratio.

In another study, two triphenyl phosphine analogues, (4-tert-butylphenyl)

diphenyl phosphine and bis-(4-tert-butylphenyl) phenylphosphine ligands, have been

synthesized for the preparation of Rh–P complexes with a formula of Rh(CO)Cl(L)2

(L-ligand). The synthesized complexes were immobilized in amino-functionalized

MCM-41 and MCM-48 [95]. The heterogenized catalysts showed catalytic activity

and n-heptanal selectivity comparable with that of the corresponding homogeneous

complexes for 1-hexene hydroformylation. There interactions had been occurred

between the surface amino-groups and the rhodium complex during the

immobilization, resulting in highly dispersed active Rh-moieties and a significant

modification in the catalytic stability.

Chapter 1

PhD Thesis 27

Ali and co-workers studied the heteropolyacid supported Rh(I) and Rh(III)

complexes supported on MCM-41 for hydroformylation. Heteropolyacids

(H3PW12O40, 25H2O) impregnated with Rh(I) and (III) complexes were prepared and

used as supported catalysts in the hydroformylation of alkyl alkenes [96]. The results

showed that the catalysts with heteropolyacids had better activity than that of the

catalysts without heteropolyacid. In another study the same catalyst is used for

hydroformylation-acetalization domino reactions of aryl alkenes [97]. Rh(I) supported

MCM-41 combined with the heteropolyacid H3PW12O40 showed high catalytic

activity towards the formation of acetals. Whereas the Rh(III) showed better activity

for acetals in the absence of any additives.

Supported ionic liquid-phase catalyst (SILPC) on MCM-41 was investigated

with Rh-TPPTS complex dissolved in various ionic liquids, 1-butyl-3-methyl-

imidazolium tetrafluoroborate (BMI·BF4), 1-butyl-3-methyl-imidazolium

hexafluorophosphate (BMI·PF6) and 1,1,3,3-tetramethylguanidinium lactate (TMGL)

[98]. The supported ionic liquid-phase catalysts synthesized were very active for the

hydroformylation of higher olefins. The catalytic performance of SILPC was almost

independent of the type of ionic liquid used.

Other than MCM-41 or MCM-48 type materials, SBA-15, HMS etc. also were

used as a support for hydroformylation reactions. Rh tethered on Ti modified

hexagonal mesoporous silica functionalized with 2,2’ bipyridine (Rh/Ti-HMS/bipy)

was investigated for heterogeneous hydroformylation of olefins [99]. In this catalyst

system Ti-HMS was calcined in air at 650 °C for 4 h and was functionalized by 2,2’

bipyridine (bipy). The catalyst was active for hydroformylation of alkenes. Yan et al.

have developed SBA-15 as a support for homogenous Rh-complexes [100]. Rh, Rh-

PPh3 and HRh(CO)(PPh3)3 were used for the catalyst synthesis. The catalyst Rh-PPh3

supported on SBA-15 of medium pore size of 6.1 nm gave higher n/iso ratio and

comparable activity. It was confirmed that at the nanometer sized pores the

HRh(CO)2(PPh3)2 active species were formed in situ and increases the activity and

regioselectivity.

Chapter 1

PhD Thesis 28

Si

PH3

Rh

OC

Cl

Si

HP

3

Higher olefins with different lengths,

C=C positions, structures

+CO +H2

Hydroformylation

Fig. 1.11. Rh-PrPPh2-SBA-15 catalysed hydroformylation [101]

In another piece of study, RhCl3 was immobilized to diphenylphosphinopropyl

(–PrPPh2)-modified mesoporous silica SBA-15 through a multi-step-assembly

process (Fig. 1.11) [101]. The catalysts were tested for hydroformylation activity of

several higher olefins of different lengths (C6, C8, and C10), different double bond

positions (terminal or internal) or different structures (linear or branched). Shorter

linear olefin substrates were more easily activated with higher catalyst specific

activity, while the catalyst showed recycling stability in hydroformylation of longer

and branched olefin substrates.

Other heterogenized catalysts are also reported by using hydrotalcite like

materials as a support for heterogenization. Jasra et al., have used these type of

heterogenized catalysts for the synthesis of C8 aldols and alcohols from propene via

hydroformylation, aldol condensation and hydrogenation in a single pot [102–106].

This study has been extended for the synthesis of 2-methylpentanol from ethene by

this multistep reaction performed in single pot using similar catalytic systems [107].

The same catalyst was used for the hydroformylation of various alkenes by changing

the parameters without formation of aldol and/or hydrogenated products [108].

Chapter 1

PhD Thesis 29

1.4. Hydroaminomethylation: Synthesis of Amines

Amines are important class of bulk and fine chemicals in chemical and

pharmaceutical industries with a production of million-ton scale per year [109].

Amines are organic compounds and functional groups that contain a basic nitrogen

atom with a lone pair. Amines are derivatives of ammonia, wherein one or more

hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group

[110].

Amines can be classified as primary, secondary or tertiary, meaning one, two

and three alkyl groups bonded to the nitrogen respectively as shown in Fig. 1.12.

Important amines include amino acids, biogenic amines, methylamine,

trimethylamine, and aniline. Amines play prominent roles in biochemical systems;

they are widely distributed in nature in the form of amino acids, alkaloids, and

vitamins. Many complex amines have pronounced physiological activity, for example,

epinephrine (adrenalin), thiamin or vitamin B1, and Novocaine. The odor of decaying

fish is due to simple amines produced by bacterial action. Amines are used to

manufacture many medicinal chemicals, such as sulfa drugs and anesthetics. The

important synthetic fiber nylon is an amine derivative [111].

NH2

H3C C NH2

CH3

CH3

NH

CH3

NH

N

CH3

CH3

N

Primary amine

Secondary amine

Tertiary amine

Fig. 1.12. Primary, secondary and tertiary amines

Chapter 1

PhD Thesis 30

1.4.1. Synthesis of amines

1.4.1.1. Industrial synthesis of amines

Commercial preparation of aliphatic amines can be accomplished by direct

alkylation of ammonia or by catalytic alkylation of amines with alcohols (Reductive

amination) at elevated temperatures [112].

ROH + NH3 → RNH2 + H2O (1.10)

RX + 2 R'NH2 → RR'NH + [RR'NH2]X (1.11)

Alkylation of ammonia is sometimes employed in industrial processes; the

resulting mixture of amines is separated by distillation. The ultimate starting materials

for the industrial preparation of allylamine are propene, chlorine, and ammonia.

Alkylation of ammonia can lead to a complex mixture of products, it is used to

prepare primary amines only when the starting alkyl halide is not particularly

expensive and the desired amine can be easily separated from the other components of

the reaction mixture.

Reductive amination processes involve reaction of alcohol with ammonia over

a supported metal catalyst, generally nickel or cobalt on silica or alumina [113, 114]

at temperatures ranging from 150 to 210 °C and pressures of 18 to 200 bar. The

reaction is conducted in the presence of hydrogen to maintain catalyst activity [115].

Some industries use aldehydes or ketones, such as acetaldehyde or acetone, as

feedstocks for reasons of availability and cost relative to the alcohol. When these

unsaturated feedstocks are used, the hydrogen requirement exceeds stoichiometric

amounts based on the alkyl feed. Continuous, fixed bed vapor phase or liquid

phase/trickle bed reactors may be used for alcohol or aldehyde/ketone amination. The

heat of reaction is significantly higher for amination of aldehydes/ketones relative to

alcohols, and some means of controlling the reactor temperature generally is required.

In addition to fixed bed reactors, liquid phase stirred tank reactors also are used

commercially, particularly for amination of carbonyl feedstocks. The reactions are

usually run under conditions selected to achieve high conversion of the alkyl

feedstock, and the product selectivities are controlled by equilibrium as the amination

catalysts also catalyze disproportionation.

Chapter 1

PhD Thesis 31

1.4.1.2. Other routes to amine synthesis

Gabriel synthesis

Gabriel synthesis is the reaction that transforms primary alkyl halides into

primary amines using potassium phthalimide [116–118]. The utility of the method is

based on the fact that the alkylation of ammonia is an unselective and inefficient route

to amines in the laboratory. The conjugate base of ammonia, sodium amide (NaNH2),

is more basic than it is nucleophilic. In fact, sodium amide is used to deliberately

obtain the dehydrohalogenation product. In this method, the sodium or potassium salt

of phthalimide is N-alkylated with a primary alkyl halide to give the corresponding N-

alkylphthalimide. The reaction fails with most secondary alkyl halides. Acid

hydrolysis of N-alkylphthalimide liberates primary amine salt [119].

Staudinger reaction

Staudinger reaction is the combination of an azide with a phosphine or phosphite

which produces an iminophosphorane intermediate. The hydrolysis of the aza-ylide

produces a phosphine oxide and an amine, this reaction is a mild method of reducing

an azide to an amine (Scheme. 1.5). Triphenylphosphine is commonly used as the

reducing agent, yielding triphenylphosphine oxide as the side product in addition to

the amine [120, 121].

Scheme. 1.5. Staudinger reaction for the synthesis of pinwheel compound

Schmidt reaction

The Schmidt reaction involves alkyl migration over the carbon-nitrogen

chemical bond in an azide with expulsion of nitrogen [122]. The reagent used is

hydrazoic acid and the reaction product depends on the type of reactant. Carboxylic

acids form amines through an isocyanate intermediate and ketones form amides. A

catalyst is required which can be a protic acid usually sulfuric acid or a Lewis acid. It

Chapter 1

PhD Thesis 32

is a tool regularly used in organic chemistry for the synthesis of new organic

compounds eg. 2-quinuclidone.

Hofmann rearrangement

The Hofmann rearrangement is the rearrangement of a primary amide in

presence of bromine and NaOH to a primary amine with one fewer carbon atom than

the starting primary amide [123, 124]. The reaction of bromine with sodium

hydroxide in situ forms sodium hypobromite, which converts the primary amide into

an intermediate isocyanate. The intermediate isocyanate is hydrolyzed to a primary

amine giving off carbon dioxide.

Nitrile reduction

In nitrile reduction a nitrile is reduced to either an amine or an aldehyde with a

suitable chemical reagent (Scheme 1.6). Reagents for the conversion to amines are

lithium aluminium hydride, Raney nickel/hydrogen/or diborane. This organic reaction

is one of several nitrogen-hydrogen bond forming reactions [125].

Diisopropylaminoborane [BH2N(iPr)2] in the presence of a catalytic amount of

lithium borohydride (LiBH4) reduces a large variety of aliphatic and aromatic nitriles

in excellent yields. BH2N(iPr)2 can also reduce nitriles in the presence of

unconjugated alkenes and alkynes [126].

Scheme.1.6. Nitrile reduction to form amine

Hydroamination

The hydroamination reaction is the addition of an N-H bond across the C=C or

C≡C bonds of an alkene or alkyne (Scheme 1.7) [127, 128].

Scheme 1.7. Hydroamination of alkene and alkyne

Chapter 1

PhD Thesis 33

This is highly an atom economic method for preparing substituted amines that

are attractive targets for organic synthesis and the pharmaceutical industry. The

hydroamination reaction is approximately thermodynamically neutral, there is a high

activation barrier due to the repulsion of the electron-rich substrate and the amine

nucleophile. The reaction also has high negative entropy, making it unfavorable at

high temperatures. As a result, catalysts are necessary for this reaction to proceed

[129]. Despite of substantial effort put in this area, the development of a general and

efficient catalytic process for this reaction remains subtle. Progress has been reported

on the hydroamination of alkynes and alkenes using lanthanides and late transition

metals [130-133].

1.4.2. Hydroaminomethylation-Advancement in last decade

The hydroaminomethylation (HAM), discovered in 1949 in the laboratories of

BASF by Walter Reppe, using [Fe(CO)5] [134, 135] is a promising reaction to fulfill

the requirement of waste reduction since water is the only side product. HAM is a

one-pot cascade reaction, starting with the hydroformylation of an alkene, consecutive

condensation of the intermediate aldehyde with the substrate amine, and subsequent

hydrogenation of the formed enamine or imine to the desired amine product. In this

reaction, primary and secondary amines, as well as ammonia can be used as the amine

substrate. The HAM with ammonia is particularly challenging in terms of

chemoselectivity, since the desired primary amine is more nucleophilic than ammonia,

leading to a higher reactivity towards the intermediate aldehyde, which in turn results

in the formation of a secondary amine.

HAM consists of a domino reaction, hydroformylation and a reductive

amination. This implies that side products of both reactions might be observed in the

HAM reaction (Scheme 1.8). In the HAM of alkenes, both the linear and the branched

amines can be formed. The regioselectivity of the product amines are important in

which one of the isomer is preferred over the other to have easy separation and

commercial viability of the reaction. This regioselectivity is already determined in the

first reaction step, the hydroformylation where the n-aldehyde or iso-aldehyde are

formed. Chemoselectivity, which comprises the selectivity to the amine product, is

mainly determined in the reductive amination step. Very important in this respect is

the hydrogenation of the C=N double bond of the enamine or imine. If the reduction

with H2 is not effective the reaction ends up with imine or enamine.

Chapter 1

PhD Thesis 34

(R1 = R2 = R3= H, alkyl or aryl groups)

Scheme. 1.8. Possible reactions (desired and side products) during

hydroaminomethylation

Although the hydroaminomethylation (HAM) has been discovered already in

the late 1940s, the majority of the reports concerning this reaction stems from the last

10-12 years. The researches on hydroaminomethylation are still in its early stage

having promising potential for its well exploration. In available literatures [136-138]

most of the works are focused on homogeneous hydroaminomethylations using

various ligands keeping Rh as the metal center. Some reports [139, 140] are also

available with biphasic systems. Rather than detail catalytic studies the research is

more focused on synthesis of various amine containing organic compounds using

hydroaminomethylation. The contributions of Elibracht [141-143] and Beller [144,

145] to hydroaminomethylation are outstanding.

1.4.2.1. Contributions of P. Elibracht and co-workers to hydroaminomethylation

Peter Elibracht and co-workers have done an extraordinary research in the

field of homogeneous hydroaminomethylation for the synthesis of various valuable

organic molecules. In the time of starting of their noteworthy research in

hydroaminomethylation symmetrically and unsymmetrically substituted secondary

and tertiary amines are selectively synthesized in high yields by a one-pot

Chapter 1

PhD Thesis 35

hydroaminomethylation of ammonia or primary amines with styrene and/or cyclic

olefins, carbon monoxide and hydrogen in the presence of [Rh(cod)Cl]2, catalyst [146,

147].

Scheme 1.9. Bisalkylation of styrene with ammonia [146]

They could get isolated yields above 70% for methyl styrene with amines like

butylamine, aniline and benzylamine. Bisalkylation of styrene with ammonia was also

possible with the catalyst (Scheme 1.9). In another study using [Rh(cod)Cl]2 and

Rh(acac)(CO)2 Elibracht et al., could synthesize azomacrocycles via ring closing

hydroaminomethylation (Scheme 1.10 ) [148]. The substrates were diolefins and

diamines. The macrocycles of up to 36 ring size were synthesized.

Scheme 1.10. Ring closing hydroaminomethylation: Synthesis of macroheterocycles

The catalyst Rh(acac)(CO)2 was used for the synthesis of α−

and β−aminofunctionalized amines and silanes via hydroaminomethylation of

enamines and silanes [149]. The hydroaminomethylation of vinylsilanes with

morpholine yielded more than 80% of the product. The reaction with benzylamine

and isopropylamine gave low yields because of the cleavage of vinylsilane bond

leading to the generation of (diphenyl)-methylsilanol. This vinylsilane bond cleavage

is depending on the substituents in the silyl moiety. If trialkyl substituents instead of

aryl functionalities are introduced, the hydroaminomethylation sequence can be

performed in medium yields without vinylsilane cleavage. Hydroaminomethylation of

Chapter 1

PhD Thesis 36

an enamine, N-vinyl pyrrolidone with morpholine (Scheme 1.11) gave 89% yield of

the α− and β−aminofunctionalized amines with iso/n ratio of 1.9/1.

Scheme 1.11. Hydroaminomethylation of N-vinyl pyrrolidine with morpholine

Secondary and tertiary naphthylpropylamines are prepared in high yields by

the reaction of 2-vinylnaphthalene, primary or secondary amines, carbon monoxide

and hydrogen in presence of [Rh(cod)Cl]2 as catalyst via a single pot

hydroformylation-amine condensation-reduction sequence [150].

Scheme 1.12. Hydroaminomethylation of allylic ethers

The reaction of 2-vinylnaphthalene with primary and secondary amines gave

yields near to 90%. Heterofunctionalized allylic ethers, silanes and amines were

hydroaminomethylated in presence of primary and secondary amines to form

corresponding γ- and δ-amino functionalized compounds (Scheme 1.12) [151].

Elibracht et al., also synthesized biologically active 1,3- and 1,4-diamines (Fig.

1.13) via hydroaminomethylation of heterocyclic allylic amines [152]. They could

synthesize phenothiazine, imonodibenzyl, carbazole and pyrazole derivatives using

hydroaminomethylation. These experiments were extended further towards the

synthesis of pharmacologically active secondary and tertiary 1-(3,3-

diarylpropyl)amines by the reaction of 1,1-diarylethenes with primary or secondary

amines [153]. [Rh(cod)Cl]2 with PBu3 as ligand was used as the catalyst. 1,1-

Chapter 1

PhD Thesis 37

diphenylethene with piperidine gave fenpiprane, which is a antiallergic medicinal

compound.

Fig. 1.13. Examples of biologically active 1,3- and 1,4-diamines

Similarly didisopromine, tolpropamine, prozapine and fendiline were

synthesized in high yields (>70%). Polyazamacroheterocycles were synthesized from

dienes and α, ω-diamines and the resultant macrocycles were debenzylated and that

the resulting macrocyclic diamines undergo a second ring-closing

bis(hydroaminomethylation) to give cryptand systems [154].

Hydroaminomethylation of fattyacids like oleic acid ethyl ester with the

primary amines hexylamine, benzylamine, and with the secondary amine morpholine

gave interesting set of substituted surfactants (Scheme 1.13) [155]. Reactions gave

yields of >97% for all these substrates.

Scheme. 1.13. Hydroaminomethylation of oleic acid ethyl ester

Chapter 1

PhD Thesis 38

Rhodium(I) catalyzed regioselective hydroformylation of diolefins and

subsequent reductive amination of the dialdehydes in the presence of α,ω-diamines is

applied to azamacroheterocyclic ring synthesis [156]. Starting from aromatic diallyl

ethers of hydroquinone, biphenol and binaphthol 20–28 membered macroheterocycles

were obtained up to 78% yield. Synthesis of hydroquinone-, biphenol-, and

binaphthol-azamacro heterocycles via regioselective hydroaminomethylation were

conducted using Rh(acac)(CO)2 and then was studied with ligands BIPHEPHOS and

XANTPHOS (Fig. 1.14) for the required regioselectivity [157]. The experiment with

BIPHEPHOS was unsuccessful because of the instability of ligand under harsh

conditions of hydroaminomethylation. Therefore XANTPHOS ligand was used which

is stable under hydroaminomethylation conditions with good regioselectivity.

OO

O O

P P

O

O

O

O

O

P P

BIPHEPHOS XANTPHOS

Fig. 1.14. Structure of BIPHEPHOS and XANTPHOS ligands

The pharmaceutically important 3,3-diarylpropylamine was synthesized using

hydroaminomethylation [158]. This product finds application in the treatment of

urinary incontinence and other spasmogenic conditions. Many other significant

contributions of Eilbracht and co-workers are reported in literature [159–162].

1.4.2.2. Contributions of M. Beller and co-workers to hydroaminomethylation

Matthias Beller et al. have significant contributions for

hydroaminomethylation reactions. They have used different ligands and improved

protocols for the hydroaminomethylation [163]. The first efficient

hydroaminomethylation with ammonia using dual metal catalysts and two-phase

catalysis to primary amines were successfully introduced [164]. The catalyst used was

Rh/Ir dual metal with TPPTS ligand. The important objective of the research was a

Chapter 1

PhD Thesis 39

more rapid hydrogenation of the imine to amine and thus fewer side reactions of

intermediates by the use of dual metal catalysts (Rh/Ir), and a simple catalyst

separation through phase separation and control of selectivity with respect to the

formation of primary, secondary, and tertiary amines [165] by the use of the principle

of biphasic catalysis. The use of BINAS (sulphonated NAPHOS) ligand [166] with

the dual metal could give higher yields than TPPTS with n/iso ratio of 99:1. In

another study, hydroformylation was conducted with various ligands like triphenyl

phosphine (TPP), IPHOS, XANTPHOS, dppe (1,2-bisdiphenyl phosphinoethane),

dppb (1,2-bisdiphenyl phosphine butane) with Rh(cod)2BF4 (cationic) as catalyst

precursor [167]. Hydroaminomethylation of 1-pentene with piperidine was conducted

and XANTPHOS was found as a better ligand with high yields and selectivity. This

study on aliphatic olefins gave for the first time the corresponding linear amines in

general with regioselectivities >98:2.

Fig. 1.15. Pharmaceutical pheniramine drugs synthesized by hydroaminomethylation

Chapter 1

PhD Thesis 40

A rhodium carbene complex Rh(cod)(Imes)Cl (Imes=1,3-dimesitylimidazol-2-

ylidene, cod=cyclooctadiene) was prepared from [Rh(cod)Cl]2 and used as a

hydroaminomethylation catalyst [168]. Similarly five different rhodium carbene

complexes were synthesized and used for the synthesis of 3,3-diarylpropylamines.

Various pharmacologically active 3,3-diarylpropylamines were synthesized using

these catalysts as shown in Fig. 1.15. The hydroaminomethylation of 1-pentene with

piperidine (Scheme 1.14) in different solvents toluene, methanol and THF showed

that THF is having, higher hydrogenation activity than that of toluene and higher

chemoselectivity than that of methanol for the rhodium carbene complex.

Scheme. 1.14. Hydroaminomethylation with Rh-carbene catalyst

The catalysts were synthesized from Rh(cod)Cl2 precursor with five different

substituted 1,3-dimesitylimidazol-2-ylidene (Fig. 1.16) [169]. The synthesis of

pheniramines were yielded with maximum TOF (turn over frequency) of 288 h-1 with

rhodium carbene catalyst, 4 . The conversion levels were >90% with high n/iso ratio

of 99:1.

Chapter 1

PhD Thesis 41

Fig. 1.16. Rh-carbene complexes

The hydroaminomethylation of arylethylenes with anilines proceeds under

mild conditions in the presence of [Rh(cod)2BF4] as catalyst precursor and dppf (1,1’-

bisdiphenyl phosphine ferrocene) as ligand to give the corresponding branched

amphetamine derivatives in good selectivity and yield [170]. The catalyst gave better

yields by the addition of a catalytic amount of tetrafluoroboric acid with a slight

increase in the iso/n ratio. The role of the acid is not fully known, the enhancement of

the yield can be partly attributed to the formation of iminium ions, which are reduced

to the corresponding amines.

Internal alkenes were efficiently hydroaminomethylated to linear amines using

a variety of ligands [171]. Substituted xantphenaxophos, homoxantphenaxophos,

Chapter 1

PhD Thesis 42

thixantphenaxophos, nixantphenaxophos etc., were used as ligands for this reaction.

Pent-2-ene was used as internal alkene with piperidine to give linear amines with

>65% selectivity in a toluene/methanol mixed solvent. [Rh(cod)2]BF4 was used as the

catalyst precursor. A conversion of 100% with linear amine selectivity of 95% for 2-

pentene and piperidine was obtained using xantphenaxophos ligand.

Similarly other reports using supercritical ammonia [172], effect of lewis acid

on rhodium complexes with phosphine ligands bearing donor sites [173] were

investigated by Beller et al.

1.4.2.3. Important contributions to hydroaminomethylation by other groups

The contributions of Alper et al. to hydroaminomethylations are noteworthy.

A novel route to 1,2,3,4-tetrahydroquinolines via rhodium(I) catalyzed

hydroaminomethylation of 2-isopropenylanilines was an important achievement

[174]. Tetrahydroquinolines play an important role in the fields of natural products

and medicinal chemistry. They are of synthetic interest for the preparation of

pharmaceuticals and agrochemicals, as well as in material sciences. Ionic diamine

rhodium(I) complexes were used as the catalyst (Fig. 1.17). The catalysis could give

tetrahydroquinolines in high yields.

Fig. 1.17. Structure of ionic diamine rhodium(I) complex

The same catalyst (Fig. 1.17) was used for the synthesis of 2,3,4,5-Tetrahydro-

1H-2-benzazepines [175]. Notable features of the method were, the air stable catalyst

not requiring added phosphine, the ease of access of substrates and the high product

yields.

Hydroaminomethylation of long chain alkenes with dimethylamine catalyzed

by a water-soluble rhodium–phosphine complex, RhCl(CO)(TPPTS)2 in an aqueous–

organic two-phase system in the presence of the cationic surfactant

cetyltrimethylammonium bromide (CTAB) was investigated by Luo and co-workers

Chapter 1

PhD Thesis 43

[176]. The addition of the cationic surfactant CTAB accelerated the reaction due to

the micelle effect. Lou et al. also extended their studies on biphasic

hydroaminomethylation in ionic liquids (1-n-alkyl-3-methylimidazolium tosylates)

with Rh-BISBIS (sulfonated 2,2’-bis(diphenylphosphinomethyl)-1,1’ -biphenyl)

complex as catalyst [177, 178]. High activity and selectivity for amines were achieved

using this biphasic hydroaminomethylation. The ionic liquid containing catalyst was

easily separated and recycled several times with only a slight decrease in activity.

Anti-depressant drug aripiprazole and anti-arrhythmia drug ibutilide were

synthesized using Rh-bisphosphite catalyst via hydroaminomethylation [179]. The

reaction at 75 oC in THF at 18 h gave 55 and 67% yield to ibutilide and aripiprazole

respectively (Scheme 1.15).

HN

MeO2S

OH

+ HNn-heptyl

EtRh(CO)2(acac), bisphosphite

CO/H2, THF, temp.

HN

MeO2S

OH

Nn-heptyl

Et

Ibutilide

NH

O O

+ HN N

Cl Cl

Rh(CO)2(acac), bisphosphite

CO/H2, THF, temp.

NH

O ON

N

Cl

Cl

Aripoprazole

Scheme 1.15. Synthesis of ibutilide and aripiprazole via hydroaminomethylation

Rhodium complex, Rh(nbd)Cl2 (nbd = 1,5-norbornadiene) catalyzed

hydroaminomethylation of steroids in the presence of aminoalcohols gave hydroxy-

aminomethyl derivatives in moderate to good yields [180]. The multi-step reaction

being highly chemo and regioselective giving new compounds containing the hydroxy

function can serve as starting material for further functionalization of the steroid

skeleton. The rhodium catalyzed hydroaminomethylation of 1-octene with morpholine

has been studied using temperature-dependent solvent, i.e., thermomorphic solvent

systems (TMS systems). High conversions of the olefin and high selectivities to the

amines are obtained in TMS systems consisting of propylene carbonate, an alkane and

a semi-polar mediator [181]. Hydroaminomethylation reactions were conducted in

imidazolium-based ionic liquid using a rhodium-sulfoxantphos system by reacting

Chapter 1

PhD Thesis 44

piperidine with different alkenes and have given yields >95% of the product amine

with turnover frequencies of up to 16,000 h-1, along with high regioselectivity for the

linear amines with linear/branch ratios up to 78 [182]. Hydroaminomethylation using

various olefins and amines substrates and metal complexes were studied and

investigated in detail [183–187].

Hence in view of the above, hydroformylation which is extensively

investigated and hydroaminomethylation which is scantly investigated, both in

homogeneous conditions are the topic of interest to carry out in heterogeneous

conditions. Therefore the scope in this regards are very much. Attempt in the present

work is towards the development of suitable heterogeneous catalysts using a suitable

solid support for the synthesis of aldehydes (hydroformylation) and amines

(hydroaminomethylation). The heterogenization of existing homogenous catalyst was

done into the pores of a porous support which could act as nanophase reactors for

hydroformylation and hydroaminomethylation reactions.

1.5. Aim and objectives of the present work

The aim of the present work in this thesis is to synthesize rhodium based

heterogeneous catalyst for utilization in two important reactions, (1)

hydroformylation for the synthesis of aldehydes and (2) hydroaminomethylation for

the synthesis of amines. This heterogenization is done using a solid inorganic support.

Heterogenized catalyst has the potential of easy separation from the product mixture

and recyclability.

Hexagonal mesoporous silica (HMS) is an ordered mesoporous material which

is not well explored for heterogenization for hydroformylation reactions. Synthesis of

HMS is very elegant and done at room temperature. Here the objective is to

heterogenize HRh(CO)(PPh3)3 and Rh(Cl)(TPPTS) complexes in to the pores of HMS.

The complexes are in situ encapsulated thus avoiding the calcination and

functionalization of the support. The complex is trapped in the reverse micelles of the

surfactant or structure directing agent, C10 to C18 amines, which is in the pores of

HMS.

The catalyst is synthesized by in situ method as shown in Fig. 1.18. The

synthesized catalyst has shown the potential to act as nanophase reactor.

Chapter 1

PhD Thesis 45

Fig. 1.18. Synthesis of HRh(CO)(PPh3)3 encapsulated HMS

The synthesized heterogeneous catalyst using HRh(CO)(PPh3)3 is used for the

hydroformylation of propene. Propene hydroformylation is industrially high

demanding. The reaction is investigated for parametric variations and reaction

kinetics. A study on chemical engineering parameters is useful for the understanding

of the extent of mass transfer resistance. The same catalyst is then investigated for the

effect of different chain length of surfactant amine and thus the pore structure of HMS

on hydroformylation. Three different substrates, 1-hexene, styrene and cylcloheptene,

are hydroformylated. A detailed kinetic studies and kinetic modeling is investigated

for 1-hexene hydroformylation.

Fig. 1.19. Synthesis of RhCl(TPPTS)3 in HMS

Similarly RhCl(TPPTS)3 is in situ encapsulated in HMS as shown in Fig. 1.19.

The water soluble complex may have the better solubility thus increasing the better

encapsulation capacity inside the pores of HMS. Hydroformylation of functionalized

olefin, vinyl esters, are important in the production of industrially important

Chapter 1

PhD Thesis 46

intermediates. RhCl(TPPTS)3 complex is encapsulated in the hexagonal mesoporous

silica for this purpose. A study on parametric variations is conducted with vinyl

acetate as a representative vinyl ester.

Hydroaminomethylation is atom economic synthesis of amines which is less

studied in heterogeneous catalysis. Calcined HMS functionalized with aminopropyl

trimethoxy silane (APTMS) was used as a support for heterogenization of

HRh(CO)(PPh3)3 complex. The methodology of functionalization and encapsulation

of complex is given in Scheme. 1.16. The catalyst is investigated in detail for

hydroaminomethylation with various alkene and amine substrates.

Scheme 1.16. Functionalization of HMS and encapsulation of HRh(CO)(PPh3)3

complex

The investigations are further carried out with Rh exchanged Na-ETS-4 and

Na-ETS-10 (titanosilicates). The acidic nature of the ETS support can help in the

formation of enamine intermediates that facilitates the hydroaminomethylation. The

activity of both the catalysts is evaluated for various alkenes and amines for

hydroaminomethylation.

Chapter 1

PhD Thesis 47

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