Open Access Chemistry: Organic synthesis

Benazepril, brand name Lotensin (Novartis), is a medication used to treat high blood pressure (hypertension), congestive heart failure, and chronic renal failure. Upon cleavage of its ester group by the liver, benazepril is converted into its active form benazeprilat, a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor.

Benazepril, brand name Lotensin, is a medication used to treat high blood pressure (hypertension), congestive heart failure, and chronic renal failure. Upon cleavage of its ester group by the liver, benazepril is converted into its active form benazeprilat, a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor.

The reaction of 2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (I) with PCl5 in hot xylene gives 3,3-dichloro-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (II), whichis treated with sodium acetate and reduced with H2 over Pd/C in acetic acid yielding 3-chloro-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (III). The reaction of (III) with sodium azide in DMSO affords 3-azido-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (IV), which is condensed with benzyl bromoacetate (V) by means of NaH in DMF giving 3-azido-1-(benzyloxycarbonylmethyl)-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (VI). The treatment of (VI) with Raney-Ni inethanol-water yields 3-amino-1-(benzyloxycarbonylmethyl)-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (VII), which is debenzylated by hydrogenation with H2 over Pd/C in ethanol affording 3-amino-1-(carboxymethyl)-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (VIII). Finally, this compound is condensed with ethyl3-benzylpyruvate (IX) by means of sodium cyanoborohydride in methanol acetic acid.

REFERENCE

1. Casta馿r, J.; Serradell, M.N.; CGS-14824 A. Drugs Fut 1984, 9, 5, 317.Ciba-Geigy Corp. (USA).

2. Watthey, J.W.H. (Ciba-Geigy AG); EP 72.352, GB 2.103.614, JP 83.38.260.

The reaction of 3-bromo-1-phenylpropane (I) with KCN gives 4-phenylbutyronitrile (II), which is hydrolyzed to the corresponding butyric acid (III). The cyclization of (III) with polyphosphoric acid affords 1-tetralone (IV), which is brominated to 2-bromo-1-tetralone (V) and treated with hydroxylamine to give the oxime (VI). The Beckman rearrangement of (VI) yields 3-bromo-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (VII), which is treated with sodium azide to afford the azide derivative (VIII). The N-alkylation of (VIII) with ethyl bromoacetate (IX) by means of KOH and tetrabutylammonium bromide in THF gives the N-alkylated azide (X), which is reduced by catalytic hydrogenation to the corresponding amine (XI). The hydrolysis of the ester group of (XI) with NaOH yields the free acetic acid derivative (XII), which is finally reductocondensed with ethyl 2-oxo-4-phenylbutyrate (XIII) by means of sodium cyanoborohydride

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de: Struktur von Glycerin; en: Structure of gl...

Structure of glycerol (Photo credit: Wikipedia)

Using solvents in chemical synthesis represents a greater challenge in the respect of Green Chemistry and Solvents like Water, PEG-600 and Ionic liquids has proved as potential green solvents for organic synthesis. In the past, Using Glycerol as solvent has not used for organic synthesis and recently various developments has proved that Glycerol can be used an efficient GREEN SOLVENT.

Glycerol (or glycerine, glycerin) is a simple polyol compound. It is a colorless, odorless, viscous liquid that is widely used inpharmaceutical formulations. Glycerol has three hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature.

The glycerol backbone is central to all lipids known as triglycerides. Glycerol is sweet-tasting and of low toxicity.Glycerol can be produced either by microbial fermentation or chemical synthesis from petrochemical feedstock. It can also be recovered from soap manufacturing. In the traditional process of the latter, glycerol is released as a by-product during the hydrolysis of fats.This process is currently of less importance, since soap has been largely replaced by detergents (Wang et al., 2001).

Glycerol is usually produced as a byproduct of the transesteriﬁcation of a triglyceride in the production of natural fatty acid derivatives. These derivatives are utilized in many areas from pharmaceuticals and food industry to alternative fuels,e.g., biodiesel, and thus as the production of glycerol raises its price decreases. In addition, glycerol has also promising physical and chemical properties. It has a very high boiling point and negligible vapor pressure; it is compatible with most organic and inorganic compounds, and does not require special handling or storage. Glycerol, as other polar organic solvents such as DMSO and DMF, allows the dissolution of inorganic salts, acids, and bases, as well as enzymes and transition metal complexes (TMCs), but it also dissolves organic compounds that are poorly miscible in water and is non-hazardous.

Different hydrophobic solvents such as ethers and hydrocarbons which are immiscible in glycerol allow removing the products by simple extraction. Distillation of products is also feasible due to the high boiling point of glycerol.

Glycerol, which is a non-toxic, biodegradable, and recyclable liquid manufactured from renewable sources, shows similar properties as an ionic liquid and has a high potential to serve as green solvent for organic syntheses. This has led us to study its possible use as such in a variety of ways. Several non-catalytic and catalytic reactions using homogeneous and heterogeneous chemo- and bio-catalysts have been thus studied in glycerol. The unique physico-chemical nature of glycerol enables easy separation of the product by extraction or distillation together with catalyst recycling. These properties can also be translated into other processes which require non-aqueous polar solvents such as non-aqueous emulsions (Imhof and Pine 1997), as well as applications in microwave promoted synthesis (Kappe 2004).

Fig:Production of glycerol by trans-esterification

Applications:

for major applications...see HERE

Glycerol is present in many applications in the cosmetic, paint,automotive, food, tobacco, pharmaceutical, pulp and paper, leather and textile industries. It also is used as a feedstock for the production of various chemicals (Wang et al., 2001).
New applications are being evaluated in the food industry, the polyglycerol and polyurethane industry, the ﬁeld of wood stabilizers and production of small molecules, such as dihydroxyacetone, glyceric and hydroxypyruvic acids and glycerol carbonate (Claude, 1999).
One of the many promising applications for the use of glycerol is its bio-conversion to high value compounds through microbial fermentation. Glycerol is not only cheap and abundant, but its greater degree of reduction than sugars offers the opportunity to obtain reduced chemicals, as succinate, ethanol, xylitol, propionate, hydrogen, etc. at higher yields than those obtained using sugars (Dharmadi et al., 2006).
Glycerol can be used as solvent for catalytic reduction of organic compounds...see PDF
For catalytic transfer hydrogenations of Olefines....see PDF
For the synthesis of vinyl sulfides-as a solvent...see PDF
Used a solvent for Microwave assisted synthesis of disulfides...see PDF
As a promising carbon resource for industrial microbiology...see PDF
As an alternative solvent for the synthesis of Thiazoles...see PDF
Used as a support hydrogenolysis catalyst of Palladium catalyst...see HERE
As a renewable source of more benign solvents...see PDF
As a solvent for carbonyl comppound reductions..see PDF
Synthesis of cyanomethyl phenyl thiazoles under MW...see PDF