Ritter reaction catalyst

The Ritter reaction is an effective way to form amides by coupling nitriles with alcohols. Typically tertiary, benzylic or allylic alcohols, or substrates which form relatively stable intermediate carbocations by reaction with sulfuric acid, are used. A recent review by Cossy provides an in depth review on the recent advances in metallic and non-metallic Ritter reaction catalysts. ... 

Davies and Reider (1996) have given some details of the HIV protease inhibitor CRDCIVAN (INDINAVIR) for which (lS,2R)-c -amino indanol is required. Indene is epoxidized enantioselectively, using the lacobsen strategy (SS-salen Mn catalyst, aqueous NaOH and PiNO), to (lS,2/ )-indene oxide in a two-phase system, in which the OH concentration is controlled. Indene oxide was subjected to the Ritter reaction with MeCN, in the presence of oleum, and subsequent hydrolysis and crystallization in the presence of tartaric acid gives the desired amino indanol. 

Br prevents side reactions and makes BiBr3 a better Lewis acid catalyst, which is in accordance with our work BiBr3 affords only Ritter reaction products in the high dielectric constant solvent CH3CN, while BiCl3 originates a mixture of both v7 -/V-acylamino-hydroxy compounds and chlorohydrins. 

Exercise 15-24 It is possible to prepare amides from tertiary alcohols and alkane-nitriles, RCN, in concentrated sulfuric acid as the catalyst (Ritter reaction), as illustrated in the equation for the synthesis of W-fe/f-butylethanamide ... 

The chirality conies from the diamine and the oxidation from ordinary domestic bleach (NaOCl), which continually recreates the Mn=0 bond as it is used in the epoxidation. Only 0.7% catalyst is needed to keep the cycle going efficiently. The epoxide is as good as the diol in the Ritter reaction and the whole process gives a 50% yield of enantiomerically pure cis-ami no-indanol on a very large scale. 

If the reactions are carried out in a nitrile as solvent, rather than dichloromethane, using triflic acid as catalyst, a modified Ritter reaction takes place, and the intermediate nitrilium ion traps the liberated amine, forming an amidine (Scheme 67). In an earlier reaction cf. Scheme 67) the lithium perchlorate catalyzed reaction of sulfenyl chlorides with alkenes in the presence of nitriles had also given l-amido-2-sulfenyl adducts. Ritter products are also obtained in good yields by anodic oxidation (Pt or C, 1.2-1.4 V) of disulfides in acetonitrile, in the presence of excess alkene, using B114NBF4 as supporting electrolyte (Scheme 68). ... 

Preparation. A number of methods have been reported for both the racemic and asymmetric preparations of l-amino-2,3-dihydro-lH-inden-2-ol (1), most commonly starting from inexpensive and readily available indene. These methods have been described in detail in recent reviews. The valuable properties of 1 as both a component of a medicinally active compound and as a chirality control element, derive primarily from its rigid and well-defined stereochemical structure. As a result, the compound is most desirable in enantiomerically pure form. One of the most efficient asymmetric syntheses of 1, which may be employed for the synthesis of either enantiomer of the target molecule, involves an asymmetric epoxidation (89% yield, 88% ee) of indene to give epoxide 2 using the well-established Jacobsen catalyst. This is followed by a Ritter reaction using oleum in acetonitrile resulting in conversion to the oxazoline (3) which is subsequently hydrolysed to the amino alcohol. Fractional crystallization with a homochiral diacid permits purification to >99% ee (eq 1). ... 

A new and convenient method was found for the one-pot synthesis of symmetrical and unsymmetrical linear imides in the presence of SSA. The amidation of alcohols with nitriles in the presence of an acidic catalyst is known as the Ritter reaction. Salehi et al. have modified this method and developed the one-pot synthesis of a wide variety of linear imides instead of alcohols [97] (Scheme 5.17). 

Other acid-catalysed addition reactions include reaction with nitriles (Ritter reaction), formaldehyde (Prins reaction) and carbon monoxide and water (Koch reaction). These reactions are normally catalysed by concentrated sulphuric acid. Extensive isomerization occurs and may even lead to quaternary compounds of the type RC(CH3)XR where X is the new functional group introduced into the molecule. Homogeneous catalysts have been developed which give simpler products without extensive isomerization. 

Rapolu, R.K., NabaMukul, B.M., Bommineni, S.R., Potham, R., Mulakayala, N., Oruganti, S. 2013. Silica sulfuric acid A reusable solid catalyst for the synthesis of N-substituted amides via the Ritter reaction. RCS Advances 3 5332-5337. 

Recently, Rapolu et al. (2013) synthesized primary amides by the Ritter reaction of secondary and tertiary alcohols with nitriles catalyzed by SSA catalyst in toluene at 90°C (Scheme 5.55). As the catalyst is cost-effective, stable to air, and recyclable, the present method constitutes a noteworthy modification to the Ritter reaction for the synthesis of amides. Under these conditions, a variety of amines including sterically hindered amines were successfully reacted to form the corresponding amides in excellent yields. The reaction was observed to be chemoselective in nature. Mirjalilia and Sadeghi (2009) studied the Ritter reaction under solvent-free conditions (Scheme 5.56). 

Mirjalilia, B.B.F. and Sadeghi, B. 2009. SUica sulfuric acid An eco-friendly and reusable catalyst for synthesis of amides via Ritter reaction. Iran. J. Org. Chem. 2 76-79. 

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