Hydrogen and hydrolysis

The production of 1,4-butanediol (1,4-BDO) from propylene via the carbonylation of allyl acetate is noted in Chapter 8. 1,4-Butanediol from maleic anhydride is discussed later in this chapter. An alternative route for the diol is through the acetoxylation of butadiene with acetic acid followed by hydrogenation and hydrolysis. 

The other way of reducing nitriles to aldehydes involves using a metal hydride reducing agent to add 1 mol of hydrogen and hydrolysis, in situ, of the resulting imine (which is undoubtedly coordinated to the metal). This has been carried out with LiAlH4, LiAlH(OEt)3, LiAlH(NR2)3, and DIBAL-H. The metal hydride method is useful for aliphatic and aromatic nitriles. 

Cycloaddition of furans followed by a subsequent transformation is still adopted as a useful strategy to prepare fluorine-containing benzene derivatives and isoquinoline compounds <00SL550>. The cycloaddition adduct can also be converted to a trifluoromethyl substituted cyclohexanone compound via hydrogenation and hydrolysis. Examples of these transformations are illustrated below. 

Deoxy-2-fluoro-D-ribose (83) has been prepared by fluorina-tion,2,8-220 hydrogenation, and hydrolysis of 2,2 -anhydro-( 1 -/3-D-ara-binofuranosyluracil) (82), followed, for purification purposes, by ben-zoylation of the resulting product, and hydrolysis221 (see also, Ref. 222). 

A very popular alternative to aspirin and acetaminophen is ibuprofen, which has tradenames such as Motrin and Advil . It can be synthesized from isobutylbenzene by a Friedel-Crafts acylation with acetyl chloride, followed by formation of a cyanohydrin. Treatment with H2/Pd reduces the benzylic hydroxyl to a hydrogen and hydrolysis of the nitrile gives the carboxylic acid. There are at least six published syntheses of ibuprofen. This illustrates the difficulty of knowing which technology a particular company is using. At the other extreme is the proprietary nature of some syntheses, where they have not yet been published. 

The adipic acid process we have developed involves butadiene oxidative carbonylation in the presence of methanol, a l, l-dimethoxycyclohexane dehydration agent, and a palladium(ll)/ copper(ll) redox catalyst system (Equation 1.). The reaction sequence includes an oxycarbonylation, hydrogenation and hydrolysis step(17-19). The net result is utilization of butadiene, the elements of synthesis gas, l, -dimethoxycyclohexane and air to give adipic acid, cyclohexanone and methanol. 

BERGMANN AZLACTONE PEPTIDE SYNTHESIS. Conversion of an aoetylated amino add and an aldehyde into an azlactone with an alkylcnc side chain reaction with a second amino add with a second amino acid with mig opening and formation of an acylated unsaturated dipeptide, followed by catalytic hydrogenation and hydrolysis to the dipeptide. 

Although in the few months before financial support was terminated there was little time to optimize the hydrogenation and hydrolysis steps, the best hydrogenation conditions, giving a yield of dihydrohypoxanthine of >90%, were found to be as follows ... 

Scheme 12.25 Fonnation of hydrogenation and hydrolysis products from 2-methylfuran.

Aromatic methoxyamidation. The reaction of silver salts with N-ehloro-N-meth-oxyamides in an acid medium generates a nitrenium ion that is sufficiently stable to permit aromatic substitution (equation 1). The products can be converted into anilines by hydrogenation and hydrolysis. 

Addition of alkenylzirconium (51) to steroid-derived allylpalladium (52), followed by hydrogenation and hydrolysis, gives 25-hydroxycholesterol in 66% overall yield from (52 Scheme 15). Finally,... 

The H2S COS ratio of a raw gas is determined by the hydrogenation and hydrolysis reactions. Under typical gasification conditions H2S is the dominant species and approximately 93-96% of the sulfur is in this form, the rest being COS. 

The general approach was a base catalyzed condensation of the diketopiperazine with an aldehyde, followed by hydrogenation and hydrolysis. The glycine-L-aspartic acid diketopiperazine ester (5) can be prepared by standard peptide coupling procedures, but our preferred method at scale is to prepare the glycine unit from chloroacetyl chloride and ammonia (Scheme 11). 

One example of reductive amination of acylphosphonates has been reported. Thus, reaction of dimethyl 1-oxoalkylphosphonates with benzhydrylamine results in the formation of an imine reduced in situ with NalllKOAc),. The reaction is independent of the solvent, and THF, CIFCh and CHCI3 give similar results - After selective removal of the benzhydrylic group by catalytic hydrogenation and hydrolysis with concentrated HCl, the 1 -aminoalkylphosphonic acids are isolated in satisfactory yields (30-60%, Scheme 7.66) ... 

Fig. 3 Overall sequence for azlactone synthesis, hydrogenation, and hydrolysis for the preparation of amino acids.

The comparative analysis of the kinetic principles relating to the conversion of ENMP by hydrogenation and hydrolysis routes has been performed, and the parameters determining the selectivity of ENMP hydrogenation have been established. 

It has now been demonstrated that carpaine, which was previously assumed to be a pyrrolidine derivative, is actually a piperidine alkaloid. The key to the skeleton previously suggested was provided by a nitrogen-free hydroxy acid of probable composition C14H28O3, m.p. 20-25°, isolated from carpaine by a two-stage Hofmann degradation, followed by hydrogenation and hydrolysis (111). Rapoport and Baldridge (112)... 

The known 7-e carboxylic acid 506, obtained by the condensation of acrylic acid with furan, was used as a substrate for synthesis of validamine, (510) a component of validamycin antibiotics. The treatment of 506 with hydrogen peroxide in formic acid gave the tricyclic compound 507, which after reduction and hydrolysis afforded cyclitol. Treatment of 508 with 2,2-dimethoxy-propane in the presence of an acid gave a mixture of diisopropylidene derivatives in which compound 509 was predominant. Introduction of an amino group, by way of a tosyl ester and azide displacement, followed by hydrogenation and hydrolysis, completed the synthesis of DL-val-... 

The oxidative acetoxylation product l,4-diacetoxy-2-butene can be converted into 1,4-butanediol via hydrogenation and hydrolysis. The order of the hydrolysis... 

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