Oxazolinones, formation

The poor reaction with C-terminal proline most likely stems from the fact that proline cannot form the necessary oxazolinone for efficient reaction with the isothiocyanate. Work in our laboratory has obviated the need for oxazolinone formation by the use of diphenyl phosphoroisothiocyanatidate and pyridine. Reaction of this reagent with C-terminal proline directly forms the acylisothiocyanate. Once the acylisothiocyanate is formed, the addition of either liquid or gas phase acid followed by water was... 

New syntheses of alkynes through oxazolinone formation 02CC1555. 

I -Acylation. A/-Acylation and related reactions ate brought about in straightforward ways with acyl chloride or acid anhydride, although the proximity of the carboxyl group may produce other reactions, eg, oxazolinone formation, under some conditions. 

In the reaction of N-chloroacetylphenylserine with acetic anhydride, oxazolinone formation was followed by the elimination, not of HCl, but of H2O, to yield 4-benzylidene-2-chloroacetyl-A -oxazolinone (52). Hydrolysis, followed by treatment with ammonia, afforded the first example (16) of a dehydropeptide in which the dehydroamino acid was not at the N-terminal end. 

Y) Oxazolinone formation from P-hydroxyamino acids leads to unsaturated oxazolinones owing to simultaneous elimination of the P-substituent. Erlenmeyer 117) described the formation of 2-methyl-4-benzylidene-oxazolinone by the reaction of phenylserine with acetic anhydride. Carter et al 92, 93, 94) obtained 2-phenyl-4-ethylidene-oxazolin-5-one from N-benzoylthreonine, N-benzoylallothreonine, and their 0-methyl, 0-acetyl and 0-benzoyl derivatives by treatment with benzoylchloride in pyridine. Trifluoroacetic anhydride converts threonine into 4-ethylidene-2-trifluoromethyl-2-oxazolin-5-one 20). 

S) Several attempts have been made, especially in recent years, to oxidize saturated to unsaturated oxazolinones. Oxazolinone formation activates the a-carbon atom of the corresponding amino acid, so that it can, for example, by easily brominated 100, 315, 417). Morin and Gordon 267) attempted the selective oxidation of the C-terminal amino acid of a peptide chain by first converting it into an oxazolinone. Treatment of the oxazolinones obtained from N-benzoyl- or N-carbo-benzoxydipeptides with Pb(OAc)4 or Hg(OAc)2 resulted however in... 

Although oximes are ambident nucleophiles, a neat regioselectivity allows the formation of oxazolinones. The alpha effect, which is especially relevant for the substimtion of R2C=NO anions at a carbonyl carbon, may offer a good explanation for the Bac2/Bai2 sequence ((9-methoxycarbonylation and A-methylation... 

Treatment of an a-amino acid with an anhydride in the presence of pyridine, known as the Dakin-West reaction,[1431 gives access to a racemic a-amido ketone.1 44 1451 The mechanism involves formation of an oxazolinone (98)J146 In the modified Dakin-West reaction, the oxazolinone is reacted with an acid chloride (Scheme 33)J136 139] Due to the rapid epimer-ization of the oxazolinones, a diastereomeric mixture of product 99 is obtained. No detailed protocol has been published so far for the modified Dakin-West synthesis applied to (oxomethyleneamino) peptides, but the procedure is adapted from that already reported for (oxomethylene) peptides containing the tp[CO-CH2] link.1147 ... 

Although these transformations or oxazolinones and thiazolinones can be extended to imidazolones such as (271 Scheme 119), which also proceed through the acylamidrazone intermediate (272), the alkaline reagent (0.2% sodium hydroxide) may cause partial hydrolysis of the amide with the formation of acid (273 2%) or the amide (274) (69AC(R)434). 

The failure of previous methods to derivatize C-terminal proline may be due to the inability of proline to form an oxazolinone, a necessary step in many of the previous methods. The use of DPP-ITC/pyridine for derivatization permits the direct formation of an acylisothiocyanate at the C-terminus without the... 

The map of Bronsted p values for the cyclisation are shown in Scheme 12. The Utg for the reaction of the conjugate base is 0.55. When the reference equilibrium for the effective charge of one substituent effect is not the same as that for the other (as in Problem 12) the bonding changes can only be compared when the P or p values are normalised as Leffler indices. In the case of cyclisation to the oxazolinone it is most convenient that bond fission is measured by a Bronsted relationship and bond formation by a Hammett equation. Both p and p can be... 

Only two reactions leading to the formation of ring-opened products have been reported for dihydrothiazine oxides. Thus when treated with acetyl chloride, the sulfoxide 221 was converted into the oxazolinone 235, probably by way of the intermediate 234. Raney nickel has been shown to effect the desulfurization of the compound 236, to give the oxazolidine 237. ... 

The oxazolinone (378) reacts with nitrosobenzene to yield the 1,2,4-oxadiazoline-derivative (380) by way of the 1,3-dipolar tautomer (379). —On the other hand, the formation of the dihydropyridone (382) from compound (378) and cinnamylideneaniline represents a Diels-Alder addition of the tautomeric hydro-... 

A Dakin-West reaction on plant scale is demonstrated by elaboration of a modified procedure avoiding uncontrolled release of carbon dioxide. It seems to be generally accepted that the mechanism involves dehydrative formation of an azlactone (oxazolinone), which is then C-acylated (in equilibria with G-acylation), undergoes ring-opening hydrolysis, and then decarboxylates to form the acylamino ketone. Pyrimidine ring formation is achieved in a simple one-pot reaction, which is followed by a simple isomerization. Laboratory experiments had made clear that the mechanism... 

Merrifield s original idea was based on the general scheme of stepwise condensation of N-protected amino acids to the first one, which is linked with its carboxyl function by an ester bond to the insoluble polymer support. This way of solid phase peptide synthesis resulted from the well-known risk of racemization during activation of peptidic carboxyl components, which is minimized in activated amino acid derivatives, N-acylated by urethane-type protecting groups [40] (Fig. 7). Depending on the chosen method, the C-terminal activation of N-protected peptides tends to racemize a certain amount of the material because of the possible formation of an oxazolinone intermediate [41] (Fig. 8). 

The oxazolinone 107, a new recoverable chiral auxiliary that gives a high level of asymmetric induction in model aldol reactions and Diels-Alder cycloadditions (in which the reactant is connected to the auxiliary by -acylation), has been synthesized from L-gulonic acid. The key step in its synthesis was the thermal intramolecular nitiene insertion shown in Scheme 21. The formation of oxazolinethiones on hydrolysis of isothiocyanato-sugar derivatives is covered in detail in Chapter 9, section 3.3. Base-catalysed reaction of StS-O-isopropylidene-D-xylofuranosylamine with P-isothiocyanato-alkanals led to tricyclic derivatives such as 108, considered as cyclonucleoside analogues. ... 

Example 4.4 Formation of Z-boronates derived from chiral oxazolinones 9-13 is preferred because of reduced non-bonding through-space interactions between the R and wo-propyl group on the chiral center (Scheme 4.11). It is therefore understandable that most aldol reactions with this substrate run in the iyn-selective mode. Prevailing absolute configurations (IS, 2R) on the new chiral centers in 14-18 (shown in the Scheme ) are determined by the absolute stereochemistry of chiral oxazolidinone. Absolute stereochemistry comprises a set of configurational and conformational properties of certain chiral molecules. It dictates facial selectivity in chiral oxazolidinones the direction of approach by the carbonyl group of R -CHO is as an electrophile to the double C=C bond of Z-enole. 

Scheme 11 Formation of imidazolinone groups by cyclodehydration of dipeptide-like moieties formed during amine-oxazolinone chain coupling.

Oxazoles.—Recent developments in the chemistry of oxazolinones have been reviewed. Tosylalkyl isocyanides TosCHRNC (R = alkyl) react with aromatic aldehydes to form oxazoles (546). The action of hydrogen chloride on a mixture of benzoyl cyanide and an aromatic aldehyde results in chloro-oxazoles (547). Tungsten(vi) chloride catalyses the formation of 2-methyl-5-phenyl-oxazole (548) from acetonitrile and diazoacetophenone/ Thermolysis of the... 

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