Amino acetals, preparation

Substituted 5-hydroxythiazoles (267b), Rj = alkylmercapto, acyl-amino, and sec-amino, are prepared by cydization of N-thioacyl-amino acids (266) with phosphorus tribromide or acetic anhydride (Scheme 137) (317, 350). i en the cydization of 266, R2 = H, is carried out with acetic anhydride in the presence of benzaldehyde (317, 325) or ethylformate (317), the benzylidene (268), R2=Ph, Rj = SR or CH2Ph, or 4-ethoxymethylene (268), Rj = SR and R2 = OEt, derivative is obtained directly (Scheme 138). 

The less highly substituted Mannich bases can also be prepared directly from ketones and dimethyl(methylene)ammonium trifluoroacetate by the procedure reported here, which takes advantage of the isomerization of Mannich bases in trifluoroacetic acid. (In acetic acid the Mannich bases undergo elimination of dimethylamine to give a-methylene ketones.) This method is rapid and affords products having an isomeric purity of at least 90% without difficult separations. The 49-57% yield of l-(di-methylamino)-4-methyl-3-pentanone obtained with this procedure compares favorably with the overall yields of amino ketones prepared by the indirect routes mentioned previously. 

Scheme 29 Preparation of fert-Butyl j[l-(4,5-Dimethoxy-2-nitrophenyl)ethyl]amino acetate and 4-tert-Butyl 1-(4,5-Dimethoxy-2-nitrophenyl)ethyl iV-(tert-Butoxycarbonyl)aspartate Diesterl230 ...

Betaine(Trimethyl Glycine Trimethyl Glycocoll or Trimethyl Amino-Acetic Acid), (CH3)aIsI.CHg.CO.O or (CH3)3fo.CH2.CO.O mw 117.15, N 11.96%, OB to COz-184.4%. Prisms(from ale), mp 293°(decomp) sol in w in ale insol in ether occurs in plants (usually together with choline) and in some sea animals. Can be prepd by methylation of amino-acetic acid or by other methods. Betaine has been used in org synthesis to render various compds water-soluble. For instance, Girard s reagent(which is a deriv of betaine) is used to prepare water-sol derivs of insol ketones and aIdehydes(Ref 2,p 510) Betaine forms additive compds with acids and salts, some of them explosive (See below)... 

Peptide aldehydes can be synthesized by backbone attachment of the corresponding amino acetal to a BAL resin 30.b A modification of this method involves the preparation of a peptide alcohol (with the free alcohol group) by side-chain attachment, and after elongation of the peptide chain the alcohol is converted into the aldehyde using sulfur trioxide and pyridine.t l... 

This dipeptide bears to amino acetic acid a relationship similar to that which aceto acetic acid bears to acetic acid. This is indicated by the name amino aceto amino acetic acid. Another method of preparing the polypeptides is by the action of the acid chloride of the amino acid on the amino acid itself. 

It is similar in its constitution to a dipeptide except that one acid constituent has no amino group. A compound exactly analogous to it is aceto amino acetic acid, CH3—CO—NH—CH2—COOH. Such semi-peptides result when an amino acid is treated with the acid chloride of a non-amino acid analogous to the second method of preparing poly-... 

JOC2099). Syntheses of derivatives of the hitherto unknown homo-isopavinane ring system, containing a bicyclo[4.2.2]azadecane system, were described by Dyke and Warren (79T1857). Starting with the amino acetal derivative 60 under conditions used successfully for the preparation of isopavinanes, the homoisopavinane 62 was obtained in 39% yield. It was methylated to 63. The acid-catalyzed cyclization of the amino acetal 61 gave a mixture of components, from which the phenolic homoisopavinane 64 was isolated (63%). 

The first preparation of a benzazocine (105 R = S02Ph) was carried out by Braun and Bayer via the cyclization of ethyl A/-benzenesulfonyl-A-(4-phenylbutyl)amino acetate.230 Numerous methods for the synthesis of benzazocines utilizing aromatic electrophilic substitution have been reported. For example, 106 was prepared by cyclization of the appropriate... 

Peptide synthesis. Vinyl esters of amino acids, prepared by transesterification with vinyl acetate, have been used as activated esters in peptide synthesis. The coupling reaction is best carried out in ethyl cyanoacetate, for this solvent suppresses the formation of colored products derived from liberated acetaldehyde. Racemization appears to be slight. 

Pomeranz-Fritsch reaction. Formation of isoquinolines by the acid-catalyzed cyclization of benzalaminoacetals prepared from aromatic aldehydes and amino acetal. 

Aminomethanebisphosphonic acid derivatives (11) have been prepared by a number of methods, including the reaction of diethyl phosphite with amino-acetals and the reaction of triethyl phosphite with the halogenoiminium salts (12). 

Nofre, C., Tinti, J.-M., and Chatzopoulos-Ouar, F. (1988). Preparation of (phenylguanidino)-and [[l-(phenylamino)ethyl]amino]acetic acids as sweeteners Eur Pat Appl EP 241,395, 1987. Chem. Abstr. 109,190047k. 

Aiming to prepare a library of derivatives of the medicinally relevant piperidine scaffold, Veerman [393] and co-workers exploited N-acyhminium ion chemistry, starting from a stable aminal precursor. Coupling of six different amino acetals onto sulfonylethoxycarbonyl-modified (SEC-modified) polystyrene resin afforded the potential precursors. However, attempts to transform these into the desired piperidine derivatives via one-pot generation of N-acyliminium ions and functionalization failed, essentially because direct attack of the nucleophile on the acid-mediated oxycarbenium ion took place at a similar rate to that of the intramolecular carbamate-nitrogen attack. 

Dihydropyridines react with s-triazine in the presence of sodium hydride to give l,4-dihydro-l,6-naphthridones in fair to good yields (Table VII, entry 5). Alternative reagents for this reaction are amino-acetals followed by ammonia (Table VII, entry 6). Naphthyridines have also been prepared by the reactions of enaminones derived from cyclohexane-1,3-diones with pentafluorobenzaldehyde in glacial acetic acid (85JHC159). 

In these molecules, several amine groups and one or more carboxylic acid groups are combined to give highly functionalized surfactants. In particular, alkyl amino acetic acids prepared from polyamines have found interest since these amphoterics show microbio-cidal properties (36). An example is dodecyl propylene diamine acetic acid, which is derived from a diamine and chloroacetic acid by carboxymethylation (Figure 15.23). 

Rapoport reported preparations of amino guanidines for studies of UV-/iH profiles. It was found that the addition of a substituted amine must precede the addition of ammonia, otherwise no desired amino guanidines will be found (eq 21). Finally, another example involved addition of the dianion of a-amino acetic acid to reagent 1 (eq 22). ... 

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