Alanine, acid chloride

DNA sequencing and. 1113 Electrospray ionization (ESI) mass spectrometry, 417-418 Electrostatic potential map, 37 acetaldehyde, 688 acetamide, 791,922 acetate ion. 43. 53, 56, 757 acetic acid. 53. 55 acetic acid dimer, 755 acetic anhydride, 791 acetone, 55, 56. 78 acetone anion, 56 acetyl azide, 830 acetyl chloride, 791 acetylene. 262 acetylide anion, 271 acid anhydride, 791 acid chloride, 791 acyl cation, 558 adenine, 1104 alanine, 1017 alanine zwitterion, 1017 alcohol. 75 alkene, 74, 147 alkyl halide, 75 alkyne. 74... 

N-Silylated peptide esters are acylated by the acid chloride of N-Cbo-glycine to N-acylated peptide bonds [11]. Likewise, acid chlorides, prepared by treatment of carboxylic acids with oxalyl chloride, react with HMDS 2 at 24°C in CH2CI2 to give Me3SiCl 14 and primary amides in 50-92% yield [12]. Free amino acids such as L-phenylalanine or /5-alanine are silylated by Me2SiCl2 48 in pyridine to 0,N-protected and activated cyclic intermediates, which are not isolated but reacted in situ with three equivalents of benzylamine to give, after 16 h and subsequent chro-... 

Much the same activity is retained when the nitrogen atoms in the heterocyclic nucleus are shifted around. The convergent scheme to this related compound starts with the acylation of alanine (35-1) with butyryl chloride (35-2). The thus-produced amide (35-3) is then again acylated, this time with the half-acid chloride from ethyl oxalate in the presence of DMAP and pyridine to afford the intermediate (35-4). In the second arm of the scheme, the benzonitrile (35-5) is reacted with the aluminate (35-6), itself prepared from trimethyl aluminum and ammonium chloride, to form the imidate (35-7). Treatment of this intermediate with hydrazine leads to the replacement of one of the imidate nitrogen atoms by the reagent by an addition-elimination sequence to form (35-8). Condensation of this product with (35-4) leads to the formation of the triazine (35-9). Phosphorus oxychloride then closes the second ring... 

A stereospecific synthesis of (S)-(—)-cathinone that utilizes the Friedel-Crafts reaction has been described (3/7). Reaction of the acid chloride obtained from /V-(methoxycarbonyl)-L-alanine (10) in benzene by A1C13 catalysis provided the N-protected a-amino ketone 11 with retention of chiralty 11 was deprotected by hydrolysis with potassium hydroxide. A more recently published method (408)... 

Addition tube, 20, 21 Alanine, /3-(3,4-dihydroxyphenyl)-N-METHYL-, 22, 89, 91 Alcoholic hydrochloric acid, 22, 77, 83 standardization, 22, 80 Alcoholysis, 20, 67 Aldehyde synthesis, 20, 14 from acid chlorides by Rosenmund reaction, 21, 84, 87, 88, 110 Alkylation of thiourea, 22, 59 Alkylchlororesorcinols, 20, 59 Alkylene bromide, 20, 24 S-Alkylthiuronium halides, 22, 60 dl-ALLOTHREONINE, 20, 10 ... 

Since the isolation of cathinone and the other khat phenylalkylamines from fresh material, and their structural and stereochemical characterization, there has been interest in producing these compounds synthetically in chiral form. Buckley and Rapoport (24) have shown that N-ethoxycarbonyl-L-alanine, as its acid chloride (10), can successfully acylate benzene in the presence of aluminum... 

Wc could, for example, benzoylate glycine (Q = C6H5CO), convert this into the acid chloride, allow the acid chloride to react with alanine, and thus obtain benzoylglycylalanine. But if we attempted to remove the benzoyl group by hydrolysis, we would simultaneously hydrolyze the other amide linkage (the peptide linkage) and thus destroy the peptide we were trying to make. ... 

Reaction of trimer 28 of the imine obtained from formaldehyde and the appropriate arylglyci-nate with the acid chloride-pyridine complex 27 gives 87% of the cycloadduct 29 in 50% de71. Reaction of azidoketene with imine 30, obtained from benzaldehyde and alanine tm-butyl ester, gives a 1 1 mixture of ds-J -lactams 31 and 3272. 

Optically pure (R)-2-chloropropionic acid (90) is available by diazotization of L-alanine in 6n HCl [31]. Using the corresponding acid chloride 91 as an acylating agent, Friedel-Crafts reaction with isobutylbenzene produces aryl ketone 92 with an enantiomeric purity of 85%. 

The interesting TBS-protected acid chloride 310, available from monoester 23a by dual silylation of the hydroxyl and ester groups followed by treatment with oxalyl chloride, is an important intermediate in the synthesis of a key fragment (312) of rhisobactin (314), a microbial siderophore (Scheme 42) [92]. Completion of the synthesis of 314 is accomplished by reductive amination of 312 with D-alanine-derived aldehyde 313 followed by hydrolysis of the methyl esters and hydrogenolysis of the Cbz protecting group. 

An important class of IPTC reactions involves the conversion of a reactant and the IPTC catalyst in the organic phase to an ionic intermediate that is transported into the aqueous phase for reaction with the second reactant to yield the organic product and to regenerate the catalyst. This class of IPTC catalysts includes 4-(dimethylamino)pyridine (DMAP), 4-pyrrolidinopyridine, pyridine-1-oxide (PNO), tetrahydrothiophene, and diethylsulfide, etc. Mathias and Vaidya studied the first acylation reaction of alanine with decanoyl- or p-chlorobenzoyl chloride in H2O/CH2CI2 medium catalyzed by DMAP [124]. In this system, the acid chloride reacted with DMAP in the organic phase to form the ionic intermediate,... 

Yamada and co-workers elaborated a general approach to 6-deoxy-L-hexoses starting from L-alanine. Deamination of this amino acid in acetic acid gave 25-acetoxy-propionic acid (411). After conversion to the acid chloride it was reacted with propiolaldehyde dimethylacetal magnesium bromide to afford the acetylene 412. Half-reduction to the cij-olefin followed by deacetylation and heating with phosphoric acid gave both anomeric methyl 2,3,6-trideoxy-L-hex-... 

In one synthetic approach (Veld 1990, 1992), alanine is first converted to the bromo derivative via the reaction of the diazonium salt of the amine with hydrogen bromide. In the next step the acid functionality is activated by converting it to the acid chloride using thionyl chloride. The activated acid is condensed with a protected a-amino acid to yield the dipeptide intermediate which is then cyclized by heating in presence of Celite (ion exchange resin) to yield the final product. However, the overall yield of this reaction is fairly low. A more elegant approach is shown in Scheme 5. In this approach, an a-amino acid wth a protected side chain (e.g., e-Z-lysine) is reacted with 2-bromo-propionyl bromide under Schotten-Bauman condidons (Fischer 1908) to yield the intermediate 5a, which is then cyclized under basic conditions to the depsipeptide 5b. 

Peptides. N-p-Toluenesulfonyl-DL-alanine mixed with N-phenyltrimethylacet-imidoyl chloride, allowed to stand several hrs. at room temp., the resulting acid chloride dissolved in ether, treated slowly with alanine benzyl ester, and the crude product hydrogenated with Pd-on-carbon in ethyl acetate N-p-toluene-sulfonyl-DL-alanylalanine. Y 80%. F. Cramer and K. Baer, B. 93, 1231 (1960). 

One simple strategy for avoiding undesired reactions between alanine and leucine would be to activate the carbonyl group of alanine by transforming the acid group of alanine into the acid chloride, and then treating it with leucine (Fig. 23.42). 

However, even this procedure is hopeless What is to prevent the amino group of the original alanine from reacting with the acid chloride Nothing. Again, a mixture is certain to result (Fig. 23.43). Remember, we ultimately will have to make dozens, perhaps hundreds of amide bonds. We can tolerate no mediocre yields or even worse, mixtures, if we hope to make useful amounts of product. We need to find the most efficient way of making the amide bond specifically at the point we want it, and at the same time avoiding side reactions. 

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