Lego , Here is a related approach,.......java
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Brief....Recently, 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) has been described as a versatile reagent for the selective formation of amides1. Although CDMT has been shown to be a useful non-carbodiimide reagent, in terms of stability, mild reaction conditions and cost, it has the disadvantage to be irritating to the eye and nose. In addition, reactions are generally conducted under dry conditions by a two-step procedure: the carboxylic acid is first treated with CDMT in the presence of N-methylmorpholine to activate the acid, then an amine or an alcohol is added to obtain the product. This requires confirmation of the completion of the first step for successful results. To resolve these issues, a more convenient one-step approach is desired. In 1999 Kunishima et. al. reported the synthesis2 and use of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) in amide and ester forming reactions. This coupling agent is a crystalline, air-stable, non-hygroscopic, easy-to-handle compound. In comparison with a carbodiimide reaction, the co-products formed may be easily removed from the reaction mixture (by washing with water), offering a convenient preparation of the acid derivative. Though comprehensive toxicological data is not yet available, this material is expected to be a less toxic agent than the many alternatives mentioned already.
Chem. Pharm. Bull. 50(4) 549—550 (2002) 549
A Racemization Test in Peptide Synthesis Using 4-(4,6-Dimethoxy-1,3,5-
triazin-2-yl)-4-methylmorpholinium Chloride (DMT-MM)
[Munetaka KUNISHIMA,*,a,b Akiko KITAO,a Chiho KAWACHI,a Yasunobu WATANABE,a Shin IGUCHI,a,b
Kazuhito HIOKI,a and Shohei TANIa,b[/i]
Abstract Racemization of the C-terminal amino acid (Ala) has been studied in various solvents during coupling
between 4-methoxybenzyloxycarbonyl (Z(OMe))-Gly-L-Ala-OH and phenylalanine benzyl ester (H-Phe-OBzl)
with 4-(4,6-dimethoxy-1,3,5-thiazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). The reaction occurred
without substantial racemization in AcOEt, tetrahydrofuran (THF), N,N-dimethylformamide (DMF), CH3CN,
and 2-PrOH, while a slight racemization was observed in dimethyl sulfoxide (DMSO), EtOH, and MeOH. The
extent of racemization may correlate with the polarity of the solvents.
Excerp..... In addition, it is noteworthythat DMT-MM enables us to carry out the direct one pot condensation of carboxylic acids and amines in protic solvents like methanol, ethanol, 2-propanol, or water, as well as in a variety of aprotic organic solvents.
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Just so that everything is kept in a continous file , here are the synthesis of DMT-MM and CMDT as provided by Kinetic
Post 514650 (https://www.thevespiary.org/talk/index.php?topic=7327.msg51465000#msg51465000)
(Kinetic: "DMT-MM articles", Chemistry Discourse)
Synthesis of aromatic aldehydes via NiCl2 reduction and hydrolysis of oxazolines
M. Suresh Babu and K.M. Lokanatha Rai
Tet. Lett., 2004, 45(42) , 7969-7970
DOI:10.1016/j.tetlet.2004.07.119 (http://dx.doi.org/10.1016/j.tetlet.2004.07.119)
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Abstract: Reduction of 2-aryl-oxazolines with NiCl2/NaBH4 followed by hydrolysis gives the corresponding aldehydes in good yields.
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Benzoic acid was converted into the corresponding oxazoline using a literature method.11 The oxazoline was treated with NiCl2/NaBH4 at -10 °C followed by hydrolysis with 5% aq HCl to give the corresponding aldehyde in 90% yield. This encouraging result prompted us to study some other commercially available aromatic acids and indeed excellent yields of the corresponding aldehydes were obtained (Table 1). Unfortunately reduction of the oxazoline derived from propanoic acid under identical conditions gave only a very low yield of propanal. All the products prepared were identical by bp or mp and by IR and NMR spectroscopy with known aldehydes.12
General procedure for the preparation of benzaldehyde from benzoic acid
In the first step of the reaction, 2-phenyl-2-oxazoline (5 mmol, 0.735 g) and NiCl2 (2.37 g, 10 mmol) were taken in methanol and cooled to -10 °C. Sodium borohydride (0.74 g, 20 mmol) was added in small amounts over 30 min whilst maintaining the temperature at -10 °C. The mixture was then kept at 10 °C for a further 30 min to complete the reaction. The reaction mixture was filtered through Celite and the solvent evaporated under vacuum. The residue was treated with 5% HCl (10 mL) at 40 °C for 10-15 min, then cooled to room temperature and extracted with diethyl ether (25 mL). The organic layer was washed with water, dried over anhydrous sodium sulfate and evaporated under vacuum to give benzaldehyde as a colourless oily liquid in 90% yield (0.477 g).
11. Wiley, R. H.; Bennett, L. L., Jr. Chem. Rev. 1949, 44, 447–476 [Re?uxing hydroxyamides (ArCONHCH2CH2OH) with SOCl2 followed by treatment with Na2CO3 gave the oxazolines derivatives in typically 65% overall yield; Fry E. M. J. Org. Chem. 1949, 14, 887–894].
12. Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R. In Vogel’s Text Book of Practical Organic Chemistry, 5th ed.; 1994; pp 1334–1335.
The chemistry of the oxazolines
Wiley, R. H., Bennett, L. L.
Chem. Rev., 1949, 44, 447–476
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Oxazolines
Fry E. M.
J. Org. Chem., 1949, 14, 887–894
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Ethanolamine was benzoylated in sodium bicarbonate solution at 15°. The product was taken into chloroform, recovered, and distilled at 179-189° (1 mm.). The crude product (85% yield) was recrystallized by dissolving in warm ethyl acetate, then adding dry ether; m.p. 61-63', 64% yield.
1-Phenyloxazoline hydrochloride (III-HCl). beta-Hydroxyethylbenzamide (2.0 g.) was added portionwise to 4 ml of chilled thionyl chloride at not over 13°. The solution was kept in the ice-bath for one hour; excess thionyl chloride was then removed under reduced pressure and the crystalline product brought to constant weight (2.3 g.) while keeping cold. The theoretical weight for the oxazoline hydrochloride is 2.22 g. The salt melted at 101-103° with a slight sinter at 77°. It was decomposed with sodium carbonate solution, the base removed with ether and the carbonate solution analyzed for sulfite and chloride ions. The ratio of the moles of sulfur dioxide to that of starting material was 0.03 to 1.0. Chloride was found in small excess, 105 % of theory. As reported (4) the oxazoline hydrochloride is stable in solution at room temperature. Recrystallization was effected by adding acetone to an aqueous solution; m.p. 75-76°. The value previously given (4) is 80-81°, and it is possible the lower melting point and low analytical value are due t o loss of hydrogen chloride. The phenomenon of slight sintering at the melting point with transformation into p-chloro-ethylbenzamide, m.p. 101-103°, (see above) was observed solely with the crude reaction product.