Chloroformic acid esters isobutyl chloroformate

Isobutyl chloroformate Formic acid, chloro-, isobutyl ester (8) Carbonochloridic acid, isobutyl ester (9) (543-27-1) S-tcrf-Butyl-L-cysteine ferf-butyl ester L-Cysteine, S-(l,l-dim-ethylethyl), 1,1-dimethylethyl ester (9) ( —) acetate (38024-19-0) hydrochloride (2481-11-0)... 

The separation of P(V) from other elements, in particular from Si, is often achieved by extracting phosphorus as a heteropoly acid from a slightly acidic solution of pH -1.4. Higher alcohols, esters, and ethers are suitable extractants [3-5]. By extraction with a mixture of butanol and chloroform, molybdophosphoric acid can be separated from molybdoarsenic acid [6]. Isobutyl acetate extracts molybdophosphoric acid, but not molybdosilicic acid, from a solution at pH 0.3-1.0. 

In addition to the general usefulness of this class of compounds, the popularity of this chemistry is largely due to the facile preparation of the starting materials (Scheme 7). The most straightforward method of preparation of Barton esters of types I to IV is acylation by activation of the corresponding carboxylic acid (paths A and B). Accordingly, the hydroxamic acid sodium salt can be O-acylated with the acyl chlorides or, alternatively, the free hydroxamic acid can be condensed with primary carboxylic acids in the presence of N,W -dicyclohexylcarbodiimide and dimethylaminopyridine (DMAP). Likewise, condensation of the free thiohydroxamic acid or the corresponding sodium salt with the mixed anhydride formed from the acid and isobutyl chloroformate in the presence of N-methylmorpholine has proven to... 

The Z-protected derivative, again prepared by standard methods using benzyl chloroformate,t208 may serve in the case of racemic pipecolic acid for resolution into the pure enantiomers by fractional crystallization with L-tyrosine hydrazide/208 Acylation with N-protected pipecolic acid or of pipecolyl peptides is performed by standard procedures via the active ester methods, e.g. A-hydroxysuccinimide ester/121 by the mixed anhydride method, e.g. with isobutyl chloro-formate 95-114 or pivalic acid chloride/121 as well as by DCC/HOBt/118 In the synthesis on solid support, longer coupling times are required when compared to N-protected proline.1[235 ... 

Some of the versions of the mixed anhydride technique discussed may involve components other than a-hydroxy acids. Therefore, the resultant products cannot be considered as main-chain modified peptidomimetics. However, on many grounds these methods are of general importance in depsipeptide synthesis. For example the classical peptide reagent isobutyl chloroformate appears to be suitable for ester bond formation through the corresponding mixed anhydride with Boc- or Z-protected amino acids and the Thr (3-hydroxy group in the synthesis of a number of natural peptide lactones.145 7 ... 

Stereospecific synthesis of succinyl derivatives is now commonly carried out as shown in Scheme 7. The tert-butyl ester of the succinyl amino acid methylamides 16 was treated with TFA to deprotect the carboxy group, which was then activated by isobutyl chloroformate and reacted with H2NOTMS.[18] The OTMS protection was removed during the isolation and purification of the hydroxamic acid 17. 

In one case, methyl terephthalic acid, obtained in two steps from p-formyl-benzoic acid, was converted to the phenacyl bromide (340) in the usual manner. Alkylation of 2,5-diamino-4,6-dihydroxypyrimidine with (340) with subsequent cyclization produced the dihydrooxazine pteroate ester (341), which was hydrolyzed to (342) [173]. Coupling (342) with diethyl L-glutamate using isobutyl chloroformate [ 174] yielded the diester (343a) which was then saponified to the dihydrooxazine FA analogue without the C-9,N-10 bridge (343b). 

Other acyl alkyl esters have been utilized only sporadically. Makita et al. [241] analysed N-isobutyloxycarbonyl methyl esters of protein amino acids. During the first step of the preparation, the amino group reacts with isobutyl chloroformate according to Scheme 5.21. The reaction is accomplished in 10 min in an aqueous medium in the presence of sodium carbonate at room temperature. Excess of the reagent is extracted with diethyl ether and the reaction mixture is saturated with NaCl, acidified with ortho-phosphoric acid to pH 1—2 and extracted with diethyl ether. Methanol is added to the ethereal extract and the carboxyl group is esterified with diazomethane at room temperature for 5 min, The solvent is removed under a stream of nitrogen at 50°C and the residue is dissolved in ethyl acetate. Arg does not provide a volatile derivative when sub-... 

Isobutyl chloroformate is most frequently applied in peptide chemistryfollowed by ethyl chloto-formate (see Table 1). The advantage of this method is that the mixed anhydride does not have to be isolated, and during work-up only carbonic acid half esters are formed, which decompose to an alcohol and carbon dioxide. Only in the case of sterically hindered amino acids does the opening of the anhydride at the undesired carbonyl occur in considerable amounts. Furthermore, short activation times (30 s) at low temperatures lead to peptides with minimal racemization. With isopropenyl chloroformate the mixed anhydride is prepared at room temperature, and during reaction only acetone and carbon dioxide are formed. 

The JV-unsubstituted carboxamide 95 (R=H) can be prepared if the ester 90 is allowed to stand for about a week at room temperature in methanol containing 25% ammonia [58,112], A-Substituted derivatives of 95 were prepared from Boc- or Z-protected amino acids with mixed anhydride methods, using isobutyl chloroformate and the corresponding amine [78, 84, 113-115]. 

To investigate the antifungal activity of cispentacin derivatives, six dipeptide derivatives of ( )-c -2-ACPC were synthetized. The syntheses were straightforward the Z-protected ( )-c -2-ACPC was activated with isobutyl chloroformate and treated with the corresponding amines, followed by deprotection to give the carboxamides 122 (R =Me, R2=H R =H, R2=Me R1=CH2Ph, R2=H) [167]. The A-acyl derivatives 2 (R =Me, R2=H R =H, R2=Me RI=CH2Ph, R2=H) were prepared from the methyl ester of ( )-ci s,-2-ACPC, which was acylated with Boc-amino acids, followed by hydrolysis and deprotection, to afford 123 [167]. 

Gas chromatography Acesulfame-K, aspartame, cyclamate, saccharin, and stevioside are determined by gas chromatography, but the main drawback of this technique is that a derivatization is required. Acesulfame-K is methylated with ethereal diazomethane, aspartame is converted into its N- 2-methylpropoxycarbonyl) methyl ester derivative, menthol and isobutyl chloroformate are used to convert aspartame to 3-[(isobutoxycarbonyl)amino]-4-[[a-(methoxycarbonyl)phenethyl]amino]-4-oxobutyric acid, cyclamate is determined as cyclohexene resulting from the reaction with nitrite, saccharin is converted to N-methylsaccharin, and stevioside is hydrolyzed. Detection is carried out utilizing flame-ionization, flame-photometric electron-capture detectors or nitrogen-phosphorus detection. 

Some of the more innovative and creative aspects of peptide chemistry have centered around the peptide bond-forming reaction. Because of the asymmetric center adjacent to the carboxylic acid carbonyl group, the superficially simple operation of amide formation has required study, unparalleled in detail, to avoid racemization. While racemization can usually be limited to less than 1% there is still no universally infallible reaction technique and the advantages of having several good methods at one s disposal is well known to every peptide organic chemist. Presently, in our laboratory, we prefer to first use the MCA method employing isobutyl chloroformate with one equivalent of a relatively weak base such as N-methylmorpholine in tetrahydrofuran. If this proves unsatisfactory we then resort to a method from one of the series A, DCCl-HOBT, ED Cl, WRK, or one of the active ester methods such as OSU, OPCP, or ONP. Soon, we may find it appropriate to add the BBDQ, NCA, SPY, and DPPA methods to this list for reasons outlined below. 

N-Boc leucine was converted to an acid chloride by treatment with isobutyl chloroformate. Subsequent treatment with diazomethane gave the diazoketone (6.241), which was treated with silver benzoate. This led to a Wolff rearrange-mentl40 and formation of 6.242. I ll Reduction of the ester moiety to an aldehyde with diisobutylaluminum hydride allowed condensation with the lithium enolate of ethyl acetate to give 6.243. Saponification led to N-Boc-5-amino-3-hydroxy-7-methyloctanoic acid (6.244, given the pseudonym AHM0A).1 H Amino acid... 

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