Diethyl dicarbonate reactions

Gejvall [114] analysed low-molecular-weight amines in the form of urethanes produced by their reaction with diethyl dicarbonate (Scheme 5.12). The reaction can be carried out in aqueous solution. A 10-mg amount of diethyl dicarbonate was allowed to react with 0.05—0.7 mg of the amine at room temperature for 30—40 min, the pH being adjusted to 9.5 with NaOH. A good separation with symmetric peaks was obtained by using SE-30 as the stationary phase. 

In general, lower reaction temperatures are used to increase selectivity and to avoid side reactions. The reaction of cyclohexanone with diethyl dicarbonate (18) led to the O-acylated product 19 at —78°C (Figure 5.7), with the C-acylated product 20 being produced at about 80°C [17]. Cooling a lipase-mediated esterification to — 40°C enriched the product ester 21 to 97% ee (Figure 5.7) [18]. Reaction rates slow with decreasing temperatures, and the rule of thumb is that increasing the reaction temperature by 10°C will usually double the reaction rate. 

A variety of reagents will effect the conversion C(XTH2 - C(XrHC02R the decarbonylation of glyoxalate esters was described above. The most recently described reagent, methyl cyanoformate, reported by Mander and Sethi in 1983, allows the conversion of a preformed lithium enolate to the 3-keto ester in high yield (Scheme 68). Diethyl dicarbonate with potassium hydride in benzene effects the same reaction wiA symmetrical ketones, and with lithium dicyclohexylamide in ether introduces the ethoxycarbonyl group into the a -position of a,3-unsaturated ketones (Scheme 69)."" Diethyl carbon-... 

N-(l-Alkoxyalkyl)-aniides or -carbamates (2 X = OR), most frequently used as stable precursors for A -acyliminium ions, are usually prepared by one of the following routes (equations 7-13). For five- or six-membered cyclic cases a simple acid-catalyzed solvolysis of the hydroxy compound provides the alk-oxy derivative (equation 7). A silicon-assisted approach involves the TMSOTf-catalyzed reaction of bis(trimethylsilyl)formamide with aldehydes (equation 8). /V-(l-Trimethylsilyloxyalkyl)formamides are thus formed in good yields, which on TMSOTf-catalyzed solvolysis lead to the /V-( 1-alkoxyalkyl)form-amides. A third method is based on the NaBH4 reduction of imidates (equation 9), and has proved useful for a total synthesis of the insect poison pederine. Addition of reactive acid derivatives to imines constitutes another method (equations 10 and 11). Acylation with acid chlorides followed by treatment with ethanol in the presence of base leads to N-(l-alkoxyalkyl)amides. A one-step protocol using diethyl dicarbonate provides the corresponding carbamates. 2... 

Due to the ability of coordinating with 1,3-dicarbonyl compounds, Mg(C104)2 reacts with diethyl dicarbonate to form complex (II), which can undergo the addition of the alcohol to form intermediate (in). An internal proton shift in (m) can produce intermediate (IV), which can irreversibly decompose to the mixed carbonate (VI) and to the carbonic acid monoester (V). Owing to its high instability, (V) immediately produces EtOH and CO2. The irreversibility of the last two steps drives the overall process towards (HI). This explanation accounts for the formation of the mixed carbonate (VI) as the major product of the reaction (Jousseaume et al., 2003). 

Figure 11.3. Reaction of diethyl dicarbonate and ammonia to yield ethyl carbamate, ethanol, and carbon dioxide. Adapted from Ough et al. (1988b) with the kind permission...

Diethyl dicarbonate (diethyl pyrocarbonate) was used in the past as a preservative for soft drinks and some alcohohc beverages (including wine). In aqueous solution, however, diethyl dicarbonate is rapidly hydrolysed to ethanol and carbon dioxide, and in alcoholic beverages it is transformed into diethyl carbonate by reaction with ethanol. In the presence of ammonium salts toxic ethyl carbamate then results, which is also known as urethane (Figure 11.2). For these reasons, diethyl dicarbonate is not approved in the EU, but the approved compound is dimethyl dicarbonate (E242), which can be used for the preservation of soft drinks, teas, herbal teas and in some countries to stabilise wine. The methyl carbamate produced from dimethtyl dicarbonate is a non-toxic substance. In treated wines it occurs in amounts up to 10 xg/l. 

Cassaday (1950), Shostakovski et al. (1951) and Melnikov et al. (1952) investigated extensively the addition reactions of dialkyl phosphorodithioic acids to unsaturated dicarbonic acid esters, and found that the dialkyl phosphorodithioic acids are added at the double bond in the same way as are mercaptans. This reaction was used by Cassaday (1950) who prepared 0,0-dimethyl-S-(l,2-dicarbethoxy)-ethyl phosphorodithioate by the addition reaction of dimethyl phosphorodithioic acid and maleic acid diethyl ester. This compound, known by the name malathion (89), became one of the most important phosphorus ester insecticides because of its low toxicity to warm-blooded animals. 

Azide cleavage of 821, utilizing a modification in which trimethylsilylazide first forms a reactive complex with DMAP that allows the reaction to occur at room temperature, affords in 85% yield diethyl (2 S, 3R)-2-azido-3-hydroxysuccinate (822). An advantage of this synthesis is that hazardous hydrazoic acid (HN3) is avoided. A one-pot two-step conversion of 822 involving hydrogenation over palladium on charcoal in the presence of di- er -butyl dicarbonate provides enantiomerically pure 823 in 66—73% yield [238,239] (Scheme 180). 

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