Acetyl cyanide

Reaction type 3 (equation 10), where the complete hetero-l,3-diene skeleton is incorporated into the newly formed ring system, occurs with compounds having both a nucleophilic center and an electrophilic center If these two functionalities are in positions 1 and 2, various types of six-membered ring systems become accessible 4,4-Bis(trifluoromethyl)-I,3-diaza-1,3-butadienes require only room temperature to react with acetyl cyanide to yield l,4,5,6-tetrahydropynmidin-6-ones [96] Likewise, certain open-chain 1,3-diketones (acetylacetone and acetoacetates) and the heterodiene form six-membered nng systems [97] (equation 19)... 

Pyruvic acid is the simplest homologue of the a-keto acid, whose established procedures for synthesis are the dehydrative decarboxylation of tartaric acid and the hydrolysis of acetyl cyanide. On the other hand, vapor-phase contact oxidation of alkyl lactates to corresponding alkyl pyruvates using V2C - and MoOa-baseds mixed oxide catalysts has also been known [1-4]. Recently we found that pyruvic acid is obtained directly from a vapor-phase oxidative-dehydrogenation of lactic acid over iron phosphate catalysts with a P/Fe atomic ratio of 1.2 at a temperature around 230°C [5]. 

Addition reactions of secondary phosphine oxides to acetyl cyanide (35),30 and to azo-esters (36),31 have been described. Complexes of dimethylphosphine sulphide... 

Lundgren, S. Wingstrand, E. Penhoat, M. Moberg, C. Dual Lewis acid-Lewis base activation in enantioselective cyanation of aldehydes using acetyl cyanide and cyanoformate as cyanide sources. J. Am. Chem. Soc. 2005,127, 11592-11593. 

Cyanation of aldehydes and ketones is an important chemical process for C C bond formation." " Trimethylsilyl cyanide and/or HCN are commonly used as cyanide sources. The intrinsic toxicity and instability of these reagents are problematic in their applications. Acetyl cyanide and cyanoformates were used as cyanide sources in the enantioselective cyanation of aldehydes catalyzed by a chiral Ti complex and Lewis base (Scheme 5.31)." The Lewis base was necessary for the good yields and selectivities of these reactions. The desired products were obtained in the presence of 10mol% triethyl amine and 5mol% chiral titanium catalyst (Figure 5.14). Various aliphatic and aromatic aldehydes could be used in these reactions. 

Scheme 6.14 Product range of the 9-catalyzed acetyl cyanation reaction of aldimines with acetyl cyanide as the cyanide source.

List and co-workers reported the 47-catalyzed (lmol% loading) asymmetric acetylcyanation of N-benzyl-protected aliphatic and aromatic aldimines by using commercially available liquid acetyl cyanide as the cyanide source instead of HCN [161]. Under optimized reaction parameters (toluene, -40 °C) the procedure resulted in the desired N-protected a-amino nitriles 1-5 in yields ranging from 62... 

Scheme 6.47 Strecker products obtained from the 47-catalyzed asymmetric acetylcyanation using acetyl cyanide as cyanide source.

Monocyanohydrins of P-diketones.3 In the presence of TiCl4, acetyl cyanide reacts with enol silyl ethers of ketones at - 78° to afford monocyanohydrins of diketoncs in excellent yield. The corresponding reaction with enol silyl ethers aldehydes proceeds in only about 35% yield. A low temperature is essential for this reaction. A similar reaction is possible with allyltrimethylsilane. 

Considerable variation is also possible in the carbonyl function, and in addition to simple aldehydes and ketones, acetyl cyanide,292 diethyl oxomalonate,293 diethyl oxalate,294 and ethyl cyanoformate 295 [Eq. (77)] will all undergo cycloaddition to alkenes to form the corresponding oxetanes. Oxetanes are also formed in certain circumstances from both a,j8-unsaturated aldehydes298 and acetylenic ketones.297... 

Nitrogen trifluoride Difluoramine Nitrous acid Nitric acid Cyano fluoride Formyl fluoride Carbonyl fluoride Acetyl fluoride Acetyl cyanide Isocyanic acid Methyl isocyanate Formamide Nitromethane Nitrobenzene... 

Methylcyclopentene co-ozonolyzed with formaldehyde, acetyl cyanide, or benzoyl cyanide afforded only the normal 1,2,4-trioxolane (secondary ozonide, 88) by contrast, 1-methylcyclohexene co-ozonolyzed with formaldehyde or acetyl cyanide gave no such ozonide, but almost equal amounts of the aldehyde-ozonide 86 and the diozonide 87, as shown in Equation (8) and Table 10. 

Co-ozonolysis of 1,2-dihydronaphthalene with formaldehyde, acetyl cyanide (pyruvonitrile), benzoyl cyanide, or acetaldehyde afforded an ozonide attached to a benzaldehyde group 89 and none of the isomeric ozonide with a propionaldehyde group. This indicates the preference for scission of the molozonide so as to favor conjugation between the aromatic ring and the aldehyde group rather than with the carbonyl oxide group. Subsequent co-ozonolysis of products 89 with vinyl acetate produced diozonides 90, as shown in Scheme 26 and Table 11. 

Norbornene co-ozonized with formaldehyde, acetyl cyanide, or benzoyl cyanide gave similarly the aldehydic ozonide 91, which then on co-ozonolysis with vinyl acetate (i.e., the source of formaldehyde oxide) afforded a diozonide 92, as indicated in Scheme 27 and Table 12. 

Acenaphthene co-ozonized with formaldehyde, acetyl cyanide, or benzoyl cyanide gave no cross-product, but only the normal ozonide 93 (resulted by cleavage of the reactive double bond of the non-aromatic five-membered ring), together with a hydroxy-perinaphthanone 94 (Equation 9). 

Phenanthrene has also a reactive 9,10-double bond, in agreement with the Clar structure having two aromatic sextets and a C=C fixed double bond in the median ring. On co-ozonolysis with formaldehyde, acetyl cyanide, or benzoyl cyanide, phenanthrene reacted accordingly, affording an aldehydic ozonide 112, which in a separate co-ozonolysis with vinyl acetate that produced formaldehyde oxide (H2C-0-0) gave rise to a diozonide 113 (Scheme 35 and Table 14). 

In the case of pyrene, there are two sextets and two fixed double bonds similar to the phenanthrenic double bond. In agreement with this argument and with the result for phenanthrene, co-ozonolysis of pyrene with formaldehyde or acetyl cyanide afforded the expected normal ozonide 114 and the cross-ozonide 115 with an aldehydic group. In a separate co-ozonolysis of 115 with vinyl acetate, diozonides 116 were prepared. No cross-ozonide was obtained in the presence of benzoyl cyanide, which afforded only the normal mono-ozonide 114 (Scheme 36 and Table 15). 

The final polycyclic aromatic hydrocarbon that was investigated <2000EJ0335> is benzo[fixed double bond like phenanthrene. Its cross-ozonolysis with formaldehyde gave none of the normal ozonide 120, but mainly the aldehydic ozonide 117. At room temperature, a substantial amount of opening of the ozonide ring occurred with the formation of the acid aldehyde 121. Both products 117 and 121 could be stabilized by treatment with O-methylhydroxylamine, yielding products 118 and 122, respectively. The separate co-ozonolysis of compound 117 with vinyl acetate afforded the diozonide 119 (Scheme 37 and Table 16). The cross-ozonolysis with acetyl cyanide followed by treatment of the crude reaction mixture with O-methylhydroxylamine yielded the O-methyloxime of the cross-product. Cross-ozonolysis with benzoyl cyanide was not successful, and only the normal mono-ozonide 120 was formed. 

Synthesis from Acelyl Chloride.— As can be readily seen this is the simplest ketone acid that is possible and it is an alpha-V.tiont acid. Its name is derived from the fact that it is obtained from racemic acid by heat. It is a liquid boiling at 165°. Its constitution is best shown by the following syntheses. Acetyl chloride by means of silver cyanide yields acetyl cyanide which by hydrolysis gives pyro-racemic acid. 

Orthocarbonates and their analogs do exchange just one alkoxy group with TMS-CN/SnCU (Scheme 17). In earlier pt rs even the direct reaction with HCN and ZnCb at room temperature was reported to give (after several days or even some weeks) high yields. Treatment with acetyl cyanide (Scheme 17) represents another possibility for transforming orthoesters into bisalkoxynitriles. ... 

Optically pure cyanohydrins serve as highly versatile synthetic building blocks [24], Much effort has, therefore, been devoted to the development of efficient catalytic systems for the enantioselective cyanation of aldehydes and ketones using HCN or trimethylsilyl cyanide (TMSCN) as a cyanide source [24], More recently, cyanoformic esters (ROC(O)CN), acetyl cyanide (CH3C(0)CN), and diethyl cyanophosphonate have also been successfully employed as cyanide sources to afford the corresponding functionalized cyanohydrins. It should be noted here that, as mentioned in Chapter 1, the cinchona alkaloid catalyzed asymmetric hydrocyanation of aldehydes discovered... 

Table 4.5 Dual Lewis acid-Lewis base activation in enantioselective cyanation of aldehydes using acetyl cyanide.

Cu,Zn-SOD is composed of two identical subunits of molecular weight 32,000. Each subunit contains one Cu and one Zn molecule, noncovalently linked. The complete amino acid sequence has been determined for various Cu,Zn-SODs (B5,B6,J1,S16,S17). The N-terminus of the enzymes from higher vertebrate species is acetylated. Cyanide is a reversible inhibitor of the Cu,Zn-SOD (C5,R5). The enzyme is also sensitive to diethyldithiocarbamate (H10) and H202 (B16,F9,R6,S12). The diethyldithiocarbamate binds copper at the active site and removes the metal from the enzyme. The copper ion appears to function in the enzymatic reaction, whereas the zinc ion does not function in the catalytic activity but stabilizes the enzyme. 

Acetoxyacrylonitrile has also been prepared1" by the reaction of chloroacctalde-hyde (1) in aqueous solution with sodium cyanide at—10-0°. 2-Chloro-l-cyanoethyl acetate (2) is obtained in 90% yield by way of the postulated intermediates (a) and (b). Formation of the cyanohydrin (a) is believed to be the first step, followed by loss of hydrogen chloride and ketonization to give acetyl cyanide (b) the latter intermediate is considered to acetylate the cyanohydrin (a) to give 2-chloro-l-... 

When a quaternary carbon atom is produced in the acylation process, racemization is not possible and the stereochemical outcome can be affected by the presence of an adjacent stereocenter. Treatment of the chiral lactone (168) with LDA and acetyl cyanide gave the diastereomeric products (169) and (170) in the ratio 60 1 (equation 44). ... 

A mixture of 1-C14 K-acetate and benzoic acid distilled with benzoyl bromide -> 1-C14 acetyl bromide (Y 75-90%) added to dry CuCN, sufficient anhydrous cyclohexane added to wet all of the CuCN, and allowed to stand 3 days in a sealed ampoule — 1-C14 acetyl cyanide (Y 75-80%). (H.S. Anker, J. Biol. Chem. 176, 1333 (1948).)... 

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